Prognostic Implications of Fractional Flow Reserve and Coronary Flow Reserve After Drug-Eluting Stent Implantation.
Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) provides prognostic information, but limited data are available regarding prognostication using post-PCI coronary flow reserve (CFR). In this study we aimed to assess the prognostic value of post-procedural FFR and CFR for target vessel failure (TVF) after PCI.Methods and Results: This lesion-based post-hoc pooled analysis of previously published registry data involved 466 patients with chronic coronary syndrome with single-vessel disease who underwent pre- and post-PCI FFR and CFR measurements, and were followed-up to determine the predictors of TVF. The prognostic value of post-PCI CFR and FFR was compared with that of FFR or CFR alone. Post-PCI FFR/CFR discordant results were observed in 42.5%, and 10.3% of patients had documented TVF. Receiver-operating characteristic curve analysis revealed that the optimal cutoff values of post-PCI FFR and CFR to predict the occurrence of TVF were 0.85 and 2.26, respectively. Significant differences in TVF were detected according to post-PCI FFR (≤0.85 vs. >0.85, P=0.007) and post-PCI CFR (<2.26 vs. ≥2.26, P<0.001). Post-PCI FFR ≤0.85 and post-PCI CFR <2.26 were independent prognostic predictors. After PCI completion, discordant results between FFR and CFR were not uncommon. Post-PCI CFR categorization showed incremental prognostic value for predicting TVF independent of post-PCI FFR risk stratification.


The Concept of Body Language in the Medical Consultation.
In this paper we wish to argue that the human body is an instrument of communication that can be used by the individual. This can be shown by the use of phenomenology, as described by Husserl, and that indeed empathy, as described by phenomenology, can be seen as a link enabling two human bodies/persons to communicate. We then wish to show from neuroscience that empathy can itself be seen as a bodily function. We then will describe how the doctor-patient relationship in the consultation is an extremely important type of communication between two persons, and how teaching of consultation skills has developed. We will show that, once consultation skills teaching was established, then study of body language became an essential part of this teaching, as soon as the technology was developed, and finally we will demonstrate that it is now possible to confirm by observational and controlled trials that appropriate use of body language does indeed enhance the effectiveness of the consultation, including, we would suggest, by appropriate communication of empathy and understanding.


Large-scale patterned multi-layer graphene films as transparent conducting electrodes for GaN light-emitting diodes.
This work demonstrates a large-scale batch fabrication of GaN light-emitting diodes (LEDs) with patterned multi-layer graphene (MLG) as transparent conducting electrodes. MLG films were synthesized using a chemical vapor deposition (CVD) technique on nickel films and showed typical CVD-synthesized MLG film properties, possessing a sheet resistance of [Formula: see text] with a transparency of more than 85% in the 400-800 nm wavelength range. The MLG was applied as the transparent conducting electrodes of GaN-based blue LEDs, and the light output performance was compared to that of conventional GaN LEDs with indium tin oxide electrodes. Our results present a potential development toward future practical application of graphene electrodes in optoelectronic devices.


New approaches to the industrial synthesis of HIV protease inhibitors.
Efficient and industrially applicable synthetic processes for precursors of HIV protease inhibitors (Amprenavir, Fosamprenavir) are described. These involve a novel and economical method for the preparation of a key intermediate, (3S)-hydroxytetrahydrofuran, from l-malic acid. Three new approaches to the assembly of Amprenavir are also discussed. Of these, a synthetic route in which an (S)-tetrahydrofuranyloxy carbonyl is attached to l-phenylalanine appears to be the most promising manufacturing process, in that it offers satisfactory stereoselectivity in fewer steps.


The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis.
The cell cycle is exquisitely controlled by multiple sequential regulatory inputs to ensure fidelity. Here we demonstrate that the final step in division, the physical separation of daughter cells, is controlled by a member of the PKC gene superfamily. Specifically, we have identified three phosphorylation sites within PKCepsilon that control its association with 14-3-3. These phosphorylations are executed by p38 MAP kinase (Ser 350), GSK3 (Ser 346) and PKC itself (Ser 368). Integration of these signals is essential during mitosis because mutations that prevent phosphorylation of PKCepsilon and/or PKCepsilon binding to 14-3-3 also cause defects in the completion of cytokinesis. Using chemical genetic and dominant-negative approaches it is shown that selective inhibition of PKCepsilon halts cells at the final stages of separation. This arrest is associated with persistent RhoA activation at the midbody and a delay in actomyosin ring dissociation. This study therefore identifies a new regulatory mechanism that controls exit from cytokinesis, which has implications for carcinogenesis.


Strategies to manage gastrointestinal symptoms complicating enteral feeding.
Diarrhea and abdominal distension are common complications associated with enteral feeding. Often the cause is unknown, the enteral formula is blamed and changes to the mode of delivery or formula are instituted. However, the evidence base for many strategies used is limited. Altering the osmolality and temperature of the formula and/or the rate of infusion are commonly practiced but evidence for their benefit is largely anecdotal. Preventing microbial contamination of the feed is important and clear guidelines exist to achieve this. The formulation itself can be modified. While the addition of fiber is well supported theoretically, outcome data are less convincing. Avoidance of osmotically active, poorly absorbed short-chain carbohydrates in the formula (often used as the major carbohydrate source) is a new tactic to minimize diarrhea. It has compelling theoretical support, but requires further investigation. A methodical clinical approach to gastrointestinal complications of enteral feeding is warranted and an algorithm for management is proposed.


Energy Landscape of Alginate-Epimerase Interactions Assessed by Optical Tweezers and Atomic Force Microscopy.
Mannuronan C-5 epimerases are a family of enzymes that catalyze epimerization of alginates at the polymer level. This group of enzymes thus enables the tailor-making of various alginate residue sequences to attain various functional properties, e.g. viscosity, gelation and ion binding. Here, the interactions between epimerases AlgE4 and AlgE6 and alginate substrates as well as epimerization products were determined. The interactions of the various epimerase-polysaccharide pairs were determined over an extended range of force loading rates by the combined use of optical tweezers and atomic force microscopy. When studying systems that in nature are not subjected to external forces the access to observations obtained at low loading rates, as provided by optical tweezers, is a great advantage since the low loading rate region for these systems reflect the properties of the rate limiting energy barrier. The AlgE epimerases have a modular structure comprising both A and R modules, and the role of each of these modules in the epimerization process were examined through studies of the A- module of AlgE6, AlgE6A. Dynamic strength spectra obtained through combination of atomic force microscopy and the optical tweezers revealed the existence of two energy barriers in the alginate-epimerase complexes, of which one was not revealed in previous AFM based studies of these complexes. Furthermore, based on these spectra estimates of the locations of energy transition states (xβ), lifetimes in the absence of external perturbation (τ0) and free energies (ΔG#) were determined for the different epimerase-alginate complexes. This is the first determination of ΔG# for these complexes. The values determined were up to 8 kBT for the outer barrier, and smaller values for the inner barriers. The size of the free energies determined are consistent with the interpretation that the enzyme and substrate are thus not tightly locked at all times but are able to relocate. Together with the observed different affinities determined for AlgE4-polymannuronic acid (poly-M) and AlgE4-polyalternating alginate (poly-MG) macromolecular pairs these data give important contribution to the growing understanding of the mechanisms underlying the processive mode of these enzymes.


Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis.
Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.


Public health perspectives of channelized and unchannelized headwater streams in central Ohio: a case study.
Headwater streams constitute the majority of watersheds in the United States and many in the midwest have been channelized for agricultural drainage. Public health implications of water chemistry and aquatic insects within channelized and unchannelized headwater streams have not been explored. We sampled water chemistry and aquatic insects in two channelized and two unchannelized headwater streams in central Ohio from December 2005 until November 2008. Maximum concentrations of ammonium, nitrate plus nitrite, and chlorothalonil were greater in channelized streams. Nitrate plus nitrite and atrazine also exceeded drinking water standards more often in channelized streams. Maximum concentrations of simazine and the percentage of times it exceeded the drinking water standards were greater in unchannelized streams. The predicted hazard potential of nutrient and pesticide mixtures was greater in channelized streams. Mosquito abundance did not differ between stream types. Chironomid abundance was greater in channelized streams. Biting dipterans did not exhibit consistent abundance trends and only differed between stream types in the summer and fall. Our results suggest that if whole stream uptake of nutrients and pesticides is minimal in channelized headwater streams then nutrient and pesticide inputs from these streams may impact downstream drinking water sources. Our results also suggest channelized and unchannelized headwater streams are not serving as a significant source of mosquitoes.


Defect structures and torque on an elongated colloidal particle immersed in a liquid crystal host.
Combining molecular dynamics and Monte Carlo simulation, we study defect structures around an elongated colloidal particle embedded in a nematic liquid crystal host. By studying nematic ordering near the particle and the disclination core region, we are able to examine the defect core structure and the difference between two simulation techniques. In addition, we also study the torque on a particle tilted with respect to the director, and modification of this torque when the particle is close to the cell wall.


Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes.
Signaling pathways in eukaryotic cells are often controlled by the formation of specific signaling complexes, which are coordinated by scaffold and adaptor proteins. Elucidating their molecular architecture is essential to understand the spatial and temporal regulation of cellular signaling. p14 and MP1 form a tight (K(d) = 12.8 nM) endosomal adaptor/scaffold complex, which regulates mitogen-activated protein kinase (MAPK) signaling. Here, we present the 1.9-A crystal structure of a biologically functional p14/MP1 complex. The overall topology of the individual MP1 and p14 proteins is almost identical, having a central five-stranded beta-sheet sandwiched between a two-helix and a one-helix layer. Formation of the p14/MP1 heterodimer proceeds by beta-sheet augmentation and yields a unique, almost symmetrical, complex with several potential protein-binding sites on its surface. Mutational analysis allowed identification of the p14 endosomal adaptor motif, which seems to orient the complex relative to the endosomal membrane. Two highly conserved and hydrophobic protein-binding sites are located on the opposite "cytoplasmic" face of the p14/MP1 heterodimer and might therefore function as docking sites for the target proteins extracellular regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore, detailed sequence analyses revealed that MP1/p14, together with profilins, define a protein superfamily of small subcellular adaptor proteins, named ProflAP. Taken together, the presented work provides insight into the spatial regulation of MAPK signaling, illustrating how p14 and MP1 collaborate as an endosomal adaptor/scaffold complex.


Expression of lavender AGAMOUS-like and SEPALLATA3-like genes promote early flowering and alter leaf morphology in Arabidopsis thaliana.
The expression of full-length cDNAs encoding lavender AGAMOUS-like (LaAG-like) and SEPALLATA3-like (LaSEP3-like) transcription factors induces early flowering and impacts the leaf morphology at a strong expression level in Arabidopsis. Lavandula angustifolia is widely cultivated as an ornamental plant due to its attractive flower structure, and as a source of valuable essential oils for use in cosmetics, alternative medicines, and culinary products. We recently employed RNA-Seq and transcript profiling to describe a number of transcription factors (TFs) that potentially control flower development in this plant. In this study, we investigated the roles of two TFs, LaAGAMOUS-like (LaAG-like) and LaSEPALLATA3-like (LaSEP3-like), that exhibited substantial homology to Arabidopsis thaliana floral development genes, AGAMOUS and SEPALLATA3, respectively, in flowering initiation in Arabidopsis. We stably and constitutively expressed LaAG-like and LaSEP3-like cDNAs in separate Arabidopsis plants. All transgenic plants flowered earlier than the wild-type controls. However, plants that modestly overexpressed the gene were phenotypically normal, while those that strongly expressed the transgene developed curly leaves. We also assessed the expression of five endogenous flowering time regulating genes, from which high expression of Flowering Locus T (AtFT) mRNA in both LaAG-like (type-I and -II) and LaSEP3-like (type-I), and Leafy (AtLFY) mRNAs in LaSEP3-like (type-I) transgenic plants were detected, compared to wild-type controls. Our results suggest that with controlled expression, lavender AG-like and SEP3-like genes are potentially useful for the regulation of flowering time in commercial lavender species, and could be used for plant improvement studies through molecular genetics and targeted breeding programs.


High performing smart electrochromic device based on honeycomb nanostructured h-WO3 thin films: hydrothermal assisted synthesis.
Herein, we report honeycomb nanostructured single crystalline hexagonal WO(3) (h-WO(3)) thin films in order to improve electrochromic performance. In the present investigation, honeycomb nanostructured WO(3) with different unit size and nanowire array with highly nanocrystalline frameworks have been synthesized via a hydrothermal technique. The influence of hydrothermal reaction time on the honeycomb unit cells, crystallite size, lithium ion diffusion coefficient and switching time for coloration/bleaching were studied systematically. The electrochromic study reveals that the honeycomb unit cell size has a significant impact on the electrochromic performance. Small unit cells in the honeycomb lead to large optical modulation and fast switching response. A large optical modulation in the visible spectral region (60.74% at λ = 630 nm) at a potential of -1.2 V with fast switching time (4.29 s for coloration and 3.38 s for bleaching) and high coloration efficiency (87.23 cm(2) C(-1)) is observed in the honeycomb WO(3) thin films with a unit cell diameter of 1.7 μm. The variation in color on reduction of WO(3) with applied potential has been plotted on an xy-chromaticity diagram and the color space coordinate shows the transition from a colorless to deep blue state.


N-domain angiotensin-converting enzyme isoform expression in tissues of Wistar and spontaneously hypertensive rats.
Angiotensin I-converting enzyme (ACE) is a protein containing two active sites, called N- and C-domains, according to their position in the protein. The aim of the present study was to verify whether the expression of the N-domain ACEs detected in the urine of Wistar and spontaneously hypertensive (SHR) rats was restricted to the kidney. Adrenal, aorta, heart, liver, lung, kidney and testicle tissue from Wistar rats and spontaneously hypertensive rats were homogenized in assay buffer and analyzed by gel filtration, Western blotting and radio-immunoassay. Two peaks (at 136 and 69 kDa) with ACE activity upon ZPhe-His-Leu were separated by gel filtration from homogenate tissues of Wistar rats, in contrast with the tissue from hypertensive rats, which showed ACE forms of 96 and 69 kDa. The bands detected by Western blotting for all studied tissue from Wistar and spontaneously hypertensive rats showed a correspondence with the two peaks containing ACE activity detected in the polyacrylamide gel slices. Angiotensin II levels were increased in hypertensive rat tissue when compared with Wistar rat tissues. In addition, captopril 3 micromol/l inhibited the enzymic activity, where the Km was in the order of mmol/l and micromol/l using hippuryl-His-Leu and Abz-Ser-Asp-Lys(Dnp)Pro-OH as substrates, respectively. All tissues from Wistar rats presented ACE with 136 kDa, similar to somatic ACE, and N-domain ACE with 69 kDa. In the same tissue of spontaneously hypertensive rats, 96 and 69 kDa N-domain ACEs were detected. Our results demonstrated that N-domain ACEs were not exclusively produced in the kidney and excreted in the urine; they were expressed in all tissue studied, suggesting that these enzymes could influence local angiotensin II production, contributing to organ-specific regulation.


Imaging of joint tumors.
The paper gives an overview of the present nosological classification and imaging features of synovial tumors and tumor-like conditions of joints. The merits of each imaging technique will be emphasized.


Management of Chronic Kidney Disease in Morocco: A Cost-of-Illness Study.
Chronic kidney disease (CKD) is a global public health problem. The aim of this study is to estimate the mean annual direct medical cost per patient with CKD before the start of renal replacement therapy (RRT) in Morocco. This is a cross-sectional cost-of-illness study, using a prevalence approach among adults with CKD before RRT in a Moroccan university hospital. Information on direct medical costs was collected from the patient's report and associated costs were estimated according to national tariff/fee catalogues. We computed annual direct medical costs using society perspective. Costs were then estimated and compared according to CKD stages, health insurance categories, and monthly income. Eighty-eight participants were included; 63.6% of them were female, their mean age was 61.8±14.0 years, and 76.1% were in stages 4 or 5. The estimated annual direct medical cost of CKD was estimated at $ 2008.80 (95%CI 1528.28-2489.31), Hospitalization, diagnosis, and treatment represented the main expenses of the direct medical cost (32.2%, 29.7%, and 32.2%, respectively). The direct medical cost components were not significantly different between CKD stages. The cost of CKD in Morocco in its early stages is still lower than the cost of RRT, which brings to light the necessity of secondary prevention of CKD to postpone or prevent the progression to end-stage renal disease.


Characterization of inhibitory effects of an anti-murine CD2 monoclonal antibody on the proliferation of T cell clones.
Though the functional roles of human CD2 are well characterized, murine studies have been lacking until very recent years. Our previous work showed that a mAb against the T11(1)-like domain of CD2 clearly inhibited T cell proliferation induced by mitogenic and allo-antigenic stimuli, but the degree of inhibition was much smaller than had been demonstrated in the human system. In the present study, we observed functional aspects of murine CD2 on CD4+ T cell clones. It was shown that all T cell clones tested were CD2-positive, and that proliferation induced by APC + Ag was inhibited by anti-CD2 mAb. The maximum inhibition was also partial (40-60% inhibition) but CD2-mediated inhibition was observed even at concentrations as low as 0.2 microgram/ml. In contrast to the APC + Ag stimulation, the proliferation induced by lymphokines or immobilized anti-CD3 mAb was not inhibited at all. Taken together, these findings indicate that: (1) CD2 is also involved in the interaction between HTL and APC in murine system; but (2) perturbation of murine CD2 does not influence TCD/CD3- and lymphokine-mediated signal transduction.


Genetic recombination and the cell cycle: what we have learned from chromosome dimers.
Genetic recombination is central to DNA metabolism. It promotes sequence diversity and maintains genome integrity in all organisms. However, it can have perverse effects and profoundly influence the cell cycle. In bacteria harbouring circular chromosomes, recombination frequently has an unwanted outcome, the formation of chromosome dimers. Dimers form by homologous recombination between sister chromosomes and are eventually resolved by the action of two site-specific recombinases, XerC and XerD, at their target site, dif, located in the replication terminus of the chromosome. Studies of the Xer system and of the modalities of dimer formation and resolution have yielded important knowledge on how both homologous and site-specific recombination are controlled and integrated in the cell cycle. Here, we briefly review these advances and highlight the important questions they raise.


General Principles for Preoperative Planning and Microsurgical Treatment of Pediatric Brain Arteriovenous Malformations: 2-Dimensional Operative Video.
Children with arteriovenous malformations (AVMs) are at cumulative, life-long risk of debilitating and fatal intracranial hemorrhage, especially with syndromes such as hereditary hemorrhagic telangiectasia. Cerebral angiography is the gold standard for diagnosis and allows simultaneous adjunctive embolization limiting radiation and contrast exposure and intraoperative blood loss, important in pediatric patients with low blood volume. Microsurgical resection of low-grade AVMs offers cure with minimal morbidity. The plasticity of the pediatric brain may allow resection of AVMs near eloquent regions. Multidisciplinary care offers the best outcomes in these cases. Discussion of the operative plan with all team members at the start of surgery is carried out. Confirmation that blood products are present and that the microscope, additional suction, and surgical clips are available is performed. A generous craniotomy is created, adequately exposing the lesion. The dura is carefully opened to avoid injury to draining veins. Circumferential dissection and isolation of the AVM is performed, coagulating small arterial feeders, dissecting to the lesion's apex to coagulate, and divide major deep feeders. Once all feeders have been obliterated, venous drainage is disconnected. Indocyanine green distinguishes arterial feeders from arterialized veins and confirms complete resection. Since 2008, all of our patients undergo perioperative angiography in our dedicated suite, greatly improving resection rates. Strict blood pressure control and close neurological monitoring in the intensive care unit is performed postoperatively. In conclusion, microsurgical resection of AVMs can be performed safely with low rates of morbidity. Protocols for preoperative evaluation and planning appear to improve outcomes. Anonymous video is permitted when done without identifying patient related information.


[Cancer stem cells in prostate cancer].
The cancer stem cell (CSC) hypothesis shows that tumors contain a reservoir of self-renewing cells that maintain the tumor. Such cancer cells were first identified in leukemia in the 1990s. These cells appear to be resistant to various therapies and can survive to repopulate the tumor. Therefore, this concept has important therapeutic implications for recurrence and metastasis. In this review, we introduce the CSC hypothesis and the origin, method of identification and functions of prostate CSCs. In addition, we review the therapeutic challenges of targeting prostate CSCs.


[Effects and related mechanisms of ghrelin on myocardial neovascularization in diabetic rats with experimental myocardial infarction].
To investigate the effects and related mechanisms of ghrelin on myocardial neovascularization in diabetic rats with experimental myocardial infarction (MI). Adult male SD rats were divided into six groups (n = 20 each group): control, diabetes mellitus (DM), MI, DM+MI, DM+MI+ghrelin, DM+MI+ghrelin+D-Lys3-GHRP-6 (GHSR1a inhibitor). DM was induced by streptozotocin (STZ, 60 mg/kg), 3 months later, MI was induced by left anterior descending artery ligation in DM rats. DM+MI+ghrelin group received ghrelin 200 µg×kg(-1)×d(-1) and DM+MI+ghrelin+D-Lys3-GHRP-6 group received ghrelin 200 µg×kg(-1)×d(-1) and D-Lys3-GHRP-6 50 mg×kg(-1)×d(-1) for 4 weeks. Then, cardiac function was measured by echocardiography, microvascular density (MVD) was measured by CD34 immunohistochemistry, myocardial infarct size was determined by Masson staining, the mRNA and protein expressions of vascular endothelial growth factor (VEGF) and receptors Flk-1, Flt-1 were detected by real-time PCR and Western-blot, respectively. Compared with MI group, MVD (15.3 ± 1.0 vs.20.7 ± 1.6, P < 0.05), left ventricular ejection fraction (LVEF) ((64.2 ± 3.4)% vs. (81.3 ± 3.8)%, P < 0.01), left ventricular fractional shortening (LVFS) ((31.7 ± 1.1)% vs. (48.8 ± 3.3)%, P < 0.01) and the mRNA and protein expression of VEGF, Flk-1 and Flt-1 (P < 0.01) were reduced, while myocardial infarct size ((55.8 ± 3.1)% vs. (35.7 ± 2.5)%, P < 0.01) was increased in DM+MI group. These effects were partly reversed in DM+MI+ghrelin group and the beneficial effects of ghrelin were partly abolished by D-Lys3-GHRP-6 (all P < 0.05). Our results demonstrate that ghrelin could improve microvascular density, cardiac function, and reduce myocardial infarct size of diabetic rats with myocardial infarction via modulating GHSR1a-mediated expressions of VEGF, Flk-1 and Flt-1.


Phencyclidine and violence: clinical and legal issues.
Phencyclidine (PCP) abuse has diminished since PCP's intrusion into American culture in the late 1970s. One of its legacies is the assumption that it provokes violent behavior in humans with predictable regularity. This assumption is so accepted that ingestion of the drug both accidentally and knowingly prior to committing a crime has been used as a defense in criminal trials. We reviewed 81 clinical reports of toxicity in humans published chiefly in North American medical journals. We searched for descriptions of violent behavior in these reports and subjected them to the following questions: (1) Was the violent behavior corroborated or only self-reported? (2) Was the presence of PCP confirmed by analysis of bodily fluids or postmortem tissue? (3) Was the presence of other drugs excluded by similar analysis of bodily fluids? We had planned to examine the reports to see whether clinicians sought evidence of previous violent behavior, but such an inquiry was rarely conducted. Of the hundreds of patients described, only three satisfied these criteria. Further, some of the papers offered evidence that reports of violence were exaggerated. These findings plus the pre-1970 prospective evaluation of thousands of patients with PCP, in which violence was never reported, led us to conclude that clinical and forensic assumptions about PCP and violence are not warranted.


Takayasu's arteritis.
Two recent cases of Takayasu's arteritis illustrate the wide spectrum of disease presentation. The first patient demonstrated rapid development of ischemic manifestations; the second patient presented with septal panniculitis. Worldwide distribution of Takayasu's arteritis has increased.


Development of a Pulmonary Rehabilitation Patient Decision Aid for Patients with Chronic Obstructive Pulmonary Disease: Mixed Methods Study.
Pulmonary rehabilitation is an important part of the management of chronic obstructive pulmonary disease (COPD), but the participation rate of pulmonary rehabilitation in COPD patients is low. Patient decision aids can facilitate patient participation in pulmonary rehabilitation decisions by providing information and incorporating patient values. The aim of this study was to develop a pulmonary rehabilitation decision aid for patients with COPD. The aim of this study was to develop a WeChat-based pulmonary rehabilitation patient decision aid to help older patients with COPD participate in pulmonary rehabilitation decision-making. We developed the decision aid in 3 stages: (1) a literature review was performed to determine the evidence for pulmonary rehabilitation options and outcomes for patients with COPD. (2) a semi-structured interview study was conducted to develop and iterate patient decision aids. (3) usability, acceptability and language expression testing in patients and healthcare professionals. A total of 16 randomized controlled studies were included in the literature review. Thirty-six participants received semi-structured interviews. The results of interview include four themes: key points of age-friendly design, content of the tool, presentation requirements of contents and study evidence of the tool and other views and suggestions. The resultant goals-of-care decision aid achieved good usability and acceptability. The frequency of language expression increased in both patients and healthcare professionals. This study uses a systematic development process to develop the first pulmonary rehabilitation decision aid for patients with COPD. It has good usability, acceptability and increased communication between patients and healthcare professionals in the pulmonary rehabilitation decision-making process. Chinese Clinical Trial Registry (ChiCTR): ChiCTR1900028563; http://apps.who.int/trialsearch/default.aspx.


Synthesis of a base-protected xylo-LNA adenine nucleoside.
Synthesis of (1S,3R,4R,7R)-7-hydroxy-1-hydroxymethyl-3-(6-N-benzoyl-adenin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane (2), a base-protected xylo-LNA adenine nucleoside, has been accomplished using a convergent synthetic strategy starting from 1,2-di-O-acetylfuranose 3.


The Antiarrhythmic Mechanisms of Flecainide in Catecholaminergic Polymorphic Ventricular Tachycardia.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe yet rare inherited arrhythmia disorder. The cornerstone of CPVT medical therapy is the use of β-blockers; 30% of patients with CPVT do not respond well to optimal β-blocker treatment. Studies have shown that flecainide effectively prevents life-threatening arrhythmias in CPVT. Flecainide is a class IC antiarrhythmic drug blocking cardiac sodium channels. RyR2 inhibition is proposed as the principal mechanism of antiarrhythmic action of flecainide in CPVT, while it is highly debated. In this article, we review the current progress of this issue.


Perspective taking and opinions about forms of reparation for victims of historical harm.
The authors investigated the effects of perspective taking on opinions about reparations for victims of historical harm. In two studies, they showed that when non-Indigenous Australians took an Indigenous Australian perspective, this increased perceived entitlement to, and decreased anger toward, monetary compensation. Moreover, perceived entitlement mediated the relationship between anger about monetary compensation and perspective taking. Study 2 demonstrated the mutual influence of emotions and perceived entitlement. In particular, self-image shame rather than group-based guilt or anger predicted support for reparation when an Indigenous Australian perspective was adopted. The results suggest that taking the perspective of people who have experienced harm from one's own group can bolster a commitment to positive social change in relation to a pressing social issue.


First Application of Fecal Microbiota Transplantation in Adult Asperger Syndrome With Digestive Symptoms-A Case Report.
Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.


Microvascular anatomy of striate vessels in dogs: contribution to an experimental model of forebrain ischemia.
Basal perforating vessels such as Heubner's artery are involved in various arteriopathic conditions resulting in cognitive and memory deficits. In order to evaluate if a model of focal forebrain ischemia can be obtained in dogs, a systematic study of the microvascular anatomy of the striate vessels was performed using intravascular injections of acrylic paint and/or India ink. Medial and lateral striate arteries were identified and found distinct either by their superficial anatomy as well as their deep perfusion territories. One medial striate artery emerging consistently from the junction of the A1 segment of the anterior cerebral artery and the ethmoidal artery resembles the human recurrent artery of Heubner. Therefore, the dog may provide a suitable model of forebrain ischemia involving solely the perfusion territory of the medial striate arteries.


Comparative and integrative analysis of RNA structural profiling data: current practices and emerging questions.
Structure profiling experiments provide single-nucleotide information on RNA structure. Recent advances in chemistry combined with application of high-throughput sequencing have enabled structure profiling at transcriptome scale and in living cells, creating unprecedented opportunities for RNA biology. Propelled by these experimental advances, massive data with ever-increasing diversity and complexity have been generated, which give rise to new challenges in interpreting and analyzing these data. We review current practices in analysis of structure profiling data with emphasis on comparative and integrative analysis as well as highlight emerging questions. Comparative analysis has revealed structural patterns across transcriptomes and has become an integral component of recent profiling studies. Additionally, profiling data can be integrated into traditional structure prediction algorithms to improve prediction accuracy. To keep pace with experimental developments, methods to facilitate, enhance and refine such analyses are needed. Parallel advances in analysis methodology will complement profiling technologies and help them reach their full potential.


Organic photo sensors for multi-angle light scattering characterization of particle systems.
Organic Photo Sensor (OPS) technology allows printing on conformable plastic-like substrates complex-shaped, arbitrarily-sized and pre-aligned photosensitive elements. This article reports, to the best of our knowledge, the first investigation to implement this emerging technology for Multi-Angle Light Scattering (MALS) characterization of nano- and microparticle suspensions. Monte Carlo and Lorenz-Mie theory calculations as well as preliminary experimental results on latex suspensions clearly demonstrate the potential of the proposed approach.


Topological Alterations and Symptom-Relevant Modules in the Whole-Brain Structural Network in Semantic Dementia.
Semantic dementia (SD) is characterized by a selective decline in semantic processing. Although the neuropsychological pattern of this disease has been identified, its topological global alterations and symptom-relevant modules in the whole-brain anatomical network have not been fully elucidated. This study aims to explore the topological alteration of anatomical network in SD and reveal the modules associated with semantic deficits in this disease. We first constructed the whole-brain white-matter networks of 20 healthy controls and 19 patients with SD. Then, the network metrics of graph theory were compared between these two groups. Finally, we separated the network of SD patients into different modules and correlated the structural integrity of each module with the severity of the semantic deficits across patients. The network of the SD patients presented a significantly reduced global efficiency, indicating that the long-distance connections were damaged. The network was divided into the following four distinctive modules: the left temporal/occipital/parietal, frontal, right temporal/occipital, and frontal/parietal modules. The first two modules were associated with the semantic deficits of SD. These findings illustrate the skeleton of the neuroanatomical network of SD patients and highlight the key role of the left temporal/occipital/parietal module and the left frontal module in semantic processing.


[Determination of proteinuria in children: changes in results according to the methods used (author's transl)].
Five methods for determination of proteinuria are compared : gravimetry, colorimetry (bromocresol green, Biuret test, Lowry's test), opacimetry (sulfosalicylic acid). Determinations were performed on normal urine, overloaded with albumin or gammaglobulins or on abnormal urine, after varying several parameters (pH, osmolarity, glucose, fructose, red blood cells, hemoglobin. leukocytes, germs). Some methods give non linear results depending on the concentrations (gravimetry, sulfosalicylic acid, bromocresol green). Some systematically give over-results (Biuret test, Lowry's test). Some almost exclusively determine albumin levels (bromocresol green, sulfosalicylic acid). In some, results are altered by glucose or fructose (Biuret, Lowry) or by red blood cells (Biuret, Lowry, sulfosalicylic acid). None of the tested methods can be used as a reference method. The method using sulfosalicylic acid is suitable for routine determination; however, results should be interpreted according to the parameters mentioned above.


Occurrence of multidrug resistant Gram-negative bacteria and resistance genes in semi-aquatic wildlife - Trachemys scripta, Neovison vison and Lutra lutra - as sentinels of environmental health.
Emergence of antimicrobial resistance (AMR) in bacterial pathogens has been recognized as a major public health concern worldwide. In the present study, antimicrobial resistant Gram-negative bacteria (AMRGNB) and AMR genes were assessed in semi-aquatic wild animals from a highly populated and intensive farming region of Spain, Catalonia. Cloacal/rectal swab samples were collected from 241 animals coming from invasive species Trachemys scripta (n = 91) and Neovison vison (n = 131), and endangered-protected species Lutra lutra (n = 19). Accordingly, 133 (55.2%) isolates were identified as AMRGNB. Escherichia coli and Pseudomonas fluorescens were among the bacteria most frequently isolated in all animal species, but other nosocomial agents such as Klebsiella pneumoniae, Salmonella spp. or Citrobacter freundii, were also prevalent. The phenotypic susceptibility testing showed the highest resistance to β-lactams (91%). Molecular analysis showed 25.3% of turtles (15.4% ESBL/Ampc genes), 21% of Eurasian otters (10.5% ESBL/Ampc genes) and 14.5% of American minks (8.4% ESBL/Ampc genes) were positive to AMR genes. The genotyping frequency was tetM (20.6%), blaCMY-2 (13%), ermB (6.1%), blaCMY-1 (4.6%), blaCTX-M-15 (3.1%) and mcr-4 (0.8%). Turtles had a larger prevalence of AMRGNB and AMR genes than mustelids, but American mink carried mcr-4 colistin-resistance gene. Moreover, cluster analysis of AMR gene distribution revealed that an ESBL/AmpC cluster in a highly populated area comprising big metropolitan regions, and another tetM/emrB cluster in an expended area with highly intensive livestock production. Although the mcr-4 positive case was not included in those clusters, that case was found in a county with a high pig farm density. In conclusion, semi-aquatic wild animals are a good sentinel for environmental contamination with AMRGNB and AMR genes. Therefore, One Health Approach is urgently needed in highly populated regions, and with intensive livestock production like Catalonia.


Derivation of neurospheres from bone marrow stromal cells.
Nerve stem cells have a unique characteristic in that they form spherical aggregates, also termed neurospheres, in vitro. The study demonstrated the successful derivation of these neurospheres from bone marrow culture. Their plasticity as nerve stem cells was confirmed. The findings further strengthens the pluripotency of cell populations within the bone marrow.


Pathomechanisms in cell metabolism: a key to treatment of Bell's palsy.
In light of current research the classic theory on the vicious circle of Bell's palsy has to be reconsidered. New findings through electron microscopy and biochemistry concerning the structure and metabolism of cells have presented aspects which have consequences for treatment of the disease. These aspects deal mainly with the pathomechanisms of cell metabolism whose interactions also cause a vicious circle, leading to a breakdown of microcirculation and ultimately to the death of the cells due to hypoxia and acidosis. It is therefore suggested that the aim of an effective therapy must be the early normalization of cell metabolism by improving microcirculation. A fitting treatment protocol is presented and the extraordinarily good results are discussed.


Response of gene expression in Saccharomyces cerevisiae to amphotericin B and nystatin measured by microarrays.
The response of the yeast Saccharomyces cerevisiae to two polyene antibiotics, amphotericin B and nystatin, was studied by genomic expression profiling. The two agents produced highly similar expression pattern changes, which was consistent with their known identical mechanisms of action on cell membranes. Detailed analysis was focused on the amphotericin B-treated sample in this study. Our data showed that genes involved in mitochondrial ribosomal protein synthesis were more severely repressed than those in the cytoplasm, which might contribute to the cytotoxicity of amphotericin B. To counteract the leakage of intracellular nutrients and ions from the pores in the cell membrane caused by amphotericin B, c. 17 genes involved in transport facilitation were induced, presumably to allow more efficient uptake of nutrients and ions. The expression level of five genes involved in ergosterol synthesis dropped and three genes related to cell wall biogenesis were induced, indicating that the cell membrane and cell wall were also affected by the presence of polyene antibiotics. It was observed that the pleiotropic drug resistance network in yeast cells was activated after exposure to amphotericin B, possibly contributing to the acquisition of amphotericin B resistance. Part of the gene expression alteration measured by microarray was confirmed by quantitative RT-PCR.


Maternal and Neonatal Outcomes of Sub-clinical Hypothyroidism Treated With Levothyroxine in Pregnancy: A Retrospective Cohort Study.
The effect of sub-clinical hypothyroidism (SCH) in pregnancy has been controversial. Furthermore, the impact of levothyroxine replacement on improving outcomes in pregnant women with SCH is unknown. This study aimed to assess the maternal and neonatal outcomes of pregnant women with SCH who were treated with levothyroxine replacement. This retrospective chart review was conducted at a tertiary hospital in Iran between 2020 and 2022. All pregnant women who had given birth during the study period were recruited. Those who did not have thyroid function test results within 10-12 weeks, as well as those with SCH who did not have levothyroxine replacement, were excluded. The subjects were divided into two groups based on the 2017 American Thyroid Association (ATA) criteria: non-SCH (TSH values 0.27-2.5 mIU/L) and SCH (TSH values more than 4.0 mIU/L). The demographic, obstetric, maternal, and neonatal outcomes of both groups were compared. The Chi-square test was used to compare the categorical variables. Binary logistic regression was used to assess differences in categorical variables. With a frequency of 10.5%, 935 women out of 8888 were diagnosed with SCH. In terms of age, educational level, living residency, medical insurance, access to prenatal care, and smoking status, there were no differences between the two groups. In terms of gestational age, parity, onset of labor, history of infertility, hypertension, cardiovascular disease, anemia, and overt diabetes, there were no differences between the two groups; however, gestational diabetes was more common in those with SCH. Compared with the non-SCH group, the prevalence and risks of gestational diabetes [19.8 vs. 14.2, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.72-3.95] were significantly higher in the SCH group after controlling for confounding factors. There were no differences in neonatal outcomes between the two groups. Except for gestational diabetes, we found no significant adverse events in terms of maternal and neonatal outcomes among women with SCH who were treated with levothyroxine.


Anorexia nervosa and dialysis: we have no time when the body is so damaged!
Anorexia nervosa remains challenging to treat and difficult to prevent. Nearly 5% of affected individuals die of this disease and 20% develop a chronic eating disorder. Anorexia nervosa may be associated with several medical complications of varying severity, including dysfunction of the renal system. Though there are some reports of renal failure in patients with anorexia nervosa, few reports are available concerning patients who required maintenance dialysis. We report a case of a patient with long-term untreated anorexia nervosa-binge eating/purging type who started psychiatric treatment when in a life-threatening situation (renal failure requiring dialysis), with unsuccessful weight recovery while on dialysis and died of septicaemia. The mechanisms that seem to be involved in the development of end-stage renal disease in this patient and the challenges associated with her treatment are reviewed. Patients with anorexia nervosa should be carefully monitored to discover the subtle manifestations of early renal failure.


Metabolomics and fetal alcohol spectrum disorder.
Fetal alcohol spectrum disorder (FASD) is a major public health issue that encompass an array of physical, neurological, and behavioral effects due to alcohol consumption during pregnancy. The classical biomarkers of FASD that are currently used lack sensitivity and specificity, and as such there is an opportunity through the use of novel metabolomics analysis to identify new biomarkers to identify those at risk for FASD, which could more effectively aid in early intervention. The focus of this minireview is to identify current work that is being done in the field of metabolomics in FASD in utero, and to highlight promising metabolites that could act as biomarkers in the future. We will conclude with suggestions for further research, as there is a large gap of knowledge in this particular area of metabolomics.


Method of fixation does not influence the overall risk of rerevision in first-time cup revisions.
During the last two decades, uncemented fixation has been increasingly preferred worldwide during cup revision surgery. In Sweden, the number of uncemented cup revisions has been increasing during the last decade. However, it is unclear whether the risk of rerevision differs between cemented and uncemented cups. We determined (1) the risk of rerevision after cemented and uncemented fixation; (2) the influence of concomitant stem revision on the risk of rerevision of the cup; (3) the difference in risk of rerevision of an uncemented cup revision compared with liner revision only; and (4) whether the surgical incision influenced the risk of rerevision. Between 1979 and 2010, 19,342 first-time cup revisions were reported to the Swedish Hip Arthroplasty Register. From these, 749 were excluded (hip resurfacing, cases with tumor diagnoses, and missing data) leaving 18,593 (73% cemented) for further analysis. We used a Cox regression model adjusted for age, sex, primary diagnosis, method of fixation, concomitant stem revision, and cemented/uncemented fixation to assess risk of rerevision. The relative risk for rerevision for any reason did not differ between cemented and uncemented fixation (relative risk [RR], 0.94). If the stem was not revised at index revision, the risk of further cup revision increased twofold (RR, 1.91). Liner revisions were associated with a 70% increased risk for rerevision of the cup as a result of any reason and especially because of dislocation (RR, 2.94). The surgical incision did not influence the overall risk for rerevision (direct lateral/posterolateral: RR, 1.02) or the risk of rerevision resulting from dislocation (RR, 0.91). We found no difference in the overall risk of rerevision between cemented and uncemented fixation. Liner exchange had a higher risk for rerevision when compared with cases being rerevised with a new uncemented cup.


Role-taking skills and perceived similarity in baccalaureate nursing students.
The importance of exercising effective role-taking skills as a nursing care provider is described. Twenty-six baccalaureate nursing students provided role-taking responses to four real life events. Students also reported whether or not they had ever experienced similar events and to what degree they perceived themselves as similar to the individuals in the events on a number of personal characteristics. Role taking was compared across the situations. Having experienced a similar life event or perceiving similarity to the main character did not appear to enhance role-taking responses. The results suggest that it may not be necessary to have had a life experience or background similar to that of the client's in order to be perceived as a nurse who is caring and understanding. Implications for nursing students are discussed.


Lymphocytic bronchitis unrelated to acute graft-versus-host disease in canine marrow graft recipients.
We reviewed coded autopsy material from 71 dogs, 46 receiving allogeneic and 25 receiving autologous bone marrow transplants, to evaluate the hypothesis that lymphocytic bronchitis is associated with severe acute graft-versus-host disease (GVHD). We found no significant correlation between the presence of lymphocytic bronchitis and severe acute GVHD (P greater than 0.16). Using a binary regression model that corrected for possible confounding relationships, we failed to show a correlation between lymphocytic bronchitis and acute GVHD of each of the 3 classically affected organ systems. Also, no correlation was found between lymphocytic bronchitis and acute bacterial pneumonia (P greater than 0.32). Finally, lymphocytic bronchitis was present in autografted dogs with a prevalence at autopsy not significantly different from that of allografted dogs (P greater than 0.32). We conclude that lymphocytic bronchitis in this canine model represents nonspecific inflammation rather than acute pulmonary GVHD.


Vocal and finger reaction times in stutterers and nonstutterers: differences and correlations.
The purposes of this study were (a) to assess whether the slower reaction times of stutterers are related to the etiology of the disorder or whether they are a by-product of it, and (b) to see if previously reported correlations between vocal and manual reaction times resulted from large numbers of trials. Fourteen adult stutterers and matched controls said "uh" or pressed a button in response to the offset of tones varying randomly in duration. Ten trials were used. The stutterers were significantly slower in both speech and nonspeech tasks, but the correlations between voice and manual reaction times were not significant. This suggested that stutterers' slower reaction times may be obtained without using large numbers of trials and that the correlation between the two tasks may depend on the number of trials used. The stutterers showed a significantly larger difference between vocal and manual reaction times than the nonstutterers. This suggested that the slower reaction times of stutterers are not entirely a by-product of the disorder.


A Direct Demonstration of Functional Differences between Subdivisions of Human V5/MT.
Two subdivisions of human V5/MT+: one located posteriorly (MT/TO-1) and the other more anteriorly (MST/TO-2) were identified in human participants using functional magnetic resonance imaging on the basis of their representations of the ipsilateral versus contralateral visual field. These subdivisions were then targeted for disruption by the application of repetitive transcranial magnetic stimulation (rTMS). The rTMS was delivered to cortical areas while participants performed direction discrimination tasks involving 3 different types of moving stimuli defined by the translational, radial, or rotational motion of dot patterns. For translational motion, performance was significantly reduced relative to baseline when rTMS was applied to both MT/TO-1 and MST/TO-2. For radial motion, there was a differential effect between MT/TO-1 and MST/TO-2, with only disruption of the latter area affecting performance. The rTMS failed to reveal a complete dissociation between MT/TO-1 and MST/TO-2 in terms of their contribution to the perception of rotational motion. On the basis of these results, MT/TO-1 and MST/TO-2 appear to be functionally distinct subdivisions of hV5/MT+. While both areas appear to be implicated in the processing of translational motion, only the anterior region (MST/TO-2) makes a causal contribution to the perception of radial motion.


Carbon Nanomaterials Alter Global Gene Expression Profiles.
Carbon nanomaterials (CNMs), which include carbon nanotubes (CNTs) and their derivatives, have diverse technological and biomedical applications. The potential toxicity of CNMs to cells and tissues has become an important emerging question in nanotechnology. To assess the toxicity of CNTs and fullerenol C60(OH)24, we in the present work used the budding yeast Saccharomyces cerevisiae, one of the simplest eukaryotic organisms that share fundamental aspects of eukaryotic cell biology. We found that treatment with CNMs, regardless of their physical shape, negatively affected the growth rates, end-point cell densities and doubling times of CNM-exposed yeast cells when compared to unexposed cells. To investigate potential mechanisms behind the CNMs-induced growth defects, we performed RNA-Seq dependent transcriptional analysis and constructed global gene expression profiles of fullerenol C60(OH)24- and CNT-treated cells. When compared to non-treated control cells, CNM-treated cells displayed differential expression of genes whose functions are implicated in membrane transporters and stress response, although differentially expressed genes were not consistent between CNT- and fullerenol C60(OH)24-treated groups, leading to our conclusion that CNMs could serve as environmental toxic factors to eukaryotic cells.


Fluid responsiveness and right ventricular function in cardiac surgical patients. A multicenter study.
We investigated fluid responsiveness in a population of patients undergoing coronary artery revascularization, with respect to their right ventricular ejection fraction. This was a multicenter trial involving 11 cardiac surgical Institutions and 65 patients undergoing elective coronary artery revascularization. Hemodynamic parameters were measured before and after volume expansion using a modified pulmonary artery catheter and transesophageal echocardiographic monitoring. Patients demonstrating an increase of stroke volume >20% after volume expansion were considered as responders. Volume expansion with 7 ml/kg of plasma expander was performed when required on a clinical basis. In the overall population, only the change in aortic blood velocity (cut-off 13%) was a predictor of fluid responsiveness. In patients with a reduced (<0.3) right ventricular ejection fraction only the value of mean pulmonary arterial pressure was predictive of fluid responsiveness (cut-off 18 mmHg). Patients with right ventricular ejection fraction ≥0.3 demonstrated three predictors: changes in aortic blood velocity (cut-off 15%), right ventricular end diastolic volume index (cut-off 80 ml/m(2)), and left ventricular end diastolic area index (cut-off 9 cm(2)/m(2)). When right ventricular systolic function is depressed, the right ventricle inability to fill the left chambers results in a lack of the left-sided responsiveness predictors. When the right ventricular systolic function is preserved, all the classical fluid responsiveness predictors are confirmed. Right ventricular function is therefore to be always considered when addressing the problem of fluid responsiveness.


Heterogeneous sensitivity of cerebral and muscle tissues to acute normobaric hyperoxia at rest.
The purpose was to investigate the effects of acute normobaric hyperoxia at rest on cerebral, respiratory and leg muscle oxygenation. Ten healthy men were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air and on the other 100% normobaric O(2) for a 2-hour time period. Oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total (Δ[tHb]) hemoglobin in the cerebral frontal cortex, and in the intercostal and vastus lateralis muscles were simultaneously monitored with near-infrared spectroscopy. The hyperoxic stimulus promptly increased Δ[O(2)Hb] (~2 μM) and decreased Δ[HHb] (~3.6 μM) in the frontal cortex. These cerebral responses were directly and fully countered by resumption of normoxic air breathing. In contrast, Δ[HHb] significantly decreased due to the acute hyperoxic stimulus in both intercostal and vastus lateralis muscles. The temporal changes in muscle oxygenation were slower compared to those in the cerebral area; and they only partially recovered during the 15-min normoxic-recovery period. Acute supplementation of normobaric O(2) at rest influences cerebral, leg and respiratory muscle oxygenation of healthy individuals, but not in the same manner. Namely, the frontal cortex seems to be more sensitive to hyperoxia than are the skeletal muscle regions.


Effects of plastic anti-pecking devices on food intake and behaviour of laying hens fed on pellets or mash.
1. This study investigated effects of plastic anti-pecking devices on food intake and behaviour to assess their applicability in commercial layer flocks. 2. In experiment 1, 72 individually caged ISA Brown pullets were fitted at 16 weeks of age (point of lay) with either 'ring' or 'bumper' beak devices or no device (control), half being fed on pellets and half on mash. The devices were held in place by lugs inserted in the nares. 3. There was evidence of discomfort immediately after fitting the devices, but not thereafter. In the first week, the devices reduced food intake, and were removed from 7 (15%) birds that lost weight consistently. Between 16 and 21 weeks, however, there were no significant effects of beak treatment or food form on either total food intake or egg production with the 65 remaining birds. 4. Beak treatment did not affect feeding efficiency (food intake per minute of feeding). The only behaviour affected was pecking at birds in adjacent cages, which was reduced with the ring device. 5. At 21 weeks, the birds were placed together in groups of 4 to 6 in 12 pens, each group consisting of birds from one of the 6 original treatments, and their behaviour was observed in experiment 2 between 21 and 23 weeks. 6. The only effects of beak treatment on behaviour were that pecking at pen walls was increased with the ring device, while pulling and eating feathers from group mates was seen mainly with control birds fed on pellets. Two birds were cannibalised in a control group on pellets. 7. Devices came off 3 (7%) birds in experiment 1 and were replaced, and rings slipped over lower mandibles of 2 (5%) birds in experiment 2 and were corrected. 8. At 23 weeks, beak lengths were increased with ring and bumper treatments, and pecking damage scores were low with all treatments. 9. It is concluded that these devices are not applicable commercially, but further trials would be justified with new improved designs.


Parallel adaptation in autopolyploid Arabidopsis arenosa is dominated by repeated recruitment of shared alleles.
Relative contributions of pre-existing vs de novo genomic variation to adaptation are poorly understood, especially in polyploid organisms. We assess this in high resolution using autotetraploid Arabidopsis arenosa, which repeatedly adapted to toxic serpentine soils that exhibit skewed elemental profiles. Leveraging a fivefold replicated serpentine invasion, we assess selection on SNPs and structural variants (TEs) in 78 resequenced individuals and discover significant parallelism in candidate genes involved in ion homeostasis. We further model parallel selection and infer repeated sweeps on a shared pool of variants in nearly all these loci, supporting theoretical expectations. A single striking exception is represented by TWO PORE CHANNEL 1, which exhibits convergent evolution from independent de novo mutations at an identical, otherwise conserved site at the calcium channel selectivity gate. Taken together, this suggests that polyploid populations can rapidly adapt to environmental extremes, calling on both pre-existing variation and novel polymorphisms.


Movement-provoked muscle torque and EMG activity in longstanding motor complete spinal cord injured individuals.
Muscle resistance was evaluated by measurement of movement-provoked torque performed during simultaneous thigh muscle EMG recordings in individuals with a motor complete spinal cord injury (SCI). Fifteen men with a motor complete (ASIA grade A or B) cervical injury participated in the study. The activity started at an average of 0.11 seconds after the start of the provoking movement as evidenced by EMG recordings. However, no activity at all was found before the end of the movement provocation for 0.3 seconds in >60% of the test situations, whereas muscle torque was recorded in all cases. Significantly higher resistive muscle torque (p = 0.049) was provoked during extension movement compared with that of flexion. On the contrary, the maximum muscle activity was significantly higher (p = 0.009) during flexion movement compared with that during extension, with no differences between muscle groups. The resistive muscle torque seems to measure the passive viscoelastic component rather then the active spastic component of the movement-provoked muscle resistance in our group of motor complete SCI individuals.


Efficient transfection method for primary cells.
Transfection of primary cells and stem cells is a problem in the laboratory routine and further in tissue engineering and gene therapy. Most methods working effectively for cell lines in culture fail to transfect primary cells. Here we describe the use of the Nucleofector technology developed by amaxa biosystems. We were able to transfect primary human melanocytes, human coronary smooth muscle cells, human chondrocytes, and human mesenchymal stem cells with high efficiencies (28.9-45.3%). All primary cell types failed to be transfected satisfactorily by methods based on liposome-mediated transfection in our hands. The viability of the transfected cells varied between 11.2% and 75% in comparison to untreated cells. Only 200,000 cells per transfection sample were needed. In summary, this method presents an effective and fast mean for transfection of primary and stem cells demonstrated by four cell types which are only transfected with low efficiency by other methods.


[Analysis of the control level and the affecting factors in 4-11 years old children with asthma].
To assess the control level of 4-11 years old children with asthma and to explore the correlative factors affecting the control level of asthma. One cross-sectional study was conducted of the 4-11 years old children with asthma from Pediatrics Outpatient Department of Peking University Third Hospital from October 2013 to February 2014. According to asthma control test (ACT), the control levels of asthma children could be divided into three levels: fully controlled, partly controlled and non-controlled. The partly controlled group and the non-controlled group were merged into the non-full controlled group. Life quality was compared between the full controlled group and the non-full controlled group. The correlative factors affecting the controlled level of asthma were analyzed by Logistic regression. The correlative case information was collected and the data were entered with EpiData software and analyzed with SPSS 17.0 software. Ninety asthma children were enrolled.The children from the full controlled group and the non-full controlled group accounted for 61.1% (55/90) and 38.9% (35/90), respectively. Life quality of the full controlled group was higher than that of the non-fully controlled group. There was no significant difference between the two groups on body mass index (BMI), education level of parents, parents or relative smoking, times of respiratory tract infection within 3 months, using asthma control drugs within 4 weeks before seeing a doctor and regularly taking medicine according to the doctor's advice (P>0.05). The binary Logistic regression analysis obtained three correlative factors affecting the control level of asthma: non-regular follow-up (OR=8.364, 95%CI: 1.816-38.532, P<0.05), being diagnosed with or suffering from allergic rhinitis (OR=6.728, 95% CI: 1.699-26.644, P<0.05) and accompanying with other allergic diseases (OR=3.926, 95%CI: 1.210-12.744, P<0.05). The results from the single center have shown that the asthma full-controlled rate of 4-11 years old children with asthma is not high. The higher control level, the better the life quality. Non-regular follow-up and being diagnosed with or suffering from allergic rhinitis are the correlative factors affecting the control level of 4-11 years old children with asthma. Meanwhile, accompanying with other allergic diseases, such as atopic dermatitis and food allergy is the protective factor for asthma control. The data from the multi-center and further study will be needed to demonstrate the results of this study.


B lymphocytes repress hepatic tumorigenesis but not development in Hras12V transgenic mice.
Increasing reports show noninflammation underlying HCC, challenging our understanding of the roles of the immune system in hepatocarcinogenesis. By exploring a mouse model of hepatic tumor induced by hepatocyte-specific expression of the Hras12V oncogene without obvious inflammation, we found that the proportion of B cells, but not T cells, progressively and significantly decreased in 3, 5-month-old transgenic mice (Tg) compared with non-transgenic mice. Notably, the proportions of total and activated B and T cells all significantly decreased in 9-month-old Tg with multiple massive hepatic tumors. Together with the decreased B cell proportion, serum IgG1/2 also significantly decreased in 5, 9-month-old Tg. Interestingly, homozygous Tg showed significantly higher B cell proportion and IgG2 levels, accompanied by significantly lower incidences of liver nodules but not adenomas and carcinomas compared with heterozygous Tg. Treatment of Tg with PCI-32765, a potent Bruton's tyrosine kinase (BTK) inhibitor for suppressing B cell proliferation and activation, significantly decreased the B cell proportion and IgG2 levels, accompanied by a significantly higher incidence of liver nodules, but had no effects on adenoma and carcinoma. Treatment of Tg with insulin-like growth factor 1 (IGF-1) significantly increased the B cell proportion and IgG2 levels, accompanied by a significantly lower incidence of liver nodules and carcinoma, but had no effects on adenoma. Conclusively, B cells and IgG2 may play important roles in suppressing hepatic tumorigenesis, but not development. In addition, hepatocyte-specific expression of the ras oncogene may play roles in suppressing B cells, while developed hepatic tumors suppress both B and T cells.


The coamplification pattern of the MYCN amplicon is an invariable attribute of most MYCN-amplified human neuroblastomas.
Fifteen percent to 20% of human neuroblastomas show amplification of the MYCN oncogene physiologically located at chromosome 2p24-25, indicating an aggressive subtype of human neuroblastoma with a poor clinical outcome. Recent findings revealed that the structure of the amplicon differs interindividually and that coamplification of genes in telomeric proximity to MYCN might play a relevant role in neuroblastoma development and response to treatment, respectively. We now asked if the amplicon structure is an invariable attribute of an individual tumor or if the coamplification pattern could change during progress or in case of recurrent disease. We used a previously described multiplex PCR approach to analyze the coamplification status of MYCN-amplified human neuroblastomas (n = 33) in tumor tissue at the time of initial diagnosis and in consecutive tissue specimens at later time points after initial treatment or from relapsing disease. The MYCN copy number per haploid genome (Mcn/hg) in these specimens was determined in a separate duplex PCR. In 32 of the 33 investigated tumors, the amplicon structure showed no changes after initial chemotherapy and in recurrent disease. Mcn/hg showed a decrease after initial treatment (n = 23), whereas we found a significant increase in recurrent disease (n = 10). Our data indicate that the initial determined structure of the 2p24-25 amplicon is a consistent attribute in the great majority of the individual MYCN-amplified neuroblastomas and shows no plasticity during or after chemotherapy. Observed changes in the Mcn/hg over the course of disease are in line with preexisting cell culture findings.


Influence of interference among parallel absorbers on acoustic characteristics of an absorbing panel.
This paper proposes a modified theory for synthesizing the acoustic impedance of an absorbing panel by considering the interference among parallel absorbers. The absorbing panel comprises periodically distributed absorbers with different acoustic characteristics, and the periodic distribution allows the impedance of the panel to be characterized by that of a unit cell. However, at frequencies between the resonances of the absorbers in the unit cell, the unit-cell impedance given by traditional theory deviates significantly from that given by a finite-element model. Inspecting the flow field near the surface of the unit cell reveals that the out-of-phase flow plays an important role in the interaction among the parallel absorbers and induces the deviation. A modified theory is proposed by multiplying the original resultant impedance by a factor that considers the interaction. The modified theory is verified by numerical results for several typical absorbing panels with different patterns of unit cells and different geometrical parameters of absorbers, and experimental validation is also carried out. As further evidence for the correctness and universality of the modified theoretical model, a comparison is presented with the mutual-radiation-impedance theoretical model based on a Helmholtz resonator array panel. The results of validation on different absorbing panels and the comparison with the mutual-radiation-impedance method show that the modified theoretical model is better at predicting the absorption coefficient than is the traditional theory.


Fetal type 2 pneumocytes form alveolar-like structures and maintain long-term differentiation on extracellular matrix.
We investigated the effects of reconstituted basement membrane (a crude extract of the Engelbreth-Holm-Swarm tumor) on type 2 pneumocyte differentiation during long-term culture. Cells were derived from mature 29 d fetal rabbits. Morphology was studied by light and electron microscopy. On thin gel, the cells initially segregated into clumps; they were cuboidal with apical microvilli and contained lamellar bodies, but dedifferentiated by 8 d. On thick gel, epithelial cells associated into spherical clusters surrounding a central lumen. These alveolarlike structures persisted at least 22 d. The cells were cuboidal and had lamellar bodies and intercellular tight junctions; they exhibited polarity, with apical microvilli facing the lumen, basally located nuclei, and gel matrix abutting the basal surface. In contrast, cells cultured on plastic formed colonies, then a monolayer, but dedifferentiated 5-7 d after plating. [14C]Acetate was used to label newly synthesized phospholipids. The amount of disaturated phosphatidylcholine (DSPC), expressed as a percentage of total phosphatidylcholine (PC), was used as an indicator of surfactant lipid production; percentage DSPC synthesized by cells cultured on thick gel did not change significantly, from 55 +/- 3 at 3 d, to 63 +/- 2 at 22 d in culture. DSPC synthesized by cells cultured on plastic decreased from 57 +/- 1% at 3 d to 45 +/- 2% at 22 d (p less than 0.001), which is consistent with the morphologic evidence of dedifferentiation. Synthesis of total PC compared with total phospholipid did not vary with either time in culture or substrate. This study emphasizes the importance of a complex extracellular matrix for maintenance of type 2 pneumocyte differentiation. The system should prove useful for studying the interaction of these cells with basement membrane, including the role of events occurring at the cell surface in modulating expression of a differentiated phenotype.


Dietary intake of boiled breadfruit (Treculia africana) seeds did not improve hyperglycemia in streptozotocin induced diabetic rats: Effect on the oral glucose tolerance of normoglycemic rats.
Although African breadfruit (Treculia africana) is said to be useful in the dietary management of diabetes, the effect of cooking on its glycemic index has not been reported. Hence this study has investi- gated the effect of a dietary intake of boiled breadfruit on the serum glucose, glucose tolerance, body weights and relative organ weights of streptozotocin (STZ) induced diabetic rats. Twenty albino rats were used and were divided into four groups of five rats. Groups 1 (normal control) and 2 (diabetic control) received standard rat pellets while groups 3 (diabetic-test group) and 4 (non-diabetic) rats received breadfruit. The blood glucose of the normoglycemic rats fed standard rat feeds peaked at 30 min (149.75 ±11.12 mg/dl) following oral glucose loading (3 g/kg) but reduced to 85.25 ±21.05 mg/dl after another 90 min, while the blood glucose of the normoglycemic rats fed breadfruit peaked at 30 min (146.25 ±15.22 mg/dl) follow- ing oral glucose loading, but elevated (130.75 ±36.69 mg/dl) after another 90 min. There was significant elevation (P < 0.05) of the serum glucose, relative liver weight (RLW) and relative kidney weight (RKW) but a significant decrease in the body weights of the diabetic control compared with the normal control; no sig- nificant difference (P > 0.05) in the serum glucose, body weights, RLW and RKW of the test group compared with the diabetic control, and no significant differences (P > 0.05) in the serum glucose, body weights, RLW and RKW of the normal rats fed the breadfruit diet compared to the normal control. The study showed that the traditional method of cooking African breadfruit negatively affects its hypoglycemic property.


Enhanced release of rosmarinic acid from Coleus blumei permeabilized by dimethyl sulfoxide (DMSO) while preserving cell viability and growth.
Continuous permeabilization of preconditioned Coleus blumei cells with dimethyl sulfoxide (DMSO) is shown to be an effective strategy for the enhanced release of rosmarinic acid (RA) while preserving cell viability. When nonpreconditioned cells were permeabilized with DMSO, they lost their viability at DMSO concentrations higher than a critical value located between 0.1% and 0.5% DMSO. Product release was low [0.49 g RA/100 g dry cell weight (DCW)] at 0.1% DMSO. Preconditioning cells at 0.1% DMSO ensured high viability at DMSO concentrations of 0.5%, 1.0%, and 1.5%. Product release reached a maximum of 2.85 g RA/100 g DCW at 0.5% DMSO, which was 66.4% of the total rosmarinic acid produced.


Preclinical evaluation of antitumor activity of acid-sensitive PEGylated doxorubicin.
The acid-sensitive PEGylated doxorubicin (DOX) with exact chemical structure was designed and prepared as a potential tumor intracellular microenvironment-responsive drug delivery system. First, the insensitive succinic anhydride-functionalized DOX (i.e., SAD) and acid-sensitive cis-aconitic anhydride-modified DOX (i.e., CAD) were synthesized through the ring-opening reaction. Subsequently, the insensitive and acid-sensitive PEGylated DOX (i.e., mPEG-SAD and mPEG-CAD) was prepared by the condensation reaction between the terminal hydroxyl group of mPEG and the carboxyl group in SAD and CAD, respectively. The obtained mPEG-SAD and mPEG-CAD could spontaneously self-assemble into micelles in phosphate-buffered saline at pH 7.4 with diameters of about 100 nm. The DOX release of mPEG-CAD micelle could be accelerated by the decrease of pH from 7.4, 6.8, to 5.5 in relation to that of mPEG-SAD micelle. On the other hand, the result of the cellular proliferation inhibition test indicated that mPEG-CAD micelle exhibited favorable antiproliferative activity in vitro. In addition, the selective intratumoral accumulation and antitumor efficacy of mPEG-CAD micelle were significantly better than those of free DOX and mPEG-SAD. More importantly, the prodrug micelles exhibited upregulated security in vivo as compared to free DOX. Overall, the mPEG-CAD micelle with enhanced antitumor efficacy and decreased side effects was a fascinating prospect for the clinical chemotherapy of malignancy.


Iterative time-reversed ultrasonically encoded light focusing in backscattering mode.
The Time-Reversed Ultrasound-Encoded (TRUE) light technique enables noninvasive focusing deep inside scattering media. However, the time-reversal procedure usually has a low signal-to-noise ratio because the intensity of ultrasound-encoded light is intrinsically low. Consequently, the contrast and resolution of TRUE focus is far from ideal, especially in the backscattering geometry, which is more practical in many biomedical applications. To improve the light intensity and resolution of TRUE focus, we developed an iterative TRUE (iTRUE) light focusing technique that employs the TRUE focus itself as a signal source (rather than diffused light) for subsequent TRUE procedures. Importantly, this iTRUE technique enables light focusing in backscattering mode. Here, we demonstrate the concept by focusing light in between scattering layers in a backscattering configuration and show that the light intensity at the focus is progressively enhanced by a factor of ~20. By scanning across a fluorescent bead between these two scattering layers, the focusing resolution in the ultrasound axial and lateral directions was improved ~2-fold and ~3-fold, respectively. We further explored the application of iTRUE in biological samples by focusing light between 1 mm thick chicken tissue and cartilage, and light intensity enhancements of the same order were also observed.


Oral hygiene, periodontal conditions and carious lesions in patients treated with dental bridges. A 15-year clinical and radiographic follow-up study.
A longitudinal study, extending over a period of 15 years, was carried out in a group of 102 patients who received 108 bridges made by the senior students at the Dental Faculty, University of Oslo, in 1967/68. The study included 343 abutment teeth, and the remaining teeth in the same jaw which received the restoration, 525 in all, served as control. The oral hygiene, gingival condition, pocket depth, caries on crowned teeth, location of crown margins and changes of alveolar bone level were recorded during the study. During the first 10 years, the patients received oral hygiene prophylaxis every 6 months. The mean age of the patients at the beginning of the study was 48 years. Of the original group of 102 patients, 88 attended the clinical examination after 5 years, 71 after 10 years, and 55 after 15 years. The amount of plaque did not differ between the crowned teeth and the control teeth during the observation period, while GI score 2 and 3 was more frequent in crowned teeth than in the control teeth during this period. This was mainly observed when the crown margins were located sub-gingivally. A slight increase in mean pocket depth was recorded in the crowned teeth while the mean pocket depth for the control teeth remained at the same level during the 15 years. Caries lesions were recorded in 3.3% of the abutment tooth surfaces at the 5th year, in 10.0% at the 10th year and in 12.0% at the 15th year examination. No statistical differences in bone loss could be detected between the control teeth and the crowned teeth.


Influence of antibiotic therapy on faecal carriage of P-fimbriated Escherichia coli and other gram-negative bacteria in neonates.
The influence of previous antibiotic therapy on the aerobic faecal flora, including P-fimbriated Escherichia coli, was studied in 953 neonates at discharge from 22 neonatal wards in Sweden. Antibiotics, mainly ampicillin (with or without gentamicin) or cefuroxime, had been received by 37% of the infants. Treatment with ampicillin (with or without gentamicin) increased Klebsiella/Enterobacter and reduced Esch. coli colonization. Cephalosporin therapy (71% cefuroxime) reduced the frequency of colonization with both Esch. coli and Klebsiella/Enterobacter spp. but doubled the isolation rate of other Gram-negative bacteria (Citrobacter, Pseudomonas, Proteus and Acinetobacter spp.) and tripled the incidence of specimens yielding no aerobic Gram-negative growth. Gentamicin showed no significant ecological impact. The selection of Klebsiella/Enterobacter and P-negative Esch. coli strains by ampicillin was correlated with their resistance to this agent, while the association between P-fimbriated Esch. coli and cefuroxime therapy was not related to cefuroxime resistance.


Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.
Alzheimer's disease (AD) is one of the progressive neurodegenerative diseases characterized by β-amyloid (Aβ) production and Phosphorylated-Tau (p-Tau) protein in the cerebral cortex. The precise mechanisms of the cause, responsible for disease pathology and progression, are not well understood because there are multiple risk factors associated with the disease. Viral infection is one of the risk factors for AD, and we demonstrated that Zika virus (ZIKV) infection in brain organoids could trigger AD pathological features, including Aβ and p-Tau expression. AD-related phenotypes in brain organoids were upregulated via endoplasmic reticulum (ER) stress and unfolded protein response (UPR) after ZIKV infection in brain organoids. Under persistent ER stress, activated-double stranded RNA-dependent protein kinase-like ER-resident (PERK) triggered the phosphorylation of Eukaryotic initiation factor 2 (eIF2α) and then BACE, and GSK3α/β related to AD. Furthermore, we demonstrated that pharmacological inhibitors of PERK attenuated Aβ and p-Tau in brain organoids after ZIKV infection.


Correlation between enhancement pattern of hepatocellular carcinoma on real-time contrast-enhanced ultrasound and tumour cellular differentiation on histopathology.
The objective of this study was to evaluate the correlation between the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) and tumour cellular differentiation on histopathology. 189 HCC lesions in 189 patients were retrospectively evaluated with CEUS and histopathological examination. CEUS was performed with SonoVue and contrast pulse sequencing. Histopathological diagnoses were made according to the Edmonson grading system. Significant differences were shown between the time that the HCC became hypoenhancing or remained echogenic in late phase and tumour cellular differentiation (p = 0.006; p = 0.036), but not with the time of commencement of hyperenhancing or commencement of isoenhancing in arterial phase and portal phase (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The timing of HCC becoming hypoenhancing on CEUS is correlated with tumour cellular differentiation; well differentiated tumours wash out more slowly than poorly differentiated ones.


The tyrosine kinase inhibitor AG126 restores receptor signaling and blocks release functions in activated microglia (brain macrophages) by preventing a chronic rise in the intracellular calcium level.
We recently reported that lasting activation of mouse microglial cells with bacterial lipopolysaccharide (LPS) chronically elevated the basal intracellular calcium concentration ([Ca2+]i). This correlated to an attenuated calcium signaling of complement (C5a) and purinergic (UTP) receptors as well as to the capacity for effective production of cytokines-chemokines. Here, we demonstrate that these adjustments in the [Ca2+]i regulation require a critical protein tyrosine kinase (PTK) function--even in varying stimulation scenarios. Changes in basal [Ca2+]i and calcium signaling are not restricted to Gram-negative bacterial confrontation. Pneumococcal cell wall (PCW) modelling Gram-positive infection causes virtually the same effects. Moreover, decreases in calcium signaling efficacy are neither associated with altered receptor expression, nor mediated by autocrine loops. Administration of microglial release products, transfer of conditioned supernatant or presence of a radical scavenger during LPS or PCW treatments have no consequence. However, both the elevation in basal [Ca2+]i as well as the suppression of C5a- and UTP-evoked calcium signals are selectively and dose-dependently reversed by tyrphostin AG126, a PTK inhibitor that, moreover, blocks inducible nitric oxide and cytokine-chemokine release. The findings suggest that the AG126-sensitive PTK critically controls both sensory and executive features of the microglial activation process via sustained up-regulation of basal [Ca2+]i.


The influence of tamoxifen on the secretion of transforming growth factor-beta2 (TGF-beta2) in glioblastomas: in vitro and in vivo findings.
Only a minority of patients with malignant gliomas respond to continuous high-dose tamoxifen (TAM) treatment. Therefore a method to predict the efficiency of TAM-treatment would be desirable. Analogous to previous studies in breast cancer patients, we investigated whether the dynamics of TGF-beta2 plasma levels allow the prediction of response to TAM-treatment in glioblastoma patients as well. TGF-beta2 plasma levels of glioblastoma patients treated with 200 mg TAM/day on a continuous basis and of control patients not treated with TAM were measured by using an ELISA. In addition, the effect of TAM and 4-OH-TAM on the secretion of TGF-beta2 by established glioma cell lines as well as the effect of TGF-beta2 itself on cell proliferation were investigated in vitro. The effect of TAM on TGF-beta2 plasma levels did not correlate with the clinical response to TAM-therapy in glioblastoma patients. The in vitro experiments showed that TAM and 4-OH-TAM stimulate established glioma cell lines to increase their secretion of TGF-beta2. Externally added TGF-beta2 (nM) had no effect on cell proliferation of the same cell lines. In contrast to breast cancer patients, the clinical response to TAM in glioblastoma patients is not reflected by changes of TGF-beta2 plasma levels. It has to be assumed that, despite an increase of TGF-beta2 production by glioblastoma cells in response to TAM in vitro, such elevated production in vivo does not reach the plasma due to either the lower tumor burden in glioblastoma disease compared to breast cancer patients or due to some local sequestration process.


Suicide intervention skills in health professionals: a multidisciplinary comparison.
Training in the recognition and management of suicidal risk is of crucial importance for prevention. The aim of our study was to compare competence in assessing and managing suicidal patients in different groups of Italian professionals. Two hundred and thirty two professionals (38 psychiatrists, 50 general practitioners, 34 psychiatric nurses, 60 doctors and nurses working in accident and emergency services, and 50 medical students) completed the Suicide Intervention Response Inventory (SIRI-2) (Neimeyer & Bonelle, 1997) and a questionnaire on perceptions of risk and protective factors in suicidal patients. Exposure to suicidal patients was found to be widespread in all groups, but specific training in suicide assessment and intervention was conspicuously rare. Psychiatrists outscored all other groups and psychiatric nurses scored significantly higher than general practitioners in identifying appropriate responses to suicidal patients. Taken together, our findings suggest the necessity of further training in suicide intervention for Italian health professionals, and especially for emergency service personnel and general practitioners.


Nicotinic acetylcholine receptor alpha5 subunits modulate oxotremorine-induced salivation and tremor.
Neuronal nicotinic acetylcholine receptors (nAChRs) are composed of 12 subunits (alpha2-alpha10 and beta2-beta4). alpha5 Subunits, expressed throughout the central nervous system (CNS) and the autonomic nervous system (ANS), possess unique pharmacological properties. The effects of oxotremorine (OXO) on autonomic functions and tremor were examined in mice lacking alpha5 nAChR subunits (alpha5-/-) and compared with those in wild-type (WT) control mice. The alpha5-/- mice showed significantly increased salivation and tremor responses to OXO. The hypothermia, bradycardia and defecation induced by OXO were of similar magnitudes in the two mouse strains. The enhanced OXO effects in alpha5-/- mice indicate inhibitory effects of alpha5 subunits in autonomic ganglia, and support the participation of these subunits in cholinergic transmission in autonomic ganglia.


Detection of spatially regulated gene expression by hybridization histochemistry.
Steady state measurements of kidney androgen-regulated protein (KAP) mRNA suggested that KAP gene expression was unusually sensitive to low hormone-receptor levels. Two of the criteria used to reach this conclusion involved relative insensitivity to treatment with a competitive antiandrogen and a partial androgen response of the gene in Tfm/Y androgen receptor (AR) deficient mice. These data may indicate the ability of the KAP gene to respond to an extremely low level of androgen-AR complex or that the effect of androgens is, at least in part, indirect. Hybridization in situ revealed that KAP mRNA expression was restricted to proximal tubule epithelial cells in the juxtamedullary region of castrated animals rather than throughout the cortex as in intact males. Examination of sections of kidneys from Tfm/Y mice before and after testosterone (T) treatment revealed that only the juxtamedullary tubules expressed KAP mRNA and that T increased the level of KAP mRNA in these cells. Treatment of Tfm/Y animals with other steroids showed that beta-estradiol treatment mimicked the effect of T while dihydrotestosterone (DHT) had no effect. The facts that DHT and T both stimulate cortical expression of KAP mRNA in normal animals but DHT has no effect on the juxtamedullary cells in the Tfm/Y variant may indicate that the action of T is due to an estrogenic metabolite. Castrated, hypophysectomized males exhibited no KAP gene expression, while in the presence of T, expression was observed throughout the cortex as in intact males. These results clearly indicate the involvement of pituitary hormones in KAP gene expression in the juxtamedullary tubules. These studies have shown that the regulation of KAP gene expression in the mouse kidney is much more complex than originally believed. Future studies will further investigate the roles of estrogen and specific pituitary hormones in KAP gene expression.


The TeraFERMI terahertz source at the seeded FERMI free-electron-laser facility.
We describe the project for the construction of a terahertz (THz) beamline to be called TeraFERMI at the seeded FERMI free electron laser (FEL) facility in Trieste, Italy. We discuss topics as the underlying scientific case, the choice of the source, the expected performance, and THz beam propagation. Through electron beam dynamics simulations we show that the installation of the THz source in the beam dump section provides a new approach for compressing the electron bunch length without affecting FEL operation. Thanks to this further compression of the FEL electron bunch, the TeraFERMI facility is expected to provide THz pulses with energies up to the mJ range during normal FEL operation.


Strategy for Quantitative Analysis of Isomeric Bis(monoacylglycero)phosphate and Phosphatidylglycerol Species by Shotgun Lipidomics after One-Step Methylation.
Understanding the cellular function and metabolism of bis(monoacylglycero)phosphate (BMP), an important but low-abundance class of phospholipids, has been hindered due to its difficulties to be resolved from its structural isomer (i.e., phosphatidylglycerol, PG, another low-abundance class of phospholipids). A novel strategy for quantitative analysis of BMP and PG species was developed after one-step methylation of lipid extracts in combination with high mass accuracy/resolution mass spectrometry after direct infusion (i.e., shotgun lipidomics). The novel strategy was applied for quantitative analysis of mouse hepatic BMP and PG species and their changes induced by long-term high-fat diet (HFD) feeding. Interestingly, we revealed that HFD-fed mice display a dramatic accumulation of hepatic BMP compared to chow-fed littermates. We believe the development of this novel strategy could greatly facilitate our understanding of the role of BMP in biological systems.


Effect of treatment on the evolution of renal abnormalities in lupus nephritis.
We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.