Conventional versus Ultrasound-Guided Transbronchial Needle Aspiration for the Diagnosis of Hilar/Mediastinal Lymph Adenopathies: A Randomized Controlled Trial.
Conventional transbronchial needle aspiration (c-TBNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are both valuable diagnostic techniques for the diagnosis of hilar/mediastinal lesions. Although a superiority of EBUS-TBNA over c-TBNA may be expected, evidence-based data on a direct comparison between these 2 procedures are still lacking. We aimed to test the superiority of EBUS-TBNA over c-TBNA in a randomized trial and to evaluate the cost-effectiveness profile of a staged strategy, including c-TBNA as initial test followed by EBUS-TBNA, in case of inconclusive results at rapid on-site evaluation. Eligible patients were randomized 1:1 to either the EBUS-TBNA or c-TBNA group. The primary endpoint was to test the superiority of EBUS-TBNA sensitivity over c-TBNA. The secondary endpoints included the sensitivity of the staged strategy, as well as costs and safety related to each procedure and to their sequential combination. A total of 253 patients were randomized to either EBUS-TBNA (n = 127) or c-TBNA (n = 126), and 31 patients of the c-TBNA group subsequently underwent EBUS-TBNA. The sensitivity of EBUS-TBNA was higher, but not significantly superior to that of c-TBNA (respectively. 92% [95% CI 87-97] and 82% [95% CI 75-90], p > 0.05). The sensitivity of the staged strategy was 94% (95% CI 89-98). No major adverse events occurred. EBUS-TBNA was the single best diagnostic tool, although not significantly superior to c-TBNA. Due to the favorable cost-effectiveness profile of their sequential combination, in selected scenarios with a high probability of success from the standard procedure, these should not be necessarily intended as competitive and the staged strategy could be considered in clinical practice.


Tetrodotoxin-insensitive Na+ channel activator palytoxin inhibits tyrosine uptake into cultured bovine adrenal chromaffin cells.
The effects of the tetrodotoxin-insensitive Na+ channel activator palytoxin on both the secretion of endogenous catecholamines and the formation of 14C-catecholamines from [14C]tyrosine were examined using cultured bovine adrenal chromaffin cells. Palytoxin was shown to cause the stimulation of catecholamine secretion in a concentration-dependent manner. However, this toxin caused the reduction rather than the stimulation of 14C-catecholamine formation at the same concentrations. Palytoxin failed to cause any alteration in the activity of tyrosine hydroxylase prepared from bovine adrenal medulla. Furthermore, the uptake of [14C]tyrosine into the cells was shown to be inhibited by this toxin under the conditions in which the suppression of 14C-catecholamine formation was observed, and this inhibitory action on tyrosine uptake was closely correlated with that on catecholamine formation. The inhibitory action of palytoxin on tyrosine uptake into the cells was observed to be noncompetitive, and this effect was not altered by the removal of Na+ from the incubation mixture. These results suggest that palytoxin may be able to inhibit the uptake of [14C]tyrosine into the cells, resulting in the suppression of 14C-catecholamine formation, probably through its direct action on the plasma membranes of bovine adrenal chromaffin cells.


Alterations in antioxidant system, mitochondrial biogenesis and autophagy in preeclamptic myometrium.
Preeclampsia is a pregnancy complication which causes significant maternal and fetal morbidity and mortality worldwide. Although intensive research has been performed in the last 40 years, the pathology of preeclampsia is still poorly understood. The present work is a comparative study of the myometrium of women with normal pregnancy, and those with late- and early-onset preeclampsia (n = 10 for each group). We observed significant changes in the levels of antioxidant enzymes, markers of mitochondrial biogenesis and autophagy proteins in preeclamptic myometrium. Levels of superoxide dismutase 1 and catalase were lower in both preeclamptic groups than the control group. In late-onset preeclampsia, expression levels of essential mitochondria-related proteins VDAC1, TFAM, hexokinase 1, PGC-1α and PGC-1β, and autophagy marker LC3A, were significantly elevated. In the myometrium of the early-onset preeclampsia group OPA1 and Bcl-2 were up-regulated compared to those of the control (p < 0.05). These findings suggest that crucial molecular changes in the maternal myometrium occur with the development of preeclampsia.


Effects of the carrier-envelope phase of chirped laser pulses in the multiphoton ionization regime.
By solving the time-dependent Schrödinger equation for the Cs atom, we find that, as long as the spectral bandwidth is sufficiently broad, the asymmetry of photoelectron ejection is strongly phase dependent and persists even when the chirped pulse duration becomes more than several cycles. The asymmetry survives even after the angle integration over the hemisphere, implying that the detection efficiency can be significantly improved. This counterintuitive and robust finding provides a simple way to measure the phase for both transform-limited and chirped pulses.


Synthesis and antimicrobial activity of some N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles.
Several N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles (4) were synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 4 were also tested for antifungal activity against Saccharomyces cerevisiae. The findings clearly showed that all the compounds 4 were devoid of antifungal activity, whereas the compounds 4i-m,o-r were effective against the bacterial strains used. Compounds 4k,m,p,q proved to be the most active antibacterial agents showing in some cases minimum inhibitory concentrations (MIC) lower than chloramphenicol and gentamicin, used as reference compounds. In the case of two representative bacterial strains (Gram-positive and Gram-negative, respectively), a parabolic relationship was found between the antibacterial activity of compounds 4i-m,o-r expressed as log1/MIC and the molecular lipophilicity measured as RM values.


CXC chemokines suppress proliferation of myeloid progenitor cells by activation of the CXC chemokine receptor 2.
IL-8 is one of the major mediators of the transendothelial migration of neutrophils from the circulation to the site of injury and infection. In this work we demonstrate that the CXC or alpha-chemokines, IL-8 and melanoma growth stimulatory activity (MGSA) induce myeloid suppression via direct action on progenitor cells, mediated by activation of the murine homologue of the CXC chemokine receptor-2 (CXCR2) or IL-8R B. We first show that proliferation of the IL-3-dependent murine myeloid progenitor cell line 32D is suppressed by human IL-8 and the functionally and structurally related peptide, MGSA. Second, we show for the first time the high endogenous expression of the murine CXCR2 in 32D cells, as demonstrated by Northern blot analysis, binding to [125I]macrophage inflammatory protein-2, and macrophage inflammatory protein-2-induced calcium responses in 32D cells. Third, we demonstrate that IL-8 and MGSA induce a rise in intracellular calcium in 32D cells. The IL-8-induced Ca2+ response is desensitizing, since a second dose of IL-8 did not trigger a second calcium response. Other chemokines, including neutrophil-activating protein-2, platelet factor-4, RANTES, and macrophage chemotactic protein-1, neither suppressed the proliferation of 32D cells nor induced a rise in intracellular calcium. Finally, the IC50 of IL-8- and MGSA-dependent suppression of proliferation of 32D cells is in good agreement with the EC50 of IL-8- and MGSA-dependent activation of neutrophil Mac-1 up-regulation and chemotaxis. Our studies are consistent with the idea that IL-8 and MGSA suppress the proliferation of 32D cells by activation of murine CXCR2.


Aptamers targeted to an RNA hairpin show improved specificity compared to that of complementary oligonucleotides.
Aptamers interacting with RNA hairpins through loop-loop (so-called kissing) interactions have been described as an alternative to antisense oligomers for the recognition of RNA hairpins. R06, an RNA aptamer, was previously shown to form a kissing complex with the TAR (trans-activating responsive) hairpin of HIV-1 RNA (Ducongé and Toulmé (1999) RNA 5, 1605). We derived a chimeric locked nucleic acid (LNA)/DNA aptamer from R06 that retains the binding properties of the originally selected R06 aptamer. We demonstrated that this LNA/DNA aptamer competes with a peptide of the retroviral protein Tat for binding to TAR, even though the binding sites of the two ligands do not overlap each other. This suggests that upon binding, the aptamer TAR adopts a conformation that is no longer appropriate for Tat association. In contrast, a LNA/DNA antisense oligomer, which exhibits the same binding constant and displays the same base-pairing potential as the chimeric aptamer, does not compete with Tat. Moreover, we showed that the LNA/DNA aptamer is a more specific TAR binder than the LNA/DNA antisense sequence. These results demonstrate the benefit of reading the three-dimensional shape of an RNA target rather than its primary sequence for the design of highly specific oligonucleotides.


[Perioperative management of patients on long-term administration of psychotropic drugs].
We experienced perioperative management of thirty two surgical patients complicated with either schizophrenia or depression on long-term administration of psychotropic drugs during a period of three years from 1989 through 1991. They underwent various operative procedures under either general anesthesia or epidural anesthesia. Mental confusion was most frequently encountered in immediate postoperative period. The longer the patients had been treated with psychotropic drugs, the more postoperative complications were observed. We lost four patients within two weeks postoperatively. They all underwent laparotomy and had been treated with psychotropic drugs for a prolonged period. No significant association between the types of anesthesia and postoperative complications was observed. Surgical patients on long-term administration of psychotropic drugs should be managed carefully particularly during postoperative period.


Malus includes Docynia (Maleae, Rosaceae): evidence from phylogenomics and morphology.
Docynia has been treated as a separate genus or merged into Cydonia or Docyniopsis. Our phylogenomic evidence from 797 single-copy nuclear genes and plastomes confirmed the sister relationship between Docynia and Docyniopsis. By integrating the phylogenomic and morphological evidence, we propose to accept a broad generic concept of Malus and merge Docynia into Malus. Three new combinations are also made here: Malusdelavayi (Franch.) B.B.Liu, M.indica (Wall.) B.B.Liu and M.longiunguis (Q.Luo & J.L.Liu) B.B.Liu.


Production of a Chaetomium globosum enolase monoclonal antibody.
Chaetomium globosum is a hydrophilic fungal species and a contaminant of water-damaged building materials in North America. Methods to detect Chaetomium species include subjective identification of ascospores, viable culture, or molecular-based detection methods. In this study, we describe the production and initial characterization of a monoclonal antibody (MAb) for C. globosum enolase. MAb 1C7, a murine IgG1 isotype MAb, was produced and reacted with recombinant C. globosum enolase (rCgEno) in an enzyme-linked immunosorbent assay and with a putative C. globosum enolase in a Western blot. Epitope mapping showed MAb 1C7 specific reactivity to an enolase decapeptide, LTYEELANLY, that is highly conserved within the fungal class Sordariomycetes. Cross-reactivity studies showed MAb 1C7 reactivity to C. atrobrunneum but not C. indicum. MAb 1C7 did not react with enolase from Aspergillus fumigatus, which is divergent in only two amino acids within this epitope. The results of this study suggest potential utility of MAb 1C7 in Western blot applications for the detection of Chaetomium and other Sordariomycetes species.


Multiple Environment Integral Reinforcement Learning-Based Fault-Tolerant Control for Affine Nonlinear Systems.
This paper studies the fault-tolerant control (FTC) problem for unknown affine nonlinear systems with actuators faults. The considered types of faults are stuck (lock-in-place), loss-in-effectiveness (LIE), and bias, under which a part of the actuators is disabled. The objective is to find the remaining (not fully LIE) actuators, and manipulate them to obtain the best achievable performance in real time. First, considering that the best achievable performance is determined by the remaining actuators, a set of basic policies is predesigned with multiple levels of performances for different groups of activated actuators. Second, an identifier is designed based on history data to find the remaining actuators and, thus, the suitable predesigned basic policy. Third, to further accommodate the partial LIEs and biases, a compensator works together with the selected basic policy, to build the predesigned performance. In addressing the FTC problem, several techniques are developed: adjustable mechanisms are novelly integrated to deal with the state-dependent nonlinearities in neural network (NN) approximation, disturbances, and mismatch errors; history data are newly applied to estimate the faulty parameters; and a compensator is specially designed to deal with LIEs and biases in different input channels. Also in theory, the convergences of algorithms and the stability of closed-loop systems are proved, by formally giving the invariant sets of the initial state and the NN weights. Unlike the existing FTC methods dealing with LIE and bias based on model information to optimize the tracking error, this result can handle stuck faults without knowing system dynamics and satisfy different levels of performances described by Hamilton-Jacobi-Bellman equations. Finally, a simulation example of quadrotor unmanned aerial vehicle is given to verify the effectiveness of the proposed FTC scheme.


A Doppler Radar System for Sensing Physiological Parameters in Walking and Standing Positions.
Doppler radar can be implemented for sensing physiological parameters wirelessly at a distance. Detecting respiration rate, an important human body parameter, is essential in a range of applications like emergency and military healthcare environments, and Doppler radar records actual chest motion. One challenge in using Doppler radar is being able to monitor several patients simultaneously and in different situations like standing, walking, or lying. This paper presents a complete transmitter-receiver Doppler radar system, which uses a 4 GHz continuous wave radar signal transmission and receiving system, to extract base-band data from a phase-shifted signal. This work reports experimental evaluations of the system for one and two subjects in various standing and walking positions. It provides a detailed signal analysis of various breathing rates of these two subjects simultaneously. These results will be useful in future medical monitoring applications.


Catecholamine receptors involved in the inhibitory effects of dopamine on vagally stimulated gastric acid secretion and mucosal blood flow in rats.
The mechanisms of inhibitory effects of dopamine on the vagally stimulated gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized rats with a gastric fistula. Intravenous infusion of dopamine significantly reduced both gastric acid secretion and MBF. The inhibitory effect of dopamine on the vagally stimulated gastric acid secretion was not attenuated by sulpiride, metoclopramide or domperidone. Haloperidol abolished the inhibitory effect of dopamine on the acid secretion; it also abolished the inhibitory effect of norepinephrine on the vagally stimulated acid secretion. The inhibitory effect of dopamine on the acid secretion was abolished by phentolamine and yohimbine but not by propranolol or prazosin. Dopamine-induced reduction in the vagally stimulated gastric MBF was abolished by haloperidol and was partially antagonized by sulpiride or metoclopramide. In addition, the dopamine-induced reduction in the MBF was abolished by phentolamine and prazosin and was partially antagonized by yohimbine. These results indicate that the inhibitory effect of dopamine on the vagally stimulated gastric acid secretion is mediated by alpha-2 adrenoceptor mechanisms and that the inhibitory effect of dopamine on the MBF is, at least in part, mediated by alpha-1 adrenoceptor mechanisms. The authors did not obtain evidence for the existence of dopamine receptor-mediated mechanisms.


Expression of HLA-DP0401 molecules for identification of DP0401 restricted antigen specific T cells.
Human histocompatibility leukocyte antigen (HLA)-DPA1*0103/DPB1*0401 (DP0401) is the most common HLA class II molecule and is present in approximately 45% of the Caucasian population. In this study, soluble HLA-DP0401 molecules were expressed as "empty'' class II molecules in insect cells. Utilizing these soluble DP molecules and the Tetramer Guided Epitope Mapping (TGEM) approach, the influenza A Puerto Rico/8/34 matrix protein (MP) derived peptide MP(41-60) VLMEWLKTRPILSPLTKGIL and the Clostridium tetani Tetanus Toxin (TT) derived peptide TT(634-653) DKISDVSTIVPYIGPALNIV were identified as the DP0401 restricted MP and TT epitopes, respectively. In addition, T cells specific for the cancer testis antigen NY-ESO-1 and the breast/ovarian cancer over-expressing antigen Her-2/neu were detected in DP0401 subjects by DP0401 tetramers. The availability of HLA-DP0401 tetramers should facilitate the study of DP restricted T cell responses.


Identification of human trophoblast membrane antigens in maternal blood during pregnancy.
The development of an immunoradiometric assay for the detection of human trophoblast-specific membrane antigens is described. The test revealed for the first time circulating trophoblast-specific cell membrane antigens in the peripheral blood of pregnant women, but none in non-pregnant female or male controls. Comparison of the circulating levels of these trophoblast-specific proteins between normal and pre-eclamptic blood samples showed no significant differences, thus casting doubt on the role of differential trophoblast antigen deportation in the etiology of toxaemic pregnancy. Matched retroplacental cord blood from several normal and pre-eclamptic pregnancies were examined and found either negative or near the lower sensitivity limit of the assay, suggesting that deportation of trophoblast membrane antigens during gestation is limited to the maternal aspect of the placenta.


Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK-STAT pathway in Sézary syndrome.
Sézary syndrome (SS) is an aggressive leukaemia of mature T cells with poor prognosis and limited options for targeted therapies. The comprehensive genetic alterations underlying the pathogenesis of SS are unknown. Here we integrate whole-genome sequencing (n=6), whole-exome sequencing (n=66) and array comparative genomic hybridization-based copy-number analysis (n=80) of primary SS samples. We identify previously unknown recurrent loss-of-function aberrations targeting members of the chromatin remodelling/histone modification and trithorax families, including ARID1A in which functional loss from nonsense and frameshift mutations and/or targeted deletions is observed in 40.3% of SS genomes. We also identify recurrent gain-of-function mutations targeting PLCG1 (9%) and JAK1, JAK3, STAT3 and STAT5B (JAK/STAT total ∼11%). Functional studies reveal sensitivity of JAK1-mutated primary SS cells to JAK inhibitor treatment. These results highlight the complex genomic landscape of SS and a role for inhibition of JAK/STAT pathways for the treatment of SS.


Androgen effects on bone and muscle.
Bone health and strength are dependent on the coupling of cone resorption and bone formation. This process is governed by the interaction of osteoclasts and osteoblasts plus the modulating influence of the bone mechanicosensory cells-the osteocytes. Both sex steroids-estrogen (E) and testosterone (T)- have receptors on all bone cells, with androgen dominance on osteoblasts and osteocytes. Specific receptors for the weaker androgens, such as DHEA have also been identified. The activity of the sex steroids, influenced by various enzymes found in bone, is reflective of the hormone ligand before its binding to the bone cells. As a result, T acts both directly and via its aromatization to estradiol. The activity of the androgens also varies with the bone surface; periosteal cells, for example, do not have 5alpha-reductase activity, indicating that T is the active metabolite at this clinically important site. Androgens influence bone cell function via local and systemic growth factors and cytokines. By enhancing osteoblast differentiation, androgens regulate bone matrix production, organization, and mineralization. Androgens also regulate osteoclast recruitment and activity. Endogenous androgens increase bone mineral density (BMD) in both adolescent and adult premenopausal women. Women with excess endogenous androgen-for example, those with hirsutism and polycystic ovary syndrome (PCOS)-have increased BMD compared with normal young women. E and androgen therapy increases BMD to a greater degree than does E therapy alone. This is true for both oral combinations of esterified E and methyltestosterone and for subcutaneous T implants. Androgenic progestins have an additive effect on BMD when combined with E therapy and have the further advantage of being protective to the endometrium in E-treated women. Androgens increase muscle mass and strength. The resulting improvement in physical activity leads to the activation of bone-forming sites and the stimulation of the bone formation-modulating cells, the osteocytes. Mechanical loading, when combined with hormone therapy, results in greater osteogenic response than does either alone.


CD24 Expression May Play a Role as a Predictive Indicator and a Modulator of Cisplatin Treatment Response in Head and Neck Squamous Cellular Carcinoma.
Platinum-based therapy is most often used to treat advanced cases of head and neck cancers, but only a small fraction of the patient population responds to cisplatin, with a median survival time of less than a year. Although gene signatures and molecular etiology of head and neck cancers have been previously described, none of them are predictive indicators of cisplatin treatment response in particular. Therefore, currently, there is a lack of clinically employable predictive indicators of the disease beyond HPV status to specifically predict patients' response to platinum-based therapy. It beckons a substantial effort to look for predictive indicators of cisplatin treatment response. In this regard, CD24 expression level appears to be a significant molecular phenotype of cisplatin-resistant residual cells in laryngeal carcinoma lines. CD24 expression level directly affects cisplatin sensitivity and affects the expression of critical apoptotic, stem and drug resistance genes. A relatively small retrospective patient tumor analysis suggests that CD24 high tumors go on to show an unfavorable response to cisplatin treatment. Overall, based on the strength of further analysis, CD24 presents a strong rationale to be utilized as a predictive indicator to stratify head and neck cancer patients for platinum-based therapy. It also provides a rationale for using CD24 as a therapeutic adjuvant target along with standard cisplatin therapy.


Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence.
Progress in the treatment of patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) has been limited. An improvement in the understanding of tumor immunosurveillance has resulted in the development of the immune checkpoint inhibitors such as nivolumab. Nivolumab (Opdivo(®)), a human immunoglobulin (Ig)G4 anti-programmed death (PD)-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of patients with advanced stage squamous cell NSCLC following platinum-based chemotherapy. CHECKMATE 017, a randomized phase III study of second-line nivolumab versus docetaxel, significantly improved overall survival (OS), progression-free survival (PFS), patient reported outcomes and the safety and tolerability favored patients treated with nivolumab. The ligand (PD-L1) expression did not predict for outcome. In this paper, we review the role of nivolumab in the treatment of NSCLC with particular attention on recent studies, ongoing combination studies, toxicity profile, current and potential predictive biomarkers.


HIV/AIDS and drug use in China--interactions, impacts, and issues.
The interrelationships of HIV/AIDS and drug use and misuse result in complex problems that have been addressed by a variety of sociolegal approaches that often are in contrast to evidence-based medical practices proven effective in reducing associated harms. Like other countries struggling to reduce the incidence and consequences of addiction and HIV/AIDS, China is working to improve systems of care and to revise policies toward drug use and misuse and HIV/AIDS. Greater interaction with researchers and clinicians from around the world can foster increased awareness of effective practices and help implement effective strategies to deal with the problems of HIV/AIDS, and addiction.


Keratoconus. Contact lens or keratoplasty?
The success rate of contact lens fitting and rate of progression to keratoplasty were evaluated for 115 consecutive patients with keratoconus. Of 190 nonoperated eyes that needed to be fit, 25 (13%) could not be fit, whereas 165 eyes (87%) could be fit. Most of these eyes had been referred for keratoplasty after previous contact lens fittings had no longer been successful. Of the 165 eyes that could be fit, 51 (31%) ultimately needed keratoplasty after an average of 38.4 months of lens wear, and 114 eyes (69%) did not require keratoplasty over an average follow-up interval of 63 months of wearing contact lenses. The average initial keratoplasty reading in these two groups was 56.8 and 51.8 diopters (D), respectively. Special design, bispheric lenses were required in 125 of these 165 eyes (76%) and frequent lens changes were necessary. Of 88 postoperative eyes, 53 (60%) wore contact lenses for best vision. Keratoplasty can be delayed or avoided in many keratoconus patients by using contact lenses, especially special design, bispheric lenses. Also, keratoconus eyes often need contact lenses after keratoplasty.


[Evaluating performance capacity and assessing disability in alcoholism].
General aspects of the problem of addiction are outlined and followed by a discussion of the organic effects of alcoholism. Internal, neurological, and psychiatric complications in chronic alcoholism are set forth, and their ranking in the assessment process determined. There follow some conclusions relevant to assessment of the alcoholic's incapacity to work.


Clathrin-dependent endocytosis of membrane-bound RANKL in differentiated osteoclasts.
Bone is continuously repaired and remodelled through well-coordinated activity of osteoblasts that form new bone and osteoclasts, which resorb it. Osteoblasts synthesize and secrete two key molecules that are important for osteoclast differentiation, namely the ligand for the receptor of activator of nuclear factor kappaB (RANKL) and its decoy receptor osteoprotegerin (OPG). Active membrane transport is a typical feature of the resorbing osteoclast during bone resorption. Normally, one resorption cycle takes several hours as observed by monitoring actin ring formation and consequent disappearance in vitro. During these cyclic changes, the cytoskeleton undergoes remarkable dynamic rearrangement. Active cells show a continuous process of exocytosis that plays an essential role in transport of membrane components, soluble molecules and receptor-mediated ligands thus allowing them to communicate with the environment. The processes that govern intracellular transport and trafficking in mature osteoclasts are poorly known. The principal methodological problem that have made these studies difficult is a physiological culture of osteoclasts that permit observing the vesicle apparatus in conditions similar to the in vivo conditions. In the present study we have used a number of morphological approaches to characterize the composition, formation and the endocytic and biosynthetic pathways that play roles in dynamics of differentiation of mature bone resorbing cells using a tri-dimensional system of physiologic coculture.


[An experimental study on SRCA (subrenal capsule assay)--using immunosuppressive maneuvers].
Six-day SRCA using normal mice developed by Bogden et al. is one of the most promising methods for in vivo chemosensitivity tests. However, this method has a problem on the influence of the host reaction during six days. Therefore, we examined the tumour growth kinetics, host reaction and expression of antitumor effect on three immunosuppressive maneuvers; cyclophosphamide (EX), cyclosporin A (CSA), and total body irradiation (TBI). The tumour diameter increased until day 16 in EX and CSA-treated groups and day 10 in TBI-treated group, but the results of the histological examination showed that tumour cells were preserved in tissue on day 14 in CSA-treated group and day 6 in EX and TBI-treated groups. These results were supported by flow cytometrical analysis. The autoradiogram using 3H-TdR showed that labelling index of the tumour cells was not affected by these immunosuppressive maneuvers. From the investigation of the antitumour activity of adriamycin and mitomycin C, it was suggested that the 12-day assay was suitable if nude mice were used in SRCA, and six-day assay, if EX-treated normal mice were used. In CSA-treated group, toxicity of anticancer drugs was manifested than usual.


Influenza Virus: Dealing with a Drifting and Shifting Pathogen.
Numerous modern technological and scientific advances have changed the vaccine industry. However, nearly 70 years of influenza vaccine usage have passed without substantial changes in the underlying principles of the vaccine. The challenge of vaccinating against influenza lies in the constantly changing nature of the virus itself. Influenza viruses undergo antigenic evolution through antigenic drift and shift in their surface glycoproteins. This has forced frequent updates of vaccine antigens to ensure that the somewhat narrowly focused vaccine-induced immune responses defend against circulating strains. Few vaccine production systems have been developed that can entertain such constant changes. Although influenza virus infection induces long-lived immunologic memory to the same or similar strains, most people do not encounter the same strain repeatedly in their lifespan, suggesting that enhancement of natural immunity is required to improve influenza vaccines. It is clear that transformative change of influenza vaccines requires a rethink of how we immunize. In this study, we review the problems associated with the changing nature of the virus, and highlight some of the approaches being employed to improve influenza vaccines.


Optogenetic Modulation of Intracellular Signalling and Transcription: Focus on Neuronal Plasticity.
Several fields in neuroscience have been revolutionized by the advent of optogenetics, a technique that offers the possibility to modulate neuronal physiology in response to light stimulation. This innovative and far-reaching tool provided unprecedented spatial and temporal resolution to explore the activity of neural circuits underlying cognition and behaviour. With an exponential growth in the discovery and synthesis of new photosensitive actuators capable of modulating neuronal networks function, other fields in biology are experiencing a similar re-evolution. Here, we review the various optogenetic toolboxes developed to influence cellular physiology as well as the diverse ways in which these can be engineered to precisely modulate intracellular signalling and transcription. We also explore the processes required to successfully express and stimulate these photo-actuators in vivo before discussing how such tools can enlighten our understanding of neuronal plasticity at the systems level.


Precise Amphiphilic Giant Polymeric Chain Based on Nanosized Monomers with Exact Regio-Configuration.
Polymeric chains made of "giant" monomers at a larger length scale provide intriguing insights into the fundamental principles of polymer science. In this study, we modularly prepared a library of discrete amphiphilic polymeric chains using molecular nanoparticles as repeat units, with exact control of composition, chain length, surface property, and regio-configuration. These giant polymeric chains self-assembled into a rich collection of highly ordered phases. The precise chemical structure and uniform chain length eliminate all the inherent molecular "defects", while the nanosized monomer amplifies minute structural differences, providing an ideal platform for a systematic scrutiny of the self-assembly behaviors at a larger length scale. The compositional and regio-configurational contribution was carefully studied. The regio-regularity is found to have a direct and profound impact on the chain conformation, leading to a distinct molecular packing scheme and therefore shifting the phase boundaries. With increasing the length of the linker, the regio-constraint gradually diminishes, and the neighboring particles would eventually be decoupled.


Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension.
Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO(x)) may affect the systemic and pulmonary NO-generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear. The aims of the present study were to measure changes in exhaled NO in relation to circulating NO(x), RAAS, and haemodynamics. Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO(x) and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D(L)CO). Eight matched healthy individuals served as controls. All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and D(L)CO. NO(x) concentrations were not significantly increased in the patients. NO(x) correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations. In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO(x) do not seem to reflect pulmonary and systemic NO release, but NO(x) seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis.


Domestic violence: no place for a smile.
Because dentists routinely assess a patient's head, neck and mouth, they have a unique and excellent opportunity to recognize whether or not a patient is being abused. This article seeks to enlist the collaboration of the dental community in the effort to prevent domestic/intimate partner violence and provide more information about the signs and symptoms of domestic violence injuries, including strangulation, which is often overlooked by medical and dental professionals. Strangulation has only been identified in recent years as one of the most lethal forms of domestic violence. Unconsciousness may occur within seconds and death within minutes. It is known that victims may have no visible injuries whatsoever yet because of underlying brain damage by a lack of oxygen from being strangled, victims may have many serious internal injuries or die days or several weeks later. Strangulation is often indicative of a high level of domestic violence in a relationship. Attempted strangulation may cause physiological changes evident in the course of a dental examination. For these reasons, dentists should be vigilant in looking for its symptoms.


Gene expression profiling during adventitious root formation in carnation stem cuttings.
Adventitious root (AR) formation is a critical step in vegetative propagation of most ornamental plants, such as carnation. AR formation from stem cuttings is usually divided into several stages according to physiological and metabolic markers. Auxin is often applied exogenously to promote the development of ARs on stem cuttings of difficult-to-root genotypes. By whole transcriptome sequencing, we identified the genes involved in AR formation in carnation cuttings and in response to exogenous auxin. Their expression profiles have been analysed through RNA-Seq during a time-course experiment in the stem cutting base of two cultivars with contrasting efficiencies of AR formation. We explored the kinetics of root primordia formation in these two cultivars and in response to exogenously-applied auxin through detailed histological and physiological analyses. Our results provide, for the first time, a number of molecular, histological and physiological markers that characterize the different stages of AR formation in this species and that could be used to monitor adventitious rooting on a wide collection of carnation germplasm with the aim to identify the best-rooting cultivars for breeding purposes.


Augmentation with atypical antipsychotics for depression: a review of evidence-based support from the medical literature.
Major depressive disorder (MDD) is a chronic mental illness that affects an estimated 5-26% of adults at some time in their lives. Treatment is often started as pharmacotherapy using a single drug such as a selective serotonin reuptake inhibitor. If a patient fails to respond adequately to the initial antidepressant, typically three pharmacotherapy options are available to the practitioner. The dose of the current therapy can be maximized, a change can be made to a different drug, or the current regimen can be augmented with another drug. Atypical antipsychotics have recently become a major focus for augmentation of traditional antidepressant therapy. This review summarizes the evidence for efficacy and safety of augmenting treatment-refractory or treatment-resistant depression with atypical antipsychotics. The National Library of Medicine's MEDLINE database was searched for all English-language articles published from January 1966-December 2011 describing the use of atypical antipsychotics in treatment-resistant depression. The literature retrieved was limited to case series, open-label trials, and randomized controlled trials (RCT). Studies of bipolar depression, psychotic depression, or studies conducted in children and adolescents were excluded. Thirty-five studies using atypical antipsychotics for augmentation treatment of depression were included in this analysis. Trials were identified for aripiprazole (six open-label; three RCT), clozapine (one case series), olanzapine (three open-label, including two case series; four RCT), quetiapine (four open-label; five RCT), risperidone (two open-label; five RCT), and ziprasidone (two open-label). The atypical antipsychotics may be effective as adjunctive therapy in MDD; however, their adverse effect profile may be unfavorable to some patients. Trying at least one alternative treatment strategy after an initial antidepressant is indicated before augmentation is implemented with these agents. If atypical antipsychotics are used, safety and efficacy should be frequently reassessed and dosage should be individualized.


Resilience of the standard predictions for primordial tensor modes.
We show that the prediction for the primordial tensor power spectrum cannot be modified at leading order in derivatives. Indeed, one can always set to unity the speed of propagation of gravitational waves during inflation by a suitable disformal transformation of the metric, while a conformal one can make the Planck mass time independent. Therefore, the tensor amplitude unambiguously fixes the energy scale of inflation. Using the effective field theory of inflation, we check that predictions are independent of the choice of frame, as expected. The first corrections to the standard prediction come from two parity violating operators with three derivatives. Also the correlator ⟨γγγ⟩ is standard and only receives higher derivative corrections. These results hold also in multifield models of inflation and in alternatives to inflation and make the connection between a (quasi-)scale-invariant tensor spectrum and inflation completely robust.


SIRT1 transgenic mice show phenotypes resembling calorie restriction.
We generated mice that overexpress the sirtuin, SIRT1. Transgenic mice have been generated by knocking in SIRT1 cDNA into the beta-actin locus. Mice that are hemizygous for this transgene express normal levels of beta-actin and higher levels of SIRT1 protein in several tissues. Transgenic mice display some phenotypes similar to mice on a calorie-restricted diet: they are leaner than littermate controls; are more metabolically active; display reductions in blood cholesterol, adipokines, insulin and fasted glucose; and are more glucose tolerant. Furthermore, transgenic mice perform better on a rotarod challenge and also show a delay in reproduction. Our findings suggest that increased expression of SIRT1 in mice elicits beneficial phenotypes that may be relevant to human health and longevity.


An interferometric system for measuring thickness of parallel glass plates without 2π ambiguity using phase analysis of quadrature Haidinger fringes.
An interferometric system is proposed for measuring the thickness of parallel glass plates by analyzing Haidinger fringes. Although a conventional Haidinger interferometer can measure thickness without 2π ambiguity using positions of peak and valley points in the interferogram, measurement accuracy is directly affected by the number of these points involved in the calculation. The proposed method obtains phase values over the entire interferogram by analyzing the quadrature Haidinger fringes generated by a current modulated laser diode. Therefore, it can achieve high speed measurement and nanometric resolution without mechanical rotation and thickness limitation of specimens. In the experiments, the standard deviation of repeated thickness measurement was evaluated as less than 0.3 nm, and the measured thickness profile of the proposed system agreed with that of a conventional thickness interferometer within ±15 nm. We also discussed the required accuracy of refractive index of specimens to implement the proposed method successfully and presented an exemplary measurement result of a multi-layer coated sample having a discontinuous thickness profile.


Baduanjin exercise can alleviate anxiety and depression of patients with COVID-19 in Square cabin hospital: A cross-sectional survey.
To investigate the anxiety and depression of patients with the coronavirus disease 2019 (COVID-19) who participated in Baduanjin exercise.From February 20, 2020 to March 7, 2020, the Hospital Anxiety and Depression scale (HAD) were used to investigate the anxiety and depression levels of patients with COVID-19 who participated in Baduanjin exercise. Ninety one questionnaires were received, including 40 males and 51 females. Stepwise regression analysis was used to analyze the effects of related factors on anxiety and depression levels.In Square cabin hospital, 91% of patients participated in Baduanjin exercise had no obvious anxiety and 82% had no obvious depression. The scores of anxiety and depression of female patients were significantly higher than that of male patients. Bachelor degree or above with low scores for anxiety and depression. The frequency of Baduanjin exercise was negatively correlated with anxiety and depression score.The development of Baduanjin exercise has a certain positive influence on the COVID-19 patients in the Square cabin hospital, which is conducive to alleviate anxiety and depression symptoms of the patients.


Persistent Afebrile Abdominal Pain: An Unusual Case of Segmental Colitis in an Immunocompromised Host.
In this report we describe a case of a 66-year-old woman who presented with right upper quadrant abdominal pain and bloody diarrhea. A workup revealed immunodeficiency, an immunologic profile with low complement levels resembling systemic lupus erythematosus, and a circumferential colonic wall lesion located in the ascending colon. After endoscopy and biopsy, the mass lesion was attributed to "double hit" diffuse large B-cell lymphoma, categorized as high grade large B-cell non-Hodgkin lymphoma according to the most recent revised 2016 World Health Organisation classification and considered to be a rare and highly aggressive tumor. The diagnosis of colonic lymphoma can be challenging due to a diversity of clinical presentation and requires a high index of suspicion. As the literature of such documented reports is limited, this case suggests further investigations. GI: gastrointestinal tract, DLBCL: diffuse large B cell lymphoma, DH: double hit lymphoma, SLE: systemic lupus erythematosus, ANA: antinuclear antibodies, anti-ssDNA: anti-single-stranded DNA, BCL: B-cell lymphoma protein, MUM-1/IRF4: multiple myeloma oncogene 1/interferon regulatory factor 4, HGBL: high grade B-cell lymphoma, anti-dsDNA: anti-double-stranded DNA.


Cyclophilin A Isomerisation of Septin 2 Mediates Abscission during Cytokinesis.
The isomerase activity of Cyclophilin A is important for midbody abscission during cell division, however, to date, midbody substrates remain unknown. In this study, we report that the GTP-binding protein Septin 2 interacts with Cyclophilin A. We highlight a dynamic series of Septin 2 phenotypes at the midbody, previously undescribed in human cells. Furthermore, Cyclophilin A depletion or loss of isomerase activity is sufficient to induce phenotypic Septin 2 defects at the midbody. Structural and molecular analysis reveals that Septin 2 proline 259 is important for interaction with Cyclophilin A. Moreover, an isomerisation-deficient EGFP-Septin 2 proline 259 mutant displays defective midbody localisation and undergoes impaired abscission, which is consistent with data from cells with loss of Cyclophilin A expression or activity. Collectively, these data reveal Septin 2 as a novel interacting partner and isomerase substrate of Cyclophilin A at the midbody that is required for abscission during cytokinesis in cancer cells.


Parenchyma-preserving hepatectomy including segments I + IV resection and bile duct resection in a patient with type IV perihilar cholangiocarcinoma: A case report with video clip.
It has been reported that parenchyma-preserving hepatectomy (PPH) might lower surgical curability with an increased likelihood of bile duct resection margins (BDRMs). Apparently, PPH is indicated for patients expected to achieve curative resection. The author herein presents a case of a 77-year-old male patient with type IV perihilar cholangiocarcinoma and decreased cardiac function treated with hepatic segments I + IV resection and bile duct resection. During the operation, he underwent two hepatic parenchymal transections matched with right trisectionectomy and left hepatectomy. After removing segments VI and I and extrahepatic bile duct, six hepatic duct openings were exposed at the left and right hila. As some of them were conjoined, two hepaticojejunostomies at the right liver and one hepaticojejunostomy at the left lateral section were performed consecutively. This operation took 7 hours. Eight sessions of intraoperative frozen-section biopsy were performed. All BDRMs were tumor-negative. According to the 8th edition of the American Joint Committee on Cancer staging system, the extent of the tumor was pT2bN2M0. It was regarded as stage IVA tumor. The patient recovered uneventfully. He was discharged on the 18th postoperative day. The patient underwent concurrent chemoradiation therapy and adjuvant chemotherapy. The patient has been doing well without tumor recurrence for the past 24 months to date. In conclusion, PPH can lead to curative resection and improved outcomes through reasonable adjustment of the extent of hepatectomy.


Diagnosis and treatment of lichen sclerosus: an update.
Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin. LS is a debilitating disease, causing itch, pain, dysuria and restriction of micturition, dyspareunia, and significant sexual dysfunction in women and men. Many findings obtained in recent years point more and more towards an autoimmune-induced disease in genetically predisposed patients and further away from an important impact of hormonal factors. Preceding infections may play a provocative part. The role for Borrelia is still controversial. Trauma and an occlusive moist environment may act as precipitating factors. Potent and ultrapotent topical corticosteroids still head the therapeutic armamentarium. Topical calcineurin inhibitors are discussed as alternatives in the treatment of LS in patients who have failed therapy with ultrapotent corticosteroids, or who have a contraindication for the use of corticosteroids. Topical and systemic retinoids may be useful in selected cases. Phototherapy for extragenital LS and photodynamic therapy for genital LS may be therapeutic options in rare cases refractory to the already mentioned treatment. Surgery is restricted to scarring processes leading to functional impairment. In men, circumcision is effective in the majority of cases, but recurrences are well described. Anogenital LS is associated with an increased risk for squamous cell carcinoma of the vulva or penis. This review updates the epidemiology, clinical presentation, histopathology, pathogenesis, and management of LS of the female and male genitals and extragenital LS in adults and children.


Pharmacy practice acts: a five-year follow-up.
To rereview the status of state pharmacy practice acts since 1987. Additionally, this report discusses adoption of the 1992 National Association of Boards of Pharmacy Model State Pharmacy Practice Act as the standard state pharmacy practice statute. State codes for 50 states and the District of Columbia, with attention focused on the pharmacy practice acts; Puerto Rico and the Virgin Islands were excluded. CASE LAW SELECTION: Case law utilizing state pharmacy statutes was selected to demonstrate pharmacists' liability. The focus on each statute was the statutory definition of the "practice of pharmacy." Twelve pharmacy laws (24 percent) contain no definition of the practice of pharmacy. Compounding (92 percent), dispensing (100 percent), interpretation and evaluation of prescriptions (72 percent), consultation (85 percent), drug utilization review (69 percent), drug product selection (54 percent), drug administration (21 percent), pharmacokinetic consultation and patient assessment (13 percent) were noted in the laws for the remaining 38 states and the District of Columbia. Significant pharmacy activities codified since 1987 include consultation, drug administration, pharmacokinetic consultation, and patient assessment. Statutes defining pharmacy practice impact the profession by affecting liability and by mirroring society's view of the role of the profession. States have enacted new statutes principally in the areas of progressive pharmacy practice functions since 1987. Enactment of the definition of professional practice contained in the National Association of Boards of Pharmacy Model State Pharmacy Practice Act would serve the pharmacy profession by: (1) creating a uniform professional purpose; (2) creating legal responsibility that reflects contemporary practice; (3) allowing pharmacists to enlarge the scope of their practice as the profession's societal role evolves; and (4) conserving revenues normally consumed by lobbying for constant legislative revisions.


[Lateral view of the thorax: the profile].
The lateral view of the chest is a complementary incidence performed less frequently nowadays with the great frequency of chest CT. In fact, this lateral radiograph has important potential and can even give some exclusive information. With the 3-dimensional visualization provided by CT, the lateral radiograph of the chest is even easier to understand. Following in the footsteps of our great predecessors (Felson, Heitzman, Proto) we propose the left lateral view and offer our opinion about indications, techniques and results. The left lateral view can be performed with perfect perpendicular orientation or with a slight lateral shift that can be chosen with the right shoulder forwards (shifted right anterior lateral) or the contrary (shifted left anterior lateral). The left lateral view, like the antero-posterior view must be interpreted in a circular-concentric fashion.


Radioimmunoassay for the aminoterminal peptide of procollagen p alpha 1(I)-chain.
Peptides derived from the aminoterminal portion of the palpha1(I)-chain of calf and sheep procollagen were labeled with iodine-125. Despite changes in electrophoretic homogeneity after labeling, reaction of the labeled peptide with antisera to unlabeled peptide was retained. Antisera to procollagen or the isolated procollagen peptide showed high titers for the native peptide, a much weaker binding with the reduced and alkylated peptide and little or no reaction with collagen. Antisera to collagen showed strong binding with collagen and a weaker but distinct reaction with the procollagen peptide. Evidence was obtained that a minor contaminant of procollagen peptide was present in the acid-extracted collagen and that there were no shared antigenic determinants. Bovine serum and amniotic fluid contained 1-10 mug/ml reactive antigen. These results indicate that the labeled peptides can be used as a specific, sensitive and accurate assay for the amino-terminal portion of procollagen in biological samples.


Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men.
To assess and compare the effects of short-term aromatase inhibition on glucose metabolism, lipid profile, and adipocytokine levels in young and elderly men. Ten elderly and nine young healthy men were randomized to receive letrozole 2.5 mg daily or placebo for 28 days in a crossover design. Both in young and elderly men, active treatment significantly increased serum testosterone (+128 and +99%, respectively) and decreased estradiol levels (-41 and -62%, respectively). Fasting glucose and insulin levels decreased in young men after active intervention (-7 and -37%, respectively) compared with placebo. Leptin levels fell markedly in both age groups (-24 and -25%, respectively), while adiponectin levels were not affected by the intervention. Lipid profile was slightly impaired in both groups, with increasing low density lipoprotein-cholesterol levels (+14%) in the younger age group and 10% lower levels of APOA1 in the elderly. A decline in IGF1 levels (-15%) was observed in the younger age group. No changes in weight or body mass index were observed in either young or old men. Short-term aromatase inhibition appears to affect glucose metabolism in young men, and lipid metabolism, including leptin secretion, in young and elderly men. Furthermore, the short period of exposure suggests that these changes might be mediated by direct effects of sex steroids rather than by changes in body composition.


Poly(3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects - an animal study with minipigs.
We conclude that PHB patch material may fulfil the specific requirements that are necessary for a dural substitute, including defect closure, stability and biocompatibility. Our results support the assumed positive influence of PHB on bone regeneration. Although many experimental and clinical studies have been performed to identify a suitable material to repair defects of the dura mater, no ideal dural substitute is currently available. PHB is a biodegradable and biocompatible polymer that might serve as dural substitute and osteosynthesis material in cranial bone defects. Different standardized PHB patches were used in six minipigs for covering defined bone defects in the anterior skull base including a dura mater lesion as well as in the frontal sinus front wall. After a defined time of implantation of 3, 6, and 9 months PHB patches were explanted and examined for clinical findings, biodegradation, presence of microorganisms, histological findings, and electron microscopy. The examinations revealed an increasing closure of bone defect corresponding with time. The anterior skull base bone defect was completely closed after 9 months. The histological findings revealed a connective tissue and callus formation around the PHB patches with fibroblasts and foreign body/giant cell reaction growing through PHB membrane pores. There were no reactions or adhesions between brain and PHB or dura mater and PHB, respectively. Investigations of biodegradation and electron microscopy revealed a continuous breakdown of PHB in the course of time with variations due to different PHB structures. Microbiological investigations could not detect any florid intracranial infection.


Detection of Salmonella human carriers in Colombian outbreak areas.
Salmonellosis, a zoonotic and foodborne disease, is a public health problem in developing countries. With the aim of identifying human carriers of Salmonella, a survey was performed in five regions of Colombia with reported salmonellosis outbreaks. The general population and cholecystectomy surgical patients were included in this study. Stool samples from 667 volunteers and gallbladder bile samples from 199 surgical patients were examined. Detection of Salmonella from cultured stool and bile samples was determined by polymerase chain reaction (PCR). Multiplex PCR and biochemical and serological tests were performed to identify the serovars of the isolates. Nine (1.35%) stool samples were positive for Salmonella: two S. Newport, two S. Anatum, one S. Sinstorf, and four Salmonella spp. A total of 11 gallbladder bile samples were positive: S. Enteritidis was isolated from 3 bile cultures (1.5%), and 8 samples (4%) were positive for Salmonella spp. Our results show the presence of Salmonella carriers in the inhabitants of regions with reported outbreaks and suggest that these carriers are potential sources of infection in endemic and epidemic cases. Carriers also suggest Salmonella zoonotic transmission, since broiler and beef cattle are hosts to the Salmonella serotypes isolated. It is important to establish the source of infection in regions where salmonellosis is endemic in order to control transmission.


Dynamics of Microtubule Instabilities.
We investigate an idealized model of microtubule dynamics that involves: (i) attachment of guanosine triphosphate (GTP) at rate λ, (ii) conversion of GTP to guanosine diphosphate (GDP) at rate 1, and (iii) detachment of GDP at rate μ. As a function of these rates, a microtubule can grow steadily or its length can fluctuate wildly. For μ = 0, we find the exact tubule and GTP cap length distributions, and power-law length distributions of GTP and GDP islands. For μ = ∞, we argue that the time between catastrophes, where the microtubule shrinks to zero length, scales as e(λ). We also discuss the nature of the phase boundary between a growing and shrinking microtubule.


[Diagnostic imaging in constipation].
Diagnostic imaging modalities play a key role in the definition of the possible causes of constipation. Barium Enema (BE), Defecography (DG), Intestinal Transit Time (ITT), Computed Axial Tomography (CT) and Magnetic Resonance (MR) are necessary diagnostic tools for the identification either of the possible organic causes of the disease or of the functional disorders. The ITT evaluation is the main investigation to look for functional colic constipation; this method is in fact able to distinguish between the hypertonic type (in which the fecal progression is slowed down to such an extent that radiopaque markers accumulate in the most proximal part of the colon) and the atonic one (characterized by a global slowing down with the markers distributed along the whole colon). DG gives very accurate dynamic documentation of the pathologic alteration of the rectum-anal conduit, as well as of the disease of the supporting and anchoring system and of the levator complex; this type of investigation allows the definition (characterisation) of the different types of the functional rectum-anal constipation. Even in this case TAC and RM can greatly contribute to the definition of the whole picture of the constipation.


Serial MR intensity changes of the posterior pituitary in patients with diabetes insipidus after transsphenoidal surgery for pituitary adenomas: report of two cases.
This is the first report describing magnetic resonance (MR) intensity changes of the posterior pituitary gland in the patients suffering from the classical "triphasic" diabetes insipidus (DI) after transsphenoidal surgery for pituitary adenomas. A 21-year-old female and a 54-year-old female were admitted to our hospital with the diagnosis of Cushing's disease and acromegaly due to pituitary microadenomas, respectively. No evidence of DI was found, and T1-weighted MR images exhibited "bright spot" corresponding to the posterior pituitary in both cases. Both experienced the classical "triphasic" pattern of water metabolism disturbance after successful transsphenoidal resection of pituitary adenomas, that is, polyuria-oliguria-polyuria. The MR signal hyperintensity in posterior pituitary was detected during the first polyuric phase, but the hyperintensity disappeared during the second polyuric phase. In addition, "bright spot" was restored along with the recovery from DI in the chronic phase. These findings of serial MR images supported that the first DI phase of the classical triphasic course of water metabolism disturbance was caused by secretional dysfunction of stored vasopressin from the posterior gland, whereas the second DI phase was due to impairment in the functional integrity producing vasopressin-containing granules after depletion of vasopressin in the oliguric phase.


Isoflurane exerts a short-term but not a long-term preconditioning effect in neonatal rats exposed to a hypoxic-ischaemic neuronal injury.
Isoflurane has been shown to induce tolerance against ischaemic injury in adult rodents. Although the delayed preconditioning effect of isoflurane has been demonstrated in neonatal rat pups, the acute preconditioning effects of isoflurane remained undetermined. The present study was therefore conducted to evaluate the acute preconditioning efficacy of isoflurane in neonatal rats subjected to a hypoxic-ischaemic (HI) injury. Post-natal day 7 pups were exposed to 1 or 2% isoflurane in oxygen for either 30, 60 or 90 min. Fifteen minutes after isoflurane exposure, the pups were subjected to an HI injury induced by left common carotid artery ligation and exposure to 8% oxygen for 2 h. Pups not exposed to isoflurane or not subjected to HI served as controls. Histopathologic injury to the cortex and hippocampus was evaluated 7 and 49 days after HI. Isoflurane 2% exposure for 60 or 90 min before HI induced tolerance in the hippocampus and the number of normal neurons in the CA1 sector 7 days after HI was significantly greater than in non-preconditioned animals. This protective efficacy of isoflurane preconditioning was not observed 49 days after HI. Exposure of 2% isoflurane for at least 60 min is required to induce tolerance against HI injury in rat pups. However, this neuroprotective efficacy results in only transient neuroprotection.


Differences in soil properties and bacterial communities between the rhizosphere and bulk soil and among different production areas of the medicinal plant Fritillaria thunbergii.
To explore rhizosphere effects, geographical differences and their effects on the bacterial community associated with the geoherb Fritillaria thunbergii, some physicochemical properties of soil samples (3 sampling sites × 2 habitats (rhizosphere and bulk soil)) were measured and the soil bacterial community detected by PCR-denaturing gradient gel electrophoresis (DGGE). Among the three regions, soil pH varied between 4.48 and 7.73 indicating that F. thunbergii could grow both in acid and slightly alkaline soil. As the authentic Dao-di producing area, Ningbo showed the highest soil quality with the highest content of organic matter (OM) (2.46%), phosphatase (268 mg kg(-1) 24 h(-1)) and urease activity (1481 mg kg(-1) 24 h(-1)). In comparison with the bulk soil, pH, organic carbon content, and phosphatase and urease activities were all lower in the rhizosphere, suggesting that the roots may secrete some unique metabolites in root exudates. Statistical analyses showed that soil properties of Ningbo and Panan in Zhejiang province were more similar to each other than those in Nantong in Jiangsu province. In addition, PCR-DGGE analysis showed that main bacterial population identified in F. thunbergii was proteobacteria (18 bands, 55%), acidobacteria (4, 12%), actinobacteria (4, 12%) and bacterioidetes (6, 18%). Overall, soil properties and microbial communities varied not only between the rhizosphere and bulk soil but also among the three regions. We suggest that the plant, together with the soil properties, cooperatively shape the structure of the rhizosphere bacteria, and that the soil properties have a close relationship with the geoherbalism of F. thunbergii.


[Characteristics of the antitoxic and antibacterial immune response in children with diphtheria].
As found in this study, the development of the manifest forms of diphtheria occurred in the presence of lower levels of antitoxic antibodies, than bacterial carrier state. The level of antitoxic antibodies in all patients, irrespective of the time of their examination, was higher than that of antibacterial antibodies. In the dynamics of the disease a considerable increase in antitoxic and antibacterial antibodies was observed in localized and disseminated forms of diphtheria and, to a considerably lesser degree, in toxic and subtoxic forms of diphtheria, while not observed in the process of the formation of bacterial carrier state. The dynamics of a rise in the levels of antitoxic and antibacterial antibodies in the manifest forms of diphtheria infection made it possible to differentiate between the cases of toxigenic Corynebacterium diphtheriae carrier state and those of the disease.


Translational coupling between the ilvD and ilvA genes of Escherichia coli.
The hypothesis that translation of the ilvD and ilvA genes of Escherichia coli may be linked has been examined in strains in which lacZ-ilvD protein fusions are translated in all three reading frames with respect to ilvD. In these strains, the nucleotide sequence was altered to obtain premature termination of ilvD translation, and in one strain translation termination of ilvD DNA occurred two bases downstream of the ilvA initiation codon. In the wild-type strain, the ilvD translation termination site was located two bases upstream of the ilvA start codon. In each of the mutant strains, expression of ilvA, as determined by the level of threonine deaminase activity, was strikingly lower than in the wild-type strain. The data suggest that expression of ilvD and ilvA is translationally coupled. By inserting a promoterless cat gene downstream of ilvA, it was shown that the differences in enzyme activity were not the result of differences in the amount of ilvA mRNA produced.


Altered cell function and increased replication of rhinoviruses and EV-D68 in airway epithelia of asthma patients.
Rhinovirus (RV) infections constitute one of the main triggers of asthma exacerbations and an important burden in pediatric yard. However, the mechanisms underlying this association remain poorly understood. In the present study, we compared infections of in vitro reconstituted airway epithelia originating from asthmatic versus healthy donors with representative strains of RV-A major group and minor groups, RV-C, RV-B, and the respiratory enterovirus EV-D68. We found that viral replication was higher in tissues derived from asthmatic donors for all tested viruses. Viral receptor expression was comparable in non-infected tissues from both groups. After infection, ICAM1 and LDLR were upregulated, while CDHR3 was downregulated. Overall, these variations were related to viral replication levels. The presence of the CDHR3 asthma susceptibility allele (rs6967330) was not associated with increased RV-C replication. Regarding the tissue response, a significantly higher interferon (IFN) induction was demonstrated in infected tissues derived from asthmatic donors, which excludes a defect in IFN-response. Unbiased transcriptomic comparison of asthmatic versus control tissues revealed significant modifications, such as alterations of cilia structure and motility, in both infected and non-infected tissues. These observations were supported by a reduced mucociliary clearance and increased mucus secretion in non-infected tissues from asthmatic donors. Altogether, we demonstrated an increased permissiveness and susceptibility to RV and respiratory EV infections in HAE derived from asthmatic patients, which was associated with a global alteration in epithelial cell functions. These results unveil the mechanisms underlying the pathogenesis of asthma exacerbation and suggest interesting therapeutic targets.


Lineage divergence, local adaptation across a biogeographic break, and artificial transport, shape the genetic structure in the ascidian Pyura chilensis.
Marine benthic organisms inhabit a heterogeneous environment in which connectivity between populations occurs mainly through dispersive larval stages, while local selective pressures acting on early life history stages lead to non-random mortality, shaping adaptive genetic structure. In order to test the influence of local adaptation and neutral processes in a marine benthic species with low dispersal, in this study we used Genotyping by Sequencing technology to compare the neutral and putatively selected signals (neutral and outlier loci, respectively) in SNPs scattered throughout the genome in six local populations of the commercially exploited ascidian Pyura chilensis along the southeast Pacific coast (24°-42°S). This species is sessile as an adult, has a short-lived larval stage, and may also be dispersed by artificial transport as biofouling. We found that the main signal in neutral loci was a highly divergent lineage present at 39°S, and a subjacent signal that indicated a separation at 30°S (north/south), widely reported in the area. North/south separation was the main signal in outlier loci, and the linage divergence at 39°S was subjacent. We conclude that the geographic structure of the genetic diversity of outlier and neutral loci was established by different strengths of environmental, historical and anthropogenic factors.


Flexibility in the specificity site of serine proteases.
The statistical availability of tryptophan and tyrosine residues with one ring face fully exposed to solvent was examined for two serine proteases and their derivatives by investigating the formation of charge transfer (CT) complexes between the aromatic donor residues of the protein and the acceptor 1-methylnicotinamide chloride. The availability of the ring face of one of the two exposed tryptophan residues in trypsin has been previously shown to be pH dependent and to parallel the acid side of the pH-activity profile of the enzyme. The present results indicate that, in diisopropylphosphoryl-trypsin (DIP-trypsin), this residue [which was identified as Trp-215 in native trypsin (chymotrypsin numbering)] is locked in a relatively rigid, pH-independent conformation with one ring face rotated out toward the solvent. In the zymogen and DIP-zymogen, the ring face is essentially unavailable. Chymotrypsin, like trypsin, has a pH-depent tryptophan residue available for complexation with the CT acceptor, but unlike trypsin, the pH dependence is apparently associated with dimerization of the enzyme. These and other data suggest this residue is the same as in the homologous trypsin structure, i.e., Trp 215, and that the ring face is mostly buried in the zymogen. Comparison of the crystal structure models of chymotrypsin and chymotrypsinogen shows that, as the specificity pocket opens up from its collapsed structure upon zymogen activation, the ring face of Trp-215 moves out and rotates relative to the surface of the enzyme in such a fashion as to become more accessible to solvent. These observations are in accord with the present CT results and provide additional support for the assignment of changes in Trp-215 availability to parallel changes in the conformation of the specificity pocket of these serine proteases. The present investigation also shows that, although a tryptophan ring face is partly exposed in DIP-chymotrypsin, its statistical availability more closely resembles that of the zymogen than the native enzyme. The reverse appears to be true for DIP-trypsin, which suggests the possibility that the specificity pocket in DIP-chymotrypsin may be partially collapsed while the catalytic residues are frozen in the conformation of the acyl-enzyme.


Where wilderness, medicine, technology, and religion collide.
We report a case of a man injured in Yosemite National Park (YNP) whose use of technology and refusal of medical care, based on his Christian Science religious beliefs, created multiple challenges to the providers working to rescue and care for him. This case illustrates how our increasingly diverse and complex world requires flexibility and openness to provide the optimal care, both in the wilderness and in the front country.


Living in stable social groups is associated with reduced brain size in woodpeckers (Picidae).
Group size predicts brain size in primates and some other mammal groups, but no such relationship has been found in birds. Instead, stable pair-bonding and bi-parental care have been identified as correlates of larger brains in birds. We investigated the relationship between brain size and social system within the family Picidae, using phylogenetically controlled regression analysis. We found no specific effect of duration or strength of pair-bonds, but brain sizes were systematically smaller in species living in long-lasting social groups of larger sizes. Group-living may only present a cognitive challenge in groups in which members have individually competitive relationships; we therefore propose that groups functioning for cooperative benefit may allow disinvestment in expensive brain tissue.


Negative effect of high pH on biocidal efficacy of copper and silver ions in controlling Legionella pneumophila.
Copper-silver (Cu-Ag) ionization has effectively controlled Legionella spp. in the hot water systems of numerous hospitals. However, it was ineffective at controlling Legionella in one Ohio hospital despite the confirmation of adequate total concentrations of copper and silver ions. The pH of the water at this hospital was found to be 8.5 to 9.0. The purpose of this study was to investigate the impact of pH and other water quality parameters, including alkalinity (HCO3-), hardness (Ca2+ and Mg2+), and amount of dissolved organic carbon (DOC), on the control of Legionella by Cu-Ag ionization. Initial concentrations of Legionella and copper and silver ions used in batch experiments were 3 x 10(6) CFU/ml and 0.4 and 0.08 mg/liter, respectively. Changes in bicarbonate ion concentration (50, 100, and 150 mg/liter), water hardness (Ca2+ at 50 and 100 mg/liter; Mg2+ at 40 and 80 mg/liter), and level of DOC (0.5 and 2 mg/liter) had no significant impact on the efficacy of copper and silver ions in killing Legionella at a neutral pH. When the pH was elevated to 9 in these experiments, copper ions achieved only a 10-fold reduction in the number of Legionella organisms in 24 h, compared to a millionfold decrease at pH 7.0. Silver ions were able to achieve a millionfold reduction in 24 h at all ranges of water quality parameters tested. Precipitation of insoluble copper complexes was observed at a pH above 6.0. These results suggest that pH may be an important factor in the efficacy of copper-silver ionization in controlling Legionella in water systems.


Biomonitoring of exposure to N-methyl-2-pyrrolidone in workers of the automobile industry.
N-methyl-2-pyrrolidone (NMP) is an important organic solvent for varnishes in industry. NMP has been previously shown to be a developmental toxicant in rodents. This study reports current exposures to NMP in the spraying department of an automobile plant using biological monitoring. Two specific metabolites, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methyl-succinimide (2-HMSI), were analyzed in 69 urine samples of 14 workers exposed to NMP and 9 nonexposed controls. Three different working tasks ('loading' and 'cleaning' of the sprayer system and 'wiping/packing' of the sprayed materials) and three sampling times (preshift, postshift, and preshift of the following day) were studied in exposed workers. Median exposures of 5-HNMP and 2-HMSI in postshift urine of exposed workers were 0.91 and 0.52mg g(-1) creatinine, respectively, whereas median levels in controls were below the limit of detection. Decreased levels of 5-HNMP were observed in preshift urine samples on the following day (0.39mg g(-1) creatinine) in exposed workers, while the concentration of 2-HMSI did not change (0.49mg g(-1) creatinine). Highest exposures occurred during sprayer cleaning with a maximum level of 8.31mg g(-1) creatinine of 5-HNMP in postshift urine. In contrast to 'wipers/packers', no decrease in 5-HNMP could be observed in preshift urine samples on day 2 of the 'loaders' and 'cleaners'. Overall, exposure in terms of 5-HNMP postshift and 2-HMSI preshift of the following day were well below the current biological limit values of the European Union (70 and 20mg g(-1) creatinine). Our results provide initial data on NMP exposure in the automobile industry and suggest that the analysis of 5-HNMP in preshift samples also provides essential information, particularly in situations involving direct handling of liquid NMP-containing formulations.


Efficient Conversion of Light to Chemical Energy: Directional, Chiral Photoswitches with Very High Quantum Yields.
Photochromic systems have been used to achieve a number of engineering functions such as light energy conversion, molecular motors, pumps, actuators, and sensors. Key to practical applications is a high efficiency in the conversion of light to chemical energy, a rigid structure for the transmission of force to the environment, and directed motion during isomerization. We present a novel type of photochromic system (diindane diazocines) that converts visible light with an efficiency of 18 % to chemical energy. Quantum yields are exceptionally high with >70 % for the cis-trans isomerization and 90 % for the back-reaction and thus higher than the biochemical system rhodopsin (64 %). Two diastereomers (meso and racemate) were obtained in only two steps in high yields. Both isomers are directional switches with high conversion rates (76-99 %). No fatigue was observed after several thousands of switching cycles in both systems.


Nickel nanoparticle decorated silicon carbide as a thermal filler in thermal conductive aramid nanofiber-based composite films for heat dissipation applications.
Aramid nanofibers (ANFs) have shown potential applications in the fields of nanocomposite reinforcement, battery separators, thermal insulation and flexible electronics. However, the inherent low thermal conductivity limits the application of ANFs, currently, to ensure long lifetime in electronics. In this work, new nickel (Ni) nanoparticles were employed to decorate the silicon carbide (SiC) filler by a rapid and non-polluting method, in which nickel acetate tetrahydrate (Ni(CH3COO)2·4H2O) and SiC were mixed and heated under an inert atmosphere. The composites as thermal fillers were applied to prepare an aramid nanofiber (ANF)-based composite film. Our results showed that the decoration of SiC by an appropriate amount of Ni nanoparticles played an important role in improving the thermal conductivity, hydrophobicity, thermal stability, and puncture resistance of the ANF composite film. After adjusting the balling time at 10 h, the optimized content of 10 mol% Ni nanoparticles improved the thermal conductivity to 0.502 W m-1 K-1, 298.4% higher than that of the original ANF film. Moreover, increasing the content of thermal fillers to 30 wt% realized a high thermal conductivity of 0.937 W m-1 K-1, which is 643.7% higher than that of the pristine ANF film. Moreover, the compatibility between thermal fillers and ANFs and thermal stability were improved for the ANF-composite films. The effective heat transfer function of our composite films was further confirmed using a LED lamp and thermoelectric device. In addition, the obtained composite films show certain mechanical properties and better hydrophobicity; these results exhibit their great potential applications in electronic devices.


Comparison of blood sampling methods for plasma corticosterone measurements in mice associated with minimal stress-related artefacts.
Accurate measurement of circulating glucocorticoid concentrations in rodents is often hampered by the stress-related activation of the hypothalamic-pituitaryadrenal axis during animal handling. The present study aims to identify methods of blood collection associated with minimal stress and thus artificial increases in plasma glucocorticoid levels. Using two strains of mice, we evaluated common laboratory methods of non-terminal (tail blood sampling with or without restraint; retro-orbital puncture) and terminal blood collection (cardiac puncture) and their immediate and prolonged effect on plasma corticosterone levels. Compared to retro-orbital and cardiac puncture, mice from both the unrestrained and restrained tail snip collection groups displayed the lowest plasma corticosterone levels in both mouse strains. Plasma corticosterone levels in samples obtained from retro-orbital and cardiac puncture collection were up to twenty times higher than those measured in mice undergoing blood collection via tail snip. Repeat tail snip collections (every 30 min for 120 min, or once after 120 min) revealed sustained hypercortisolaemia, compared to the initial collection. We conclude that blood sampling via tail snip without restraint remains the gold-standard method of collection that is associated with minimal stress-related artefacts and hence feasible for single time point corticosterone analyses.


Phosphine Analysis in Postmortem Specimens Following Inhalation of Phosphine: Fatal Aluminum Phosphide Poisoning in Children.
Phosphine is an insecticide for the fumigation of grains, animal feed, and leaf-stored tobacco, and it was used as a rodenticide in bulk grain stores. Phosphine poisoning may occur after accidental inhalation of phosphine, sometimes leading to death. Analysis of phosphine and its metabolites in postmortem specimens from seven fatal cases was conducted in this study, as well as postmortem specimens collected from rabbits exposed to phosphine. The total phosphine in postmortem specimens was analyzed by headspace gas chromatography coupled with mass spectrometry. Diagnosis of aluminum phosphide poisoning was made after postmortem toxicological analysis and confirmed by police investigation. The deaths of the children occurred after inhalation of phosphine generated from aluminum phosphide contacting moisture in the air in all seven fatal cases. The concentration of total phosphine in the biological fluids and tissues of victims ranged from 0.2 to 4.7 μg/mL (μg/g). Animal experiments demonstrated that the phosphine generated from aluminum phosphide could rapidly cause death. The toxicological analysis of postmortem specimens provides useful information in diagnosis of aluminum phosphide poisoning in forensic science. As an important fumigation pesticide, aluminum phosphide deserves special attention, especially since there is no specific antidote and there is a high fatality rate.


Young Group Identification and Motives as Predictors of Ageism, Aging Anxiety, and Life Satisfaction.
The present study examined young group identification and young group motives (i.e., self-esteem, distinctiveness, belonging, meaning, efficacy, and continuity) as predictors of ambivalent ageism, stereotyping of older people, aging anxiety, and life satisfaction among Turkish university students. Participants (N = 226) completed scales measuring age group identification, social identity motives, ambivalent ageism, stereotyping of older people, aging anxiety, and life satisfaction. Multiple hierarchical regression analyses showed that belonging to a young group was a significant predictor for ambivalent ageism. Young group identification and meaning were significant predictors for negative stereotyping of older people. Young group self-esteem was a significant predictor for aging anxiety. Young group identification, self-esteem, and meaning were significant predictors for life satisfaction. None of the independent variables was a significant predictor for positive stereotyping of older people.


Selected eating behaviours of girls and boys attending sport-oriented classes
Eating behaviours play a key role in lives of young people who stay physically active. They influence both their correct development and performance. Evaluation of selected eating behaviours of girls and boys attending sport-oriented classes and identification of differences between eating behaviours of studied groups. 460 students attending sport-oriented classes in Poland participated in the study. A questionnaire prepared by the author of the study was the research tool. The data was gathered in Microsoft Office Excel 2010 worksheet. Statistical analysis was made with the use of StatSoft, Inc. Statistica version 10.0. The questioned students most often had 4-5 meals a day- such an answer was given by 59.09% of the boys and 41.38% of the girls. 55.59% and 41.95% of them respectively had breakfast within 30 minutes from waking up and 41,96% of the girls and 39.51% of the boys had supper 2-3 hours before going to sleep. Whole meal bread and/or groats were most frequently consumed a few times a day as it was declared by 50.35% of the boys and 45.98% of the girls. The highest percentage of the respondents consumed vegetables at least once a day (31.61% of the girls and 31.47% of the boys). 44.83% of the girls and 40.9% of the boys declared eating fruit a few times a day. Studied eating behaviours of girls and boys in sport-oriented classes are largely wrong and require correction. The analysis of the gathered data indicated statistically significant differences between boys' and girls' eating behaviours, however, the boys' habits were better.


Manipulating the Energetics and Rates of Electron Transfer in Rhodobacter capsulatus Reaction Centers with Asymmetric Pigment Content.
Seemingly redundant parallel pathways for electron transfer (ET), composed of identical sets of cofactors, are a cornerstone feature of photosynthetic reaction centers (RCs) involved in light-energy conversion. In native bacterial RCs, both A and B branches house one bacteriochlorophyll (BChl) and one bacteriopheophytin (BPh), but the A branch is used exclusively. Described herein are the results obtained for two Rhodobacter capsulatus RCs with an unnaturally high degree of cofactor asymmetry, two BPh on the RC's B side and two BChl on the A side. These pigment changes derive, respectively, from the His(M180)Leu mutation [a BPh (ΦB) replaces the B-side BChl (BB)], and the Leu(M212)His mutation [a BChl (βA) replaces the A-side BPh (HA)]. Additionally, Tyr(M208)Phe was employed to disfavor ET to the A branch; in one mutant, Val(M131)Glu creates a hydrogen bond to HB to enhance ET to HB. In both ΦB mutants, the decay kinetics of the excited primary ET donor (P*) resolve three populations with lifetimes of ∼9 ps (50-60%), ∼40 ps (10-20%), and ∼200 ps (20-30%), with P+ΦB- formed predominantly from the 9 ps fraction. The 50-60% yield of P+ΦB- is the highest yet observed for a ΦB-containing RC. The results provide insight into factors needed for efficient multistep ET.


Necrosis and bacterial infection in channel catfish (Ictalurus punctatus) following hypoxia.
Apparently sterile lesions developed in the skin and musculature of channel catfish (Ictalurus punctatus) six days after fish were severely stressed by an oxygen depletion associated with a phytoplankton die-off in an 8.9 ha pond. Lesions were characterized by hemorrhage and necrosis. Aeromonas hydrophila was isolated from either the lesions ot internal organs of all moribund fish necropsied the day after lesions were first found. As the water quality improved the health of the fish improved. Water quality data collected before and after the oxygen depletion, and associated fish mortality, are presented.


The risk of bisphosphonate-related osteonecrosis of the jaw in children. A case report and literature review.
Bisphosphonate use has been described in children diagnosed with osteogenesis imperfecta (OI), fibrous dysplasia, neuromuscular disorders, bone dysplasia, idiopathic juvenile osteoporosis, rheumatologic disorder and even Crohn's disease. In OI patients, bisphosphonates have become an important symptomatic therapy for moderate and severe forms of the disease, because their inhibitory effect on osteoclasts increases bone mineralization and density, thereby reducing the risk of bone fractures. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has become an increasingly common complication as the use of these drugs is becoming more widespread in adults. However, the evidence for BRONJ in paediatric patients is scarce. We present a case of a patient with OI on IV bisphosphonate therapy who required dental extractions and review the literature of the risk of BRONJ in this group of patients. Dental clinicians need to be aware of the potential risk of BRONJ in paediatric patients who have had intravenous bisphosphonate therapy. It is important that these patients are identified and managed appropriately.


Structure-Based Virtual Screening, Compound Synthesis, and Bioassay for the Design of Chitinase Inhibitors.
Chitinases play a vital part in the molting phase of insect pests. Inhibiting their activities by the use of drug-like small chemical molecules is thought to be an efficient strategy in pesticide design and development. On the basis of the crystal structure of OfChtI, a chitinase indispensable for the molting of the insect pest Ostrinia furnacalis (Asian corn borer), here we report a chemical fragment and five variant compounds as inhibitors of OfChtI obtained from a library of over 200 000 chemicals by a structure-based-virtual-screening approach. The compounds were synthesized with high atom economy and tested for their OfChtI-inhibitory activities in a bioassay. Compound 3 showed preferential inhibitory activity with a Ki value of 1.5 μΜ against OfChtI. Analysis of the structure-activity relationships of the compounds provided insight into their interactions with the enzyme active site, which may inform future work in improving the potencies of their inhibitory activities.


Neuropeptide Y-induced intestinal absorption: mediation by alpha 2-adrenergic receptors.
In the intestine neuropeptide Y (NPY) is contained in sympathetic nerves, in neuroendocrine cells of the mucosa, and in neurons of the enteric plexuses. After a meal is ingested the concentration of NPY in the blood rises, and intestinal absorption of water and ions increases. We have recently demonstrated a proabsorptive effect of NPY on water and ion transport in the small intestine. The current experiments tested the hypothesis that the alpha 2-adrenergic receptor mediates NPY-induced intestinal absorption. Rabbit ileal segments (n = 35) were harvested and arterially perfused ex vivo. The intestinal lumen was perfused with an isotonic solution containing carbon 14-labeled polyethylene glycol. Net fluxes of H2O, Na+, and Cl- were calculated for three 20-minute periods: basal, drug infusion, and recovery. Five groups were randomly studied: (1) NPY (500 pmol/min); (2) terazosin (1 microgram/min, alpha 1-adrenergic receptor antagonist); (3) NPY + terazosin; (4) yohimbine (1 microgram/min, alpha 2-adrenergic receptor antagonist); and (5) NPY + yohimbine. The infusion of NPY alone caused a significant (p less than 0.05) proabsorptive response for H2O, Na+, and Cl-. Neither terazosin nor yohimbine alone had a significant effect on the transport state of the intestine. Yohimbine, but not terazosin, completely prevented the NPY-induced proabsorptive response. These data support the hypothesis that the proabsorptive effect of NPY is mediated by the alpha 2-adrenergic receptor system.


Contribution of citrulline to the formation of ethyl carbamate during Chinese rice wine production.
Ethyl carbamate is a well-known carcinogen and widely occurs in Chinese rice wine. To provide more clues to minimise ethyl carbamate accumulation, the levels of possible precursors of ethyl carbamate in Chinese rice wine were investigated by HPLC. Studies of the possible precursors of ethyl carbamate in Chinese raw rice wine with various additives and treatments indicated that significant amounts of urea can account for ethyl carbamate formation. It was also recognised that citrulline is another important precursor that significantly affects ethyl carbamate production during the boiling procedure used in the Chinese rice wine manufacturing process. Besides urea and citrulline, arginine was also found to be an indirect ethyl carbamate precursor due to its ability to form urea and citrulline by microorganism metabolism.


Purification of human cholesteryl ester transfer protein by affinity chromatography on immobilized triazine dyes.
Human cholesteryl ester transfer protein was purified from lipoprotein-depleted serum or plasma in a three-step procedure utilizing commercially available triazine dyes immobilized on agarose. The method used consisted of successive chromatography steps on Reactive Red 120 agarose (Procion Red H-E3B, Cibachron Brilliant Red 4G-E), CM Sepharose, and Reactive Yellow 86 agarose (Procion Yellow M-8G). Upon analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the resultant protein preparation displayed two bands of variable intensity. The two components had apparent molecular weights of approximately 64,000 and approximately 65,000, respectively. Both bands reacted strongly to a monoclonal antibody directed against an epitope consisting of the last eight amino acids at the carboxy terminus of human CETP. Yields of cholesteryl ester transfer activity are 10-40% of the activity present in lipoprotein-depleted serum. The activity is approximately 50,000- to 100,000-fold purified relative to the starting material.


[Micromanipulation of gametes and pre-implantation mammalian embryos--a review].
With the successful management of the in vitro fertilization and embryo transfer in humans and in several mammalians it became possible to introduce further methods of the cellbiology in the practice. One complex in this connection is hereby shown to be the micromanipulation on gametes and on preimplantative embryos. With this technique the way was opened for some procedures which are known as microfertilization, transplantation of the nucleus and gene transfer somatic gene therapy. With these experiments a broad field of possibilities would be opened although about these can be only speculated.


Bioethics and artificial intelligence: between deliberation on values and rational choice theory.
The present work revisits how artificial intelligence, as technology and ideology, is based on the rational choice theory and the techno-liberal discourse, supported by large corporations and investment funds. Those that promote using different algorithmic processes (such as filter bubbles or echo chambers) create homogeneous and polarized spaces that reinforces people's ethical, ideological, and political narratives. These mechanisms validate bubbles of choices as statements of fact and contravene the prerequisites for exercising deliberation in pluralistic societies, such as the distinction between data and values, the affirmation of reasonable dissent, and the relevance of diversity as a condition indispensable for democratic deliberation.