Physiological expression of the 2',5'-oligoadenylate synthetase gene in mouse intestine.
2',5'-Oligoadenylate synthetase (2-5A synthetase) is an enzyme induced by interferon (IFN) that is considered to play an important role in IFN action. The normal mouse, not treated exogenously with any IFN or IFN inducers, has been shown to have an enhanced level of 2-5A synthetase activity, which is distributed among several lymphoid tissues. In the present report, we investigated the expression of the 42-kD 2-5A synthetase mRNA in the organs of normal mice using RNA blot hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). Among the organs tested, intestinal tissues had the highest levels of this mRNA. Furthermore, the 42-kD 2-5A synthetase mRNA was expressed in intestines from germ-free mice and fetuses. Immunoblotting analysis using a monoclonal antibody against the 42-kD 2-5A synthetase revealed that the 42-kD enzyme as well as a cross-reactive protein of 30 kD were produced in the organs of the normal mouse.


On the origin of vorticity in magnetic particle suspensions subjected to triaxial fields.
We have recently reported that two classes of time-dependent triaxial magnetic fields can induce vorticity in magnetic particle suspensions. The first class - symmetry-breaking fields - is comprised of two ac components and one dc component. The second class - rational triad fields - is comprised of three ac components. In both cases deterministic vorticity occurs when the ratios of the field frequencies form rational numbers. A strange aspect of these fields is that they produce fluid vorticity without generally having a circulating field vector, such as would occur in a rotating field. It has been shown, however, that the symmetry of the field trajectory, considered jointly with that of the converse field, allows vorticity to occur around one particular field axis. This axis might be any of the field components, and is determined by the relative frequencies of the field components. However, the symmetry theories give absolutely no insight into why vorticity should occur. In this paper we propose a particle-based model of vorticity in these driven fluids. This model proposes that particles form volatile chains that follow, but lag behind, the dynamic field vector. This model is consistent with the predictions of symmetry theory and gives reasonable agreement with previously reported torque density measurements for a variety of triaxial fields.


Enzyme- and immuno-histochemical study of the thymic stroma in the rainbow trout, Salmo gairdneri, Richardson.
Owing to the lack of data about thymic non-lymphoid cells in fish we decided to perform a histochemical characterization of these cells in order to ascertain their relationships to other thymic components. In the present study we analyze the enzyme-histochemical patterns for acid phosphatase, alkaline phosphatase, non-specific sigma-naphthyl acetate esterase and 5' nucleotidase activities, as well as the presence of keratin demonstrated by immunoperoxidase staining, in the non-lymphoid cell populations of the thymus of the rainbow trout, Salmo gairdneri. According to their location in the organ, morphology and histochemical reactivities, we were able to define seven different subpopulations of keratin-positive epithelial cells: 1) Epithelial cells limiting with the capsular and septal connective tissues; 2) Subcapsular epithelial cells; 3) Stellate epithelial cells of the inner thymic zone; 4) Large, ovoid epithelial cells of the inner thymic zone; 5) Acidophilic epithelial cells of the outer thymic zone; 6) Cystic cells; and 7) Goblet cells. The significance of the heterogeneity of the epithelial cell (EC) population, its specific distribution in the organ, which apparently conforms distinct cell microenvironments, as well as the possible phylogenetical relationships between these microenvironments and the classical cortex and medulla of the mammalian thymus, are discussed.


Genetic Diversity and Association Characters of Bacteria Isolated from Arbuscular Mycorrhizal Fungal Spore Walls.
Association between arbuscular mycorrhizal fungi (AMF) and bacteria has long been studied. However, the factors influencing their association in the natural environment is still unknown. This study aimed to isolate bacteria associated with spore walls of AMF and identify their potential characters for association. Spores collected from coastal reclamation land were differentiated based on their morphology and identified by 18S rDNA sequencing as Funneliformis caledonium, Racocetra alborosea and Funneliformis mosseae. Bacteria associated with AMF spore walls were isolated after treating them with disinfection solution at different time intervals. After 0, 10 and 20 min of spore disinfection, 86, 24 and 10 spore associated bacteria (SAB) were isolated, respectively. BOX-PCR fingerprinting analysis showed that diverse bacterial communities were associated to AMF spores. Bacteria belonging to the same genera could associate with different AMF spores. Gram positive bacteria were more closely associated with AMF spores. Isolated SAB were characterized and tested for spore association characters such as chitinase, protease, cellulase enzymes and exopolysaccharide production (EPS). Among the 120 SAB, 113 SAB were able to show one or more characters for association and seven SAB did not show any association characters. The 16S rDNA sequence of SAB revealed that bacteria belonging to the phyla Firmicutes, Proteobacteria, Actinobacteria and Bactereiodes were associated with AMF spore walls.


UP12, a novel ursolic acid derivative with potential for targeting multiple signaling pathways in hepatocellular carcinoma.
Targeting cancer cell glucose metabolism is a promising strategy for cancer therapy. In past approaches to cancer drug discovery, ursolic acid (UA) has been chemically modified to improve its antitumor activities and bioavailability. Here, a novel ursolic acid (UA) derivative UP12 was developed via computer-aided drug design to explore potent anti-cancer agents and to examine possible mechanisms. The structural docking analyses suggested that UP12 could bind to the active sites of glucokinase (GK), glucose transporter 1 (GLUT1) and ATPase, which are the main enzymes involved in cancer glucose metabolism. We further investigated the synergistic effect between UP12 and glycolysis inhibitor 2-deoxy-d-glucose (2-DG) in inhibiting glucose metabolism of cancer cells. The pharmacological results showed that the combination enhanced depletion of intracellular ATP and decrease in lactate production, and pushed more cancer cells arrested in the S and G2/M cycle phases. The combination selectively down-regulated the expression of Bcl-2 and HKII proteins, up-regulated the expression of Bax and p53, and collectively resulted in enhanced apoptosis related to caspase-3, -8, and -9 activities, in addition to inhibition on the cell mitochondrial membrane potential. The animal studies further demonstrated that the combination exhibited significant antitumor activity without obvious toxicity. In summary, UP12 can interfere cancer cell metabolism pathway and further enhance the therapeutic effects of 2-DG likely through synergistic suppression of cancer cell glucose metabolism, making UP12 a likely new candidate for anti-cancer drug development.


Microbial Diversity and Mercury Methylation Activity in Periphytic Biofilms at a Run-of-River Hydroelectric Dam and Constructed Wetlands.
Periphytic biofilms have the potential to greatly influence the microbial production of the neurotoxicant monomethylmercury in freshwaters although few studies have simultaneously assessed periphyton mercury methylation and demethylation rates and the microbial communities associated with these transformations. We performed a field study on periphyton from a river affected by run-of-river power plants and artificial wetlands in a boreal landscape (Québec, Canada). In situ incubations were performed on three sites using environmental concentrations of isotopically enriched monomethylmercury (MM198Hg) and inorganic mercury (200Hg) for demethylation and methylation rate measurements. Periphytic microbial communities were investigated through 16S rRNA gene analyses and metagenomic screenings for the hgcA gene, involved in mercury methylation. Positive mercury methylation rates ([5.9 ± 3.4] × 10-3 day-1) were observed only in the wetlands, and demethylation rates averaged 1.78 ± 0.21 day-1 for the three studied sites. The 16S rRNA gene analyses revealed Proteobacteria as the most abundant phylum across all sites (36.3% ± 1.4%), from which families associated with mercury methylation were mostly found in the wetland site. Metagenome screening for HgcA identified 24 different hgcA sequences in the constructed wetland site only, associated with 8 known families, where the iron-reducing Geobacteraceae were the most abundant. This work brings new information on mercury methylation in periphyton from habitats of impacted rivers, associating it mostly with putative iron-reducing bacteria.IMPORTANCE Monomethylmercury (MMHg) is a biomagnifiable neurotoxin of global concern with risks to human health mostly associated with fish consumption. Hydroelectric reservoirs are known to be sources of MMHg many years after their impoundment. Little is known, however, on run-of-river dams flooding smaller terrestrial areas, although their numbers are expected to increase considerably worldwide in decades to come. Production of MMHg is associated mostly with anaerobic processes, but Hg methylation has been shown to occur in periphytic biofilms located in oxic zones of the water column. Therefore, in this study, we investigated in situ production of MMHg by periphytic communities in habitats impacted by the construction of a run-of-river dam by combining transformation rate measurements with genomic approaches targeting hgcAB genes, responsible for mercury methylation. These results provide extended knowledge on mercury methylators in river ecosystems impacted by run-of-river dams in temperate habitats.


Acute hepatitis A virus infection: a review of prognostic factors from 25 years experience in a tertiary referral center.
Hepatitis A is usually a mild, self-limiting illness but can result in severe or fatal disease. We reviewed 25 years experience to determine what factors predispose to severe or fatal disease. We identified 97 patients admitted between 1974-1999 with acute hepatitis A. Clinical, biochemical and histological data were correlated with outcome and patients were screened for evidence of hepatitis B or C virus coinfection and coexisting autoimmunity. Fifty-five patients had liver failure with hepatic encephalopathy of whom 29 died and 6 underwent liver transplantation. Patients with liver failure were significantly older than those without (mean age: 42.2 +/- 13.3 vs. 29.2 +/- 7.8, P = 0.0001), and liver failure patients who died were older than those surviving (47.5 +/- 12.7 vs. 36.3 +/- 11.6, P = 0.0001). Hyperacute liver failure predicted good outcome (P = 0.0001). Three patients with viral coinfection had established cirrhosis and died. Detectable autoantibodies did not correlate with outcome or severity. Patients acquiring infection abroad were more likely to have liver failure than those acquiring infection in the UK (P = 0.023). Age is the best predictor for outcome in patients with liver failure from hepatitis A. Underlying chronic liver disease, and the time of onset of encephalopathy are also factors affecting outcome. Infection acquired abroad has a worse prognosis.


Attentional filtering in the design of electronic map displays: a comparison of color coding, intensity coding, and decluttering techniques.
In a series of experiments color coding, intensity coding, and decluttering were compared in order to assess their potential benefits for accessing information from electronic map displays. Participants viewed electronic battlefield maps containing 5 classes of information discriminable by color or intensity, or, in the decluttering condition, displayed or removed entirely by a key press. Participants were asked questions requiring them to focus on objects within a class (objects presented at the same color or intensity) or to integrate data between objects in different classes (objects presented at different colors and intensities). The results suggested that the benefits of color and intensity coding appear to be in segregating the visual field rather than calling attention to the objects presented at a certain color or intensity. Interactivity proved to be a disadvantage; the time cost of information retrieval outweighed the time benefits of presenting less information on the display or even allowing map users to customize their displays. Potential applications of this research include a cost-benefit analysis for the use of 3 attentional filtering techniques and an attempt to quantitatively measure map complexity.


Information integration in a decision support system.
Electronic medical records pose a challenge because of the complex types of data which are included. Decision support systems must be able to deal effectively with these data types. In the expert system demonstrated here, a diversity of data types are included. These data are processed by three different methods. However, the different methods of processing are transparent to the user. An overall rule-based interface integrates the different methods into one comprehensive system.


Increased tryptophan decarboxylase and monoamine oxidase activities induce Sekiguchi lesion formation in rice infected with Magnaporthe grisea.
Sekiguchi lesion (sl)-mutant rice infected with Magnaporthe grisea showed increased light-dependent tryptophan decarboxylase (TDC) and monoamine oxidase (MAO) activities. TDC and MAO activities were observed before the penetration of M. grisea to rice cells and maintained high levels even after Sekiguchi lesion formation. Light-dependent expression of TDC gene was observed in leaves inoculated with M. grisea before Sekiguchi lesion formation. Spore germination fluid (SGF) of M. grisea also induced Sekiguchi lesion formation accompanied by increased enzymes activities and tryptamine accumulation. Sekiguchi lesion was also induced by treatments with tryptamine and beta-phenylethylamine, which are substrates for MAO, but was not induced by non-substrates such as indole-3-propionic acid, (+/-)-phenylethylamine and tryptophan under light. Light-dependent induction of Sekiguchi lesion by tryptamine was significantly inhibited in the presence of MAO inhibitors, metalaxyl and semicarbazide, and H2O2-scavengers, ascorbic acid and catalase. H2O2 in M. grisea-infected leaves with and without Sekiguchi lesions was demonstrated directly in situ by strong 3,3'-diaminobenzidine (DAB) staining. On the other hand, H2O2 induced Sekiguchi lesions on leaves of cv. Sekiguchi-asahi under light, but not in darkness. This difference was associated with the decrease of catalase activity in infected leaves under light and the absence of decrease in darkness. We hypothesize that the H2O2-induced breakdown of cellular organelles such as chloroplasts and mitochondria in mesophyll cells may cause high TDC and MAO activities and the development of Sekiguchi lesion, and that the sl gene products in wild-type rice may function as a suppressor of organelle breakdown caused by chemical or environmental stress.


Repellent Effects of Insecticides Against Protaphorura fimata (Collembola: Poduromorpha: Onychiuridae).
Protaphorura fimata Gisin (Poduromorpha: Onychiuridae) is a serious pest of lettuce [Lactuca sativa L. (Asteraceae)] in the Salinas Valley of California. Because P. fimata is a subterranean springtail species adapted to soil environments, individuals are assumed to be able to sense and behaviorally avoid insecticide-treated soil, and this capacity could be used strategically to control P. fimata. A series of laboratory bioassays was conducted to examine the behavior of P. fimata with respect to insecticides via noncontact and contact assays. In the noncontact assay, significantly more P. fimata individuals were collected away from the insecticide source than closer to the source (P < 0.05) when clothianidin, flonicamid, bifenthrin, diamethoate, essential oils, extracts of C. subtsugae, methomyl, chlorpyrifos, zeta-cypermethrin, thiamethoxam, pyrethrins, extracts of Burkholderia spp., cyantraniliprole, and oxamyl were used as insecticides. In the contact assay, P. fimata individuals spent significantly less time on discs treated with spinetoram and lambda-cyhalothrin during each crossing than on flonicamid- and oxamyl-treated discs. P. fimata individuals changed direction more frequently while crossing discs when the discs were treated with azadirachtin, clothianidin, bifenthrin, thiamethoxam + chlorantraniliprole, chlorpyrifos, cyantraniliprole, and lambda-cyhalothrin than when they were treated with water. In another contact assay, the number of seedlings injured by P. fimata feeding was significantly lower when germinating seeds were enclosed in a barrier treated with clothianidin, chlopyrifos, pyrethrins, and cyantraniliprole than when they were enclosed in a spinosad-treated barrier. The implications of these data for P. fimata management in the Salinas Valley are discussed.


Anticardiolipin antibodies and recurrent early pregnancy loss: a century of equivocal evidence.
In 1987, Nigel Harris cautioned against over-diagnosing the antiphospholipid syndrome (APS). In what was a rather prophetic editorial titled 'The Syndrome of the Black Swan', he suggested that while patients with APS do indeed exist, they are probably much more unusual than many medical professionals might like to believe. He expressed concern that the value of studying antiphospholipid antibodies (aPLs) as interesting non-organ specific autoantibodies, would become lost in a 'sea of over-interpreted and over-reported laboratory and clinical findings'. It is our contention that 25 years later, this prediction has come to pass, particularly with respect to one type of aPL and its relation to a clinical event, namely anticardiolipin antibodies and early recurrent pregnancy loss. In this commentary, we trace the evolution of the current dogma and propose that reevaluation of available data from an alternative perspective results in quite a different understanding, the acceptance of which would necessitate not only a revision of the classification criteria for APS but also the subsequent revision of many diagnoses.


[Measuring the instant].
The instant is the infinitesimal fraction of time nearest to zero. Its computational measurement is not feasable in that it should be an infinitesimal commensurable portion of infinite time, which is incommensurabile by principle. The philosophical implication is that the instant has to be intended as an abstract entity belonging to metaphysical, transcendent, supranormal, suprasensitive, infinite time. In other words, the instant does not represent an experential deduction of our intellect, but an aprioristic innate idea letting us to be aware of physical, immanent, natural, sensible, finite temporality.


Prevalence of myofascial pain in general internal medicine practice.
Myofascial pain is a regional pain syndrome characterized in part by a trigger point in a taut band of skeletal muscle and its associated referred pain. We examined a series of 172 patients presenting to a university primary care general internal medicine practice. Of 54 patients whose reason for a visit included pain, 16 (30%) satisfied criteria for a clinical diagnosis of myofascial pain. These patients were similar in age and sex to other patients with pain, and the frequency of pain as a primary complaint was similar for myofascial pain as compared with other reasons for pain. The usual intensity of myofascial pain as assessed by a visual analog scale was high, comparable to or possibly greater than pain due to other causes. Patients with upper body pain were more likely to have myofascial pain than patients with pain located elsewhere. Physicians rarely recognized the myofascial pain syndrome. Commonly applied therapies for myofascial pain provided substantial abrupt reduction in pain intensity. The prevalence and severity of myofascial pain in this university internal medicine setting suggest that regional myofascial pain may be an important cause of pain complaints in the practice of general internal medicine.


Models of nursing as the basis for curriculum development: some rationales and implications.
Within this paper the notion of a model of nursing as a basis for curriculum development is explored. Firstly the factors which a curriculum developer in nursing might take under initial consideration are discussed. It is then argued that a nursing faculty must identify and define its conceptualization of nursing and what it is to be a nurse. The process of conceptualizing nursing itself is examined. The paper goes onto argue that once a nursing faculty has reached a consensus view as to what constitutes nursing, then it either designs or selects a model of nursing which supports their particular conceptualization. Educational literature is cited to support the view that curriculum design, process and content are interrelated and that student learning is facilitated when the relationship between these three factors is coordinated. It is suggested that a nursing curriculum can achieve such an integration if a model of nursing is used as the conceptual framework. Finally some of the implications of adopting a model of nursing are stated.


Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics.
Colloidal nanoparticulate technology has been described in the literature as a versatile drug delivery system. But it possesses some inherent lacunae in their formulation. Cyclodextrins (CDs) have been extensively reported for the solubility enhancement of poorly water-soluble drugs. The CDs can cause intervention in aspects related to nanoparticles (NPs) that include improving drug loading in nano-system, improving stability, site-specific/targeted drug delivery, improving solubility profile and absorption of the drug in nanosystem with consequent improvement in bioavailability, with the possibility of controlled release, safety and efficacy. They find application in for simultaneous diagnosis and therapeutics for better treatment procedures. The current communication is focused on the application of CDs to overcome troubles in nanoparticulate formulation and enhancement of their performance. It also envisages the theranostic aspects of CDs.


Becoming a nurse-writer: advice on writing for professional publication.
Successful nursing professionals already have what it takes to write for publication, namely, strong oral and written communication skills honed every day in the workplace. Nurses spend much time and effort in training and actual practice refining their rhetorical skills, that is, their ability to communicate ideas clearly and persuasively to a variety of audiences composed of physicians, other nursing professionals, pharmaceutical representatives, patients, and their families. Without a doubt, experienced nurses have what it takes to write for professional publication.


Bile salt export pump (BSEP/ABCB11): trafficking and sorting disturbances.
Bile salt export pump (BSEP/ABCB11), a member of the family of ATP-binding cassette transporters, is localized on the canalicular membrane of hepatocytes and mediates the efficient biliary excretion of bile acid. The secretion of bile acid into bile by BSEP provides the primary osmotic driving force for bile flow generation. Intrahepatic cholestasis resulting from dysfunction of BSEP can be caused by a mutation in the gene encoding this protein or by acquired factors, such as the side effects of xenobiotics and drugs. In some pathophysiological states, inhibition of BSEP function is associated with its reduced expression on the canalicular membrane caused by impaired trafficking and sorting of BSEP. This fact has generated interest in better understanding the trafficking and sorting mechanism of BSEP. This review describes the molecular characteristics and physiological roles of BSEP, the trafficking and sorting machinery of BSEP, and the mechanisms responsible for disturbance of BSEP, which causes intrahepatic cholestasis.


Alterations in lung structure caused by inhalation of oxidants.
Morphometric and morphologic methods have been used to evaluate changes in rat lungs caused by the inhalation of a variety of oxidants. Exposure to 100% oxygen causes diffuse pulmonary injury and leads to death after 66-72 h of exposure. The primary insult leading to death in rats exposed to hyperoxia is injury to pulmonary capillary endothelium. Sublethal exposure to hyperoxia was found to cause diffuse injury to all major components of the alveolar septum and was associated with destruction of approximately 50% of the pulmonary capillary endothelial cells. A corresponding decrease in pulmonary capillary surface area and capillary lumen volume also occurred. Exposure to ozone and to nitrogen dioxide in low concentrations did not cause a diffuse injury throughout the alveolar region of the lung, but rather led predominantly to structural alterations in terminal bronchioles and in their adjacent alveoli. Morphometric evaluation of animals exposed to 0.25 ppm ozone and to 2 ppm NO2 demonstrated quantitatively and qualitatively similar lesions. These lesions primarily involve injury and remodelling of the alveolar epithelium. These changes in the alveolar epithelium were also associated with the recruitment of increased numbers of alveolar macrophages to the proximal alveolar region. The different types of lung injury caused by various oxidants are most likely to be related to differences in their reactivity with tissue components and to differences in concentration, distribution, and diffusion characteristics of the oxidant gases.


Relationship between serum sialic acid levels and prolidase activity with airflow obstruction in patients with COPD.
Our aim in this study was to evaluate the prognostic significance of sialic acid (SA) and prolidase activity and to evaluate the association between airflow obstruction severity and these parameters in chronic obstructive pulmonary disease (COPD) patients.Ninety-four patients (84 M, 10 F) and 34 healthy subjects (19 M, 15 F) were included into the study. COPD staging was performed to COPD patients according to new global initiative for chronic obstructive lung disease criteria which includes pulmonary function tests, symptoms and hospitalization; COPD patients were divided into 4 subgroups as group A (n = 25), group B (n = 19), group C (n = 20), and group D (n = 28).SA and C-reactive protein levels were significantly higher than the control group in all COPD groups. SA levels were significantly higher in group B patients than the control and group A. Prolidase activity was significantly lower than control group in total COPD groups (P < .05). There was a weak negative correlation between SA and forced vital capacity (r = -0.217, P = .038) and forced expiratory volume in 1 second (FEV1) (r = -0.210, P = .045), whereas weak positive correlation was present between SA and Creactive protein (r = 0.247, P = .018) in all patient groups. There was weak positive correlation between prolidase and FEV1 (r = 0.222, P = .033) and FEV1/forced vital capacity (r = 0.230, P = .027).Our study shows that systemic inflammation, prolidase activity, and SA levels in stable COPD patients are associated with airflow obstruction severity. In addition to the prolidase activity; SA levels might be associated with inflammation.


Parvovirus B19 infection of brain: possible role of gender in determining mental illness and autoimmune thyroid disorders.
Major theories about the etiologies of chronic mental illnesses such as bipolar disorder and schizophrenia include genetic and environmental factors such as famine and infection. It is likely that multiple genes play a role in the pathogenesis of these disorders, but no single gene has been identified as causative. Several viruses have been investigated as potential candidates, but conflicting reports exist. Although a relationship between bipolar disorder and schizophrenia with autoimmune disorders has also been documented for many years, reports are often conflicting. We hypothesize that parvovirus B19 (B19), a common human pathogen, due to its ability to infect the brain and induce autoimmunity, is a strong candidate that may unite prevailing theories. In particular, our preliminary data suggest that B19 may be most likely involved in co-morbid bipolar and autoimmune thyroid disorders in females. In schizophrenics, the gender trend may be reversed. We propose that there is a complex interaction between immuno-genetics, autoimmunity, gender, and B19 infection that leads to at least some forms of bipolar disorder and schizophrenia. Future studies that investigate this hypothesis are warranted and outlined.


A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic agents with a folate-independent locus.
Three lipophilic quinazoline-based aminomethyl pyridine compounds, which differ only in the position of the nitrogen in their pyridine ring, are described. CB300179 (2-pyridine), CB300189 (4-pyridine) and CB30865 (3-pyridine) all inhibited isolated mammalian TS with IC50 values of 508, 250 and 156 nM respectively. CB30865 was the most potent growth inhibitory agent (IC50 values in the range 1-100 nM for several mouse and human cell types). CB300179 and CB300189 were active in the micromolar range. Against W1L2 cells, CB300179 and CB300189 demonstrated reduced potency in the presence of exogenous thymidine (dThd), and against a W1L2:C1 TS overproducing cell line. In contrast, CB30865 retained activity in these systems. Furthermore, combinations of precursors and end products of folate metabolism, e.g. dThd/hypoxanthine (HX) or leucovorin (LV), did not prevent activity. CB30865 did not interfere with the incorporation of tritiated dThd, uridine or leucine after 4 h. A cell line was raised with acquired resistance to CB30865 (W1L2:R865; > 200-fold), which was not cross-resistant to CB300179 or CB300189. In addition, W1L2:R865 cells were as sensitive as parental cells to agents from all the major chemotherapeutic drug classes. CB300179 and CB300189 induced an S phase accumulation (preventable by co-administration of dThd). No cell cycle redistribution was observed following exposure (4-48 h) to an equitoxic concentration of CB30865. In the NCI anticancer drug-discovery screen, CB30865 displayed a pattern of activity which was not consistent with known anti-tumour agents. These data suggest that CB30865 represents a class of potent potential anti-tumour agents with a novel mechanism of action.


Diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration in pancreatic lesions.
This aim of this study is to investigate the diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic lesions. Patients with pancreatic lesions after CT (or MRI) and EUS-FNA examination were retrospectively enrolled. Cytopathological diagnosis of pancreas tissue were obtained by surgery or EUS-FNA. Clinical follow-up results were used as golden standard for diagnosis of pancreatic lesions. Statistical analysis was performed by Student's t-test for continuous data and Fischer exact test for categorical data. A total of 18 patients with pancreatic lesions were included in this study, 7 of which were diagnosed as benign lesions and 11 were diagnosed as malignant lesions. Endoscopic ultrasonography (ESU) showed that most of the lesions were in pancreatic body (42.9%), followed by pancreatic head, pancreatic tail, and pancreatic neck. The maximum diameter of malignant lesions was larger compared with that of benign and the difference was statistically significant (p < 0.05). The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of EUS-FNA for differentiating diagnosis of malignant and benign pancreatic lesions was 83.3%, 80%, 83.3%, 90.9%, and 71.4%, respectively. EUS-FNA cytological diagnosis is safe and effective for differentiating diagnosis of malignant and benign pancreatic lesions.


Music before undergoing cardiac catheterisation between preference and reality. A pilot study.
Previous studies have reported beneficial effects of music in the context of health care: anxiolytic, distracting, pain reliever, promoting nutrition, socialization and comfortable environment. In this pilot study, the patient's point of view before undergoing cardiac catheterization procedure was described. Attitudes to music, including habitual listening by genre and broadcasting were compared with its useful in hospital and in the specific pre-procedural condition. In this cross-sectional study, the interview was conducted through a semi-structured paper questionnaire, subjected to face validity. The sample consisted of patients waiting for the procedure (N=45) included by randomized sampling. A Spearman coefficient was conducted to observe statistically significant correlations. Data were analysed using 24.0 SPSS software. 80% of respondents prefer Italian pop music during procedural waiting, played by loudspeakers (71%). they think music can help them engage the wait (55.6%) and alleviate unpleasant feelings (33.3%). Favorable attitude to music in hospital (91.1%) is significantly correlated to its useful in hospital (p=0.01) but only 8.9% actually use it. Music Preferences support pre-recorded Italian pop music played with loudspeakers, recognized by the patient as the most desired activity while waiting for the procedure. The patient's choice to attribute to music the ability to alleviate unpleasant sensations before the procedure is due to the need for emotional support, to which it can effectively respond. Studies are needed to explore preferences before, during and after music listening and also educate stakeholders in the use of guidelines for music based interventions.


Case Studies in Physiology: Using premature ventricular contractions to understand the regulation of carotid artery longitudinal wall motion.
Recent observations have identified a distinct longitudinal motion pattern of the common carotid artery, where the wall oscillates along its length both with (anterograde) and against (retrograde) the direction of blood flow. The regulation of the longitudinal pattern remains largely undetermined, in part due to difficulty uncoupling local pressure and flow stimuli from upstream energy sources. In this case study of a 29-yr-old male, we examine the regulation of longitudinal wall motion from the perspective of spontaneous premature ventricular contractions (PVCs). With respect to the pre-PVC beat, during the PVC, there was an 81% reduction in carotid blood velocity (96.8 to 18.4 cm/s), a 69% reduction in pulse pressure (58 to 18 mmHg), and a 59% reduction in apical left ventricular (LV) rotation (6.9 to 2.8°) as a result of reduced LV filling time. During this time, anterograde longitudinal wall motion was unchanged (0.06 mm), whereas retrograde motion was reduced by 91% (0.75 to 0.07 mm). During the compensated post-PVC beat, there were large increases in all outcomes, except for anterograde wall motion. Taken together, there appears to be little influence of either local or upstream factors on anterograde wall motion. Although retrograde wall motion generally mirrored blood pressure, blood velocity, and upstream cardiac movement, the primary motion regulator remains unclear. In this Case Study, we provide evidence against the role of blood velocity in regulating local wall motion and reinforce the potential importance of cardiac mechanics dictating the unique longitudinal motion pattern at the common carotid artery.NEW & NOTEWORTHY Benign arrhythmias can be a useful tool to probe new hypotheses in physiology. We tested the control of longitudinal motion of the common carotid artery wall using observations from spontaneous premature ventricular contractions in a healthy male. Forwards wall motion remained unchanged despite large deviations in local blood velocity and backwards wall motion mirrored changes in pulse pressure, blood velocity, and cardiac motion, thereby revising our original hypothesis of the control of longitudinal wall motion.


Differential antinociception by morphine and methadone in two sub-strains of Sprague-Dawley rats and its potentiation by dextromethorphan.
The antinociceptive effect of morphine and methadone was tested in two substrains of Sprague-Dawley (SD) rats, from B&K Universal, Sweden (BK) and Mollegård, Denmark (DK). In both sub-strains of SD rats subcutaneous morphine or methadone produced dose-dependent antinociception on the hot plate test. However, the effect of the opioids was less in DK-SD than BK-SD rats, particularly for morphine as it failed to produce maximal antinociception even at high doses. Dextromethorphan, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, potentiated the antinociceptive effect of morphine and methadone in the DK-SD rats. The potentiation of morphine by dextromethorphan was significantly greater than its effect on methadone at equipotent doses. The results showed that there is a sub-strain difference for SD rats in the response to the antinociceptive effect of opioids, which may be due to greater NMDA receptor activity in DK-SD than in BK-SD rats. The higher efficacy of methadone may be derived from its proposed NMDA receptor blocking property and/or high intrinsic activity.


Controlled oxidation of hydrocarbons by the membrane-bound methane monooxygenase: the case for a tricopper cluster.
[Figure: see text]. The growing need for inexpensive methods to convert methane to methanol has sparked considerable interest in methods that catalyze this process. The integral membrane protein particulate methane monooxygenase (pMMO) mediates the facile conversion of methane to methanol in methanotrophic bacteria. Most evidence indicates that pMMO is a multicopper enzyme, and these copper ions support redox, dioxygen, and oxo-transfer chemistry. However, the exact identity of the copper species that mediates the oxo-transfer chemistry remains an area of intense debate. This highly complex enzyme is notoriously difficult to purify because of its instability outside the lipid bilayer and tendency to lose its essential metal cofactors. For this reason, pMMO has resisted both initial identification and subsequent isolation and purification for biochemical and biophysical characterization. In this Account, we describe evidence that pMMO is a multicopper protein. Its unique trinuclear copper cluster mediates dioxygen chemistry and O-atom transfer during alkane hydroxylation. Although a recent crystal structure did not show this tricopper cluster, we provide compelling evidence for such a cluster through redox potentiometry and EPR experiments on the "holo" enzyme in pMMO-enriched membranes. We also identify a site in the structure of pMMO that could accommodate this cluster. A hydrophobic pocket capable of harboring pentane, the enzyme's largest known substrate, lies adjacent to this site. In addition, we have designed and synthesized model tricopper clusters to provide further chemical evidence that a tricopper cluster mediates the enzyme's oxo-transfer chemistry. These biomimetic models exhibit similar spectroscopic properties and chemical reactivity to the putative tricopper cluster in pMMO. Based on computational analysis using density functional theory (DFT), triangular tricopper clusters are capable of harnessing a "singlet oxene" upon activation by dioxygen. An oxygen atom is then inserted via a concerted process into the C-H bond of an alkane in the transition state during hydroxylation. The turnover frequency and kinetic isotope effect predicted by DFT show excellent agreement with experimental data.


Supplemental fructooligosaccharides and mannanoligosaccharides influence immune function, ileal and total tract nutrient digestibilities, microbial populations and concentrations of protein catabolites in the large bowel of dogs.
The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) and (or) mannanoligosaccharides (MOS) influenced indices of gut health of dogs. Adult female dogs (n = 4) surgically fitted with ileal cannulas were fed a dry, extruded, kibble diet twice daily. At each feeding, the following treatments were administered: 1) Control (no FOS or MOS); 2) 1 g FOS; 3) 1 g MOS; or 4) 1 g FOS + 1 g MOS. Fecal, ileal and blood samples were collected during the last 4 d of each 14-d period to measure protein catabolite concentrations, microbial populations, immune characteristics and nutrient digestibilities. Treatment means were compared using preplanned orthogonal contrasts. Dogs supplemented with MOS had lower (P = 0.05) fecal total aerobes and tended to have greater (P = 0.13) Lactobacillus populations. Ileal immunoglobulin (Ig) A concentrations were greater (P = 0.05) in dogs supplemented with FOS + MOS vs. control. Lymphocytes (% of total white blood cells) were greater (P < 0.05) in dogs supplemented with MOS. Serum IgA concentrations also tended (P = 0.13) to be greater in dogs supplemented with MOS. Dogs supplemented with FOS and FOS + MOS had lower (P < 0.05) fecal total indole and phenol concentrations. Dogs supplemented with MOS tended to have lower ileal DM (P = 0.149) and OM (P = 0.146) digestibilities vs. control. Results of this study suggest that dietary supplementation of FOS and MOS may have beneficial effects on colonic health and immune status of dogs.


Broad-spectrum bactericidal activity of Ag(2)O-doped bioactive glass.
Bioactive glass has found extensive application as an orthopedic and dental graft material and most recently also as a tissue engineering scaffold. Here we report an initial investigation of the in vitro antibacterial properties of AgBG, a novel bioactive glass composition doped with Ag(2)O. The bacteriostatic and bactericidal properties of this new material and of two other bioactive glass compositions, 45S5 Bioglass and BG, have been studied by using Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus as test microorganisms. Concentrations of AgBG in the range of 0.05 to 0.20 mg of AgBG per ml of culture medium were found to inhibit the growth of these bacteria. Not only was AgBG bacteriostatic, but it also elicited a rapid bactericidal action. A complete bactericidal effect was elicited within the first hours of incubation at AgBG concentrations of 10 mg ml(-1). 45S5 Bioglass and BG had no effect on bacterial growth or viability. The antibacterial action of AgBG is attributed exclusively to the leaching of Ag(+) ions from the glass matrix. Analytical measurements rule out any contribution to AgBG-mediated bacterial killing by changes in pH or ionic strength or the dissolution of other ionic species from the biomaterials. Our observations of the dissolution profiles of Ag(+) from AgBG in the presence and absence of bacteria are consistent with silver accumulation by the bacteria.


What's in a Name? Recent Key Projects of the Committee on Organization and Delivery of Burn Care.
The Committee for the Organization and Delivery of Burn Care (ODBC) was charged by President Palmieri and the American Burn Association (ABA) Board of Directors with presenting a plenary session at the 45th Meeting of the ABA in Palm Springs, CA, in 2013. The objective of the plenary session was to inform the membership about the wide range of the activities performed by the ODBC committee. The hope was that this session would encourage active involvement within the ABA as a means to improve the delivery of future burn care. Selected current activities were summarized by key leaders of each project and highlighted in the plenary session. The history of the committee, current projects in disaster management, regionalization, best practice guidelines, federal partnerships, product development, new technologies, electronic medical records, and manpower issues in the burn workforce were summarized. The ODBC committee is a keystone committee of the ABA. It is tasked by the ABA leadership with addressing and leading progress in many areas that constitute current challenges in the delivery of burn care.


Rapid Involution of Pustules during Topical Steroid Treatment of Acute Generalized Exanthematous Pustulosis.
Acute generalized exanthematous pustulosis (AGEP) is a dramatic generalized pustular rash of severe onset, which is considered a serious cutaneous adverse reaction to drugs. However, even though the clinical features are impressive and are often accompanied by systemic inflammation, it can be controlled quickly and safely by topical steroids subsequent to interruption of the offending drug. Here, we describe the management of a case and the evolution of the pustular rash. An elderly woman consulted with a generalized crop of 2-3 mm, nonfollicular pustules on erythematous background. In the 4 preceding weeks, she had been using amoxicillin/clavulanic acid for a bacterial implant infection and rivaroxaban. The clinical EuroSCAR criteria including the histology confirmed AGEP. Her medication was stopped and topical clobetasol propionate was used. Within 24 h, the development of new pustules ceased and the patient was discharged after 7 days of hospitalization with only a faint, diffuse erythema and focal desquamation remaining. This and many other cases in the literature suggest that topical steroids should be considered as a first-line treatment option, especially as systemic steroids themselves can sometimes induce generalized pustulosis.


The association between electronic cigarettes, sleep duration, and the adverse cardiovascular outcomes: Findings from behavioral risk factor surveillance system, 2020.
The joint effect of electronic cigarette smoking and insufficient sleep duration on cardiovascular disease (CVD) was unclear. This cross-sectional study aimed to evaluate the association between electronic cigarettes, sleep duration, and risk of CVD among American adults. The participants who completed the survey from the behavioral risk factor surveillance system in 2020 were included in this study. The status of electronic cigarette smoking was divided into never, former, and current use. The duration of sleep was categorized into insufficient (<6 h), appropriate (6-9 h), and excessive (>9 h) groups. The CVD group was defined as a patient having any of the following conditions: heart attack, coronary heart disease, or stroke according to self-report. The multivariate logistic regression model was adopted to determine the association between electronic cigarettes, sleep duration, and the risk of CVD. Sensitivity analyses were performed to assess the joint effects on the risk of CVD subtypes, including heart attack, coronary heart disease, and strokes, respectively. Subgroup analyses were performed to estimate the joint effects within the stratum of the age group. The total number of participants included in the present study was 253,561. Of which, 22,908 patients had CVD. In total, 61,293 participants had previously or currently used electronic cigarettes and 37,429 participants had inappropriate sleep duration. Former electronic cigarette users had a 10.8% increased risk of having CVD (OR = 1.108, 95% CI: 1.001-1.227) compared to users who never had electronic cigarettes. Insufficient and excessive sleep durations are associated with increased risks of CVD (OR = 1.592, 95% CI: 1.460-1.735; OR = 1.523, 95% CI: 1.320-1.758). The participants with current vaping status and lack of sleep had a 159.6% increased risk of CVD (OR = 2.596, 95% CI: 1.810-3.723). Sensitivity analyses found similar joint effects of current vaping and insufficient sleep on the risk of heart attack, coronary heart attack, and stroke. The subgroup analyses across each age stratum found that the middle-aged group is most vulnerable to the joint effect of current vaping and insufficient sleep. This study found that both current vaping and inappropriate sleep duration were associated with CVD. Additionally, there was a significant joint effect of current vaping and insufficient sleep on the risk of CVD, especially for middle-aged participants.


Regulation of FAK Activity by Tetraspan Proteins: Potential Clinical Implications in Cancer.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates multiple cell signaling pathways in both physiological and pathological conditions. Overexpression and activation of FAK is associated with many advanced stage cancers through promoting cancer cell tumorigenicity and progression as well as by regulating the tumor microenvironment. FAK has multiple binding partners through which FAK exerts its functions including RhoGEF, Src family, talin, cortactin, and paxilin. Over the last few years, it has been proposed that a novel group of four transmembrane proteins can interact with FAK and regulate its activity. These include select tetraspanins such as CD151 and CD9 as well as the GAS3 family members epithelial membrane protein-2 (EMP2) and peripheral myelin protein-22 (PMP22). In this review, we discuss the current knowledge of the interaction between FAK and tetraspan proteins in physiological and pathological conditions, with an emphasis on the potential of tetraspan family members as therapeutic targets in cancer.


Ubiquitin specific peptidase 21 regulates interleukin-8 expression, stem-cell like property of human renal cell carcinoma.
USP family proteins play essential roles in cancer cell proliferation and apoptosis and represent as candidate targets for cancer therapeutics. However, the effects and underlying mechanism of USP21 on renal cell carcinomas (RCC) remain unclear. In the present study, we investigate the effects of USP21 on proliferation, invasion and cancer stem cells (CSCs) property of RCC cell lines. As a result, siRNA-mediated depletion of USP21 inhibits cell proliferation, invasion ability and decreases the CSCs percentage of RCC cell lines. Complementarily, forced expression of USP21 leads to increase of tumorigenic properties. In addition, CSCs properties assessed by sphere formation assays demonstrated that depletion of USP21 impair the self-renewal capability of CSCs. Furthermore, decrease USP21 levels is associated with repression of interleukin 8 (IL-8), a chemokine that regulates CSCs characteristics in RCC. Mechanistically, USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation. These data suggest that USP21/IL-8 could be a pair of the critical molecular targets for the development of therapeutic strategies for RCC.


MicroRNAs as regulators of beta-cell function and dysfunction.
In the last decade, there has been an explosion in both the number of and knowledge about miRNAs associated with both type 1 and type 2 diabetes. Even though we are presently in the initial stages of understanding how this novel class of posttranscriptional regulators are involved in diabetes, recent studies have demonstrated that miRNAs are important regulators of the islet transcriptome, controlling apoptosis, differentiation and proliferation, as well as regulating unique islet and beta-cell functions and pathways such as insulin expression, processing and secretion. Furthermore, a large number of miRNAs have been linked to diabetogenic processes induced by elevated levels of glucose, free fatty acids and inflammatory cytokines. Thus, miRNAs are novel therapeutic targets with the potential of protecting the beta-cell, and there is proof of principle that miRNA antagonists, so-called antagomirs, are effective in vivo for other disorders. miRNAs are exported out of cells in exosomes, raising the intriguing possibility of cell-to-cell communication between distant tissues via miRNAs and that miRNAs can be used as biomarkers of beta-cell function, mass and survival. The purpose of this review is to provide a status on how miRNAs control beta-cell function and viability in health and disease.


Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study.
Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure. Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks. A total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort. RF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment.


Synechococcus sp. (PTCC 6021) cultivation under different light irradiances-Modeling of growth rate-light response.
Synechococcus sp. (PTCC 6021), a cyanobacterium species, was cultivated in an internally illuminated photobioreactor. The reactor was designed to achieve a monoseptic cultivation of the species. The goal was to study the growth-irradiance behavior of Synechococcus sp. (PTCC 6021). To accomplish this, different initial light irradiances were implemented inside the photobioreactor and the growth of the cells was monitored. It was observed that cell growth increased with higher light intensity until the photoinhibition occurrence at light irradiance higher than 250 μE m(-2) s(-1). The maximum OD600, maximum growth rate, and biomass productivity increased, and hence the extinction coefficient decreased, with the increase in light irradiance before photoinhibition. The maximum optical density (OD600) of 5.91 was obtained with irradiance below 250 μE m(-2) s(-1) during a growth period of 80 days. The modified Monod function could model the growth-irradiance of cells with satisfactory agreement with the experimental data. The comparison of growth-irradiance of the studied species with other photosynthetic organisms showed the same trend as for cyanobacteria with photoinhibition.


A study of the influence of genetic variance and sex on the density and thickness of the calvarial bone in collaborative cross mice.
Bone microarchitecture is affected by multiple genes, each having a small effect on the external appearance. It is thus challenging to characterize the genes and their specific effect on bone thickness and porosity. The purpose of this study was to assess the heritability and the genetic variation effect, as well as the sex effect on the calvarial bone thickness (Ca.Th) and calvarial porosity (%PoV) using the Collaborative Cross (CC) mouse population. In the study we examined the parietal bones of 56 mice from 9 lines of CC mice. Morphometric parameters were evaluated using microcomputed tomography (μCT) and included Ca.Th and %PoV. We then evaluated heritability, genetic versus environmental variance and the sex effect for these parameters. Our morphometric analysis showed that Ca.Th and %PoV are both significantly different among the CC lines with a broad sense heritability of 0.78 and 0.90, respectively. The sex effect within the lines was significant in line IL111 and showed higher values of Ca.Th and %PoV in females compared to males. In line IL19 there was a borderline sex effect in Ca.Th in which males showed higher values than females. These results stress the complexity of sex and genotype interactions controlling Ca.Th and %PoV, as the skeletal sexual dimorphism was dependent on the genetic background. This study also shows that the CC population is a powerful tool for establishing the genetic effect on these traits.


Research Note: Study on the antibacterial activity of Chinese herbal medicine against Aspergillus flavus and Aspergillus fumigatus of duck origin in laying hens.
Aspergillus flavus and Aspergillus fumigatus were derived and identified from the ducks infected with fungi. In order to investigate the effectiveness of Chinese herbal medicines against Aspergillus flavus and Aspergillus fumigatus, in vitro antibacterial test and animal infection control test were conducted to study the antibacterial activity of the Chinese medicine mixture which was compatible with Acorus gramineus, Phellodendron chinensis, and Cassia obtusifolia. According to the results, the liver of chickens infected with Aspergillus flavus and Aspergillus fumigatus displayed granulomatous lesions, indicating that the isolation of pathogen from the lungs of sick ducks is also pathogenic to chickens. As suggested by the results of in vitro drug sensitivity test, the mixture 1 MIC80 was the minimum, the MIC80 of Aspergillus flavus was 16 μg/μL, and the MIC80 of Aspergillus fumigatus was 4 μg/μL. In a petri dish of the same concentration, the colony diameter of Aspergillus flavus and Aspergillus fumigatus in Mixture 1 was the minimum. Besides, Aspergillus flavus colonies grew when the concentration was 64 μg/μL, and Aspergillus fumigatus colonies grew when the concentration was 4 μg/μL, which suggests the more significant inhibitory effect of Mixture 1 on Aspergillus flavus and Aspergillus fumigatus. According to the results of animal experiments, there was a significantly lower activity level of Glutamic oxaloacetic transaminase (GOT) and Glutamate pyruvic transaminase (GPT) in the protection group and the treatment group than in the bacterial infection group. As indicated by the blood smear results, there were more neutrophils in the infected group than in the prevention group and the treatment group. Thus, it can be seen from that the Mixture 1 produced preventive and therapeutic effects on the chickens infected with Aspergillus flavus and Aspergillus fumigatus.


Two-dimensional separations of peptides and proteins by comprehensive liquid chromatography-capillary electrophoresis.
Analysis of biological samples is problematic because of their complex composition. Reversed phase liquid chromatography (RPLC), size exclusion chromatography (SEC), and, more recently, capillary zone electrophoresis (CZE) are routinely used for the analysis of these samples, but are eventually limited because they are one-dimensional (1-D) methods. As sample complexity increases, the separation efficiency necessary to resolve a large number of sample components in one dimension becomes prohibitively high. A solution to this problem has been to use a two-dimensional (2-D) approach. Each dimension in a 2-D separation relies on a different separating mechanism. By expanding the separation into two dimensions, sample components unresolved in the first dimension can often be separated in the second. This circumvents the requirement for extremely high efficiencies in either dimension. Two-dimensional slab gel electrophoresis has been used successfully in this area, but a more instrumental approach is desired. In this paper we describe three coupled-column approaches to 2-D separations. First, microcolumn SEC-CZE is explored as a means of 2-D protein analysis. Next, RPLC-CZE is investigated for analysis of peptides in tryptic maps. Finally, RPLC is coupled with fast CZE (FCZE), a unique form of CZE analysis, for fast 2-D analysis of peptides. Details of the instrumentation used in these 2-D systems will be presented along with the results of some typical 2-D analyses.


Can paralytic poliomyelitis be eliminated?
The question of whether paralytic poliomyelitis can be eliminated can be approached either from the theoretic and scientific perspective or from the practical perspective of a program. From the former perspective, the answer is probably yes; from the latter, the answer would be that global eradication of this disease cannot be achieved by the year 2000. The global eradication of smallpox was a remarkable achievement and is held up as an example to show that the deliberate worldwide elimination of a human infectious-disease agent can be scheduled and accomplished. However, there are significant differences in the epidemiology and in the control programs for smallpox and poliomyelitis that make the global eradication of poliomyelitis more difficult. Presently, scarce resources for improving health throughout the world cannot be easily diverted for the specific purpose of eradicating paralytic poliomyelitis. The control of poliomyelitis for the next decade will have to proceed at the same relative pace as other major disease control programs of the World Health Organization, such as the Expanded Programme on Immunization and the International Drinking Water Supply and Sanitation Decade. After 1990, the extent to which these programs have controlled or regionally eliminated paralytic poliomyelitis can be assessed. It may be more appropriate then to ask the question, can paralytic poliomyelitis be eliminated?


Acute hemorrhagic edema of infancy: a case report.
Acute hemorrhagic edema of infancy is a cutaneous leukocytoclastic vasculitis, clinically characterized by the acute development of peripheral edema and targetoid purpuric lesions on the face and extremities. The clinical picture has a violent onset with a short benign course followed by spontaneous complete recovery. We describe a five-month-old boy with acute hemorrhagic edema, in whom the disease appeared after antibiotic treatment for a cellulitis in front of the tragus.


Glycogen synthase kinase-3 plays a central role in mediating glucocorticoid-induced apoptosis.
It is still unclear how glucocorticoids (GCs) induce apoptosis of thymocytes and T lymphoma cells. Emergence of GC-resistant lymphoma cells is a major obstacle in GC therapy, emphasizing the need for novel strategies that maintain the sensitivity of lymphoma cells to the proapoptotic effects of GC. We have undertaken a kinome study to elucidate the signal transduction pathways involved in mediating GC-induced apoptosis. Our study shows that glycogen synthase kinase (GSK3) plays a central role in promoting GC-induced apoptosis. In the absence of a ligand, GSK3alpha, but not GSK3beta, is sequestered to the glucocorticoid receptor (GR). Exposure to GCs leads to dissociation of GSK3alpha from GR and subsequent interaction of GSK3alpha and GSK3beta with the proapoptotic Bim protein, an essential mediator of GC-induced apoptosis. Chemical inhibition of GSK3 by SB216763, BIO-Acetoxime, or LiCl and GSK3 inhibition using a dominant-negative mutant of GSK3 impede this cell death process, indicating that GSK3 is involved in transmitting the apoptotic signal. GC resistance in lymphoma cells can be relieved by inhibiting the phosphatidylinositol-3 kinase-Akt survival pathway, which inactivates GSK3. Notch1, a transcription factor frequently activated in T acute lymphoblastic leukemia cells, confers GC resistance through activation of Akt. Altogether, this study illuminates the link connecting upstream GR signals to the downstream mediators of GC-induced apoptosis. Our data suggest that targeting protein kinases involved in GSK3 inactivation should improve the outcome of GC therapy.


The Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) voltage-gated sodium channel and mutations associated with pyrethroid resistance in field-collected adult males.
Helicoverpa zea is one of the most costly insect pests of food and fiber crops throughout the Americas. Pyrethroid insecticides are widely applied for its control as they are effective and relatively inexpensive; however, resistance to pyrethroids threatens agricultural systems sustainability because alternative insecticides are often more expensive or less effective. Although pyrethroid resistance has been identified in this pest since 1990, the mechanisms of resistance have not yet been elucidated at the molecular level. Pyrethroids exert their toxicity by prolonging the open state of the voltage-gated sodium channel. Here we report the cDNA sequence of the H. zea sodium channel alpha-subunit homologous to the para gene from Drosophila melanogaster. In field-collected males which were resistant to cypermethrin as determined by the adult vial test, we identify known resistance-conferring mutations L1029H and V421M, along with two novel mutations at the V421 residue, V421A and V421G. An additional mutation, I951V, may be the first example of a pyrethroid resistance mutation caused by RNA editing. Identification of the sodium channel cDNA sequence will allow for testing hypotheses on target-site resistance for insecticides acting on this channel through modeling and expression studies. Understanding the mechanisms responsible for resistance will greatly improve our ability to identify and predict resistance, as well as preserve susceptibility to pyrethroid insecticides.


[Medicine in the ghettos during the Holocaust].
The Health systems in several ghettos in Europe during the holocaust were studied in an attempt to construct a typical structural profile. The medical system in a typical ghetto consisted of a department of public health (sanitation) that belonged to the Yudenrat, several hospitals, outpatient clinics, first aid stations and physicians in the labor groups. The structure of the system in several ghettos is discussed and the functions of the various units in the prevention of epidemics, and health education are reviewed. Also described is the medical research that was carried out in the ghettos, emphasizing the work on "Hunger Disease" in the Warsaw ghetto, as well as the heroic endeavor to establish a clandestine medical school in the Warsaw ghetto during the holocaust.


A simple protocol for combinatorial cyclic depsipeptide libraries sequencing by matrix-assisted laser desorption/ionisation mass spectrometry.
Short cyclic peptides have a great interest in therapeutic, diagnostic and affinity chromatography applications. The screening of 'one-bead-one-peptide' combinatorial libraries combined with mass spectrometry (MS) is an excellent tool to find peptides with affinity for any target protein. The fragmentation patterns of cyclic peptides are quite more complex than those of their linear counterparts, and the elucidation of the resulting tandem mass spectra is rather more difficult. Here, we propose a simple protocol for combinatorial cyclic libraries synthesis and ring opening before MS analysis. In this strategy, 4-hydroxymethylbenzoic acid, which forms a benzyl ester with the first amino acid, was used as the linker. A glycolamidic ester group was incorporated after the combinatorial positions by adding glycolic acid. The library synthesis protocol consisted in the following: (i) incorporation of Fmoc-Asp[2-phenylisopropyl (OPp)]-OH to Ala-Gly-oxymethylbenzamide-ChemMatrix, (ii) synthesis of the combinatorial library, (iii) assembly of a glycolic acid, (iv) couple of an Ala residue in the N-terminal, (v) removal of OPp, (vi) peptide cyclisation through side chain Asp and N-Ala amino terminus and (vii) removal of side chain protecting groups. In order to simultaneously open the ring and release each peptide, benzyl and glycolamidic esters were cleaved with ammonia. Peptide sequences could be deduced from the tandem mass spectra of each single bead evaluated. The strategy herein proposed is suitable for the preparation of one-bead-one-cyclic depsipeptide libraries that can be easily open for its sequencing by matrix-assisted laser desorption/ionisation MS. It employs techniques and reagents frequently used in a broad range of laboratories without special expertise in organic synthesis.


Simplified evaluation of the jugular venous pressure: significance of inspiratory collapse of jugular veins.
The evaluation of the jugular venous pulse (JVP) remains one of the most important elements of the physical examination. Unfortunately, the examination remains difficult for most clinicians since traditional methodology is not commonly used or understood. Echocardiography has shown that the right atrial pressure can accurately be predicted as normal by observing a 50% inspiratory collapse of the inferior vena cava. We have adapted this finding to the clinical examination and experience has shown that if the jugular vein collapses during deep inspiration that both the right atrial pressure and the JVP are normal. We propose that this finding, which is easily detected in most patients, be incorporated as a standard observation in the assessment of the JVP. Thus, when evaluated in the supine position, distended neck veins that do not collapse indicate an abnormally elevated venous pressure, while visible veins that collapse during deep inspiration or with a vigorous sniff suggest a normal JVP, and those that are not (or barely) visible that collapse indicate a low JVP. This methodology is applicable to most clinical situations.


Knockdown of ACTA2‑AS1 promotes liver cancer cell proliferation, migration and invasion.
Long noncoding RNAs (lncRNAs) are important regulators of various cellular and biological processes. The present study aimed to investigate the functions of a novel lncRNA, ACTA2‑AS1:4, a transcript variant of smooth muscle α‑actin 2‑antisense 1 (ACTA2‑AS1), in regulating liver cancer progression. Expression of lncRNAs in liver cancer tissues and cell lines were analyzed by reverse transcription quantitative polymerase chain reaction (RT‑qPCR). Knockdown of ACTA2‑AS1:4 expression in LM3 liver cancer cells was achieved by transfection with small interfering RNAs (siRNAs) that specifically targeted ACTA2‑AS1:4. The proliferation and cell cycle progression of ACTA2‑AS1:4‑silenced LM3 cells were determined using MTS assay and flow cytometry, respectively. A Transwell system assay was used to evaluate the migration and invasion capacities of LM3 cells transfected with ACTA2‑AS1:4 siRNA. The expression levels of major genes associated with important cellular processes were finally determined by RT‑qPCR and western blot analysis. ACTA2‑AS1:4 expression in liver cancer tissues and multiple cell lines was markedly downregulated by specific siRNAs. This inhibition of ACTA2‑AS1:4 expression significantly promoted the proliferation, cell cycle progression, migration and invasion of LM3 cells. A decrease in ACTA2‑AS1:4 expression also suppressed E‑cadherin expression, increased N‑cadherin expression, decreased caspase 3 expression and increased cyclin D1 and matrix metalloproteinase expression in liver cancer cells. Downregulation of ACTA2‑AS1:4 affects a number of key mechanisms involved in liver cancer progression. These data may be important for the future of liver cancer diagnosis and subsequent treatments.


Bipartite axiation follows incomplete epiboly in zebrafish embryos treated with chemical teratogens.
Medial clefts in the axis of the trunk region are malformations known from many chordates and are mostly referred to as rachischisis anterior. In teleosts, rachischisis was previously ascribed either to secondary rifting of a single uniform axial rudiment, or to the establishment of two (half) axes and body halves physically separate from the very beginning. In order to decide between these conflicting interpretations, we treated zebrafish embryos during blastodisc stages and epiboly with several chemical teratogens causing rachischisis anterior. Treatment with ethanol, Colcemid, hydroxyurea, or cycloheximide was found to delay the proliferation and movements of the deep cells more strongly than the timing of cell differentiation, so that the deep cells embark on organogenesis before having reached their destinations in the uniform germ shield. Treatment with alpha-amanitin, on the other hand, seems primarily to affect the periblast and enveloping layer; the incomplete epiboly observed in these layers appears to restrain deep cell epiboly physically and thus to cause rachischisis. In both instances, the split condition of the embryo's trunk region is clearly due to the ectopic formation of physically separate body halves right from the beginning, a mode we call bipartite axiation. We also describe secondary anomalies specific for individual teratogens, and briefly discuss the possible origins of rachischisis anterior among other chordates including man.


Fast time-lens-based line-scan single-pixel camera with multi-wavelength source.
A fast time-lens-based line-scan single-pixel camera with multi-wavelength source is proposed and experimentally demonstrated in this paper. A multi-wavelength laser instead of a mode-locked laser is used as the optical source. With a diffraction grating and dispersion compensating fibers, the spatial information of an object is converted into temporal waveforms which are then randomly encoded, temporally compressed and captured by a single-pixel photodetector. Two algorithms (the dictionary learning algorithm and the discrete cosine transform-based algorithm) for image reconstruction are employed, respectively. Results show that the dictionary learning algorithm has greater capability to reduce the number of compressive measurements than the DCT-based algorithm. The effective imaging frame rate increases from 200 kHz to 1 MHz, which shows a significant improvement in imaging speed over conventional single-pixel cameras.


Axonal domain disorganization in Caspr1 and Caspr2 mutant myelinated axons affects neuromuscular junction integrity, leading to muscle atrophy.
Bidirectional interactions between neurons and myelinating glial cells result in formation of axonal domains along myelinated fibers. Loss of axonal domains leads to detrimental consequences on nerve structure and function, resulting in reduced conductive properties and the diminished ability to reliably transmit signals to the targets they innervate. Thus, impairment of peripheral myelinated axons that project to the surface of muscle fibers and form neuromuscular junction (NMJ) synapses leads to muscle dysfunction. The goal of our studies was to determine how altered electrophysiological properties due to axonal domain disorganization lead to muscle pathology, which is relevant to a variety of peripheral neuropathies, demyelinating diseases, and neurodegenerative disorders. Using conventional Contactin-Associated Protein 1 (Caspr1) and Caspr2 single or double mutants with disrupted paranodal, juxtaparanodal, or both regions, respectively, in peripheral myelinated axons, we correlated defects in NMJ integrity and muscle pathology. Our data show that loss of axonal domains in Caspr1 and Caspr2 single and double mutants primarily alters distal myelinated fibers together with presynaptic terminals, eventually leading to NMJ denervation and reduction in postsynaptic endplate areas. Moreover, reduction in conductive properties of peripheral myelinated fibers together with NMJ disintegration leads to muscle atrophy in Caspr1 mutants or muscle fiber degeneration accompanied by mitochondrial dysfunction in Caspr1/Caspr2 double mutants. Together, our data indicate that proper organization of axonal domains in myelinated fibers is critical for optimal propagation of electrical signals, NMJ integrity, and muscle health, and provide insights into a wide range of pathologies that result in reduced nerve conduction leading to muscle atrophy. © 2017 Wiley Periodicals, Inc.


[The clinical significance of the unstable bladder (author's transl)].
The anamnestic, clinical and urodynamic findings of 377 consecutively investigated women were evaluated. 86 (23%) patients showed bladder instability. The intensity of involuntary bladder contractions and the occurrence of incontinence in association with involuntary detrusor contractions influenced the clinical significance of unstable bladders. The maximum urethral closure pressure however had no influence on it. Urge incontinence was the most reliable symptom distinguishing those patients with bladder instability. Frequency of micturition, nocturia and nocturnal enuresis were less reliable in this respect. Urinary tract infections showed no correlation to bladder instability.


Effect of curing on water diffusivities in acrylate free films as measured via a sorption technique.
Studies were performed to investigate the effect of curing on the diffusion coefficients of water, as measured via the sorption technique, in acrylate polymeric films. The mathematical model selected for obtaining diffusion constants from the vapor-phase sorption studies was derived from the long-time Fourier equation used for diffusion into a planar sheet. For Eudragit NE films, the diffusion coefficients of water decreased continuously until a constant minimum value was reached. Diffusion coefficients in Eudragit RS films decreased initially but increased beyond 4 hours of curing at 70 degrees C and 90 degrees C. This latter result suggested the possible evaporation of plasticizer, which also results in a more dramatic increase in glass transition temperature with curing for the Eudragit RS free film in comparison to the Eudragit NE free film. Such loss of plasticizer could also lead to the formation of molecular-scale channels within the films, which would result in increased film permeability. To verify this proposed explanation, the amounts of triethyl citrate plasticizer in Eudragit RS free films were determined using Fourier-transform infrared spectrophotometry. An optimal curing condition was predicted for Eudragit NE and Eudragit RS films based upon the curing conditions at which a minimum value of the diffusion coefficient was reached.


Temperature-dependent quantitative 3omega scanning thermal microscopy: Local thermal conductivity changes in NiTi microstructures induced by martensite-austenite phase transition.
We develop the theoretical description of 3omega signals from the resistive Wollaston thermal probe (ThP) of a scanning thermal microscope (SThM) in terms of an equivalent low-pass filter. The normalized amplitude and phase frequency spectra are completely characterized by a single parameter, the crossover frequency f(c)(k) depending on the sample thermal conductivity k. The application concerns polycrystalline NiTi shape memory alloy microstructured by focused Ga ion beam milling and implantation. The calibration of the ThP combined with a novel two-step normalization procedure allowed quantitative exploitation of 3omega signal variations as small as -1.75% in amplitude and 0.60 degrees in phase upon heating the sample from room temperature to 100 degrees C. This corresponds to k increase of 23.9% that is consistent with the expected thermal conductivity variation due to martensite-austenite structural phase transition. To our knowledge this is for the first time that SThM 3omega phase information is used quantitatively as well. The static, calibrated 3omega measurements are complementary to 3omega SThM images of the patterned sample surface. The local SThM measurement of temperature-dependent thermal conductivity opens the possibility to imaging structural phase transitions at submicron scale.


Generation of Synthetic Copolymer Libraries by Combinatorial Assembly on Nucleic Acid Templates.
Recent advances in nucleic acid-templated copolymerization have expanded the scope of sequence-controlled synthetic copolymers beyond the molecular architectures witnessed in nature. This has enabled the power of molecular evolution to be applied to synthetic copolymer libraries to evolve molecular function ranging from molecular recognition to catalysis. This Review seeks to summarize different approaches available to generate sequence-defined monodispersed synthetic copolymer libraries using nucleic acid-templated polymerization. Key concepts and principles governing nucleic acid-templated polymerization, as well as the fidelity of various copolymerization technologies, will be described. The Review will focus on methods that enable the combinatorial generation of copolymer libraries and their molecular evolution for desired function.


Two novel effectors of trafficking and maturation of the yeast plasma membrane H+ -ATPase.
The endoplasmic reticulum (ER) is the entry site of proteins into the endomembrane system. Proteins exit the ER via coat protein II (COPII) vesicles in a selective manner, mediated either by direct interaction with the COPII coat or aided by cargo receptors. Despite the fundamental role of such receptors in protein sorting, only a few have been identified. To further define the machinery that packages secretory cargo and targets proteins from the ER to Golgi membranes, we used multiple systematic approaches, which revealed 2 uncharacterized proteins that mediate the trafficking and maturation of Pma1, the essential yeast plasma membrane proton ATPase. Ydl121c (Exp1) is an ER protein that binds Pma1, is packaged into COPII vesicles, and whose deletion causes ER retention of Pma1. Ykl077w (Psg1) physically interacts with Exp1 and can be found in the Golgi and coat protein I (COPI) vesicles but does not directly bind Pma1. Loss of Psg1 causes enhanced degradation of Pma1 in the vacuole. Our findings suggest that Exp1 is a Pma1 cargo receptor and that Psg1 aids Pma1 maturation in the Golgi or affects its retrieval. More generally our work shows the utility of high content screens in the identification of novel trafficking components.


Sustainability assessments of regional water supply interventions - Combining cost-benefit and multi-criteria decision analyses.
To cope with present and future challenges, a growing number of water utilities in Sweden, Europe and elsewhere initiate various forms of inter-municipal cooperations creating a new regional level of drinking water governance. In order to reach viable decisions of alternative ways forward, there is an international consensus that sustainability needs to be addressed in water supply planning, design and decision-making. There are, however, few decision aids focusing on assessing the sustainability of inter-municipal cooperations and the inter-municipal policies and interventions that regional decision-makers are faced with. This paper presents a decision support model based on a combination of cost-benefit analysis and multi-criteria decision analysis for assessing the sustainability of regional water supply interventions, including formations of inter-municipal cooperations. The proposed decision support model integrates quantitative and semi-quantitative information on sustainability criteria. It provides a novel way of presenting monetized benefits and costs, capturing utilitarian aspects of alternative interventions, with non-monetized social and environmental effects, capturing aspects based in the deontological theories of moral ethics. The model is based on a probabilistic approach where uncertainties are defined by statistical probability distributions. A case study is used to exemplify and evaluate model application in decision situations regarding regionalization, (de)centralization, source water quality and redundancy. All evaluated alternatives were expected to contribute to a slightly improved social sustainability, whereas the results were more varying in the economic and environmental domains. A structured and transparent treatment of uncertainties facilitates a better understanding of the results as well as communication between decision-makers, stakeholders and the community.


Ovarian cancer management. Practice guidelines for nuclear physicians.
Ovarian cancer is a frequent and severe malignancy. Over 75% of cases are diagnosed at an advanced stage with disease spread beyond the ovaries. Despite the high response rates of initial treatments (i.e.,70-80%), the median progression-free survival of advanced ovarian cancer is 16-22 months, and the 5-year overall survival, 20-30%. The majority of these patients relapse, with metastatic peritoneal spread, unresectable, or drug resistant disease. Our goal was to outline current knowledge about diagnosis, prognostic factors, and treatments, and to dwell on non-nuclear medicine and nuclear-medicine diagnostic procedures.


The scientific basis for dental implant therapy.
Dental and oral implantology have rapidly moved into the mainstream of dentistry in the last ten years with a phenomenal growth based on rapidly expanding technology, increasing public interest, and the reporting of sound scientific data. This paper reviews current knowledge about implant tissue reactions and identifies areas where additional scientific inquiry is needed. Bone- and soft-tissue healing around dental implants varies greatly depending upon the form of the implant, biomaterial used, and surgical approach. Controversy exists as to whether a direct bony-biomaterial interface is preferable over a bone-connective tissue-biomaterial interface. Scientific data are required to document whether intervening molecular layers of glycoproteins exist between implant and bone, and what role is played by these structures relative to the implant-bone interface. The adaptation of regenerated gingival epithelium to an implant is critical for the development of a perimucosal seal. Many scientific questions remain unanswered about this seal and its role in maintenance of implant longevity. Controlled clinical trials must be carried out to determine clinical serviceability standards for patients. Resolving these areas of concern and understanding the biological reactions involved will require in-depth scientific inquiry by clinician and scientist alike to make dental implantology a highly acceptable and predictable treatment modality. Even with these controversies and lack of comprehensive comparison studies, dental implantology is an exciting treatment concept that makes considerable demands upon the surgical, prosthetic, periodontal, and restorative skills of today's practitioners, and on their scientific understanding as well.


TRANSIENT PSEUDOHYPOALDOSTERONISM SECONDARY TO URINARY TRACT INFECTION IN A MALE INFANT WITH UNILATERAL HYDRONEPHROSIS DUE TO PRIMARY OBSTRUCTIVE MEGAURETER: A CASE REPORT.
We present a case of transient form of type 1 pseudohypoaldosteronism (S-PHA) in a 1.5-month-old male infant who presented with lethargy, failure to thrive, severe hyponatremia (Na=118 mmol/L), hypochloremia (Cl=93 mmol/L) and fever due to urinary tract infection. Potassium levels were normal. Markedly elevated serum aldosterone level and elevated serum renin confirmed the diagnosis of pseudohypoaldosteronism. Renal ultrasound showed grade III hydronephrosis on the left kidney while contrast-enhanced voiding urosonography excluded the existence of vesicoureteral reflux, which raised suspicion of obstructive uropathy at the level of vesicoureteral junction. Serum sodium normalized after several days of intravenous fluids and antibiotic therapy, after which oral supplementation of sodium was introduced. The levels of 17-hydroxyprogesterone, adrenocorticotropic hormone, cortisol and thyroid-stimulating hormone were normal. Functional magnetic resonance urography conducted at the age of 3 months confirmed the diagnosis of primary congenital obstructive megaureter and the infant was referred to a pediatric surgeon. Although a rare occurrence, S-PHA can be a potentially life-threatening condition in infants if not recognized and treated appropriately. Therefore, serum concentrations of electrolytes should be obtained in every child diagnosed with obstructive anomaly of the urinary tract and/or acute cystopyelonephritis. On the other hand, every child diagnosed with S-PHA should be evaluated for obstructive anomaly of the urinary tract.


Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation.
Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE) was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS) was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress.


Acute myocardial infarction complicated by respiratory failure. The effects of mechanical ventilation.
The cardiopulmonary effects of ventilatory support were studied in 12 patients with an acute myocardial infarction complicated by respiratory failure. At constant end-expiratory pressure, controlled mechanical ventilation, intermittent mandatory ventilation with 50 percent mechanical support, and spontaneous breathing all resulted in acceptable blood gas values. Intermittent mandatory ventilation offered hemodynamic advantages over controlled mechanical ventilation, as evidenced by a higher cardiac index and a lower arteriovenous oxygen content difference. Electrocardiographic evidence of myocardial ischemia was observed in one patient during controlled mechanical ventilation, in one during partial ventilatory support, and in five patients during spontaneous breathing. Myocardial ischemia should be one of the major determinants of mechanical ventilation when a patient with ischemic heart disease is subjected to ventilator treatment. The total withdrawal of ventilatory support carries a risk of marked ischemia and is not recommended until the patient can be extubated.


Attenuation of renal ischemia-reperfusion injury in rats by allopurinol and prostaglandin E1.
50 Sprague-Dawley rats were used to study the effect of allopurinol and prostaglandin E1 (PGE1) on renal ischemia-reperfusion injury. They underwent left renal ischemia for 1 h and reperfusion. A right nephrectomy was performed, and 5 groups were made. Group AP received allopurinol 50 mg/kg and PGE1 20 micrograms/kg; group A, allopurinol; group P, PGE1; group C, control, and group S, sham group. Five animals from each group were used to study renal functions and 5 for renal histology. The serum creatinine values were lower in the treatment groups compared to the controls on days 1-3 and 7 (p < 0.05). The blood urea nitrogen values showed a similar trend. Maximum histological damage was seen in group C, followed by groups A, P and AP, in this order. We conclude that allopurinol and PGE1 attenuate renal ischemia-reperfusion injury in rats.


Identification of TENP as the Gene Encoding Chicken Egg White Ovoglobulin G2 and Demonstration of Its High Genetic Variability in Chickens.
Ovoglobulin G2 (G2) has long been known as a major protein constituent of chicken egg white. However, little is known about the biochemical properties and biological functions of G2 because the gene encoding G2 has not been identified. Therefore, the identification of the gene encoding G2 and an analysis of its genetic variability is an important step toward the goal of understanding the biological functions of the G2 protein and its utility in poultry production. To identify and characterize the gene encoding G2, we separated G2 from egg white using electrophoresis on a non-denaturing polyacrylamide gel. Two polymorphic forms of G2 protein (G2A and G2B), with different mobilities (fast and slow respectively), were detected by staining. The protein band corresponding to G2B was electro-eluted from the native gel, re-electrophoresed under denaturing conditions and its N-terminal sequence was determined by Edman degradation following transfer onto a membrane. Sequencing of the 47 kDa G2B band revealed it to be identical to TENP (transiently expressed in neural precursors), also known as BPI fold-containing family B, member 2 (BPIFB2), a protein with strong homology to a bacterial permeability-increasing protein family (BPI) in mammals. Full-length chicken TENP cDNA sequences were determined for 78 individuals across 29 chicken breeds, lines, and populations, and consequently eleven non-synonymous substitutions were detected in the coding region. Of the eleven non-synonymous substitutions, A329G leading to Arg110Gln was completely associated with the noted differential electrophoretic mobility of G2. Specifically G2B, with a slower mobility is encoded by A329 (Arg110), whereas G2A, with a faster mobility, is encoded by G329 (Gln110). The sequence data, derived from the coding region, also revealed that the gene encoding G2 demonstrates significant genetic variability across different chicken breeds/lines/populations. These variants, and how they correlate with egg white properties, may allow us to understand further G2's functions.


A skin test for pseudorabies virus infection in swine.
Heat-inactivated pseudorabies virus caused cutaneous delayed-type hypersensitive reactions when injected intradermally on the dorsolateral aspect of the thorax and tips of the ears of pigs previously exposed to the homologous virus. The reaction induced by subcutaneous injection in the lower eyelid was more easily administered and evaluated. Nonexposed control pigs did not react to the antigen and exposed and control pigs did not react when injected with a cell control antigen prepared in a similar manner. A positive response was detectable as early as seven days after exposure, reached near maximal levels by 28 days, and remained at similar levels for at least 90 days.


The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth.
Plasmodium parasites remodel their vertebrate host cells by translocating hundreds of proteins across an encasing membrane into the host cell cytosol via a putative export machinery termed PTEX. Previously PTEX150, HSP101 and EXP2 have been shown to be bona fide members of PTEX. Here we validate that PTEX88 and TRX2 are also genuine members of PTEX and provide evidence that expression of PTEX components are also expressed in early gametocytes, mosquito and liver stages, consistent with observations that protein export is not restricted to asexual stages. Although amenable to genetic tagging, HSP101, PTEX150, EXP2 and PTEX88 could not be genetically deleted in Plasmodium berghei, in keeping with the obligatory role this complex is postulated to have in maintaining normal blood-stage growth. In contrast, the putative thioredoxin-like protein TRX2 could be deleted, with knockout parasites displaying reduced grow-rates, both in vivo and in vitro, and reduced capacity to cause severe disease in a cerebral malaria model. Thus, while not essential for parasite survival, TRX2 may help to optimize PTEX activity. Importantly, the generation of TRX2 knockout parasites that display altered phenotypes provides a much-needed tool to dissect PTEX function.


Synthesis of axially chiral biaryls through sulfoxide-directed asymmetric mild C-H activation and dynamic kinetic resolution.
A mild and robust direct C-H functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non-prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.


Update on "Treatment of orthostatic headache without intracranial hypotension: A case report" - nine years later.
In 2013, one of the authors described a 36-year-old female with orthostatic headache without documented intracranial hypotension or evidence of cerebrospinal fluid leak, despite extensive workup. Headache was unresponsive to conservative treatment since 2010, showed only transient benefit after repeated epidural blood patches while vitamin A supplementation resulted in progressive improvement. Since 2013, the patient followed a relapsing and remitting course yet relapse control became difficult after a drug induced liver injury required vitamin A discontinuation in 2017, when her headache became chronic. Greater occipital nerve blocks provided pain relief as alternative but were stopped due to the pandemic and her latest severe relapse, in late 2020, required not only restarting anaesthetic blocks and aggressive medication management, but also reassessing and treating comorbidities (obstructive sleep apnoea and major depressive disorder) with modest benefit. Orthostatic headache without intracranial hypotension is rare, with only 28 cases reported so far, all treated empirically and all treatment options revealing to be mostly ineffective. Vitamin A anecdotally appeared to be useful in our case but had to be stopped for severe side effects, so unfavourable long-term prognosis, in ours and 2/3 of the reported cases, seems to be the rule in this intriguing entity.