Mediastinal synovial sarcoma: report of two cases with molecular genetic analysis.
Synovial sarcoma occurs predominantly in the paraarticular regions of the extremities. Synovial sarcoma of the mediastinum is an exceedingly rare neoplasm that has overlapping histologic and immunophenotypic features with other tumors in the differential diagnosis. We describe two cases. One is a 67-year-old patient who presented with chest pain and shortness of breath. Diagnostic imaging revealed a mediastinal mass extending over the cardiac apex. Histopathology, immunohistochemistry, and molecular genetic analysis confirmed the diagnosis of synovial sarcoma. The patient underwent surgical resection and postoperative radiation therapy. He is alive and well 18 months after diagnosis. This case illustrates the importance of proper procurement of frozen tissue for molecular genetic analysis for the identification of the t(X;18), characteristic of synovial sarcoma. Detection of this translocation is of paramount importance to confirm this diagnosis, particularly when this neoplasm arises in atypical locations outside the extremities.


Repeat Dosing of AAV2.5T to Ferret Lungs Elicits an Antibody Response That Diminishes Transduction in an Age-Dependent Manner.
Readministration of recombinant adeno-associated virus (rAAV) may be necessary to treat cystic fibrosis (CF) lung disease using gene therapy. However, little is known about rAAV-mediated immune responses in the lung. Here, we demonstrate the suitability of the ferret for testing AAV2.5T-mediated CFTR delivery to the lung and characterization of neutralizing-antibody (NAb) responses. AAV2.5T-SP183-hCFTRΔR efficiently transduced both human and ferret airway epithelial cultures and complemented CFTR Cl- currents in CF airway cultures. Delivery of AAV2.5T-hCFTRΔR to neonatal and juvenile ferret lungs produced hCFTR mRNA at 200%-300% greater levels than endogenous fCFTR. Single-dose (AAV2.5T-SP183-gLuc) or repeat dosing (AAV2.5T-SP183-fCFTRΔR followed by AAV2.5T-SP183-gLuc) of AAV2.5T was performed in neonatal and juvenile ferrets. Repeat dosing significantly reduced transgene expression (11-fold) and increased bronchoalveolar lavage fluid (BALF) NAbs only in juvenile, but not neonatal, ferrets, despite near-equivalent plasma NAb responses in both age groups. Notably, both age groups demonstrated a reduction in BALF anti-capsid binding immunoglobulin (Ig) G, IgM, and IgA antibodies after repeat dosing. Unique to juvenile ferrets was a suppression of plasma anti-capsid-binding IgM after the second vector administration. Thus, age-dependent immune system maturation and isotype switching may affect the development of high-affinity lung NAbs after repeat dosing of AAV2.5T and may provide a path to blunt AAV-neutralizing responses in the lung.


Influence of PMA and a low extracellular Ca2+ concentration on the development of the Na(+)-dependent hexose carrier in LLC-PK1 cells.
We have analyzed the development of Na(+)-dependent hexose transport during differentiation and during polarization of LLC-PK1, an established cell line with characteristics of the proximal tubule. When cell-cell contact was disturbed by a low extracellular Ca2+ concentration or by a phorbol myristate acetate (PMA) treatment, the development of Na(+)-dependent hexose transport was completely inhibited. The effect of PMA on the development of hexose transport could be uncoupled from its effect on the tight junctions. The PMA concentration needed for the latter effect was approx. 10-fold higher than for the former. As the primary cause of the PMA effect, an influence on the cytoskeleton is suggested. In contrast to PMA, the concentration dependence of both phenomena on the extracellular Ca2+ concentration was almost the same. Moreover, the incorporation of hexose carriers in the plasma membrane could be induced by changing the extracellular CA2+ concentration from low to normal. We conclude that there is a relation between the formation of tight junctions and the development of the Na(+)-dependent hexose carrier, possibly because Ca(2+)-dependent cell adhesion molecules play a role in both phenomena. However, a direct relation between Ca(2+)-dependent elements of the tight junctions and the insertion of the hexose carrier can not be excluded. The Ca(2+)-dependent development seems to be a common characteristic of apical membrane proteins in contrast to the development of the basolateral membrane protein, (Na(+)+K+)-ATPase.


The interaction of tetraiodofluorescein with creatine kinase.
The dye 2',4',5',7'-tetraiodofluorescein is a potent inhibitor of creatine kinase (ATP:creatine N-phosphotransferase, EC 188.8.131.52) with an apparent competitive inhibition constant with respect to MgATP2- of 2.6 - 10(-5) M. The association of the dye with the enzyme elicited a red shift in the dye's spectrum, indicative of a binding site less polar than water. The dye binds to the enzyme with an equilibrium constant of dissociation of 1.7 - 10(-5) M. MgATP or MgADP competes for the dye-binding site. Creatine binds to creatine kinase-tetraiodofluorescein complex to form a ternary complex and further causes a blue-shift in the spectrum of the bound dye. The binding of the dye to fully active creatine kinase causes conformational change that was monitored by enzyme-bound 2-mercuri-4-nitrophenol, a conformation-dependent "reporter group".


Ether-soluble resin glycosides from the roots of Ipomoea batatas.
Two new resin glycosides, batataosides I (1) and II (2), and five known compounds, friedelin (3), scopoletin (4), octadecyl caffeate (5), beta-sistosterol (6) and daucosterol (7), were isolated from the roots of Ipomoea batatas. Their structures have been determined based on the chemical and spectral data. Batataosides I and II have novel structures because the core simonic acid B was esterised with cinnamic acid for the first time, and three different substituent esterification groups in one resin glycoside is scarce. The absolute configuration of the aglycone was elucidated to be S by Mosher's method.


Endothelial vesiculo-vacuolar organelles, pockets and multi-layered fenestrated lamellae in the capillaries of the mouse carotid body.
Fenestrated capillaries represent the basic structural unit in the carotid body. They mediate a characteristic hyperpermeability state in this organ. Endothelial fenestrae and plasmalemmal vesicles are of particular importance in this respect. The present electron microscopic study of the capillaries of the mouse carotid body demonstrates prominent endothelial cell structures that are suggested to be closely related to endothelial fenestrae and plasmalemmal vesicles. These structures include: (1) Vesiculo-vacuolar organelles formed by fusion and intercommunication of vesicles and vacuoles of variable dimensions. (2) Pockets in the form of fenestrated membrane-bound vacuoles that communicate either with the capillary lumen, pericapillary space or both via multiple apertures or fenestrae. (3) Multi-layered fenestrated Lamellae where the endothelial cytoplasm is divided into multiple attenuated sheets provided with several fenestrae. The latter two structures are preferentially located in the thick perinuclear region of the endothelial cell. Their fenestrae are always distributed in linear series and show close similarity to the usual chains of fenestrae in the attenuated periphery of the endothelial cells. The individual apertures of the fenestrated vacuoles and multi-layered fenestrated lamellae are closely similar to the stomata of fully opened plasmalemmal vesicles suggesting a relationship between them. Morphological and morphometrical analysis of a series of fenestrae belonging to these structures revealed that they are identical to the usual chains of fenestrae in the attenuated periphery of the endothelial cells.


Changes of serum cytokine profiles in Korean vivax malarial patients after chemotherapy.
Changes of serum cytokines including interferon gamma inducible protein-10 (IP-10) chemokine were analyzed in a total of eight vivax malarial patients before and after chemotherapy by immunostaining for human cytokine antibodies attached to membranes. IP-10 was strongly reactive in the period before chloroquine/primaquine combined chemotherapy and disappeared after chemotherapy in all patients. Therefore, IP-10 chemokine may be of importance in the pathogenesis of vivax malaria and a good marker of a complete cure.


An in vivo technique for pharmacological manipulation of Drosophila brain during optical recording.
Drosophila melanogaster, an established model for genetic manipulation, has recently been used for studying olfactory perception, learning, and memory. Some of these important behavioral phenomena have been dissected with defined mutants, some to a single biochemical lesion, expressed in central brain structures known as the mushroom bodies. A previously introduced preparation used a window in the head capsule through which these structures could be imaged using genetically expressed fluorescent calcium sensors while applying physiological odorant stimuli. Unfortunately, technical constraints prevented direct manipulation of the mushroom bodies with this preparation. I describe here a preparation that will allow, for the first time, the direct pharmacological manipulation of these important structures during imaging in the living adult fly. Responses to discreet applications of acetylcholine were reversibly blocked with tubocurare and reversibly eliminated in calcium-free Ringers. This new technique will significantly enhance the usefulness of the Drosophila model system, allowing a more quantitative examination of the mechanisms involved in olfactory learning and memory.


Cluster headache mimics.
This article discusses cluster headache and a variety of cluster mimics, with the intention of aiding the practitioner in differentiating between primary cluster headache and secondary forms of cluster. Secondary causes of cluster headache include infections, tumors, vascular abnormalities, and head trauma. In addition, other trigeminal autonomic cephalgias occasionally can be difficult to distinguish from primary cluster headache.


Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin.
Heterochromatin assembly, involving methylation of histone H3 lysine 9 (H3K9me), regulates various chromosomal processes. In fission yeast, heterochromatin targeted to specific repeat loci in an RNAi-dependent manner spreads across extended domains to exert regional epigenetic control. The Clr4 methyltransferase complex (ClrC) is responsible for nucleation and spreading of heterochromatin; however, its recruitment to heterochromatic repeats is poorly understood. Here we demonstrate that ClrC components are distributed throughout heterochromatic domains. To nucleate heterochromatin, Rik1, a WD domain-containing subunit of ClrC, is loaded onto the transcribed repeats via RNAi machinery including the RNA-induced transcriptional silencing (RITS) complex. Furthermore, we show that the chromodomain of Clr4 binds specifically to H3K9me that is essential for the spreading of heterochromatin. Our analyses delineate sequential steps for the assembly of heterochromatic domains and suggest that the ability of Clr4 to both 'write' and 'read' H3K9me facilitates heterochromatin maintenance through successive cell divisions.


The presence in human spermatozoa of sites binding some proteins of the outer membrane of Escherichia coli.
In previous works, we noted that porins, surface components of Gram negative bacteria, are toxic for human spermatozoa. In this work we see that porins of E. coli labeled with I125 (0.1-1.0 microgram/ml) bind to spermatozoa, showing the presence of saturable molecular configurations of 0.5-0.6 micrograms/ml. In the presence of non labeled porins, the binding of labeled porins to the spermatozoa is greatly reduced. At saturating concentrations of 0.6 micrograms/ml labeled porins, the binding reaches a saturation plateau at about 15 min.


Highly pathogenic influenza H5N1 virus of clade 126.96.36.199c in Western Siberia.
In the spring of 2015, avian influenza virus surveillance in Western Siberia resulted in isolation of several influenza H5N1 virus strains. The strains were isolated from several wild bird species. Investigation of biological features of those strains demonstrated their high pathogenicity for mammals. Phylogenetic analysis of the HA gene showed that the strains belong to clade 126.96.36.199c.


Identification and functional analysis of choline transporter in tongue cancer: A novel molecular target for tongue cancer therapy.
We examined the functional characteristics of choline uptake in human tongue carcinoma using the cell line HSC-3. Furthermore, we explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. Both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were expressed, and were located in plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is pH-dependent. Several cationic drugs inhibited cell viability and [(3)H]choline uptake. Choline uptake inhibitors and choline deficiency inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1 that relies on a directed H(+) gradient as a driving force. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be the major site for the control of choline oxidation in mitochondria and hence for the supply of endogenous betaine and S-adenosyl methionine, which serves as a major methyl donor. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for tongue cancer therapy.


Validation of EST-derived STS markers localized on Qfhs.ndsu-3BS for Fusarium head blight resistance in wheat using a 'Wangshuibai' derived population.
A few EST-derived STS markers localized on Qfhs.ndsu-3BS, a major QTL for resistance to Fusarium head blight (FHB) in wheat, have been previously identified in the 'Sumai 3'/'Stoa' population. In this study, we used a 'Wangshuibai' (resistant) /'Seri82' (susceptible) derived population, linkage group, QTL, and quantitative gene expression analysis to assess the genetic background dependence and stability of the EST-derived STS markers for use in marker aided selection to improve FHB resistance in wheat. Based on our results, a QTL in the map interval of Xsts3B-138_1-Xgwm493 on chromosome 3BS was detected for FHB resistance, which accounted for up to 16% of the phenotypic variation. BLASTN analysis indicated that Xsts3B-138_1 sequence had significant similarity with the resistance gene analogue. Real-time quantitative PCR showed that the relative expression of Xsts3B-138_1 in 'Wangshuibai' at 96 h after inoculation was 2.6 times higher than 'Seri82'. Our results underlined that EST-derived STS3B-138 markers could be predominantly used in marker aided selection to improve FHB resistance in wheat.


Temporally precise cell-specific coherence develops in corticostriatal networks during learning.
It has been postulated that selective temporal coordination between neurons and development of functional neuronal assemblies are fundamental for brain function and behavior. Still, there is little evidence that functionally relevant coordination emerges preferentially in neuronal assemblies directly controlling behavioral output. We investigated coherence between primary motor cortex and the dorsal striatum as rats learn an abstract operant task. Striking coherence developed between these regions during learning. Interestingly, coherence was selectively increased in cells controlling behavioral output relative to adjacent cells. Furthermore, the temporal offset of these interactions aligned closely with corticostriatal conduction delays, demonstrating highly precise timing. Spikes from either region were followed by a consistent phase in the other, suggesting that network feedback reinforces coherence. Together, these results demonstrate that temporally precise coherence develops during learning specifically in output-relevant neuronal populations and further suggest that correlations in oscillatory activity serve to synchronize widespread brain networks to produce behavior.


Lesions of the inferior olive do not affect long- or short-term habituation of the acoustic startle response in rats.
Short- and long-term habituation of the acoustic startle response were assessed in a group of inferior olive-lesioned rats. Neither short- and long-term habituation, nor the performance of the reflex, were affected by the lesion. Since the cerebellar vermis is essential for long-term habituation of this reflex, we suggest that climbing fibres are not involved in this form of learning, which would therefore be mediated by the other cerebellar input, presumably the mossy fibres.


Tissue pulsatility imaging of cerebral vasoreactivity during hyperventilation.
Tissue pulsatility imaging (TPI) is an ultrasonic technique that is being developed at the University of Washington to measure tissue displacement or strain as a result of blood flow over the cardiac and respiratory cycles. This technique is based in principle on plethysmography, an older nonultrasound technology for measuring expansion of a whole limb or body part due to perfusion. TPI adapts tissue Doppler signal processing methods to measure the "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. This paper presents a feasibility study to determine if TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected transcranially through the temporal acoustic window from four subjects before, during and after voluntary hyperventilation. In each subject, decreases in tissue pulsatility during hyperventilation were observed that were statistically correlated with the subject's end-tidal CO2 measurements. (


Trace elements in relation to trophic ecology of long-distance migratory shorebirds and seabirds in West Africa.
Shorebirds and seabirds are abundant predators in coastal habitats worldwide, relying upon a high diversity of benthic invertebrates and fish, respectively. While occupying different trophic guilds, they are differently exposed to element contamination entering the coastal food web. Therefore, these birds have been used as bioindicators of environmental contamination in marine ecosystems. We analysed the concentration of trace elements in blood samples of 16 shorebird and seabird migratory species in a major non-breeding site, the Bijagós Archipelago, in regard to their trophic ecology. Overall, our study shows low exposure of this bird community to toxic elements, except for Hg. Most species presented Hg burdens within the moderate toxicity threshold, but one species (Dunlin) presented values at a potential high Hg toxicity risk. We found a positive relationship between Se and Ni concentrations and δ15N values (a proxy for trophic level). In addition, a positive relationship was found between δ13C (a proxy for habitat characteristics) and Hg, Fe, Cu and Mn, while the opposite pattern was recorded for As. Differences were also shown for several trace elements between the two studied trophic guilds: concentrations of As, Pb and Se were higher in pelagic fish consumers (seabirds), whereas Cr, Fe and Sr burdens were higher in benthic invertebrate consumers (shorebirds). Although previous studies in the same site revealed very high concentrations of Cd and Pb in some of the prey species of shorebirds and seabirds (bivalves and fishes), values found in birds for these two elements suggest no toxicological risk. Thus, exposure to toxic elements is not currently a threat to coastal bird populations, namely those facing apparent local declines in Guinea-Bissau, one of the most important non-breeding quarters for of West Africa. Still, Hg burdens were high in some species, deserving further monitoring.


Engineering of antibacterial/recyclable difunctional nanoparticles via synergism of quaternary ammonia salt site and N-halamine sites on magnetic surface.
A biocidal composite unit with improved synergism, using one cationic quaternary ammonia salt (QAS) site to attract electronegative bacteria to three highly biocidal N-halamine sites, was designed for the first time and attached onto surface of magnetic silica coated Fe3O4 nanoparticles (silica@Fe3O4NPs) for superior biocidability, large killing area, and easy recyclability. Briefly, a compound containing one imide and two amide NH bonds, 2-(2,5-dioxoimidazolidin-4-yl)-N-(4-hydroxyphenyl)acetamide (DHPA), was prepared by amidation of hydantoin acetic acid with p-aminophenol. A biocidal precursor of one QAS site and three N-halamine sites was then constructed by alcoholysis of 3-triethoxysilylpropyl succinic anhydride with 2-(dimethylamino)ethan-1-ol to introduce a tertiary amine and subsequent esterification with DHPA to introduce three NH bonds. The triethoxysilyl groups in the precursor were hydrolyzed to silanol groups to condense with their counterparts on silica@Fe3O4 NPs. The surface of resultant NPs carried units each contains one QAS site and three N-halamine sites after quaternization and chlorination. The biocidal surface showed superior biocidability against Escherichia coli and Staphylococcus aureus than reported systems due to the improved synergism between multiple antibacterial groups of different types and was stable towards quenching-chlorinating process and storage. The successful design opens insight in the syntheses of more powerful biocides.


Synthesis and Penicillin-binding Protein Inhibitory Assessment of Dipeptidic 4-Phenyl-β-lactams from α-Amino Acid-derived Imines.
Monocyclic β-lactams revive the research field on antibiotics, which are threatened by the emergence of resistant bacteria. A six-step synthetic route was developed, providing easy access to new 3-amino-1-carboxymethyl-4-phenyl-β-lactams, of which the penicillin-binding protein (PBP) inhibitory potency was demonstrated biochemically.


This review investigates the correlation between atopic dermatis and educational performance. Atopic dermatitis (AD) leads to intense itching, affecting sleep and health-related quality of life. AD negatively influences working life and poses a financial burden on society. Information about the impact of AD in childhood/adolescence on school life and the completion of education is sparse and previous studies have not found an association between AD and educational attainment. Recent studies have found AD to be associated with learning disability and decreased educational attainment. Future studies should investigate causality and the effects of optimised treatment.


The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle (Urtica dioica) leaves at low, field-relevant concentrations.
We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet (Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 microg g(-1) dw. Seven snails per treatment were fed for 38 days. Leaf Cd concentrations did not affect food consumption rates, and consequently Cd intake rates increased with increasing leaf concentrations. No differences were detected among treatments in the final soft tissue Cd concentrations and body burdens in the snails. Regression analyses showed no positive relationship between either snail Cd concentrations or body burdens and total Cd intake. This suggests a regulation of internal Cd concentrations at low food Cd concentrations. Our data suggest that Cd excretion via the mucus plays a substantial role in this regulation, in addition to Cd excretion via the faeces. Snail shells were no sinks for Cd.


Lactose intolerance: a self-fulfilling prophecy leading to osteoporosis?
Symptoms of lactose intolerance are unlikely to occur under usual dietary conditions. Yet, self-described "lactose-intolerant" individuals often restrict dairy and calcium intake. A new study suggests that such individuals have reduced peak bone mass and increased incidence of osteopenia, and are at greater risk of osteoporosis and bone fractures.


On the length scale dependence of DNA conformational change under local perturbation.
Conformational change of a DNA molecule is frequently observed in multiple biological processes and has been modeled using a chain of strongly coupled oscillators with a nonlinear bistable potential. While the mechanism and properties of conformational change in the model have been investigated and several reduced order models developed, the conformational dynamics as a function of the length of the oscillator chain is relatively less clear. To address this, we use a modified Lindstedt-Poincare method and numerical computations. We calculate a perturbation expansion of the frequency of the model's nonzero modes, finding that approximating these modes with their unperturbed dynamics, as in a previous reduced order model, may not hold when the length of the DNA model increases. We investigate the conformational change to the local perturbation in models of varying lengths, finding that for the chosen input and parameters, there are two regions of DNA length in the model - first, where the minimum energy required to undergo the conformational change increases with the DNA length; and second, where it is almost independent of the length of the DNA model. We analyze the conformational change in these models by adding randomness to the local perturbation, finding that the tendency of the system to remain in a stable conformation against random perturbation decreases with increase in DNA length. These results should help to understand the role of the length of a DNA molecule in influencing its conformational dynamics.


Prior poliomyelitis: an immunohistochemical study of cytoskeletal proteins and a marker for muscle fibre regeneration in relation to usage of remaining motor units.
Patients with prior poliomyelitis with paresis and excessive use (n = 8) and low use (n = 6) of residual anterior tibial motor units (MUs) during walking were subjected to muscle biopsy of the anterior tibial muscle (TA). Antibodies directed against cytoskeletal proteins, spectrin and desmin, and against Leu-19, a myoblast and satellite cell related antigen, were applied. In the patients with excessive use of residual MUs there was an almost total predominance of hypertrophic type I fibres. In the hypertrophic fibres, staining for spectrin and desmin was normal while staining for Leu-19 was seen in a few fibres. Scattered atrophic fibres seen in the patients with excessive use showed staining for spectrin, desmin and Leu-19. In the patients with low use of residual MUs there were extensive pathological muscle fibre changes. Increased staining for spectrin, desmin and Leu-19 was found in most of the atrophic fibres. The predominance of type I fibres in the patients with excessive use of residual MUs is suggested to be due to muscle fibre transformation. The normal staining pattern for spectrin and desmin in the hypertrophic fibres indicates a normal cytoskeletal structure which might suggest that the adaptive muscle fibre changes are adequate to meet the increased demand. The increased staining for spectrin, desmin and Leu-19 in the atrophic fibres might indicate an ongoing denervation process which earlier has been suggested as an important factor for the development of postpolio progressive muscular atrophy.


N2O profiles in the enhanced CANON process via long-term N2H4 addition: minimized N2O production and the influence of exogenous N2H4 on N2O sources.
Production of the greenhouse gas nitrous oxide (N2O) from the completely autotrophic nitrogen removal over nitrite (CANON) process is of growing concern. In this study, the effect of added hydrazine (N2H4) on N2O production during the CANON process was investigated. Long-term trace N2H4 addition minimized N2O production (0.018% ± 0.013% per unit total nitrogen removed) and maintaining high nitrogen removal capacity of CANON process (nitrogen removal rate and TN removal efficiency was 450 ± 60 mg N/L/day and 71 ± 8%, respectively). Ammonium oxidizing bacteria (AOB) was the main N2O producer. AOB activity inhibition by N2H4 decreased N2O production during aeration, and the N2H4 concentration was negatively correlated with N2O production rate in NH4+ oxidation via AOB, whereas N2O production was facilitated under anaerobic conditions because hydroxylamine (NH2OH) production was accelerated due to anammox bacteria (AnAOB) activity strengthen via N2H4. Added N2H4 completely degraded in the initial aeration phases of the CANON SBR, during which some N2H4 intensified anammox for total nitrogen removal to eliminate N2O production from nitrifier denitrification (ND) by anammox-associated, while the remaining N2H4 competed with NH2OH for hydroxylamine oxidoreductase (HAO) in AOB to inhibit intermediates formation that result in N2O production via NH2OH oxidation (HO) pathway, consequently decreasing total N2O production.


Further report of Bariaka alopiae Cressey, 1966 (Copepoda, Siphonostomatoida) from the Indian Ocean with new host and geographic record.
A copepod parasite, Bariaka alopiae Wilson, 1932 (Eudactylinidae) infested on thresher sharks caught from the Indian Exclusive Economic Zone off Andaman and Nicobar archipelago, eastern Indian Ocean is further reported. Adult females of B. alopiae were collected from the gill filaments of two host species, Alopias pelagicus Nakamura and A. superciliosus Lowe. The species B. alopiae can be easily distinguished from other species within the genus by the following characteristic features: cylindrical body devoid of spines, eighteen segmented antennules and four segmented abdomen. In the Indian Ocean, this parasite was known only from its original description 51 years ago, based on materials from western Indian Ocean off Madagascar. Further the present study reports, A. pelagicus as a new host for this parasite.


Photo-immobilization of proteins on carbons.
The photofunctionalization of three different carbons with two proteins was studied at room temperature. Water solutions of bovine serum albumin, BSA, and α-amylase, AA, were photolyzed at 21 °C in the presence of graphite microparticles (6.20 μm), MPG, graphene oxide, MPGO, and graphene oxide modified with SO2, mMPGO. The insertion of BSA on carbon matrixes occurred with a deoxygenation reaction, most likely due to a dehydration step of a water molecule. XPS, TOC and TGA, showed that the BSA photo-insertion on MPG was highly efficient with 34.9% of the weight of MPG after photolysis, with an initial concentration of 1 g∙L-1 of BSA. A high yield of AA photoinsertion on the carbons was also obtained. The calculated weight of AA inserted on MPG and MPGO after photolysis was 22.30% and 18.08%, respectively, with respect to the initial weight of carbon, when the initial concentration of AA was 60 mg∙L-1. AA immobilized on MPG was active while the enzyme on MPGO showed a smaller activity, within the experimental error. Although a certain extent of denaturalization of both proteins was observed during photolysis, the molecular weight and composition changed very little during the photolysis, which would produce mainly conformational changes and isomerization reactions.


Protective effect of naringenin against cadmium-induced testicular toxicity in male SD rats.
This study aimed to investigate the effect of naringenin (Nar) on cadmium (Cd)-induced testicular toxicity. Twenty-four male Sprague-Dawley (SD) rats aged 5 weeks were used. Rats were administered with 0.9% NaCl (control group), CdCl2 (2 mg/kg b.w. intraperitoneally), Nar (50 mg/kg b.w, orally), and CdCl2 + Nar (2 mg/kg b.w intraperitoneally and 50 mg/kg b.w. orally, respectively) for 4 weeks. Results showed that body weight, relative testis weights, and sperm quality decreased in the Cd-treated group, and Cd accumulated in serum and testes. Pathological examination showed that Cd can cause testicular damage. Cd decreased the serum concentrations of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. It also decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, exposure to Cd resulted in decreased content of reduced glutathione (GSH) and total antioxidant capacity (T-AOC) concentrations, as well as increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents. Cd also provoked testis autophagy by upregulating the expression of the autophagy-related proteins P62 and LC3 II. However, the combined administration of Nar and Cd significantly attenuated the Cd-induced negative effects by increasing the body weight, relative testis weights, and sperm quality and by decreasing testicular damage. Simultaneous supplementation of Nar and Cd markedly restored the decreased levels of GnRH, FSH, LH, testosterone, GSH, and T-AOC and the activities of SOD, CAT, and GPx caused by Cd treatment. Nar further suppressed MDA and H2O2 production and protected the testes from Cd-induced autophagy by downregulating P62 and LC3 II expression. Therefore, Nar protected the testes from Cd-induced toxicity.


Repurposing Non-Antibiotic Drugs Auranofin and Pentamidine in Combination to Combat Multidrug-Resistant Gram-Negative Bacteria.
Infections caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative bacteria, have posed a great challenge to healthcare systems globally. To address the shortage of effective antibiotics against MDR Gram-negative bacterial infections, two non-antibiotic drugs - auranofin (rheumatoid arthritis drug) and pentamidine (antiprotozoal drug) - are being repurposed to treat MDR Gram-negative bacteria by a combination approach. Chequerboard microdilution assay was used to determine the interaction of auranofin and pentamidine against drug-susceptible and MDR Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii and Klebsiella pneumoniae). Fluorescence microscopy, scanning electron microscopy and inductively coupled plasma mass spectrometry were used to explore the mechanism of synergistic antibacterial effect. These two non-antibiotic drugs displayed a strong synergistic antibacterial effect, with the fraction inhibitory concentration index ranging 0.094-0.506. The MIC of auranofin reduced by as much as ≥ 1024-fold when combined with pentamidine at sub-MIC. Fluorescence and inductively coupled plasma mass spectrometry analyses revealed that bacterial membrane disruption caused by pentamidine treatment at sub-MIC led to an increased intracellular auranofin content with the combination treatment. The enhanced auranofin uptake in bacteria resulted in efficient bacterial killing. More importantly, the auranofin/pentamidine combination slowed down auranofin resistance development in clinically isolated MDR bacteria (Klebsiella pneumoniae) more than the combination of auranofin and colistin, which is a last-line antibiotic with a membrane-lytic antibacterial mechanism. The combination of non-antibiotic drugs with complementary antibacterial mechanisms provides a potentially promising approach to discover new antibacterial drugs and delay drug resistance development.


Stereological evaluation of volumetric asymmetry in healthy human cerebellum.
Age-related volumetric differences in brain anatomy or volumetric brain analyses in many disorders are of interest. Delineating the normal anatomical cerebellar volume is of importance for both the anatomists and clinicians. In the present study, we aimed to evaluate the cerebellar volume using a stereological technique and to determine the possible volumetric asymmetry depending on age and gender. Volumetric asymmetry of cerebellar hemispheres was evaluated using stereological method on the magnetic resonance images (MRI) of healthy male and female subjects. Randomly selected individuals (27 males, 27 females) aged between 10-86 years who have normal brain MRI were enclosed in the study. All the subjects were right handed. The individuals were divided into three groups according to age as 18-34 (young), 35-60 (middle aged) and 60-84 (elder) and their MRI images were analyzed. The data set were analyzed by two factor repeated measure analysis. Although the cerebellum was smaller between young and middle aged groups and also middle aged and elder groups, there were no any statistically significant differences between compared groups' mean (P > 0.05). There were not statistically differences according to sex and age groups (P > 0.05). There was no cerebellar asymmetry between compared groups. The stereological evaluation of cerebellar asymmetry in humans correlate with both gender and age groups is of importance for both clinicians and anatomists. The technique is simple, reliable, unbiased and inexpensive.


The Biofire® Filmarray® Pneumonia Plus panel for management of lower respiratory tract infection in mechanically-ventilated patients in the COVID-19 era: a diagnostic and cost-benefit evaluation.
We assessed the diagnostic performance of the Biofire® Filmarray® Pneumonia Plus panel (FA-PP) compared to standard culture in Intensive Care Unit patients with suspected ventilator-associated lower respiratory tract infection in the COVID-19 era. We determined whether its implementation in routine diagnostic algorithms would be cost-beneficial from a hospital perspective. Of 163 specimens, 96 (59%) returned negative results with FA-PP and conventional culture, and 29 specimens (17.8%) were positive with both diagnostic methods and yielded concordant qualitative bacterial identification/isolation. Thirty-nine specimens (23.9%) gave discordant results (positive via FA-PP and negative via culture). Real-life adjustments of empirical antimicrobial therapy (EAT) after FA-PP results resulted in additional costs beyond EAT alone of 1868.7 €. Adequate EAT adjustments upon FA-PP results would have resulted in a saving of 6675.8 €. In conclusion, the data presented supports the potential utility of FA-PP for early EAT adjustment in patients with ventilator-associated lower respiratory tract infection.


Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Disorders: Experience from a Referral Center in India.
To share experience of over 15 years in hematopoietic stem cell transplantation in children with primary immunodeficiency disorders. Medical record review. A referral center for pediatric hemato-oncological disorders. Children (<18 y) diagnosed to have primary immune deficiencies who underwent hematopoietic stem cell transplantation between 2002 and August 2017. Disease-free survival, morbidity and mortality. 85 primary immunodeficiency disorder transplants were performed with engraftment noted in 80 (94%) transplants and an overall survival of 67%. The conditioning regimen was individualized based on the underlying immune defect. Mixed chimerism was noted in 20% children with 56% (9/16) remaining disease-free. Graft versus host disease was noted in 33 (39.2%) children with most seen in children with chronic granulomatous disease. Severe combined immune deficiency transplants were mainly complicated by infections. Immune cytopenias complicated Wiskott Aldrich syndrome and Hemophagocytic lymphohistiocytosis transplants. 29.4% (25/85) children underwent haploidentical transplant in our cohort with a survival of 70% in this group. Infectious complications were the most common cause of death. Primary immunodeficiency disorders are curable in India when transplanted in centers with experienced and trained pediatric transplant physicians and intensivists.


Summary Report Panel 3: Gap Analysis from the Perspective of Animal Biology: Results of the Panel Discussion from the Third International Conference on the Effects of Noise on Aquatic Life.
There is little disagreement among regulators, scientists, and other interested parties as to the complexity surrounding our understanding of the potential and realized impacts of anthropogenic noise on marine life. Given the challenges of research in an aquatic environment, the breadth of species of interest and the range of human-made noise-producing activities, it is difficult at best to identify the most important science needs that improve our understanding and ultimately regulation of the issue.


IS26-associated In4-type integrons forming multiresistance loci in enterobacterial plasmids.
Three distinct multiresistant loci from enterobacterial plasmids each comprised an integron and an IS26-associated sequence. Sequence comparison suggested a common ancestral structure that derived from an IS26 insertion into the 5' conserved segment of an In4-type integron and evolved through acquisition of gene cassettes and IS26-mediated recruitment of additional resistance genes of diverse origin.


Treatment of alcohol organic mental disorder with piracetam.
1. The paper presents an investigation of the efficiency of piracetam in alcohol organic mental disorder. 2. A double blind placebo controlled study design was used to compare two dosages of the substance (2 x 3g versus 2 x 12g). 3. The cognitive functions of the patients, especially short term memory and concentration, were assessed on the days 0, 7, 14, 28 and 42 using various psychological instruments. 4. An analysis of 39 patients showed an improvement of cognitive functions in all three groups. 5. Patients receiving drug treatment showed earlier responses than patients receiving placebo; differences between the three investigational groups were not statistically significant. 6. The results achieved make the effect of piracetam appear somewhat questionable.


[Graduate medical education in old age psychiatry: a scoping literature review].
Gerontopsychiatry will become increasingly relevant as a discipline for primary care based on current demographic forecasts, destigmatization of mental illness and specific diagnostic and therapeutic developments. Hence, high quality graduate medical training in old age psychiatry is needed. Objectives The goal of this review was to summarize the literature on medical education relevant to residency training in old age psychiatry and to contrast the findings with international developments in competency-based medical education. The authors used the scoping review method of Arksey and O'Malley. The initial search yielded 913 hits. After full text screening, 20 original articles were used for data extraction. The study content was summarized under three categories: trainee recruitment, length and structure of graduate training curricula in old age psychiatry, and learning goals and competencies in old age psychiatry training. Surveys and expert consensus were mostly used as study methods. High-quality clinical training experience with gerontopsychiatric patients and supervision of residents was an important factor for stimulating interest in old age psychiatry. Few studies provided evidence for educational benefit of digital learning and teaching formats and simulation training in old age psychiatry. Overall, there were no studies in old age psychiatry with explicit reference to concepts of competency-based graduate medical education. Clinical rotations and mentoring foster interest of clinical residents in the discipline of old age psychiatry. Systematically introducing clinical rotations in old age psychiatry in general psychiatry residency programs seems necessary to enable residents to gain relevant knowledge and skills. Educational research in old age psychiatry considering patient outcomes seems to be a meaningful next step.


A staining method for the detection of impaired photosynthetic electron transport in green algae strains.
The utilization of strain CW 15 of Chlamydomonas reinhardtii enables the biochemical staining test for characterizing a defective photosynthetic electron-transport chain on colonies grown on agar medium. It may be used in order to screen for mutants specifically blocked in different parts of the transport chain.


Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and autism spectrum disorder.
Patients diagnosed with Lyme disease share many of the same physical manifestations as those diagnosed with an Autism Spectrum Disorder (ASD). In this study four male children (ages 26-55 months) who have an ASD diagnosis and one male child (age -O meets state and federal requirements for providing a comprehensive, ongoing assessment of a child with an ASD [33]. The SAP-O form measures children's abilities using observational, authentic assessment procedures in the domains of joint attention, symbol use, mutual regulation, and self regulation via observations of specific behaviors in familiar settings [33]. The five children tested positive for Lyme disease and their SAP-O score was evaluated before and after 6 months of antibiotic therapy. Each child was prescribed 200mg of amoxicillin three times per day and three of the five children were prescribed an additional 50mg of Azithromycin once per day. All of the children's scores on the SAP-O assessment improved after 6 months of antibiotic therapy. The assessors also reported anecdotal data of improved speech, eye contact, sleep behaviors, and a reduction of repetitive behaviors.


Combination of the insulin sensitizer, pioglitazone, and the long-acting GLP-1 human analog, liraglutide, exerts potent synergistic glucose-lowering efficacy in severely diabetic ZDF rats.
Severe insulin resistance and impaired pancreatic beta-cell function are pathophysiological contributors to type 2 diabetes, and ideally, antihyperglycaemic strategies should address both. Therapeutic benefits of combining the long-acting human glucagon-like peptide-1 (GLP-1) analog, liraglutide (0.4 mg/kg/day), with insulin sensitizer, pioglitazone (10 mg/kg/day), were assessed in severely diabetic Zucker diabetic fatty rats for 42 days. Impact on glycaemic control was assessed by glycated haemoglobin (HbA(1C)) at day 28 and by oral glucose tolerance test at day 42. Liraglutide and pioglitazone synergistically improved glycaemic control as reflected by a marked decrease in HbA(1C) (liraglutide + pioglitazone: 4.8 +/- 0.3%; liraglutide: 8.8 +/- 0.6%; pioglitazone: 7.9 +/- 0.4%; vehicle: 9.7 +/- 0.3%) and improved oral glucose tolerance at day 42 (area under the curve; liraglutide + pioglitazone: 4244 +/- 445 mmol/l x min; liraglutide: 7164 +/- 187 mmol/l x min; pioglitazone: 7430 +/- 446 mmol/l x min; vehicle: 8093 +/- 139 mmol/l x min). A 24-h plasma glucose profile at day 38 was significantly decreased only in the liraglutide + pioglitazone group. In addition, 24-h insulin profile was significantly elevated only in the liraglutide + pioglitazone group. Liraglutide significantly decreased food intake alone and in combination with pioglitazone, while pioglitazone alone increased cumulated food intake. As a result, rats on liraglutide alone gained significantly less weight than vehicle-treated rats, whereas rats on pioglitazone alone gained significantly more body weight than vehicle-treated rats. However, combination therapy with liraglutide and pioglitazone caused the largest weight gain, probably reflecting marked improvement of energy balance because of reduction of glucosuria. Combination therapy with insulinotropic GLP-1 agonist liraglutide and insulin sensitizer, pioglitazone, improves glycaemic control above and beyond what would be expected from additive effects of the two antidiabetic agents.


Ova-looking feminist theory: a call for consideration within health professions education and research.
The role of feminist theory in health professions education is often 'ova-looked'. Gender is one cause of healthcare inequalities within contemporary medicine. Shockingly, according to the World Health Organisation, no European member state has achieved full gender equity in regard to health outcomes. Further, contemporary curricula have not evolved to reflect the realities of a diverse society that remains riddled with inequity. This paper outlines the history of feminist theory, and applies it to health professions education research and teaching, in order to advocate for its continued relevance within contemporary healthcare.


Sequencing, biochemical characterization, crystal structure and molecular dynamics of cellobiohydrolase Cel7A from Geotrichum candidum 3C.
The ascomycete Geotrichum candidum is a versatile and efficient decay fungus that is involved, for example, in biodeterioration of compact discs; notably, the 3C strain was previously shown to degrade filter paper and cotton more efficiently than several industrial enzyme preparations. Glycoside hydrolase (GH) family 7 cellobiohydrolases (CBHs) are the primary constituents of industrial cellulase cocktails employed in biomass conversion, and feature tunnel-enclosed active sites that enable processive hydrolytic cleavage of cellulose chains. Understanding the structure-function relationships defining the activity and stability of GH7 CBHs is thus of keen interest. Accordingly, we report the comprehensive characterization of the GH7 CBH secreted by G. candidum (GcaCel7A). The bimodular cellulase consists of a family 1 cellulose-binding module (CBM) and linker connected to a GH7 catalytic domain that shares 64% sequence identity with the archetypal industrial GH7 CBH of Hypocrea jecorina (HjeCel7A). GcaCel7A shows activity on Avicel cellulose similar to HjeCel7A, with less product inhibition, but has a lower temperature optimum (50 °C versus 60-65 °C, respectively). Five crystal structures, with and without bound thio-oligosaccharides, show conformational diversity of tunnel-enclosing loops, including a form with partial tunnel collapse at subsite -4 not reported previously in GH7. Also, the first O-glycosylation site in a GH7 crystal structure is reported--on a loop where the glycan probably influences loop contacts across the active site and interactions with the cellulose surface. The GcaCel7A structures indicate higher loop flexibility than HjeCel7A, in accordance with sequence modifications. However, GcaCel7A retains small fluctuations in molecular simulations, suggesting high processivity and low endo-initiation probability, similar to HjeCel7A. Structural data are available in the Protein Data Bank under the accession numbers 5AMP, 4ZZV, 4ZZW, 4ZZT, and 4ZZU. The Geotrichum candidum GH family 7 cellobiohydrolase nucleotide sequence is available in GenBank under accession number KJ958925. Glycoside hydrolase family 7 reducing end acting cellobiohydrolase.


Structural requirements within protoporphyrin IX in the inhibition of heat shock protein 90.
Porphyrins are used for photodynamic therapy for their light-absorbing properties, and some of them were approved for the treatment of certain types of cancers. Porphyrins prevent activation of hypoxia inducible factor-1α (HIF-1α) by inhibiting heat shock protein 90 (HSP90). This study investigated the structural requirements within protoporphyrin IX (PPIX) for the inhibition of HSP90 activity. In HCT116, HT29 and DLD-1 cells, PPIX treatment directly hindered the binding between HSP90 and HIF-1α; PPIX treatment inhibited the chaperone activity of HSP90, accelerating protein degradation of HIF-1α. In addition, PPIX treatment suppressed cancer cell migration, endothelial cell tube formation, and aortic ring sprouting, being consistent with its anti-tumor and anti-angiogenic activities. In silico analysis, molecular docking model indicated that a tetrapyrrole macrocycle and two propionate chains within PPIX are necessary for the binding to the adenosine triphosphate (ATP)-binding pocket of HSP90. The predicted structural requirement was verified by the differential inhibitory effects of PPIX analogs, or the precursor of PPIX, on HIF-1α; compounds lacking either the tetrapyrrole macrocycle or the propionate chains were inactive. Our results show that a tetrapyrrole macrocycle and two attached propionate chains in PPIX coordinately interact with the ATP-binding pocket of HSP90, offering structural information on the inhibitory effect of porphyrins on angiogenesis.


A continuous culture study of the regulation of extracellular protease production in Vibrio SA1.
During growth of Vibrio SA1 in a lactate-limited chemostate in the presence of 2mM phenylalanine as an inducer, the rate of production of two proteolytic enzymes, namely an endopeptidase and an aminopeptidase, was dependent upon the dilution rate. An optimum in the rate of synthesis of both proteases was observed at a dilution rate of 0.23 h-1 and enzyme production only occurred between dilution rates of 0.06 and 0.45 h-1. Without inducer a low rate of aminopeptidase production was found with an optimum at 0.19 h-1, but only trace amounts of endopeptidase were detectable in the culture. In the presence of inducer the rate of enzyme production increased with increasing dilution rates over the range 0.06 to 0.23 h-1 which was explained by an increase in saturation of inducer sites. The progressive decrease in the rate of protease production at higher dilution rates was ascribed to an increasing effect of catabolite repression by the increasing concentration of the growth substrate. It was shown that 5 mM cyclic AMP could not relieve catabolite repression caused by glucose or lactate. Repression of protease production also occurred in the presence of higher concentrations (5 mM) phenylalanine and other amino acids and by ammonium ions. It is suggested that the energy-status of the cell may play an important role in the regulation of protease synthesis in Vibrio SA1.


Case Report: A case of HNF1B mutation patient with first presentation of diabetic ketosis.
Maturity-onset diabetes of the young 5 (MODY5), a rare diabetes syndrome of young adults, is associated with variants in hepatocyte nuclear factor 1B (HNF1B) gene. We reported a case of MODY5, which presented with diabetic ketosis, multiple renal cysts, and hypokalemia. In this case, the HNF1B score was estimated as 13 and a heterozygous variant of HNF1B in exon 4 (c.826C>T, p.Arg276*) was identified through Sanger sequencing. Multiple renal cysts and youth-onset diabetes are common manifestations in patients with HNF1B mutations, and insufficient insulin secretion may be a potential cause of diabetic ketosis in MODY5.


The effects of chronic lead treatment and hypertension on the severity of cardiac arrhythmias induced by coronary artery occlusion or by noradrenaline in anaesthetised rats.
The aim of this study was to investigate whether chronic (3 months) lead (250 or 1000 ppm), administered as lead acetate in the drinking water, commencing either after weaning (in normotensive or spontaneously hypertensive male rats) or from conception (normotensive rats only) altered the susceptibility of the heart to arrhythmias induced either by coronary artery occlusion or by noradrenaline. Treatment with lead alone had no marked effect on the arrhythmias elicited by either method. Spontaneously hypertensive rats treated with either dose of lead exhibited more ectopic beats following coronary artery occlusion than normotensive rats but not more than those observed in control spontaneously hypertensive rats. An enhanced arrhythmogenic effect of noradrenaline was observed only in hypertensive rats administered 250 ppm lead. Both doses of lead accelerated the development of high blood pressure and in normotensive rats the higher dose also resulted in an elevated pressure. Following administration of lead, blood lead concentrations were elevated to 0.96 and 2.11 mumol l-1 after 250 and 1000 ppm, respectively. Accumulation of lead in heart and bone was also observed. We conclude that chronic exposure to these concentrations of lead, when combined with high blood pressure, slightly enhances the susceptibility of the heart to arrhythmias induced by myocardial ischaemia.


Nitric oxide cycle in mammals and the cyclicity principle.
This paper continues a series of reports considering nitric oxide (NO) and its cyclic conversions in mammals. Numerous facts are summarized with the goal of developing a general concept that would allow the statement of the multiple effects of NO on various systems of living organisms in the form of a short and comprehensive law. The current state of biological aspects of NO research is analyzed in term of elucidation of possible role of these studies in the system of biological sciences. The general concept is based on a notion on cyclic conversions of NO and its metabolites. NO cycles in living organisms and nitrogen turnover in the biosphere and also the Bethe nitrogen-carbon cycle in star matter are considered. A hypothesis that the cyclic organization of processes in living organisms and the biosphere reflects the evolution of life is proposed: the development of physiological functions and metabolism are suggested to be closely related to space and evolution of the Earth as a planet of the Solar System.


Maternal urinary metal(loid)s and risk of preterm birth: A cohort study in the Tibetan Plateau.
Maternal metal(loid)s exposure has been related to preterm birth (PTB), but the results are still inconclusive. Previous studies have mainly discussed the harmful metal(loid)s, neglecting beneficial ones. We examined the association of maternal metal(loid)s with PTB and gestational age (GA) in a birth cohort from the Tibetan Plateau. We measured 29 metal(loid)s in urine samples from 1081 pregnant women in the third trimester. Information regarding demographics, socioeconomic status, diet, medication, and lifestyle was collected through standardized interviews. The associations of single metal(loid)s with PTB or GA were evaluated using a generalized linear mixed-effects model or linear mixed-effects model. Elastic net and Bayesian kernel machine regressions were used to explore the joint associations. Magnesium (Mg), Copper (Cu), and Tin (Sn) were the main "harmful" metal(loid)s positively and negatively associated with PTB or GA, respectively. Mg was the dominant "harmful" metal(loid)s associated with PTB in a J-shape. A one-fold increase in Mg was associated with a 38% increased risk of PTB [OR (95% CI) = 1.38 (1.15, 1.65), PFDR<0.05] and 0.17 weeks shortening of GA [β (95% CI) = -0.25 (-0.35, -0.14), PFDR<0.05]. Cesium (Cs), rubidium (Rb), and Molybdenum (Mo) were the main "beneficial" metals. Cs dominated the "beneficial" associations and was negatively associated with PTB in a linear manner. A one-fold increase in Cs was associated with a 67% decreased risk of PTB [OR (95% CI) = 0.43 (0.27, 0.67), PFDR<0.05] and 0.24 weeks of prolonged GA [β (95% CI) = 0.35 (0.13, 0.56), PFDR<0.05]. Ethnicity and living altitude modified the association of Mg and Cu with PTB or GA. In conclusion, Maternal urinary metal(loid)s were bi-directionally associated with PTB in a population in the Tibetan Plateau. Mg and Cs were the dominant "harmful" and "beneficial" metal(loid)s, respectively.


[Use of an immunoenzyme method with monoclonal antibodies in cytologic studies for the optimal diagnosis of non-Hodgkin's lymphoma in children].
From January 1987 to April 1988 six children we studied cytologically with the use of alkaline phosphatase-anti-alkaline phosphatase (APAAP) method and monoclonal antibodies (MoP) in order to establish the diagnosis of Non-Hodgkin Lymphoma. (NHL). Cytologic studies concerned pleural fluid (3 patients) imprints of the lymph node (3 patients), bone marrow smears (2 patients) and cerebrospinal fluid (1 patient). We performed simultaneously routine cytologic and histopathologic studies of the lymph nodes. Antigen T6 (thymocytes) was present in blasts of all patients, which permitted us to classify the blasts as common stage II group according to Reinherz. In all cases we found at least two positive antigen detected by MoP pan T (CD2, CD3, CD5, CD7) in one case--no expression of antigen T3 (CD3) and in two cases no antigen detected by an antibody CD2. Antigen Ia was found in one patient, and weak expression of antigen CALLA (CD10) in one patients. In three patients we showed a simultaneous expression of antigens T4, T8, whereas in two patients they were not observed. One child possessed mature phenotype T4, T6. By using APAAP method with MoP in cytologic studies it was possible to diagnose T-lymphoblastic lymphoma in six children before the results of histopathologic examination of the lymph nodes.


The Effect of Interlayer Materials on Ceramic Damage in SiC/Al Composite Structure.
The effect of interlayer materials on the damage of ceramics in the SiC/Al compositestructure was analyzed through experiments and simulation. Using 0.25 mm thermoplasticpolyurethane (TPU) as a reference, a 0.5 mm aramid fabric (AFRP) or a 0.5 mm carbon fiberreinforced epoxy matrix composite (CFRP) was added to the interlayer, respectively. Through theimpact tests, it was discovered that the ceramic damaged area in the TPU composite structure wassevere. With the addition of AFRP, the damaged area of the ceramic layer was reduced by 73%under the same impact conditions. The addition of CFRP also reduced the damage of ceramics. Theevolution process of the tensile stress on the ceramic rear surface was presented by simulation. Thetensile evolution process analysis can explain the experimental phenomenon well and can be usedto predict the damage of the ceramics.


Warts transmitted in families and schools: a prospective cohort.
Cutaneous warts are common in primary schoolchildren; however, knowledge on the routes of transmission of human papillomavirus (HPV) causing warts is scarce. This study examines the association between the degree of HPV exposure and incidence of warts in primary schoolchildren to support evidence-based recommendations on wart prevention. In this prospective cohort study, the hands and feet of all children in grades 1 to 7 (aged 4-12 years) of 3 Dutch primary schools were inspected for the presence of warts at baseline and after 11 to 18 months of follow-up. Data on the degree of HPV exposure included information obtained from parental questionnaires: preexistent warts, warts in family, prevalence of warts at baseline in the class, and use of public places (eg, swimming pools). Of the 1134 eligible children, 97% participated; the response rate from parental questionnaires was 77%, and loss to follow-up was 9%. The incidence for developing warts was 29 per 100 person-years at risk (95% confidence interval [CI] 26-32). Children with a white skin type had an increased risk of developing warts (hazard ratio [HR] 2.3, 95% CI 1.3-3.9). Having family members with warts (HR 2.08, 95% CI 1.52-2.86) and wart prevalence in the class (HR 1.20 per 10% increase, 95% CI 1.03-1.41) were independent environmental risk factors. The degree of HPV exposure in the family and school class contributes to the development of warts in schoolchildren. Preventive recommendations should focus more on limiting HPV transmission in families and school classes, rather than in public places.


A simple and rapid competitive enzyme-linked immunosorbent assay to identify HPA-1a (PlA1)-negative donor platelet units.
Alloantibodies to HPA-1a (PlA1) are the major cause of neonatal alloimmune thrombocytopenia and posttransfusion purpura and have been implicated in refractoriness to random-donor platelet transfusions. However, most assays used to phenotype platelets are cumbersome or time-consuming for large numbers of samples. A simple, competitive (inhibition) enzyme-linked immunosorbent assay for HPA-1a phenotyping of donor platelets was developed. A segment from the donor platelet unit transfer line was sealed to obtain a small aliquot of platelets. These platelets were washed once and added to a predetermined dilution of serum containing alloantibodies to HPA-1a. Residual anti-HPA-1a binding to the glycoprotein IIb/IIIa purified by lectin and high-performance liquid chromatography and coated on microtiter wells was detected with a conjugated antihuman IgG. A lack of inhibition equivalent to control (no platelets) was used to determine that the platelets were HPA-1b/b. Of the 557 platelet units tested, 14 (2.5%) were found to be HPA-1a negative, and they were confirmed to be HPA-1b/b by DNA genotyping. Two of the 14 HPA-1b/b units were also HPA-3b/b (approx. 0.35% of the random population). Use of the microtiter format allows 100 to 200 samples to be processed per day. This simple and inexpensive assay is useful for identifying HPA-1b/b units for platelet-compatible transfusions or for platelet antibody investigations.


Modifications of sodium channel gating in Myxicola giant axons by deuterium oxide, temperature, and internal cations.
In dialyzed Myxicola axons substitution of heavy water (D2O) externally and internally slows both sodium and potassium kinetics and decreases the maximum conductances. Furthermore, this effect is strongly temperature dependent, the magnitude of the slowing produced by D2O substitution decreasing with increasing temperature over the range 3-14 degrees C with a Q10 of approximately 0.71. The relatively small magnitude of the D2O effect, combined with its strong temperature dependence, suggests that the rate limiting process producing a conducting channel involves appreciable local changes in solvent structure. Maximum conductances in the presence of D2O were decreased by approximately 30%, while the voltage dependences of both gNa and gK were not appreciably changed. In contrast to the effects of heavy water substitution on the ionic currents, membrane asymmetry currents were not altered by D2O, suggesting that gating charge movement may preceed by several steps the final transformation of the Na+ channel to a conducting state. In Myxicola axons the effect of temperature alone on asymmetry current kinetics can be well described via a simple temporal expansion equivalent to a Q10 of 2.2, which is somewhat less than the Q10 of GNa activation. The integral of membrane asymmetry current, representing maximum charge movement, is however not appreciably altered by temperature.


HOXA gene cluster rearrangement in a t(7;9)(p15;q34) in a child with MDS.
We describe the molecular characterization of a t(7;9)(p15;q34) found in a 15-month-old female patient, diagnosed with refractory anemia with excess blasts in transformation (RAEBt), in progression to acute myeloid leukemia (AML) M7. Molecular characterization of the 7p15 breakpoint showed that this was localized within a fully sequenced PAC clone RP1-170O19 containing the HOXA4 to HOXA13 genes and the EVX1 gene. The 9q34 breakpoint was mapped distal to ABL1 and proximal to NOTCH1 excluding their involvement as fusion gene partners. Our findings suggest a causal role for HOXA genes in childhood myelodysplasia and warrant investigation of this locus in a larger series of patients.


Effect of surgical stress on the erythrocyte insulin receptor.
The aim of this study was to investigate whether surgical trauma causes changes in insulin receptors which may have significance on the causation of post-traumatic insulin resistance. Twenty-four patients scheduled for lumbar intervertebral disc operations or thoracotomy were investigated. In patients who did not receive glucose during operation blood glucose and plasma insulin concentrations did not change but lipolysis was induced as indicated by the increase of serum free fatty acids concentration. Glucose infusion (5% w/v) caused a hyperglycaemic and hyperinsulaenemic response without lipolysis. In patients not receiving a glucose load the number of insulin receptors on erythrocyte measured 4 h postoperatively increased from the preoperative values and the affinity of the receptors to insulin in physiological concentration range increased. In patients with glucose load the number of receptors decreased and receptor affinity to insulin at physiological concentration decreased. The results suggest that in patients receiving a glucose load the receptor changes indicate the perioperative development of insulin resistance at receptor level.


Preferential late replication of one of the two morphologically distinguishable X-chromosomes in a female muntjac.
In a female barking deer, Muntiacus muntjak, whose 2 X-chromosomes are mutually distinguishable from each other, one X has been found to be late replicating in 57.8% cells compared to the other which is late replicating in 42.2% cells. These data are suggestive of preferential inactivation of one X-chromosome. These findings have been discussed in the light of Lyon's hypothesis of random X-inactivation in eutherian mammals.


Women's weight and disordered eating in a large Norwegian community sample: the Nord-Trøndelag Health Study (HUNT).
An increasing part of the population is affected by disordered eating (DE) even though they do not meet the full eating disorder (ED) criteria. To improve treatment in the range of weight-related disorders, there is a need to improve our knowledge about DE and relevant correlates of weight problems such as underweight, overweight and obesity. However, studies investigating DE and weight problems in a wide range of ages in the general population have been lacking. This paper explores DE, weight problems, dieting and weight dissatisfaction among women in a general population sample. Cross-sectional study. The third survey of the Nord-Trøndelag Health Study (HUNT3). The population included 27,252 women, aged 19-99 years, with information on DE outcomes and covariates. DE was assessed with an 8-item version of the Eating Attitude Test and the Eating Disorder Scale-5. Body mass index (BMI) was objectively measured. Data on dieting and weight dissatisfaction were collected from self-reported questionnaires and analysed across weight categories. Crude and adjusted logistic and multinomial logistic regression models were used. High rates of overweight (38%) and obesity (23%) were found. DE was associated with weight problems. In women aged <30 years, 11.8% (95% CI 10.3 to 13.1) reported DE, and 12% (95% CI 11.5 to 12.6) reported DE in women aged >30 years. In those of younger ages (19-29 years), lower weight predicted DE, while increasing weight predicted DE in older aged women (30-99 years). The majority of women were dissatisfied with their weight (58.8%), and 54.1% of the women reported dieting. Neither BMI status nor age was associated with dieting or weight dissatisfaction. A high prevalence of DE was observed, and findings suggest that weight problems and DE are not distinct from one another. Dieting was associated with women's weight dissatisfaction, rather than with actual weight. This requires further investigations about directionality of effects.


The successful management for long-term intractable enteroatmospheric fistula: A case report.
Efficacy of open abdomen management with negative pressure wound therapy for enteroatmospheric fistula has been performed. But, few reports have shown its utility for enteroatmospheric fistula several years after onset. A 46 year-old woman underwent total colectomy due to total ulcerative colitis in her twenties. Three years before the onset of enteroatmospheric fistula, she underwent simple total hysterectomy for uterine smooth muscle tumor. Small bowel obstruction occurred early and a small bowel bypass was performed. However, she had sudden abdominal pain and was diagnosed with anastomotic leakage of small bowel bypass. Although antibiotic treatment was initiated, infection was difficult to control, and a midline abdominal incision was performed, followed by the formation of enteroatmospheric fistula. She declined early surgical intervention and started receiving home parenteral nutrition with antibiotic treatment. Although central vein management was continued, catheter infection became frequent. Hence, surgical intervention was planned 30 months after the formation of enteroatmospheric fistula. Two-stage abdominal wall reconstruction using open abdomen management with negative pressure wound therapy was planned. The definitive abdominal wall reconstruction was performed 14 days after the initial operation. Finally, she was discharged without reoperation. Enteroatmospheric fistula has no overlying soft tissue and no real fistula tract. Besides these complications, there were complications of the scarred abdominal wall from intestinal fluid exposure for 30 months. The strategy using open abdomen management with negative pressure wound therapy for long-term enteroatmospheric fistula will have a good postoperative outcome with the same as early intervention.


Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription.
To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers and genes connected by loops exhibit stronger correlations between histone H3K27 acetylation and expression than can be explained by genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes in acetylation at distal enhancers precede changes in gene expression. Changes in gene expression exhibit a directional bias at differential loop anchors; gained loops are associated with increased expression of genes oriented away from the center of the loop, and lost loops are often accompanied by high levels of transcription within the loop boundaries themselves. These results are consistent with a reciprocal relationship where loops can facilitate increased transcription by connecting promoters to distal enhancers, whereas high levels of transcription can impede loop formation.


E. coli F1-ATPase interacts with a membrane protein component of a proton channel.
The ATP synthases of bacteria, mitochondria and chloroplasts, which use the energy of a transmembrane proton gradient to power the synthesis of ATP, consist of an integral membrane component F0--thought to contain a proton channel--and a catalytic component, F1. To help investigate the way F0 and F1 are coupled, we have sequenced the b-subunit of the Escherichia coli F0, which seems to be the counterpart of a thermophilic bacteria F0 subunit thought to be essential for F1 binding. We report here that its sequence is remarkable, being hydrophobic around the N-terminus and highly charged in the remainder. We propose that the N-terminal segment lies in the membrane and the rest outside. The extramembranous section contains two adjacent stretches of 31 amino acids where the sequence is very similar: in the second of these stretches there is further internal homology. These duplicated stretches of the polypeptide probably fold into two alpha-helices which have many common features able to make contact with F1 subunits. Thus protein b occupies a central position in the enzyme, where it may be involved in proton translocation. It is possibly also important in biosynthetic assembly.


Placing intersectional inequalities in health.
Research into geographical inequalities in health has focused almost exclusively on examining the effects of area-level deprivation and has been largely framed through a compositional-contextual lens, their inter-relationship and the influence of vertical macro-economic and political/policy drivers. However, in the broader health inequalities field, intersectionality has recently emerged as a critical theoretical and methodical approach which examines the concurrent and interacting influences on health of multiple axes of inequality (such as socio-economic status, gender, race/ethnicity and sexuality or gender-identity). Simultaneously, social geography has been explicitly using intersectionality to analyse how mutually constitutive forms of social oppression interact and interrelate with place. This paper exploits the analytical space opened up by this 'intersectional turn' by outlining the benefits for research into geographical inequalities in health that can be achieved by taking a more explicit approach to intersectional inequalities. It argues that: (1) geographical research into health inequalities should more explicitly and widely apply an intersectional lens; and relatedly that, in turn, (2) place needs to be considered as an aspect of intersectionality and integrated into the wider intersectional inequalities in health literature. The paper summarises the evolution of theories of place and health inequalities and outlines intersectional theory and the work to date that has been undertaken to integrate this perspective into our understanding of health inequalities. Drawing on the social geography literature into place and intersectionality, the paper explores how this perspective is being used to enhance our understanding of place effects more generally - and how place itself can be considered as an element of intersectional inequalities. Drawing these different bodies of work together, the paper concludes by considering the implications for theories of geographical inequalities in health.


Estrogen-induced ultrastructural changes in cultured chick embryo hepatocytes.
Administration of estradiol-17-beta induces the synthesis of vitellogenin in primary cultures of chick embryo liver. The ultrastructural changes accompanying steroid induced vitellogenin synthesis were investigated in hepatocytes cultures incubated for 0, 12 and 24 h following hormonal treatment. Both electron microscopy and immuno-chemical techniques were used. The immuno-fluorescence data indicate that the cultures contain a cell population of 90--95% hepatocytes, both in control and estradiol-treated groups. Ultrastructurally, cultured hepatocytes are similar to in vivo ones, except for a reduced accumulation of storage materials, glycogen and lipids. In the estradiol-treated cultures hepatocytes show an accumulation of free ribosomes, enlargement of rough endoplasmic reticulum, and development of the Golgi apparatus.


[Changes in the radiologic and spirometric profile in subjects with pulmonary silicosis].
All admissions with diagnosis of silicosis from 1980 to 2000, in the Occupational Medicine Division of Fondazione S. Maugeri, Cassano Murge (Bari), were examined. From 586 gathered medical records we selected 106 subjects with double admissions and detected their X-rays of chest, FVC and FEV1. The stationary results of their chest X-rays and the light declines of their respiratory functions confirm the slow evolution in time of this pathology.


Impact of a hypertension management/health promotion program on commercial driver's license employees of a self-insured utility company.
Federal regulations governing transportation safety disqualify commercial drivers with persistent uncontrolled hypertension. We sought to determine whether a hypertension management and health promotion program designed for commercial drivers improved blood pressure (BP) outcomes among drivers employed by a self-insured utility company. This retrospective study examined the employment-related medical examinations of 501 randomly selected commercial drivers for measurements of BP, height, and weight taken before and after the intervention. After the program, significantly fewer employees had uncontrolled hypertension according to the Department of Transportation hypertension guidelines (17.2% vs 26.1%, P < 0.01). This improvement was consistent across subgroups defined by diabetes, obesity, and use of antihypertensive medication. An education program improved control of BP among commercial drivers, improving their health and safety, and reducing the number at high risk of medical disqualification.


Powering ≈50 µm Motion by a Molecular Event in DNA Crystals.
A major challenge in material design is to couple nanoscale molecular and supramolecular events into desired chemical, physical, and mechanical properties at the macroscopic scale. Here, a novel self-assembled DNA crystal actuator is reported, which has reversible, directional expansion and contraction for over 50 μm in response to versatile stimuli, including temperature, ionic strength, pH, and redox potential. The macroscopic actuation is powered by cooperative dissociation or cohesion of thousands of DNA sticky ends at the designed crystal contacts. The increase in crystal porosity and cavity in the expanded state dramatically enhances the crystal capability to accommodate/encapsulate nanoparticles/proteins, while the contraction enables a "sponge squeezing" motion for releasing nanoparticles. This crystal actuator is envisioned to be useful for a wide range of applications, including powering self-propelled robotics, sensing subtle environmental changes, constructing functional hybrid materials, and working in drug controlled-release systems.


Re-writing Oral Pharmacokinetics Using Physiologically Based Finite Time Pharmacokinetic (PBFTPK) Models.
To develop physiologically based finite time pharmacokinetic (PBFTPK) models for the analysis of oral pharmacokinetic data. The models are based on the passive drug diffusion mechanism under the sink conditions principle. Up to three drug successive input functions of constant rate operating for a total time τ are considered. Differential equations were written for all these models assuming linear one- or two-compartment-model disposition. The differential equations were solved and functions describing the concentration of drug as a function of time for the central and the peripheral compartment were derived. The equations were used to generate simulated data and they were also fitted to a variety of experimental literature oral pharmacokinetic data. The simulated curves resemble real life data. The end of the absorption processes τ is either equal to tmax or longer than tmax at the descending portion of the concentration time curve. Literature oral pharmacokinetic data of paracetamol, ibuprofen, almotriptan, cyclosporine (a total of four sets of data), and niraparib were analyzed using the PBFTPK models. Estimates for τ corresponding to a single or two or three different in magnitude input rates were derived along with the other model parameters for all data analyzed. The PBFTPK models are a powerful tool for the analysis of oral pharmacokinetic data since they rely on the physiologically sound concept of finite absorption time.


Pulmonary embolism in COVID-19 pneumonia patients admitted to temporary hospital - The follow-up study.
Coronavirus disease 2019 (COVID-19) is linked with major coagulation disorders, especially higher risk of developing pulmonary embolism (PE). Our study summarizes COVID-19 patients' management with concomitant PE during the first weeks of pandemic and underlines the importance of D-dimer concentration assessment at admission in terms of prognosis. Study group consisted of 107 outpatients (mean age 68.91 ± 12.83 years) admitted to the Temporary COVID-19 Hospital in Bialystok, Poland with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and suspicion of PE based on elevated D-dimer concentration (>500 μg/l) and/or low saturation rate (<90%). The clinical follow-up lasted 6 months. Death or re-hospitalization were used as composite clinical endpoint (CEP). Cumulative incidence of PE was 62.3% (73/107 patients). Most of the patients were in the intermediate PE risk group according to the pulmonary embolism severity index (PESI) score. The mean total computed tomography (CT) lung involvement of COVID-19 findings was 48.42 ± 27.71%. Neither D-dimers nor NT-proBNP concentrations correlated significantly with the percentage of lung abnormalities in CT. Patients with baseline D-dimer concentration higher than 1429 μg/l had worse prognosis in 6-months observation, log-rank test, p = 0.009. Ongoing SARS-CoV-2 infection along with massive involvement of lung tissue and concomitant thrombi in pulmonary arteries are challenging for physicians. It seems that simple D-dimer concentration assessment at admission may be a helpful tool not only to predict PE but also to estimate the long-term prognosis.


Effects of heat treatment on physicochemical and microstructure properties of myofibrillar proteins combined with glucose and cellulose nanofibers.
The effects of unheated, 80 °C, 100 °C, and 121 °C on the physicochemical and microstructural properties of myofibrillary protein (MP) supplemented with glucose (Glc) and cellulose nanofibers (CNFs) were studied. The results showed that Glc and CNFs cross-linked with MP through non-covalent bonds when unheated compared with the unheated MP group, which increased the particle size and surface hydrophobicity of MP, and changed the secondary structure. At 80 °C and 100 °C, the particle size and hydrophobicity of MP significantly increased. At 121 °C, the contents of leucine and lysine in MP decreased by 16.2% and 19.9%, respectively, however, both Glc and CNFs could prevent this decrease. Meanwhile, microscopic images showed that the dispersion of Glc-MP and CNFs-MP were more uniform than the MP groups. Compared with Glc-MP, CNFs-MP had more uniform particle size distribution and better thermal stability at high temperatures (121 °C).


Primary explant culture: an in vitro model of the human prostate.
Human prostate tissue gave rise to essentially pure cultures of basal cells in vitro. Careful analysis by phase-contrast microscopy and photography suggested that these cells attempt to differentiate into secretory acinar cells. This was confirmed by immunocytochemical analysis for prekeratin which is present only in basal cells in situ and for prostatic acid phosphatase, prostate-specific antigen, and prostate fluid antigen, which are present only in secretory acinar cells in situ.


A plasmid-born Rap-Phr system regulates surfactin production, sporulation and genetic competence in the heterologous host, Bacillus subtilis OKB105.
According to the change of environment, soil-dwelling Bacillus species differentiate into distinct subpopulations, such as spores and competent cells. Rap-Phr systems have been found to be involved in this differentiation circuit by interacting with major regulatory proteins, such as Spo0A, ComA, and DegU. In this study, we report that the plasmid-born RapQ-PhrQ system found in Bacillus amyloliquefaciens B3 affects three regulatory pathways in the heterologous host Bacillus subtilis. Expression of rapQ in B. subtilis OKB105 strongly suppressed its sporulation efficiency, transformation efficiency, and surfactin production. Co-expression of phrQ or addition of synthesized PhrQ pentapeptide in vitro could compensate for the suppressive effects caused by rapQ. We also found that expression of rapQ decreased the transcriptional level of the sporulation-related gene spoIIE and surfactin synthesis-related gene srfA; meanwhile, the transcriptional levels of these genes could be rescued by co-expression of phrQ and in vitro addition of PhrQ pentapeptide. Electrophoretic mobility shift (EMSA) result also showed that RapQ could bind to ComA without interacting with ComA binding to DNA, and PhrQ pentapeptide antagonized RapQ activity in vitro. These results indicate that this new plasmid-born RapQ-PhrQ system controls sporulation, competent cell formation, and surfactin production in B. subtilis OKB105.


p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway.
The pathogenesis of acute lung injury/acute respiratory distress syndrome (ARDS) is complex and involves multiple signal transduction processes. It is believed that p38MAPK (mitogen-activated protein kinase) is one of the most kinases in inflammatory signaling. At present study, we demonstrated the role of p38MAPK in lipopolysaccharide (LPS)-induced acute lung injury with pharmacologic p38MAPK inhibition by SB203580. SB203580, p38MAPK specific inhibitor, was injected (10 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). The hematoxylin-eosin staining of lung tissues showed that p38MAPK inhibition significantly attenuated the pulmonary inflammatory responses induced by LPS. Moreover, SB203580 can also inhibit the inflammatory cytokine release, and reduce the mortality rate of LPS-induced acute lung injury. Further, western blot analysis that showed SB203580 administration can inhibit the activation of NF-kappaB, which was associated with the inhibition of IkappaBalpha degradation in cytoplasm. These data suggest that p38MAPK signaling may be involved in the activation of NF-kappaB, and activation of p38MAPK signaling may be one of the mechanisms of acute lung injury.


Drug Testing Practices and Policies of Labor and Delivery Units Across the Southeastern United States.
To describe drug testing practices used in labor and delivery units in seven southeastern U.S. states (Alabama, Georgia, Florida, Mississippi, North Carolina, South Carolina, and Tennessee), determine what risk factors prompt drug testing, and determine whether selective policies or factors that prompt testing differ based on hospital characteristics (type, size, or predominant payer source). Cross-sectional descriptive design. Labor and delivery units in seven southeastern U.S. states. Nurse administrators of labor and delivery units (N = 49) who responded for their units. We used a purposive sampling technique to construct a database of hospitals with obstetric services and e-mail addresses for nurse administrators. We created a 35-item survey to collect hospital characteristics and drug testing policy information. We distributed the survey to 291 nurse administrators. We received 49 responses (response rate = 16.8%). Respondents reported that 63% (31/49) of hospitals were not-for-profit, 87% (40/46) had Medicaid as the predominant payer source, 80% (37/46) had a formal perinatal drug testing policy, and 61% (30/49) used selective drug testing protocols. Current or past history of substance use was reported as the risk factor that most often prompted drug testing. We did not find any differences in hospital characteristics (type, size, or predominant payer source) that prompted testing. Most respondents reported that their labor and delivery units had a written drug testing policy and often used selective drug testing protocols. Drug testing protocols did not differ based on hospital type, size, or predominant payer source. Nurses have a role in implementing a best practice with unit-based drug testing.


Human AQP1 is a constitutively open channel that closes by a membrane-tension-mediated mechanism.
This work presents experimental results combined with model-dependent predictions regarding the osmotic-permeability regulation of human aquaporin 1 (hAQP1) expressed in Xenopus oocyte membranes. Membrane elastic properties were studied under fully controlled conditions to obtain a function that relates internal volume and pressure. This function was used to design a model in which osmotic permeability could be studied as a pressure-dependent variable. The model states that hAQP1 closes with membrane-tension increments. It is important to emphasize that the only parameter of the model is the initial osmotic permeability coefficient, which was obtained by model-dependent fitting. The model was contrasted with experimental records from emptied-out Xenopus laevis oocytes expressing hAQP1. Simulated results reproduce and predict volume changes in high-water-permeability membranes under hypoosmotic gradients of different magnitude, as well as under consecutive hypo- and hyperosmotic conditions. In all cases, the simulated permeability coefficients are similar to experimental values. Predicted pressure, volume, and permeability changes indicate that hAQP1 water channels can transit from a high-water-permeability state to a closed state. This behavior is reversible and occurs in a cooperative manner among monomers. We conclude that hAQP1 is a constitutively open channel that closes mediated by membrane-tension increments.


Changes in gene expression of Actinobacillus pleuropneumoniae in response to anaerobic stress reveal induction of central metabolism and biofilm formation.
Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry worldwide. Oxygen deprivation is a stress that A. pleuropneumoniae will encounter during both early infection and the later, persistent stage. To understand modulation of A. pleuropneumoniae gene expression in response to the stress caused by anaerobic conditions, gene expression profiles under anaerobic and aerobic conditions were compared in this study. The microarray results showed that 631 genes (27.7% of the total ORFs) were differentially expressed in anaerobic conditions. Many genes encoding proteins involved in glycolysis, carbon source uptake systems, pyruvate metabolism, fermentation and the electron respiration transport chain were up-regulated. These changes led to an increased amount of pyruvate, lactate, ethanol and acetate in the bacterial cells as confirmed by metabolite detection. Genes encoding proteins involved in cell surface structures, especially biofilm formation, peptidoglycan biosynthesis and lipopolysaccharide biosynthesis were up-regulated as well. Biofilm formation was significantly enhanced under anaerobic conditions. These results indicate that induction of central metabolism is important for basic survival of A. pleuropneumoniae after a shift to an anaerobic environment. Enhanced biofilm formation may contribute to the persistence of this pathogen in the damaged anaerobic host tissue and also in the early colonization stage. These discoveries give new insights into adaptation mechanisms of A. pleuropneumoniae in response to environmental stress.


Potential laser hazards to the clinician during photocoagulation.
We measured reflected laser beams from seven different contact lenses used during laser photocoagulation to evaluate the potential hazards to the eyes of the clinician and bystanders. We found that although collimated beam reflections from the aiming beam of an argon laser photocoagulator could produce disability glare and discomfort to the laser operator (or to an individual viewing through the auxiliary eyepiece), the levels are not hazardous, by current occupational safety limits. Reflected laser light may exceed occupational exposure limits for momentary viewing by bystanders if they are within 1 meter of the laser contact lens.


GPCR sorting at multivesicular endosomes.
The lysosomal degradation of G protein-coupled receptors (GPCRs) is essential for receptor signaling and down regulation. Once internalized, GPCRs are sorted within the endocytic pathway and packaged into intraluminal vesicles (ILVs) that bud inward to form the multivesicular endosome (MVE). The mechanisms that control GPCR sorting and ILV formation are poorly understood. Quantitative strategies are important for evaluating the function of adaptor and scaffold proteins that regulate sorting of GPCRs at MVEs. In this chapter, we outline two strategies for the quantification and visualization of GPCR sorting into the lumen of MVEs. The first protocol utilizes a biochemical approach to assay the sorting of GPCRs in a population of cells, whereas the second strategy examines GPCR sorting in individual cells using immunofluorescence confocal microscopy. Combined, these assays can be used to establish the kinetics of activated GPCR lysosomal trafficking in response to specific ligands, as well as evaluate the contribution of endosomal adaptors to GPCR sorting at MVEs. The protocols presented in this chapter can be adapted to analyze GPCR sorting in a myriad of cell types and tissues, and expanded to analyze the mechanisms that regulate MVE sorting of other cargoes.


Isolated single umbilical artery poses neonates at increased risk of long-term respiratory morbidity.
To investigate whether children born with isolated single umbilical artery (iSUA) at term are at an increased risk for long-term pediatric hospitalizations due to respiratory morbidity. Design: a population-based cohort study compared the incidence of long-term, pediatric hospitalizations due to respiratory morbidity in children born with and without iSUA at term. Soroka University Medical Center. all singleton pregnancies of women who delivered between 1991 and 2013. hospitalization due to respiratory morbidity. Kaplan-Meier survival curves were used to estimate cumulative incidence of respiratory morbidity. A Cox hazards model analysis was used to establish an independent association between iSUA and pediatric respiratory morbidity of the offspring while controlling for clinically relevant confounders. The study included 232,281 deliveries. 0.3% were of newborns with iSUA (n = 766). Newborns with iSUA had a significantly higher rate of long-term respiratory morbidity compared to newborns without iSUA (7.6 vs 5.5%, p = 0.01). Using a Kaplan-Meier survival curve, newborns with iSUA had a significantly higher cumulative incidence of respiratory hospitalizations (log rank = 0.006). In the Cox model, while controlling for the maternal age, gestational age, and birthweight, iSUA at term was found to be an independent risk factor for long-term respiratory morbidity (adjusted HR = 1.39, 95% CI 1.08-1.81; p = 0.012). Newborns with iSUA are at an increased risk for long-term respiratory morbidity.


Direct detection of tissue nitric oxide in septic mice.
Although nitric oxide (NO) is a central mediator during endotoxin-induced sepsis, direct detection of tissue NO in vivo, has until recently been difficult, and techniques have relied on indirect measurement of bi-products in blood or invasive technology. We have utilized electron paramagnetic resonance (EPR) in conjunction with the spin-trapping technique to detect NO directly, and non-invasively, from the tissue of septic mice. Relative signal intensity arising from NO complexed with iron and diethyldithiocarbamate (DETC) measured directly from the liver and kidney of mice given endotoxin was maximal at 6 hours post endotoxin. We failed to detect an EPR signal from mice given pyrogen-free saline. The quality of the EPR signal obtained (high signal to noise ratio of 15:1) using our experimental set-up and L-band EPR hardware was such that we were able to establish a time course of NO production in tissue following endotoxin, and measurement of NO from other organs (kidney and spleen). Our EPR results probably reflected NO arising from inducible NO-synthase enzymes as a result of endotoxin stimulation. This technique was extended to experiments in which we first implanted an oxygen sensitive material (gloxy) into the liver of mice, and then monitored NO production following endotoxin. Due to the fact that the EPR spectrum from gloxy and that of NO-Fe-(DETC)2 do not overlap, we were able to monitor NO production and pO2 simultaneously in tissue, in real time.