Radiation dose among different cardiac and vascular invasive procedures: The RODEO study.
Interventional radiology and cardiology procedures contribute significantly to the collective dose of radiation exposure from medical interventions. Recent and dedicated studies comparing directly these procedures in term of patient radiation exposure are lacking. Our aim was to compare radiation exposure among different interventional procedures performed under fluoroscopic guidance. The RODEO study (NCT: 02972736) is an international observational retrospective multicenter study enrolling all patients undergoing diagnostic or interventional procedures performed by different interventional operators (i.e. radiologists, interventional cardiologists or electrophysiologists) in 6 centers, without exclusion criteria. The primary end-point of the study was the comparison of dose area product (DAP) among interventional cardiology, electrophysiology or interventional radiology procedures. A total of 17,711 procedures were included in the study: 13,522 interventional cardiology, 2352 electrophysiology and 1864 interventional radiology procedures. The highest DAP values were observed for interventional radiology procedures (74Gy∗cm2 [Interquartile range 27-178Gy∗cm2]), followed by interventional cardiology (40Gy∗cm2 [22-78Gy∗cm2]) and electrophysiology procedures (13Gy∗cm2 [4-44Gy∗cm2], p<0.0001). In term of specific procedures, the highest DAP values were observed in structural or valvular cardiac procedures (134Gy∗cm2 [51-260Gy∗cm2]) whereas the lowest DAP values in pacemaker insertion (11Gy∗cm2 [4-28Gy∗cm2]). In this large multicenter study, the highest radiation exposure was observed in procedures performed by interventional radiologists. However, among specific procedures, structural or valvular cardiac procedures were associated with the highest radiation exposure.


Fast but durable megakaryocyte repopulation and platelet production in NOD/SCID mice transplanted with ex-vivo expanded human cord blood CD34+ cells.
We have previously established a stroma-free culture with Flt-3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO) that allows the maintenance and the expansion for several weeks of a cord blood (CB) CD34+ cell population capable of multilineage and long-lasting hematopoietic repopulation in non-obese diabetic/ severe combined immunodeficient (NOD/SCID) mice. In this work the kinetics of megakarocyte (Mk)-engraftment that is often poor and delayed in CB transplantation, and human platelet (HuPlt) generation in NOD/SCID mice of baseline CD34+ cells (b34+), and of CD34+ cells reisolated after a 4-week expansion with FL+SCF+TPO (4w34+) were compared. With b34+ cells Mk-engraftment was first seen at week 3 (CD41+: 0.4%); 4w34+ cells allowed a more rapid Mk-engraftment (at weeks 2 and 3 the CD41+ cells were 0.3% and 0.8%). Circulating HuPlts were first seen at weeks 2 and 1, respectively. Mk-engraftment levels of b34+ and 4w34+ cells 6-8 weeks after transplantation were similar (12 +/- 3.5 versus 15 +/- 5% CD45+; 1.3 +/- 0.5 versus 1.8 +/- 0.5% CD41+ cells). Also serial transplant experiments were performed with expanded and reselected CB cells. In secondary and tertiary recipients the Mk population was detected with bone marrow fluorescence-activated cell sorter analysis; these experiments indicate the effective long-term repopulation of expanded cells. Selected CD34+ cells after a 4-week expansion with FL+SCF+TPO are more efficient in Mk engraftment than the same number of unmanipulated cells.


Explaining social isolation through concept analysis.
Psychiatric nurses need to develop protocols and interventions for clients who are at risk for social isolation or who are socially isolated. Development of protocols and interventions should not be performed unless nurses have a clear understanding of what the term social isolation means. Existing definitions of social isolation have been vague and contradictory. This article presents a concept analysis of social isolation.


Retromaxillary Cell: Radiological Analysis and Clinical Significance.
Retromaxillary cell (RMC), one of the anatomical variations of the posterior ethmoidal cell and is often overlooked during primary functional endoscopic sinus surgery. The incomplete removal of the disease from RMC leads to need for revision surgery. This study was aimed at analyzing Computed tomography scans of patients' paranasal sinuses for the incidence, types and radiological evaluation of Retromaxillary cell. Incidence of RMC was 74% (74/100 sides). The sex distribution was 31 (62%) males and 19 (38%) females. 34 patients (85%) had bilateral RMC and 6 patients (15%) had unilateral RMC. Lateral extension of RMC ranged from 1.03 to 11.3 mm. Out of 74 sides examined, 20 (27.02) were type I, 36 were type II (48.64%) and 18 (24.32%) were type III. The incidence of maxillary sinus disease on RMC sides and non-RMC sides has no significant difference (p < 0.5). RMC is lateral extension of posterior ethmoidal cell beneath the orbit and posterosuperior to maxillary sinus. The depth of the RMC is highly variable. The risk of residual disease in FESS is high in Type III RMC and one should pay attention to presence or absence of RMC and type of RMC prior to the endoscopic sinus surgery. Radiological study of RMC helps in preoperative planning and therefore intraoperative complete clearance of disease in endoscopic sinus surgery.


Cleavage of annexin I in human neutrophils is mediated by a membrane-localized metalloprotease.
A truncated form of annexin I, formed during Ca2+-induced translocation to neutrophil specific granules and secretory vesicles/plasma membranes, is generated through the action of an endogenous membrane protease. The cleavage of annexin I is inhibited by the metalloprotease inhibitor 1,10-phenanthroline as well as by Triton X-100 and dithiothreitol, classifying the protease as a membrane-bound, thiol-dependent metalloprotease. The cleavage site is located close to the N-terminal of annexin I, leaving a truncated form of the molecule, des1-8 annexin I, that contains the Ca2+-binding sites, as well as a number of phosphorylation sites of importance for the function of the protein. When assessing binding capacity to different neutrophil organelles, full-length annexin I bound to azurophil granules, specific granules, and secretory vesicles/plasma membranes, while des1-8 annexin I only bound to specific granules and secretory vesicles/plasma membranes, but not to azurophil granules (C. Sjölin, C. Dahlgren, Biochim. Biophys. Acta 1281 (1996) 227-234). This implies that there are different mechanisms of binding to neutrophil organelles of full-length annexin I and the truncated form, and that cleavage of annexin I might be of regulatory importance for the degranulation process.


Induction of transitional cell carcinoma of the urinary bladder in rats by feeding N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Histological and ultrastructural findings.
After feeding with 0.188% N-[4-(5-nitro-2 furyl)-2-thiazolyl] formamide (FANFT), transitional cell carcinoma of the urinary bladder was induced in all female Wistar rats tested. Histological changes of the urothelium consisted of various degrees of hyperplasia and dysplasia. An infiltrating transitional cell carcinoma first appeared after 8 months. These results are compared with the findings of other authors, and divergencies of the tumour induction rates are discussed with respect to strain, sex and weight of experimental animals as well as concentration and amount of ingested carcinogen. Electron microscopy shows microvillous transformation of the luminal plasma membrane and appearance of a thick fluffy cell coat (glycocalyx). These changes are explained by an altered function of the Golgi complex occurring during malignancy and leading to a loss of the specific discoid vesicles of the urothelial cells.


Predation versus resource limitation in survival of adult burrowing wolf spiders (Araneae: Lycosidae).
The influences of food supply and density on adult survival were examined in the burrowing wolf spider Geolycosa rafaelana (Lycosidae), using manipulations of spider populations on eight 400 sq m experimental plots. A total of 110 adult spiders were captured, weighed, marked, and returned to their burrows during April-May 1983. Treatments of (1) food supplementation, (2) density reduction, (3) food supplementation combined with density reduction, and (4) no manipulation (control) were applied to the eight populations, and adult survival and reproduction were monitored during May-October 1983. Survival rates were higher for nonreproducing adult female populations with reduced density, and lower for nonreproducing females in populations with food supplementation. A pompilid wasp, Paracyphononyx funereus, was documented as a parasitoid of G. rafaelana, producing 50%-65% mortality in adult females during winter, and 4-5% mortality in adult females during summer. The observed survival responses were correlated with variations in predation, while parasitism did not appear to be strongly density-dependent.


Genetic polymorphism of CYP2D6 in Chinese subjects in Malaysia.
Although Malaysian Chinese share an origin with the mainland Chinese, their evolution has been influenced by intermarriages. With a gene such as CYP2D6, which is highly polymorphic, it is expected that the Malaysian Chinese would exhibit a polymorphism profile different from those of the Chinese populations in other geographical locations. To study the genotype distribution of CYP2D6 among the Chinese people in Malaysia. We obtained DNA from 236 Chinese individuals in Malaysia and used PCR-based methods to identify any common CYP2D6 alleles. A total of 236 subjects were enrolled and were successfully genotyped. Malaysian Chinese were relatively heterogeneous in terms of their CYP2D6 genotypes with nine genotypes recorded. CYP2D6*4, *5, *9, *10 and *17 were detected with the most common genotype being *1/*10. No subject had genotypes that predicted poor metabolic activity. However, 40% showed genotypes (e.g. CYP2D6*10/*10, *17, *4 and *9 and *9/*9) that predicted an intermediate metabolizer phenotype. Another subject carried the defective CYP2D6*17 allele and six carried the defective CYP2D6*9 allele. Both these alleles have not been reported in other earlier Chinese studies. This study revealed that, in terms of CYP2D6 polymorphism, Malaysian Chinese were a heterogeneous group of people. Although sharing some similarities with other Orientals, they also seemed to have some notable differences. The alleles CYP2D6*4, *5, *9, *10 and *17 were all detected. CYP2D6*3 was however absent.


Accuracy of Narrow-Band Imaging International Colorectal Endoscopic Classification for Predicting the Histology of Colon Polyps by Experienced Endoscopists and Trainees.
Digital chromoendoscopy has proven to be useful in the histological prediction of premalignant lesions in the colon. The aim of the study was to describe the diagnostic performance of Narrow-Band Imaging International Colorectal Endoscopic Classification in the histological differentiation of colonic lesions, applied by expert endoscopists and trainees. Cross-sectional study that includes high-definition endoscopic images and histopathological reports of 94 patients over 50 years. Images were evaluated and classified as Narrow-Band Imaging International Colorectal Endoscopic 1, 2, or 3 by 2 experts and 2 trainee endoscopists, all of them blinded to histological results. Diagnostic accuracy for each Narrow-Band Imaging International Colorectal Endoscopic category was calculated for trainees and expert endoscopists. Intra-observer agreement was evaluated by means of Cohen's kappa coefficient; meanwhile, inter-observer agreement was calculated by means of Fleiss' kappa. Evaluations performed by expert and trainee endoscopists showed a performance for Narrow-Band Imaging International Colorectal Endoscopic category 1: sensitivity 62%, specificity 85%, area under receiver operator characteristic 0.73; Narrow-Band Imaging International Colorectal Endoscopic category 2: sensitivity 61%, specificity 73%, area under receiver operator characteristic 0.66; and Narrow-Band Imaging International Colorectal Endoscopic category 3: sensitivity 88%, specificity 91%, area under receiver operator characteristic 0.86. The total agreement of the evaluations was 72.5%, with an inter-observer variability of K 0.60 (95% CI 0.52-0.74). When the diagnostic performance for non-dysplastic lesions and dysplastic lesions (Narrow-Band Imaging International Colorectal Endoscopic 1 vs 2 and 3) was compared, we observed an increase in sensitivity for differentiated adenomas (Narrow-Band Imaging International Colorectal Endoscopic 2). Narrow-Band Imaging International Colorectal Endoscopic Classification applied in the histological prediction of static images of colonic lesions has a good diagnostic performance for Narrow-Band Imaging International Colorectal Endoscopic category 3, as well as an acceptable performance for Narrow-Band Imaging International Colorectal Endoscopic category 1, with a moderate agreement among observers.


Fovea-sparing internal limiting membrane peeling versus complete internal limiting membrane peeling for myopic traction maculopathy.
To compare the outcomes of vitrectomy with fovea-sparing internal limiting membrane peeling (FSIP) and complete internal limiting membrane peeling (ILMP) for myopic traction maculopathy (MTM). A retrospective, observational study. In this study, we included 22 eyes of 21 consecutive patients who underwent vitrectomy with FSIP or ILMP for MTM and were monitored for at least 6 months. Eleven eyes were treated with FSIP, and 11, with ILMP. With FSIP, the postoperative best-corrected visual acuity (BCVA) significantly improved from 0.61 (20/82) to 0.34 (20/44; P = .009) logarithm of the minimum angle of resolution (logMAR) units. With ILMP, the postoperative BCVA improved from 0.65 (20/89) to 0.52 (20/66) logMAR units, but was not significant (P = .106). The postoperative final central foveal thickness (CFT) reduced significantly after FSIP (from 557.6 to 128.8 µm, P = .003) and ILMP (from 547.3 to 130.3 µm, P = .008). The postoperative incidence of a macular hole was 0% (0/11 eyes) with FSIP and 27.3% (3/11 eyes) with ILMP. All patients with a macular hole had foveal detachment in association with a thin fovea preoperatively. With ILMP, postoperative BCVA with a macular hole worsened by -3.5 letters; in contrast, postoperative BCVA without a macular hole improved by +10.5 letters. With FSIP, postoperative BCVA without a macular hole significantly improved by +13.5 letters (P = .009). FSIP resulted in significant improvement in MTM and prevented postoperative macular hole development.


Translocation of PKC[theta] in T cells is mediated by a nonconventional, PI3-K- and Vav-dependent pathway, but does not absolutely require phospholipase C.
PKCtheta plays an essential role in activation of mature T cells via stimulation of AP-1 and NF-kappaB, and is known to selectively translocate to the immunological synapse in antigen-stimulated T cells. Recently, we reported that a Vav/Rac pathway which depends on actin cytoskeleton reorganization mediates selective recruitment of PKCtheta to the membrane or cytoskeleton and its catalytic activation by anti-CD3/CD28 costimulation. Because this pathway acted selectively on PKCtheta, we addressed here the question of whether the translocation and activation of PKCtheta in T cells is regulated by a unique pathway distinct from the conventional mechanism for PKC activation, i.e., PLC-mediated production of DAG. Using three independent approaches, i.e., a selective PLC inhibitor, a PLCgamma1-deficient T cell line, or a dominant negative PLCgamma1 mutant, we demonstrate that CD3/CD28-induced membrane recruitment and COOH-terminal phosphorylation of PKCtheta are largely independent of PLC. In contrast, the same inhibitory strategies blocked the membrane translocation of PKCalpha. Membrane or lipid raft recruitment of PKCtheta (but not PKCalpha) was absent in T cells treated with phosphatidylinositol 3-kinase (PI3-K) inhibitors or in Vav-deficient T cells, and was enhanced by constitutively active PI3-K. 3-phosphoinositide-dependent kinase-1 (PDK1) also upregulated the membrane translocation of PKCtheta;, but did not associate with it. These results provide evidence that a nonconventional PI3-K- and Vav-dependent pathway mediates the selective membrane recruitment and, possibly, activation of PKCtheta in T cells.


Bilateral diaphragmatic rupture due to blunt trauma--a rare injury.
A young male patient with bilateral rupture of the diaphragm due to blunt trauma is presented. A separate tear occurred in each hemidiaphragm but recognition and repair of the right side was delayed. After healing of other injuries successful operation was performed 55 days postinjury by a transthoracic approach.


Topographic characteristics of the left atrial medial isthmus.
The purpose of this study was to provide detailed topography of the left atrial medial isthmus (situated between the right inferior pulmonary vein ostium and the medial part of the mitral annulus). Two hundred human hearts (Caucasian, 22.5% females, 48.7 ± 4.9 years old) were investigated. The mean length of the medial isthmus was 42.4 ± 8.6 mm. Additionally, the medial isthmus line was divided by the oval fossa into three sections with equal mean lengths (upper: 14.2 ± 7.2 vs middle: 14.1 ± 6.1 vs lower: 14.9 ± 4.6 mm; P > .05). The left upper section of the atrial wall was thinner than the lower section (2.5 ± 1.1 vs 3.4 ± 1.6 mm; P < .0001). This study noted three separate spatial arrangements of the isthmus line. Type I (54.5%) had an oval fossa located outside the isthmus line; type II (32.5%) had an oval fossa crossed by the isthmus line, and type III (13.0%) had an oval fossa rim located tangentially to the isthmus line. In 68.5% of the examined specimens, the isthmus area had a smooth surface. Conversely, the remaining 31.5% had additional structures within its borders such as diverticula, recesses, and tissue bridges. This study is the first to describe the morphometric and topographical features of the left atrial medial isthmus. Interventions within the medial isthmus line should be performed cautiously, especially when they are transected by the oval fossa (32.5%). Careful navigation of the area is also recommended due to the possibility of existent additional structures. The latter could lead to catheter entrapment during ablation procedures.


The effects of substance P on histamine and 5-hydroxytryptamine release in the rat.
1. Substance P (SP) induces histamine release from isolated rat peritoneal mast cells at concentrations of 0.1-10 muM.2. Inhibitors of glycolysis and oxidative phosphorylation prevent the release of histamine induced by SP.3. Cells heated to 47 degrees C for 20 min release histamine when treated with an agent causing cell lysis but fail to release in response to SP.4. SP does not release histamine by interacting with cell-bound IgE.5. Histamine release by SP is rapid, with more than 90% of the response occurring within 1 min of the addition of the peptide to mast cells at 37 degrees C.6. Substance P, unlike antigen-antibody or compound 48/80, does not show enhanced release of histamine when calcium (0.1-1 mM) is present in the extracellular medium but calcium increases the response to SP when the ion is added after the peptide. Extracellular calcium (0.1-1 mM), magnesium (1-10 mM) and cobalt (0.01-0.1 mM) all inhibit SP-induced histamine release when added before the peptide. Pre-treatment of the cells with EDTA (10 mM) and washing in calcium-free medium inhibits the histamine release induced by SP.7. Histamine release induced by SP was optimum at an extracellular pH of 7.2.8. A number of peptides structurally related to SP were examined for histamine-releasing activity. At the concentrations tested, the N-terminal dipeptides Lys-Pro and Arg-Pro, tuftsin, physalaemin, eledoisin, SP(3-11), SP(4-11) and [p-Glu(6), p-amino Phe(7)]-SP(6-11) were all found to be inactive. The relative activities of the other peptides were: [Formula: see text]9. Rat basophilic leukaemia cells (RBL-2H3) fail to respond to SP at concentrations which activate rat mast cells. Release of 5-hydroxytryptamine by immunological activation of RBL cells is not changed by the presence of SP.10. The mechanism of action of SP on mast cells and the nature of the SP receptor on mast cells is discussed in relation to SP receptors in other cell types.


Child restraint seat use behavior and attitude among Japanese mothers.
The purpose of the study was to assess associations between child restraint seat use and attitudes among Japanese mothers. Mothers whose children were under 6 years of age were recruited through 11 kindergartens located in Kanagawa prefecture, Japan. Questions were developed based on the Health Belief Model and the Theory of Reasoned Action. Past use and future intentions to use, perceived risk of injury, knowledge of safety, attitudes toward use, subjective norms, and safety values related to safety seats were asked. A total of 552 complete questionnaires was obtained. Of 500 car owning households, 54.2% used child restraint seats inconsistently on short drives, and 36.4% did so on long drives. Three variables were associated with inconsistent use on short drives: frequent child resistance to sitting in a restraint seat; mothers' feeling hassled by child restraint seat use; and, mothers' agreement with the lack of need to use a restraint seat when another adult is in a car. Two variables were associated with inconsistent use on long drives: lower subjective norm of husband and frequent child resistance. In-car environmental modification and parent education need to be considered to increase child restraint seat use among Japanese households.


Cross-modal self-recognition: the role of visual, auditory, and olfactory primes.
Three priming experiments were conducted to determine how information about the self from different sensory modalities/cognitive domains affects self-face recognition. Being exposed to your body odor, seeing your name, and hearing your name all facilitated self-face recognition in a reaction time task. No similar cross-modal facilitation was found among stimuli from familiar or novel individuals. The finding of a left-hand advantage for self-face recognition was replicated when no primes were presented. These data, along with other recent results suggest the brain processes/represents information about the self in highly integrated ways.


Cripto signaling in differentiating embryonic stem cells.
Embryonic stem (ES) cells have been suggested as candidate therapeutic tools for regenerative medicine approaches. In this scenario, great efforts are made to define protocols to preferentially direct ES cells toward a defined cell type. To this end, it becomes crucial to characterize the molecular mechanisms as well as the signaling pathways implicated in ES cell differentiation. Findings highlight a key role of cripto, the founding member of a new class of extracellular factors, called EGF-CFC. Indeed, Cripto signaling is strictly required in an early acting window to negatively regulate neural differentiation and to permit differentiation of ES cells to cardiac fate. The protocols defined in this chapter allow preferential direction of ES cell differentiation as embryoid bodies toward either cardiomyocytes or neurons. Although referred to as modulation of Cripto signaling, these methods build the basis for the use of other classes of secreted molecules to control ES cell differentiation.


Effects of desipramine on regional serotonin synthesis in the rat brain: acute and chronic autoradiographic studies.
Various studies have implicated the involvement of noradrenaline (NA) and/or serotonin (5-hydroxytryptamine (5-HT)) in the pathogenesis and treatment of depression. The aim of the present study was to investigate the effects of acute and 7 days of administration of desipramine, a NA re-uptake inhibitor, on the rate of 5-HT synthesis in the rat brain. The study was done by an autoradiographic method using alpha-[14C]-methyl-L-tryptophan as a tracer. The acute (10mg/kg, i.p., 2h before i.v. infusion of the tracer) or 7 days of desipramine (10mg/kg per day, i.p.) did not affect plasma tryptophan (Trp) concentrations, as compared to control (saline treated) rats. Acute treatment with desipramine decreased the rate of 5-HT synthesis in the brain regions that contain 5-HT cell bodies between 19 and 28%, and increased the rate of 5-HT synthesis in the majority of areas containing 5-HT terminals between 21 and 65%. In contrast to the acute treatment, a 7-day administration increased 5-HT synthesis rates in the dorsal raphe (24%), but decreased it in raphe magnus (35%), superior olive (45%), caudate (31%), superior (38%) and inferior (53%) colliculus, and in the auditory cortex (35%). This suggests that the effect of desipramine on 5-HT synthesis rate is time-dependent and differs in the cell bodies and structures containing 5-HT nerve terminals.


Immunoregulatory pathways in adult responder mice. I. Induction of GAT-specific tolerance and suppressor T cells for cellular and humoral responses.
This report describes the alteration of helper-suppressor balances in an immune response (Ir) gene-controlled system by varying the route and form of antigen injection. Adult responder BALB/c mice develop Lyt 1+2-, T cells for delayed-type hypersensitivity (DTH), and T-cell proliferative (Tprlf) responses to subcutaneous injection of either poly(Glu60Ala30Tyr10) (GAT)-coupled syngeneic spleen cells (GAT-SP) or GAT emulsified in complete Freund's adjuvant. In contrast, intravenous injection of adult responders with GAT-SP results in specific unresponsiveness for DTH, Tprlf, interleukin-2, and plaque-forming cell (PFC) responses. This tolerance is mediated by both suppressor T cells (Ts) and a functional clonal inhibition. Lyt 1-2+ Ts suppress the induction (afferent limb) of GAT-specific DTH and PFC but not Tprlf responses. The reduced T-cell proliferation observed in GAT-tolerant mice is due to a non-transferable mechanism(s), possibly functional clonal inhibition. Our data are compatible with a multi-step pathway involving both proliferating and non-proliferating helper T (Th) cells. In addition, the fine specificity of tolerance induction for DTH and Tprlf responses was examined by using the related antigens poly(Glu60Ala40) (GA) and poly(Glu50Tyr50) (GT). Tolerance is exquisitely specific, as GA tolerizes responses to GA and GAT, whereas GT tolerizes GAT but not GA responses. Thus, both the route and form of antigen administration are important to the induction and regulation of immune response in Ir gene-controlled systems. Possible mechanisms governing the Th/Ts balance and the induction of GAT-specific tolerance and suppression for cellular and humoral responses in adult responders are discussed.


Neurostimulation in the treatment of refractory and super-refractory status epilepticus.
Status epilepticus (SE) is a life-threatening condition with a mortality of up to 60% in the advanced and comatose forms of SE. In one out of five adults, first and second line fails to control epileptic activity, leading to refractory status epilepticus (RSE) and in around 3% to super-refractory status epilepticus (SRSE), where SE continues despite anesthetic treatment for 24 h or more. In this rare but devastating condition, innovative and safe treatments are needed. In a recent review on the use of vagal nerve stimulation in RSE and SRSE, a 74% response rate for abrogation of SE was reported. Here, we review the currently available evidence supporting the use of neurostimulation, including vagal nerve stimulation, direct cortical stimulation, transcranial magnetic stimulation, electroconvulsive therapy, and deep brain stimulation in RSE and SRSE. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".


Pulmonary vasodilator action of tolazoline.
The pulmonary vasodilator action of tolazoline in newborn lambs was shown to be mediated via histamine receptors. Maximal changes in pulmonary vascular resistance, deltaPVR, were calculated as percents of the base line value, %deltaPVR. The mean %deltaPVR after tolazoline, 1 mg/kg, was -25 +/- 4% for eight lambs. Four lambs then received the histamine H1 receptor antagonist, diphenhydramine, and the mean %deltaPVR due to tolazoline was -12 +/- 4%. Four lambs received the H2 receptor antagonist, metiamide, and the mean %delta PVR due to tolazoline was -18 +/- 5%. After both H1 and H2 antagonists, the mean %deltaPVR due to tolazoline was +6 +/- 8%. Therefore, both histamine H1 and H2 receptors were involved in the vasodilator response to tolazoline.


Focal treatment for refractory epilepsy: hope for the future?
Despite advances in anti-epileptic drug therapy and epilepsy surgery in recent years, intractable epilepsy remains a large clinical problem. Surgical resection, which can have an excellent outcome, is appropriate for only a minority of patients in whom an identifiable focus in non-eloquent brain can be identified. Systemic drug delivery is inevitably limited by the potential for unwanted side effects, due to actions both outside the CNS and in non-epileptic brain regions. Thus for a substantial number of patients novel treatment approaches are urgently needed. Both focal drug delivery and neuronal stem cell grafting have been evaluated in a variety of experimental epilepsy models in recent years, targeting either the seizure focus or key propagation pathways. The literature in this field is critically reviewed and considered in a clinical context. Studies in both areas are hampered by the limitations of available animal models, and by uncertainties in discerning which changes in the epileptic brain directly promote seizures, and which are compensatory. However, in many cases promising, though short-term, results have been obtained. Before such studies could be considered in humans further investigations that include long-term seizure and behavioural outcomes, in clinically relevant experimental models, are required. However, the current literature does provide proof in principle for a focal treatment approach, which may offer hope for many currently intractable patients for whom drug developments and surgical advances have proved disappointing.


Subanalysis of the location of white matter hyperintensities and their association with suicidality in children and youth.
Our previous research with psychiatrically hospitalized children and youth indicates that white matter hyperintensities (WMH) on T2-weighted MRI images are associated with a history of suicide attempt. This subanalysis of the specific locations of the WMH suggests that youth with deep WMH in the parietal lobe but not in the frontal lobe have a significantly higher prevalence of reported past suicide attempt.


Prevalence and correlates of bullying and victimization among school students in rural Egypt.
Knowledge on risk factors of bullying and victimization among school students is crucial for the implementation of preventive measures. This study was conducted to determine the prevalence and correlates of school bullying and victimization and their association with behavioral disorders among preparatory and secondary school students in rural Egypt. Cross-sectional METHODS: A total of 476 students from two mixed public schools in rural Egypt (one preparatory and one secondary) were enrolled. A pretested self-administered questionnaire was used to collect sociodemographic characteristics and correlates of bullying and victimization including personal and social, family, school, and community factors. Frequency of bullying and victimization was measured using the short version aggression and victimization scale. The Strengths and Difficulties Questionnaire (SDQ) was used for screening behavioral problems. Prevalence of bullying behavior was high (77.8%) among the studied group, of those 9.5% were unique bullies, 10.5% were unique victims, and 57.8% were bully-victims. On multivariate logistic regression analysis, failure in previous scholastic years (OR = 11.1, 95% CI 1.1-101.4, P = 0.033), witnessing family members using weapons (OR = 6.1, 95% CI 1.1-34.0, P = 0.038), male gender (OR = 2.3, 95% CI 1.1-5.0, P = 0.027), and mothers' education (university or higher) (OR = 0.1, 95% CI 0.02-0.7, P = 0.017) remained the significant predictors for bullying. However, only having a drug addict friend (OR 2.5, 95% CI 1.1-5.4, P = 0.025) was the significant predictor for victimization. The independent predictors for being bully-victims in order of importance were exposure to physical violence in the street (OR = 5.1, 95% CI 1.2-22.7, P = 0.031), male gender (OR = 3.2, 95% CI 1.8-5.6, P < 0.001), witnessing fights (OR = 3.1, 95% CI 1.7-5.7, P < 0.001) and insulting words (OR = 2.5, 95% CI 1.3-4.7, P = 0.007) among family members, exposure to insulting words in the street (OR = 2.1, 95% CI 1.2-3.7, P = 0.010), watching violent movies (OR = 2.0, 95% CI 1.2-3.4, P = 0.008), and younger age (OR = 0.7, 95% CI 0.6-0.8, P < 0.001). The self-reported SDQ revealed that the conduct problems scale scored significantly higher among bully-victims (2.8 ± 1.7 vs. 2.3 ± 1.6, P = 0.004). Prevalence of bullying behavior was high among rural adolescent school students. Establishment of a bullying prevention committee at school including all school personnel for addressing different factors associated with bullying behavior is recommended. Further follow-up and psychiatric assessment of students for predicting those prone to behavioral abnormalities are also recommended.


Correction to: Suitable Use of Injectable Agents to Overcome Hypoglycemia Risk, Barriers, and Clinical Inertia in Community-Dwelling Older Adults with Type 2 Diabetes Mellitus.
The article Suitable Use of Injectable Agents to Overcome Hypoglycemia Risk, Barriers, and Clinical Inertia in Community-Dwelling Older Adults with Type 2 Diabetes Mellitus, written by Willy M. Valencia, Hermes J. Florez and Ana M. Palacio was originally published Online First without open access.


Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal dopamine turnover in de novo Parkinson's disease.
The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD). This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PD patients. Patients carrying the MAOBCC/(C)/CT genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOBTT/(T) genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes. The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Diagnosis of spacer-associated infection using quantitative cultures from sonicated antibiotics-loaded spacers: implications for the clinical outcome.
Recent studies showed that a positive microbiological result from sonication of the PMMA spacer was associated with poor outcome of patients, but no quantitative analysis has yet been performed. For this purpose, a prospective analysis of 50 spacers (46 patients) was performed. All spacers were processed according to a previously described protocol, including centrifugation and quantitative culture. Clinical data and outcome were also analysed. A statistical relationship between the results of the cultures and the outcome of the patient was assessed. Sixteen patients were diagnosed with spacer-associated infection. Thirteen out of 50 spacers gave a positive culture. Nine of 13 presented with growth of an organism not isolated in the first-stage cultures, and in 7 out of 13 the organisms count was high (>10,000 CFU/ml). We have detected a significant statistical relationship between poor outcome and positive cultures, high colony counts, isolation of different organisms, positive periprosthetic cultures and spacer-associated infection. The detection in a sonicated, antibiotic-loaded PMMA spacer of organisms other than those isolated in the first surgical samples or high colony counts of any organisms is diagnostic with regard to spacer-associated infection.


Clinical insights into the origins of thrombosis in myeloproliferative neoplasms.
Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are hematopoietic stem cell disorders that are defined by activating mutations in signal transduction pathways and are characterized clinically by the overproduction of platelets, red blood cells, and neutrophils, significant burden of disease-specific symptoms, and high rates of vascular events. The focus of this review is to critically reevaluate the clinical burden of thrombosis in MPNs, to review the clinical associations among clonal hematopoiesis, JAK2V617F burden, inflammation, and thrombosis, and to provide insights into novel primary and secondary thrombosis-prevention strategies.


A patient with possible TRALI who developed pulmonary hypertensive crisis and acute pulmonary edema during cardiac surgery.
There are very few case reports of transfusion-related acute lung injury (TRALI) under close hemodynamic monitoring. We encountered a case of possible TRALI during on-pump coronary artery bypass grafting (CABG). A 66-year-old man who had undergone on-pump CABG was administered fresh frozen plasma (FFP). One hour after FFP transfusion, pulmonary hypertensive crisis and subsequent hypoxic decompensation occurred. A second cardiopulmonary bypass (CPB) was needed for circulatory and respiratory deterioration. Extracorporeal life support (ECLS), intraaortic balloon pumping (IABP), and nitric oxide therapy were required after the surgery. Despite the severity of the initial state, his recovery was comparatively smooth. ECLS and IABP were removed on postoperative day (POD)1; the patient was extubated and discharged from the ICU on POD7 and POD12, respectively. The diagnosis of TRALI was confirmed by human leukocyte antigen antibody detection in the administered FFP. In addition, lymphocytic immunofluorescence test showed that a cross-match of the plasma from the pooled FFP against the recipient leukocytes was positive. The clinical course of the pulmonary artery hypertension was followed by a decrease in dynamic lung compliance. The mechanism of this phenomenon is unclear. However, it might suggest the possibility of vasoconstriction or obstruction of the peripheral pulmonary artery preceding lung damage, as in the case in animal models reported previously.


Mandibular pseudocarcinomatous hyperplasia.
Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site. In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy. PH shows an inverted pattern when compared with the centro-medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.


Left Volume Atrial Index and P-wave Dispersion as Predictors of Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft: A Retrospective Cohort Study.
Preoperative left atrial remodeling as Postoperative atrial fibrillation (POAF) predisposing factors could be measured by left atrial volume index (LAVI) and P-wave dispersion. This study aimed to assess P-wave dispersion and LAVI as preoperative predictors of POAF among patients who underwent Coronary Artery Bypass Graft (CABG). An analytical retrospective cohort study was performed on patients who underwent CABG. The P-wave dispersion and POAF were evaluated based on documented ECG results. LAVI size was collected from echocardiographic reports. Hazard ratios of P-wave dispersion and LAVI for POAF were analyzed using Cox proportional hazard model. A total of 42 subjects (57 ± 1 years) were included in this study. POAF occurred in 28.6% of patients at a median of 2 days after CABG. P-wave dispersion was significantly longer in patients in whom AF was developed (53.03 ± 3.82 ms vs 44.01 ± 1.98ms, p:0.028), while LAVI difference was not significant. The Cox proportional hazard model showed a significant association between P-wave dispersion and risk of POAF (HR 1.05, CI95%, 1.001-1.103; P = 0.048). There was no association between LAVI and risk of POAF (HR 1.003, CI 95%, 0.965-1.044; P = 0.864). P-wave dispersion is a predictor of POAF in patients who underwent CABG. Risk stratification using P-wave dispersion enables clinicians to identify high-risk patients before CABG surgery.


Structure-based design of glycyrrhetinic acid derivatives as potent anti-sepsis agents targeting high-mobility group box-1.
Novel Glycyrrhetinic Acid (GA) derivatives with fused heterocycles on A ring were structure-based designed and synthesized. Their potential anti-inflammatory effects were investigated by a classical LPS stimulated macrophage model. Surface plasmon resonance (SPR) was used to verify the binding of GA analogues with HMGB1. A preliminary structure-activity relationship was summarized and an analogue GA-60 with ortho-methoxybenzyl pyrozole showed stronger anti-inflammatory effect and higher affinity for HMGB1 with a Kd value of 12.5 μM. In addition, this compound exhibited excellent inhibitory functions on NO (96%), TNF-α (94%), and IL-6 (100%), by interfering with phosphorylation of p38, ERK, JNK MAPKs, as well as that of NF-κB p65 and IKKα/β. Moreover, GA-60 extended the survival of either the classic CLP-induced or LPS-induced sepsis mouse models. Molecular modeling predictions further supported these findings, clearly indicating that inhibiting HMGB1 release, using fused heterocyclic GA derivatives, is a promising strategy for treatment of sepsis.


Extraction of formic and acetic acids from aqueous solution by dynamic headspace-needle trap extraction temperature and pH optimization.
A combined method of dynamic headspace-needle trap sample preparation and gas chromatography for the determination of formic and acetic acids in aqueous solution was developed in this study. A needle extraction device coupled with a gas aspirating pump was intended to perform sampling and preconcentration of target compounds from aqueous sample before gas chromatographic analysis. The needle trap extraction (NTE) technique allows for the successful sampling of short chain fatty acids under dynamic conditions while keeping the headspace (HS) volume constant. Two important parameters, including extraction temperature and effect of acidification, have been optimized and evaluated using the needle trap device. The method detection limits for the compounds estimated were 87.2microg/L for acetic acid and 234.8microg/L for formic acid in spite of the low flame ionization detection response for formic acid and its low Henry's law constant in aqueous solution. Precision was determined based on the two real samples and ranged between 4.7 and 10.7%. The validated headspace-needle trap extraction method was also successfully applied to several environmental samples.


The Relationship Between the Pneumatization Patterns of the Frontal Sinus, Crista Galli and Nasal Septum: A Tomography Study.
To provide detailed information about anterior skull base anatomy. In terms of gender and laterality, the drainage pathways and anatomical variations of the frontal sinus, crista galli and nasal septum in 402 patients were evaluated via computed tomography scans. The pneumatization patterns of the frontal sinus were as follows: absent, 3.7%; unilateral, 8%; bilateral, 75.1% and triple, 13.2%. The pneumatized crista galli was identified in 120 (29.8%) patients, and its drainage pathway was observed in 54.1% of patients. The sinus septi nasi was identified in 92 (22.8%) and its drainage pathway was observed in 16.3%. The prevalences of the position types of crista galli regarding the cribriform plate were as follows; type I, 18.3%; type II, 64.9%; type III, 16.8%. Despite meticulous knowledge of anatomy, preoperative radiologic evaluation creates the base for successful treatment of anterior skull base pathologies with safer and effective surgery.


2-[(5'-Chloro-1,1':3',1''-terphenyl-4'-yl)imino]-acenaphthylen-1(2H)-one.
The title compound, C30H18ClNO, is a product of the condensation reaction of acenaphthyl-ene-1,2-dione and 5'-chloro-1,1':3',1''-terphenyl-4'-amine. The acenaphthyl-ene fragment and two terminal phenyl rings are rotated relative to the central benzene ring by 72.2 (3), 43.2 (3) and 41.2 (3)°, respectively. This mol-ecular conformation is supported by weak C-H⋯π inter-actions. In the crystal, mol-ecules form centrosymmetric dimers by the stacking inter-actions between two neighboring acenaphthyl-ene fragments, with an inter-planar distance of 3.365 (3) Å. The dimers are bound to each other by weak C-H⋯N and C-H⋯π inter-actions, forming a three-dimensional framework.


Clinical significance of routine urinary bacterial culture after transurethral surgery: results of a prospective multicenter study.
The objective of this study was to evaluate the prevalence and the clinical outcomes of asymptomatic postoperative bacteriuria after transurethral operations, along with the need for postoperative urinalysis. A prospective study of 456 patients who underwent transurethral resection of the prostate (TURP) or transurethral resection of the bladder (TURB) at 2 urological centers in France, between January 2008 and March 2009. All patients had urine cultures preoperatively, on the day of catheter removal, and at 1 month postoperatively. Only patients with symptoms suggesting a urinary tract infection were treated. Univariate logistic regression and multiple logistic regression were used to estimate the odds ratios and P values. TURP was performed in 217 patients, and TURB was performed in 239 patients. A total of 35 patients (7.6%) had positive postoperative urine cultures. Only 9 patients (1.9%) were treated. Patient age and postoperative catheterization duration were identified as risk factors for postoperative bacteriuria (OR = 1; 95% CI = 1.0-1.1; P = .03 and OR = 3.6; 95% CI = 2.3-5.7; P = .0001, respectively), and preoperative bacteriuria was not risk factor for postoperative bacteriuria (OR = 0.9; 95% CI = 0.3-1.4; P = .8). A total of 45 patients had a positive urinalysis at 1 month, and 29 presented an infectious complication during follow-up. A positive postoperative urinalysis was not a risk factor either for a positive urinalysis at 1 month or for an infectious complication during follow-up (OR = 3.2; 95% CI = 0.4-22.4, P = .2 and OR = 1.4; 95% CI = 0.4-4.9, P = .5, respectively). Based on our study findings, postoperative bacteriuria is not a risk factor for infectious postoperative complications. Therefore, routine postoperative urinalysis should be advocated only in symptomatic patients.


Adaptation pathways of global wheat production: Importance of strategic adaptation to climate change.
Agricultural adaptation is necessary to reduce the negative impacts of climate change on crop yields and to maintain food production. However, few studies have assessed the course of adaptation along with the progress of climate change in each of the current major food producing countries. Adaptation pathways, which describe the temporal sequences of adaptations, are helpful for illustrating the timing and intensity of the adaptation required. Here we present adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. We considered two adaptation options: (i) expanding irrigation infrastructure; and (ii) switching crop varieties and developing new heat-tolerant varieties. We find that the adaptation pathways differ markedly among the countries. The adaptation pathways are sensitive to both the climate model uncertainty and natural variability of the climate system, and the degree of sensitivity differs among countries. Finally, the negative impacts of climate change could be moderated by implementing adaptations steadily according to forecasts of the necessary future adaptations, as compared to missing the appropriate timing to implement adaptations.


Application of sodium fluorescein for spinal cord lesions: intraoperative localization for tissue biopsy and surgical resection.
Sodium fluorescein (NaFL) has been used to aid in the resection of primary and secondary lesions within the brain. Comparatively, there is limited research on clinical applications for lesions within the spinal cord. Fluorescein-guided microsurgery may increase the ability to localize and safely surgically treat spinal lesions. Twelve patients with spinal cord lesions received fluorescein sodium 10% (Alcon Laboratories INC, Fort Worth, TX, USA) at 3 mg/kg prior to surgical resection. Intraoperative visualization of fluorescence was performed using a Zeiss Pentero (Carl Zeiss AG, Oberkochen, Germany) microscope equipped with a Yellow560 filter or a Leica OH6 (Leica Microsystems, Wetzlar, Germany) equipped with a FL560 filter. Administration of NaFL resulted in lesional fluorescent contrast extravasation and facilitated surgical resection and localization in all twelve patients. In patients with a goal of complete resection, NaFL aided in complete resection of the spinal lesions in seven patients. In surgical resection patients, pathology was consistent with WHO grade I myxopapillary ependymoma in one patient, WHO grade II ependymoma in five patients, and nerve sheath tumor in one patient. In the other five patients, NaFL allowed for intraoperative tissue identification and successful tissue biopsy. In patients undergoing biopsy, tissue samples were positive for an intramedullary abscess, EBV-driven lymphoproliferative disease, and primary glial neoplasms. Fluorescein is a helpful microsurgical tool in guiding surgical resection and in the localization of intramedullary spinal lesions. Further research is necessary to explore fluorescein sodium applications in the resection of spinal cord lesions.


Metamodeling and the Critic-based approach to multi-level optimization.
Large-scale networks with hundreds of thousands of variables and constraints are becoming more and more common in logistics, communications, and distribution domains. Traditionally, the utility functions defined on such networks are optimized using some variation of Linear Programming, such as Mixed Integer Programming (MIP). Despite enormous progress both in hardware (multiprocessor systems and specialized processors) and software (Gurobi) we are reaching the limits of what these tools can handle in real time. Modern logistic problems, for example, call for expanding the problem both vertically (from one day up to several days) and horizontally (combining separate solution stages into an integrated model). The complexity of such integrated models calls for alternative methods of solution, such as Approximate Dynamic Programming (ADP), which provide a further increase in the performance necessary for the daily operation. In this paper, we present the theoretical basis and related experiments for solving the multistage decision problems based on the results obtained for shorter periods, as building blocks for the models and the solution, via Critic-Model-Action cycles, where various types of neural networks are combined with traditional MIP models in a unified optimization system. In this system architecture, fast and simple feed-forward networks are trained to reasonably initialize more complicated recurrent networks, which serve as approximators of the value function (Critic). The combination of interrelated neural networks and optimization modules allows for multiple queries for the same system, providing flexibility and optimizing performance for large-scale real-life problems. A MATLAB implementation of our solution procedure for a realistic set of data and constraints shows promising results, compared to the iterative MIP approach.


[Prognostic significance of PIN and Atypical Small Acinar Proliferation on transrectal ultrasound-guided prostate biopsy].
To review the incidence of PIN and Atypical Small Acinar Proliferation (ASAP) on first biopsy, the risk to find cancer on following biopsies and what is the importance given to this findings, analizing how frequently and how long after the initial finding this patients are rebiopsied. We selected 6000 patients who underwent TRUS biopsy between 1994 and 2002. Patients with prior cancer diagnosis were not included. 861 of them underwent more than one biopsy, adding up to a total of 7127 biopsies. A descriptive study has been done including percentages and percentiles for qualitative variables, mean and median for continuous variables. Incidence of cancer on the first biopsy was 39,1%. PIN and ASAP are stable or slightly increase from 2 and 2,1% respectively on the first biopsy to more than 6% on the fourth and fifth ones. Mean time between biopsies when ASAP or PIN are the initial findings is 180 +/- 221,6 and 264 +/- 213,8 days respectively. Just 42 and 40% of patients with prior PIN or ASAP diagnose are rebiopsied. On subsequent biopsies 45 and 40% of cancers were respectively found. Presence of PIN or ASAP implies a higher cancer risk on subsequent biopsies; in spite of that, less than half of them are biopsied again. Performing two more biopsies or an amplified biopsy can find most of the tumors associated.


Preimplantation genetic testing for aneuploidy is not related to adverse obstetric and neonatal outcomes in singleton pregnancies.
What is the potential impact of preimplantation genetic testing for aneuploidy (PGT-A) on obstetric and neonatal outcomes? PGT-A is not associated with increased rates of adverse maternal and neonatal outcomes in singleton pregnancies following IVF/ICSI cycles. PGT-A pregnancies may be associated with increased risks of lower birthweight, preterm delivery, and hypertensive disorders compared with natural pregnancies. In a recent meta-analysis, the overall obstetric and neonatal outcomes of PGT-A pregnancies were favorable compared with those of IVF/ICSI pregnancies, although PGT-A pregnancies were associated with a higher risk of hypertensive disorders. A multicenter retrospective cohort study was performed in University-affiliated infertility centers. Single live births following IVF/ICSI between October 2016 and January 2021 were included in the study. A total of 7146 live births after single embryo transfers with (n = 3296) or without (n = 3850) PGT-A were included. The primary outcome was pre-eclampsia and secondary outcomes included gestational diabetes, low birthweight and very low birthweight, cesarean section delivery, emergency cesarean section, as well as preterm birth, birthweight, congenital abnormalities, neonatal sex, Apgar score at 5 min, and neonatal intensive care unit admission. In a subgroup analysis, were included only blastocysts screened with next-generation sequencing (NGS). Univariate analysis showed that pre-eclampsia, cesarean section incidence, and low Apgar score were higher in women undergoing PGT-A. However, after performing multivariate logistic and linear regression models accounting for many possible confounders, pregnancies that had been conceived after embryo biopsy showed no increase in adverse obstetric and neonatal outcomes. The subgroup analysis including patients with blastocysts screened by NGS showed a decreased risk of preterm birth in the group undergoing PGT-A. Caution should be used when interpreting the data because of its limitations, mainly related to its retrospective design. Although this is a large multicenter study, data acquisition included self-reporting questionnaires, and the deliveries occurred in different institutions with distinct protocols. The current study does not show any major adverse clinical outcomes after PGT-A. Efforts should be made to promote good quality research on embryo biopsy in terms of neonatal and obstetric outcomes, as well as its long-term consequences. No specific funding was obtained for this study. The authors declare no conflicts of interest. N/A.


An Outbreak Presents An Opportunity to Learn About A Rare Phenotype: Autoimmune Hepatitis After Acute Hepatitis A.
There are rare instances where patients with acute hepatitis A virus infection subsequently developed autoimmune hepatitis. The diagnosis of autoimmune hepatitis in this setting is challenging. Furthermore, information on treatment with steroids or other immune suppressants, duration of therapy and possibility of treatment discontinuation is currently unclear. Here we report a case series of four patients with histology proven autoimmune hepatitis after hepatitis A virus infection. We describe the presenting features, diagnosis, treatment and long-term outcomes of these cases. This case series provides a insight into the clinical presentation and treatment of autoimmune hepatitis after hepatitis A infection with interesting take home points for clinical hepatologists.


KM-408, a novel phenoxyalkyl derivative as a potential anticonvulsant and analgesic compound for the treatment of neuropathic pain.
Epilepsy frequently coexists with neuropathic pain. Our approach is based on the search for active compounds with multitarget profiles beneficial in terms of potential side effects and on the implementation of screening for potential multidirectional central activity. Compounds were synthesized by means of chemical synthesis. After antiseizure and neurotoxicity screening in vivo, KM-408 and its enantiomers were chosen for analgesic activity evaluations. Further safety studies included acute toxicity in mice, the effect on normal electrocardiogram and on blood pressure in rats, whole body plethysmography in rats, and in vitro and biochemical assays. Pharmacokinetics has been studied in rats after iv and po administration. Metabolism has been studied in vivo in rat serum and urine. Radioligand binding studies were performed as part of the mechanism of action investigation. Selected results for KM-408: Ki sigma = 7.2*10-8; Ki 5-HT1A = 8.0*10-7; ED50 MES (mice, ip) = 13.3 mg/kg; formalin test (I phase, mice, ip)-active at 30 mg/kg; SNL (rats, ip)-active at 6 mg/kg; STZ-induced pain (mice, ip)-active at 1 mg/kg (von Frey) and 10 mg/kg (hot plate); hot plate test (mice, ip)-active at 30 mg/kg; ED50 capsaicin test (mice, ip) = 18.99 mg/kg; tail immersion test (mice)-active at 0.5%; corneal anesthesia (guinea pigs)-active at 0.125%; infiltration anesthesia (guinea pigs)-active at 0.125%. Within the presented study a novel compound, R,S-2-((2-(2-chloro-6-methylphenoxy)ethyl)amino)butan-1-ol hydrochloride (KM-408) with dual antiseizure and analgesic activity has been developed for potential use in neuropathic pain treatment.


Easily biodegradable substrates are crucial for enhancing antibiotic risk reduction: Low-carbon discharging policies need to be more specified.
Governments have formulated stricter wastewater treatment plant (WWTP) discharge standards to address water pollution; however, with the cost of aggravating the refractory of the discharges. These policies are not in line with the classic co-metabolism theory; thus, we evaluated the effects of an easily biodegradable substrate on the removal efficiency of antibiotics and antibiotic resistance genes (ARGs) in the receiving water. In this study, reactor with 8 d of hydraulic retention time (HRT) was constructed to simulate a receiving river, and several antibiotics (0.30 mg/L each) were continuously discharged to the reactor (tetracycline, ciprofloxacin, amoxicillin, chloramphenicol, and sulfamethoxazole). Sodium acetate (NaAc) was used as a representative easily biodegradable substrate, and treatment protocols with and without a co-substrate were compared. The attenuation of the antibiotics in the simulated river and the production and dissemination of ARGs were analyzed. The results showed that 50 mg/L NaAc activated non-specific enzymes (a log2-fold change of 3.1-8.8 compared with 0 mg/L NaAc). The removal rate of the antibiotics was increased by 4-32%, and the toxicity of the downstream water was reduced by 35%. The upregulation of antioxidant enzymes caused the intracellular reactive oxygen species (ROSs) decreased by up to 47%, inhibiting horizontal gene transfer and reducing mobile genetic element-mediated ARGs (mARGs) by 18-56%. Furthermore, NaAc also increased the alpha diversity of the microbial community by 5-15% (Shannon-Wiener Index) and reduced the abundance of human bacterial pathogens by 22-36%. In summary, easily biodegradable substrates in the receiving water are crucial for reducing antibiotic risk.


The roles of microRNAs in the progression of castration-resistant prostate cancer.
Prostate cancer (PCa) is one of the leading causes of cancer-related death in men. PCa is androgen-dependent, and androgen-deprivation therapy is effective for first-line hormonal treatment, but the androgen-independent phenotype of PCa eventually develops, which is difficult to treat and has no effective cure. Recently, microRNAs have been discovered to have important roles in the initiation and progression of PCa, suggesting their use in diagnosis, predicting prognosis and development of treatment for castration-resistant PCa (CRPC). Understanding the networks of microRNAs and their target genes is necessary to ascertain their roles and importance in the development and progression of PCa. This review summarizes the current knowledge about microRNAs regulating PCa progression and elucidates the mechanism of progression to CRPC.


Numerical analysis of liquid flow measurement using multipath ultrasonic phased array flowmeter.
In this paper, multipath ultrasonic flowmeter using phased array transducer is introduced to measure the flowrate. In the proposed flowmeter, the path velocities are achieved by dynamic beam steering via phased array sensor then numerical integration is used to calculate the flowrate. Turbulent flow profile through a straight pipe, flow field downstream of single bend, and double bend are studied in this paper. For each case, the influence of the number of paths, beam angle, and installation angle on the performance of the proposed flowmeter is discussed. Because of symmetric velocity profile for turbulent flow through the straight pipe, relative errors are not dependent on the installation angle and its minimum value is obtained 0.03 % under [±56.6°, 0] path arrangement. Relative errors after single and double bend depend on the installation angle due to the asymmetric flow field. In 3-path configuration, for velocity profile after single bend and double bend, the minimum error range is 1.35 % and 2.38 % under [±55o, 0] and [±45o, 0] path arrangement, respectively. In 5-path arrangement, after single bend and double bend, the minimum error range is achieved by 0.14 % and 1.03 % under [±70o, ±35o, 0] and [±65o, ±25o, 0], respectively. The validity of multipath ultrasonic phased array flowmeter after the single bend in Re = 2 × 105 to 106 has been examined with the computational fluid dynamics simulation. The maximum absolute relative error under [±55o,0] and [±70o,±35o,0] was achieved at about 3 % and 1.8 % respectively.


5-Hydroxytryptamine (5-HT) contracts the guinea-pig isolated iliac artery via 5-HT1-like and 5-HT2 receptors.
The characterization of 5-hydroxytryptamine (5-HT) receptors mediating contractions of the guinea-pig isolated iliac artery was studied when the basal tone was slightly increased by prostaglandin F2 alpha (PGF2 alpha). In the presence of ketanserin (1 mumol/l), 5-HT and several 5-HT receptor agonists induced contractile responses with the rank order of agonist potency: 5-HT = 5-carboxyamidotryptamine (5-CT) = lysergol > ergometrine = methylergometrine > RU 24969 approximately 5-methoxytryptamine (5-MeOT) > methysergide > sumatriptan > tryptamine. Concentration-effect curves to the ergot alkaloids, lysergol, ergometrine, methylergometrine and methylsergide, were biphasic. In the presence of ketanserin (1 mumol/l), contractile responses to 5-HT, 5-CT, RU 24969, 5-MeOT, sumatriptan and tryptamine were antagonized by methiothepin (30 nmol/l) and flesinoxan (3 mumol/l) with approximate pKB values of 8.5-9.0 and 6.0-6.3, respectively. The first phase of contraction produced by the ergot alkaloids, lysergol, ergometrine, methylergometrine and methysergide, were blocked by methiothepin (30 nmol/l) and flesinoxan (3 mumol/l), respectively, with approximate pKB values about 8.4-8.7 and 6.2-6.4, respectively. The mechanism underlying the second phase of contraction remains to be established. Maximum responses of the concentration-effect curves to 5-HT (1 nmol/l-1 mumol/l) were concentration-dependently depressed by ketanserin (1 nmol/l-1 mumol) and spiperone (30 nmol/l-0.3 mumol/l) and reached approximately 60% of the 5-HT maximum response in the presence of ketanserin (1 mumol/l) and spiperone (0.1 mumol/l), respectively. Agonist potency of 5-HT was not affected by the antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer.
Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We tested miR-221 and miR-375, which are frequently reported to be highly and poorly expressed in pancreatic cancer (PCa), as candidates for plasma biomarkers in PCa. This study was divided into three parts: (1) Confirmation of higher miR-221 levels in primary PCa tissue and cell lines than normal pancreatic tissues. (2) Evaluation of plasma miR-221 and miR-375 concentrations by comparing results from 47 consecutive PCa patients and 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in PCa patients. (1) Expression of miR-221 was significantly higher in PCa tissues and cell lines than normal pancreatic tissues. (2) Plasma miR-221 concentrations were significantly higher in PCa patients than that in benign pancreatic tumours (P=0.016) and controls (P<0.0005), while plasma miR-375 concentrations tended to be lower in PCa patients (P=0.064), and the miR-221/miR-375 ratio was significantly higher (P<0.0001) in PCa patients than in controls. (3) Plasma miR-221 concentrations were significantly reduced in postoperative samples (P=0.018). Furthermore, PCa patients with high plasma miR-221 concentrations had significant correlation with distant metastasis (P=0.041), and non-resectable status (P=0.021). Plasma miR-221 could be a useful biomarker for cancer detection, monitoring tumour dynamics and predicting malignant outcomes in PCa patients, and may contribute to clinical decision making in PCa treatments.


Monoclonal and biclonal immunoglobulin-producing disorders.
Monoclonal gammopathies are B lymphocyte-derived disorders producing a specific monoclonal immunoglobulin. The group includes multiple myeloma, Waldenström's macroglobulinaemia, monoclonal gammopathy of undetermined significance (MGUS) and heavy-chain disease. In 1% of the cases a double M-component is present which is referred to as a biclonal gammopathy. The pathogeneses of these disorders are unknown, but several possibly related environmental factors have been identified. In multiple myeloma, an increased incidence and mortality rate has been noted during the last 20 years. Strong lines of evidence are presented showing that, in monoclonal gammopathies, the cell clone consists of B lymphocytes in different stages of maturation. In most cases of biclonal gammopathy there is probably a common cellular origin.


Receptor flexibility for large-scale in silico ligand screens: chances and challenges.
An important contribution to today's computer-aided drug design is the automated screening of large compound databases against structurally resolved protein receptors targets. The introduction of ligand flexibility has, by now, become a standardized procedure. In contrast, a general approach to treat target degrees of freedom is still to be found, a consequence of the extreme increase of computational complexity, which comes along with the relaxation of protein degrees of freedom. In this chapter, we discuss in some detail both benefits and present limitations of target flexibility for high-throughput in silico database screens. Among the benefits are an improved diversity of binding modes, which allows one to identify a wider class of drug candidates. The limitations are related to a diminishing docking accuracy and an increased number of false hits. Using the thymidine kinase receptor and ten known inhibitors as an example, we describe in detail how target flexibility was implemented and how it affected the screening performance.


Integrating self-managed medication abortion with medical care.
In this commentary, we distill key messages from a new framework for self-managed medication abortion developed by Global Doctors for Choice. Since Global Doctors for Choice supports doctors working in different contexts around the world, the document also highlights clinical concerns and advocacy opportunities for clinicians in both low- and high-resource settings, and in places with varying legal and administrative restrictions on abortion.


c-Fos activity in the insular cortex, nucleus accumbens and basolateral amygdala following the intraperitoneal injection of saccharin and lithium chloride.
This study examined c-Fos expression in selected brain areas consequent to intraperitoneal (IP) administration of saccharin and lithium chloride. Rats were tested for aversion to the saccharin as measured by flavor consumption and orofacial reactions in the taste reactivity (TR) test. It was found that intraperitoneal conditioning resulted in the reduction in voluntary consumption but not in the production of aversive orofacial responses to the saccharin. The immunohistochemistry quantification revealed increased c-Fos activity in the insular cortex, the shell and core regions of the nucleus accumbens, and the basolateral nucleus of the amygdala. These results show that a conditioned taste aversion can be induced without direct oropharyngeal gustatory stimulation at the time of conditioning. In addition, this study provide evidence of increased neural activity in response to intraperitoneal saccharin injections.


Impacts of synthetic androgen and estrogenic antagonist administration on growth performance, sex steroids hormones, and immune markers of male and female broilers.
The influence of synthetic androgen and estrogenic antagonists (Tamoxifen) on body characteristics and immune response of male and female broilers and the correlation between sex hormone levels were estimated in our experiment. One day old chicks were sexed, and chicks of each sex were randomly distributed on three experimental treatments; the first treatment group (TAM20) chicks were supplied with estrogenic antagonist tamoxifen citrate 20 mg/kg body weight through oral administration for four times every other day from third until ninth d; Androgen treatment chicks were injected intramuscular with veterinary androgen AD GAN@ (Boldenone Undecylenate 50 mg) 1 cm/10 kg body weight at fifth and ninth day, and the third treatment was control. Androgen treatment reported the highest feed intake with the lowest for TAM20 treatment. Concerning carcass characteristics, early androgen injection increased breast percentage significantly compared to TAM20 treatment. Androgen supplementation increased significantly comb the percentage. However, TAM20 decreased it particularly compared to control. Moreover, the percentage of comb and shanks was substantially higher for males than females. Concerning the effects of both treatments on sex hormones, androgen showed favorable effects on testosterone and estrogen compared to Tamoxifen 20 treatment. On the other hand, the administration of TAM 20 improves phagocytic activity compared to androgen administration.


Soil organic matter dynamics and microbial metabolism along an altitudinal gradient in Highland tropical forests.
The highland forests of tropical regions are highly vulnerable to climate change because changes in soil organic quality due to the increased soil water deficit conditions through rising temperatures. Several authors have reported that labile molecules dominate soil organic matter at higher elevations, and it is therefore more vulnerable to the rising temperatures associated with climate change. The objective of the present study was to analyze the effect of interaction between the chemical composition of organic matter derived from the dominant plant species and the metabolism of microbial community along an elevational gradient in a highland forest in Central Mexico. The study compared three vegetation-soil systems that represent three different elevational levels: Alnus-system (3100 m.a.s.l.), Abies-system (3500 m.a.s.l.) and Pinus-system (3700 m.a.s.l.). The SOM produced in the lowest site is more recalcitrant (i.e., higher Alkyl:O-Alkyl ratio) as a result of the lower water availability than in the highest site. The results of Threshold Elemental RatioC:N (TERC:N) and TERC:P for the organic layer were lower than their C:N and C:P ratios in the organic layer, supporting that the microbial community of the organic layer in the site of lowest elevation must be limited by the carbon source, rather than by N and P. However, these results were not found in the mineral soil, suggesting that the drivers of organic matter decomposition differ between the organic layer and the mineral soil. As a conclusion, our results suggest that the chemical recalcitrance of organic matter (at the lowest site) and temperature (at the highest site) reduce the microbial metabolic activity in the forest floor. Integrated study of plant-derived organic material and the microbial metabolism of the forest floor is therefore required to achieve a full understanding of the vulnerability of tropical mountain ecosystems to climate change.


Perceiving land-degrading activities from the lay perspective in northern China.
Investigation into local peoples' perceptions can produce useful information that could be incorporated into the decision-making process to help resolve environmental problems. Within the arena of land degradation, a number of studies have also been conducted to explore local peoples' views of the problem. However, the perceptions of land-degrading practices of the general public have so far not been actively solicited. This study aimed to contribute to this area of research by adopting the psychometric scaling technique to empirically explore the lay public's ecological risk perceptions of land-degrading activities in Minqin County in Gansu Province, northern China. The primary data were collected via a questionnaire survey (n=1,138) administered between 14 and 31 December 2002. The major findings of the survey were: (1) Respondents perceived the ecological risks posed by different land-degrading activities to be different. (2) There was a considerable incongruence in the way in which mining of groundwater was conceived by experts and laymen, respectively. (3) Respondents were pretty unsure of expert knowledge. (4) Respondents' ecological risk perceptions were significantly affected by their personal attributes. As far as the policy implications of these findings are concerned, this study accentuates that we must be aware of, and involved in, the environmental perceptions of the lay public in order to succeed in guiding any human-environment tensions along more sustainable trajectories and navigating the transition to sustainability.


Individuals with hypertension have lower plasma volume regardless of weight status.
Increased plasma volume is often reported as a cause or symptom of hypertension in individuals with obesity. However, these individuals are often compared to normal weight normotensive individuals. Since higher plasma volumes have been reported in larger individuals, it is possible that plasma volume is actually lower in obese hypertensive individuals compared to normotensive obese individuals. This may be important for better understanding the clinical manifestation of hypertension between weight categories. National Health and Nutritional Examination Survey (cycles 1999-2018) data were used to examine the relationship between plasma (derived from the Straus formula), blood pressure (measured with an automated device) and body mass index. We observed an inverse relationship between estimated plasma volume and systolic (B = -1.68 (95% CI: -2.06, -1.30) mmHg), p < 0.0001), diastolic (B = -3.35 (95% CI: -3.61, -3.08) mmHg) p < 0.0001), and mean arterial pressure (B = -2.79 (95% CI: -3.05, -2.53) mmHg) p < 0.0001). The relationship between estimated plasma volume and diastolic blood pressure (interaction term: B = -0.069 (-0.10, -0.03), p < 0.0001) did depend on BMI. The "normal weight" group had the lowest slope and this slope was significantly different from the "obese" (B = -1.47 (95% CI: -1.88, -1.07)) and "overweight" (B = -1.11 (-1.55, -0.67)) groups. Plasma volume is lower in hypertensive individuals regardless of weight status, but this relationship is more pronounced among obese individuals.


Oral health and academic performance or absenteeism: Findings from a University in Southern Brazil.
To evaluate the association between oral health conditions and academic performance and absenteeism in university students. This cross-sectional study was carried out on a comprehensive sample of 1865 freshman students from the Federal University of Pelotas/Southern Brazil in 2017. A self-administered questionnaire was applied in the classroom, inquiring about socioeconomic, demographic, psychological, academic characteristics and oral conditions (tooth loss, self-reported oral health and toothache). For the dependent variables, academic performance was evaluated by the question: 'How would you describe your academic performance?' while absenteeism was assessed with the question 'In the last six months, have you missed some class for dental reasons?'. Multivariable analyses used hierarchical Poisson regression with backward selection. The prevalence of low academic performance was 38.6% and absenteeism due to dental reasons 6.2%. The prevalence of toothache and poor self-perceived oral health was 28% and 20%, respectively. Multivariable analysis found low academic performance to be more prevalent in students with poor self-perceived oral health (PR 1.46; 95% CI 1.22-1.77), and absenteeism to be almost six times more prevalent (PR 5.85; 95% CI 3.84-8.90) in students reporting toothache. Poor oral health is associated with both poor academic performance and absenteeism in university students.


Ambient-temperature oxidative coupling of methane in an electric field by a cerium phosphate nanorod catalyst.
CePO4 nanorods with uniform surface Ce sites could work as a durable catalyst and showed the highest C2 yield of 18% in an electric field without the need for external heating, which was comparable to that reported for high-performance catalysts at high temperature (>900 K).


Antagonism by d-amphetamine of learning deficits in rats induced by exposure to antipsychotic drugs during early postnatal life.
The acquisition of a conditioned avoidance response (CAR) was investigated in rats of nursing mothers given pimozide 0.5 mg/kg on days 1, 2, 3, 4, 5, 6, and 7 after delivery. Four weeks after birth, the male litter-mates were tested for CAR acquisition in a two-way avoidance situation or for correct CAR acquisition in a brightness discrimination situation. Offspring of mothers treated with pimozide were markedly inferior in the CAR acquisition in both behavioural situations as compared to those of mothers given glucose. The administration of d-amphetamine 15 min prior to the training session specifically counteracted the behavioural impairment obtained in the offspring of pimozide-treated mothers. The results obtained in the present investigation lend further support to the contention that the behavioural deficits in offspring of nursing mothers treated with neuroleptic agents are due to a developmental disturbance in central catecholamine neurones.


Serological identification and bioinformatics analysis of immunogenic antigens in multiple myeloma.
Identifying appropriate tumor antigens is critical to the development of successful specific cancer immunotherapy. Serological analysis of tumor antigens by a recombinant cDNA expression library (SEREX) allows the systematic cloning of tumor antigens recognized by the spontaneous autoantibody repertoire of cancer patients. We applied SEREX to the cDNA expression library of cell line HMy2, which led to the isolation of six known characterized genes and 12 novel genes. Known genes, including ring finger protein 167, KLF10, TPT1, p02 protein, cDNA FLJ46859 fis, and DNMT1, were related to the development of different tumors. Bioinformatics was performed to predict 12 novel MMSA (multiple myeloma special antigen) genes. The prediction of tumor antigens provides potential targets for the immunotherapy of patients with multiple myeloma (MM) and help in the understanding of carcinogenesis. Crude lysate ELISA methodology indicated that the optical density value of MMSA-3 and MMSA-7 were significantly higher in MM patients than in healthy donors. Furthermore, SYBR Green real-time PCR showed that MMSA-1 presented with a high number of copy messages in MM. In summary, the antigens identified in this study may be potential candidates for diagnosis and targets for immunotherapy in MM.


Survival with Collateral Circulation after Gastrointestinal Ischemia Caused by Aortic Dissection: A Case Report.
We report a case of a 43-year-old man who presented with gradually intensifying abdominal pain of acute onset and was shown by contrast-enhanced computed tomography (CT) examination to have acute aortic dissection (Stanford type B). A diagnosis of gastrointestinal necrosis was made and he underwent emergency surgery. At laparoscopy, he was found to have no superior mesenteric arterial pulse and intestinal necrosis from the upper jejunum to the right transverse colon. Resection of the superior mesenteric artery (SMA) perfusion area was performed. Postoperatively, ischemia in the perfusion area of the celiac artery was also diagnosed, manifesting as gallbladder necrosis, portal vein gas accompanying gastric wall necrosis, perforation of the remaining upper jejunum, and hepatic and splenic infarction. However, development of a collateral circulation originating in the left colic branch of the inferior mesenteric artery (IMA) enabled retrograde provision of blood to the celiac artery through the SMA pancreaticoduodenal arcade. Thus, in this case, spontaneous development of a natural bypass created a new route for arterial perfusion, contributing to the patient's survival. When ischemia of the celiac artery and SMA perfusion areas occur, collateral circulation can develop from the IMA.


Relationships Between Hair Chemical Elements and Nutritional Status in Oldest-Old and Centenarian Populations.
Hair chemical elements reflect physical condition over time. Collection, transporting, and storing hair is more convenient than handling blood. Hair elements show higher levels for a long time, which allows for more accurate and sensitive results than using blood. Studies explored the relationships between elements and age, without full consideration of nutritional status, in older people. This study explored the relationships between hair chemical elements and Geriatric Nutritional Risk Index (GNRI) in oldest-old and centenarian populations to provide an updated reference for nutritional evaluation of older people. A total of 152 participants over 80 years old underwent home interviews and physical examinations. An inductively coupled plasma mass spectrometer was used to detect hair chemical elements. Women accounted for 77.0% of participants. Women had lower levels of zinc, and higher levels of selenium, manganese, lead, iron, and copper than men (P<0.05 for all). Ninety-two participants formed the 80-99 year group, and 60 participants formed the 100+ year group. Centenarians had lower levels of selenium, lead, iron, and copper than those aged 80-99 years (P<0.05 for all). Hair selenium levels were positively associated with GNRI (odds ratio: 11.55, 95% confidence interval: 3.42-19.68, P < 0.05) based on a multivariate linear regression analysis. Other chemical elements had no significant associations with GNRI based on a multivariate linear regression analysis. Chemical elements and nutrient status were altered based on age and gender, and an association existed between hair selenium and nutritional status in older people. Chemical elements may influence and indicate nutritional status in older people.


[Mycophenolatemofetil in ocular immunological disorders. A survey of the literature with 3 case reports].
Up to now ophthalmologists have only a small number of substances in their therapeutic armamentarium for the treatment of ocular immunological disorders. These are very potent agents, and any rapidly proliferating cells are extremely sensitive to such agents, thus the possibility of severe side effects is great. Mycophenolatemofetil (MMF) has been shown to be effective in preventing acute graft rejection following clinical renal and cardiac transplantation with a low risk of adverse events. Likewise MMF was effective in the treatment of experimental immunological disorders. A review of literature was performed in Medline. We report on the effective use of MMF in a patient with ocular cicatricial pemphigoid, the switch from Cyclosporin A (CSA) therapy to MMF therapy following high-risk keratoplasty due to CSA allergy and about the combination therapy (CSA/MMF) in a patient following high risk keratoplasty, in whom CSA monotherapy was not sufficient to prevent allograft rejection. In these three cases MMF has been shown to be a safe and effective agent for the treatment of ocular immunological disorders. Whether these beneficial casuistic experiences will hold true will be depended on the outcome of longterm studies underway.


Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria.
Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18-42 years, with a duration of diabetes of 4-8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min(-1) 1.73 m(-2) (equivalent to 2 SD above mean for a control population). Analysis was by paired Student's t-testing and linear regression. GFR correlated significantly with HbA1c (r= 0.47, p < 0.0001) and fructosamine (r= 0.24, p = 0.035). Mean HbA1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA1c: 9.2% (95% C.I. 7.9-10.4%) vs 7.6 % (7.2-7.9), p= 0.002; fructosamine: 479 micromol l(-1) (450-507) vs 410 micromol l(-1) (388-432), p = 0.009. This significant difference persisted even when the two highest values of HbA1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA1c (r=0.31, p=0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM.


Regression of renal cell hepatic metastasis following removal of primary lesions.
Although spontaneous regression of metastatic renal cell carcinoma occurs it is so uncommon that it should not be considered the primary basis for recommending removal of the asymptomatic primary lesion. Such a recommendation should be made when other treatment modalitis are available to augment the factors influencing the patient-tumor interface. Spontaneous regression of a documented solitary liver metastatic lesion is reported. Removal of the residual hepatic lesion failed to prolong the patient's life.


Melatonin alleviates PM2.5 -induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic reticulum stress.
Exposure to fine particulate matter (PM2.5 ) was associated with an increased incidence of liver metabolic disease. Melatonin has been shown to prevent liver glucolipid metabolism disorders. However, whether melatonin could rescue PM2.5 -induced liver metabolic abnormalities remains uncertain. This study was to evaluate the mitigating effect of melatonin on PM2.5 -accelerated hepatic glucose metabolism imbalance in vivo and in vitro. Schiff periodic acid shiff staining and other results showed that PM2.5 led to a decrease in hepatic glycogen reserve and an increase in glucose content, which was effectively alleviated by melatonin. Targeted lipidomics is used to identify lipid biomarkers associated with this process, including glycerolipids, glycerophospholipids, and sphingolipids. In addition, gene microarray and quantitative polymerase chain reaction analysis of ApoE-/- mice liver suggested that PM2.5 activated the miR-200a-3p and inhibited DNAJB9, and the targeting relationship was verified by luciferase reports for the first time. Further investigation demonstrated that DNAJB9 might motivate endoplasmic reticulum (ER) stress by regulating Ca2+ homeostasis, thus altering the protein expression of GSK3B, FOXO1, and PCK2. Meanwhile, melatonin effectively inhibited miR-200a-3p and glucose metabolism disorder. Knockout of miR-200a-3p in L02 cells revealed that miR-200a-3p is indispensable in the damage of PM2.5 and the therapeutic effect of melatonin. In summary, melatonin alleviated PM2.5 -induced liver metabolic dysregulation by regulating ER stress via miR-200a-3p/DNAJB9 signaling pathway. Our data provide a prospective targeted therapy for air pollution-related liver metabolism disorders.


Seasonal drought events in tropical East Asia over the last 60,000 y.
The cause of seasonal hydrologic changes in tropical East Asia during interstadial/stadial oscillations of the last glaciation remains controversial. Here, we show seven seasonal drought events that occurred during the relatively warm interstadials by phytolith and pollen records. These events are significantly manifested as high percentages of bilobate phytoliths and are consistent with the large zonal sea-surface temperature (SST) gradient from the western to eastern tropical Pacific, suggesting that the reduction in seasonal precipitation could be interpreted by westward shifts of the western Pacific subtropical high triggered by changes of zonal SST gradient over the tropical Pacific and Hadley circulation in the Northern Hemisphere. Our findings highlight that both zonal and meridional ocean-atmosphere circulations, rather than solely the Intertropical Convergence Zone or El Niño-Southern Oscillation, controlled the hydrologic changes in tropical East Asia during the last glaciation.


Dihydroergotamine: a review of formulation approaches for the acute treatment of migraine.
Dihydroergotamine (DHE) was first used to treat migraine in 1945 and is currently included among migraine-specific treatments for moderate-severe migraine. DHE may be administered through several routes of delivery, with efficacy and tolerability varying among formulations. We review DHE formulation approaches for the acute treatment of migraine, reviewing pharmacokinetics/dynamics and comparing clinical response among various formulations. Pharmacokinetic properties vary among DHE formulations, with peak concentration occurring in 6 min with intravenous, 34 min with intramuscular, 56 min with intranasal, 12 min with oral inhalation and 75 min with oral administration. DHE is a potent agonist at serotonin 5-HT1B and 5-HT1D receptors. Adverse effects due to binding to select adrenergic and dopaminergic receptors are significantly less with orally inhaled than intravenous DHE when comparing therapeutically effective doses. Among parenteral formulations (including subcutaneous, intramuscular, intravenous and nasal spray), efficacy is superior with injectable dosing. Nasal spray DHE is generally more effective than placebo, but less effective than sumatriptan. Orally inhaled DHE is likewise more effective than placebo, but there are no head-to-head comparisons with triptans available for review. Adverse effects, particularly nausea, may limit use of parenteral DHE. Nausea is generally less frequent with non-injectable dosing.


[Standard-ECG].
The ECG is still the basis of technical investigations in cardiology. New descriptions and interpretations have been developed for left ventricular hypertrophy, Q-wave, arrhythmogenic diseases such as long and short QT syndrome, Brugada syndrome, syndrome of early repolarization, and arrhythmogenic right ventricular disease.


Adolescent mental well-being, religion and family activities: a cross-sectional study (Northern Ireland Schools and Wellbeing Study).
In this study, we seek to explore the relationship between adolescent mental well-being, religion and family activities among a school-based adolescent sample from Northern Ireland. The Northern Ireland Schools and Wellbeing Study is a cross-sectional study (2014-2016) of pupils in Northern Ireland aged 13-18 years. 1618 adolescents from eight schools participated in this study. Our primary outcome measure was derived using the Warwick-Edinburgh Mental Wellbeing Scale. We used hierarchical linear regression to explore the independent effects of a range of personal/social factors, including religious affiliation, importance of religion and family activities. In fully adjusted models, older adolescents and females reported lower mental well-being scores-for the year-on-year increase in age β=-0.45 (95% CI=-0.84, -0.06), and for females (compared with males) β=-5.25 (95% CI=-6.16, -4.33). More affluent adolescents reported better mental well-being. No significant differences in mental well-being scores across religious groups was found: compared with Catholics, Protestant adolescents recorded β=-0.83 (95% CI=-2.17, 0.51), other religious groups β=-2.44 (95% CI=-5.49, 0.62) and atheist adolescents β=-1.01 (95% CI=-2.60, 0.58). The importance of religion in the adolescents' lives was also tested: (compared with those for whom it was not important) those for whom it was very important had better mental well-being (β=1.63: 95% CI=0.32, 2.95). Higher levels of family activities were associated with higher mental well-being: each unit increase in family activity produced a 1.45% increase in the mental well-being score (β=0.78: 95% CI=0.67, 0.90). This study indicates that non-religious adolescents may have lower mental well-being scores when compared with their more religious peers, irrespective of religious denomination. This may relate to both a sense of lack of firm identity and perceived marginalisation. Additionally, adolescents with poor family cohesion are more vulnerable to poor mental well-being.


RCB20, an experimental benzimidazole derivative, affects tubulin expression and induces gross anatomical changes in Taenia crassiceps cysticerci.
Helminth β-tubulins are the targets of benzimidazole (BZM) carbamate compounds. The specificity of the interactions between such compounds and their in vivo targets depends on the presence of specific amino acid residues in the target molecules. To discover new and effective anthelmintic drugs, we used a medicinal chemistry approach to synthesize a series of BZM derivatives that exploited the BZM moiety as a template. We have previously found that one compound, 2-(trifluoromethyl)-1H-benzimidazole (RCB20), has better in vitro and in vivo activity than albendazole sulfoxide (ABZSO). In the present study, the effect of RCB20 and ABZSO treatment on expression of Taenia crassiceps cysticerci cytoskeletal proteins such as actin, myosin II, and tubulin isoforms was examined. The effects of RCB20 and ABZSO after 11 days treatment of the parasites was evaluated by light, confocal, and electron microscopy, and by immunochemistry and immunohistochemistry. The RCB20-induced effects were more rapid than the ABZSO-induced effects on the parasites. In the RCB20-treated parasites, we observed gross-structural damage at the whole parasite level, particularly in the inner tissues and flame cells. Changes in the expression patterns of the cytoskeletal proteins, as assessed by immunohistochemistry and immunoblotting, revealed that the most important drug-induced effect on the parasites was a reduction in the expression level of tyrosinated α-tubulins. Our research findings suggest that RCB20 treatment affected posttranslational modification of parasite α-tubulin molecules, which involved removal of the α-tubulin carboxy-terminal tyrosine.