Selective Conversion of Syngas to Olefins via Novel Cu-Promoted Fe/RGO and Fe-Mn/RGO Fischer-Tropsch Catalysts: Fixed-Bed Reactor vs Slurry-Bed Reactor.
Fischer-Tropsch has become an indispensable choice in the gas-to-liquid conversion reactions to produce a wide range of petrochemicals using recently emerging biomass or other types of feedstock such as coal or natural gas. Herein we report the incorporation of novel Cu nanoparticles with two Fischer-Tropsch synthesis (FTS) catalytic systems, Fe/reduced graphene oxide (rGO) and Fe-Mn/rGO, to evaluate their FTS performance and olefin productivity in two types of reactors: slurry-bed reactor (SBR) and fixed-bed reactor (FBR). Four catalysts were compared and investigated, namely Fe, FeCu7, FeMn10Cu7, and FeMn16, which were highly dispersed over reduced graphene oxide nanosheets. The catalysts were first characterized by transmission electron microscopy (TEM), nitrogen physisorption, X-ray fluorescence (XRF), X-ray diffraction (XRD), and H-TPR techniques. In the SBR, Cu enhanced olefinity only when used alone in FeCu7 without Mn promotion. When used with Mn, the olefin yield was not changed, but light olefins decreased slightly at the expense of heavier olefins. In the FBR system, Cu as a reduction promoter improved the catalyst activity. It increased the olefin yield mainly due to increased activity, even if the CO2 decreased by the action of Cu promoters. The olefinity of the product was improved by Cu promotion but it did not exceed the landmark made by FeMn16 at 320 °C. The paraffinity was also enhanced by Cu promotion especially in the presence of Mn, indicating a strong synergistic effect. Cu was found to be better than Mn in enhancing the paraffin yield, while Mn is a better olefin yield enhancer. Finally, Cu promotion was found to enhance the selectivity towards light olefins C2-4. This study gives a deep insight into the effect of different highly dispersed FTS catalyst systems on the olefin hydrocarbon productivity and selectivity in two major types of FTS reactors.


Additive Manufacturing of Caffeic Acid-Inspired Mineral Trioxide Aggregate/Poly-ε-Caprolactone Scaffold for Regulating Vascular Induction and Osteogenic Regeneration of Dental Pulp Stem Cells.
Mineral trioxide aggregate (MTA) is a common biomaterial used in endodontics regeneration due to its antibacterial properties, good biocompatibility and high bioactivity. Surface modification technology allows us to endow biomaterials with the necessary biological targets for activation of specific downstream functions such as promoting angiogenesis and osteogenesis. In this study, we used caffeic acid (CA)-coated MTA/polycaprolactone (PCL) composites and fabricated 3D scaffolds to evaluate the influence on the physicochemical and biological aspects of CA-coated MTA scaffolds. As seen from the results, modification of CA does not change the original structural characteristics of MTA, thus allowing us to retain the properties of MTA. CA-coated MTA scaffolds were shown to have 25% to 55% higher results than bare scaffold. In addition, CA-coated MTA scaffolds were able to significantly adsorb more vascular endothelial growth factors (p < 0.05) secreted from human dental pulp stem cells (hDPSCs). More importantly, CA-coated MTA scaffolds not only promoted the adhesion and proliferation behaviors of hDPSCs, but also enhanced angiogenesis and osteogenesis. Finally, CA-coated MTA scaffolds led to enhanced subsequent in vivo bone regeneration of the femur of rabbits, which was confirmed using micro-computed tomography and histological staining. Taken together, CA can be used as a potently functional bioactive coating for various scaffolds in bone tissue engineering and other biomedical applications in the future.


IL-1β Implications in Type 1 Diabetes Mellitus Progression: Systematic Review and Meta-Analysis.
During Type 1 Diabetes Mellitus (T1DM) progression, there is chronic and low-grade inflammation that could be related to the evolution of the disease. We carried out a systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers such as interleukin-1 beta (IL-1β) is significantly different among patients with or without T1DM, in gender, management of the T1DM, detection in several biological fluids, study design, age range, and glycated hemoglobin. We searched PubMed, Embase, Web of Science, and Scopus databases, and 26 relevant studies (2186 with T1DM, 2047 controls) were included. We evaluated the studies' quality using the Newcastle−Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Compared with controls, IL-1β determined by immunoassays (pooled standardized mean difference (SMD): 2.45, 95% CI = 1.73 to 3.17; p < 0.001) was significantly elevated in T1DM. The compared IL-1β levels in patients <18 years (SMD = 2.81, 95% CI = 1.88−3.74) was significantly elevated. The hemoglobin-glycated (Hbg) levels in patients <18 years were compared (Hbg > 7: SMD = 5.43, 95% CI = 3.31−7.56; p = 0.001). Compared with the study design, IL-1β evaluated by ELISA (pooled SMD = 3.29, 95% CI = 2.27 to 4.30, p < 0.001) was significantly elevated in T1DM patients. IL-1β remained significantly higher in patients with a worse management of T1DM and in the early stage of T1DM. IL-1β levels determine the inflammatory environment during T1DM.


Infectious mid basilar artery aneurysm from Pseudomonas meningitis.
Pseudomonas aeruginosa meningitis is an uncommon complication of neurosurgical procedures or head trauma. Here, a case of infectious mid basilar artery aneurysm from Pseudomonas meningitis, and its angiographic remission from timely antibiotic therapy, is reported.


Block of hERG channel by ziprasidone: biophysical properties and molecular determinants.
Ziprasidone, an antipsychotic agent, delays cardiac repolarization and, thus, prolongs the QT interval of the cardiac ECG. In this study, we examined the biophysical properties and the molecular determinants of the ziprasidone block of wild-type hERG potassium channels stably expressed in HEK-293 cells or wild-type and mutant hERG channels expressed in Xenopus oocytes. In stably transfected HEK-293 cells, ziprasidone blocked wild-type hERG current in a voltage- and concentration-dependent manner (IC(50)=120nM, 0mV, 37 degrees C). Ziprasidone showed minimal tonic block of hERG current estimated during a depolarizing voltage (-20 or +30mV) or evaluated by the envelope of tails test (+30mV). Rate of the block onset was rapid, but not significantly affected by test potentials ranging from -20 to +30mV (time constant (tau)=114+/-14ms at +30mV). The time constant of the slow component of hERG current deactivation (at -50mV) was significantly increased by ziprasidone (tau=1776+/-90 versus 1008+/-71ms, P<0.01). Time course of channel inactivation was slowed by ziprasidone in a voltage-dependent manner. The V(1/2) values for steady-state activation and inactivation of hERG channel in HEK-293 cells were not significantly altered by ziprasidone. In Xenopus oocytes, ziprasidone exhibited less potent block of wild-type hERG current (IC(50)=2.8microM, 0mV, 23 degrees C). Mutation of the aromatic residues (Tyr-652 or Phe-656) located in the S6 domain of hERG dramatically reduced the potency of channel block by ziprasidone (IC(50)>0.4 and 1mM at 0mV for Y652A and F656A, respectively). In conclusion, ziprasidone preferentially binds to and blocks open hERG channels. Tyr-652 and Phe-656 are two critical residues in the ziprasidone-binding site.


Case report: Disease phenotype associated with simultaneous biallelic mutations in ABCA4 and USH2A due to uniparental disomy of chromosome 1.
Inherited retinal diseases (IRDs) represent a spectrum of clinically and genetically heterogeneous disorders. Our study describes an IRD patient carrying ABCA4 and USH2A pathogenic biallelic mutations as a result of paternal uniparental disomy (UPD) in chromosome 1. The proband is a 9-year-old girl born from non-consanguineous parents. Both parents were asymptomatic and denied family history of ocular disease. Clinical history and ophthalmologic examination of the proband were consistent with Stargardt disease. Whispered voice testing disclosed moderate hearing loss. Next-generation sequencing and Sanger sequencing identified pathogenic variants in ABCA4 (c.4926C>G and c.5044_5058del) and USH2A (c.2276G>T). All variants were present homozygously in DNA from the proband and heterozygously in DNA from the father. No variants were found in maternal DNA. Further analysis of single nucleotide polymorphisms confirmed paternal UPD of chromosome 1. This is the first known patient with confirmed UPD for two recessively mutated IRD genes. Our study expands on the genetic heterogeneity of IRDs and highlights the importance of UPD as a mechanism of autosomal recessive disease in non-consanguineous parents. Moreover, a long-term follow-up is essential for the identification of retinal features that may develop as a result of USH2A-related conditions.


Acrocephalopolysyndactyly type II--Carpenter syndrome: clinical spectrum and an attempt at unification with Goodman and Summit syndromes.
Carpenter syndrome (ACPS type II) was first described by Carpenter in 1901. The syndrome consists of acrocephaly, soft tissue syndactyly, brachy- or agenesis mesophalangy of the hands and feet, preaxial polydactyly, congenital heart disease, mental retardation, hypogenitalism, obesity, and umbilical hernia. Here we review the literature on Carpenter syndrome and add 2 affected sibs with marked intrafamilial variability. This review showed that 2 reported variations of Carpenter syndrome, Goodman and Summitt syndromes, actually fall within the clinical spectrum of this disorder. This confirms earlier suggestions of Gorlin (personal communication 1982) and Hall et al [Am J Med Genet 5:423-434, 1980].


Trends in the prevalence of metabolic syndrome and its components in South Korea: Findings from the Korean National Health Insurance Service Database (2009-2013).
The prevalence of metabolic syndrome has markedly increased worldwide. However, studies in the United States show that it has remained stable or slightly declined in recent years. Whether this applies to other countries is presently unclear. We examined the trends in the prevalence of metabolic syndrome and its components in Korea. The prevalence of metabolic syndrome and its components was estimated in adults aged >30 years from the Korean National Health Insurance Service data from 2009 to 2013. The revised National Cholesterol Education Program criteria were used to define metabolic syndrome. Approximately 10 million individuals were analyzed annually. The age-adjusted prevalence of metabolic syndrome increased from 28.84% to 30.52%, and the increasing trend was more prominent in men. Prevalence of hypertriglyceridemia, low HDL-cholesterol, and impaired fasting plasma glucose significantly increased. However, the prevalence of hypertension decreased in both genders. The prevalence of abdominal obesity decreased in women over 50 years-of-age but significantly increased in young women and men (<50 years). The prevalence of metabolic syndrome is still increasing in Korea. Trends in each component of metabolic syndrome are disparate according to the gender, or age groups. Notably, abdominal obesity among young adults increased significantly; thus, interventional strategies should be implemented particularly for this age group.


Management of Breathlessness in Patients With Advanced Cancer: A Narrative Review.
Breathlessness is defined as "a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity." It is a common and distressing symptom reported by patients with advanced malignancy. It occurs in up to 70% of patients with advanced cancer, and the symptom is aggravated with disease progression. This article reviews the etiology, assessment, and measurement of dyspnea in patients with advanced cancer. Because of its complex biopsychological etiology and manifestations, multidisciplinary approach with combination of both pharmacological and nonpharmacological interventions provides the best treatment plan for patients with dyspnea.


Pregnancy Management in Women with Antiphospholidic Syndrome.
The antiphospholipid syndrome (APS or Hughes Syndrome) is a systemic autoimmune disease characterised by the presence of specific and persistent circulating antiphospholipid antibodies (APL) and the subsequent morbidities they cause, including pregnancy complications and thrombosis. The three main antiphospholipid antibodies are: lupus anticoagulant (LA); anticardiolipin antibodies (aCL) IgG and IgM; and anti-â2-glycoprotein 1 IgG and IgM antibodies. Antiphospholipid syndrome is associated with pregnancy complications such as recurrent early fetal loss, fetal death, preeclampsia (PE), and fetal growth restriction (FGR). Although autoimmune disorders may have serious implication during pregnancy important advancements in pregnancy outcome have been reported in women with APL. The challenge arises in case of women refractory to conventional treatment (heparine/aspirin combination), which occurs in about 20-30% of cases. The management of pregnant women with non-criteria APS manifestations and that of APL carriers during their first pregnancy is also discussed. This paper aims to discuss the risk stratification, clinical and pregnancy implications and current treatment strategies for pregnant women.


HIV care cascade among cisgender men who have sex with men in a key population-led community center in the Philippines.
The HIV epidemic in the Philippines is the fastest growing globally, and disproportionately affects cisgender men who have sex with men (cis-MSM) demanding effective strategies for this key population (KP) group. KP-specific and community-based (CB) interventions have improved the HIV response elsewhere, but these have yet to be evaluated locally. We analyzed the HIV care cascade outcomes in a KP-led, CB HIV test-and-treat center and determined factors that affect these by performing a retrospective study of medical records of 3137 patients diagnosed from January 2016 to March 2019 in LoveYourself in Manila, Philippines. Multivariate logistic regression was performed to determine predictors affecting the likelihood of antiretroviral therapy (ART) initiation and viral load (VL) suppression. As to UNAIDS 90-90-90 targets, LoveYourself had higher rates than national outcomes with 78% initiated ART and 84% achieved VL suppression. Such satisfactory performance is consistent with other studies exploring CB, KP-led approaches among cis-MSM. Patients who presented with WHO Stages 2-4 and those with sexually transmitted infections were less likely to initiate ART. Patients who presented with WHO Stages 2-4 and those whose ART was started late were less likely to be virally suppressed. These findings suggest the need to develop responsive interventions to reach the UNAIDS targets.


The incidence and mortality of ovarian cancer and their relationship with the Human Development Index in Asia.
The incidence and mortality estimates of ovarian cancer based on human development are essential for planning by policy makers. This study is aimed at investigating the standardised incidence rates (SIR) and standardised mortality rates (SMR) of ovarian cancer and their relationship with the Human Development Index (HDI) in Asian countries. This study was an ecologic study in Asia for assessment of the correlation between SIR, age standardised rates (ASR), and HDI and their details, including life expectancy at birth, mean years of schooling, and gross national income (GNI) per capita. We used the correlation bivariate method for assessment of the correlation between ASR and HDI, and its details. Statistical significance was assumed if P < 0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.). The highest SIR of ovarian cancer was observed in Singapore, Kazakhstan, and Brunei respectively. Indonesia, Brunei, and Afghanistan had the highest SMR. There was a positive correlation between the HDI and SIR (r = 0.143, p = 0.006). Correlation between SMR of ovarian cancer and HDI was not significant (r = 0.005, p = 052.0). According to the findings of this study, between the HDI and SIR, there was a positive correlation, but there was no correlation between the SMR and HDI.


The effects of exposure to gang violence on adolescent boys' mental health.
Gang violence is a growing public health concern in the United States, and adolescents are influenced by exposure to gang violence. This study explored the influence of exposure to gang violence on adolescent boys' mental health using a multi-method design. A semi-structured interview guide and the Trauma Symptom Checklist for Children were used to collect data from adolescents. Parents, primary caregivers, and community center employees completed the Child Behavior Checklist or Teacher Report Form. Ten adolescent boys, their parents or primary caregivers, and six community center employees participated in the study. Exposure to gang violence was common among these adolescents and they had a variety of reactions. Parents, primary caregivers, and community center employees had differing perceptions of adolescents' exposure to violence and their mental health. Adolescent boys' exposure to gang violence in the community is alarming. These adolescents encountered situations with violence that influenced their mental health.


Comparison of cone-beam computed tomography, clinical and surgical analysis for detection of maxillary molar furcation.
The aim of this study was to compare the performance of conebeam computed tomography (CBCT), clinical and surgical probing in assessing maxillary molar furcation involvement (FI). Furcation defects (n= 120) were assessed through CBCT, clinical and intra-surgical evaluation (ISE). Furcation Involvement, vertical and horizontal bone loss were assessed through clinical probing, CBCT and probing during ISE. Three trained radiologists evaluated CBCT images and intra- and interobserver agreement were calculated by Kappa test and Intraclass Correlation Coefficient (ICC). McNemar and Wilcoxon tests were used to compare clinical probing, ISE and CBCT. Accuracy, sensitivity, specificity, positive and negative predictive values were calculated to detect FI. Clinical findings showed 28 sites with Degree I, 25 sites with Degree II, and 8 sites with Degree III. Good intra- (k=1.00) and interobserver agreement (k=0.773) were observed. Intraobserver and interobserver agreement for horizontal bone loss were moderate, k=0.485 and k=0.549, respectively. Intra-surgical findings showed Degree I at 21 sites, and Degree II and Degree III FI at fifteen sites each. Clinical evaluation showed 75% agreement with ISE and 78% with CBCT. Accuracy for clinical detection of FI was 75%, while for CBCT evaluation ranged from 72.5% to 77.5%, considering the 3 observers. Significant differences were found at distal sites using CBCT (p<0.05). Clinical evaluation and CBCT showed similar results for the presence or absence of FI. Concerning horizontal and vertical bone loss, CBCT was not considered a precise examination method for incipient bone defects.


Pathological relevance and treatment perspective of JAK targeting in systemic lupus erythematosus.
The pathogenesis of systemic lupus erythematosus (SLE) involves abnormalities in both acquired and innate immune system, which is mediated by numerous cytokines. Janus kinase (JAK) plays important roles in the signaling pathways of those cytokines and is an attractive therapeutic target for SLE. Currently, multiple clinical trials using JAK inhibitors with different selectivities for JAK family proteins are being conducted in SLE. In this article, we provide an overview of the pathological relevance of JAK and the clinical implications of JAK inhibitors in SLE based on recent reports. JAK inhibitors have the potential to modulate various immune networks through a variety of mechanisms, potentially regulating the complex immunopathogenesis in SLE. SLE is a clinically and immunologically heterogeneous disease; therefore, precision medicine is required to maximize the efficacy of JAK inhibitors. Further studies are needed to determine their risk-benefit ratio and selection of the most appropriate patients for JAK inhibitors.


Basic mechanisms of cellular calcium homeostasis.
This contribution summarizes some basic principles of calcium distribution and calcium movements in eukaryotic cells. Emphasis is placed upon modes of calcium entry into cells, routes of calcium extrusion from cells, subcellular distribution of calcium, and the regulatory role of calcium for the control of membrane permeability to calcium itself and to other ions.


[Mesenchymal tumors of the pancreas: computed tomography patterns].
To report the CT patterns of pancreatic mesenchymal lesions and to investigate the capabilities and limitations of this technique in terms of characterization. We selected the CT examinations of 23 patients from all CT examinations of the pancreas performed from 1986 to 1998. The patients were 10 to 85 years old and all lesions but two (1 lipoma and 1 lymphoma) had pathologic confirmation. Two lymphangiomas, 2 lipomas, 4 Schwannomas (SCH), 1 plexiform neurofibroma, 1 cystic teratoma, 1 pancreatoblastoma, 9 non-Hodgkin's lymphomas (NHL), 1 undifferentiated sarcoma and 2 leiomyosarcomas were diagnosed. Lipomas had typically homogeneous negative HU values, and NHL a homogeneous hypodense pattern with mild contrast enhancement, with no necrosis or calcifications in both diffuse and nodular forms; SCH had variable appearance, with water/slightly negative HU numbers or highly enhanced patterns with a central necrotic core depending on the main Antoni A or B histology. Lymphangiomas appeared as complex cysts, with thin and regular or calcified walls and intracystic septa, while the plexiform neurofibroma had near-water homogeneous density with mild contrast enhancement and an infiltrating growth pattern. Our teratoma had multiple calcifications, mucinous and lipid components. The pancreatoblastoma, sarcomas, and leiomyosarcomas exhibited no specific findings. In selected cases, CT can provide virtually diagnostic information (lipoma and teratoma), or at least highly suggestive findings (NHL, plexiform neurofibroma, lymphangioma). Moreover, knowledge of the variable morphostructural patterns of mesenchymal histotypes (SCH, sarcoma etc.) permits to include them in the differential diagnosis of pancreatic masses.


Association of the invasive Haemaphysalis longicornis tick with vertebrate hosts, other native tick vectors, and tick-borne pathogens in New York City, USA.
Haemaphysalis longicornis, the Asian longhorned tick, is an invasive ixodid tick that has rapidly spread across the northeastern and southeastern regions of the United States since first reported in 2017. The emergence of H. longicornis presents a potential threat for livestock, wildlife, and human health as the host associations and vector potential of this invasive pest in the United States are poorly understood. Previous field data from the United States has shown that H. longicornis was not associated with natural populations of small mammals or birds, but they show a preference for medium sized mammals in laboratory experiments. Therefore, medium and large sized mammals were sampled on Staten Island, New York, United States, to determine H. longicornis host associations and vector potential for a range of human and veterinary pathogens. A total of 97 hosts were sampled and five species of tick (Amblyomma americanum, Dermacentor variabilis, H. longicornis, Ixodes scapularis, Ixodes cookei) were found feeding concurrently on these hosts. Haemaphysalis longicornis was found in the highest proportions compared with other native tick species on raccoons (55.4%), Virginia opossums (28.9%), and white-tailed deer (11.5%). Tissue, blood, and engorged larvae were tested for 17 different pathogens using a nanoscale PCR platform. Infection with five pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, Rickettsia spp., Mycoplasma haemocanis, and Bartonella spp.) was detected in host samples, but no pathogens were found in any larval samples. These results suggest that although large and medium sized mammals feed large numbers of H. longicornis ticks in the environment, there is presently a low potential for H. longicornis to acquire pathogens from these wildlife hosts.


Synthesis of fluorescent ring-fused 2-pyridone peptidomimetics.
Thiazolino fused 2-pyridone peptidomimetics are of significant biological importance due to their ability to interfere with adhesive fiber formation in uropathogenic Escherichia coli and oligomerization of amyloid fibers. We have developed an efficient synthetic route to fluorescent BODIPY analogues, with structural diversification from a key intermediate enabling introduction of C-2 substituents and late incorporation of the BODIPY moiety. A mild lithium halide mediated hydrolysis enabled preparation of peptidomimetic fluorophores with useful photophysical properties for further chemical biology applications.


Driveway-related motor vehicle injuries in the paediatric population: a preventable tragedy.
To describe the incidence and demographics of children injured by slow-moving vehicles in Auckland driveways in order to develop preventative strategies. We retrospectively reviewed all children less than 15 years, 76 in total, who were injured by a vehicle in a driveway within Auckland between January 1998 and October 2001. Patient demographics and risk factors were identified by clinical note review, contacting the parents, and inspecting the driveways involved. These injuries occur most commonly in children less than 4 years old (86%), usually boys (58%), who are reversed over by a relative (68%) at the home driveway (71%). There were six deaths within the study period. Head and thoracic injuries predominated and were typically associated with lower limb injuries. Maori and Pacific Island children represented 74% of all the cases. Nineteen drivers saw the child immediately prior to reversal in a presumed safe position. None of the driveways had any fencing to separate the driveway from rest of the property. A combination of targeted public health messages to increase awareness, safer driveway design and the fencing of domestic rental properties will prevent these injuries.


Basin of attraction of a bounded self-organized critical state.
The robustness of the self-organized critical (SOC) state observed in the motion of an annular plate rotating over a granular medium is studied in this paper. In particular, we investigate the effect of parameters to which the emergent SOC state may be sensitive, including the initialization scheme, driving velocity, and confining pressure. The results indicate that the critical state is not a universal attractor, but has a finite basin of attraction. Furthermore, this state is only one of the three observed, which compare well with subcritical, critical, and supercritical states. The results call into question the precise definition of the term "self-organized criticality," an issue we address.


Potassium availability triggers Mycobacterium tuberculosis transition to, and resuscitation from, non-culturable (dormant) states.
Dormancy in non-sporulating bacteria is an interesting and underexplored phenomenon with significant medical implications. In particular, latent tuberculosis may result from the maintenance of Mycobacterium tuberculosis bacilli in non-replicating states in infected individuals. Uniquely, growth of M. tuberculosis in aerobic conditions in potassium-deficient media resulted in the generation of bacilli that were non-culturable (NC) on solid media but detectable in liquid media. These bacilli were morphologically distinct and tolerant to cell-wall-targeting antimicrobials. Bacterial counts on solid media quickly recovered after washing and incubating bacilli in fresh resuscitation media containing potassium. This resuscitation of growth occurred too quickly to be attributed to M. tuberculosis replication. Transcriptomic and proteomic profiling through adaptation to, and resuscitation from, this NC state revealed a switch to anaerobic respiration and a shift to lipid and amino acid metabolism. High concordance with mRNA signatures derived from M. tuberculosis infection models suggests that analogous NC mycobacterial phenotypes may exist during disease and may represent unrecognized populations in vivo. Resuscitation of NC bacilli in potassium-sufficient media was characterized by time-dependent activation of metabolic pathways in a programmed series of processes that probably transit bacilli through challenging microenvironments during infection.


Acute disseminated encephalomyelitis in middle-aged or elderly patients.
Acute disseminated encephalomyelitis (ADEM) in middle-aged or elderly adults is rarely reported. We present here three ADEM patients of these age groups, who manifested behavioral changes, mutism or psychosis. Single clinical episodes, widespread encephalopathic disturbances and magnetic resonance imaging (MRI) findings favored the diagnosis of ADEM. However, no obvious preceding infections could be discovered. Two of them had traveled to mainland China prior to admission to psychiatric wards. All three patients had fair-to-good recovery after steroid treatment. A review of the literature showed that clinical and neuroimage findings of ADEM in the elderly group did not differ from those in the younger group. However, ADEM has rarely been reported in older age groups, probably due to: (1) differences between the elderly and young people in susceptibility or immune response to infectious agents, and (2) lack of a sensitive tool to examine patients prior to the wide-spread use of MRI. We suggest ADEM as one of the possible etiologies of acute or subacute onset of psychosis in adult patients, especially in those with a history of traveling.


Immunogenicity of two peptide determinants in the cytolytic T-cell response to flavivirus infection: inverse correlation between peptide affinity for MHC class I and T-cell precursor frequency.
We used the CD8+ cytotoxic T (Tc) cell immune response against the flavivirus, Murray Valley encephalitis virus (MVE), restricted by the H-2Kk major histocompatibility complex (MHC) class I molecule, to investigate immunodominance. Split-clone limiting dilution analysis revealed almost exclusive recognition of two peptides, MVE1785 and MVE1971, derived from the viral NS3 protein. The precursor frequency of MVE-reactive Tc cells was determined by limiting dilution analysis for cytotoxic function and intracellular staining for interferon-gamma; the latter gave a 100-fold higher estimate of MVE-reactive Tc cell precursors. MHC class I cell surface stabilization assays revealed that affinity for H-2Kk as well as halflives of the peptide-H-2Kk-complexes were markedly different for the two peptides. However, a kinetic study of antigen presentation showed that both peptides are presented for recognition by Tc cells with a comparable kinetics during the latent period of virus infection. Nevertheless, the lower affinity peptide MVE1785 elicited roughly twofold more Tc cell clones than the high-affinity peptide MVE1971. While the cytolytic activity against both determinants was similar after in vitro restimulation at the peak of the primary response, the smaller pool of memory anti-MVE1971 Tc cells correlated with an impaired memory response against that determinant, suggesting that the available T-cell repertoire is a major factor influencing the establishment of T-cell memory.


A Novel Cost-Effective Simulation Model for Continuous Curvilinear Capsulorhexis.
We describe and validate a low-cost simulation model for practicing anterior lens capsule continuous curvilinear capsulorhexis (CCC). A simulation model for CCC was developed from widely available low-cost materials. Ophthalmologists attending the annual scientific meeting of the Research Institute of Ophthalmology, Giza, Egypt, were asked to perform a five CCC model task and then anonymously answer a questionnaire that assessed the realism and training utility of the model using a five-point Likert scale (1 = unacceptable, 2 = poor, 3 = acceptable, 4 = favorable and 5 = excellent). Twenty-seven ophthalmologists completed the task and the anonymous questionnaire. Overall, participants felt that the model simulated CCC step in cataract surgery well (mean: 3.5) and was comparable to other kinds of CCC simulation models (mean: 3.3). The model scored highly for its overall educational value (mean: 4.00) and for enlarging a small CCC (mean:3.7), while the feasibility of this model in practicing the management of a runaway leading edge of CCC scored 2.9. This model may provide an alternative method for training for CCC and other anterior lens capsule-related maneuvers. This option may be particularly helpful for residency training programs with limited access to virtual reality simulators or commercially available synthetic eye models.


Phytoplankton growth and PSII efficiency sensitivity to a glyphosate-based herbicide (Factor 540®).
The use of glyphosate-based herbicides in agriculture has increased steadily since the mid 90's and there is now evidence of glyphosate leaching and contamination of aquatic ecosystems. The aim of this study was to evaluate the effects of a glyphosate-based herbicide (Factor 540®) on growth and photosynthetic capacity of algae and cyanobacteria. Six algal and three cyanobacterial species/strains, of three different taxonomic groups, were exposed to five glyphosate concentrations (10, 50, 100, 500 and 1000μgl-1) during 48h. All species have significant growth inhibition at concentrations varying between 50 and 500μgl-1. The photosynthetic response, after glyphosate exposure, varied among species, but a general pattern has emerged. There was an increase in the amount of photons absorbed (ABS/RC), in dissipated (DIO/RC) and trapped (TRO/RC) energy in the photosystem II reaction centers, along with a decreased of the maximum photosystem II quantum yield (FV/FM) and electron transport per reaction center (ETO/RC). The EC50 and LOEC values for growth and photosynthesis were calculated and established that growth was the most affected parameter by glyphosate-based herbicide, while parameter TRO/RC was the least affected. All species showed reduced growth at glyphosate concentrations lower than the Canadian standard for the protection of aquatic life, set at 800μgl-1 or the American aquatic life benchmark for acute toxicity in non vascular plants of 12 100μgl-1 questioning the validity of these thresholds in assessing the risks related to the presence of glyphosate and glyphosate-based herbicides in aquatic systems.


Machined immersion grating with theoretically predicted diffraction efficiency.
An immersion grating composed of a transmissive material with a high refractive index (n>2) is a powerful device for high-resolution spectroscopy in the infrared region. Although the original idea is attributed to Fraunhofer about 200 years ago, an immersion grating with high diffraction efficiency has never been realized due to the difficulty in processing infrared crystals that are mostly brittle. While anisotropic etching is one successful method for fabricating a fine groove pattern on Si crystal, machining is necessary for realizing the ideal groove shape on any kind of infrared crystal. In this paper, we report the realization of the first, to the best of our knowledge, machined immersion grating made of single-crystal CdZnTe with a high diffraction efficiency that is almost identical to that theoretically predicted by rigorous coupled-wave analysis.


Urban Latino Families' Food Built Environment and Young Children's Produce Consumption.
This study explored the association between objective and subjective ratings of the food environment and child produce consumption for Latino preschoolers at-risk for obesity. Parental surveys (N = 115) assessed perceptions of food availability, affordability, and acceptability. Comparable factors were objectively rated by a trained observer, using the Nutrition Environment Measures Survey for Stores (NEMS-S), in commonly frequented grocery stores cited by participants. There were no significant correlations between objective and subjective measures of food availability, affordability, and acceptability. Greater household income was associated with higher participant perceptions of food acceptability (r = .33, p = .003) and affordability (r = .22, p = .04). Participant-perceived affordability of food was correlated with more frequent child fruit and vegetable consumption (r = .21, p = .03). These findings support that parental subjective ratings of the food environment affects their child's eating behaviors more than objective ratings.


Novel patterns of ectopic cell plate growth and lipid body distribution in the Arabidopsis gemini pollen1 mutant.
The nature of aberrant gametophytic cell divisions and altered pollen cell fate in the gemini pollen1 (gem1) mutant was investigated through ultrastructural analysis. The earliest noticeable defect in gem1 was the appearance of extended membrane profiles at the early bicellular stage. These were replaced by ectopic internal walls, which divided the cytoplasm into twin or multiple cell compartments. Complete or partial internal walls were callosic with highly complex profiles, indicating failed guidance or deregulated cell plate growth. Extended membrane profiles and delayed callose synthesis at division sites further suggested a novel pattern of cell plate assembly in gem1. Multiple cell compartments in gem1 adopted vegetative cell fate with regard to lipid body distribution. In the wild type, lipid bodies appear specifically in the vegetative cell, whereas in gem1, lipid bodies accumulated in all cytoplasmic compartments. Our results support the hypothesis that altered pollen cell fate in gem1 results from abnormal inheritance of cell fate determinants as a result of disturbed cytokinesis.


AP-3 vesicle uncoating occurs after HOPS-dependent vacuole tethering.
Heterotetrameric adapter (AP) complexes cooperate with the small GTPase Arf1 or lipids in cargo selection, vesicle formation, and budding at endomembranes in eukaryotic cells. While most AP complexes also require clathrin as the outer vesicle shell, formation of AP-3-coated vesicles involved in Golgi-to-vacuole transport in yeast has been postulated to depend on Vps41, a subunit of the vacuolar HOPS tethering complex. HOPS has also been identified as the tether of AP-3 vesicles on vacuoles. To unravel this conundrum of a dual Vps41 function, we anchored Vps41 stably to the mitochondrial outer membrane. By monitoring AP-3 recruitment, we now show that Vps41 can tether AP-3 vesicles to mitochondria, yet AP-3 vesicles can form in the absence of Vps41 or clathrin. By proximity labeling and mass spectrometry, we identify the Arf1 GTPase-activating protein (GAP) Age2 at the AP-3 coat and show that tethering, but not fusion at the vacuole can occur without complete uncoating. We conclude that AP-3 vesicles retain their coat after budding and that their complete uncoating occurs only after tethering at the vacuole.


[Evaluation of pancreatic cancers using thallium-201 single photon emission computed tomography].
Radionuclide study has not been frequently applied to pancreatic cancers because of the absence of suitable radiopharmaceuticals for their positive depiction. We evaluated thallium-201 chloride (201T1) SPECT for the investigation of pancreatic cancers. The subjects included 24 patients with pancreatic cancer, seven with benign disorders and 10 controls. Each patient fasted prior to the examination for more than 12 hr, and 201T1 SPECT was obtained 10 min after the injection of 148-222 MBq of 201T1. When the boundary of tumor uptake of 201T1 was unclear because of the adjacent physiological liver activity, subtracted SPECT using 99mTc-phytate was performed to clarify it. 201T1 did not accumulate in the pancreas of the controls. In contrast, of the 24 pancreatic cancers, 21 demonstrated positive uptake, for a sensitivity rate of 87.5%, and the mean tumor/liver ratio was 0.76 +/- 0.16 (range, 0.58-1.28). Abnormal uptake was also noted in three of the seven benign disorders, but with a comparatively lower lesion/liver ratio (range, 0.35-0.51). 201T1 activity per mg tissue in the resected specimens of two patients with pancreatic cancer revealed higher activity in the tumor than in normal parenchyma. 201T1 uptake in the five conservatively treated pancreatic cancers showed alteration similar to the serum level of tumor markers. These results suggest that 201T1 SPECT may have clinical potential for investigating pancreatic cancers as well as for the monitoring of treatment effect.


A Systematic Review of Clinical Validated and Potential miRNA Markers Related to the Efficacy of Fluoropyrimidine Drugs.
Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.


Analytic Device Model of Organic Field-Effect Transistors with Doped Channels.
Doping has been shown to not only provide additional degrees of freedom in the design of organic field-effect transistors (OFETs) but to increase their performance and stability as well. An analytical model based on the assumption of a square doping profile inside the channel is presented here that describes the effect of doping on the transfer characteristic of OFETs. The model is validated experimentally by a series of OFETs with varying doping conditions. The precise doping profile in the transistor channel is determined by fitting the capacitance/voltage response of doped metal-insulator-semiconductor (MIS) junctions using an AC small-signal drift-diffusion simulation. It is shown that the real doping profile deviates from the simplifying assumptions of the analytical model, i.e., it is found that the effective doping concentration at the dielectric/semiconductor interface is reduced. However, it is shown that the analytical model is not sensitive to this deviation as only the total density charges per unit area determine the changes in the transistor behavior. Overall, the presented theory provides new design rules that can be used to guide the development of doped OFETs with high performance.


Synchronization of chaos due to linear response in optically driven semiconductor lasers.
This paper presents physical aspects on chaos synchronization in semiconductor lasers (SLs) by studying synchronization from a fundamental standpoint of driven damped oscillators. We investigate the simple configuration, a chaotic master SL with optical feedback and a solitary slave SL. The point we emphasize is that the slave laser is regarded as a damped oscillator with relaxation oscillation. Linear stability analysis demonstrates that strong injection can enhance the damping of the slave SL. Consequently, the slave SL can have broad and nearly flat spectral characteristics in its driven response, which is sufficient for covering the broadband chaotic driving signal from the master SL. Numerical simulations verify that the slave SL subject to such strong injection synchronizes well with the chaotic driving signal. We consider that the synchronization phenomenon results from a quasilinear driven response of the slave SL with the remarkable spectral characteristics. Moreover, we discuss this type of chaos synchronization in comparison to anticipating-chaos synchronization occurring in our case from conventional complete synchronization theories, and clarify the different physical aspects of the chaos synchronization scheme. We also show that our analysis agrees well with the earlier experiments that could not have been explained by complete synchronization theory.


Pluripotent Stem Cells for Cardiac Regeneration - Current Status, Challenges, and Future Perspectives.
Loss of myocardium permanently impairs cardiac function because the adult mammalian heart has limited regenerative capacity. Strategies to regenerate injured heart tissue include the transplantation of multiple types of stem cells. Among them, pluripotent stem cells (PSCs) are a promising option because of their unlimited self-renewal and unequivocal cardiomyogenic ability. To date, advances in stem cell biology allow generation of relatively homogeneous human PSC-derived cardiomyocytes (CMs). In this regard, preclinical studies of PSC-CM transplantation in rodents and larger animal models have provided convincing proof-of-concept results, triggering clinical studies in multiple countries. However, a few important uncertainties are yet to be addressed, warranting further investigation before clinical implementation of this novel therapy. An overview of the potential of stem cell therapy to provide new CMs for cardiac regeneration is presented.


Evaluation of a recombinant Trypanosoma cruzi mucin-like antigen for serodiagnosis of Chagas' disease.
Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and is one of the most important endemic problems in Latin America. Lately, it has also become a health concern in the United States and Europe. Currently, a diagnosis of Chagas' disease and the screening of blood supplies for antiparasite antibodies are achieved by conventional serological tests that show substantial variation in the reproducibility and reliability of their results. In addition, the specificity of these assays is curtailed by antigenic cross-reactivity with sera from patients affected by other endemic diseases, such as leishmaniasis. Here we used a highly sensitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to evaluate a recombinant protein core of a mucin-like molecule (termed trypomastigote small surface antigen [TSSA]) for the detection of specific serum antibodies in a broad panel of human sera. The same samples were evaluated by CL-ELISA using as the antigen either a mixture of native T. cruzi trypomastigote mucins or an epimastigote extract and, for further comparison, by conventional serologic tests, such as an indirect hemagglutination assay and indirect immunofluorescence assay. TSSA showed ∼87% sensitivity among the seropositive Chagasic panel, a value which was increased up to >98% when only parasitologically positive samples were considered. More importantly, TSSA showed a significant increase in specificity (97.4%) compared to those of currently used assays, which averaged 80 to 90%. Overall, our data demonstrate that recombinant TSSA may be a useful antigen for the immunodiagnosis of Chagas' disease.


An overview of the gulf coast aerosol research and characterization study: the Houston fine particulate matter supersite.
The Gulf Coast Aerosol Research and Characterization Study ([GC-ARCH], also known as the Houston Fine Particulate Matter [PM] Supersite) examined the spatial and temporal variability in fine PM source contributions and composition and the physical and chemical processes that govern PM formation and transformation in southeastern Texas. This was accomplished through the analysis of data collected in a 16-month field sampling program (August 2000 through November 2001). Three core sites and approximately 15 peripheral sites, jointly operated by the study team and the Texas Commission on Environmental Quality (TCEQ), were used. Key scientific findings related to spatial and temporal variability in fine PM concentrations, sizes and composition of the fine PM, the strength of primary emission sources and causes of secondary fine PM formation are reported.


[Analyzing the evolution of a Pharmacy Department using a relative value unit system].
This study proposes the use of relative value units (RVU) as a clinical management tool to evaluate departmental services. To measure productivity from 2000 to 2002 by estimating RVU. To determine RVU cost in constant Euros and evaluate system efficiency during this period of time. Retrospective, observational study of a pharmacy department s production. RVU assigned to each activity have been obtained from a standardized document drawn up by the Sociedad Española de Farmacia Hospitalaria. Cost of each RVU was determined based on total cost assigned to the pharmacy department and the total number of RVUs produced. Drug dispensation activities account for 76% of the total production, followed by elaboration activities (21%). Productivity in our department has increased 46.48% in this period of time, while efficiency has increased by 23.8%.


[Use of Statizol film-forming glue for treating gastric and duodenal ulcers].
Patients with chronic gastroduodenal ulcers (210) and gastric ulcers (256) were treated in the out-patient clinic. The ulcerous defect of the mucous membrane was covered by the aerosolic film-making glue "Statizol" through a fibroendoscope (about 10 applications of the drug). The method was used in 110 patients after polypectomy in addition to the routine therapeutic treatment given to all the patients. The application of the film-making glue "Statizol" in the complex therapy of peptic ulcers was shown to shorten the period of healing the ulcerous defects, to give less amount of recurrent ulcer diseases (not more than 14.5%) and to be a prophylactic measure against bleedings after polypectomy.


Addressing Implementation Challenges to Digital Care Delivery for Adults With Multiple Chronic Conditions: Stakeholder Feedback in a Randomized Controlled Trial.
Digital tools accessed via smartphones can promote chronic condition management, reduce disparities in health care and hospital readmissions, and improve quality of life. However, whether digital care strategies can be implemented successfully on a large scale with traditionally underserved populations remains uncertain. As part of a randomized trial comparing care delivery strategies for Medicaid and Medicare-Medicaid beneficiaries with multiple chronic conditions, our stakeholders identified implementation challenges, and we developed stakeholder-driven adaptions to improve a digitally delivered care management strategy (high-tech care). We used 4 mechanisms (study support log, Patient Partners Work Group log, case interview log, and implementation meeting minutes) to capture stakeholder feedback about technology-related challenges and solutions from 9 patient partners, 129 participants, and 32 care managers and used these data to develop and implement solutions. To assess the impact, we analyzed high-tech care exit surveys and intervention engagement outcomes (video visits and condition-specific text message check-ins sent at varying intervals) before and after each solution was implemented. Challenges centered around 2 themes: difficulty using both smartphones and high-tech care components and difficulty using high-tech care components due to connectivity issues. To respond to the first theme's challenges, we devised 3 solutions: tech visits (eg, in-person technology support visits), tech packet (eg, participant-facing technology user guide), and tailored condition-specific text message check-ins. During the first 20 months of implementation, 73 participants received at least one tech visit. We observed a 15% increase in video call completion for participants with data before and after the tech visit (n=25) and a 7% increase in check-in completion for participants with data before and after the tech visit (n=59). Of the 379 participants given a tech packet, 179 completed care during this timeframe and were eligible for an exit survey. Of the survey respondents, 76% (73/96) found the tech packet helpful and 64% (62/96) actively used it during care. To support condition-specific text message check-in completion, we allowed for adaption of day and/or time of the text message with 31 participants changing the time they received check-ins and change in standard biometric settings with 13 physicians requesting personalized settings for participants. To respond to the second theme's challenges, tech visits or phone calls were made to demonstrate how to use a smartphone to connect or disconnect from the internet, to schedule video calls, or for condition-specific text message check-ins in a location with broadband/internet. Having structured stakeholder feedback mechanisms is key to identify challenges and solutions to digital care engagement. Creating flexible and scalable solutions to technology-related challenges will increase equity in accessing digital care and support more effective engagement of chronically ill populations in the use of these digital care tools. ClinicalTrials.gov NCT03451630; https://clinicaltrials.gov/ct2/show/NCT03451630.


Group and Organizational Safety Norms Set the Stage for Good Post-Fall Huddles.
We explored group and organizational safety norms as antecedents to meeting leader behaviors and achievement of desired outcomes in a special after-action review case-a post-fall huddle. A longitudinal survey design was used to investigate the relationship between organizational/group safety norms, huddle leader behavior, and huddle meeting effectiveness. The sample included healthcare workers in critical access hospitals (N = 206) who completed a baseline safety norm assessment and an assessment of post-fall huddle experiences three to six months later. Findings indicate that organizational and group safety norms relate to perceived huddle meeting effectiveness through appropriate huddle leader behavior in a partial mediated framework. In contrast to previous research showing after-action reviews predicting group and organizational safety norms, the longitudinal study presented here suggests that group and organizational safety norms set the stage for the enactment of post-fall huddles in an effective manner.


Intracoronary stent implantation in Jamaica. The initial experience.
Intracoronary stent implantation resulted in the complete or near complete dilatation of high grade occlusions of the left anterior descending coronary arteries in the four patients in whom it was undertaken. Intracoronary stent implantation is a useful adjunct to Percutaneous Transluminal Angioplasty (PTCA) and is applicable in selected patients with symptomatic ischaemic heart disease in a developing country with limited health resources like Jamaica. This is so since financial data presented here document the significant savings this technique (when appropriately utilised) could realise compared to the use of balloon angioplasty alone.


SmokeHaz: Systematic Reviews and Meta-analyses of the Effects of Smoking on Respiratory Health.
Smoking tobacco increases the risk of respiratory disease in adults and children, but communicating the magnitude of these effects in a scientific manner that is accessible and usable by the public and policymakers presents a challenge. We have therefore summarized scientific data on the impact of smoking on respiratory diseases to provide the content for a unique resource, SmokeHaz. We conducted systematic reviews and meta-analyses of longitudinal studies (published to 2013) identified from electronic databases, gray literature, and experts. Random effect meta-analyses were used to pool the findings. We included 216 articles. Among adult smokers, we confirmed substantially increased risks of lung cancer (risk ratio (RR), 10.92; 95% CI, 8.28-14.40; 34 studies), COPD (RR, 4.01; 95% CI, 3.18-5.05; 22 studies), and asthma (RR, 1.61; 95% CI, 1.07-2.42; eight studies). Exposure to passive smoke significantly increased the risk of lung cancer in adult nonsmokers and increased the risks of asthma, wheeze, lower respiratory infections, and reduced lung function in children. Smoking significantly increased the risk of sleep apnea and asthma exacerbations in adult and pregnant populations, and active and passive smoking increased the risk of tuberculosis. These findings have been translated into easily digestible content and published on the SmokeHaz website.


Trends in Medication Use Over 11 Years in Patients Presenting to a Rural and Remote Memory Clinic.
Anticholinergic and sedating medications are generally contraindicated in those with cognitive decline. We examined trends in medication use by patients at initial presentation to a rural and remote memory clinic (RRMC) between March 2004 and June 2015 to determine whether patterns of medication use have changed. The first 444 patients seen at the RRMC between 2004 and 2015 were included in this analysis. Medication lists were collected at the patient's initial visit, and it was noted whether patients were taking anticholinergic or potentially sedating drugs. Statistical analysis (Spearman's correlation) was conducted to examine trends in medication use over time. Patients were on a mean of 5.18 medications (standard deviation, 3.46). Ninety-one patients (20.5%) were taking at least one anticholinergic medication. There was a decline (25.0% in 2004 to 12.5% in 2014) in percentage of patients presenting with anticholinergic medications over the 11 years of this study (Spearman's correlation coefficient =-0.64, p=0.035). The prevalence of drugs acting on the central nervous system trended toward an increase, but this was not statistically significant. Sixty-three patients (14.2%) presented to the RRMC already taking a cholinesterase inhibitor. The most encouraging statistic to come from this study is a decline in anticholinergic medication use in this rural population. Prescribers must be properly informed to ensure that the number of medications per patient does not continue to rise, that medications are used only as necessary, and that potentially deleterious medications are avoided.


[Immunoregulatory effects of pertussis protein on allergic asthma in mouse].
To investigate the immunoregulatory effects of pertussis protein on airway inflammatory, IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids(BALF) and airway hyperresponsiveness (AHR) in the sensitized mice. The sensitized mice were reexposed to ovalbumin and the airway response to methacholine injection was monitored. Inflammatory cells and cytokines IFN-gamma/IL-4 ratio in BALF were measured. Lung tissue specimens were collected for histological examination. Intramuscular injection or intranasal instillation of pertussis protein inhibited changes in lung resistance and lung dynamic compliance, upregulated IFN-gamma/IL-4 ratio and decreased eosinophil accumulation in a dose-dependent manner. Pathological examination showed that goblet cell hyperplasia and inflammatory cells infiltration in lung tissue were suppressed by pertussis protein. Pertussis protein inhibits the inflammation and regulates the function of lungs in asthma mice, suggesting its potential application in treatment of asthma.


Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations.
The receptor tyrosine kinase Flt3 is expressed and functionally important in early myeloid progenitor cells and in the majority of acute myeloid leukemia (AML) blasts. Internal tandem duplications (ITDs) in the juxtamembrane domain of the receptor occur in 25% of AML cases. Previously, we have shown that these mutations activate the receptor and induce leukemic transformation. In this study, we performed genome-wide parallel expression analyses of 32Dcl3 cells stably transfected with either wild-type or 3 different ITD isoforms of Flt3. Comparison of microarray expression analyses revealed that 767 of 6586 genes differed in expression between FLT3-WT- and FLT3-ITD-expressing cell lines. The target genes of mutationally activated Flt3 resembled more closely those of the interleukin 3 (IL-3) receptor than those of ligand-activated Flt3. The serine-threonine kinase Pim-2 was up-regulated on the mRNA and the protein level in Flt3-ITD-expressing cells. Further experiments indicated that Pim-2 function was important for clonal growth of 32D cells. Several genes repressed by the mutations were found to be involved in myeloid gene regulation. Pu.1 and C/EBPalpha, both induced by ligand-activation of wild-type Flt3, were suppressed in their expression and function by the Flt3 mutations. In conclusion, internal tandem duplication mutations of Flt3 activate transcriptional programs that partially mimic IL-3 activity. Interestingly, other parts of the transcriptional program involve novel, IL-3-independent pathways that antagonize differentiation-inducing effects of wild-type Flt3. The identification of the transcriptional program induced by ITD mutations should ease the development of specific therapies.


Multilayer Tribofilm: An Unique Structure to Strengthen Interface Tribological Behaviors.
Tribofilm configuration under the boundary lubrication region is an essential concern to gain insight into the tribological enhancement of the two-dimensional (2D) nano materials toward base oils. In this work, several alkyl carboxylic acids modified 2D triazine-based covalent organic frameworks (ATC) nano platelets were fabricated and served as lubrication additives. When carbon atoms add up to 16, the best lubricating performance is exhibited at an additive concentration of 0.05 wt % and the friction coefficient and wear volume are, respectively, reduced by 56.0% and 89.6% as compared to those of pure PAO 10 base oil. The analysis of the focused ion beam-transmission electron microscope (FIB-TEM) on the worn surface reveals that an alternately multilayer tribofilm consisting of 2D platelet additives and oxides and/or metallic soap salts is formed on the frictional interface of steel substrate, with a well-ordered arrangement along the sliding direction, which dominates the contributions of the excellent lubrication.


Case study. Using case-mix information for budgeting.
The following case study illustrates the use of case-mix information in the budget process. Using case-mix data from a management information system such as PBCS, hospital managers can obtain the assistance of those who influence the delivery of care to develop a sound statistical budget upon which to allocate available resources. Such a budget should be based on honest goals which can be used to evaluate actual accomplishments.


[Regulation of smooth muscles of the vascular wall in the rabbit pulmonary artery].
The cholinergic, histaminergic and adrenergic features of regulation of the small muscles contractile activity in a vascular wall of a pulmonary artery in rabbits and involvement of an endothelium in these processes, were investigated. The cholinergic release phenomenon of small muscles of the rabbit pulmonary artery has a two-component character of dose dependence. The low-threshold components of Pilocarpinum relaxing effect has an endothelium-dependent nature. The important feature of histaminergic regulation of contractile activity of segments involves a direct contractile effect of histamine that is not inherent. The endothelium renders a suppressing effect on histaminergic contraction of small muscles of the rabbit pulmonary artery. A basic feature of adrenergic regulation of the pulmonary artery involves registered-beta-adrenergic contractile effects in small muscles of a vascular wall. The activation of the cAMP-dependent signal system in small muscles of a pulmonary artery is capable of rendering a contractile effect. The detected features of a regulation in the small circle can have an essential clinical-physiological value.


R.E.N.A.L. Nephrometry Score Predicts Non-neoplastic Parenchymal Volume Removed During Robotic Partial Nephrectomy.
To assess the association between the R.E.N.A.L. Nephrometry score, the amount of non-neoplastic parenchymal volume (NNPV) removed, and the renal function decline in patients undergoing robotic partial nephrectomy (RPN). The Multi-institutional Mount Sinai Kidney Cancer Database was used to identify 1235 patients who underwent RPN between January 2008 and February 2016, of whom 366 had complete data, including NNPV removed. Mann-Whitney U tests and univariable linear regression models were used to assess the relationships between R.E.N.A.L. Nephrometry score, warm ischemia time (WIT), and NNPV removed. Univariable and multivariable regression models were then used to assess the independent relationships of each of these variables with percent change in estimated glomerular filtration rates (eGFR) and acute kidney injury (AKI) within the first 30 postoperative days in addition to percent change in eGFR and progression to chronic kidney disease at a median follow-up of 6.9 months. Increasing R.E.N.A.L. Nephrometry score was shown to be a predictor of WIT (β = 0.92, p < 0.001) and of NNPV removed (β = 6.21, p < 0.001) in univariable analyses. In multivariable analysis, postoperative reduction in eGFR within the first 30 days of surgery was associated with both R.E.N.A.L. Nephrometry score (β = -2.02, p < 0.001) and NNPV removed (β = -5.19, p = 0.015). R.E.N.A.L. Nephrometry score (OR = 1.21, p = 0.013) and NNPV removed (OR = 1.90, p = 0.013) were also associated with an increased likelihood of AKI within the first 30 days. No significant association in this cohort was found between R.E.N.A.L. Nephrometry score, NNPV removed, or WIT and renal function decline at 6.9 months. The preoperative R.E.N.A.L. Nephrometry score can be used to predict postoperative pathologically determined healthy renal volume loss or NNPV removed. Removal of not just the tumor but also the healthy surrounding parenchyma is important in determining renal function decline. As our understanding of the importance of renal volume loss grows, NNPV removed gains increasing utility as an easily determinable postoperative variable.


Lupus Panniculitis as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report.
Lupus erythematosus panniculitis (LEP) is a variant of chronic cutaneous lupus erythematosus (CCLE). Reported cases of LEP lesions before the diagnosis of systemic lupus erythematosus (SLE) were very rare; only 9 cases have been reported, to the best of our knowledge. We now describe the case of a 19-year-old male patient, with an overall review of the English literature. In the earliest stage of the present case, nodules and ulcers involved his left leg and face, with no other accompanied symptoms. The skin lesions disappeared after treatment with methylprednisolone, 16 mg/d for 1 month. Seven months after discontinuing methylprednisolone, the cutaneous nodules and ulcers on his back recurred and were accompanied by fever, hair loss, and polyarthritis. Blood tests revealed leucopenia, positive antinuclear antibody and Smith antibody, and proteinuria. Histopathological findings were most consistent with LEP. This was followed sequentially by the diagnosis of SLE. The patient improved again after treatment with methylprednisolone and cyclophosphamide.Patients with LEP should have regular follow-ups because the development of SLE is possible. Early diagnosis and proper treatment is pivotal to improve the prognosis of such patients.


Role of thoracoscopy (VATS) in pleural and pulmonary pathology.
Although thoracoscopy is not a new procedure, there was a real revival after the introduction of laparoscopy. VATS (video-assisted thoracic surgery) has potential advantages of reduced pain due to smaller incisions and a shorter hospital stay. Main disadvantages are expensive equipment and a probably less adequate operation, especially for therapy of malignant disorders where long-term results are not known. VATS is very useful for investigation of pleural effusion and malignancy. Spontaneous pneumothorax is a very good indication for thoracoscopic treatment, as well as lung biopsy and diagnostic resection of lung metastases. Therapeutic metastasectomy, however, should not be performed by VATS. Regarding bronchogenic carcinoma, VATS is indicated for staging of lung cancer, facilitating sampling of mediastinal and hilar lymph nodes, investigation of pleural effusion, possible pleural dissemination and suspicion of intrapulmonary metastases. Wedge excision of solitary pulmonary nodules by VATS readily reveals the exact diagnosis, but its role in therapy of lung cancer is very limited at the present time.


Dilution rate increases production of plant cell-wall degrading enzymes by anaerobic fungi in continuous-flow culture.
The gut anaerobic fungi,Neocallimastix hurleyensis and aOrpinomyces sp., were grown in 100 mL batch and continuous-flow cultures on wheat straw at a concentration of 80 g dry matter/L of culture liquid. In batch cultures,N. hurleyensis and Orpinomyces sp. degraded only ca. 9% and 5% of the wheat straw, respectively. In continuous-flow cultures, however, the two fungi degraded 52-56% of the apparent dry matter of wheat straw. Both fungi were able to produce greater quantities (up to x 30) of cell-wall degrading enzymes (CMCase, xylanase, beta-glucosidase and beta-xylosidase) in continuous-flow cultures than in the corresponding batch cultures. Increasing the dilution rate in continuous-flow culture resulted in the production of increased enzyme activity for all the measured cell-wall degrading enzymes, with proportional relationships between dilution rate and the cumulative activities of beta-glucosidase and beta-xylosidase. Dilution rates, however, had no consistent effect on the cumulative production of the fermentation end-products, acetate, formate, D- and L-lactate from both fungi. In addition to acetate and formate,N. hurleyens is produced D- and L-lactate in both batch and continuous-flow cultures, whereas only trace amounts of L-lactate were detected in the Orpinomyces sp. cultures.


Where have all the young girls gone or where do all the men come from? Change and lack of change in demographic characteristics of the norwegian heroin user population.
A rough estimate indicates that women amount to one third of the heroin user population in Norway. However, among the youngest users females account and have accounted for a larger proportion. Given this greater representation of females in the younger age groups one would expect that the gender difference in the general population of users would be reduced over time due to a cohort effect. However, the ratio of male to female users has remained stable. The prevailing explanation for this stability is based on the claim that women are more likely to overcome their abuse. This paper addresses both the basis for the assumption of a missing cohort effect and examines an alternative explanation linked to the way into abuse rather than the way out. The study primarily draws upon two distinct data sources. The first body of material consists of interviews carried out in the period 1993-1997 with people attending the only needle exchange service in Oslo. The second data source consists of police records, which provide the number of persons arrested each year in the period 1984-1997 for using, possessing or selling heroin distributed by age and gender. We find that the age of injection debut has increased and that this is especially true for male users. Applying a simple quantitative model, the effect a change in recruitment may have on the male-to-female ratio is analysed. The results indicate that a higher debut age may have contributed to stabilizing the gender gap. The finding suggests that more research is needed on the conditions of recruitment in order to better predict the future population demographics and to avoid hasty and incorrect conclusions.


FlyAtlas 2: a new version of the Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data.
FlyAtlas 2 (www.flyatlas2.org) is part successor, part complement to the FlyAtlas database and web application for studying the expression of the genes of Drosophila melanogaster in different tissues of adults and larvae. Although generated in the same lab with the same fly line raised on the same diet as FlyAtlas, the FlyAtlas2 resource employs a completely new set of expression data based on RNA-Seq, rather than microarray analysis, and so it allows the user to obtain information for the expression of different transcripts of a gene. Furthermore, the data for somatic tissues are now available for both male and female adult flies, allowing studies of sexual dimorphism. Gene coverage has been extended by the inclusion of microRNAs and many of the RNA genes included in Release 6 of the Drosophila reference genome. The web interface has been modified to accommodate the extra data, but at the same time has been adapted for viewing on small mobile devices. Users also have access to the RNA-Seq reads displayed alongside the annotated Drosophila genome in the (external) UCSC browser, and are able to link out to the previous FlyAtlas resource to compare the data obtained by RNA-Seq with that obtained using microarrays.


Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder.
To describe the efficacy of inhaled loxapine for the treatment of agitation associated with schizophrenia or bipolar disorder using different examples of effect size (ES). Psychopharmacologic Drug Advisory Committee briefing documents as prepared by the product manufacturer and by the US Food and Drug Administration. Phase III clinical trials. Effect size for primary and secondary efficacy outcomes. Two similarly designed Phase III studies were completed with one conducted in patients with agitation associated with schizophrenia and one in patients with agitation associated with bipolar I disorder, manic or mixed episodes. In both studies, onset of anti-agitation effect was observed at 10 min (first time-point measured) for both the 5 mg and 10 mg doses, as evidenced by time to first statistically significant change from baseline on the Positive and Negative Syndrome Scale, Excited Component (PEC) as compared to placebo. Loxapine remained superior to placebo throughout the remainder of the study at all-time points measured. In the schizophrenia study, the ES difference from placebo on the PEC at 2 h was 0.45 for the 5 mg dose and 0.60 for the 10 mg dose (Cohen's d). ES differences for Clinical Global Impressions-Improvement (CGI-I) were similar. Prior to rounding up, the number needed to treat (NNT) for PEC response and CGI-I response vs. placebo were 4.1 and 4.6, respectively, for loxapine 5 mg and 3.2 and 3.2, respectively, for the 10 mg dose. For the outcome of requiring only one dose of study medication and no rescue medication, the NNT vs. placebo for the 5 mg dose was not statistically significant but was statistically significant for the 10 mg dose vs. placebo with a value of 7. When plotting the PEC responders over time NNT becomes more robust as time after dosing elapses, with the 10 mg dose reaching a NNT of 4 by 20 min. For the bipolar disorder study, the ES difference from placebo on the PEC at 2 h was 0.73 for the 5 mg dose and 0.94 for the 10 mg dose. ES differences for the CGI-I were somewhat higher. Prior to rounding up, NNT for response vs. placebo for PEC and CGI-I criteria were 2.9 and 2.6, respectively, for the loxapine 5 mg dose and 2.2 and 2.1, respectively, for the 10 mg dose. For the outcome of requiring only one dose of study medication and no rescue medication, the NNT vs. placebo for the 5 mg dose was 7 and for the 10 mg dose was 3. The NNT difference between 5 mg vs. 10 mg was statistically significant in favour of the 10 mg dose and had a value of 5. When plotting the PEC responders over time NNT becomes more robust as time after dosing elapses, with the 10 mg dose reaching a NNT of 3 by 20 min. Additional information regarding pulmonary safety demonstrated low rates of pulmonary adverse events among those subjects in the efficacy trials, however, in separate Phase I safety studies conducted in persons with asthma and COPD, respiratory symptoms and/or changes in flow parameters were common. Inhaled loxapine is a non-invasive treatment option for the management of agitation associated with schizophrenia or bipolar disorder. Effect sizes for inhaled loxapine vs. placebo are robust and on par with those observed with intramuscular antipsychotics and benzodiazepines. Onset of action is rapid. The magnitudes of the effect sizes were generally larger for the 10 mg dose vs. the 5 mg dose, and the overall data supports the 10 mg dose as the dominant choice. The efficacy profile of inhaled loxapine will need to be viewed within the context of its pulmonary safety profile. The advisers to the Food and Drug Administration recommended that inhaled loxapine be restricted to a single dose in 24 h and be subject to a Risk Evaluation and Mitigation Strategy programme.


Actions of neuropeptide Y on the rat adrenal cortex.
Although several studies have demonstrated the presence of neuropeptide Y (NPY) in nerves supplying the mammalian adrenal cortex, its function in this tissue remains unclear, with reports of both stimulatory and inhibitory effects on aldosterone secretion apparently depending on the tissue preparation used. In the present study the effects of NPY on rat adrenal capsular tissue were investigated. NPY significantly stimulated aldosterone secretion in a dose-dependent manner, and this effect was abolished by atenolol, a beta1-adrenergic antagonist. NPY also stimulated the release of catecholamines from intact rat adrenal capsular tissue with the same dose-dependent relationship as the stimulation of aldosterone release. These observations suggest that the actions of NPY may be mediated by the local release of catecholamines from chromaffin cells within adrenal capsular tissue, as we have previously described for vasoactive intestinal peptide. The second part of this study concerned the NPY receptor subtype mediating the actions of NPY on the adrenal cortex. It was found that peptide YY stimulated aldosterone release with a comparable potency to NPY, whereas pancreatic polypeptide (PP) was without effect. The Y1 selective NPY analog Leu31Pro34NPY had a greater effect on aldosterone release than the Y2 selective analog NPY18-36. Studies using the specific Y1 receptor antagonist BIBP 3226 showed significant attenuation of the aldosterone response to NPY, but no effect on the response to added norepinephrine. Binding studies carried out using [125I]NPY revealed the presence of a single population of NPY-binding sites with a Kd of 12.25 nmol/liter and a binding capacity of 623 fmol/mg protein. Competition studies revealed displacement of [125I]NPY specific binding by NPY, peptide YY, and Leu31Pro34NPY, but not by other peptides. Messenger RNA analysis revealed the presence of messenger RNA coding for both the Y1 receptor and the Y4 receptor, but not the other subtypes. Taken together these data suggest that the effects of NPY on the rat adrenal cortex are mediated by the Y1 receptor subtype.


Molecular property investigations of an ortho-hydroxy Schiff base type compound with the first-principle molecular dynamics approach.
The structure, proton transfer, and vibrational dynamics under ambient conditions of a selected ortho-hydroxy Schiff base type compound, 2-(N-methyl-alpha-iminoethyl)-4-chlorophenol, containing a very short intramolecular hydrogen bond, were investigated computationally in the gas phase and in the crystal by density functional theory (DFT) based first-principle molecular dynamics (FPMD). It is found that the proton is well localized on the nitrogen side of the O...H...N bridge in the crystal phase, in agreement with X-ray diffraction experiments, while a more labile proton is located most of the time on the oxygen side in a vacuum. Environmental effects on this very strong hydrogen bond thus appear crucial and lead to drastic changes of the infrared (IR) spectrum: The computed gas-phase IR spectrum shows a very broad absorption band that covers frequencies from about 1000 to 3000 cm(-1) assigned to the labile proton. In mere contrast, a much more localized absorption band around 2600-2700 cm(-1) is predicted in the crystal phase. Finally, effects of the quantization of the proton motion on the hydrogen bond structure were estimated in two ways. First, we constructed the one-dimensional (1D) potential energy surface (PES) for the proton along the O...H...N bridge in a vacuum. The 1D Schrodinger equation was then solved. Next, path integral molecular dynamics (PIMD) was performed in the solid state. Inclusion of quantum effects does not affect the observed change of the most probable tautomer, upon going from the gas phase to the crystal.


Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo.
Metastasis is the process by which tumor cells spread from their site of origin to distant sites after gaining access to the circulatory system. An understanding of the factors contributing to the metastatic potential of breast cancer cells to bone will enhance the prospect of developing new therapies that impede metastasis. In this study, we have used an in vivo selection scheme involving left cardiac ventricle injection into nude mice to identify a highly metastatic human breast cancer cell line (MDA-MET) from a less metastatic (MDA-231) parental cell line. In this model, tumor-bearing mice exhibit features similar to those associated with human metastatic bone disease such as osteolytic bone destruction. After inoculation, MDA-MET cells form devastating lesions within 4 weeks, whereas the parental cells do not, even after 10 weeks. In vitro, the MDA-MET cells have a similar growth rate to the parental MDA-231 cells yet demonstrate distinct adhesive and invasive phenotypes. MDA-MET cells show increased early adhesion to type IV collagen and are significantly more invasive through Matrigel than MDA-231 cells. Analysis of the gene expression profile in the metastatic MDA-MET versus poorly metastatic MDA-231 cells identified relatively few genes whose expression was altered >2-fold. Of particular interest was the lack of parathyroid hormone-related protein (PTHrP) mRNA expression, which was supported at the protein level by immunoradiometric assay. These data support the idea that PTHrP is not predictive of the metastasis of human breast cancer to bone. Another important difference between the two cell lines was the elevated expression by MDA-MET cells of the cytokine IL-8. Reverse transcriptase-PCR and ELISA confirmed the increased expression of IL-8 in MDA-MET cells. In addition, IL-8 mRNA expression is also elevated in a variety of human cancer cell lines with different metastatic potential in vivo. These experiments suggest that the elevated expression of IL-8 (and not PTHrP) by MDA-MET cells is a phenotypic change that may be related to their enhanced ability to metastasize to the skeleton.


Accumulation of weathered p,p'-DDTs in grafted watermelon.
The grafting of melon plants onto cucurbit rootstocks is a common commercial practice in many parts of the world. However, certain cucurbits have been shown to accumulate large quantities of weathered persistent organic pollutants from the soil, and the potential contamination of grafted produce has not been thoroughly evaluated. Large pot and field experiments were conducted to assess the effect of grafting on accumulation of weathered DDX (the sum of p,p'-DDT, p,p'-DDD, and p,p'-DDE) from soils. Intact squash (Cucurbita maxima × moschata) and watermelon (Citrullus lanatus), their homografts, and compatible heterografts were grown in pots containing soil with weathered DDX at 1480-1760 ng/g soil or under field conditions in soil at 150-300 ng/g DDX. Movement of DDX through the soil-plant system was investigated by determining contaminant levels in the bulk soil and in the xylem sap, roots, stems, leaves, and fruit of the grafted and nongrafted plants. In all plants, the highest DDX concentrations were detected in the roots, followed by decreasing amounts in the stems, leaves, and fruit. Dry weight concentrations of DDX in the roots ranged from 7900 ng/g (intact watermelon) to 30100 ng/g (heterografted watermelon) in the pot study and from 650 ng/g (intact watermelon) to 2430 ng/g (homografted squash) in the field experiment. Grafting watermelon onto squash rootstock significantly increased contaminant uptake into the melon shoot system. In the pot and field studies, the highest stem DDX content was measured in heterografted watermelon at 1220 and 244 ng/g, respectively; these values are 140 and 19 times greater than contaminant concentrations in the intact watermelon, respectively. The xylem sap DDX concentrations of pot-grown plants were greatest in the heterografted watermelon (6.10 μg/L). The DDX contents of the leaves and fruit of watermelon heterografts were 3-12 and 0.53-8.25 ng/g, respectively, indicating that although the heterografted watermelon accumulated greater pollutant levels, the resulting contamination is not likely a food safety concern.


Hemorrhagic progression of a contusion after traumatic brain injury: a review.
The magnitude of damage to cerebral tissues following head trauma is determined by the primary injury, caused by the kinetic energy delivered at the time of impact, plus numerous secondary injury responses that almost inevitably worsen the primary injury. When head trauma results in a cerebral contusion, the hemorrhagic lesion often progresses during the first several hours after impact, either expanding or developing new, non-contiguous hemorrhagic lesions, a phenomenon termed hemorrhagic progression of a contusion (HPC). Because a hemorrhagic contusion marks tissues with essentially total unrecoverable loss of function, and because blood is one of the most toxic substances to which the brain can be exposed, HPC is one of the most severe types of secondary injury encountered following traumatic brain injury (TBI). Historically, HPC has been attributed to continued bleeding of microvessels fractured at the time of primary injury. This concept has given rise to the notion that continued bleeding might be due to overt or latent coagulopathy, prompting attempts to normalize coagulation with agents such as recombinant factor VIIa. Recently, a novel mechanism was postulated to account for HPC that involves delayed, progressive microvascular failure initiated by the impact. Here we review the topic of HPC, we examine data relevant to the concept of a coagulopathy, and we detail emerging data elucidating the mechanism of progressive microvascular failure that predisposes to HPC after head trauma.


Radiological abnormalities in children born as a result of assisted conception.
Over 15,000 children are born each year as a result of the various techniques of assisted conception. In 1991, there were 2083 live births in Australia and New Zealand as a result of these techniques. Radiological abnormalities relating to the increased rate of prematurity, a probable increase in the risk of congenital malformations and a number of cases of neural crest tumours seen in these infants will be presented.


Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, parallel-group pragmatic trial in infertile women with at least one patent tube at hysterosalpingo-foam sonography (HYFOIL study).
Tubal patency testing is an essential part in the fertility workup of many subfertile women. Hysterosalpingography (HSG) has long been the test of choice in many clinics. There is evidence from a large randomised multicentre trial and from a recent meta-analysis that women who had HSG using oil soluble contrast medium (OSCM) had higher rates of ongoing pregnancy compared with women who underwent this procedure using water contrast. However, the field is moving away from HSG and nowadays hysterosalpingo-foam sonography (Hyfosy) using ultrasound guidance is considered as the first line office tubal patency test. Therefore, a large multicentre randomised clinical trial (RCT) will be initiated to evaluate if flushing the fallopian tubes with OSCM after a normal Hyfosy showing at least one patent fallopian tube will increase the live birth rate as compared with no flushing. We plan a multicentre two arm, 1:1 randomised, open-label pragmatic comparative trial in 12 Belgian centres. After informed consent, we will randomise infertile women between 18 and 40 years of age, undergoing Hyfosy as part of the fertility workup to Hyfosy with additional tubal flushing with OSCM versus Hyfosy without additional flushing. Infertility is defined as lack of conception despite 12 months of unprotected intercourse, or three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy, all three in combination with at least one patent tube on Hyfosy. Primary endpoint will be live birth with conception within 6 months after randomisation. Approval on 11 May 2021 by the Ethics Committee from ZNA Hospital Antwerp who was the central Ethics Committee for the Clinical Trial Regulation Pilot (Pilot 412) in the 12 centres. The findings from this RCT will be disseminated in peer-reviewed publications and presentations at scientific international meetings. EudraCT number: 2020-002135-30 and NCT04379973.


Interaural temporal discrimination using two sinusoidally amplitude-modulated, high-frequency tones: conditions of summation and interference.
This paper concerns sensitivity to interaural temporal delays (ITD) in the envelopes of two, sometimes simultaneously presented, sinusoidally amplitude-modulated (SAM) tones. The SAM tones were fully modulated (typically at a rate of 250 Hz) and had carrier frequencies of either 2 or 4 kHz. Of particular interest were cases in which the delay to be detected (target ITD) occurred in only one spectral region or in both. The reference ITD, to which the target ITD was added, was either 0, 300, or 600 microseconds. There were three general outcomes: (1) When both regions contained a target ITD, there was an improvement in sensitivity that was quantitatively consistent with an optimal use of independent information. This type of summation was seen even when the target ITDs were added to a pair of SAM tones with two different reference ITDs; (2) when the target ITD was restricted to the higher spectral region, sensitivity was reduced, indicating interference. Interference occurred when the two spectral regions had the same or different reference ITDs and the same or different rates of modulation; (3) sensitivity was unaffected (i.e., no interference occurred) when the target ITD was restricted to the lower spectral region of the pair of SAM tones. These results supplement the observations of Buell and Hafter [J. Acoust. Soc. Am. 90, 1894-1900 (1991)], who used low-frequency tones.


Comparative study on the responses of plasma GH to synthetic GH-releasing factor and other stimulatory and inhibitory agents in patients with acromegaly.
Ten patients with active acromegaly received synthetic human pancreatic GH releasing factor (hpGHRF-44), and the GH responses to GHRF were compared with the basal GH levels and with the GH responses to arginine, TRH, LH-RH, somatostatin, and L-dopa. There were no significant relationships between the plasma GH responses to GHRF and the results of the stimulatory and inhibitory tests mentioned above, except that the responses to GHRF showed weak positive or negative correlations with the responses to LH-RH (r = +0.56) or with the basal GH levels (r = -0.57). These results indicate that acromegalic somatotrophs would have GHRF receptors as well as several other receptors to hypothalamic hormones and to dopamine, and that there might be no distinct relationship between the somatotroph sensitivities to GHRF and to other stimulatory or inhibitory stimuli. Further studies are required regarding the weak correlations between the response to GHRF and that to LH-RH or basal GH value.


Functionally Graded Al2O3-CTZ Ceramics Fabricated by Spark Plasma Sintering.
We studied the fabrication of functionally graded Al2O3-CeO2-stabilized-ZrO2 (CTZ) ceramics by spark plasma sintering. The ceramic composite exhibits a gradual change in terms of composition and porosity in the axial direction. The composition gradient was created by layering starting powders with different Al2O3 to CTZ ratios, whereas the porosity gradient was established with a large temperature difference, which was induced by an asymmetric graphite tool configuration during sintering. SEM investigations confirmed the development of a porosity gradient from the top toward the bottom side of the Al2O3-CTZ ceramic and the relative pore volume distributed in a wide range from 0.02 to 100 µm for the samples sintered in asymmetric configuration (ASY), while for the reference samples (STD), the size of pores was limited in the nanometer scale. The microhardness test exhibited a gradual change along the axis of the ASY samples, reaching 10 GPa difference between the two opposite sides of the Al2O3-CTZ ceramics without any sign of delamination or cracks between the layers. The flexural strength of the samples for both series showed an increasing tendency with higher sintering temperatures. However, the ASY samples achieved higher strength due to their lower total porosity and the newly formed elongated CeAl11O18 particles.


[Investigations on the latent infection of herpes simplex virus-1 in the cornea].
The relapsing rate in 216 patients of recurrent herpes simplex keratitis (HSK) treated with penetrating keratoplasty was 4.2% in 6.5 years, while experimental studies showed that HSV-1 antigens in the cornea disappeared 45 days after the primary corneal infection. Among 18 cases of quiescent HSK, HSV-1 antigens were negative in the corneal tissue, which however turned positive in 6 (66.7%) of 9 cases that were cultured for reactivation, and became infectious to primary rabbit kidney cells. Tests of susceptibility revealed that rabbit keratocytes were most sensitive to infection with HSV-1 strain Mckrae. The authors opined that the cornea might be an additional site to the trigeminal ganglion to harbor HSV-1.


Quality assurance procedures during commissioning of a treatment planning system as a tool to establish new standards before migration.
Treatment planning system commissioning is one of the most important parts of the quality assurance system in a working brachytherapy department. Migration to a more sophisticated system is always a step forward for the planning team but careful verification of the workflow and obtained results is mandatory. The question is not only whether the quality and safety of the previous standards can be preserved, but also about the possibility of reaching a higher level. The general objective of this study was to compare and verify calculation algorithms implemented in the treatment planning systems Plato Brachytherapy v.14.3.7 and Oncentra Masterplan (Brachy) V.3.1 SP 3. In order to revise the optimization algorithms implemented in the compared treatment systems, a series of 20 interstitial breast cancer applications were used. Treatment plans were optimized using geometric optimization with distance option. The parameters V, D90, D100, V100, V150, V200 and DNR were gained for target volume. On the basis of the value of Student's t-test parameters (α = 0.05) plans prepared using optimization algorithms implemented in the two treatment planning systems were compared. For the treatment plans prepared using Oncentra Masterplan a lower value of DNR (p = 0.018) was obtained. Uniformity of the dose distribution does not collide with comparable D90 values for both treatment planning systems (p = 0.109). Dose throughout the target volume (D100) was also proved to be higher in plans prepared using Oncentra Masterplan (p = 0.012). For interstitial applications Oncentra Masterplan planning system enables one to prepare a more homogeneous dose distribution but also a higher dose in the whole treated volume, while the volume covered with the therapeutic dose does not statistically differ.


Efficient unrestricted identity-based aggregate signature scheme.
An aggregate signature scheme allows anyone to compress multiple individual signatures from various users into a single compact signature. The main objective of such a scheme is to reduce the costs on storage, communication and computation. However, among existing aggregate signature schemes in the identity-based setting, some of them fail to achieve constant-length aggregate signature or require a large amount of pairing operations which grows linearly with the number of signers, while others have some limitations on the aggregated signatures. The main challenge in building efficient aggregate signature scheme is to compress signatures into a compact, constant-length signature without any restriction. To address the above drawbacks, by using the bilinear pairings, we propose an efficient unrestricted identity-based aggregate signature. Our scheme achieves both full aggregation and constant pairing computation. We prove that our scheme has existential unforgeability under the computational Diffie-Hellman assumption.