Improving the Assessment of Implicit Motives Using IRT: Cultural Differences and Differential Item Functioning.
Researchers have long been interested in studying differences in implicit motive between different groups. Implicit motives are typically measured by scoring text that respondents have written in response to picture cues. Recently, research on the measurement of implicit motives has made progress through the application of a dynamic Thurstonian item-response theory model (DTM; Lang, 2014 ) that captures 2 basic motivational processes in motivational research: motive competition and dynamic reduction of motive strength after a motive has been acted out. In this article, the authors use the DTM to investigate differential item functioning (DIF) in implicit motive measures. The article first discusses DIF in the context of the DTM. The authors then conduct a DIF analysis of data from a study that used a picture set of the Operant Motive Test (OMT; Kuhl & Scheffer, 2002) with participants from Cameroon, Germany, and Costa Rica. Results showed no evidence of DIF in 9 pictures and some evidence for DIF in 3 pictures. The authors show a partial invariance model can be specified and use this partial invariance model to study latent mean differences between Cameroon, Germany, and Costa Rica. The discussion focuses on the use of IRT DIF methods in future research on implicit motives.


Endoscopic harvest of the medial gastrocnemius muscle flap: a cadaveric study.
The aim of our study was to prove that endoscopic-assisted harvest of the medial gastrocnemius muscle is as effective as the conventional technique. We performed endoscopic dissection on 10 fresh human cadavers, and found that the medial gastrocnemius muscle was easily harvested through a minor donor-site incision, because of its topography and constant dominant proximal vascular pedicle. The operative technique is described.


Human cardiac myosin heavy chain genes and their linkage in the genome.
Human myosin heavy chains are encoded by a multigene family consisting of at least 10 members. A gene-specific oligonucleotide has been used to isolate the human beta myosin heavy chain gene from a group of twelve nonoverlapping genomic clones. We have shown that this gene (which is expressed in both cardiac and skeletal muscle) is located 3.6kb upstream of the alpha cardiac myosin gene. We find that DNA sequences located upstream of rat and human alpha cardiac myosin heavy chain genes are very homologous over a 300bp region. Analogous regions of two other myosin genes expressed in different muscles (cardiac and skeletal) show no such homology to each other. While a human skeletal muscle myosin heavy chain gene cluster is located on chromosome 17, we show that the beta and alpha human cardiac myosin heavy chain genes are located on chromosome 14.


Expression of the proliferation marker Ki-67 and of p53 tumor protein in trophoblastic tissue of preeclamptic, HELLP, and intrauterine growth-restricted pregnancies.
The human placenta owns the biochemical machinery to proliferate throughout gestation. The aim of this study was to investigate the expression of the proliferation marker Ki-67 in trophoblastic tissue of intrauterine growth retarded (IUGR) placentas, preeclamptic, HELLP, and in normal trophoblastic tissue. Slides of paraffin-embedded trophoblastic tissue of patients with IUGR, preeclamptic patients, HELLP patients, and normal term placentas were incubated with monoclonal antibodies against Ki-67 and p53. Staining reaction was performed with the ABC reagent. Intensity of immunohistochemical reaction on the slides was analyzed using a semiquantitative score. Identification of Ki-67-expressing cells was done by immunofluorescence double staining with Ki-67 and cytokeratin antibodies. Expression of Ki-67 and p53 are significantly elevated in cytotrophoblastic cells of placentas with HELLP as investigated by immunohistochemistry and double immunofluorescence. However, preeclamptic cytotrophoblastic tissue on the other hand showed no significantly different expression intensity of Ki-67 compared with normal placental tissue controls and no changes in p53 expression compared with controls. In IUGR cytotrophoblastic cells, we found no statistically significant change in Ki-67 expression but a statistically significant down-regulation of p53. An elevated proliferation of cytotrophoblastic cells seems to be related to HELLP, and this enhanced proliferation seems to be controlled by p53.


Development and characterisation of a panel of phosphatidylinositide 3-kinase - mammalian target of rapamycin inhibitor resistant lung cancer cell lines.
The PI3K-mTOR pathway is involved in regulating all hallmarks of cancer, and is often dysregulated in NSCLC, making it an attractive therapeutic target in this setting. Acquired resistance to PI3K-mTOR inhibition is a major hurdle to overcome in the success of PI3K-mTOR targeted agents. H460, A549, and H1975 resistant cells were generated by prolonged treatment in culture with Apitolisib (GDC-0980), a dual PI3K-mTOR inhibitor over a period of several months, from age-matched parent cells. Resistance was deemed to have developed when a log fold difference in IC50 had been achieved. Resistant cell lines also exhibited resistance to another widely investigated PI3K-mTOR dual inhibitor; Dactolisib (BEZ235). Cell lines were characterised at the level of mRNA (expression array profiling expression of >150 genes), miRNA (expression array profiling of 2100 miRNAs), protein (bottoms-up label-free mass spectrometry) and phosphoprotein (expression array profiling of 84 phospho/total proteins). Key alterations were validated by qPCR and Western blot. H1975 cells were initially most sensitive to Apitolisib (GDC-0980), but developed resistance more quickly than the other cell lines, perhaps due to increased selective pressure from the impressive initial effect. In-depth molecular profiling suggested epithelial-mesenchymal transition (EMT) may play a role in resistance to PI3K-mTOR dual inhibition in NSCLC.


Remarkable enhancement in the Kapitza resistance and electron potential barrier of chemically modified In2O3(ZnO)9 natural superlattice interfaces.
Superlattice interfaces can efficiently scatter phonons and filter low-energy electrons, thereby reducing the thermal conductivity to the "alloy limit" of crystalline solids and increasing the Seebeck coefficient substantially. In this paper, we report a two-fold reduction in the thermal conductivity and an improvement of about 170% in the Seebeck coefficient of an existing In2O3(ZnO)9 superlattice by chemically modifying the interface with small additions of aluminum. Using a classical model for the interface transport, we attribute such significant changes to the increase in both the Kapitza (thermal) resistance and the electron potential barrier height of the InO2(-) superlattice interfaces that are modified by Al(3+). The present work opens a new avenue of research showing that the superlattice interfaces can be chemically tuned for specific properties, which can be investigated in both experimental and computational ways, and also suggests a new route for material design for applications in areas like thermoelectrics.


Two- and three-dimensional imaging of multicomponent systems using scanning thermal microscopy and localized thermomechanical analysis.
The aim of this study was to develop a novel approach to the spatial characterization of multicomponent samples, based on the emergent technique of microthermal analysis. More specifically, we present an assessment of the use of scanning thermal microscopy as a means of component mapping via thermal conductivity; we include a new statistical approach to data handling, which allows reduction of topographic effects. We also introduce a novel three-dimensional mapping technique based on localized thermomechanical analysis. Tablets of paracetamol and hyproxypropyl methylcellulose (HPMC) and 50:50 mixes of the two were prepared and the materials characterized in scanning and localized modes using a TA Instruments 2990 microthermal analyzer with a Thermomicroscopes Explorer AFM head and Wollaston wire thermal probe. L-TMA studies of the pure components indicated markedly differing thermal responses, with the paracetamol showing a sharp melting accompanied by a probe pull-in effect, while HPMC showed only thermal expansion over the temperature range studied. Thermal conductivity and topographic images indicated that two-dimensional differentiation between the components was possible in scanning mode. A means of delineating the relative contribution of the topographic and conductivity effects was developed based on a regression analysis of the thermal conductivity measurements on a set of terms representing the local surface curvature. The results of three-dimensional imaging using a grid of L-TMA measurements is presented. This technique utilized the distinct thermal responses of the two components to allow the probe to melt through the paracetamol down to the underlying HPMC. The advantages and limitations of this novel imaging method are discussed in the context of pharmaceutical and broader uses of the approach.


Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance.
Inheritance of the callipyge phenotype in sheep is an example of polar overdominance inheritance, an unusual mode of inheritance. To investigate the underlying molecular mechanism, we profiled the expression of the genes located in the Delta-like 1 homolog (Dlk1)-type III iodothyronine deiodinase (Dio3) imprinting region in mice. We found that the transcripts of the microRNA (miR) 379/miR-544 cluster were highly expressed in neonatal muscle and paralleled the expression of the Dlk1. We then determined the in vivo role of the miR-379/miR-544 cluster by establishing a mouse line in which the cluster was ablated. The maternal heterozygotes of young mutant mice displayed a hypertrophic tibialis anterior muscle, extensor digitorum longus muscle, gastrocnemius muscle, and gluteus maximus muscle and elevated expression of the DLK1 protein. Reduced expression of DLK1 was mediated by miR-329, a member of this cluster. Our results suggest that maternal expression of the imprinted miR-379/miR-544 cluster regulates paternal expression of the Dlk1 gene in mice. We therefore propose a miR-based molecular working model for polar overdominance inheritance.


RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis.
Analyses of 164 RUNX1 mutations (RUNX1mut) in 147 of 449 patients (32.7%) with normal karyotype or noncomplex chromosomal imbalances were performed. RUNX1mut were most frequent in acute myeloid leukemia French-American-British classification M0 (65.2%) followed by M2 (32.4%) and M1 (30.2%). Considering cytogenetics, RUNX1mut were most frequent in cases with +13 (27 of 30, 90%), whereas frequencies were similar in other cytogenetic groups (26%-36%). The molecular genetic markers most frequently associated with RUNX1mut were partial tandem duplication in the MLL gene (19.7%), internal tandem duplication in the FLT3 gene (FLT3-ITD; 16.3%), and NRAS mutations (9.5%). Patients with RUNX1mut had shorter overall and event-free survival compared with RUNX1 wild-type cases (median, 378 days vs not reached, P = .003; and median, 285 vs 450 days, P = .003, respectively). In addition, it was shown that the adverse effect of RUNX1 was independent of the adverse effect of FLT3-ITD as well as of the high frequency of prognostically favorable NPM1mut and CEBPAmut in the RUNX1wt group. No effect of the type or localization of the individual RUNX1 mutations was observed. Multivariate analysis showed independent prognostic relevance for overall survival for RUNX1mut (P = .029), FLT3-ITD (P = .003), age (P < .001), and white blood cell count (P < .002).


Identification of a novel frameshift mutation in PAX6 gene and the clinical management in an Asian Indian aniridia family.
This study aimed to characterize an Asian Indian aniridia family for both the phenotype and genotype of the disease for a better clinical management. The phenotype and genotype of the affected and unaffected individuals in the aniridia family were evaluated. The subjects underwent a standard ophthalmic evaluation followed by molecular screening of PAX6 gene in the peripheral blood for mutation detection. The three affected individuals had aniridia with several common features and an uncommon presentation of bilateral congenital ptosis. Two affected siblings, a brother and a sister, had aniridia, nystagmus, ptosis, increase in central corneal thickness, cataract, and foveal hypoplasia. The sister had features of glaucoma. The offspring of the sister had all the features except cataract and rise in intraocular pressure. Mutation screening of PAX6 gene helped in identifying a novel heterozygous pathogenic variation g. 31801757dupG (c. 216-19dupG) that resulted in a frameshift mutation that extended into exon 7. Based on the evaluation and diagnostic testing, the family was clinically managed along with genetic counselling. Molecular diagnostic testing helps in genetic counseling of the family with aniridia to understand the nature of the disease and detection of complications early for better management.


Elucidation of charge-transfer SERS selection rules by considering the excited state properties and the role of electrode potential.
The goal of this study is to shed light on the charge-transfer (CT) mechanism of surface-enhanced Raman scattering (SERS) by considering the properties of CT excited states. The calculations have been done by means of an excited-state gradient approximation for a pyridine molecule interacting with a silver cluster, and provided a satisfactory improvement in comparison to previous work. The effect of electrode potential on the SERS-CT spectra has been modelled theoretically by applying an external electric field for selected CT transitions and the enhancement of the ν6a and ν9a modes and a decline in the intensity of the ν8a mode under a negative electric field (which is directed toward the cluster) have been observed. These results match well with the experimental studies and also explain the effect of electrode potentials on the patterns of spectra, as experimental evidence of the CT mechanism. Finally, this study demonstrated that the excited state vector gradient can be used as a distinguishing factor to explain the SERS selection rules.


Integrating Health and Social Care for Community-Dwelling Older Adults: A Description of 16 Canadian Programs.
This paper describes 16 Canadian programs designed to provide integrated primary care for older adults. Publicly available data were used to identify the "what" and the "how" of integration for each program. Most programs integrated with other healthcare or medical services (vs. social services). Mechanisms of integration varied; the most common mechanism was interprofessional teams. Only 25% of the programs formally engaged with autonomous physician-led primary care practices (where most Canadians receive their primary care). Findings suggest that integrated care is a priority across Canada but also highlight how far we have to go to achieve both vertical integration within the healthcare sector (primary, secondary and tertiary services) and horizontal integration across sectors (health and social).


Structure and thermodynamics of grafted silica/polystyrene dilute nanocomposites investigated through self-consistent field theory.
Polymer/matrix nanocomposites (PNCs) are materials with exceptional properties. They offer a plethora of promising applications in key industrial sectors. In most cases, it is preferable to disperse the nanoparticles (NPs) homogeneously across the matrix phase. However, under certain conditions NPs might lump together and lead to a composite material with undesirable properties. A common strategy to stabilize the NPs is to graft on their surface polymer chains of the same chemical constitution as the matrix chains. There are several unresolved issues concerning the optimal molar mass and areal density of grafted chains that would ensure best dispersion, given the nanoparticles and the polymer matrix. We propose a model for the prediction of key structural and thermodynamic properties of PNC and apply it to a single spherical silica (SiO2) nanoparticle or planar surface grafted with polystyrene chains embedded at low concentration in a matrix phase of the same chemical constitution. Our model is based on self-consistent field theory, formulated in terms of the Edwards diffusion equation. The properties of the PNC are explored across a broad parameter space, spanning the mushroom regime (low grafting densities, small NPs and chain lengths), the dense brush regime, and the crowding regime (large grafting densities, NP diameters, and chain lengths). We extract several key quantities regarding the distributions and the configurations of the polymer chains, such as the radial density profiles and their decomposition into contributions of adsorbed and free chains, the chains/area profiles, and the tendency of end segments to segregate at the interfaces. Based on our predictions concerning the brush thickness, we revisit the scaling behaviors proposed in the literature and we compare our findings with experiment, relevant simulations, and analytic models, such as Alexander's model for incompressible brushes.


Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia.
HESX1 is a paired-like homeodomain transcription factor that functions as a repressor of PROP1-mediated gene stimulation. Mutations in HESX1 have been implicated in cases of septooptic dysplasia and congenital hypopituitarism. All mutations in HESX1 identified to date have resulted in impaired DNA binding and defective HESX1 action. We have identified a novel HESX1 mutation in genomic nucleotide position 1684 (g.1684delG), which results in a mutant protein with increased DNA binding. In turn, this mutation causes increased repression of PROP1-dependent gene activity. These data suggest that enhancement of transcriptional repression during pituitary organogenesis is a novel mechanism for the development of congenital pituitary disorders.


Single-stage Repair of Bilateral Cleft Lip and Bilateral Transverse Facial Cleft in Goldenhar Syndrome: A Case Report.
Goldenhar syndrome (GS) is a rare congenital disorder characterized by multiple facial anomalies. This case report describes a GS presenting with bilateral cleft lip and palate and bilateral transverse facial cleft. We performed a single-stage surgery to repair the bilateral cleft lip and bilateral transverse facial cleft when the patient was 4-months-old. Bilateral cleft lip repair using the Mulliken method was performed first, and then the bilateral transverse facial cleft was corrected. Orbicularis oris muscle repair was done at each clefts. Anatomical approximation technique was used and the final oral commissure was determined considering symmetry. Satisfactory outcomes were achieved without complications.


Towards Multiple Kernel Principal Component Analysis for Integrative Analysis of Tumor Samples.
Personalized treatment of patients based on tissue-specific cancer subtypes has strongly increased the efficacy of the chosen therapies. Even though the amount of data measured for cancer patients has increased over the last years, most cancer subtypes are still diagnosed based on individual data sources (e.g. gene expression data). We propose an unsupervised data integration method based on kernel principal component analysis. Principal component analysis is one of the most widely used techniques in data analysis. Unfortunately, the straightforward multiple kernel extension of this method leads to the use of only one of the input matrices, which does not fit the goal of gaining information from all data sources. Therefore, we present a scoring function to determine the impact of each input matrix. The approach enables visualizing the integrated data and subsequent clustering for cancer subtype identification. Due to the nature of the method, no hyperparameters have to be set. We apply the methodology to five different cancer data sets and demonstrate its advantages in terms of results and usability.


Decellularized Hydrogels in Bone Tissue Engineering: A Topical Review.
Nowadays, autograft and allograft techniques represent the main solution to improve bone repair. Unfortunately, autograft technique is expensive, invasive and subject to infections and hematoma, frequently affecting both donor sites and surgical sites. A recent advance in tissue engineering is the fabrication of cell-laden hydrogels with custom-made geometry, depending on the clinical case. The use of ECM (Extra-Cellular Matrix)-derived Hydrogels from bone tissue is the new opportunity to obtain good results in bone regeneration. Several micro-engineering techniques and approaches are available to fabricate different cell gradients and zonal structures in hydrogels design, in combination with the advancement in biomaterials selection. In this review, we analyse the stereolithografy, the Bio-patterning, the 3D bioprinting and 3D assembly, the Laser-Induced Forward Transfer Bioprinting (LIFT), the Micro-extrusion bioprinting, the promising Electrospinning technology, the Microfluidics and the Micromolding. Several mechanical properties are taken into account for bone regeneration scaffolds. However, each typology of scaffold presents some advantages and some concerns. The research on biomaterials is the most promising for bone tissue engineering: the new biomimetic materials will allow us to obtain optimal results in the next clinical application of basic research.


Stigmatization of social and intimacy loneliness.
82 female and 62 male college students judged the psychosocial functioning and acceptability of hypothetical peers that depicted 2 Levels of Loneliness (Lonely versus Nonlonely) x 2 Domains of Loneliness (Social versus Intimacy). Analysis indicated the students stigmatized both social and intimacy loneliness; they ascribed lower psychosocial functioning to and were less accepting of the lonely than nonlonely peer for both the social and intimacy domains of loneliness. The students, however, displayed greater differentiation in the ascription of psychosocial functioning between the lonely and nonlonely peers for the intimacy than the social domain of loneliness.


Gaze direction and request gesture in social interactions.
One of the most important faculties of humans is to understand the behaviour of other conspecifics. The present study aimed at determining whether, in a social context, request gesture and gaze direction of an individual are enough to infer his/her intention to communicate, by searching for their effects on the kinematics of another individual's arm action. In four experiments participants reached, grasped and lifted a bottle filled of orange juice in presence of an empty glass. In experiment 1, the further presence of a conspecific not producing any request with a hand and gaze did not modify the kinematics of the sequence. Conversely, experiments 2 and 3 showed that the presence of a conspecific producing only a request of pouring by holding the glass with his/her right hand, or only a request of comunicating with the conspecific, by using his/her gaze, affected lifting and grasping of the sequence, respectively. Experiment 4 showed that hand gesture and eye contact simultaneously produced affected the entire sequence. The results suggest that the presence of both request gesture and direct gaze produced by an individual changes the control of a motor sequence executed by another individual. We propose that a social request activates a social affordance that interferes with the control of whatever sequence and that the gaze of the potential receiver who held the glass with her hand modulates the effectiveness of the manual gesture. This paradigm if applied to individuals affected by autism disorder can give new insight on the nature of their impairment in social interaction and communication.


Sphagnum palustre clone vs native Pseudoscleropodium purum: A first trial in the field to validate the future of the moss bag technique.
Although a large body of literature exists on the use of transplanted mosses for biomonitoring of air pollution, no article has addressed so far the use and the accumulation performance of a cloned moss for this purpose. In this work, a direct comparison of metal accumulation between bags filled with a Sphagnum palustre L. clone or with native Pseudoscleropodium purum Hedw., one of the most used moss species in biomonitoring surveys, was investigated. The test was performed in sites with different atmospheric contamination levels selected in urban, industrial, agricultural and background areas of Italy and Spain. Among the eighteen elements investigated, S. palustre was significantly enriched in 10 elements (Al, Ba, Cr, Cu, Fe, Hg, Pb, Sr, V and Zn), while P. purum was enriched only in 6 elements (Al, Ba, Cu, Hg, Pb and Sr), and had a consistently lower uptake capacity than S. palustre. The clone proved to be more sensitive in terms of metal uptake and showed a better performance as a bioaccumulator, providing a higher accumulation signal and allowing a finer distinction among the different land uses and levels of pollution. The excellent uptake performance of the S. palustre clone compared to the native P. purum and its low and stable baseline elemental content, evidenced in this work, are key features for the improvement of the moss bag approach and its large scale application.


Capsid Gene Divergence of Black Queen Cell Virus Isolates in Thailand and Japan Honey Bee Species.
Black queen cell virus (BQCV) has been found in honey bees worldwide. By using the reverse transcription polymerase chain reaction (RT-PCR) technique, BQCV was detected in a non-native species, Apis mellifera L., collected in both Thailand and Japan, and three other honey bee species (Apis cerana indica F., Apis dorsata F., and Apis florae F.) native to Thailand and Apis cerana japonica F. native to Japan. Based on the capsid coding region, the phylogenetic analysis showed that the BQCV strains found in A. cerana indica and A. cerana japonica were similar within the group and closer to BQCV in Asia. It is interesting to note that the genetic variation of the BQCV isolates was more associated with geographic origin than the host bee species from which the isolates were obtained.


[Interactions of HIV-1 DNA heterocyclic bases with viral DNA].
Human immunodeficiency virus type 1 integrase is one of three viral enzymes, and it realizes a key process of the viral replication cycle, i.e. viral DNA integration into infected cell genome. Integrase recognizes nucleotide sequences located at the ends of the viral DNA U3 and U5 LTRs and catalyzes 3'-processing and strand transfer reactions. To study the interactions between integrase and viral DNA at present work, we used modified integrase substrates mimicking the terminal U5 LTR sequence and containing non-nucleoside insertions in one or/and both strands. It is shown that the substrate modifications have no influence on the integrase binding rate, while the heterocyclic bases removal in the 5th and 6th substrate positions and in the 3rd position of the substrate processed strand distinctly inhibits the integrase catalytic activity. This fact demonstrates these bases significance for the active enzyme/substrate complex formation. On the contrary, modification of the 3rd position within substrate non-processed strand stimulates 3'-processing. Since heterocyclic base elimination results in disruption of the DNA complementary and staking interactions, this result shows that DNA double helix destabilization close to the cleaved bond promotes the 3'-processing.


Affinity capillary electrophoresis investigation of an epitope on human immunodeficiency virus recognized by a monoclonal antibody.
Affinity capillary electrophoresis (ACE) has been used to investigate the epitope on the human immunodeficiency virus (HIV) core protein p24 recognized by the monoclonal antibody (mAb) 13-102-100. The affinity of a series of peptides with N- and C-terminal truncations of the epitope sequence determined by mass spectrometry was studied. The peak area change assay was used for the study of the interactions of the mAb with those peptides, exhibiting tight binding to the mAb, and the migration time shift assay was used to probe the relative affinities of peptides showing weak binding to the mAb. The experimental results show that the monoclonal antibody 13-102-100 recognizes the peptide VHPVHAGPIAP with highest affinity. Smaller peptides incorporating only part of the epitope, however, are recognized to some extent in the ACE experiments.


An intradialytic aerobic exercise program ameliorates frailty and improves dialysis adequacy and quality of life among hemodialysis patients: a randomized controlled trial.
Hemodialysis patients with chronic kidney disease exhibit impaired exercise tolerance and functional decline. Despite the life-saving benefits of adequate dialysis, those declines translate into frailty and deteriorating quality of life (QoL). This study evaluated the effects of an intradialytic aerobic exercise program on frailty, dialysis adequacy, and QoL among hemodialysis patients. Patients at an university hospital-affiliated hemodialysis center were randomly assigned to an exercise group (n = 18) or a control group (n = 21). The 12-week aerobic exercise program comprised 40 to 70 minutes of ergometer cycling 3 times/wk and a single education session. The control group completed only the education session. Outcomes were assessed at the time of enrollment, week 4, week 8, and week 12 using Fried's frailty phenotype measures (gait speed, grip strength, vitality, body mass index, and physical activity), the short physical performance battery (SPPB), Kt/V urea, and the Short Form-36 questionnaire. There were significant interactions between groups and follow-up times in the frailty score (p < 0.001), gait speed (p < 0.001), SPPB (p < 0.001), and mental QoL (p = 0.03). The intention-to-treat and per-protocol analyses revealed that the exercise group exhibited significant improvements in frailty score (p < 0.001), gait speed (p < 0.001), grip strength (p < 0.001), exhaustion (p = 0.02), SPPB (p = 0.01), dialysis adequacy (p = 0.01), and physical QoL (p = 0.003). An intradialytic aerobic exercise program could be a safe, feasible, and appropriate additional strategy to routine care among hemodialysis patients for improvements in frailty, dialysis adequacy, and QoL.


Thermal-induced phase transitions in self-assembled mesostructured films studied by small-angle X-ray scattering.
Two examples of phase transition in self-assembled mesostructured hybrid thin films are reported. The materials have been synthesized using tetraethoxysilane as the silica source hydrolyzed with or without the addition of methyltriethoxysilane. The combined use of transmission electron microscopy, small-angle X-ray scattering and computer simulation has been introduced to achieve a clear identification of the organized phases. A structural study of the self-assembled mesophases as a function of thermal treatment has allowed the overall phase transition to be followed. The initial symmetries of mesophases in as-deposited films have been linked to those observed in samples after thermal treatment. The monodimensional shrinkage of silica films during calcination has induced a phase transition from face-centered orthorhombic to body-centered cubic. In hybrid films, instead, the phase transition has not involved a change in the unit cell but a contraction of the cell parameter normal to the substrate.


Overlap of C3 Glomerulopathy and Thrombotic Microangiopathy: A Case Series.
Dysregulation of alternative complement pathway underlies the pathogenesis of both C3 glomerulopathy (C3G) and thrombotic microangiopathy (TMA). In this study, we describe both disease entities occurring in 5 patients. We identified 114 patients at our institution from 2007 to 2016 with C3G in native kidney biopsies and those with concurrent TMA were included. The median age at diagnosis was 58 years (range: 28-69); all were male. Median serum creatinine and proteinuria at presentation were 2.3 mg/dl and 2089 mg/d, respectively. Three cases presented with TMA-predominant phenotype and 2 with C3G-predominant phenotype. Immunofluorescence (IF) showed bright C3 staining in mesangium and/or capillary walls. Electron microscopy showed marked subendothelial expansion by fluffy material in the capillary loops without associated deposits. However, capillary wall deposits were present in other loops in 4 cases. Mesangial deposits were present in all cases. Four cases showed low C3, of which 2 showed low C4. Complement evaluation in 3 cases showed pathogenic CFH mutation in 1 case, and multiple variant of unknown significance along with factor B autoantibody and C4 nephritic factor in 1 case. One patient negative for complement abnormalities had a monoclonal gammopathy. Three cases were treated with steroids and/or immunosuppressants. One case progressed to end-stage renal disease (ESRD) at 38.3 months; the remaining showed median serum creatinine and proteinuria of 2.5 mg/dl and 1169 mg/d, respectively at median follow-up of 17.5 months. Overlap of C3G and TMA is rare and can clinically present as C3G-predominant or TMA-predominant phenotype. The significance of concurrent C3G/TMA findings on long-term renal survival remains to be explored.


Methodological considerations for the assessment of ADP induced platelet aggregation using the Multiplate® analyser.
Factors affecting the Multiplate® assay's analytical precision have not been well defined. We investigated the effect of methodological factors on the measurement of ADP-induced platelet aggregation using the Multiplate® assay. ADP-induced platelet aggregation was analysed in whole blood using the Multiplate® assay. We tested the reproducibility of measurement, the effect of different anticoagulants (hirudin, citrate and heparin) and the effect of time delay (15, 30, 45, 60, 120 and 180 minutes) between sampling and analysis in patients. The use of a manual calibrated pipette with the Multiplate® analyser was also tested. The mean coefficient of variation (CV) using the manufacturers recommended methods was 10.8 ± 8.7% (n = 30). When compared to hirudin (359.5 ± 309 AU*min) the use of heparin (521.0 ± 316 AU*min, p = 0.0015) increased platelet aggregation, while the use of sodium citrate (245.0 ± 209 AU*min, p = 0.003) decreased the platelet aggregation (n = 20). The addition of CaCl2 to the citrate-anticoagulated blood resulted in platelet aggregation levels similar to hirudin. Platelet aggregation varied with time delay (n = 20). When compared to platelet aggregation at 30 minutes (391.1 ± 283 AU*min), platelet aggregation was reduced at 60 minutes (335.2 ± 251.6 AU*min, p < 0.05), 120 minutes (198.8 ± 122.9 AU*min, p < 0.001) and 180 minutes (160.7 ± 92 AU*min, p < 0.001). The use of a manual calibrated pipette did not significantly reduce the mean CV in the assay (n = 20). Methodological factors such as the anticoagulant used and the time delay should be standardised where possible to reduce variability, and allow thresholds derived from one study to be comparable across multiple studies.


What should psychiatry residents be taught about neurology?: A survey of psychiatry residency directors.
To improve our ability to teach psychiatry residents during their required 2 months on neurology rotations, we investigated the perceived needs of psychiatry program training directors. We contacted the program directors organization of the American Psychiatric Association and disseminated a web-based survey to all program directors. The survey asked questions about the format and content of neurology training desired for psychiatry residents. The survey was sent a second time to increase response rate. Sixty (32%) training directors responded. Overall satisfaction with neurologic education was rated at 3.6 out of 5 (standard deviation +/- 0.96). The specific content areas which elicited the most interest for focused training modules were differential diagnosis and biologic substrates of dementia, evaluation and treatment of drug-related and spontaneous movement disorders, evaluation and management of sleep disorders, cognitive and mood effects of stroke, and inherited disorders. Many program directors commented on perceived weaknesses of inpatient-based exposure to neurology; 78% of responders favored outpatient and consultation settings. In an era of deliberation about neurobehavioral integration and cross-training of neurologists and psychiatrists, neurologists should strive to provide the best possible multidisciplinary education to psychiatry trainees.


Holoprosencephaly and cyclopia visualized by two- and three-dimensional prenatal ultrasound.
We report on the ultrasound (US) detection of holoprosencephaly with cyclopia at a gestational age of 16 weeks. The sonographic diagnosis was based on the intracranial finding of fused thalami with no visible midline structures and facial abnormalities, including cyclopia and proboscis. We evaluated the fetal face by 3-dimensional (3D) transabdominal US and were able to identify the cyclopia below the proboscis. These findings are characteristic of alobar holoprosencephaly. With the informed consent of the patient, the pregnancy was terminated by prostaglandin induction after proper counseling. Chromosome study of the abortus revealed a normal karyotype (46, XY). Postmortem examination of the abortus confirmed the presence of cyclopia and a proboscis. The use of 3D prenatal US made additional diagnostic images possible.


Mastering developmental transitions in young and middle adulthood: the interplay of openness to experience and traditional gender ideology on women's self-efficacy and subjective well-being.
The present research focuses on 2 factors that might help or hurt women to cope with the uncertainties associated with developmental transitions in modern societies (i.e., starting one's first job, graduating from high school, reentry to work after parental leave). We investigate (a) the role of openness to experience in coping with challenging transitions and (b) the (mal)adaptive consequences of adopting a traditional gender ideology. Starting with the assumption that transitional uncertainty has different consequences for women high or low in openness to experience, a first experiment (N = 61; 18-30 years) demonstrated that self-efficacy and well-being decrease after being confronted with transitional uncertainty among women low in openness. Two longitudinal studies investigated the (mal)adaptive consequences of adopting a traditional gender ideology for women high or low in openness in dealing with challenging transitions. Study 2 examined whether endorsing or rejecting traditional gender role beliefs might help female (but not male) students to maintain a sense of self-efficacy and subjective well-being during the transition of graduating from high school (N = 520, 17-22 years). Study 3 (N = 297; 20-53 years) tested the same model for women in middle adulthood during the transition from parental leave to reentry into work life. For both studies, latent growth analyses showed that endorsing traditional gender role beliefs contributed to self-efficacy and subjective well-being among women low in openness. By contrast, for women high in openness, rejecting traditional gender role beliefs had a positive effect on their relative level of self-efficacy and subjective well-being. Functions of ideologies in the context of challenging transitions are discussed.


[An exceptional and misleading case of choledochal cyst].
The authors report a case of choledocal cyst extended to left and right hepatic ducts. An heterogeneous intracystic fluid, partial calcification of cystic wall, a slight positivity of echinoccosis serology in a patient from a highly endemic country erroneously led to diagnosis of hydatid cyst invading the left hepatic duct. The diagnosis of choledocal cyst was done on the resection specimen after left hepatectomy. A small patch of cyst wall with terminations of both right sectorial hepatic ducts was used for cysto-jejunal Roux-en-Y loop anastomosis. Peculiarities of this type of choledocal cyst are discussed.


Regression of coronary atherosclerosis by simvastatin: a serial intravascular ultrasound study.
Angiography of the coronary arteries reflects only changes in luminal dimensions. With intravascular ultrasound, cross-sectional images can be obtained and area measurements can be added to calculate volumes of the external elastic membrane (EEM), plaque plus media (P+M), and lumen. The aim of this study was to investigate the effect of lipid lowering by simvastatin on coronary atherosclerotic P+M as changes in volumes of EEM, P+M, and lumen. In 40 male patients with hypercholesterolemia, ischemic heart disease, and a nonsignificant coronary artery lesion in a not previously revascularized coronary artery, serial intravascular ultrasound studies with an ECG-triggered pullback were performed at baseline, after 3 months on a lipid-lowering diet, and after another 12 months on simvastatin 40 mg/d. Mean length of the analyzed atherosclerotic segments was 5.9+/-3.3 mm. After 12 months on simvastatin, a significant reduction in P+M volume of 6.3% (P=0.002) was observed, whereas only a nonsignificant reduction in EEM volume of 1.8% was seen without any concomitant change in lumen volume. A significant reduction in total cholesterol of 31.0% (6.1+/-0.8 versus 4.2+/-0.7 mmol/L, P<0.001) and LDL cholesterol of 42.6% (4.0+/-0.8 versus 2.2+/-0.6 mmol/L, P<0.001) was obtained. Lipid-lowering therapy with simvastatin for 12 months is associated with a significant P+M regression in coronary arteries measured as reduction in P+M and EEM volumes without any concomitant change in lumen volume.


Chronic binge ethanol-mediated acidemia reduces availability of glutamine and related amino acids in maternal plasma of pregnant sheep.
Heavy drinking during pregnancy can result in fetal alcohol syndrome (FAS), of which, fetal and postnatal growth retardation and central nervous system deficits are cardinal features. Although a number of mechanisms have been proposed, none fully account for these deficiencies. We have previously reported that maternal ethanol exposure (1.75 g/kg) results in transient acidemia in the mother and fetus. Alterations in pH are known to regulate glutamine homeostasis. Therefore, we hypothesized that chronic binge ethanol-mediated acidosis reduces glutamine concentrations in maternal plasma that result in decreases in the circulating levels of amino acids related to glutamine metabolism. Pregnant ewes were divided into three groups: ethanol (1.75 g/kg), saline control, and acidemia (inspired fractional carbon dioxide [CO(2)] was manipulated to mimic the maternal arterial pH pattern created by ethanol). The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109, continuing to GD 132. Plasma samples were analyzed for nutrients and metabolites using HPLC and spectrophotometric methods. Maternal plasma concentrations of glutamate increased (58%), whereas glutamine, citrulline, and arginine decreased (between 14 and 53%) in response to an acute challenge after the chronic exposure in ethanol-treated ewes. No differences in these amino acid concentrations were noted between the ethanol and acidemic group subjects. Maternal plasma lactate levels increased by approximately 100% in response to ethanol, whereas glucose and urea levels did not change in any group. We conclude that maternal chronic binge ethanol consumption results in acidosis-mediated reductions in circulating levels of glutamine and related amino acids that could be responsible for neuronal deficits, altered fetal growth, development, and programming. We also speculate that the consequent increase in fetal glutamate during critical periods of brain development may contribute to the pathogenesis of FAS.


Unsaturated trinuclear ruthenium carbonyls: large structural differences between analogous carbonyl derivatives of the first, second, and third row transition metals.
For the saturated carbonyl trimer Ru(3)(CO)(12) theoretical methods predict a doubly bridged Ru(3)(CO)(10)(mu-CO)(2) structure to lie only 0.3 kcal mol(-1) above the unbridged global minimum in accord with the fluxional properties observed experimentally by carbon-13 NMR on the very stable unbridged Ru(3)(CO)(12). For M(3)(CO)(11) and M(3)(CO)(10) the global minima for the Fe, Ru, and Os derivatives each have totally different arrangements of the carbonyl groups. Thus the global minimum of Ru(3)(CO)(11) is singly edge-semibridged Ru(3)(CO)(10)(mu-CO) in contrast to the doubly face-bridged Fe(3)(CO)(9)(mu(3)-CO)(2) and triply edge-bridged Os(3)(CO)(8)(mu-CO)(3) found as global minima for the iron and osmium analogues, respectively. Furthermore, comparison of our predicted nu(CO) frequencies for low-lying unbridged, singly bridged, and doubly bridged isomers of Ru(3)(CO)(11) with the 1987 experiments of Bentsen and Wrighton indicates that three different Ru(3)(CO)(11) isomers are generated in these low-temperature inert matrix Ru(3)(CO)(12) photolysis experiments depending on the conditions. For Ru(3)(CO)(10) the global minimum is a triply bridged structure Ru(3)(CO)(7)(mu-CO)(3), which is very different from the Fe(3)(CO)(9)(mu(3)-CO) and Os(3)(CO)(8)(mu(3)-CO)(mu-CO) global minima found for the iron and osmium analogues, respectively. For Ru(3)(CO)(9) the global minimum is a singly bridged structure Ru(3)(CO)(8)(mu-CO) analogous to the global minimum for the osmium analogue but totally different from the triply bridged global minimum of Fe(3)(CO)(9).


Assessing the Contribution of the Environmental Parameters to Eutrophication with the Use of the "PaD" and "PaD2" Methods in a Hypereutrophic Lake.
Lake Pamvotis (Greece) is a shallow hypereutrophic lake with a natural tendency to eutrophication. Several restoration measures were applied, but with no long-term success. To examine the causes for this an Artificial Neural Network (ANN) was created in order to simulate the chlorophyll-a (Chl-a) levels and to investigate the role of the associated environmental parameters. The ANN managed to simulate with good correlation the simulated Chl-a and can be considered as a reliable predictor. The relative importance of the environmental parameters to the simulated Chl-a was calculated with the use of the "Partial Derivatives" ("PaD") sensitivity method. The water temperature (WT) and soluble reactive phosphorus (SRP) had the highest relative importance, with values of 50% and 17%, respectively. The synergistic effect of the paired parameters was calculated with the use of the "PaD2" algorithm. The SRP-WT paired parameter was the most influential, with a relative contribution of 22%. The ANN showed that Lake Pamvotis is prone to suffer the effects of climatic change, because of the major contribution of WT. The ANN also revealed that combined nutrients reduction would improve water quality status. The ANN findings can act as an advisory tool regarding any restoration efforts.


Cancer in Children and Young People.
This 30-minute online course aims to support nurse practitioners and allied healthcare professionals to identify symptoms and signs that could indicate a malignancy in a child or young person.


Gamma Knife Radiosurgery for Petroclival Meningioma: Long-Term Outcome and Failure Pattern.
Total removal of petroclival meningioma is difficult, and aggressive extirpation is often associated with significant surgical morbidity and mortality. The aim of this study was to evaluate the long-term outcome and failure pattern of treatment with Gamma Knife radiosurgery (GKRS) in patients with petroclival meningiomas. Eighty-nine consecutive patients with petroclival meningiomas underwent GKRS between 1998 and 2013. Fifty-eight patients received GKRS as a primary treatment and 31 patients underwent GKRS as a secondary treatment after microsurgery. The mean tumor volume was 6.7 cm3 (range, 0.5-46.3 cm3) and the mean marginal dose was 13.2 Gy (range, 8-17 Gy). At the last radiological follow-up, tumor volume was decreased in 50 patients (56.2%), stationary in 34 patients (38.2%), and increased in 5 patients (5.6%). The actuarial progression-free survival after GKRS was 94.7% at 5 years and 88.9% at 10 years. Favorable cranial nerve outcomes were found in 81 patients (91%). A regrowth pattern was present in all 4 patients of the primary treatment group, whereas cyst formation (3 patients) and regrowth (1 patient) were observed in the secondary treatment group. GKRS is an effective and reasonable option as a primary or secondary treatment for petroclival meningioma. Further studies of failure patterns after GKRS for petroclival meningioma are mandatory.


Functions and substrates of plastoglobule-localized metallopeptidase PGM48.
Plastoglobules (PGs) in chloroplasts are monolayer lipid-protein particles attached to thylakoids. The size and number of PGs per chloroplast respond dynamically to abiotic environmental stresses and developmental transitions. During senescence, the thylakoid membranes and its constituents are dismantled in controlled fashion. Leaf senescence coincides with a dramatic increase in the size of PGs, which is consistent with a functional role of PG in remobilization of thylakoid membrane components. In a recent publication, 1 we showed that PG-localized metallopeptidase PGM48 promotes natural senescence. In plants, PGM48 has homologs in mitochondria and the endomembrane system, but PGM48 evolved specifically in photosynthetic organisms. Extensive analysis of Arabidopsis transgenic lines either under- or overexpressing PGM48, showed that PGM48 is a positive regulator of senescence, and we proposed that PG-localized carotenoid cleavage enzyme 4 (CCD4) is a potential substrate of PGM48. Here, we discuss PGM48 function and how it may accelerate natural senescence.


Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study.
The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn't come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.


Subcutaneous immunoglobulin: rapid push vs. infusion pump in pediatrics.
Subcutaneous immunoglobulin (SCIG) therapy is gaining favor for the management of primary immunodeficiency disease (PIDD) in adults and children. A retrospective chart review captured data on 96 pediatric patients with PIDD using SCIG (16% or 20%) delivered by infusion pump or SC rapid push over 620 clinic visits. Patients previously using intravenous immunoglobulin (IVIG) were converted to SCIG dosing on a 1:1 basis. Patients/caregivers voluntarily chose an administration technique. Although mean SCIG dosing was lower on a g/kg/month basis compared with prior IVIG dosing, mean steady-state serum IgG levels during SCIG administration were about 100-200 mg/dl higher than IVIG trough values. On average, much more rapid infusion was achieved with the SC rapid push method, with 49% of patients reporting infusion times of 9 min or less; median duration of infusion pump administration was 45 min. The use of 20% SCIG increased dosing efficiency compared with 16% SCIG, allowing for a smaller weekly mean SCIG volume and fewer dosing days per week. Adverse event (AE) rates were lower in the pediatric subgroup compared with adults (15.8% vs. 18.8% of visits), and the majority of AEs were local. SC rapid push was reported most frequently for patients under age 2; its use decreased between ages 2 and <10 yr and then increased in adolescence and into adulthood. Only one of the pediatric patients returned to IVIG use. Administration of replacement Ig via SC rapid push is a safe and viable option in pediatric patients with PIDD.


Radiopharmaceuticals for somatostatin receptor imaging.
The aim of this review is to summarize the developments and briefly characterize the somatostatin analogs which are currently used for somatostatin receptor imaging in clinical routine or in early phase clinical trials. Somatostatin (sst) receptor targeting with radiolabeled peptides has become an integral part in nuclear oncology during the last 20 years. This integration process has been initiated in Europe with the introduction to the market of 111In-DTPA-DPhe1-octreotide [111In-pentetreotide]. Introducing 99mTc in somatostatin receptor targeting radiopeptides resulted in much better image quality, higher sensitivity of tumor detection and lower mean effective dose for the examined patient. The next generation are 68Ga labeled somatostatin analogs. Due to the spatial resolution of PET technique and increasing number of PET scanners, the PET or PET/CT technique became very important in somatostatin receptor imaging. Until up to a couple of years ago the analogs of somatostatin were constructed aiming at their agonistic behavior, expecting that their internalization with the receptor acti-vated by the radiolabeled ligand and its retention within the tumor cell are crucial for efficient imaging and therapy. Recently it has been shown that the antagonists recognize more binding sites at the tumor cell membrane and hence offer an improved diagnostic efficacy, especially when the density of sst receptors is low. This approach may in future improve diagnostic value of somatostatin receptor imaging techniques. The developments in tracer design are followed by the improvements in imaging techniques. The new SPECT scanners offer resolution close to that of PET, which might open a new era for 99mTc and other SPECT radiotracers.


Endosperm and Maternal-specific expression of EIN2 in the endosperm affects endosperm cellularization and seed size in Arabidopsis.
Seed size is related to plant evolution and crop yield and is affected by genetic mutations, imprinting, and genome dosage. Imprinting is a widespread epigenetic phenomenon in mammals and flowering plants. ETHYLENE INSENSITIVE2 (EIN2) encodes a membrane protein that links the ethylene perception to transcriptional regulation. Interestingly, during seed development EIN2 is maternally expressed in Arabidopsis and maize, but the role of EIN2 in seed development is unknown. Here, we show that EIN2 is expressed specifically in the endosperm, and the maternal-specific EIN2 expression affects temporal regulation of endosperm cellularization. As a result, seed size increases in the genetic cross using the ein2 mutant as the maternal parent or in the ein2 mutant. The maternal-specific expression of EIN2 in the endosperm is controlled by DNA methylation but not by H3K27me3 or by ethylene and several ethylene pathway genes tested. RNA-seq analysis in the endosperm isolated by laser-capture microdissection show upregulation of many endosperm-expressed genes such as AGAMOUS-LIKEs (AGLs) in the ein2 mutant or when the maternal EIN2 allele is not expressed. EIN2 does not interact with DNA and may act through ETHYLENE INSENSITIVE3 (EIN3), a DNA-binding protein present in sporophytic tissues, to activate target genes like AGLs, which in turn mediate temporal regulation of endosperm cellularization and seed size. These results provide mechanistic insights into endosperm and maternal-specific expression of EIN2 on endosperm cellularization and seed development, which could help improve seed production in plants and crops.


Calibration standards for counting asbestos.
A laboratory proficiency testing program has been initiated by NIOSH to permit standardization of asbestos counting procedures by various state agencies. This has required preparation of multiple membrane filter samples containing "identical and predictable" concentrations of asbestos fibers, with consistent particulate backgrounds. A technique to filter liquid (toluene) suspensions was developed to provide chrysotile asbestos standards ranging from 200 to 1,500 fibers/mm-2 of filter area, with an aluminum oxide particulate background. Details of the necessary techniques are described. To evaluate variations inherent in preparing these "identical" samples and to estimate variations between different counters, extensive replicate fiber counting was performed. Count data from several counters at a single facility show that this liquid suspension filtration technique provides reproducible asbestos standards as measured by optical microscopy with a coefficient of variation of plus or minus 20% with the maximum individual variations of plus or minus 50%.


Influence of dipping practices on the seroprevalence of babesiosis and anaplasmosis in the foot-and-mouth disease buffer zone adjoining the Kruger National Park in South Africa.
A serological survey of bovine babesiosis and anaplasmosis was conducted in the foot-and-mouth disease buffer zone surrounding the Kruger National Park in South Africa between 2001 and 2003 to determine whether the withdrawal of government-subsidized dipping in certain regions had affected the seroprevalence of these tick-borne diseases. Seroprevalence of Anaplasma marginale and Babesia bovis increased during the study period. This increase was greater in Limpopo Province where farmers had to supply their own acaricide than in Mpumalanga Province where dipping materials were provided by the local Veterinary Services. The number of animals testing positive for B. bigemina decreased in both provinces during the study period, which was attributed to possible vector displacement rather than more effective tick control measures. Responses to a questionnaire on ticks and tick-borne diseases revealed local knowledge on the subject to be highly variable and sometimes incorrect.


Effects of lipid formulations on clove extract spray dried powders: comparison of physicochemical properties, storage stability and in vitro intestinal permeation.
Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove's bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25 °C and 40 °C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.


The Scottish Women's Hospital at Royaumont, France 1914-1919.
In 1915, under the aegis of the French Red Cross, volunteer medical women from the Scottish Women's Hospital Service for Foreign Service established a hospital at Royaumont Abbey in France, to treat casualties of the First World War. By working as a team comprised of radiologists, bacteriologists and surgeons, they were able to combat gas gangrene and record remarkable results. The circumstances and the way in which the doctors were portrayed in France and Britain prevented them from actively promoting their results to gain wider acceptance. After the War, medical women lost their training and employment opportunities and many left the profession.


Long-Term Consequences of Childhood Maltreatment Among Postpartum Women-Prevalence of Psychosocial Risk Factors for Child Welfare: An Independent Replication Study.
As an especially burdensome experience, childhood maltreatment (CM) can have lifelong consequences on the mental health and wellbeing of an individual well into adulthood. We have previously reported that CM constitutes a central risk factor not only for the development of mental problems, but also for facing additional psychosocial risks, endangering healthy development of mother and offspring throughout life (e.g., financial problems, intimate partner violence, substance use). This study was designed to replicate these findings in a larger, independent study cohort. In this cross-sectional replication study an independent cohort of 533 healthy postpartum women was interviewed within seven days after parturition. CM experiences were assessed retrospectively using the German version of the Childhood Trauma Questionnaire (CTQ) and current psychosocial risk factors for child welfare were assessed using the Konstanzer Index (KINDEX). Of all women, 16.1% experienced emotional and 10.1% physical abuse, 28.5% emotional neglect, 9.4% physical neglect and 10.3% experienced sexual abuse. Most importantly, the higher the CM load the more psychosocial stressors existed in women's life. In Particular, women with higher CM load had a higher risk for mental health problems, intimate partner violence, financial problems, and a higher postnatal stress load. In an independent sample, this study replicated the previous findings that CM and psychosocial risk factors for child welfare were strongly associated in a dose-response manner. Our results emphasize the higher vulnerability of women with a CM history in the postpartum period. To avoid negative consequences for mother and child, a regular and evidence-based screening for CM and psychosocial risk factors during pregnancy and puerperium is needed to identify at-risk mothers early during pregnancy and to provide appropriate support. Hence, our findings highlight the mandatory requirement for an interdisciplinary collaboration of gynecological practices, hospitals and midwifes, along with psychologists and psychotherapists and child and youth welfare services.


3D-Printed Microfluidic Devices for Enhanced Online Sampling and Direct Optical Measurements.
3D printing has emerged as a robust technique to fabricate reliable and reproducible microfluidic devices. However, a limitation of 3D-printed devices has been the low transparency even when printed in a "clear" material. There are currently no reports regarding direct optical measurements through a 3D-printed device. Here, we present for the first time that the printing orientation can affect the transparency of a 3D-printed object. With the optimal orientation, we printed a microfluidic detector that was sufficiently transparent (transmittance ≈ 80%) for optical quantitation. This finding is significant because it shows the feasibility to directly 3D-print optical components for analytical applications. In addition, we created a novel microfluidic dialysis device via 3D printing, which enabled higher flow rates (for sampling with high temporal resolution) and increased extraction efficiency than commercially available ones. By coupling the microfluidic detector and dialysis probe, we successfully measured the release kinetics of indole from biofilms in a continuous, automated, and near real-time fashion. Indole is an intercellular signaling molecule in biofilms, which may regulate antibiotic resistance. The release kinetics of this molecule had not been quantitated likely because of the lack of a suitable analytical tool. Our results fill this knowledge gap.


Surveillance strategies for renal cell carcinoma patients following nephrectomy.
Renal cell carcinoma (RCC) is the most lethal of urologic malignancies, accounting for an estimated 36,000 new cases of carcinoma and 12,000 deaths in 2005. Nephrectomy is the usual treatment; however, after nephrectomy, RCC recurs in 20% to 40% of patients with clinically localized disease. A consensus surveillance protocol does not exist for follow-up of RCC after nephrectomy. In this article, available protocols are reviewed with a goal of developing an evidence-based system including the prognostic factors for recurrent disease, chronology and sites of recurrence, available treatment options if recurrent disease is found, and modalities of diagnostic testing available to urologists. New surveillance recommendations are presented based on prognostic factors as well as the University of California, Los Angeles Integrated Staging System for RCC.


[Nutrition management for COPD].
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory reaction of the lung and of the whole body, and pulmonary cachexia often occurs during the advanced stage. The effects of nutritional support upon the management of under-nutrition in COPD remain controversial. However, a study of the effects of nutritional supplement therapy upon such patients with COPD has recently been published. The present report comprises a review of recent articles about the nutritional support of patients with COPD, especially those with cachexia, and a discussion about the roles of nutritional supplement therapy, focusing on exercise and treatment with ghrelin and vitamin D in the management of COPD.


Piecing together the HIF-1 puzzle: the role of the CTGF as a molecular mechanism of HIF-1 regulation.
Understanding the role that molecular compounds have in cancer is of significant interest, as the identification of molecular markers will aid in the prevention and elimination of cancer. Completing this expansive puzzle proves to be challenging because there is great diversity among tumors, specifically within the microenvironment. In a recent article by Chang et al. published in The Journal of the National Cancer Institute (Vol., 2006) new insight is provided of three specific molecular compounds: hypoxia-inducible factor-1alpha (HIF-1alpha), the connective tissue growth factor (CTGF) and the vascular endothelial growth factor-A (VEGF-A). As shown by Chang et al., these molecular compounds have significant implications in the role of human lung adenocarcinoma, and are shown to be integral within this microenvironment. This journal club article reviews the study of Chang et al. and briefly discusses the broader implications of their findings.


Ontogeny of Toll-like receptor mediated cytokine responses of human blood mononuclear cells.
Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an 'immature' neonatal to a 'mature' adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.


Modern trends for external fixation of fractures in children: a critical review.
There is considerable controversy about the use of external fixation to manage children's fractures. The indications for external fixation are examined in the light of the available evidence in the literature. A general overview of surgical considerations, including the type of fixator, pin placement, and duration of treatment, is given with an assessment of possible complications. External fixation offers a safe and effective management option and may perhaps be the subject of randomized controlled trials in the future.


Role of the ocular surface microbiome in allergic eye diseases.
The purpose of this review is to provide an update on emerging literature on the role of the ocular surface microbiome (OSM) in allergic eye diseases. Findings in the literature suggest that the ocular surface microbiome plays a role in the pathophysiology and course of allergic disease of the ocular surface. Knowledge regarding the role of the ocular surface microbiome in allergic disease is important to guide development of targets for future therapeutic interventions.


Inconsistency between hepatic expression and serum concentration of transthyretin in mice humanized at the transthyretin locus.
Human transthyretin (TTR) has about 110 variants, more than 90 of which are associated with human amyloidosis. Several groups have generated transgenic mice that carry various mutant TTR genes. However, formation of mouse/human TTR heterotetramers has been shown to be inhibitory to dissociation and subsequent amyloid formation. To avoid the effect of mouse Ttr and produce humanized mice carrying different TTR variants at high efficiency, we first produced a null allele in the mouse transthyretin locus using targeting vector that contained a neomycin resistance gene flanked by lox71 and loxP. Then, through Cre-mediated recombination, we created a replacement allele that carried either a human normal (Val30) or mutant (Met30) TTR cDNA. This replacement resulted in a humanized TTR mouse with similar tissue-specific profile of human TTR as that of the endogenous mouse Ttr gene. The expression levels of human TTR mRNA and protein in the liver of homozygous human TTR (Val30/Val30) mice were about twice those of heterozygous mouse/human TTR (+/Val30) mice. However, the serum human TTR levels in the Val30/Val30 mice were much less than those in the +/Val30 mice. This contradictory expression was due to unstable Val30 tetramers caused by low binding affinity to mouse retinol binding protein.


Social history of medicine in Spain: points of departure and directions for research.
The development and extension of activities in the domain of die social history of medicine in Spain since the 1960s is reviewed. Attention is paid, first, to the institutional setting and theoretical background of this broad line of research, taking the perspective of the professionalization of the subject of the 'history of medicine' as an under-graduate discipline in the syllabus of the Faculties of Medicine. Secondly, four main directions for research are outlined, namely disease and society, health policies, health professions and gender and medicine, including critical attention to the principal works, active authors, and working and narrative styles.


Channel formation by antiapoptotic protein Bcl-2.
Bcl-2 is the prototypical member of a large family of apoptosis-regulating proteins, consisting of blockers and promoters of cell death. The three-dimensional structure of a Bcl-2 homologue, Bcl-XL, suggests striking similarity to the pore-forming domains of diphtheria toxin and the bacterial colicins, prompting exploration of whether Bcl-2 is capable of forming pores in lipid membranes. Using chloride efflux from KCl-loaded unilamellar lipid vesicles as an assay, purified recombinant Bcl-2 protein exhibited pore-forming activity with properties similar to those of the bacterial toxins, diphtheria toxin, and colicins, i.e., dependence on low pH and acidic lipid membranes. In contrast, a mutant of Bcl-2 lacking the two core hydrophobic alpha-helices (helices 5 and 6), predicted to be required for membrane insertion and channel formation, produced only nonspecific effects. In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. The most frequent conductance observed (18 +/- 2 pS in 0.5 M KCl at pH 7.4) is consistent with a four-helix bundle structure arising from Bcl-2 dimers. However, larger channel conductances (41 +/- 2 pS and 90 +/- 10 pS) also were detected with progressively lower occurrence, implying the step-wise formation of larger oligomers of Bcl-2 in membranes. These findings thus provide biophysical evidence that Bcl-2 forms channels in lipid membranes, suggesting a novel function for this antiapoptotic protein.


Differences in Esterase Activity to Aspirin and p-Nitrophenyl Acetate among Human Serum Albumin Preparations.
Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and also hydrolyzes some compounds at both sites. In the present study, we investigated differences in esterase activity among HSA preparations, and also the effects of warfarin, indomethacin, and naproxen on the hydrolytic activities of HSA to aspirin and p-nitrophenyl acetate. The esterase activities of HSA to aspirin or p-nitrophenyl acetate were measured from the pseudo-first-order formation rate constant (kobs) of salicylic acid or p-nitrophenol by HSA. Inter-lot variations were observed in the esterase activities of HSA to aspirin and p-nitrophenyl acetate; however, the esterase activity of HSA to aspirin did not correlate with that to p-nitrophenyl acetate. The inhibitory effects of warfarin and indomethacin on the esterase activity of HSA to aspirin were stronger than that of naproxen. In contrast, the inhibitory effect of naproxen on the esterase activity of HSA to p-nitrophenyl acetate was stronger than those of warfarin and indomethacin. These results suggest that the administration of different commercial HSA preparations and the co-administration with site I or II high-affinity binding drugs may change the pharmacokinetic profiles of drugs that are hydrolyzed by HSA.


Adenovirus hepatitis in a patient with severe combined immunodeficiency.
An autopsy case of adenovirus hepatitis with severe combined immunodeficiency (SCID) is presented. A 7-month-old female was admitted to the Kitasato University Hospital with chief complaint of persistent fever. A diagnosis of severe combined immunodeficiency (SCID) was made because of defective function in both T and B lymphocytes. Respiratory disturbance and severe hepatic dysfunction were manifested after admission. She died of respiratory failure on the 40th hospital day. Autopsy findings revealed many focal necroses scattered irregularly throughout the liver. Degenerating hepatocytes around the focal necrosis contained nuclear inclusion bodies, and crystalline arrays of adenovirus virions were recognized in these cells by electron microscopy. Adenovirus antigens were brilliantly detected in the nuclear inclusion bodies by indirect immunofluorescence.


Preparation and Evaluation of [18F]AlF-NOTA-PBB for PET Imaging of Cyclin-dependent Kinase 4/6 in Tumors.
Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel 18F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator. The corresponding [18F]AlF-NOTA-PBB complex was prepared with high radiochemical purity (98.4 ± 0.15%) and yield (58.7 ± 4.5%) within 35 min without requiring HPLC purification through a simple one-step 18F-labeling strategy of NOTA-AlF chelation chemistry. The radiotracer was lipophilic (log P = 0.095 ± 0.003) and had good stability in vitro and in vivo. The cellular uptake studies performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) showed that radioactive uptake was blocked by preincubating with a molar dose of palbociclib and it had a nanomolar binding affinity to CDK4/6 (IC50 = 16.23 ± 1.84 nM), demonstrating a CDK4/6-mediated uptake mechanism. Its ex vivo biodistribution in nude mice-bearing MCF-7 tumors showed obvious tumor uptake and a high tumor/muscle ratio of [18F]AlF-NOTA-PBB, and tumor uptake was inhibited with 100 μg of palbociclib, demonstrating specific binding to CDK4/6. Radioactivity accumulation in MCF-7 tumors was observed in PET imaging with [18F]AlF-NOTA-PBB. Based on the results of this work, [18F]AlF-NOTA-PBB has the promising capability as a CDK4/6-targeted tumor imaging agent.


Iron(II) Spin Crossover Coordination Polymers Derived From a Redox Active Equatorial Tetrathiafulvalene Schiff-Base Ligand.
Two polymorphic FeII coordination polymers [FeIIL (TPPE)0.5] 1) and [(FeII 3L3 (TPPE)1.5)] 2), were obtained from a redox-active tetrathiafulvalene (TTF) functionalized ligand [H2L = 2,2'-(((2-(4,5-bis-(methylthio)-1,3-dithiol-2-ylidene)benzo(d) (1,3) dithiole-5,6-diyl)bis-(azanediyl))bis-(meth anylylidene)) (2E,2E')-bis(3-oxobutanoate)] and a highly luminescent connector {TPPE = 1,1,2,2-tetrakis[4-(pyridine-4-yl)phenyl]-ethene}. Complex 1 has a layered structure where the TPPE uses its four diverging pyridines from the TPPE ligand are coordinated by the trans positions to the flat TTF Schiff-base ligand, and complex 2 has an unprecedented catenation of layers within two interpenetrated frameworks. These coordination polymers reserved the redox activity of the TTF unit. Complex 1 shows gradual spin transition behavior without hysteresis. And the fluorescence intensity of TPPE in 1 changes in tandem with the spin crossover (SCO) transition indicating a possible interplay between fluorescence and SCO behavior.


Admission Glucose and In-hospital Mortality after Acute Myocardial Infarction in Patients with or without Diabetes: A Cross-sectional Study.
Hyperglycemia on admission has been found to elevate risk for mortality and adverse clinical events after acute myocardial infarction (AMI), but there are evidences that the relationship of blood glucose and mortality may differ between diabetic and nondiabetic patients. Prior studies in China have provided mixed results and are limited by statistical power. Here, we used data from a large, nationally representative sample of patients hospitalized with AMI in China in 2001, 2006, and 2011 to assess if admission glucose is of prognostic value in China and if this relationship differs depending on the presence or absence of diabetes. Using a nationally representative sample of patients with AMI in China in 2001, 2006, and 2011, we categorized patients according to their glucose levels at admission (Results: Compared to patients with euglycemia (5.8%), patients with moderate hyperglycemia (13.1%, odds ratio [OR] = 2.44, 95% confidence interval [CI, 2.08-2.86]), severe hyperglycemia (21.5%, OR = 4.42, 95% CI [3.78-5.18]), and hypoglycemia (13.8%, OR = 2.59, 95% CI [1.68-4.00]), all had higher crude in-hospital mortality after AMI regardless of the presence of recognized diabetes mellitus. After adjustment for patients' characteristics and clinical status, however, the relationship between admission glucose and in-hospital mortality was different for diabetic and nondiabetic patients (P for interaction = 0.045). Among diabetic patients, hypoglycemia (OR = 3.02, 95% CI [1.20-7.63]), moderate hyperglycemia (OR = 1.75, 95% CI [1.04-2.92]), and severe hyperglycemia (OR = 2.97, 95% CI [1.87-4.71]) remained associated with elevated risk for mortality, but among nondiabetic patients, only patients with moderate hyperglycemia (OR = 2.34, 95% CI [1.93-2.84]) and severe hyperglycemia (OR = 3.92, 95% CI [3.04-5.04]) were at elevated mortality risk and not hypoglycemia (OR = 1.12, 95% CI [0.60-2.08]). This relationship was consistent across different study years (P for interaction = 0.900). The relationship between admission glucose and in-hospital mortality differs for diabetic and nondiabetic patients. Hypoglycemia was a bad prognostic marker among diabetic patients alone. The study results could be used to guide risk assessment among AMI patients using admission glucose. www.clinicaltrials.gov, NCT01624883; https://clinicaltrials.gov/ct2/show/NCT01624883.


Ethylcellulose oleogels for lipophilic bioactive delivery - effect of oleogelation on in vitro bioaccessibility and stability of beta-carotene.
The in vitro lipolysis and β-carotene (BC) transfer from oil to aqueous phase of canola oil ethylcellulose (EC) oleogels were measured using a static monocompartmental model simulating oral, gastric, and duodenal digestive stages. The effects of EC oleogelation on gel in vitro digestibility were examined, using un-structured canola oil as a control. The physicochemical properties of oleogels containing BC were also measured. It was found that oleogels made with 10% 10 cP and 10% 20 cP did not differ significantly in their extent of lipolysis or BC transfer compared to canola oil; however 10% 45 cP and 15.5% 20 cP had a significantly lower extent of lipolysis and BC transfer compared to other formulations. The structure and mechanical strength of the oleogels were both determined to be factors affecting lipolysis and transfer. The presence of BC did not significantly affect the mechanical strength of the gels and EC oleogelation delayed BC degradation under accelerated storage conditions compared to a heated canola oil control. These findings could contribute to the development of new applications for EC oleogels, specifically for the effective delivery of lipophilic molecules.


Heterodisulfide reductase from methanogenic archaea: a new catalytic role for an iron-sulfur cluster.
Heterodisulfide reductase (HDR) from methanogenic archaea is an iron-sulfur protein that catalyzes reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic thiol-coenzymes, coenzyme M (CoM-SH) and coenzyme B (CoB-SH). Via the characterization of a paramagnetic reaction intermediate generated upon oxidation of the enzyme in the presence of coenzyme M, the enzyme was shown to contain a [4Fe-4S] cluster in its active site that catalyzes reduction of the disulfide substrate in two one-electron reduction steps. The formal thiyl radical generated by the initial one-electron reduction of the disulfide is stabilized via reduction and coordination of the resultant thiol to the [4Fe-4S] cluster.


Does pharmacotherapy for attention-deficit/hyperactivity disorder predict risk of later major depression?
This study's goal was to determine among youths with attention-deficit/hyperactivity disorder (ADHD) how the history of ADHD pharmacotherapy influenced the risk of developing major depressive disorder (MDD), compared to other commonly reported predictors. Diagnostic and treatment history data were analyzed retrospectively in 75 youths 11-18 years old with definite or probable ADHD, enrolled in an observational study at a tertiary mental health clinic. Subjects with histories of MDD (H/o MDD) (n = 36) were compared to others who had never been depressed (Never-Depressed) (n = 39) regarding histories of ADHD pharmacotherapy, psychopathology and other potential covariates of MDD risk. H/o MDD subjects reported longer delays before initiating ADHD pharmacotherapy, were more often female, reported having experienced more traumatic event types, and had higher rates of early anxiety and externalizing disorders. With all covariates allowed to enter a backward stepwise Cox regression of survival time till first episodes of MDD, only two variables remained in the model. The time-dependent variable, ADHD pharmacotherapy, prolonged survival times (p = .012), while having experienced more traumatic event types shortened them (p = .001). This study provides preliminary evidence that pharmacotherapy for ADHD may have a protective effect in ADHD youths, reducing the risk of later MDD.


Cloning and characterization of a Nicotiana tabacum methylputrescine oxidase transcript.
The oxidative deamination of N-methylputrescine is an essential step in both pyridine and tropane alkaloid biosynthesis. Reverse genetic approaches have not resulted in the cloning of a methylputrescine oxidase gene (MPO). However, we have used a homology-based approach to clone a full-length tobacco MPO1 cDNA. The MPO1 gene is part of a small multigene family comprised of approximately six members. MPO1-like transcript levels increased in roots that were either deprived of auxin or treated with methyl jasmonic acid. Similar to other known nicotine biosynthetic genes in domesticated tobacco, MPO1-like mRNA levels were lower in roots with the mutant a and b alleles. The MPO1 protein was expressed in bacteria as a recombinant Thioredoxin-His(6)-MPO1 fusion protein. The recombinant MPO1 protein utilized N-methylputrescine more efficiently than other diamines. Therefore, the kinetic properties of the MPO1 enzyme may play an important role in determining the pyridine alkaloid profiles observed in tobacco roots.


Case Report: Clinical Features of a Case of Suspected Borrelia miyamotoi Disease in Hokkaido, Japan.
We herein report a case of suspected Borrelia miyamotoi disease in Hokkaido, Japan. The patient complained of lassitude, arthralgia, and high fever after a tick bite. Furthermore, at the time of consultation, the patient exhibited momentary loss of consciousness and low blood pressure. Laboratory tests revealed elevation of liver enzymes, thrombocytopenia, and increased C-reactive protein. Seroconversion to B. miyamotoi glycerophosphoryl diester phosphodiesterase antigen suggested the patient was infected with a relapsing fever group Borrelia species.


Clinical Impact of 68Ga-PSMA PET/CT in a Patient With Biochemical Recurrence of Prostate Cancer.
A 64-year-old man with history of prostate adenocarcinoma underwent radical prostatectomy in 2003. He remained with undetectable prostate-specific antigen (PSA) levels until 2014, when he then presented rising serum PSA levels and performed a Tc-MDP bone scan that was negative for metastases. In August 2015, his PSA was 4.89 ng/dL, and restaging images with pelvic MR and F-FDG PET/CT were both negative. Therefore, the patient underwent a Ga-PSMA PET/CT that showed marked tracer uptake in a single mediastinal lymph node. Histopathology demonstrated metastatic adenocarcinoma secondary to prostate cancer, altering patient management to hormone therapy instead of pelvic radiotherapy.


Alterations in grey matter structure linked to frequency-specific cortico-subcortical connectivity in schizophrenia via multimodal data fusion.
Schizophrenia (SZ) is a complex psychiatric disorder that is currently defined by symptomatic and behavioral, rather than biological, criteria. Neuroimaging is an appealing avenue for SZ biomarker development, as several neuroimaging-based studies comparing individuals with SZ to healthy controls (HC) have shown measurable group differences in brain structure, as well as functional brain alterations in both static and dynamic functional network connectivity (sFNC and dFNC, respectively). The recently proposed filter-banked connectivity (FBC) method extends the standard dFNC sliding-window approach to estimate FNC within an arbitrary number of distinct frequency bands. The initial implementation used a set of filters spanning the full connectivity spectral range, providing a unified approach to examine both sFNC and dFNC in a single analysis. Initial FBC results found that individuals with SZ spend more time in a less structured, more disconnected low-frequency (i.e., static) FNC state than HC, as well as preferential SZ occupancy in high-frequency connectivity states, suggesting a frequency-specific component underpinning the functional dysconnectivity observed in SZ. Building on these findings, we sought to link such frequency-specific patterns of FNC to covarying data-driven structural brain networks in the context of SZ. Specifically, we employ a multi-set canonical correlation analysis + joint independent components analysis (mCCA + jICA) data fusion framework to study the connection between grey matter volume (GMV) maps and FBC states across the full connectivity frequency spectrum. Our multimodal analysis identified two joint sources that captured co-varying patterns of frequency-specific functional connectivity and alterations in GMV with significant group differences in loading parameters between the SZ group and HC. The first joint source linked frequency-modulated connections between the subcortical and sensorimotor networks and GMV alterations in the frontal and temporal lobes, while the second joint source identified a relationship between low-frequency cerebellar-sensorimotor connectivity and structural changes in both the cerebellum and motor cortex. Together, these results show a strong connection between cortico-subcortical functional connectivity at both high and low frequencies and alterations in cortical GMV that may be relevant to the pathogenesis and pathophysiology of SZ.


Two-Year Clinical Evaluation of a Nanofilled Etch-and-Rinse and a Self-Etch Adhesive System Containing MDPB and Fluoride in Non-carious Cervical Lesions.
The aim of this clinical study was to evaluate the performance of restorations for non-carious cervical lesions performed with a two-step etch-and-rinse or with a two-step self-etch adhesive. The teeth to be restored (15 patients, N = 90 restorations) were randomly assigned into 3 groups (n = 30), according to the adhesive system: group 1 (G1): Peak LC Bond; group 2 (G2): Clearfil Protect Bond; and group 3 (G3): prior selective acid etching of the enamel margins before bonding with Clearfil Protect Bond. The NCCLs were restored with Amelogen Plus composite resin. Two calibrated examiners evaluated the restorations using modified US Public Health Service criteria. The data of retention, marginal integrity, and marginal discoloration were analyzed using the Kruskal-Wallis and Wilcoxon tests. There were no significant differences in clinical performance among the groups for the variables: retention, marginal integrity, and marginal discoloration after 1 year and 2 years. The alpha rates after 2 years were: 93.3% for G1 and 96.7% for G2 and G3 for retention; 93.3%, 100%, and 90% for G1, G2, and G3 for marginal discoloration; 86.7%, 96.7%, and 90% for G1, G2, and G3 for marginal integrity, respectively. The adhesives presented similar clinical performance at the end of 2 years. Also, the prior etching with phosphoric acid did not significantly improve the clinical performance of self-etch adhesive.


Rational design of MoS2-supported Cu single-atom catalysts by machine learning potential for enhanced peroxidase-like activity.
Two-dimensional molybdenum disulfide (2D-MoS2)-supported single atom nanomaterials with enhanced enzyme-like activities are potential substitutes for natural enzymes due to their huge specific surface areas, ease of decoration, high catalytic activity and high catalytic stability. However, their catalytic mechanism remains unclear, making the rational design of nanozymes difficult to achieve. Herein, the mechanisms have been explored to enhance the peroxidase-like activity of MoS2 for H2O2 decomposition. Global neutral network (G-NN) potentials were constructed to accurately and quickly illustrate the mechanisms of MoS2 catalysts and their surface modifications. The high peroxidase-like activity of the MoS2-supported Cu single atom catalyst with sulfur vacancy (Cu@MoS2-Vs) in acidic conditions was systematically evaluated using the trained G-NN potential and density functional theory (DFT), as well as experimental validation. Further analysis of the geometric and electronic properties of pivotal stationary structures revealed the enhanced electron transfer process for high catalytic performance with the modulation of the Cu single atom loading, sulfur vacancy engineering and the surrounding acidic and alkaline environment regulation on the MoS2 basal plane. The results also showed that Cu@MoS2-Vs in an acidic environment exhibited the highest peroxidase-like activity. This work is expected to provide broad implications for the rational design of substrate-supported single-atom catalysts with superior performance and lower cost by surface modification and acidic and alkaline environment regulation.


An evaluation of photographic activity schedules to increase independent playground skills in young children with autism.
We used photographic activity schedules to increase the number of play activities completed by children with autism during unstructured time on the playground. All 3 participants engaged in more playground activities during and after training, and they continued to complete activities when novel photographs were introduced.


Slice thickness measurements.
A new slice thickness test object is discussed, with results of feasibility tests using 13 transducers from six different commercial scanners presented. Both inplane beamwidth and slice thickness measurements could be easily performed and interpreted. For proper equipment gain settings the slice thickness measurement results were found to be independent of receiver gain with a tissue-mimicking (TM) fill in the test object. This is explained by a simple model in which test object low-amplitude internal fill echoes effectively act as an invariant measurement reference level with respect to the slice thickness profile echoes. This model also predicts that in clinical images the inplane lateral resolution (and slice thickness) will be governed by the local image contrast between adjacent tissues as well as the beam profile. Slice thickness measurement results from various types of real-time transducers demonstrate their inherent slice thickness focal characteristics.


Ail proteins of Yersinia pestis and Y. pseudotuberculosis have different cell binding and invasion activities.
The Yersinia pestis adhesin Ail mediates host cell binding and facilitates delivery of cytotoxic Yop proteins. Ail from Y. pestis and Y. pseudotuberculosis is identical except for one or two amino acids at positions 43 and 126 depending on the Y. pseudotuberculosis strain. Ail from Y. pseudotuberculosis strain YPIII has been reported to lack host cell binding ability, thus we sought to determine which amino acid difference(s) are responsible for the difference in cell adhesion. Y. pseudotuberculosis YPIII Ail expressed in Escherichia coli bound host cells, albeit at ~50% the capacity of Y. pestis Ail. Y. pestis Ail single mutants, Ail-E43D and Ail-F126V, both have decreased adhesion and invasion in E. coli when compared to wild-type Y. pestis Ail. Y. pseudotuberculosis YPIII Ail also had decreased binding to the Ail substrate fibronectin, relative to Y. pestis Ail in E. coli. When expressed in Y. pestis, there was a 30-50% decrease in adhesion and invasion depending on the substitution. Ail-mediated Yop delivery by both Y. pestis Ail and Y. pseudotuberculosis Ail were similar when expressed in Y. pestis, with only Ail-F126V giving a statistically significant reduction in Yop delivery of 25%. In contrast to results in E. coli and Y. pestis, expression of Ail in Y. pseudotuberculosis led to no measurable adhesion or invasion, suggesting the longer LPS of Y. pseudotuberculosis interferes with Ail cell-binding activity. Thus, host context affects the binding activities of Ail and both Y. pestis and Y. pseudotuberculosis Ail can mediate cell binding, cell invasion and facilitate Yop delivery.