Use of several inducer and substrate antibiotic combinations in a disk approximation assay format to screen for AmpC induction in patient isolates of Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., and Serratia spp.
Two-hundred consecutive, single patient isolates of Enterobacter spp., Serratia spp., Citrobacter spp., and Pseudomonas aeruginosa were evaluated for AmpC production using a variety of inducer-substrate antibiotic combinations in a disk approximation format. The combinations examined included cefoxitin-piperacillin, imipenem-cefotaxime, imipenem-ceftazidime, imipenem-piperacillin-tazobactam, and imipenem-cefoxitin. All isolates were also screened for the presence of extended-spectrum beta-lactamase (ESBL) activity. In total, 85.5% of isolates were shown to be inducible for the production of AmpC by one or more inducer/substrate combinations and 11% of all isolates were stably derepressed for the expression of AmpC. Of all of the combinations, imipenem/piperacillin-tazobactam provided the greatest sensitivity (97.1%). All combinations were 100% specific when a positive test was observed. Given this background among these organisms in our institution, it is reasonable to develop an antibiotic reporting strategy that favors the selection of agents for therapy of these organisms that do not serve as labile substrates of AmpC.


Recent advances and prospects in the differentiation of pancreatic cells from human embryonic stem cells.
Recent studies with human embryonic stem (hES) cells have established new protocols for substantial generation of pancreatic progenitors from definitive endoderm. These findings add to the efficient derivation of definitive endoderm, which is controlled by Wnt and Nodal pathways, and delineate a step forward in the quest for alternative beta-cell sources. It also indicates that critical refining of the available strategies might help define a universal protocol for pancreatic differentiation applicable to several cell lines, therefore offering the possibility for transplantation of immune-matched or patient-specific hES-derived beta-cells. We appraise here the fundamental role that bone morphogenetic protein, fibroblast growth factor, and retinoid signaling play during pancreas development, and describe a fundamental emergence of their combination in recent studies that generated pancreatic cells from hES cells. We finally enumerate some prospects that might improve further differentiation of the progenitor cells into functional beta-cells needed in diabetes cell therapy.


Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count.
Platelet-rich plasma contains autologous thrombocyte growth factors and might be promising for acceleration of dentoalveolar bone regeneration. In this study, it was analysed for platelet counts and growth factor concentrations. Platelet-rich plasma was isolated by discontinuous cell separation from 158 healthy men and 55 women aged 17-62 years. One hundred and fifteen specimens (stratified for age and gender of the donor) were analysed for growth factor concentrations and platelet count. The platelet count in platelet-rich plasma (1,407,640+/-320,100/microl) was 5 times higher than in donor blood (266,040+/-60,530/microl). Platelet-derived growth factor AB (117+/-63 ng/ml), transforming growth factor (TGF) beta -1 (169+/-84 ng/ml), and insulin-like growth factor (IGF) I (84+/-23 ng/ml) were found in large amounts, while platelet-derived growth factor (PDGF) BB (10+/-8 ng/ml) and transforming growth factor beta -2 (0.4+/-0.3 ng/ml) were found in small amounts only. The growth factor content was not well correlated with the platelet count in whole blood nor with the platelet-rich plasma (r(p)=0.35). No influence of gender or age on platelet count or growth factor concentrations was discovered (except IGF-I). While there was substantial variation in the growth factor content of platelet-rich plasma, the factors influencing this are still worthy of further investigation. Furthermore, a technique whereby the growth factor content could be rapidly assessed in platelet-rich plasma may be of therapeutic benefit.


Normal values and ranges for ventilation and breathing pattern at maximal exercise.
Assessment of the breathing pattern at maximal exercise in patients is limited because the range of ventilatory responses (minute ventilation; tidal volume; respiratory rate) at maximal exercise in normal humans is unknown. We studied 231 normal subjects (120 women; 111 men) equally distributed according to age from 20 to 80 years. Each subject performed a progressive incremental cycle ergometer exercise test to their symptom-limited maximum. Mean ventilation at the end of exercise (Vemax) was significantly higher in men (mean +/- SD, 97 +/- 25 L/min) than in women (69 +/- 22 L/min) (p less than 0.001). Minute ventilation at the end of exercise as a fraction of predicted maximal voluntary ventilation (Vemax/MVV) for all subjects was 0.61 +/- 0.14 (range, 0.28 to 1.02). There was no difference in Vemax/MVV between men (0.62 +/- 0.14) and women (0.59 +/- 0.14). Tidal volume at the end of exercise (Vtmax) was higher in men (2.70 +/- 0.48 L) than in women (1.92 +/- 0.41 L) (p less than 0.001). Any differences in Vtmax between men and women disappeared when Vtmax was corrected for baseline FVC. Respiratory rate at the end of exercise (RRmax) was 36.1 +/- 9.2 breaths per minute for all subjects. There was no difference in RRmax between men and women. The Vemax correlated best with carbon dioxide output at the end of exercise (r = 0.91; p less than 0.001) and with maximal oxygen uptake (r = 0.90; p less than 0.001) for all subjects. This study of a large group of subjects has demonstrated the wide range of possible breathing patterns which are adopted during exercise and has provided a wide range of "normal" responses which must be taken into consideration when maximal ventilatory data from exercise tests are analyzed.


Parenting work and autism trajectories of care.
This study investigates the work and care associated with raising a child with disabilities in the United States. Based on in-depth interviews with parents who have a child with autism, it develops the notion of parenting work and trajectories of care to investigate how parents navigate and coordinate the challenges of getting an autism diagnosis, obtaining educational services, and re-contextualising the possibilities for the future. I argue that parents embody a complex mix of love, hope, and responsibility in parenting work and trajectories of care that expands temporal and social elements of illness work and trajectories initially developed by Anselm Strauss and colleagues. This type of parenting work changes over time and is influenced by social structural forces and relationships in which the care takes place. The re-articulation of these analytic tools also begins to untangle the intricate mix of both medical and social models of disability that parents embrace and continuously negotiate. This study demonstrates how parents accept the medical model of disability by seeking and pushing for a clinical autism diagnosis and subsequent treatments, while at the same time challenge the limits placed on their children by providing them with opportunities, possible futures, and a sense of personhood. A Virtual Abstract of this paper can be accessed at: https://www.youtube.com/watch?v=x0UmGvpcjeQ.


Note: Solid state photon counters with sub-picosecond timing stability.
We are reporting on a design, construction, and performance of photon counting detector packages based on solid state sensors. These photon counting devices have been optimized for extremely high stability of their detection delay. The detectors have been designed for applications in fundamental metrology and optical time transfer. The single photon avalanche diode structure manufactured on silicon using the K14 technology is used as a sensor. The active area of the sensor is circular with a diameter of 100 or 200 μm. The sensor is operated in an active quenching and gating mode. The photon detection efficiency exceeds 40% in a wavelength range spanning from 500 to 800 nm. The timing resolution is better than 20 ps rms. Its detection delay is stable within ±600 fs over several days of operation, in a sense of time deviation the detection delay stability of 150 fs has been achieved. The temperature change of the detection delay is as low as 280 fs∕K. This timing performance is preserved even under extremely high background photon fluxes exceeding 100 Mc/s. The detectors have been qualified for operation in space missions.


Recent Applications of 2D Inorganic Nanosheets for Emerging Energy Storage System.
Among many types of nanostructured inorganic materials, highly anisotropic 2D nanosheets provide unique advantages in designing and synthesizing efficient electrode and electrocatalyst materials for novel energy storage technologies. 2D inorganic nanosheets boast lots of unique characteristics such as high surface area, short ion diffusion path, tailorable compositions, and tunable electronic structures. These merits of 2D inorganic nanosheets render them promising candidate materials as electrodes for diverse secondary batteries and supercapacitors, and electrocatalysts. A wide spectrum of examples is presented for inorganic nanosheet-based electrodes and electrocatalysts. Future perspectives in research about 2D nanosheet-based functional materials are discussed to provide insight for the development of next-generation energy storage systems using 2D nanostructured materials.


Chlamydophila pneumoniae infection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host immune response.
Chlamydophila pneumonia (C. pneumonia) infection has been associated with the progression of atherosclerosis. It remains unclear, however, whether C. pneumoniae in the absence of an immune response can alone initiate atherogenic events within a complex vessel environment. Left anterior descending coronary arteries isolated from porcine hearts were dissected and placed in culture medium for 72 hours before infection with C. pneumoniae. C. pneumoniae replicated within the arterial wall for the duration of the experiment (up to 10 days). A significant increase in chlamydial-HSP60 protein expression from day 2 to 10 post-infection (pi) indicated the presence of metabolically active C. pneumonia within infected vessels. Significant arterial thickening in infected coronary segments was observed by a considerable decrease in the ratio of lumen to total vessel area (48 +/- 3% at day 4 pi versus 23 +/- 3% at day 10 pi) and a significant increase in the ratio of media to luminal area (113 +/- 16% at day 4 pi versus 365 +/- 65% at day 10 pi). Structural changes were accompanied by an up-regulation of host HSP60 and proliferating cell nuclear antigen expression levels. Immunohistochemical staining confirmed proliferating cell nuclear antigen expression to be primarily localized within smooth muscle cells of the medial area. These results demonstrate that C. pneumoniae infection can stimulate arterial thickening in a complex vessel environment without the presence of a host immune response and further supports the involvement of HSP60 in this action.


Ovarian metastasis of a lymphoma presenting as primary ovarian cancer.
Ovarian metastases are being found in a variety of different malignant diseases. A clinical case of a woman with a pelvic tumor and elevated CA125 levels, and suspected primary ovarian carcinoma is presented. Surgery revealed a metastasis of a B-cell non-Hodgkin's lymphoma. Literature research shows that elevated CA125 levels are often found in lymphomas.


Simultaneous staining of cytoplasmic iron and collagen matrix in human liver biopsy specimens.
One of the major liver fibrogenic activators is the cellular iron overload that can severely damage parenchymal and non-parenchymal cells. The aim of this study was to investigate a histochemical staining technique that allows the simultaneous detection of the irregular deposition of matrix collagen and both the amount and distribution of iron in liver cells on the same histological section. The method was evaluated using 3-microm histological sections obtained from ten standard liver biopsy specimens taken from patients with hepatitis C virus-related diseases and simultaneous liver cell iron overload. The results indicate that the double-staining technique is simple, sensitive and rapid, and can be routinely applied to liver biopsy specimens for diagnostic purposes. Furthermore, it may also facilitate the study of the complex relationship between hepatic fibrosis and iron overload during common genetic or secondary liver metabolic disorders.


The many benefits of assessment/care management.
These data provide a preliminary sense of demand for services among older people. They were collected in somewhat limited geographic areas by sponsors who are known in the community. Therefore, responses may reflect perceptions of specific sponsors, the degree to which services are available in various communities, and the level of familiarity with services. However, the data give a strong indication that long-term care services are viewed as complementary, and respondents understand the need for multiple services in assisting older people. The groups or factors were remarkably similar across the six sites, as were the rankings of services according to the percentage of people who rated each one or two on a five-point scale of importance. However, there was a great deal of variation in the percentage of respondents rating the services one or two by site. These results suggest that interest in services as packages is very consistent but that the degree of interest in services may vary from one market to another. Again, this may be the result of perceptions of the sponsor, the degree of availability of services in different markets or idiosyncrasies of different populations. Services are what will allow older people to remain in their homes and to maintain a maximum degree of independence. Whether people opt for a retirement community setting for the camaraderie, security and convenience it offers, or to remain in the broader community, coordination and integration are clearly necessary to appropriate, efficient and effective use and delivery of services. It is becoming clear that older people recognize this fact and will increasingly seek integrated service packages.(ABSTRACT TRUNCATED AT 250 WORDS)


A Case of Asymptomatic Pulmonary Artery Aneurysm with Review of Management Strategies.
Pulmonary artery aneurysm (PAA) is defined as pulmonary artery diameter greater than 4 cm. With advances in cardiac imaging, the detection rate has increased but the natural history remains unknown. We present the case of a large, incidentally identified PAA in a patient with a history of congenital pulmonic stenosis.


Prosodic Parallelism-Comparing Spoken and Written Language.
The Prosodic Parallelism hypothesis claims adjacent prosodic categories to prefer identical branching of internal adjacent constituents. According to Wiese and Speyer (2015), this preference implies feet contained in the same phonological phrase to display either binary or unary branching, but not different types of branching. The seemingly free schwa-zero alternations at the end of some words in German make it possible to test this hypothesis. The hypothesis was successfully tested by conducting a corpus study which used large-scale bodies of written German. As some open questions remain, and as it is unclear whether Prosodic Parallelism is valid for the spoken modality as well, the present study extends this inquiry to spoken German. As in the previous study, the results of a corpus analysis recruiting a variety of linguistic constructions are presented. The Prosodic Parallelism hypothesis can be demonstrated to be valid for spoken German as well as for written German. The paper thus contributes to the question whether prosodic preferences are similar between the spoken and written modes of a language. Some consequences of the results for the production of language are discussed.


Randomized controlled trial of a cognitive-behavioral motivational intervention in a group versus individual format for substance use disorders.
Although group therapy is widely used for individuals with substance use disorders (SUDs), randomized clinical trials (RCTs) comparing the same treatment in a group versus individual format are rare. This paper presents the results of a RCT comparing guided self-change (GSC) treatment, a cognitive-behavioral motivational intervention, conducted in a group versus individual format with 212 alcohol abusers and 52 drug abusers who voluntarily sought outpatient treatment. Treatment outcomes demonstrated significant and large reductions in clients' alcohol and drug use during treatment and at the 12-month follow-up, with no significant differences between the group and individual therapy conditions. A therapist time ratio analysis found that it took 41.4% less therapist time to treat clients using the group versus the individual format. Participants' end-of-treatment group cohesion scores characterized the groups as having high engagement, low levels of interpersonal conflict, and low avoidance of group work, all desirable group characteristics. These findings suggest that the GSC treatment model was effectively integrated into a brief group treatment format. Health care cost containment compels further evaluations of the efficacy of group treatments for SUDs.


Aldo-ketoreductase 1c19 ablation does not affect insulin secretion in murine islets.
Beta cell failure is a critical feature of diabetes. It includes defects of insulin production, secretion, and altered numbers of hormone-producing cells. In previous work, we have shown that beta cell failure is mechanistically linked to loss of Foxo1 function. This loss of function likely results from increased Foxo1 protein degradation, due to hyperacetylation of Foxo1 from increased nutrient turnover. To understand the mechanisms of Foxo1-related beta cell failure, we performed genome-wide analyses of its target genes, and identified putative mediators of sub-phenotypes of cellular dysfunction. Chromatin immunoprecipitation analyses demonstrated a striking pattern of Foxo1 binding to the promoters of a cluster of aldo-ketoreductases on chromosome 13: Akr1c12, Akr1c13, Akr1c19. Of these, Akr1c19 has been reported as a marker of Pdx1-positive endodermal progenitor cells. Here we show that Akr1c19 expression is dramatically decreased in db/db islets. Thus, we investigated whether Akr1c19 is involved in beta cell function. We performed gain- and loss-of-function experiments in cultured beta cells and generated Akr1c19 knockout mice. We show that Foxo1 and HNF1a cooperatively regulate Akr1c19 expression. Nonetheless, functional characterization of Akr1c19 both using islets and knockout mice did not reveal abnormalities on glucose homeostasis. We conclude that reduced expression of Akr1c19 is not sufficient to affect islet function.


[Computer-assisted diagnosis in screening mammography].
Computer-aided diagnosis schemes in mammography aim at improving the mammographic detection of breast cancer. Through special computer algorithms, it is possible to automatically detect suspicious areas in mammographic images. Typical examples are schemes for automatic detection of microcalcifications and masses in mammography. The computer results may be presented to the reporting radiologist, with the computer acting as a diagnostic aid. Various computer-aided diagnosis schemes in mammography are introduced and possible clinical applications are discussed.


Precise shaping of laser light by an acousto-optic deflector.
We present a laser beam shaping method using acousto-optic deflection of light and discuss its application to dipole trapping of ultracold atoms. By driving the acousto-optic deflector with multiple frequencies, we generate an array of overlapping diffraction-limited beams that combine to form an arbitrary-shaped smooth and continuous trapping potential. Confinement of atoms in a flat-bottomed potential formed by a laser beam with uniform intensity over its central region confers numerous advantages over the harmonic confinement intrinsic to Gaussian beam dipole traps and many other trapping schemes. We demonstrate the versatility of this beam shaping method by generating potentials with large flat-topped regions as well as intensity patterns that compensate for residual external potentials to create a uniform background to which the trapping potential of experimental interest can be added.


Sialic acid, intercellular adhesion molecule-1 and rheumatoid arthritis: a study on the erythrocyte membrane.
We measured serum levels of soluble intercellular adhesion molecule-1 and erythrocyte membrane sialic acid in patients with rheumatoid arthritis and studied their correlation with the disease activity. Serum soluble intercellular adhesion molecule-1 level was determined with sandwich ELISA and sialic acid level with the method of Shamberger in 42 patients with rheumatoid arthritis and in 30 healthy controls. Significantly lower erythrocyte membrane sialic acid and higher serum levels of soluble intercellular adhesion molecule-1 were found in patients with rheumatoid arthritis compared with healthy controls (p<0.001 for both). Significant negative correlation between soluble intercellular adhesion molecule-1 level and erythrocyte membrane sialic acid concentration (r=-0.49, p<0.001) and positive correlations between soluble intercellular adhesion molecule-1 level and Ritche Articular Index score and C-reactive protein (r=0.32, p<0.05; r=0.44, p<0.01, respectively) were observed. From these data we conclude that decreases in erythrocyte membrane sialic acid concentration and increases in soluble intercellular adhesion molecule-1, erythrocyte sedimentation rate and C-reactive protein levels are present in rheumatoid arthritis, and that the increased soluble intercellular adhesion molecule-1 in rheumatoid arthritis might be due to the decreased erythrocyte membrane sialic acid concentration. The levels of soluble intercellular adhesion molecule-1 may be a novel marker for the disease status and the activity of rheumatoid arthritis.


Primary care reform: a pilot study to test the evaluative potential of the Patient Enablement Instrument in Poland.
Primary health care reform is underpinned by a move towards patient-centred holistic care. This pilot study uses the Patient Enablement Instrument (PEI) to assess outcome at a fundamental level: that of the patient and their doctor at consultation. Our aim was to assess the evaluative potential of the PEI in relation to a reform programme in Poland by (i) comparing the outcomes of consultations (using the PEI) carried out by nine doctors (three diploma GPs who had participated in the training programme, three GPs who had not participated in the training programme and three polyclinic internists); and (ii) relating PEI scores to a proxy quality process measure (consultation length). A cross-sectional quantitative questionnaire survey was carried out using the PEI. The subjects were patients consulting with nine doctors distributed within a single region around Gdansk. The overall results with the PEI and consultation length reflected UK experience. In addition, there were significant differences between groups in this pilot study. Patients seen by diploma GPs achieved higher patient enablement scores (mean 4.33, 95% confidence interval 4.09-4.58) relative to GPs (mean 3.44, 3.21-3.67) and polyclinic doctors (mean 3.23, 2.99-3.47). However, there is evidence of appreciable between-doctor variation in PEI scores within groups. The difference in patient enablement between groups was not affected by patient case mix, in contrast to the duration of consultation, which was. Holistically trained diploma GPs spent longer with patients with psychological problems. Patients seen by diploma GPs received longer consultations (mean 12.65 min, 95% confidence interval 12.18-13.13) relative to their colleagues (the GPs' mean was 10.11, 9.82-10.41 min; that of the polyclinic internists was 10.16, 9.81-10.50 min). The duration of consultation was positively correlated with patient enablement. The results of such training courses should be examined from the perspective of both the patient and their doctor. Significant differences were found in both patient enablement and consultation length between patients attending groups of doctors delivering primary care, but working from different paradigms. This pilot shows promising results which, if repeated in a larger study, would provide an objective means of evaluating such reform programmes.


Low zone tolerance induced by systemic application of allergens inhibits Tc1-mediated skin inflammation.
The induction of tolerance may be a promising target of strategies aimed at preventing harmful allergic diseases. Low zone tolerance (LZT), induced by epicutaneous application of low doses of contact allergens, inhibits the development of T(C)1-mediated contact hypersensitivity (CHS). We evaluated the effect of systemic (oral, intravenous) administration of low amounts of haptens on specific immune reactions and tolerance induction. By using the mouse model of LZT, we analyzed immune reactions in vivo (skin inflammation) and T-cell responses in vitro after oral, intravenous, or epicutaneous application of low amounts of the contact allergen 2,4,6-trinitro-1-chlorobenzene (TNCB). Subimmunogenic doses of TNCB applied orally and intravenously induced a significant tolerance reaction in vivo comparable to epicutaneously tolerized mice, indicating that LZT is a systemically mediated tolerance reaction. In vitro analysis in all models of LZT revealed the generation of IL-10 secreting, regulatory CD4+ T cells that were absolutely required for the development of hapten-specific CD8+ T(C)2 cells. Adoptive transfer experiments identified CD8+ T(C)2 cells as effector T cells of LZT inhibiting the development of CHS-promoting T(C)1 cells and consequently the manifestation of CHS. These suppressor CD8+ T(C)2 cells were found as well in skin-draining as in mesenteric lymph nodes and in the spleen of tolerized animals independent of the route of tolerization. These data indicate that systemic uptake and presentation of small amounts of haptens (eg, contact allergens, drugs, metals) induce the development of LZT and thus prevent inappropriate activation of the immune system and protect from allergic diseases. These findings will be of particular importance because tolerance induction by protocols applying subimmunogenic, low amounts of haptens may be used as tools for immunotherapy in allergic and autoimmune diseases.


Fretting Fatigue Behaviour of Pin-Loaded Thermoset Carbon-Fibre-Reinforced Polymer (CFRP) Straps.
This paper focuses on the fretting fatigue behaviour of pin-loaded carbon-fibre-reinforced polymer (CFRP) straps studied as models for rigging systems in sailing yachts, for suspenders of arch bridges and for pendent cables in cranes. Eight straps were subjected to an ultimate tensile strength test. In total, 26 straps were subjected to a fretting fatigue test, of which ten did not fail. An S⁻N curve was generated for a load ratio R of 0.1 and a frequency f of 10 Hz, showing a fatigue limit stress of the straps around the matrix fatigue limit, corresponding to 46% of the straps' ultimate tensile strength (σUTS). The fatigue limit was defined as 3 million load cycles (N = 3 × 10⁶), but tests were even conducted up to N = 11.09 × 10⁶. Catastrophic failure of the straps was initiated in their vertex areas. Investigations on the residual strength and stiffness properties of straps tested around the fatigue limit stress (for N ≥ 1 × 10⁶) showed little influence of the fatigue loading on these properties. Quasi-static finite element analyses (FEA) were conducted. The results obtained from the FEA are in good agreement with the experiments and demonstrate a fibre parallel stress concentration in the vertex area of factor 1.3, under the realistic assumption of a coefficient of friction (cof) between pin and strap of 0.5.


Using structural equation modeling to understand child and parent perceptions of asthma quality of life.
Using structural equation modeling, test a conceptual model of associations between constructs predicting parent and child asthma quality of life. Children with a confirmed asthma diagnosis and their parents completed measures of health status and independently reported on psychological functioning, family functioning, and quality of life. Measurement and structural models for predicting parent and child quality of life provided a good fit of data to the conceptual model. Parent and child independent reports of quality of life are dependent upon family functioning and child psychological functioning. Long-term asthma symptom control is the only health status variable that impacts quality of life. With minor modifications, both parent and child data fit the conceptual model. Child psychological functioning and long-term asthma control jointly contribute to quality of life outcomes. Findings suggest that both acute and long-term asthma health status outcomes have different determinants.


BCR gene recombines with genomically distinct sites on band 11Q13 in complex BCR-ABL translocations of chronic myeloid leukemia.
We have analysed a cloned 11q13/3'BCR junction fragment, one recombination product of a complex t(9;11;22) translocation in a patient with chronic myeloid leukemia. 3'M-Bcr recombined with chromosome band 11q13 at a specific point between two Alu elements lying in opposite orientation. We present new molecular data comparing the genomic location of the 11q13 breakpoint in our patient with that of one other recently reported to lie within the GSTP1 gene. This is the first time that specific breakpoint sites within a chromosomal region highly involved in complex Ph translocations have been relatively mapped. These early results argue against a precise site in 11q13 with which M-Bcr preferentially recombines and favour instead a larger recombination-prone domain. Both of the 11q13 breakpoint regions show Alu repeat elements in close proximity to the site of recombination.


Neural signatures of social conformity: A coordinate-based activation likelihood estimation meta-analysis of functional brain imaging studies.
People often align their behaviors with group opinions, known as social conformity. Many neuroscience studies have explored the neuropsychological mechanisms underlying social conformity. Here we employed a coordinate-based meta-analysis on neuroimaging studies of social conformity with the purpose to reveal the convergence of the underlying neural architecture. We identified a convergence of reported activation foci in regions associated with normative decision-making, including ventral striatum (VS), dorsal posterior medial frontal cortex (dorsal pMFC), and anterior insula (AI). Specifically, consistent deactivation of VS and activation of dorsal pMFC and AI are identified when people's responses deviate from group opinions. In addition, the deviation-related responses in dorsal pMFC predict people's conforming behavioral adjustments. These are consistent with current models that disagreement with others might evoke "error" signals, cognitive imbalance, and/or aversive feelings, which are plausibly detected in these brain regions as control signals to facilitate subsequent conforming behaviors. Finally, group opinions result in altered neural correlates of valuation, manifested as stronger responses of VS to stimuli endorsed than disliked by others.


Genome Sequence of Bacillus subtilis SPZ1, an Evolved Strain for Higher Uptake Rate of Tributyrin.
The lipase-producing strain Bacillus subtilis SPZ1 is isolated from the medium by tributyrin as the sole carbon source. Here, we present a 4.13-Mb assembly of its genome sequence, which may provide various kinds of useful information related to Bacillus spp., such as mechanisms and control of the substrate uptake and protein secretion pathways.


Selective monophosphorylation of chitosan via phosphorus oxychloride.
Chitosan was selectively monophosphorylated via reaction with phosphorus oxychloride (POCl3) to enhance water solubility while avoiding polyphosphate formation. The use of POCl3 resulted in negligible product degradation (i.e., breakdown of O-glycosidic bonds) even after a 3 d reaction period (<5% weight loss). X-ray photoelectron spectroscopy (XPS) characterization of the POCl3-phosphorylated chitosan (P-chitosan) revealed a phosphorus to nitrogen (P/N) atomic ratio of 0.30. Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy verified the monophosphorylation of chitosan's primary and secondary alcohols, and primary amines. The calcium chelation efficiency for the phosphorylated product approached 0.05 mg Ca2+ per mg of P-chitosan as measured by inductively coupled plasma-optical emission spectrometry (ICP-OES), indicating improved chelation over native chitosan. This selective monophosphorylation approach proved useful for modifying other biopolymers, including cellulose and alginate.


Geometric and topological approaches to shape variation in Ginkgo leaves.
Leaf shape is a key plant trait that varies enormously. The range of applications for data on this trait requires frequent methodological development so that researchers have an up-to-date toolkit with which to quantify leaf shape. We generated a dataset of 468 leaves produced by Ginkgo biloba, and 24 fossil leaves produced by evolutionary relatives of extant Ginkgo. We quantified the shape of each leaf by developing a geometric method based on elastic curves and a topological method based on persistent homology. Our geometric method indicates that shape variation in modern leaves is dominated by leaf size, furrow depth and the angle of the two lobes at the leaf base that is also related to leaf width. Our topological method indicates that shape variation in modern leaves is dominated by leaf size and furrow depth. We have applied both methods to modern and fossil material: the methods are complementary, identifying similar primary patterns of variation, but also revealing different aspects of morphological variation. Our topological approach distinguishes long-shoot leaves from short-shoot leaves, both methods indicate that leaf shape influences or is at least related to leaf area, and both could be applied in palaeoclimatic and evolutionary studies of leaf shape.


Culprit and victim -- DNA topoisomerase II.
The phylogenetic antiquity of DNA topoisomerases indicates their vital function. Structure and maintenance of genomic DNA depend on the activity of these enzymes, and without them DNA replication and cell division are impossible. Topoisomerase II alpha has therefore become the main target of many antitumour therapy regimens, even though the exact mechanism of cell killing remains elusive. The success of this approach is limited by the development of spontaneous resistance, and drug-induced DNA damage can increase malignancy. Nevertheless, the combined use of topoisomerase-inhibiting drugs with different mechanisms of action promises to improve particular treatment designs. The degree of topoisomerase II expression in tumours may predict the clinical course and responsiveness to therapy.


Mitofusin 2 is involved in chemotaxis of neutrophil-like differentiated HL-60 cells.
Neutrophils rapidly migrate to infection sites after the recognition of invaders. During chemotaxis, neutrophils require energy supplied by mitochondria oxidative phosphorylation (OXPHOS), whereas neutrophils rely heavily on glycolysis under normal conditions. Mitochondrial OXPHOS correlates with mitochondrial morphology. Here, we examined the mitochondrial morphology of neutrophil-like differentiated HL-60 cells after chemoattractant N-formyl-Met-Leu-Phe (fMLP) stimulation. We found that mitochondrial morphology changes to a tubular form after fMLP stimulation. Mitochondrial OXPHOS activity and mitochondrial complex II significantly increased after fMLP stimulation. On the other hand, the silencing of mitochondrial fusion protein mitofusin 2 (MFN2) suppresses mitochondrial morphological changes. Furthermore, MFN2 silencing suppressed OXPHOS activation and chemotaxis after fMLP stimulation. These results suggest that MFN2 is involved in chemotaxis of differentiated HL-60 cells depending on mitochondria.


[Drugs as risk factors of food anaphylaxis in adults].
Anaphylaxis is the most severe type of food allergy. Factors of risk are advanced age, cardiopathy, asthma, mastocytosis. Age may be linked to an increased consumption of drugs: aspirin, nonsteroidal anti-inflammatory drugs, beta-blockers, inhibitors of angiotensin converting enzyme (ACE). A case-control study comparing anaphylaxis and mild food allergies has shown a sharp increase of consumption of these drugs in patients with anaphylaxis, with odds ratio respectively of 10.8 [CI 95%: 3.10-41.3], 8.2 [CI 95%: 1.37-62.51], 6.8 [CI 95%: 1.78-27.78] and 13 [CI 95%: 1.34-310.38]. Besides, exercise potentiates the relative risk of drug consumption. Predominant mechanisms could be an increase of gut permeability enhancing the passage of food allergens in the mucosa and in blood, and the inhibition of ACE, so that the angiotensin homeostatic mechanism deteriorates. Main sites of interference may be endothelium and gut epithelium. Preventive measures excluding the intake of aspirin and nonsteroidal anti-inflammatory drugs before the meals can be recommended for food allergic and food sensitized adults. Treatment of hypertension can address to other families of drugs than ACE inhibitors (ACEI) and beta blockers. The benefit-risk ratio of beta blockers and ACEI has to be carefully considered in the case of cardiopathy. double dagger.


Giant tunneling piezoresistance of composite elastomers with interlocked microdome arrays for ultrasensitive and multimodal electronic skins.
The development of flexible electronic skins with high sensitivities and multimodal sensing capabilities is of great interest for applications ranging from human healthcare monitoring to robotic skins to prosthetic limbs. Although piezoresistive composite elastomers have shown great promise in this area of research, typically poor sensitivities and low response times, as well as signal drifts with temperature, have prevented further development of these materials in electronic skin applications. Here, we introduce and demonstrate a design of flexible electronic skins based on composite elastomer films that contain interlocked microdome arrays and display giant tunneling piezoresistance. Our design substantially increases the change in contact area upon loading and enables an extreme resistance-switching behavior (ROFF/RON of ∼10(5)). This translates into high sensitivity to pressure (-15.1 kPa(-1), ∼0.2 Pa minimum detection) and rapid response/relaxation times (∼0.04 s), with a minimal dependence on temperature variation. We show that our sensors can sensitively monitor human breathing flows and voice vibrations, highlighting their potential use in wearable human-health monitoring systems.


Decreased seizure activity in a human neonate treated with bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1.
Neonatal seizures have devastating consequences for brain development and are inadequately treated by available antiepileptics. In neonates, gamma-aminobutyric acid (GABA) is an excitatory neurotransmitter due to elevated levels of intraneuronal chloride achieved by robust activity of the Na(+)-K(+)-2Cl( -) cotransporter (NKCC1). This depolarizing action of GABA likely contributes to the lowered seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants among infants. The diuretic bumetanide inhibits NKCC1 and silences seizure activity in rodent models of neonatal seizures, but its effect on seizures in human neonates is unknown. Continuous electroencephalography (EEG) monitoring was used to quantify the number, duration, and frequency of seizures 2 hours before and after the administration of bumetanide in a neonate with intractable multifocal seizures. Significant reductions in mean seizure duration and frequency were noted following treatment, with no associated clinical side effects or metabolic imbalances. These results suggest bumetanide may exert antiepileptic effects in human neonates.


Long-term follow-up of 246 adults with juvenile idiopathic arthritis: functional outcome.
To examine the clinical and functional outcome of adults with juvenile idiopathic arthritis (JIA) using the recent World Health Organization/International League Against Rheumatism (ILAR) classification. Two hundred and fifty-nine adults with long-standing JIA (average disease duration 28.3 yr) were eligible for the study; 246 (95%) attended for an interview, clinical examination and notes review and 231 (89.2%) returned a comprehensive functional and psychosocial self-assessment questionnaire. Of all patients, 43.3% had active arthritis clinically and 54.4% on laboratory measures (C-reactive protein). Clinical inflammation was less common in systemic-onset JIA. The percentage of all patients with severe disability (Health Assessment Questionnaire score >1.5) was 42.9. Uveitis occurred frequently in the oligoarticular-onset and enthesitis-related subsets. Over 30% of the extended oligoarticular group with uveitis developed glaucoma compared with none of the enthesitis group. Adults with JIA often have significant levels of disability, often related to continuing active disease over prolonged periods. There is a clear need for good transition from paediatric to high-quality adult rheumatology care.


Dose-related hemodynamic and electrocardiographic effects of the calcium promoter BAY y 5959 in the presence or absence of congestive heart failure.
The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure. There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes. Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 microg/kg body weight per min. In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 microg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 microg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 microg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 microg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses. BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response--combining bradycardia, reduced preload and improved cardiac output--appeared to be achieved at a dose of approximately 2.0 microg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.


Enantioselective Synthesis of Quaternary Stereocenters via Chromium Catalysis.
Asymmetric allylation of aldehydes with γ-disubstituted allyl halides has been achieved in the presence of a sulfonamide/oxazoline chromium complex. A variety of synthetically useful α-homoallylic alcohols with two consecutive stereogenic centers, including one quaternary carbon, can be accessed in a highly diastereoselective and enantioselective manner.


Comparison of pregnancy outcomes in women with sickle cell disease and trait.
To compare the pregnancy and neonatal outcome in sickle cell disease and trait women. The retrospective comparative study was conducted at Abha General Hospital, Abha, Saudi Arabia, from January 2009 to December 2011. The records of women having sickle cell disease and trait were reviewed for antenatal and postnatal complications. Pregnancy and foetal outcome was also compared in both the groups. Chi-square, Fisher's Exact and Student's t tests were used for statistical analysis. Out of 112 women, 57 (50.89%) had sickle cell disease and 55 (40.10%) had sickle cell trait. The mean gravidity and parity in the latter group (5.05+/-3.51 and 3.2+/-2.74 respectively) was more than double in the former group (2.89+/-1.36 and 1.66+/-0.96 respectively). There were significant differences in antenatal complications. In the disease group, anaemia was in 55 (96.5%) cases compared to 35 (63.6%) in the trait group. Significant number of women in the first group (n=41; 71.9%) experienced painful crisis in pregnancy compared to 4 (7.27%) in the second group. Mean haemoglobin in the disease group was 8.35g/dl, while it was 9.96 g/dl in the other (p <0.01). The requirement of blood transfusion was higher in the former, 28 (38.6%) than in the latter 3 (5.54%). Frequency of preterm delivery was only slightly higher in the disease group, 14 (28.57%) than in the trait women, 13(23.63%). The mean birth weight of babies of women with the disease and the trait was 2380 and 2480 grams. This 100 grams difference, however, was statistically insignificant. Patients with sickle cell disease had more antenatal complications than those with sickle cell trait, without affecting the foetal outcome. Though the trait is generally considered a benign disease, women need special care and attention during a stressful situation like pregnancy.


Poliomyelitis eradication in China: 1953-2012.
Poliomyelitis has historically been endemic in China and has been considered an important cause of disability and death. We reviewed strategies and measures of poliomyelitis control and eradication from 1953 to 2012. Data from notifiable disease and routine immunization reporting systems and acute flaccid paralysis (AFP) surveillance were analyzed. About 20 000 poliomyelitis cases were reported annually in the prevaccine era. During 1965-1977, live, attenuated oral poliomyelitis vaccine (OPV) was administered to children through annual mass campaigns in the winter, and the number of poliomyelitis cases started to decline. A cold chain system was established during 1982, and OPV coverage increased during the early stage of the Expanded Programme on Immunization, from 1978 to 1988. Between 1989 and 1999, routine immunization was strengthened, supplementary immunization activities (SIAs) were conducted, and the AFP surveillance system was established. China reported a last indigenous poliomyelitis case in 1994 and was certified as free of polio in 2000. To maintain its polio-free status, China kept >90% coverage of 3 doses of OPV, conducted SIAs in high-risk areas, and maintained high-quality of AFP surveillance. China succeeded in stopping the outbreak in Xinjiang in 2011. China's polio-free status was achieved and maintained through strengthening routine immunization and implementing SIAs and AFP surveillance.


Pressure erosion of the femoral trochlea, patella baja, and altered patellar surfaces.
As knee flexion increases, so do tendofemoral and patellofemoral compression forces. Three cases of long-standing uncorrected flexion contractures of the knees are presented that resulted in marked erosion of the femoral trochlea, patella baja, and remodeled patellar articular surfaces likely reflecting increased angles of flexion. It is probable that the deep femoral grooves are the result of adaptation under high-level persistent contact loads from the quadriceps tendon. These examples expand our knowledge of bone remodeling and offer information of potential use in studying ancient skeletal samples.


Gliomagenesis: a game played by few players or a team effort?
Glioblastoma multiforme (GBM) represents the most aggressive and deadliest brain tumor of adults. To date, cell heterogeneity within GBM has been explained by the "hierarchical" model of tumorigenesis, aka the "cancer stem cell" hypothesis. In agreement with this model, only rare tumor cells, namely the cancer stem cells (CSCs), are responsible for GBM initiation and, as such, are considered the favored target of therapy. However, multiple evidence has recently indicated that tumor-initiating cells (TICs) may not represent a restricted and infrequent GBM component; rather, they might constitute most of the cells within the tumor bulk. Here we review several studies that recently shed new light on the process of gliomagenesis. We critically analyze the methodological inconsistencies and drawbacks that are causing protracted controversy in the field. Finally, we discuss the clinical implications and the novel therapeutic scenarios that have been put forward by the presence of functionally and molecularly distinct subpopulations of GBM-initiating cells within the same tumor.


Diffuse Alveolar Hemorrhage Associated with Dilated Cardiomyopathy and Sleep Apnea Syndrome.
We herein report a case of diffuse alveolar hemorrhage (DAH) associated with dilated cardiomyopathy (DCM) and sleep apnea syndrome (SAS) in a 47-year-old man. The patient exhibited recurring dyspnea and bloody sputum. Chest radiography showed bilateral diffuse infiltrative opacities without pleural effusion. A bronchoscopic analysis of bronchoalveolar lavage fluid revealed hemosiderin-laden macrophages. Based on these findings, he was diagnosed with DAH. Laboratory and pathological findings ruled out the possibility of collagen diseases and vasculitis. Overnight polysomnography revealed concomitant severe obstructive SAS. Treatment with continuous positive-pressure ventilation and pharmacological therapy for DCM prevented recurrence of DAH.


Evaluation of a compact multicontrast and multiresolution X-ray phase contrast edge illumination system for small animal imaging.
In this work the performance of a compact multiresolution and multicontrast x-ray phase system based on edge illumination is investigated. It has been designed for small animal imaging and with a limited footprint for ease of deployment in laboratories. The presented edge illumination system is based on a compact microfocus tungsten x-ray source combined with a flat panel detector. The source has a maximum output of 10 W when the minimum spot size of about 15 μm is used. The system has an overall length of 70 cm. A new double sample mask design, obtained by arranging both skipped and nonskipped configurations on the same structure, provides dual resolution capability. To test the system, we carried out computed tomography (CT) scans of a plastic phantom with different source settings using both single-image and multi-image acquisition schemes at different spatial resolutions. In addition, CT scans of an ex-vivo mouse specimen were acquired at the best identified working conditions to demonstrate the application of the presented system to small animal imaging. We found this system delivers good image quality, allowing for an efficient material separation and improving detail visibility in small animals thanks to the higher signal-to-noise ratio (SNR) of phase contrast with respect to conventional attenuation contrast. The system offers high versatility in terms of spatial resolution thanks to the double sample mask design integrated into a single scanner. The availability of both multi- and single-image acquisition schemes coupled with their dedicated retrieval algorithms, allows different working modes which can be selected based on user preference. Multi-image acquisition provides quantitative separation of the real and imaginary part of the refractive index, however, it requires a long scanning time. On the other hand, the single image approach delivers the best material separation and image quality at all the investigated source settings with a shorter scanning time but at the cost of quantitativeness. Finally, we also observed that the single image approach combined with a high-power x-ray source may result in a fast acquisition protocol compatible with in-vivo imaging.


Successful repair of combined septal and biventricular free wall rupture after acute myocardial infarction.
The following case is the first report of successful repair of combined left and right ventricular free wall and ventricular septal rupture. Reports of left ventricular free wall and septal rupture and reports of right ventricular free wall and septal rupture have been published both with and without successful surgical repair. This case demonstrates the presence of left and right ventricular free wall rupture along with septal rupture based upon cardiac catheterization and operative findings. In spite of her severe mechanical complications and prolonged hospital course, the patient is completely functional 1 year after surgical repair.


Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells.
Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells. Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied. Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% ± 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells. This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.


Characterization of three cryptic plasmids from Lactobacillus plantarum G63 that was isolated from Chinese pickle.
Three plasmids from Lactobacillus plantarum G63, pG6301, pG6302 and pG6303, were sequenced and have molecular sizes of 3516-bp, 9112-bp and 10047-bp, respectively. We determined the replicons of these plasmids. The pG6301 plasmid carried a replication gene that functioned by the rolling-circle replication mechanism. The Rep protein of pG6302 shared extremely low similarity with a reported plasmid, pLME300, which replicated by a bi-directional mechanism. Both the Rep protein and OriV analyses indicated a similar replication mechanism in pG6302. Conversely, we found neither the Rep protein nor OriV when we analyzed the whole sequence of pG6303. This finding may illustrate a novel replication mechanism. Additionally, the transposon, a mobilization element, was analyzed and compared to a similar insertion sequence (IS) element. A predicted lysozyme gene, pG6303 guhA, was heterologously expressed, but no activity was detected. The pG6302 and pG6303 plasmids contain new replicons and may be useful vector candidates for future molecular manipulation of L. plantarum.


Comparison of effects of spinal manipulation and massage on motoneuron excitability.
The purpose of this study was to compare the magnitude and duration of motoneuron inhibition occurring as a sequel to spinal manipulation or paraspinal and limb massage. The physiologic mechanisms involved in spinal manipulative therapy and massage therapy are largely unknown. One possible hypothesis is based upon the theory that these two distinct and different modalities may attenuate the activity of alpha motoneurons. Both modalities have been reported to produce short-term inhibition of motoneurons. Asymptomatic volunteers were randomly assigned to either a spinal manipulation, massage, or control group. Baseline tibial nerve H-reflex amplitudes were obtained prior to the application of either lumboscaral spinal manipulation or paralumbar and limb massage. Post-interventional H-reflex recordings were recorded immediately following the application of either modality. Spinal manipulation significantly (p < 0.05) attenuated alpha motoneuronal activity immediately post-therapy, as measured by the amplitude of the tibial nerve H-reflex. Massage subjects exhibited no significant reduction in motoneuronal activity immediately following administration. Spinal manipulation produced a transient attenuation of alpha motoneuronal excitability. Paraspinal and limb massage did not inhibit the motoneuron pool as measured immediately post-therapy. These findings support the supposition that spinal manipulation procedures lead to short-term inhibitory effects on motoneuron excitability to a greater magnitude than massage.


EGFR/PI3K/Akt/mTOR pathway in head and neck squamous cell carcinoma patients with different HPV status.
The aim of the study was to compare prognostic potential of PIK3CA mutations and expression of proteins involved in or regulate EGFR/PI3K/Akt/mTOR signaling in HPV16 positive and HPV negative head and neck squamous cell carcinoma (HNSCC) patients. The expression of proteins (EGFR, Akt, pAkt(Ser473), pAkt(Thr308), mTOR, PTEN, pPTEN, APOBEC3B) were assessed immunohistochemically and PIK3CA mutations (p.E542K, p.E545K, p.H1047R) by qPCR. Significantly more HPV16 positive tumors (89.29%) with low EGFR expression were found as compared to HPV negative ones (58.82%). PIK3CA mutations were detected in 7.14% of HPV16 positive and 2.5% of HPV negative cancers. In HPV16 positive patients survival analysis has shown that positive prognostic potential for disease free survival (DFS) had low expression of APOBEC3B. In HPV negative patients prognostic significance for DFS had APOBEC3B, Akt and pAkt(Thr308) levels, and for overall survival (OS) - pAkt(Thr308) only. Independent favorable prognostic factors in the whole group of patients were: low T stage, low pAkt(Thr308) expression, active HPV16 infection (for OS and DFS) and female gender (for OS). Obtained results suggest the existence of significant differences in expression and prognostic potential of proteins involved in EGFR/PI3K/Akt/mTOR signaling between HPV16 positive and HPV negative HNSCC patients.


Effects of illumination intensity and direction on object coding in macaque inferior temporal cortex.
Single unit activity in area TE was recorded from two macaques as they viewed 3D appearing rendered objects that were illuminated from different directions (without cast shadows) and intensities of illumination. The average modulation produced by changes in illumination intensity or direction was rather moderate, with the majority of the neurons responding invariantly to these lighting variables. When neural activity was affected by illumination direction, it was not manifested as a preference for a particular direction of illumination by a given neuron. Instead, the tuning appeared to be to the relative brightness of a given shaped surface at a given orientation. The modulation to changes in illumination direction was considerably smaller than that produced by changes in object shape. Most of the neurons that were unaffected by changes in illumination direction responded much less to silhouettes of these objects, indicating that these neurons were also sensitive to an object's inner features. The neuronal invariance for shading variations may provide the basis for the invariance of object recognition under changes in illumination.


Schizophrenia Patients Demonstrate Both Inter-Voxel Level and Intra-Voxel Level White Matter Alterations.
Fractional anisotropy (FA) and mean diffusivity (MD) are the most frequently used metrics to investigate white matter impairments in mental disorders. However, these two metrics are derived from intra-voxel analyses and only reflect the diffusion properties solely within the voxel unit. Local diffusion homogeneity (LDH) is a newly developed inter-voxel metric which quantifies the local coherence of water molecule diffusion in a model-free manner. In this study, 94 schizophrenia patients and 91 sex- and age-matched healthy controls underwent diffusion tensor imaging (DTI) examinations. White matter integrity was assessed by FA, MD and LDH. Group differences in these metrics were compared using tract-based spatial statistics (TBSS). Compared with healthy controls, schizophrenia patients exhibited reduced FA and increased MD in the corpus callosum, cingulum, internal capsule, fornix and widespread superficial white matter in the frontal, parietal, occipital and temporal lobes. We also found decreased LDH in the corpus callosum, cingulum, internal capsule and fornix in schizophrenia. Our findings suggest that both intra-voxel and inter-voxel diffusion metrics are able to detect impairments in the anisotropic white matter regions, and intra-voxel diffusion metrics could detect additional impairments in the widespread isotropic white matter regions in schizophrenia.


[Mobilization of leukocytes during sub-maximal dynamic exercise].
Increase of blood leucocytes induced by a dynamic exercise has been studied in 10 adult male subjects (age: 22 +/- 2 years; body weight 73 +/- 10 kg; VO2max: 54 +/- 8 ml O2/kg.min. The exercise consisted of a 20 minutes test on a cycle ergometer at a work rate eliciting a total energy expenditure roughly equal to 80% of the maximal aerobic power (80% VO2max). During exercise the absolute number of circulating leucocytes (n Leu) increased significantly toward a maximal value reached in most cases at the end of exercise. The maximal values of n Leu--expressed as percentage of n Leu measured at rest--in the different blood leucocyte types (monocytes:n Mono; granulocytes:n GR; natural killer cells:n NK) and lymphocyte subsets (lymphocytes:n LY; lymphocytes T:n T; lymphocytes B:n B; lymphocytes T helper:n T4; lymphocytes T suppressor:n T8)--were as follows:n Mono:240%; n GR:170%; n NK:490%; n LY:220%; n T:200%; n B:190%; n T4:140%; n T8:190%. With the exception of n GR, n Leu decreased during recovery at a rate depending on the leucocyte type. The n T4/n T8 ratio, equal to 1 at rest, was reduced by about 40% during exercise. This ratio rose after exercise and reached a value equal to that measured at rest after 20 minutes recovery. In agreement with FERRY (1989), we concluded that exercise is accompanied by a selective mobilization of the different leucocyte types. The magnitude of this phenomenon and the kinetics of n Leu recuperation depend on cell types.


Superoxide radical concentration and superoxide dismutase (SOD) enzyme activity in varicose veins.
The aim of this study is to measure the level of both the superoxide dismutase (SOD) enzyme and its substrate, superoxide radicals, in the wall of varicose veins. A total of 44 vein specimens were collected from 24 patients who underwent surgery for varicose veins at Asir Central Hospital (ACH), Abha, Saudi Arabia during the period from October 1999 to November 2000. The patients were 4 males and 20 females with a mean age of 35.3+/-SD 10.4 years (15-62 years). At operation, vein specimens were collected from both the stripped, mid-thigh long saphenous vein (LSV) and the avulsed distal calf varicosities, as appropriate. The samples were processed and both the SOD level and the superoxide radicals concentration were estimated using spectrophotometry. The mean SOD level in the distal calf varicosities (14.7+/-6.0 units/mg protein) was significantly higher than that in the mid-thigh LSV (8.2+/-2.9 units/mg protein, P<0.05). The mean superoxide radical concentration in the distal calf varicosities (69.5+/-11.9 nmol/ml) was also significantly higher than that in the mid-thigh LSV (33.8+/-10.5 nmol/ml, P<0.05). These results suggest that superoxide radicals play an important role in the pathogenesis of varicose veins.


Immune activation and viral replication after vaccination with an influenza A H1N1 2009 vaccine in HIV-infected children receiving antiretroviral therapy.
Immunization with a pandemic influenza A H1N1 2009 was recommended for HIV-infected patients. However, there is limited information concerning the impact of immunization with this vaccine on immune activation and HIV viral replication. In this study, 45 HIV-infected children and adolescents receiving antiretroviral therapy were immunized with a 2-dose series of nonadjuvated monovalent influenza A H1N1 2009 vaccine upon enrollment and approximately 1 month later. Immunogenicity was determined by haemagglutination inhibition assay. The level of immune activation was determined by identification of CD38 and HLA-DR on CD8+ T cells. Patients were divided into 2 groups which include patients who had an undetectable HIV viral load (HIV detectable group) and patients who show virological failure (HIV nondetectable group). The results showed seroconversion rate of 55.2% in HIV nondetectable group, whereas 31.3% was found in HIV detectable group. Both groups of patients showed no major increase in immune activation after immunization. Interestingly, a decrease in the frequency of CD8+ T cells that coexpressed CD38 and HLA-DR was observed after immunization in both groups of patients. We suggested that immunization with influenza A H1N1 2009 vaccine can induce immune response to the pandemic virus without major impact on HIV viral replication and immune activation.


Simulation of dose distribution and secondary particle production in proton therapy of brain tumor.
The aim of this study is simulation of the proton depth-dose distribution and dose evaluation of secondary particles in proton therapy of brain tumor using the GEANT4 and FLUKA Monte Carlo codes. Proton therapy is a treatment method for variety of tumors such as brain tumor. The most important feature of high energy proton beams is the energy deposition as a Bragg curve and the possibility of creating the spread out Bragg peak (SOBP) for full coverage of the tumor. A spherical tumor with the radius of 1 cm in the brain is considered. A SNYDER head phantom has been irradiated with 30-130 MeV proton beam energy. A PMMA modulator wheel is used for covering the tumor. The simulations are performed using the GEANT4 and FLUKA codes. Using a modulator wheel, the Spread Out Bragg Peak longitudinally and laterally covers the tumor. Flux and absorbed dose of secondary particles produced by nuclear interactions of protons with elements in the head are considerably small compared to protons. Using 76.85 MeV proton beam and a modulator wheel, the tumor can be treated accurately in the 3-D, so that the distribution of proton dose in the surrounding tissues is very low. The results show that more than 99% of the total dose of secondary particles and protons is absorbed in the tumor.


Lack of pollinators limits fruit production in commercial blueberry (Vaccinium corymbosum).
Modern agriculture relies on domesticated pollinators such as the honey bee (Apis mellifera L.), and to a lesser extent on native pollinators, for the production of animal-pollinated crops. There is growing concern that pollinator availability may not keep pace with increasing agricultural production. However, whether crop production is in fact pollen-limited at the field scale has rarely been studied. Here, we ask whether commercial highbush blueberry (Vaccinium corymbosum L.) production in New Jersey is limited by a lack of pollination even when growers provide honey bees at recommended densities. We studied two varieties of blueberry over 3 yr to determine whether blueberry crop production is pollen-limited and to measure the relative contributions of honey bees and native bees to blueberry pollination. We found two lines of evidence for pollen limitation. First, berries receiving supplemental hand-pollination were generally heavier than berries receiving ambient pollination. Second, mean berry mass increased significantly and nonasymptotically with honey bee flower visitation rate. While honey bees provided 86% of pollination and thus drove the findings reported above, native bees still contributed 14% of total pollination even in our conventionally managed, high-input agricultural system. Honey bees and native bees were also similarly efficient as pollinators on a per-visit basis. Overall, our study shows that pollination can be a limiting factor in commercial fruit production. Yields might increase with increased honey bee stocking rates and improved dispersal of hives within crop fields, and with habitat restoration to increase pollination provided by native bees.


Mitochondrial DNA modulation of the anchorage-independent phenotype of transformed avian cells.
The progressive loss of mitochondrial DNA in the presence of ethidium bromide in immortal avian cell lines correlates with a decrease in their potential for anchorage-independent growth in soft agar. In short-term treated cells, this effect is reversible and the recovery of cloning potential parallels the recovery of control levels of mitochondrial DNA. Long-term ethidium-bromide-treated cells are permanently respiration-deficient and display anchorage-dependent growth. Anchorage-independent revertants can be selected, suggesting that the lack of a respiratory chain per se might not be responsible for the inability of mitochondrial DNA-depleted cells to grow in soft agar. Cybrids formed from the fusion of mitochondrial DNA-depleted, anchorage-dependent cells to cytoplasts from parental cells are capable of growth in soft agar. The mitochondria-specific inhibitor, rhodamine 6G, prevents the recovery of the anchorage-independent phenotype in similar hybrids. These results suggest that mitochondrial DNA is required to maintain the transformed phenotype of avian cells.


[Ultra high risk chronic lymphocytic leukemia - characteristics and treatment options].
Chronic lymphocytic leukemia (CLL) is the most common form adult leukemia in western world. The disease is typically cha-racterized by heterogeneous clinical behavior ranging from indolent course to rapidly progressive disease. Using clinical and bio-logical factors we can stratify patients with CLL and prospectively identify those who can be expected unfavorable course. There is a special group known as ultra highrisk chronic lymphocytic leukemia with an extremely poor prognosis. These are about 10- 15% of all patients with CLL. They do not respond to standard treatment and their survival is short with a median of 2- 3 years. For highrisk patients are considered: patients with a proven TP53 defect, refractory to purine analogues or with early relapse after chemoimmunotherapy based on fludarabine ( 24 months). While the standard 1st line treatment protocol in younger patients is chemoimmunotherapy FCR, in case of ultra highrisk CLL other methods like allogeneic hematopoietic stem cell transplantation or clinical trials testing the new drugs should be considered. In particular, allogeneic hematopoietic stem cell transplantation is a very promising treatment modality that offers longterm disease control and cure regardless of the unfavorable CLL subtype. Transplantation treatment should be therefore considered in all younger patients with ultra highrisk CLL, who should be without delay referred to a center for intensive hematological treatment.


[A case report of FOLFOX treatment for primary duodenal carcinoma with multiple liver metastases].
We report a case of a woman in her sixties having primary duodenal carcinoma with multiple liver metastases who was treated with oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 2 courses of the chemotherapy, computed tomography showed a partial response without any severe adverse events. Now at 8 months, the PR stage has been maintained. So far, no standard therapeutic strategy for metastatic duodenal carcinoma has been developed. However, we suggest a FOLFOX regimen can be highly effective as a safe approach for continuously maintaining the quality of life of patients with this rare type of cancer.


Deep brain stimulation of the subthalamic nucleus as adjunct treatment for refractory epilepsy.
We studied the efficacy and safety of bilateral subthalamic deep brain stimulation (DBS) for refractory partial-onset epilepsy in two cases. This was an open treatment pilot study for subjects who had failed numerous medications and had seizure injuries. Seizure counts and adverse events were collected during a 3-4 month baseline, and for 26-32 months after DBS surgery, with AEDs held constant. Case 1, age 45, with bitemporal seizures, had about half the seizure frequency but still fell with injuries. Case 2, age 46, with left frontal encephalomalacia, had a frequency reduction of about one-third, but a more meaningful reduction of seizure severity and injuries. Subthalamic DBS partly reduced partial-onset seizures, but the quality of life was more affected by seizure-related injuries.


In vitro evidence for the interaction of tRNA(3)(Lys) with U3 during the first strand transfer of HIV-1 reverse transcription.
Over the course of its evolution, HIV-1 has taken maximum advantage of its tRNA(3)(Lys)primer by utilizing it in several steps of reverse transcription. Here, we have identified a conserved nonanucleotide sequence in the U3 region of HIV-1 RNA that is complementary to the anticodon stem of tRNA(3)(Lys). In order to test its possible role in the first strand transfer reaction, we applied an assay using a donor RNA corresponding to the 5'-part and an acceptor RNA spanning the 3'-part of HIV-1 RNA. In addition, we constructed two acceptor RNAs in which the nonanucleotide sequence complementary to tRNA(3)(Lys)was either substituted (S) or deleted (Delta). We used either natural tRNA(3)(Lys)or an 18 nt DNA as primer and measured the efficiency of (-) strand strong stop DNA transfer in the presence of wild-type, S or Delta acceptor RNA. Mutations in U3 did not decrease the transfer efficiency when reverse transcription was primed with the 18mer DNA. However, they significantly reduced the strand transfer efficiency in the tRNA(3)(Lys)-primed reactions. This reduction was also observed in the presence of nucleocapsid protein. These results suggest that tRNA(3)(Lys)increases (-) strand strong stop transfer by interacting with the U3 region of the genomic RNA. Sequence comparisons suggest that such long range interactions also exist in other lentiviruses.


Host-plant specialization in the Drosophila melanogaster species complex: a physiological, behavioral, and genetical analysis.
Drosophila sechellia, endemic to the Seychelles, breeds in a single resource, Morinda citrifolia, whereas its close sympatric relative, Drosophila simulans, is a cosmopolitan generalist breeding in a great variety of resources. The effects of morinda on various fitness traits of these two species, their F1 hybrids, and reciprocal backcrosses were analyzed. Morinda fruit is highly toxic to Drosophila species, except D. sechellia. The toxicity is expressed in adults, embryos, and larvae. In embryos, early mortality is a maternally inherited trait, depending only on mother's genotype. The tolerance of D. sechellia to morinda is fully dominant in F1 hybrids. Egg production is stimulated by morinda in D. sechellia but inhibited in D. simulans; in hybrids, the inhibition observed in D. simulans is dominant. Morinda is an oviposition attractant for D. sechellia but a repellent for D. simulans; F1 hybrids and backcross individuals exhibit intermediate, approximately additive, behavior. In the field, adult flies of the two species exhibit opposite behavior in that D. sechellia is attracted to morinda and D. simulans is attracted to banana; hybrids have an intermediate behavior. These differences between the species explain why they do not hybridize in nature although living in sympatry. The various traits have different genetic bases: three or four different genes, or groups of genes, differentiate the ecological niches of the two species.


ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin.
The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone.


Plasticity and Adaptation in Neuromorphic Biohybrid Systems.
Neuromorphic systems take inspiration from the principles of biological information processing to form hardware platforms that enable the large-scale implementation of neural networks. The recent years have seen both advances in the theoretical aspects of spiking neural networks for their use in classification and control tasks and a progress in electrophysiological methods that is pushing the frontiers of intelligent neural interfacing and signal processing technologies. At the forefront of these new technologies, artificial and biological neural networks are tightly coupled, offering a novel "biohybrid" experimental framework for engineers and neurophysiologists. Indeed, biohybrid systems can constitute a new class of neuroprostheses opening important perspectives in the treatment of neurological disorders. Moreover, the use of biologically plausible learning rules allows forming an overall fault-tolerant system of co-developing subsystems. To identify opportunities and challenges in neuromorphic biohybrid systems, we discuss the field from the perspectives of neurobiology, computational neuroscience, and neuromorphic engineering.


Anti-inflammatory and antithrombotic effects of statins in the management of coronary artery disease.
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), a potent class of cholesterol-lowering drugs, exert a number of pleiotropic effects, including anti-inflammatory and antithrombotic properties. Evidence is now accumulating that these effects are not related to the reduction in lipid levels. In vitro studies, supported recently by in vivo data, indicate that treatment with statins results in a significant decrease in the levels of inflammation markers, such as C-reactive protein, interleukin 6, and tumor necrosis factor alpha, which appear to be predictors of acute coronary events and help stratify cardiovascular risk. Up to now, only high-sensitive C-reactive protein testing has the potential to become an adjunctive method to assess the risk of coronary events in low- and high-risk individuals. Statins can also inhibit tissue factor expression, leading to impaired activation of the blood coagulation cascade, as evidenced by a decrease in thrombin generation in vivo. Interrelated inhibition of inflammation and thrombosis induced by statins is believed to largely contribute to clinical benefits from statin therapy, regardless of cholesterol levels. Further studies will answer the question whether markers of inflammation, other than C-reactive protein and possibly indices of thrombin formation, might improve cardiovascular risk stratification.


Working memory in early-school-age children with Asperger's syndrome.
Using a battery of working memory span tasks and n-back tasks, this study aimed to explore working memory functions in early-school-age children with Asperger's syndrome (AS). Twelve children with AS and 29 healthy children matched on age and IQ were recruited. Results showed: (a) children with AS performed better in digit and word recall tasks, but worse in block recall task and variant-visual-patterns test; (b) children with AS took longer time in most conditions of n-back tasks, and showed larger effects of task load. These findings indicated imbalance of working memory development in AS children: they had advantage in the phonological loop storing, but disadvantage in the visuospatial sketchpad storing, and partial deficit in central executive.


The New Low-Profile WEB 17 System for Treatment of Intracranial Aneurysms: First Clinical Experiences.
The Woven EndoBridge (WEB) is an intrasaccular flow diverter intended to treat wide-neck aneurysms. The latest generation WEBs needed a 0.021-inch microcatheter in the small sizes. Recently, a lower profile range of WEBs compliant with a 0.017-inch microcatheter (WEB 17) has been introduced. We present the first clinical results of treatment of both ruptured and unruptured aneurysms with the WEB 17. Between December 2016 and September 2017, forty-six aneurysms in 40 patients were treated with the WEB 17. No supporting stents or balloons were used. Twenty-five aneurysms were ruptured (54%). There were 6 men and 34 women (mean age, 62 years; median, 63 years; range, 46-87 years). The mean aneurysm size was 4.9 mm (median, 5 mm; range, 2-7 mm). There were 2 thromboembolic procedural complications without clinical sequelae and no ruptures. The overall permanent procedural complication rate was 0% (0 of 40; 97.5% CI, 0%-10.4%). Imaging follow-up at 3 months was available in 33 patients with 39 aneurysms (97.5% of 40 eligible aneurysms). In 1 aneurysm, the detached WEB was undersized and the remnant was additionally treated with coils after 1 week. This same aneurysm reopened at 3 months and was again treated with a second WEB. One other aneurysm showed persistent WEB filling at 3 months. Complete occlusion was achieved in 28 of 39 aneurysms (72%), and 9 aneurysms (23%) showed a neck remnant. The WEB 17 is safe and effective for both ruptured and unruptured aneurysms. The WEB 17 is a valuable addition to the existing WEB size range, especially for very small aneurysms.


Histopathologic and Molecular Features of Cutaneous Melanoma in a Moroccan Population.
Background Cutaneous cancer is the most common malignancy type, among which melanomas are considered the most aggressive and lethal. In Morocco, skin melanoma is the 25th most common cancer. To our knowledge, this is the first and largest Moroccan study specifically describing cutaneous melanoma. Materials and methods We obtained data for 100 patients diagnosed with cutaneous melanoma in the Department of Pathology of Hassan II University Hospital, Morocco. Clinical, histopathological, molecular, and follow-up data were recorded from pathology request forms and the patient's medical records. Results The mean age of our patients was 65 years old. Histologically, the most prevalent were the nodular (48%) and acro-lentiginous (38%) melanoma subtypes. A total of 66% of the patients had a Breslow thickness of >4 mm. The presence of ulceration was noted in 46% of cases. The average mitoses was 9/1 mm². A total of 44% of patients had metastatic melanoma at the time of diagnosis. The BRAF V600E mutation was found in six cases, and the C-KIT mutation in five cases. The five-year overall survival and metastasis-free survival were 85% and 15%, respectively. There was a significant correlation between Breslow thickness and Clark's level (p<0.001), histologic subtype (p=0.012), and presence of metastasis (p=0.002). There was a significant difference between the head and neck melanomas and those of the feet, particularly in the histological subtype and the presence of ulceration. BRAF V600E mutation was found in six cases of metastatic melanomas of the head and neck, of which three cases were positive for this mutation, as compared with the 23 cases of acral melanomas, which tested negative for the same mutation. Conclusion The results of our study showed that cutaneous melanomas were characterized by advanced age at diagnosis and late-stage diagnosis with a high Breslow index. The lower limbs were the most affected sites, especially in the plantar region. The acral lentiginous subtype was the most common. The presence of BRAF V600E mutation was associated with a better prognosis.


Metamaterial lens design.
Given a surface which is not necessarily rotationally symmetric, we design a second surface such that the lens bounded between these two surfaces refracts monochromatic radiation into a given point. The lens consists of a material having a negative refractive index. We then generalize a result of Veselago when the given surface is a plane and show that there are times when the second surface can never be a plane.


Revascularization of the calcarine artery in moyamoya disease: OA-cortical PCA anastomosis--case report.
A 38-year-old male presented with moyamoya disease. Occlusion of the bilateral proximal posterior cerebral arteries (PCAs) resulted in homonymous 3/4 (right half and left lower quadrant) anopsia and various mental symptoms. To prevent impending cortical blindness, revascularization to the right PCA was performed by occipital artery (OA) to calcarine artery anastomosis. His neurological state was stabilized. OA-cortical PCA (calcarine artery) anastomosis is an alternative to omentum transplantation or occipital burr hole procedures for impending cortical blindness.


Investigation of the electrospray response of lysine-, arginine-, and homoarginine-terminal peptide mixtures by liquid chromatography/mass spectrometry.
Guanidination has been used to investigate how modification of the lysine eta-amino group into the corresponding guanidino group affects response in electrospray (ES) mass spectrometry (MS). Selected ion monitoring (SIM) analysis of equimolar mixtures containing arginine-, lysine- and the corresponding homoarginine-terminal peptides following liquid chromatography (LC) showed differences in ES response. The ionisation behaviour of the standard peptides is in accordance with the postulated higher stability of the guanidino group present on arginine- and homoarginine-terminal peptides. Modification of the separation conditions employed during LC demonstrates that relative abundances of electrosprayed peptides ions rely mostly on peptide structure.


Toxic effect of aliphatic alcohols against susceptible and permethrin-resistant Pediculus humanus capitis (Anoplura: Pediculidae).
The effectiveness of 1-octanol, 1-nonanol, 1-decanol, 1-undecanol, and 1-dodecanol was evaluated by immersion method against susceptible and permethrin-resistant head lice, Pediculus humanus capitis De Geer, from Buenos Aires, Argentina. All the tested alcohols showed knockdown effect at 10 min and mortality 18 h after treatment. The highest activity was found for the 1-dodecanol (KC50 2.55%, LC50 2.28%) and the lowest for 1-octanol (KC50 8%, LC50 4.46%). The toxicity to the head lice systematically increased with the increase in carbon atoms in the n-aliphatic alcohol moiety, and with the octanol:water coefficient (r2 = 0.94). The pediculicidal activity of 1-dodecanol was not correlated with resistance to permethrin, because no significant difference was observed between toxicity parameters in the susceptible (MAR) and the permethrin-resistant populations which had different resistant levels (RR 5.77 x for E49 population, RR 9.5 x for HL population and RR > 35.3 x for GH population). The pediculicidal effect of aliphatic alcohols demonstrated in this study and the lack of correlation with the permethrin resistance may prove to have a practical value for use in susceptible and permethrin-resistant head lice control.


Group Interventions were not Effective for Female Turkish Migrants with Recurrent Depression - Recommendations from a Randomized Controlled Study.
We tested group interventions for women with a Turkish migration background living in Austria and suffering from recurrent depression. N = 66 participants were randomized to: (1) Self-Help Groups (SHG), (2) Cognitive Behavior Therapy (CBT) Groups, and (3) a Wait-List (WL) Control condition. Neither SHG nor CBT were superior to WL. On an individual basis, about one third of the participants showed significant improvements with respect to symptoms of depression. Younger women, women with a longer duration of stay in Austria and those who had encountered a higher number of traumatic experiences, showed increased improvement of depressive symptoms. The results suggest that individual treatment by ethnic, female psychotherapists should be preferred to group interventions.


A Gradient Heterostructure Based on Tolerance Factor in High-Performance Perovskite Solar Cells with 0.84 Fill Factor.
A gradient heterosturcture is one of the basic methods to control the charge flow in perovskite solar cells (PSCs). However, a classical route for gradient heterosturctures is based on the diffusion technique, in which the guest ions gradually diffuse into the films from a concentrated source of dopants. The gradient heterosturcture is only accessible to the top side, and may be time consuming and costly. Here, the "intolerant" n-type heteroatoms (Sb3+ , In3+ ) with mismatched cation sizes and charge states can spontaneously enrich two sides of perovskite thin films. The dopants at specific sides can be extracted by a typical hole-transport layer. Theoretical calculations and experimental observations both indicate that the optimized charge management can be attributed to the tailored band structure and interfacial electronic hybridization, which promote charge separation and collection. The strategy enables the fabrication of PSCs with a spontaneous graded heterojunction showing high efficiency. A champion device based on Sb3+ doped film shows a stabilized power-conversion efficiency of 21.04% with a high fill factor of 0.84 and small hysteresis.


Nonclassical degrees of freedom in the Riemann Hamiltonian.
The Hilbert-Pólya conjecture states that the imaginary parts of the zeros of the Riemann zeta function are eigenvalues of a quantum Hamiltonian. If so, conjectures by Katz and Sarnak put this Hamiltonian in the Altland-Zirnbauer universality class C. This implies that the system must have a nonclassical two-valued degree of freedom. In such a system, the dominant primitive periodic orbits contribute to the density of states with a phase factor of -1. This resolves a previously mysterious sign problem with the oscillatory contributions to the density of the Riemann zeros.


Ethylene and senescence in petals of tradescantia.
Flowers of Tradescantia (clone O2) which are ephemeral, produce ethylene during senescence with the maximum rates occurring during the initial period of fading. Senescing isolated petals produce ethylene in a similar manner, exhibit a loss of membrane semipermeability, and exogenous ethylene hastens the onset as well as the subsequent rate of this loss. The aminoethoxy analog of 0.1 millimolar rhizobitoxine completely inhibits ethylene production by isolated petals but only partially the loss of membrane semipermeability. Isolated petals acquire a sensitivity to ethylene as they mature, becoming fully sensitive on the day of anthesis.


The significance of central nicotine receptors in the aggression of isolated mice.
The effect of nicotine, and some nicotinic antagonists on aggressive behavior of isolated mice was tested. Nicotine in doses of 0.5-2 mg/kg ip and 0.005-0.06 mg/mouse ivtr potentiated the aggressiveness. However, higher doses nicotine (4 mg/kg ip and 0.09 mg/kg (Polfa). Co-suppressed the aggression. Mecamylamine, a central nicotinic antagonist in a dose of 2 mg/kg facilitated the aggression while in doses of 4 and 8 mg/kg inhibited it. Hexamethonium, a peripheral nicotinic antagonist, partially suppressed the aggressive behavior. Our results indicate that central nicotinic receptors have also a certain role in mediating the investigated type of mouse aggression.


Biomarkers of Inflammation in Inflammatory Bowel Disease.
Recent observations suggest that subjective measures of disease activity in inflammatory bowel disease (IBD) are often misleading. Objective measures of inflammation are more closely associated with important long-term outcomes, but often depend upon invasive and costly procedures such as ileocolonoscopy and cross-sectional imaging by computed tomography or magnetic resonance imaging. Noninvasive, accurate, and inexpensive measures of intestinal inflammation would allow clinicians to adopt widely the paradigm of adjusting therapies with a goal of controlling inflammation. Blood, stool, and urine markers have all been explored as indicators of intestinal inflammation in IBD, and although none has been universally adopted, some have been well-characterized, and others hold great promise. Serum C-reactive protein and fecal calprotectin are among the best-studied noninvasive biomarkers of inflammation in IBD, and their test characteristics have been described in the setting of differentiating IBD from irritable bowel syndrome, for grading inflammation, to describe the response to therapy, and in demonstrating recurrent inflammation after medical or surgically induced remission. High-throughput research platforms, including gene expression arrays, metabolomics and proteomics, are also being applied to the discovery of novel biomarkers of inflammation. It is certain that biomarkers of inflammation will attain growing importance in the clinic as we strive for more effective and cost-effective strategies to treat patients with IBD.


Development and characterization of novel potent and stable inhibitors of endopeptidase EC 126.96.36.199.
Solid-phase synthesis was used to prepare a series of modifications to the selective and potent inhibitor of endopeptidase EC 220.127.116.11 (EP24.15), N-[1(R, S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), which is degraded at the Ala-Tyr bond, thus severely limiting its utility in vivo. Reducing the amide bond between the Ala and Tyr decreased the potency of the inhibitor to 1/1000. However, the replacement of the second alanine residue immediately adjacent to the tyrosine with alpha-aminoisobutyric acid gave a compound (JA-2) that was equipotent with cFP, with a K(i) of 23 nM. Like cFP, JA-2 inhibited the closely related endopeptidase EC 126.96.36.199 1/20 to 1/30 as potently as it did EP24.15, and did not inhibit the other thermolysin-like endopeptidases angiotensin-converting enzyme, endothelin-converting enzyme and neutral endopeptidase. The biological stability of JA-2 was investigated by incubation with a number of membrane and soluble sheep tissue extracts. In contrast with cFP, JA-2 remained intact after 48 h of incubation with all tissues examined. Further modifications to the JA-2 compound failed to improve the potency of this inhibitor. Hence JA-2 is a potent, EP24.15-preferential and biologically stable inhibitor, therefore providing a valuable tool for further assessing the biological functions of EP24.15.


Health-related Quality of Life in Children and Adolescents With β-Thalassemia Major on Different Iron Chelators in Basra, Iraq.
Few studies have investigated the quality of life of children with thalassemia in the Middle East or Mediterranean region, especially Iraq. Therefore, this study was performed to assess the health-related quality of life (HRQoL) of patients with β-thalassemia major compared with healthy children and adolescents in the same age group and to evaluate the effects of different iron chelators on HRQoL measurements. A case-control study was performed on patients with β-thalassemia major registered at the Center for Hereditary Blood Diseases in Basra from February 2012 through July 2013. The group included children and adolescents aged 2 to 17 years old. HRQoL was assessed using the Pediatric Quality of Life (PedsQL) Generic Core Scale questionnaire, version 4.0, for children 2 to 12 years old and the Short Form-36 health survey questionnaire, version 2 (SF-36v2), for children and adolescents aged 13 to 17 years old. A total of 209 age-matched and sex-matched children and adolescents were included in the control group. The study did not find a significant difference in PedsQL scores among different age groups or different iron chelators, whereas there were significant differences in all of the SF-36v2 domains, with the best quality of life observed in the deferasirox group, followed by the deferoxamine group and the combined therapy group (P<0.05). The use of deferasirox among patients aged 13 to 17 years old was associated with higher SF-36v2 scores than in the other groups (P<0.05). However, for younger patients, the PedsQL scores were not significantly different for different iron chelators. The use of oral deferasirox significantly improved the quality of life of adolescents with β-thalassemia major. However, this effect was less prominent among patients aged 2 to 12 years old.