Differences in facial emotion recognition between bipolar disorder and other clinical populations: A systematic review and meta-analysis.
Facial emotion (or expression) recognition (FER) is a domain of affective cognition impaired across various psychiatric conditions, including bipolar disorder (BD). We conducted a systematic review and meta-analysis searching for eligible articles published from inception to April 26, 2023, in PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO to examine whether and to what extent FER would differ between people with BD and those with other mental disorders. Thirty-three studies comparing 1506 BD patients with 1973 clinical controls were included in the present systematic review, and twenty-six of them were analyzed in random-effects meta-analyses exploring the discrepancies in discriminating or identifying emotional stimuli at a general and specific level. Individuals with BD were more accurate in identifying each type of emotion during a FER task compared to individuals diagnosed with schizophrenia (SCZ) (SMD = 0.27; p-value = 0.006), with specific differences in the perception of anger (SMD = 0.46; p-value = 1.19e-06), fear (SMD = 0.38; p-value = 8.2e-04), and sadness (SMD = 0.33; p-value = 0.026). In contrast, BD patients were less accurate than individuals with major depressive disorder (MDD) in identifying each type of emotion (SMD = -0.24; p-value = 0.014), but these differences were more specific for sad emotional stimuli (SMD = -0.31; p-value = 0.009). No significant differences were observed when BD was compared with children and adolescents diagnosed with attention-deficit/hyperactivity disorder. FER emerges as a potential integrative instrument for guiding diagnosis by enabling discrimination between BD and SCZ or MDD. Enhancing the standardization of adopted tasks could further enhance the accuracy of this tool, leveraging FER potential as a therapeutic target.


Is endoscopic decompression of the neonatal extravesical upper pole ureterocele necessary for prevention of urinary tract infections or bladder neck obstruction?
It has been hypothesized that endoscopic decompression of the duplex extravesical ureterocele is necessary to prevent the complications of urinary tract infections and progressive hydronephrosis. This study was performed to test this premise. Infants younger than 2 weeks with an extravesical ureterocele associated with a duplex upper pole moiety were assigned to immediate endoscopic puncture of the ureterocele followed by antibiotic prophylaxis or antibiotic prophylaxis with plans for delayed surgical intervention. Radiographic studies and catheterized urine cultures were obtained at ages 3 and 6 months and for fever greater than 38.5C. All patients included in this study were followed through 6 months of life. Of the patients 32 underwent endoscopic puncture of the ureterocele. Median patient age at endoscopy was 5 days (range 3 to 13). During the first 6 months of life complications developed in 4 (12%), including febrile urinary tract infections in 3 (9%) and with progressive hydronephrosis due to incomplete puncture of the ureterocele in 1 (3%). The remaining 40 patients were treated with antibiotic prophylaxis and delayed open surgery. Median time to open surgery was 3 months (range 2 to 6). During the first 6 months of life complications developed in 5 (13%), including 3 (8%) febrile urinary tract infections and progressive hydronephrosis in 2 (5%). No statistical difference was noted between the 2 treatment groups. In patients with extravesical duplex ureteroceles neonatal complications of urinary tract infection and progressive hydronephrosis are not significantly different between those treated with immediate endoscopic decompression versus delayed open surgical intervention.


Fog collection behavior of bionic surface and large fog collector: A review.
Water shortages are currently becoming more and more serious due to complicated factors such as the development of the economy, environmental pollution, and climate deterioration. And it is the best solution to the problems faced by people in today's world to investigate the bionic structure of nature and explore effective methods for fog collection. Herein, we've illustrated the bionic structures of the Namib desert beetle, cactus spines, and spider silk, and we imitate and further modify the respective bionic structures, as well as construct multifunctional bionic structures to improve fog collection. In addition, we also expound the fog collection behavior of a large fog collector, and an excellent fog capture effect was achieved through studying the mesh structure, the surface modification of the mesh, and the construction of the fog collector. The advantages and limitations of fog collection by a harp fog collector were also explored. We hope that through this review, relevant researchers can have a deeper understanding of this field and thus promote the development of fog collection.


Self-image and perception of mother and father in psychotic and borderline patients.
Psychotic and borderline patients rated their self-image and their perception of their mother and father using the Structural Analysis of Social Behavior model (SASB). The borderline patients had more negative images of themselves and their parents, especially their fathers, than did the psychotic patients and the normal subjects, while the psychotic patients' ratings did not differ much from those of the normal subjects. The self-image was related to the images of both parents for borderline patients and normal subjects, while for the psychotic patients only the image of the mother was important for the self-image. In addition, the psychotic patients did not differentiate between the poles of control and autonomy in the introjected self-image. It was concluded that borderline patients are characterized by negative attachment, while psychotic patients are characterized by poor separation from the mother and poor differentiation between autonomy and control. The paper also discusses how this may influence the patients' relations to others. Psychotische und Borderline Patienten beurteilten ihr Selbstbild und ihre Wahrnehmung von Mutter und Vater mit Hilfe der strukturalen Analyse sozialen Verhaltens (SASB). Die Borderline Patienten hattten negativere Selbstbilder und Elternbilder (speziell Vaterbilder) als die psychotischen Patienten und gesunde Personen. Die Beurteilungen der psychotischen Patienten unterschieden sich dagegen nicht besonders von jenen Gesunder. Das Selbstbild stand in Beziehung zu beiden Elternbildern bei den Borderline Patienten und den Gesunden, während bei den psychotischen Patienten nur das Mutterbild für das Selbstbild bedeutsam war. Außerdem konnte bei den psychotischen Patienten nicht zwischen den Polen der Kontrolle und Autonomie bzgl. der introjizierten Selbstbilder differenziert werden. Aus den Ergebnissen wird gefolgert, dass Borderline Patienten durch eine negative Bindung charackterisiert sind, psychotische Patienten dagegen durch eine mangelnde Separation von ihren Müttern und eine geringe Differenzierung zwischen Autonomie und Kontrolle. Es wird außerdem diskutiert, wie die Ergebnisse auf die realen Beziehungen der Patienten zu anderen Menschen Einflus nehmen könnten. Des patients psychotiques et Borderline ont évalué leur image d'eux-mêmes et leur perception de leur mère et père à l'aide du modèle de l'Analyse Structural du Comportement Social (SASB. Les patients Borderline avaient des imagess plus négatives d'eux-mêmes et de leurs parents, surtout de leur père, que les patients psychotiques et les sujets normaux, alors que les patients psychotiques se jugeaient à peine différemment des sujets normaux. L'image de soi était en relation avec les images des deux parents pour les patients Borderline et pour les sujets normaux, alors que pour les patients psychotiques, seulement l'image de la mère jouait un rôle pour leur image. En plus, les patients psychotiques ne différenciaient pas entre les pôles de contrôle et d'autonomie dans l'image de soi introjectée. Nous en avons conclu que les patients Borderline se caractérisent par un attachement négatif, et les patients psychotiques par une faible séparation de la mère ainsi qu'une différenciation modeste entre autonomie et contrôle. L'influence de ceci sur les relations des patients avec les autrs est discutée dans cet article. Pacientes limítrofes y psicóticos evaluaron su autoimagen y la percepción que tenían de sus padres usando el modelo de Análisis estructural del comportamiento social (SASB). Los pacientes limítrofes registraron imágenes más negativas de sí mismos y de sus progenitores, especialmente de su padre, que los pacientes psicóticos y los normales, mientras que las evaluaciones de los pacientes psicóticos no difirieron mucho de las de los sujetos normales. La autoimagen tuvo relación con la imagen de ambos progenitores tanto en el caso de los pacientes limítrofes como de los sujetos normales, mientras que para los pacientes psicóticos no diferenciaron entre control y autonomía en la autoimagen introyectada. Se concluyó que los pacientes limítrofes se caracterizan por un apego negativo, mientras que los pacientes psicóticos muestran una pobre separación de su madre y también pobre discriminación entre autonomía y control. El trabajo también discute cómo esto puede influire sobre la relación de los pacientes con los demás.


[Cystic or pseudocystic ovarian masses in young girls. The role of ultrasonic diagnosis].
Twenty adnexal tumors have been discovered between 7 and 16 years old girls. With few exceptions, the sonographic appearance in nonspecific. They were grouped in four categories: teratomas, cystadenomas, adnexal torsions, polycystic diseases. Surgery with be discussed upon consideration of age, clinical signs and sonography, and diagnostic emergency will be emphasized in case of acute adnexal torsion.


Inter-observer agreement and image quality of model-based algorithm applied to the Coronary Artery Disease-Reporting and Data System score.
To evaluate the inter-observer agreement of the CAD-RADS reporting system and compare image quality between model-based iterative reconstruction algorithm (MBIR) and standard iterative reconstruction algorithm (IR) of low-dose cardiac computed tomography angiography (CCTA). One-hundred-sixty patients undergone a 256-slice MDCT scanner using low-dose CCTA combined with prospective ECG-gated techniques were enrolled. CCTA protocols were reconstructed with both MBIR and IR. Each study was evaluated by two readers using the CAD-RADS lexicon. Vessels enhancement, image noise, signal-to-noise (SNR), and contrast-to-noise (CNR) were computed in the axial native images, and inter-observer agreement was assessed. Radiation dose exposure as dose-length product (DLP) and effective dose were finally reported. The reliability analysis between the two readers was almost perfect for all CAD-RADS standard categories. Moreover, a significantly higher value of subjective qualitative analysis, SNR, and CNR in MBIR images compared to IR were found, due to a lower noise level (all p < 0.05). The mean DLP measured was 63.9 mGy*cm, and the mean effective dose was 0.9 mSv. Inter-observer agreement of CAD-RADS was excellent confirming the importance, the feasibility, and the reproducibility of the CAD-RADS scoring system for CCTA. Moreover, lower noise and higher image quality with MBIR compared to IR were found. MBIR, by reducing noise and improving image quality, can help a better assessment of CAD-RADS, in comparison with standard IR algorithm.


Effect of phenobarbital on theophylline disposition.
The effect of chronic phenobarbital administration on the pharmacokinetics of theophylline was studied in 6 healthy, nonsmoking adults. Subject compliance was verified by the determination of plasma phenobarbital levels. Following four weeks of phenobarbital administration, all six subjects showed a resultant increase in serum clearance varying from 11% to 60% with a mean increase of 34% (from 3.01 to 4.04 L/hr/1.73 M2). Theophylline appears to be metabolized more rapidly during chronic phenobarbital administration. This effect, therefore, must be taken into account when administering barbiturates to asthmatic patients for whom theophylline therapy is prescribed.


A systematic literature review of 10 years of research on sex/gender and pain perception - part 2: do biopsychosocial factors alter pain sensitivity differently in women and men?
This systematic review summarizes the results of 10 years of laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian to access multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The second set of results presented in this review (129 articles) examined various biopsychosocial factors that may contribute to differences in pain sensitivity between healthy women and men. The results revealed that the involvement of hormonal and physiological factors is either inconsistent or absent. Some studies suggest that temporal summation, allodynia, and secondary hyperalgesia may be more pronounced in women than in men. The evidence to support less efficient endogenous pain inhibitory systems in women is mixed and does not necessarily apply to all pain modalities. With regard to psychological factors, depression may not mediate sex differences in pain perception, while the role of anxiety is ambiguous. Cognitive and social factors appear to partly explain some sex-related differences. Finally, past individual history may be influential in female pain responses. However, these conclusions must be treated with much circumspection for various methodological reasons. Furthermore, some factors/mechanisms remain understudied in the field. There is also a need to assess and improve the ecological validity of findings from laboratory studies on healthy subjects, and perhaps a change of paradigm needs to be considered at this point in time to better understand the factors that influence the experience of women and men who suffer from acute or chronic pain.


[Surveillance of HIV/AIDS-related behaviors among men who have sex with men--Switzerland, 1992-2004].
To update (1992-2004, Switzerland) trends in behaviors and opinions relative to HIV prevention among men who have sex with men. A cross sectional survey, repeated five times since 1992, among readers of the gay press and members of gay associations. An increase was observed in the median number of partners (1994: 5; 2004: 7, p < 0.05), in the proportion of participants who practiced anal penetration with their stable partner (1992: 71%; 2004: 80%, p < 0.05) or with casual partners (1994: 59% 2004: 73%; p < 0.05). Non systematic use of condoms with casual partners during anal penetration increased between 1994 and 2004 (9% to 20%; p < 0.05). Combination therapies gave rise to growing pessimism among participants regarding the decrease in preventive behaviors among homosexuals. The slow trend towards a reduction of safer sex practices continues among men who have sex with men. It is necessary to strengthen prevention interventions in this population.


Laparoscopic appendectomy with 1.7-mm instruments.
A modified technique for laparoscopic appendectomy is described. The telescope features two channels, one for the optical system and the second for forceps, scissors, and endoloops. The operation is performed through the working channel. The coaxial instrument is inserted through the umbilicus. One or two additional 1.7-mm instruments stabilize the appendix during the procedure. This technique leaves practically no scars.


Hereditary multiple exostosis: another etiology of short leg and scoliosis.
A case study is presented demonstrating a patient with a scoliosis as a result of a short leg. The etiology of the short leg was a large sessile osteochondrom in a patient with Hereditary Multiple Exostoses (HME). A review of the condition is presented.


Thoracic outlet syndrome: anatomy.
The thoracic outlet region contains three important structures: the brachial plexus, the subclavian artery, and the subclavian vein. As they travel from the upper mediastinum to the upper extremity, these structures run through three important spaces: the interscalene triangle, the costoclavicular space, and the subpectoral space. Compression can occur in any of these three spaces because of structural anomalies or trauma.


Correlation of erbB-2 gene amplification with low levels of estrogen and/or progesterone receptors in primary breast cancer: do erbB-2 products delineate hormone-independent tumors?
We analyzed erbB-2 gene amplification in 170 primary breast carcinomas. Thirty-one percent of tumors exhibited additional copies of erbB-2 gene. Chi-square analysis did not elicit any association between gene amplification and either menopausal or node status. A slight trend was observed with respect to the SBR grading. In contrast, significant correlation was associated with the age of patients and we found a strong relation with the intratumoral steroid receptor status. ErbB-2 amplification significantly occurs in tumors whose estrogen receptor and progesterone receptor were below the cut-off value or absent and tumors with dissociated estrogen receptor and progesterone receptor status were revealed as entities similar to both estrogen receptor and progesterone receptor negative tumors.


Infant saccades are not slow.
Saccadic eye movements are essential for redirecting the fovea at different visual targets. In adults and children saccades are remarkably stereotyped. Peak velocity and duration of saccades are a simple function of saccade amplitude called the 'main sequence'. Saccades that are substantially slower than normal often reflect disease of the brain stem saccade generator but may also be associated with diseases of higher level structures including the cerebral hemispheres and superior colliculus. However, little is known about the speed of saccades in infancy. A single previous study reported that infant saccades may be similar to or slower than those of adults, but few saccades were recorded. The present study re-examined this issue with the technique of measuring optokinetic (OKN) quick phases, which are readily elicited from healthy and sick infants, with a view to using saccade speed as a quantitative neurological measure. We measured the duration and peak velocity of saccades (main sequence) using direct-current electro-oculography from OKN quick phases in 18 infants (nine males, nine females) aged 2 to 18 months (mean age 8 mo [SD 4]) and seven adult comparison participants (four males, three females; age range 21-32 y, mean age 27 y [SD 3]). All infant saccades showed typical relationships between duration, peak velocity, and amplitude. Overall, there was no statistically significant difference between adult and infant main sequences for duration or peak velocity. However, the differences in the main sequence for duration almost reached significance (p=0.051) for infant saccades being faster than adults. Individual differences were also present, and some infants produced saccades faster than adults, but not slower. There was no significant age trend. We conclude that measuring saccade speed is practicable in the young infant. From the age of at least 2 months, infants generate saccades with speeds similar to or slightly higher than those of adults.


Highly specific expression of luciferase gene in lungs of naïve nude mice directed by prostate-specific antigen promoter.
PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10(9)PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of the luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases.


Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations.
We examined DNA from 116 female and four male breast cancer patients for loss of heterozygosity (LOH). DNA was analysed by polymerase chain reaction using ten microsatellite markers on chromosome 11. Three distinct regions of LOH were identified: 11p15.5, 11q13 and 11q22-qter with a LOH frequency of 19, 23 and 37-43% respectively. The marker D11S969 showing the highest frequency of LOH (43%) is located at the 11q24.1-q25 region. No previous molecular genetic studies have shown frequent LOH at the region telomeric to q23 on chromosome 11. Southern analysis revealed that LOH at 11q13 was due to amplification, whereas LOH at 11q22qter was due to deletion. LOH at 11p15.5 was associated with paucity of hormone receptor proteins, high S-phase and positive node status. An association was found between LOH at 11q13 and positive node status. LOH at the 11q22-qter region correlated with a high S-phase fraction. A significant association was found between LOH at 11p15 and chromosome regions 17q21 (the BRCA1 region) and 3p.


Effect of molybdenum on structure, microstructure and mechanical properties of biomedical Ti-20Zr-Mo alloys.
Titanium has an allotropic transformation around 883°C. Below this temperature, the crystalline structure is hexagonal close-packed (α phase), changing to body-centered cubic (β phase). Zirconium has the same allotropic transformation around 862°C. Molybdenum has body-centered cubic structure, being a strong β-stabilizer for the formation of titanium alloys. In this paper, the effect of substitutional molybdenum was analyzed on the structure, microstructure and selected mechanical properties of Ti-20Zr-Mo (wt%) alloys to be used in biomedical applications. The samples were prepared by arc-melting and characterized by x-ray diffraction with subsequent refinement by the Rietveld method, optical and scanning electron microscopy. The mechanical properties were analyzed by Vickers microhardness and dynamic elasticity modulus. X-ray measurements and Rietveld analysis revealed the presence of α' phase without molybdenum, α'+α″ phases with 2.5wt% of molybdenum, α″+β phases with 5 and 7.5wt% of molybdenum, and only β phase with 10wt% of molybdenum. These results were corroborated by microscopy results, with a microstructure composed of grains of β phase and lamellae and needles of α' and α″ phase in intra-grain the region. The hardness of the alloy was higher than the commercially pure titanium, due to the action of zirconium and molybdenum as hardening agents. The samples have a smaller elasticity modulus than the commercially pure titanium.


A simple pyramid-shaped microchamber towards highly efficient isolation of circulating tumor cells from breast cancer patients.
Isolation and detection of circulating tumor cells (CTCs) has showed a great clinical impact for tumor diagnosis and treatment monitoring. Despite significant progresses of the existing technologies, feasible and cost-effective CTC isolation techniques are more desirable. In this study, a novel method was developed for highly efficient isolation of CTCs from breast cancer patients based on biophysical properties using a pyramid-shaped microchamber. Through optimization tests, the outlet height of 6 μm and the flow rate of 200 μL/min were chosen as the optimal conditions. The capture efficiencies of more than 85% were achieved for cancer cell lines (SKBR3, BGC823, PC3, and H1975) spiked in DMEM and healthy blood samples without clogging issue. In clinic assay, the platform identified CTCs in 13 of 20 breast cancer patients (65%) with an average of 4.25 ± 4.96 CTCs/2 mL, whereas only one cell was recognized as CTC in 1 of 15 healthy blood samples. The statistical analyses results demonstrated that both CTC positive rate and CTC counts were positive correlated with TNM stage (p < 0.001; p = 0.02, respectively). This microfluidic platform successfully demonstrated the clinical feasibility of CTC isolation and would hold great potential of clinical application in predicting and monitoring the prognosis of cancer patients.


Simultaneous measurement of dopamine and its metabolites, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and tryptophan in brain tissue using liquid chromatography and electrochemical detection.
An assay has been developed for brain tryptophan using reverse-phase liquid chromatography with electrochemical detection. The method simultaneously assays dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). The method does not require elution from ion exchange resins. After deproteinization and centrifugation samples are injected directly onto the chromatographic column. It was found that small changes in mobile phase pH markedly influenced the retention time of tryptophan while elution of the indoleamines and catecholamines did not change. The assay of these endogenous compounds in a single injection proved not expedient but inexpensive. Values obtained using alumina and ion exchange resins yielded comparable values.


Use of Transabdominal Ultrasound and Maternal Hormone Testing for the Prenatal Monitoring of Equine Fetal Enlarged Bladder.
Ultrasound examination during late gestation is one of the best methods for monitoring potential pregnancy risks. Enlarged bladder is a urological disorder rarely observed in equine fetuses. This clinical case report aimed to present a case illustrating the development of equine fetal enlarged bladder using transabdominal ultrasound examinations and maternal hormone evaluation during gestation. An 8-year-old Hokkaido native pony was impregnated by embryo transfer, and at 215 days of gestation, abnormalities of the fetal bladder were detected. The bladder volume increased with gestational age, and a second bladder was observed at 257 days of gestation. No abnormalities were observed in the fetal kidneys. Moreover, the maternal plasma progesterone concentration was measured throughout the gestation period. The progesterone concentration was elevated from 36 weeks of gestation until parturition. At 363 days of gestation, parturition induction was conducted, and a foal successfully delivered. This case report is the first to describe the development of equine fetal enlarged bladder and record the corresponding ultrasound and hormone profiles.


[The cervical somatosensory evoked potential in lesions of the cortical efferents].
Cervical and cortical somatosensory evoked potentials to median nerve stimulation were analysed in 20 patients with unilateral central paresis of the arm. Neither the configuration nor the latency and amplitude measures of the neck potential did reveal any association with pathological alterations of cortical efferents or with abnormal cortically evoked responses. Thus, also in this population the evaluation of cervical potentials can be done according to the known criteria.


Expanding nurse initiated X-rays in emergency care using team-based learning and decision support.
Triage nurse initiated X-rays (NIXRs) are safe and effective, however, little is known about the ability of other RNs, particularly those without postgraduate qualifications in emergency nursing, to order NIXRs. The aim of this study was to evaluate an innovative NIXR education programme for emergency nurses. The education programme was multi-faceted, delivered using Team-Based Learning (TBL) and augmented by a decision support checklist. Using a prospective exploratory design, 276 NIXR requests from June to December 2011 were audited. Three groups were compared: (i) RNs with and without postgraduate qualifications irrespective of how they were educated in NIXR, (ii) RNs with and without postgraduate qualifications who undertook the NIXR education programme, and (iii) RNs who did and did not undertake the NIXR programme irrespective of postgraduate qualifications. There were 130 NIXRs by 28 RNs with postgraduate qualifications and 146 NIXRs by 12 RNs without postgraduate qualifications. Analysis of all RNs showed RNs without postgraduate qualifications had higher incidence of appropriate NIXRs (83.6% vs 66.2%, p=0.003) however when controlled for the NIXR education programme, statistical significance was lost (83.6% vs 67.5%, p=0.017). RNs who undertook the NIXR education programme had superior documentation of patient assessment findings and higher incidence of appropriate X-ray requests than RNs who did not undertake the NIXR education programme (80.4% vs 65.2%, p=0.042). With appropriate educational preparation, RNs without postgraduate qualifications in emergency nursing can safely engage in NIXR. Structured education using TBL and a decision support checklist produces superior assessment and X-ray requests when compared to ad hoc education and role modelling.


Robotic fabrication of high-quality lamellae for aberration-corrected transmission electron microscopy.
Aberration-corrected scanning transmission electron microscopy (STEM) is widely used for atomic-level imaging of materials but severely requires damage-free and thin samples (lamellae). So far, the preparation of the high-quality lamella from a bulk largely depends on manual processes by a skilled operator. This limits the throughput and repeatability of aberration-corrected STEM experiments. Here, inspired by the recent successes of "robot scientists", we demonstrate robotic fabrication of high-quality lamellae by focused-ion-beam (FIB) with automation software. First, we show that the robotic FIB can prepare lamellae with a high success rate, where the FIB system automatically controls rough-milling, lift-out, and final-thinning processes. Then, we systematically optimized the FIB parameters of the final-thinning process for single crystal Si. The optimized Si lamellae were evaluated by aberration-corrected STEM, showing atomic-level images with 55 pm resolution and quantitative repeatability of the spatial resolution and lamella thickness. We also demonstrate robotic fabrication of high-quality lamellae of SrTiO3 and sapphire, suggesting that the robotic FIB system may be applicable for a wide range of materials. The throughput of the robotic fabrication was typically an hour per lamella. Our robotic FIB will pave the way for the operator-free, high-throughput, and repeatable fabrication of the high-quality lamellae for aberration-corrected STEM.


Palladium-catalyzed [3+2] intramolecular cycloaddition of alk-5-ynylidenecyclopropanes: a rapid, practical approach to bicyclo[3.3.0]octenes.
Readily accessible hex-5-ynylidenecyclopropane derivatives cycloisomerize to bicyclic five-membered carbocycles upon heating with catalytic amounts of a palladium complex.


Inhibition of plaque-forming cells with anti-idiotope or hapten: variation due to hapten density on indicator red cells.
Phosphorylcholine (PC)-specific antibody plaque-forming cells (PFC) were enumerated in the spleen of BALB/c mice immunized with S. pneumoniae R36a bacterial vaccine. Two indicator red blood cells were compared: RBC coupled with the hapten, PC-RBC, and cells coupled with PC-bearing polysaccharide from the pneumococcus, PnC-RBC. Equal numbers of direct (IgM) PFC were detected with both types of indicator cells. However, a significant difference appeared in the attempt to inhibit the respective PFC either with hapten (monovalent PC chloride, PCCl) or with monoclonal antibodies against T15 idiotopes (anti-Id). At optimal coupling concentrations, inhibition of anti-PnC-RBC plaques required a 10-fold higher concentration of the hapten when compared to anti-PC-SRBC plaques. Also, the inhibition of anti-PnC-SRBC plaques with anti-Id required much higher concentration of the antibody. The phenomenon may be explained by a higher epitope density on PnC-RBC than on PC-RBC. Heavily coupled PC-RBC were more difficult to inhibit (much like the PnC-RBC) by either the hapten or the anti-Id than lightly coupled PC-RBC. A mathematical analysis of the experimental curves supports the notion that under the assay conditions used, inhibition by either the hapten or the anti-Id is influenced primarily by antibody secretion rate and epitope density on indicator cells. If the 2 variables are too high, a significant inhibition of PFC with a low affinity anti-Id may not be possible. The theory also predicted that addition of a small amount of hapten into the assay would be roughly equivalent to secretion rate reduction and would facilitate the plaque inhibition by anti-Id. Indeed, we show a synergism between a minute (non-inhibitory) amount of PCCl and anti-Id in the inhibition of PC-specific PFC. These results point out that the detection of an idiotype-bearing PFC by plaque-inhibition assay is greatly influenced by technical variation in the assay, in particular, the preparation of the indicator red cells.


Reflective interventions: Enactivism and phenomenology on ways of bringing the body into intellectual engagement.
When it comes to the body, the professional pedagogical field shows a paradoxical attitude: With regard to sense-oriented school subjects, educational policies tend to underline a close relatedness of body and mind. However, where learning is primarily connected with mental activities and intellectual engagement, the body is rarely assigned an integral role. Discussing the grounding ideologies of this paradox, I will consult phenomenological and enactivist perspectives in order to develop an approach to embodied learning which takes into account both sense-oriented as well as intellectual domains. I will argue that considering the interdependence of body and mind including their situatedness does not only benefit the cultivation of the body and the senses, but also opens up further perspectives for intellectual engagement.


Factors associated with breastfeeding duration: a 30-month cohort study in northwest China.
Factors associated with breastfeeding need to be explored in the northwest of China. This study aimed to measure the full duration of breastfeeding and identify factors associated with breastfeeding in Shihezi City in Northwest China. A prospective cohort study was undertaken to obtain details of child feeding practices using structured questionnaires in 2007-2010. Before discharge from hospitals, 681 mothers were randomly recruited and interviewed in maternity units for breastfeeding. After discharge, the mothers were contacted by telephone at monthly intervals within the first 6 months and then at 2-month intervals until discontinuation of breastfeeding. The breastfeeding initiation rate was 95.9%. The breastfeeding rates then declined to 69.6% at 6 months, 29.7% at 12 months, and 2.3% at 24 months. The median duration of "any breastfeeding" was 9 months. The exclusive breastfeeding rate was low because of the high rate of prelacteal and early complementary feeding. Cox regression analyses revealed that mothers who had preterm babies believed that breast milk could not meet infants' needs and intended to breastfeed for less than 6 months, and mothers with late onset of lactogenesis II and whose parents lived in Xinjiang were more likely to stop breastfeeding. Younger maternal age, employment, and suffering from illness were also associated with a shorter duration of breastfeeding. The duration of "exclusive" and "any breastfeeding" was below the Chinese and World Health Organization breastfeeding goals. Shorter duration of breastfeeding was associated with having grandparents residing within the same province, maternal age, illness and employment, gestational age, and delayed onset of lactogenesis.


Nystagmus in periventricular leucomalacia.
Periventricular leucomalacia (PVL) is a lesion in the immature brain involving the optic radiation. Children with PVL have visual problems including crowding, visual field defects, strabismus, and visual perceptual/cognitive deficits, together with nystagmus. They often have optic nerve hypoplasia seen either as small discs or as large cupping of normal sized optic discs. This study aimed to perform eye movement recordings in a group of children with PVL in order to characterise and classify the nystagmus. 19 children with PVL on cerebral imaging underwent eye movement recordings with the Ober-2 infrared reflection technique. 16 of the 19 subjects had horizontal nystagmus. The present study shows that nystagmus is commonly seen in children with PVL.


Clinical applications of intra-cardiac four-dimensional flow cardiovascular magnetic resonance: A systematic review.
Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) is an emerging non-invasive imaging technology used to visualise and quantify intra-cardiac blood flow. The aim of this systematic review is to assess the literature on the current clinical applications of intra-cardiac 4D flow CMR. A systematic review was conducted to evaluate the literature on the intra-cardiac clinical applications of 4D flow CMR. Structured searches were carried out on Medline, EMBASE and the Cochrane Library in October 2016. A modified Critical Skills Appraisal Programme (CASP) tool was used to objectively assess and score the included studies. Studies were categorised as 'highly clinically applicable' for scores of 67-100%, 'potentially clinically applicable' for 34-66% and 'less clinically applicable' for 0-33%. Of the 1608 articles screened, 44 studies met eligibility for systematic review. The included literature consisted of 22 (50%) mechanistic studies, 18 (40.9%) pilot studies and 4 (9.1%) diagnostic studies. Based on the modified CASP tool, 27 (62%) studies were 'highly clinically applicable', 9 (20%) were 'potentially clinically applicable' and 8 (18%) were 'less clinically applicable'. There are many proposed methods for using 4D flow CMR to quantify intra-cardiac flow. The evidence base is mainly mechanistic, featuring single-centred designs. Larger, multi-centre studies are required to validate the proposed techniques and investigate the clinical advantages that 4D flow CMR offers over standard practices. PROSPERO=CRD42016051438.


Modifiable lifestyle factors and cognitive reserve: A systematic review of current evidence.
This systematic review aims to summarize cognitive reserve (CR) evaluation approaches and to examine the role of seven selected modifiable lifestyle factors (diet, smoking, alcohol consumption, physical activity, cognitive leisure activity, sleep, and meditation) in mitigating the impacts of age- or disease-related brain changes on cognition. Eighteen population-based English empirical studies were included. We summarize the study designs and identify three CR models that were broadly used in these studies, including a residual model assessing lifestyle factors in relation to unexplained variance in cognition after accounting for brain markers, a moderation model testing whether lifestyle factors moderate the relationship between brain status and cognition, and a controlling model examining the associations between lifestyle factors and cognition when controlling for brain measures. We also present the findings for the impact of each lifestyle factor. No studies examined diet, sleep, or meditation, and only two studies focused on smoking and alcohol consumption each. Overall, the studies suggest lifestyle activity factors (physical and cognitive leisure activities) may contribute to CR and attenuate the damaging impact of brain changes on cognition. Standardized measurements of lifestyle factors and CR are needed, and mechanisms underlying CR need to be further addressed as well.


Growth of H-35 rat hepatoma cells in unsupplemented serum-free media: effect of transferrin, insulin and cell density.
Serum-free tissue culture medium consisting of a 1:1 mixture of Dulbecco's modified Eagle's medium (DMEM) and Ham's F12 medium is herein shown to support growth of Reuber H-35 cells over several days in culture. Cells were initially plated in serum containing DMEM medium for 3 h. After cell attachment, serum is removed and replaced with a serum-free 1:1 mixture of these two commercially available tissue culture media. The doubling time of cell growth in this unsupplemented serum-free medium was 46 h in lightly plated cultures over the first 5 d. The presence of transferrin (5 micrograms/ml) and insulin (3.3 nM) results in a cell doubling time of 17 h, which equaled the growth rate in medium containing 10% fetal bovine serum. In the absence of transferrin, growth rates in serum-free medium were correlated with the cell density of cultures. Conditioned medium from dense, serum-free cultures has growth-stimulating activity in recipient lightly plated cultures. This simple, serum-free culture medium will facilitate studies on the growth regulation of H-35 rat hepatoma cells.


Toluquinol, a marine fungus metabolite, is a new angiosuppresor that interferes with the Akt pathway.
Toluquinol, a methylhydroquinone produced by a marine fungus, was selected in the course of a blind screening for new potential inhibitors of angiogenesis. In the present study we provide the first evidence that toluquinol is a new anti-angiogenic-compound. In a variety of experimental systems, representing the sequential events of the angiogenic process, toluquinol treatment of activated endothelial cells resulted in strong inhibitory effect. Toluquinol inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results indicate that the observed growth inhibitory effect could be due, at least in part, to an induction of apoptosis. Toluquinol induced endothelial cell death is mediated via apoptosis after a cell cycle block and caspase activation. Capillary tube formation on Matrigel and migratory, invasive and proteolytic capabilities of endothelial cells were inhibited by addition of toluquinol at subtoxic concentrations. Inhibition of the mentioned essential steps of in vitro angiogenesis agrees with the observed inhibition of the in vivo angiogenesis, substantiated by using the chick chorioallatoic membrane assay and confirmed by the murine Matrigel plug, the zebrafish embryo neovascularization and the zebrafish caudal fin regeneration assays. Data here shown altogether indicate that toluquinol has antiangiogenic effects both in vitro and in vivo that are exerted partly by suppression of the VEGF and FGF-induced Akt activation of endothelial cells. These effects are carried out at lower concentrations to those required for other inhibitors of angiogenesis, what makes toluquinol a promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies.


Pesticide use and non-Hodgkin's lymphoma mortality in Brazil.
Brazil is one of the major pesticide consumers in the world. The continuous exposure to these substances may be etiologically associated with the development of Non-Hodgkin's Lymphoma (NHL). Estimate the correlation between the per capita sales of pesticides in 1985 (exposure) and NHL mortality rates between 1996 and 2005 (outcome), by Brazilian micro-regions. In this ecological descriptive study, the per capita consumption of pesticides in 1985 was used as a proxy of the population exposure to these chemicals in Brazil. All deaths by NHL occurred in the 446 non-urban micro-regions, between 1996 and 2005, among individuals with ages between 20 and 69, of both sexes, were retrieved from the Brazilian Mortality Information System. Micro-regions were then categorized into low, medium, high and very high pesticide consumption, according to the quartiles of per capita consumption of pesticides. NHL mortality rates and rate ratios for each quartile were obtained using the lowest quartile as reference. In addition, the Spearman's correlation coefficient between pesticide consumption and NHL mortality rates was estimated. A moderate correlation between per capita pesticides consumption and standardized mortality rate for NHL was observed (r=0.597). In addition, using the lowest quartile of pesticide consumption as a reference, the higher the quartile of pesticide consumption, the higher was NHL mortality risk: men - (second quartile - MRR=1.69, CI 95% 1.68-1.84; third quartile - MRR=2.41, CI 95% 2.27-2.57; fourth quartile - MRR=2.92, CI 95% 2.74-3.11) and females (second quartile - MRR=1.87, CI 95% 1.69-2.06; third quartile - MRR=2.28, IC 95% 2.10-2.47; fourth quartile - MRR=3.20; CI 95% 2.98-3.43). Our results suggest that pesticide exposure may play a role in the etiology of NHL.


Prevalence and Associated Factors of Erectile Dysfunction in Patients With Moderate to Severe Psoriasis and Healthy Population: A Comparative Study Considering Physical and Psychological Factors.
Recent studies have shown that psoriasis is associated with an increased prevalence of erectile dysfunction. To our knowledge, no comparative study has considered simultaneously the role of organic factors and psychological factors in this process. We performed a prospective case series study matched by age to explore the prevalence of erectile dysfunction in psoriasis patients compared to a healthy population and to investigate the role of anxiety, depression, and cardiovascular risk factors in the relationship between psoriasis and erectile dysfunction. The healthy group was matched by frequency to cases by age. Seventy-nine patients with moderate to severe psoriasis and 79 healthy controls participated in the study. Participants completed the Massachusetts General Hospital Sexual Functioning Questionnaire and the Hospital Anxiety and Depression Scale. Psoriasis patients had an increased prevalence of erectile dysfunction in comparison to controls, 34.2 vs. 17.7 % (p < .05). Multivariate analysis showed a significant association between erectile dysfunction and age, smoking and anxiety/depression, but not with psoriasis per se. In conclusion, the higher prevalence of smoking and anxiety/depression among patients with moderate to severe psoriasis probably explains the higher prevalence of erectile dysfunction in this population.


The classification of intracranial aneurysm neck: a single center research experience.
There is associating with incidence of unfavorable outcomes compared to microsurgical clippings. We are in order to investigate the outcomes of microsurgical clipping for intracranial aneurysms and determine the ideal clipping methods for different aneurysm subtypes. Retrospectively analyzed the clinical characteristics and follow-up data (completely recorded) of 123 patients with 128 aneurysms were treated. 20 cases were treated as control group from October 2013 to December 2013. Since January 2014, aneurysms were classified base on the 20 cases of aneurysm imaging data. 103 patients were treated as experimental group, the classification of aneurysms previously proposed was used to estimate the way of surgery, and the guiding value of the genotype was verified according to the intraoperative findings. The proposed aneurysm classification is based on the virtual surface of the aneurysm and the parent artery, the aneurysm neck was classified as follows: subtype I, the curved surface of the neck is a single curved surface; subtype II, the neck is hyperboloid; subtype III, neck is a three-curved surface. Aneurysms were divided into further subtypes according to the ratio of the width of the aneurysm neck surface and the length of the artery circumference: subtype A, the ratio of the aneurysm neck surface to the parent artery was not more than 0.5; subtype B, more than 0.5. There are some clamping methods include simple, sliding, interlocking and hybrid. In the control group, patients did not undergo a suitable clipping scheme without classification of aneurysm neck (unclassed clipping). While causing the occurrence of occlusion adverse events, including neck residual, Tumor artery stenosis, electrophysiological changes, the lack of blood supply and so on. The experimental[page1image12073600]group was analyzed by using a predetermined clipping scheme (classed clipping), and the use of aneurysms clamps was approximately the same as expected. Compared the preoperative assessment with the actual situation, the consistency of the control group was 50% and the experimental group was 96%. Adverse events of classed clipping is 2%, another is 60%. There is a significant difference between the two groups (P < 0.05).Classed clipping of subject IA and IB are simple (mean 1.2 and 1.3 clips); classed clipping of subject IIA is simple and interlocking(mean 1.2 clips); classed clipping of subject IIB is sliding and hybrid(mean 2.05 clips); classed clipping of subject IIIA and IIIB are hybrid(mean 2.3 clips). There is a higher consistency in surgery through the above classification of preoperative assessment of clipping. There was no adverse event of intracranial aneurysm clipping in the clipping mode selected by the above classification, and satisfactory surgical clipping rate was achieved and no recurrence was found.


[Research on effect of total saponins of yinfenglun on uterine].
To research the effect of total saponins of Yinfenglun on uterine. Models of uterine inflammation were established to observe the effect of total saponins of Yinfenglun. Uterine contractive effects were studied on rats in vitro and on rabbit in vivo. Weight of uterus and levels of estrogen and progestogen were determined. Total Saponins of Yinfenglun had the ameliorated tendency to metritis of model rats, and increased the contractive range and motorricity of uterine of rats in vitro and of rabbit in vivo. The effect to uterus in vivo maintained longer. Total saponins of Yinfenglun could increase the weight of uterus and have an increased tendency on the content of estrogen, but not the level of progestogen. There are obvious effects on uterine of total saponins of Yinfenglun, which are related to its clinical use.


Protein-Protein Interfaces in Viral Capsids Are Structurally Unique.
Viral capsids exhibit elaborate and symmetrical architectures of defined sizes and remarkable mechanical properties not seen with cellular macromolecular complexes. Given the uniqueness of the higher-order organization of viral capsid proteins in the virosphere, we explored the question of whether the patterns of protein-protein interactions within viral capsids are distinct from those in generic protein complexes. Our comparative analysis involving a non-redundant set of 551 inter-subunit interfaces in viral capsids from VIPERdb and 20,014 protein-protein interfaces in non-capsid protein complexes from the Protein Data Bank found 418 generic protein-protein interfaces that share similar physicochemical patterns with some protein-protein interfaces in the capsid set, using the program PCalign we developed for comparing protein-protein interfaces. This overlap in the structural space of protein-protein interfaces is significantly small, with a p-value <0.0001, based on a permutation test on the total set of protein-protein interfaces. Furthermore, the generic protein-protein interfaces that bear similarity in their spatial and chemical arrangement with capsid ones are mostly small in size with fewer than 20 interfacial residues, which results from the relatively limited choices of natural design for small interfaces rather than having significant biological implications in terms of functional relationships. We conclude based on this study that protein-protein interfaces in viral capsids are non-representative of patterns in the smaller, more compact cellular protein complexes. Our finding highlights the design principle of building large biological containers from repeated, self-assembling units and provides insights into specific targets for antiviral drug design for improved efficacy.


Intrauterine Growth Restriction: Postnatal Monitoring and Outcomes.
Intrauterine growth restriction (IUGR) is an important cause of fetal, perinatal and neonatal morbidity and mortality. IUGR occurs because of multiple reasons. Neonates with IUGR experience acute problems in the perinatal and early neonatal period that can be life-threatening. The unfavorable uterine environment causing growth restriction results in programming that predisposes IUGR infants to long-term health issues such as poor physical growth, metabolic syndrome, cardiovascular disease, neurodevelopmental impairment and endocrine abnormalities, warranting careful monitoring. It is imperative to strike the balance between achieving optimal catch-up to promote normal development, while preventing the onset of cardiovascular and metabolic disorders in the long-term.


DSIP/DSIP-P and circadian motor activity of rats under continuous light.
Daily intravenous injection of 30 nmol/kg DSIP (delta sleep-inducing peptide) in rats under constant illumination produced marked changes of their motor activity as compared to saline controls. Similar marked but distinctly different effects on the circadian pattern of locomotor behavior partially abolished by constant illumination were also obtained after repeated administration of 0.1 nmol/kg DSIP-P (the phosphorylated analogue of DSIP) which enhanced overall motor activity. In both instances the results additionally differed from those reported for a normal 12 hr light:dark cycle. The present results support the hypothesis that DSIP might primarily act by influencing circadian rhythmicity.


Substituted quinazolines, part 3. Synthesis, in vitro antitumor activity and molecular modeling study of certain 2-thieno-4(3H)-quinazolinone analogs.
The synthesis of some new 2-thieno-4(3H)-quinazolinone derivatives and their biological evaluation as antitumor agents using the National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Compounds 2-(2-thienylcarbonylamino)-5-iodo-N-(4-hydroxyphenyl)-benzamide (16), 2-(2-thieno)-6-iodo-3-phenylamino-3,4-dihydro-quina-zolin-4-one (26), and 2-(2-thieno)-4-[4-sulfonamidobenzylamino]-6-iodo-quinazoline (42), with GI(50) values of 12.7, 10.3, 16.9 microM, respectively, proved to be the most active members in this study, as compared to the known drug 5-FU. Conformational analysis of the most active molecules using molecular modeling and QSAR techniques enabled the understanding of the pharmacophoric requirements for 2-thieno-quinzolinone derivatives as antitumor agents. These three quinazolinone analogs (16, 26, 42) could be considered as useful templates for future development to obtain more potent antitumor agents.


Effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells.
The study investigated the effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells. Six human colorectal cancer cells were exposed to pemetrexed, gefitinib, and their combination. Antitumor effects were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Thymidylate synthase (TS) mRNA expression and EGFR mutation were studied by real-time RT-PCR and DNA sequence determination. Pharmacological interaction was studied using the combination index method. Cell cycle distribution and apoptosis were determined by flow cytometry. Activity assay was performed to assess the effects of drugs on TS activity, and Western blot was performed to assess the protein expression of pEGFR, pAKT, and pERK 1/2. Six colorectal cancer cells are all sensitive to pemetrexed, and TS gene expression of cells was negatively related to pemetrexed sensitivity. The cytotoxic synergism was observed in concurrent pemetrexed combined with gefitinib and sequential pemetrexed followed by gefitinib. The combination of pemetrexed and gefitinib modulated cell cycle and induced apoptosis. Pemetrexed combined with gefitinib decreased TS mRNA expression and in situ activity. Pemetrexed induced an EGFR-mediated activation of the phosphatidylinositol 3-kinase/AKT and ERK pathway, which was inhibited by gefitinib. Pemetrexed is a promising agent, and pemetrexed combined with gefitinib has a significantly synergistic effect on colorectal cancer cells, which seems to present a strategy of pemetrexed combined with EGFR-TKIs in colorectal cancer treatment.


Vaccination of larvae of the bony fish gilthead seabream reveals a lack of correlation between lymphocyte development and adaptive immunocompetence.
Fish eggs are released and embryos hatch into a pathogenically hostile environment, at a time when their immunological capacity is severely limited. Although the eggs are initially protected by the envelope as well as by several innate and adaptive immune substances, which are transferred to eggs during fish vitellogenesis, it seems that young specimens depend fundamentally on their innate defence mechanisms. Here we show in the gilthead seabream, an immunologically tractable teleost fish model, that the first lymphocyte marker genes, those coding for the two subunits for the recombination activating gene, were detected by RT-PCR around 21-27 days post-hatching (dph). In addition, the transcripts coding for the alpha and beta subunits of the T-cell receptor and the light and heavy chains of immunoglobulin M were detected at 27-48 dph. However, most innate immune genes analyzed were already expressed at hatching, including those coding for the toll-like receptors, pro- and anti-inflammatory molecules, antiviral and antibacterial factors, and phagocyte markers. Using the information from the gene expression study, we also examined the achievement of immunocompetence by analyzing the protection induced by a bacterin against the pathogenic bacterium Photobacterium damselae subsp. piscicida. The results show that vaccination of young larvae of this species by either immersion or oral routes resulted in increased susceptibility to infection of the specimens, and point to the lack of correlation between the achievement of immunocompetence and detection of the adaptive immunity markers.


Canopy spray deposition and related mortality impacts of commonly used insecticides on Drosophila suzukii Matsumura (Diptera: Drosophilidae) populations in blueberry.
Insecticide applications in blueberry production systems play a crucial role in the control of Drosophila suzukii populations. Here, quantitative spray deposition patterns were obtained under replicated field experiments in blueberry during two field seasons with three sprayers, i.e. cannon, electrostatic, and air-blast. Seven insecticides were tested (at 6 hours using a Potter spray tower) to determine the mortality data for adult D. suzukii. Spray deposition and mortality data for adult D. suzukii were used to create model simulations for insect populations. Model simulations included field deposition rates of sprayers and insecticide mortality as factors. Simulations were applied in different combinations with five applications over a 6-week period. Relative deposition rates for the cannon sprayer were elevated in the upper zones of the canopy, whereas for the air-blast sprayer, deposition was greater in the bottom zones. Electrostatic spray deposition was relatively uniform within the six canopy zones. Clear trends in D. suzukii laboratory mortality were found with lowest to highest mortality recorded for phosmet, spinetoram, spinosad, malathion, cyantraniliprole, zeta-cypermethrin, and methomyl respectively. Maximum D. suzukii population impacts, as shown by model outputs, were observed with air-blast sprayers together with zeta-cypermethrin. The electrostatic sprayer had the least variable canopy deposition among the three types of spray equipment, and the air-blast sprayer had the highest overall deposition rates. This study provides new hypotheses that can be used for field verification with these spray technologies and insecticides as key factors. © 2019 Society of Chemical Industry.


Evolution: pollen or pollinators - which came first?
A new study provides the first broad timeline of bee diversification. Several ancient bee clades are identified as ghost lineages that have left little fossil evidence of their existence. This timeline suggests that the rise of bees coincided with the largest flowering plant clade, the eudicots.


1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth muscle.
1,8-Cineole is a cyclic monoterpenoid used in folk medicine for treatment of numerous respiratory diseases and other infections. 1,8-Cineole has anti-inflammatory, antioxidant, and myorelaxant effects, as well as low toxicity. In the present study, the effects of 1,8-cineole on contractility and voltage-gated calcium channels (VGCC) in tracheal smooth muscle were investigated. Intact and dissociated tracheal smooth muscle were used for muscle contraction and patch-clamp recordings, respectively. In experiments involving muscle contraction, 1,8-cineole potentiated contractions at low concentrations and relaxed contractions induced by isotonic K+ at high concentrations. AMTB (a TRPM8 channel blocker) reduced the potentiation induced by 1,8-cineole while indomethacin (a COX inhibitor) did not block this effect. In dissociated myocytes, 1,8-cineole partially blocked Ba2+ currents through VGCC in a concentration-dependent manner. 1,8-Cineole shifted the steady-state activation and inactivation curves to the left and also reduced the current decay time constant. In conclusion, 1,8-cineole has a dual effect on tracheal smooth muscle contraction resulting in a biphasic effect. Our data suggest that the potentiation effect is mediated by activation of TRPM8 channels and the relaxation effect is mediated by the blockage of L-type VGCC.


BRCA1 modulates ionizing radiation-induced nuclear focus formation by the replication protein A p34 subunit.
Mutations in BRCA1 account for a significant proportion of familial breast and ovarian cancers. BRCA1 has been implicated in DNA damage responses including double-strand break (DSB) repair. However, its exact role in DSB repair and its functional relationship with other known repair proteins remain to be elucidated. In this study, we carried out a cytological analysis of the effect of BRCA1 on damage-induced nuclear focus formation mediated by the replication protein A (RPA). RPA is a multi-functional protein that participates in both DNA replication and various types of DNA repair including DSB repair. Following ionizing radiation (IR), RPA and BRCA1 formed punctate nuclear staining patterns that co-localized with each other, consistent with the implicated roles of both proteins in the same repair process. The number of damage-induced RPA foci in BRCA1-deficient cells, however, was significantly greater than that in BRCA1-positive cells. Moreover, the effect of BRCA1 on the RPA staining pattern appeared to be specific for IR but not ultraviolet (UV) irradiation. These data suggest that BRCA1 plays an important role in processing the RPA-associated intermediates during DSB repair.


Multiple short-echo (2.5-ms) quantitation of in vivo sodium T2 relaxation.
The MR behavior of the sodium-23 nucleus in vivo is a complex problem which has generated considerable interest over the last 20 years. Early studies on excised tissue samples revealed that the sodium nucleus exhibited a two-component T2 relaxation. This biexponential T2 relaxation was characterized by a short component with a T2 = 0.7-4.8 ms, and a long component with a T2 = 7.0-26.0 ms. We have developed a 3D pulse sequence capable of performing multiple Hahn echo in vivo sodium-23 imaging at echo times as short as 2.5 ms. This sequence obtains the shorter spin echo times by presaturating the spins outside of the desired imaging region, allowing the use of nonselective rf pulses. Using this sequence we have been able to quantify the long and short T2 components of normal brain tissue, vitreous humor of the eye, and a rabbit VX-2 carcinoma. We found that gray matter and white matter of normal brain have a monoexponential T2 relaxation with T2 = 17.6 +/- 2.4 ms. The vitreous humor T2 relaxation is also monoexponential with T2 = 56.8 +/- 2.1 ms. However, we find that some of the rabbit VX2 carcinomas exhibit a biexponential T2 decay with a short component of 3.3 +/- 4.6 ms and a long component of 22.0 +/- 9.0 ms.


The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo.
DMDP [N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl-m-dithane- 2-propylamine] a recently developed calcium antagonist analogue, caused a greatly increased intracellular retention of adriamycin and concomitant enhanced cytotoxicity in adriamycin-resistant P388 leukemia cells in vitro. These effects of DMDP were greater than those of another calcium channel blocker, verapamil, and occurred at one-half the dosage levels. Only slight enhancement in adriamycin toxicity was observed for either of these agents in the adriamycin-sensitive parental cell line. However, no significant therapeutic potentiation of adriamycin activity occurred with either verapamil or DMDP treatment in vivo. In vivo maximum DMDP tumor intracellular concentrations, as analyzed by HPLC, were the same in vitro tumor cell levels required to overcome adriamycin resistance. This inability to overcome drug resistance in vivo at acceptable levels of host toxicity is not only a function of maintaining necessary calcium antagonist concentrations in resistant tumor cells.


Metadata Correction: Alcohol Consumption Reduction Among a Web-Based Supportive Community Using the Hello Sunday Morning Blog Platform: Observational Study.
[This corrects the article DOI: 10.2196/jmir.9605.].


The cataract surgery of Empress Eugenie of France a century ago by the eminent Spanish ophthalmologist Ignacio Barraquer.
Topic: Empress Eugénie (1826-1920), the widow of Emperor Napoléon III of France, developed mature cataracts late in life. In 1920, at age 94, she underwent surgery to one eye by Ignacio Barraquer (1884-1965), a member of the famous dynasty of ophthalmologists originally from Barcelona, Spain. Clinical relevance: Barraquer used his new instrument which employed a vacuum cup to hold the lens for intracapsular extraction. Methods: Research of historical documents. Results: The surgery was a success; the Empress was pleased that she could read again although she did not have long to live. She was his first famous cataract patient and his fame spread internationally. Barraquer spoke at the International Congress of Ophthalmology held in Washington, DC, in 1922 and demonstrated his technique on patients in Washington, DC, New York, Boston, Philadelphia and Richmond, VA. Conclusion: Barraquer's surgery on Éugenie, who was the most powerful woman in Europe during her husband's reign, influenced the course of development of cataract surgical technique.


Phylogenetic analysis of Eimeria tenella isolated from the litter of different chicken farms in Mymensingh, Bangladesh.
Eimeria tenella is the most pathogenic intracellular protozoan parasite of seven Eimeria species causing chicken coccidiosis around the world. This species is particularly responsible for caecal coccidiosis leading to serious morbidity-mortality and financial loss in poultry production. The present study explored the genetic diversity of E. tenella. Litter slurry was collected from 18 broiler farms located in Mymensingh district, Bangladesh. Litter samples were processed for oocyst isolation-identification using parasitological techniques followed by genomic DNA extraction from sporulated oocysts. For molecular analysis, the internal transcribed spacer 1 gene of E. tenella was amplified using species-specific primers and sequenced. After editing and alignment, 263 bp sequences were used for analysis. Genetic analysis showed seven distinct genotypes and detected six single nucleotide polymorphisms among the 18 E. tenella isolates. The nucleotide and genotype diversity were 0.00507 and 0.8235, respectively. A phylogenetic tree was constructed with 66 sequences (seven studied genotypes and 59 reference sequences from GenBank database). The neighbour-joining tree represented that the studied E. tenella isolates were grouped with reference E. tenella isolates with strong nodal support (100%) and the nucleotide sequences of E. tenella, E. necatrix, E. acervulina, E. brunetti, E. maxima, E. mitis and E. praecox formed separate clusters without any geographical boundaries. This is the first study on the genetic analysis of E. tenella from Mymensingh district, Bangladesh. These findings will provide baseline data on the species conformation and genetic variations of E. tenella. Further extensive investigation will be needed to reveal the population genetic structure of this parasite and thus will facilitate the planning of effective control strategies.


A qualitative study reporting maternal perceptions of the importance of play for healthy growth and development in the first two years of life.
In order for infants and toddlers to meet recommended movement guidelines, their caregivers need to encourage play daily. This study used a qualitative approach to understand how mothers perceive and promote play and physical activity during the first 2 years of life. Mothers with children between 0 and 24 months were recruited from the SAMRC/Wits Developmental Pathways for Health Research Unit in Soweto, South Africa. 19 mothers agreed to participate and were grouped into three focus group discussions (FGDs) by age of the child: 0-6-months, 7-14-months, and 15-24-months. Thereafter, 12 mothers (4 from each FGD) were selected for inclusion in in-depth interviews (IDIs). After coding and theme/sub-theme identification had been completed for all IDIs, a process of cross-cutting theme identification and confirmation across FGDs and IDIs was carried out. The mothers were (mean ± SD) 27 (6) years old. All mothers had attended secondary school, but only nine had matriculated. Only one mother was married (and lived with the child's father), and the majority (n = 15) were unemployed. Most children were male (63%) and were aged 11 (7) months. Four main themes emerged: 1) Physical activity as an indicator for health, 2) Promoting play and development, 3) Gender bias in play, and 4) Screen time. This study showed that developmental attainment was the most important outcome for mothers, and so focussing intervention content on the promotion of child development through movement is advised. Screen time was freely available to children, and we recommend educating mothers on the movement guidelines, with a particular focus on the detrimental effects of screen time in this age group. Mothers reported many barriers to promoting play, and these are essential to consider when designing interventions in this context, in order to allow for equal opportunities for play to be provided to all children.


Role of ubiquitin-specific protease 5 in the inflammatory response of chronic periodontitis.
The systemic inflammatory response caused by chronic periodontitis is a risk factor for multiple diseases. Ubiquitin-specific protease 5 (USP5) is a kind of deubiquitinase which mainly responsible for dissociating unanchored polyubiquitin. However, the functions of USP5 in chronic periodontitis have not been reported. Chronic periodontitis patients were recruited, and their periodontal samples were collected. The levels of USP5, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in gingival crevicular fluid were evaluated by ELISA. The expression of USP5, TNF-α, IL-6, and IL-1β in human periodontal ligament stem cells (PDLSCs) was estimated by qRT-PCR assay. The activation of STAT3 signaling was examined by Western blot. USP5 was upregulated in the gingival crevicular fluid and gingival tissues of chronic periodontitis patients. USP5 expression was positively correlated with the expression of proinflammatory factors. USP5 knockdown and deubiquitinase inhibitor inhibited LPS-induced inflammatory responses in PDLSCs. Suppressing USP5 inhibited STAT3 signaling in PDLSCs. Suppression deubiquitinase USP5 inhibits the inflammatory response of chronic periodontitis by suppressing STAT3 signaling.


Cellular components in peritoneal fluid in infertile patients with and without endometriosis.
Cellular components in peritoneal fluid of infertile patients with and without endometriosis were evaluated in 102 patients with Wright's-Giemsa and Papanicolaou stains. The secretory activity of these cells was studied indirectly by assaying acid phosphatase, prostaglandin (PG) F2 alpha and PGE2 and complement components C3c and C4. The results showed that macrophages and lymphocytes were the dominant cells in peritoneal fluid of these patients. These cells were significantly increased in endometriosis patients, as compared with control subjects. In addition, peritoneal fluid acid phosphatase, PGF2 alpha and PGE2, and complement components C3c and C4 were significantly increased in patients with endometriosis. These cellular changes and their activation in peritoneal fluid may explain infertility associated with endometriosis.


Coumarin toxicity in different strains of mice.
The general toxic effects of coumarin, as well as coumarin hepatotoxicity were found to be less in DBA/2J mice than in CH3/HeJ mice. These results are discussed in the context of a strain-specific coumarin metabolism and indicate the need for suitable animal models to assess the toxicity of a given substance in man.


Developing food-grade coatings for dry-cured hams to protect against ham mite infestation.
Dry-cured hams may become infested with ham mites, Tyrophagus putrescentiae, during the aging process. Methyl bromide is the only known available fumigant pesticide that is effective at controlling ham mite infestations in dry cured ham plants. However, methyl bromide will be phased out of all industries as early as 2015 due to its status as an ozone-depleting substance. Research was conducted to develop and evaluate the potential of using food-grade film coatings to control mite infestations, without affecting the aging process and sensory properties of the dry-cured hams. Cubes coated with xanthan gum+20% propylene glycol and carrageenan/propylene glycol alginate+10% propylene glycol were effective at controlling mite infestations under laboratory conditions. Water vapor permeability was measured to estimate the impact of coatings during the aging process. It was evident that carrageenan/propylene glycol alginate coatings were permeable to moisture, which potentially makes them usable during aging.


Delivery of ubiquitinated substrates to protein-unfolding machines.
Recent work has shown that ubiquitination leads to recognition of target proteins by diverse ubiquitin receptors. One family of receptors delivers the ubiquitinated proteins to the proteasome resulting in ATP-dependent substrate unfolding and proteolysis. A related family of ubiquitin-binding proteins seems to recruit ubiquitinated proteins to Cdc48, an ATPase ring complex that can also unfold proteins. Some targets seem to dock at Cdc48 before the proteasome does, in an ordered pathway. The intimate interplay between the proteasome and Cdc48, mediated in part by loosely associated ubiquitin receptors, has important functions in cellular regulation.


The vinyl chloride-derived nucleoside, N2,3-ethenoguanosine, is a highly efficient mutagen in transcription.
N2,3-Ethenoguanine (N2,3-epsilon G) was recently identified in the liver of vinyl chloride-exposed rats. We have now synthesized the nucleoside and the 5'-diphosphate which was copolymerized with CDP. The deoxypolynucleotide complement, synthesized by AMV reverse transcriptase contained, in addition to dG, dC and dT. The total pyrimidine content was approximately equivalent to the N2,3-epsilon G content of the template. Incorporation of dC is neither lethal nor mutagenic, while dT incorporation represents a mutagenic event, occurring with approximately 20% frequency. N2,3-epsilon G X dT base pairs can have two hydrogen bonds with minimal helical distortion, as is also the case for N2,3-epsilon G X C base pairs. N2,3-epsilon G is the only derivative formed in vivo by the human carcinogen, vinyl chloride, that can be shown to have a high probability of causing transitions which could initiate malignant transformation.


miR-128 and its target genes in tumorigenesis and metastasis.
MicroRNAs (miRNAs) are a class of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that could modulate gene expression at post-transcriptional level. Previous studies have shown that miR-128 enriched in the brain plays an important role in the development of nervous system and the maintenance of normal physical functions. Aberrant expression of miR-128 has been detected in many types of human tumors and its validated target genes are involved in cancer-related biological processes such as cell proliferation, differentiation and apoptosis. In this review, we will summarize the roles of miR-128 and its target genes in tumorigenesis and metastasis.


VEGF induces proliferation, migration, and TGF-beta1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase.
The role of glomerular endothelial cells in kidney fibrosis remains incompletely understood. While endothelia are indispensable for repair of acute damage, they can produce extracellular matrix proteins and profibrogenic cytokines that promote fibrogenesis. We used a murine cell line with all features of glomerular endothelial cells (glEND.2), which dissected the effects of vascular endothelial growth factor (VEGF) on cell migration, proliferation, and profibrogenic cytokine production. VEGF dose-dependently induced glEND.2 cell migration and proliferation, accompanied by up-regulation of VEGFR-2 phosphorylation and mRNA expression. VEGF induced a profibrogenic gene expression profile, including up-regulation of TGF-beta1 mRNA, enhanced TGF-beta1 secretion, and bioactivity. VEGF-induced endothelial cell migration and TGF-beta1 induction were mediated by the phosphatidyl-inositol-3 kinase pathway, while proliferation was dependent on the Erk1/2 MAP kinase pathway. This suggests that differential modulation of glomerular angiogenesis by selective inhibition of the two identified VEGF-induced signaling pathways could be a therapeutic approach to treat kidney fibrosis.


The Axin scaffold protects the kinase GSK3β from cross-pathway inhibition.
Multiple signaling pathways regulate the kinase GSK3β by inhibitory phosphorylation at Ser9, which then occupies the GSK3β priming pocket and blocks substrate binding. Since this mechanism should affect GSK3β activity toward all primed substrates, it is unclear why Ser9 phosphorylation does not affect other GSK3β-dependent pathways, such as Wnt signaling. We used biochemical reconstitution and cell culture assays to evaluate how Wnt-associated GSK3β is insulated from cross-activation by other signals. We found that the Wnt-specific scaffold protein Axin allosterically protects GSK3β from phosphorylation at Ser9 by upstream kinases, which prevents accumulation of pS9-GSK3β in the Axin•GSK3β complex. Scaffold proteins that protect bound proteins from alternative pathway reactions could provide a general mechanism to insulate signaling pathways from improper crosstalk.


Bariatric Surgery in Patients with Obesity and Ventricular Assist Devices Considered for Heart Transplantation: Systematic Review and Individual Participant Data Meta-analysis.
Class II obesity (body mass index BMI ≥35 kg/m2) is a contraindication to heart transplantation (HT). Although few single-center studies (case reports/series and small cohorts) have reported promising outcomes of bariatric surgery (BS) in patients with obesity and ventricular assist devices, low sample sizes have made their analysis and interpretation challenging. We conducted a systematic search in ClinicalTrials.gov, Cochrane, Embase, PubMed, Google Scholar, and most relevant bariatric and heart failure journals. We extracted baseline and outcome individual participant data for every ventricular assist device patient undergoing BS with reported postoperative BMI and their respective timepoints when BMI data were measured. Fourteen references with 29 patients were included. The mean age was 41.9 ± 12.2 years, 82.8% underwent laparoscopic sleeve gastrectomy, and 39.3% had reported perioperative adverse events. The mean pre-BS BMI was 45.5 ± 6.6 kg/m2 and decreased significantly during follow-up (rho -0.671; P< .00001). Among 23 patients with documented listing status, 78.3% were listed for HT. Thirteen of 28 patients (46.4%) underwent HT at 14.4 ± 7.0 months. There were no reported deaths for the HT-free 1-year period. Median follow-up was 24 months (interquartile range, 12-30 months). Twenty-two of 28 patients (78.6%) achieved the composite outcome (BMI of<35 kg/m2/HT/listing for HT/myocardial recovery) at 11 months (interquartile range, 3-17 months). Patients with a BMI<45 kg/m2 had a higher chance of achieving the composite outcome (P< .003). BS may help patients with obesity and ventricular assist devices to lose a significant amount of weight and improve their candidacy for HT or even achieve myocardial recovery.


Abnormal neocortical development in mice lacking cGMP-dependent protein kinase I.
Cyclic GMP-dependent protein kinase type I (cGKI) is a key signaling intermediate important for synaptic potentiation in the hippocampus and cerebellum, but its expression and function in cortical development have not been elucidated. The expression of cGKI in the developing mouse neocortex was evaluated by immunofluorescence labeling, and effect of cGKI deletion on cortical development was studied in adult cGKI knockout mice. cGKI was expressed at highest levels at embryonic stages in young neurons and radial glial fibers, corresponding to the major period of radial migration and laminar development of pyramidal neurons (embryonic day E13.5-E14.5), declining upon maturation (E17.5-postnatal day P28). The cerebral cortex of homozygous null mutant mice lacking cGKI exhibited heterotopic collections of neurons in the upper cortical layers and abnormal invaginations of layer I, in accord with a neuronal migration or positioning defect. Some cGKI mutant mice displayed defects in midline development resulting in partial fusion of cerebral hemispheres with adjacent neuronal heterotopias. Apical dendrites of cortical pyramidal neurons were misoriented in the cerebral cortex of cGKI null mutants, as shown in reporter mice expressing yellow fluorescent protein in layer V pyramidal neurons and by Golgi impregnation. These results demonstrate a role for cGKI signaling in cortical development related to neuronal migration/positioning that is important for dendritic orientation and connectivity.


Geriatric anxiety inventory: factor structure and associations with cognitive status.
The factor structure and clinical correlates of the Geriatric Anxiety Inventory were determined within a sample of patients with cognitive impairment. Using a cross-sectional design, data were collected within an outpatient Memory Disorders Center. Clinical participants were diagnosed with either mild dementia (N = 45) or cognitive impairment, no dementia (N = 55). A comparison group of participants without subjective memory complaints (N = 50) was also included. The Geriatric Anxiety Inventory was administered and scored as both the 20-item version and 5-item short form. Measures of cognitive status, depressive symptoms, and functioning were also completed. Clinical participants reported more severe anxiety than did participants in the comparison group; however, the two patient groups did not differ. Principal components analysis revealed a four-factor structure of the Geriatric Anxiety Inventory. Item endorsement on factors characterized by excessive worry and difficulty making decisions were associated with a nearly twofold (odds ratio [OR]: 1.86) and nearly sixfold (OR: 5.70) odds of having cognitive impairment, respectively. The short-form version was composed of a single factor, and item endorsement was associated with a twofold increased odds of having cognitive impairment (OR: 2.02). Psychometric properties of the Geriatric Anxiety Inventory are acceptable among patients with cognitive impairment. Anxiety symptoms were common, and symptoms characterized by excessive worry and difficulty making decisions demonstrated the strongest associations with cognitive status.


The relation between Helicobactor pylori gastrointestinal tract infection and central serous chorioretinopathy among patients in Al-Diwaniya province.
Central serous chorioretinopathy (CSR) is a serous detachment of the central retina. This condition usually affects young males. Its pathogenesis is not fully understood. Helicobactor pylori is the most prevalent stomach and gastrointestinal tract (GIT) infection worldwide, and a possible correlation between these two conditions was examined in this study. Sixty-two patients with CSR (fifty-five males and seven females) were included in this study. All patients were examined by a senior ophthalmologist and fluorescein angiography was performed for each patient to confirm CSR, which has specific ophthalmic findings. It was found to be the first attack of CSR in 49 patients with the help of history and optical coherence tomography and an Amsler grid test, while in 13 patients it was shown to be recurrent disease. Diagnosis of H. pylori was done using the urea breath test at the GIT center in Diwaniya Teaching Hospital, Iraq. The control group contained 162 patients attending the GIT Department at Diwaniya Teaching Hospital with 79 patients with a positive H. pylori test and normal comprehensive eye examinations. Patients with any other ophthalmic diseases were excluded from the study. The rate of infection was significantly higher in patients than in control group (47/75.8% vs. 79/48.8%; P < 0.001). The odds ratio was 3.29 with 95% confidence interval of 1.71-6.36; therefore, patients with CSR are 3.29 times more susceptible to H. pylori infections than control subjects. A statistically significant relationship between the presence of H. pylori infections with CSR development among young patients was shown. More multi-center studies are needed to confirm this relationship.


Outcomes of very elderly patients with aggressive B-cell non-Hodgkin lymphoma treated with reduced-dose chemotherapy.
Although the number of patients aged 80 years or older with aggressive B-cell non-Hodgkin lymphoma (B-NHL) has increased in the clinical setting, management has been challenging due to lower tolerability. The aim of the present study was to evaluate the efficacy and safety of reduced-dose chemotherapy for very elderly patients. We retrospectively analyzed the clinical outcomes of patients aged ≥80 years old with diffuse large B-cell lymphoma (n = 58) or grade 3 follicular lymphoma (n = 3). Patient ages ranged from 80 to 93 years old, with a median of 83 years old. Twenty-four patients were treated with CHOP or THP-COP, the dosages of which were variably reduced, in combination with rituximab (R-vCHOP), while another 24 patients were treated with R-miniCHOP. Twelve R-vCHOP and 16 R-miniCHOP patients completed the chemotherapy cycles. The estimated 2-year progression-free and overall survival rates in the R-vCHOP and R-miniCHOP groups were 53 and 39 % (P = 0.92) and 53 and 48 % (P = 0.95), respectively. Performance status ≥2, lactate dehydrogenase level >normal, serum albumin ≤3.5 g/dL, C-reactive protein ≥2.0 mg/dL, age-adjusted International Prognostic Score 2/3, and withdrawal from the chemotherapy cycle were associated with poor survival. The frequency of chemotherapy-related hospitalization during the second or later cycles was significantly less in the R-miniCHOP group. The efficacies of R-vCHOP and R-miniCHOP were similar in patients aged ≥80 years old with aggressive B-NHL. The reduced frequency of hospitalization observed for R-miniCHOP treatment is beneficial for very elderly patients.


Environmental RNAi-based reverse genetics in the predatory mite Neoseiulus californicus: Towards improved methods of biological control.
The predatory mite Neoseiulus californicus (McGregor) (Mesostigmata: Phytoseiidae) has been commercialized by manufacturers in the pest control industry and is used worldwide as a natural enemy of spider mites. However, because its genome has not been sequenced, reverse genetics techniques that could be used to analyze gene function have not been established. Here we partially sequenced the gene that encodes the vacuolar-type H+-ATPase (V-ATPase), an ATP-dependent proton pump, in N. californicus (NcVATPase) and then conducted a functional analysis using environmental RNA interference (eRNAi) by orally administering sequence-specific exogenous dsRNA (dsRNA-NcVATPase) to larvae and adult females. The larvae treated with dsRNA-NcVATPase took longer to develop and had lower survivorship, fecundity, and offspring viability at the adult stage than those treated with a control dsRNA. Adult females treated with dsRNA-NcVATPase showed significant reductions in survival, fecundity, and prey consumption, and their endogenous gene expression level of NcVATPase was reduced by approximately 65% compared with the control. Our findings suggest that the NcVATPase gene, silencing of which inhibits feeding and reproduction, is an excellent biomarker for investigating the eRNAi mechanism in N. californicus. The highly efficient experimental system of eRNAi established in this study paves the way for applied research using eRNAi to enhance the predatory ability of N. californicus.


GISH analysis of disomic Brassica napus-Crambe abyssinica chromosome addition lines produced by microspore culture from monosomic addition lines.
Two Brassica napus-Crambe abyssinica monosomic addition lines (2n=39, AACC plus a single chromosome from C. abyssinca) were obtained from the F(2) progeny of the asymmetric somatic hybrid. The alien chromosome from C. abyssinca in the addition line was clearly distinguished by genomic in situ hybridization (GISH). Twenty-seven microspore-derived plants from the addition lines were obtained. Fourteen seedlings were determined to be diploid plants (2n=38) arising from spontaneous chromosome doubling, while 13 seedlings were confirmed as haploid plants. Doubled haploid plants produced after treatment with colchicine and two disomic chromosome addition lines (2n=40, AACC plus a single pair of homologous chromosomes from C. abyssinca) could again be identified by GISH analysis. The lines are potentially useful for molecular genetic analysis of novel C. abyssinica genes or alleles contributing to traits relevant for oilseed rape (B. napus) breeding.


Zero frequency masking and a model of contrast sensitivity.
Stimulating the visual system tends to desensitize it to certain stimulus properties. Such desensitization is usually called adaptation or masking, but the distinction between the two is unclear. Nonspecific desensitization by light is usually regarded as adaptation, whereas pattern-specific desensitization is typically considered masking. Here we unify the treatment of such desensitizing phenomena by handling both in the spatial frequency domain. The amount of adapting light in a stimulus is represented in the spatial frequency domain by the component at zero frequency. To determine whether such adapting light acts like other components in the spatial frequency domain, we compared the effect of masking by the zero frequency component with the effects of masking by components at other frequencies. We show that the zero frequency component acts like other masking components, decreasing sensitivity to nearby test frequencies and thereby producing the insensitivity to low spatial frequencies that gives the contrast sensitivity curve its band-pass shape at high light levels. Treating light adaptation as masking by the zero frequency component leads to a general model that describes visual sensitivity to test gratings of varying spatial frequency at varying mean luminance, in the presence (or absence) of masking gratings of varying spatial frequency. Individual components of the model provide insight into visual processing at the system level.


A novel free radical scavenger, NSP-116, ameliorated the brain injury in both ischemic and hemorrhagic stroke models.
Reperfusion injury is a serious problem in ischemic stroke therapy, which leads to neuronal damage and intracranial hemorrhage (ICH). A novel free radical scavenger, NSP-116, has anti-oxidative effect and may ameliorate reperfusion injury. The purpose of this study was to investigate the effects of NSP-116 on both ischemic and hemorrhagic stroke models. First, we assessed whether NSP-116 has protective effects in vitro. Pre-treatment of NSP-116 decreased neuronal cell damage induced by H2O2 or LPS. Moreover, NSP-116 also suppressed mitochondria damage and apoptosis in H2O2-induced neuronal injury model. Based on these results, we used a middle cerebral artery occlusion (MCAO)-induced ischemic stroke model or a collagenase-induced ICH model. Using the MCAO model, we evaluated the cerebral blood flow (CBF), neurological deficit, and infarct volume. Hematoma volume was assessed at 3 days after ICH. In the MCAO model, oral administration of NSP-116 at 30 mg/kg attenuated the reduction of CBF, neurological deficits, and infarct formation. Interestingly, NSP-116 also ameliorated hematoma expansion and neurological deficits in the ICH model. Additionally, pre-treatment of NSP-116 suppressed the brain microvascular endothelial cell death induced by collagenase treatment. Collectively, our findings indicated that oral administration of NSP-116 attenuates both ischemic and hemorrhagic brain injuries after stroke.


Isolation and cryopreservation of peripheral blood mononuclear cells.
The study of peripheral blood mononuclear cells (PBMCs) in immune-mediated diseases, such as celiac disease (CD), is important to uncover pathogenesis, find new biomarkers and discover and evaluate new treatments. Many studies have been published about the use and value of PBMCs in CD such as those including enzyme-linked immunospot (ELISPOT) assays, flow cytometry, peptide-MHC tetramers, genetic and proteomic analyses, and in vitro and proliferation assays. We present here and easy and efficient method for isolation of PBMCs using density gradient centrifugation. We also describe a simple way to freeze PBMCs in order to preserve their number and viability and a thawing procedure leading to high rates of viability of the cryopreserved cells to be used in subsequent applications.


Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.
We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered. To determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and to provide biological information regarding the pathophysiology of septic shock. We reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using classification and regression tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n = 77). Variable reduction revealed a network consisting of 18 mortality risk assessment genes related to tumor protein 53 (TP53). In the derivation cohort, PERSEVERE-XP had an area under the receiver operating characteristic curve (AUC) of 0.90 (95% confidence interval, 0.85-0.95) for differentiating between survivors and nonsurvivors. In the test cohort, the AUC was 0.96 (95% confidence interval, 0.91-1.0). The AUC of PERSEVERE-XP was superior to that of PERSEVERE. PERSEVERE-XP combines protein and mRNA biomarkers to provide mortality risk stratification with possible clinical utility. PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock.


On the visualisation of nonstationarities in point processes.
A method is described for graphically presenting interval data, such as neural interspike intervals or electrocardiographic R-R intervals, in a form that facilitates the identification of nonstationaries. The method is essentially a plot of isoprobability contours of the cumulative interval histogram, as functions of time. A sequential algorithm is used for updating the contour-line positions. This display is used in an interactive system for visually identifying nonstationarities, and for subsequently comparing selected segments of the data quantitatively using the Kolmogorov-Smirnov test.


Exercise tolerance test in lung cancer patients: the relationship between exercise capacity and postthoracotomy hospital mortality.
To evaluate the significance of the blood lactate threshold as a predictor of postthoracotomy hospital mortality resulting from pulmonary complications, a 3-minute incremental exercise test was administered to 33 lung cancer patients who underwent thoracotomy between October, 1981, and May, 1984. The oxygen consumption/body surface area at an arterial lactate level of 20 mg/dl (VO2/BSA at La-20) was adopted as the blood lactate threshold. Age and pulmonary function parameters such as forced expiratory volume in one second (FEV1)/body surface area (BSA), FEV1/forced vital capacity, diffusing capacity for the carbon monoxide/lung volume, and maximum ventilatory volume/BSA revealed significant differences between patients with postthoracotomy pulmonary complications and those without such complications. However, there was no difference in pulmonary function test results between the surviving and deceased patients. In contrast, although VO2/BSA at La-20 did not differ between the patients with and without pulmonary complications, it differed significantly between the surviving and deceased patients. We concluded that postthoracotomy pulmonary complications depended on the severity of preoperatively associated pulmonary function disorders and that the blood lactate threshold expressed by VO2/BSA at La-20 was an important indicator of the risk of hospital mortality.