Gametes and embryo epigenetic reprogramming affect developmental outcome: implication for assisted reproductive technologies.
There is concern about the health of children who are conceived with the use assisted reproductive technologies (ART). In addition to reports of low birth weight and chromosomal anomalies, there is evidence that ART may be associated with increased epigenetic disorders in the infants who are conceived using these procedures. Epigenetic reprogramming is critical during gametogenesis and at preimplantation stage and involves DNA methylation, imprinting, RNA silencing, covalent modifications of histones, and remodeling by other chromatin-associated complexes. Epigenetic regulation is involved in early embryo development, fetal growth, and birth weight. Disturbances in epigenetic reprogramming may lead to developmental problems and early mortality. Recent reports suggest the increased incidence of imprinting disorders such as Beckwith-Wiedemann syndrome, Angelman syndrome, and retinoblastoma in children who are conceived with the use of ART. These may result from an accumulation of epigenetic alterations during embryo culture and/or by altered embryonic developmental timing. Further research is urgently needed to determine whether a causal relationship between ART and epigenetic disorders exists. Until then, cautious review of both short-term and long-term ART outcomes at a national level is recommended.


Single-file mobility of water-like fluid in a generalized Frenkel-Kontorova model.
In this work, we used a generalized Frenkel-Kontorova model to study the mobility of water molecules inside carbon nanotubes with small radius at low temperatures. Our simulations show that the mobility of confined water decreases monotonically increasing the amplitude of the substrate potential at fixed commensurations. On the other hand, the mobility of the water molecules shows a non-monotonic behavior when varying the commensuration. This result indicates that the mobility of the confined fluid presents different behavior regimes depending on the amplitude of the water-nanotube interaction. In order to qualitatively understand these results, we study analytically the driven Frenkel-Kontorova model at finite temperatures. This analysis allows us to obtain the curves of the mobility versus commensurations, at fixed substrate potentials. Such curves show the existence of three regimes of mobility behavior as a function of the commensuration ratio. Additionally, our study indicates a nontrivial and strong dependence of the mobility with a quantity that can be interpreted as an effective amplitude of the substrate potential, depending on the bare amplitude of the substrate potential, the commensuration ratio, and temperature.


Traditional Chinese Medicine Prescriptions Decrease Diarrhea Rate by Relieving Colonic Inflammation and Ameliorating Caecum Microbiota in Piglets.
Diarrhea is a leading cause of death in piglets. XiaoJianZhong (XJZ) and Jingsananli-sepsis (JSS) were two traditional Chinese medicine (TCM) prescriptions to prevent and treat intestinal diseases, including diarrhea and inflammatory disease. Here, we investigated the effects of XJZ and JSS on diarrhea rate, growth performance, colonic inflammation, and caecum microbiota in piglets. A total of 18 piglets were selected and randomly divided into three groups. Control group was supplied with basal diets, while TCM1 and TCM2 groups were, respectively, supplied with XJZ and JSS in basal diets. Decreased diarrhea rate, colonic or caecal pH, and elevated apparent nutrient digestibility were observed in both TCM groups. Meanwhile, both prescriptions alleviated colonic inflammation by decreasing mRNA expression of proinflammatory cytokines and suppressing the TLR4/MyD88/NF-κB signaling pathway. Additionally, TCM1 and TCM2 prescriptions ameliorated caecum microbiota composition and increased the abundance of beneficial bacteria, together with regulations on several genes that are responsible for signaling pathways involved in cancers and metabolic diseases. Importantly, both TCM1 and TCM2 significantly promoted the average daily gain (ADG) and reduced the feed : gain (F : G) ratio. In conclusion, both TCM prescriptions effectively decreased diarrhea rate and increased growth performance by elevating apparent nutrient digestibility and gut health, via relieving colonic inflammation and ameliorating gut microbiota composition of piglets.


PACMan: A software package for automated single-cell chlorophyll fluorometry.
Microalgae, small photosynthetic unicells, are of great interest to ecology, ecotoxicology and biotechnology and there is a growing need to investigate the ability of cells to photosynthesize under variable conditions. Current strategies involve hand-operated pulse-amplitude-modulated (PAM) chlorophyll fluorimeters, which can provide detailed insights into the photophysiology of entire populations- or individual cells of microalgae but are typically limited in their throughput. To increase the throughput of a commercially available MICROSCOPY-PAM system, we present the PAM Automation Control Manager ('PACMan'), an open-source Python software package that automates image acquisition, microscopy stage control and the triggering of external hardware components. PACMan comes with a user-friendly graphical user interface and is released together with a stand-alone tool (PAMalysis) for the automated calculation of per-cell maximum quantum efficiencies (= Fv /Fm ). Using these two software packages, we successfully tracked the photophysiology of >1000 individual cells of green algae (Chlamydomonas reinhardtii) and dinoflagellates (genus Symbiodiniaceae) within custom-made microfluidic devices. Compared to the manual operation of MICROSCOPY-PAM systems, this represents a 10-fold increase in throughput. During experiments, PACMan coordinated the movement of the microscope stage and triggered the MICROSCOPY-PAM system to repeatedly capture high-quality image data across multiple positions. Finally, we analyzed single-cell Fv /Fm with the manufacturer-supplied software and PAMalysis, demonstrating a median difference <0.5% between both methods. We foresee that PACMan, and its auxiliary software package will help increase the experimental throughput in a range of microalgae studies currently relying on hand-operated MICROSCOPY-PAM technologies.


Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression.
A role for metallothionein in intestinal zinc absorption has been the subject of considerable debate. If metallothionein affects zinc absorption, then those factors that induce metallothionein synthesis (e.g., heavy metals, hormones) should alter zinc absorption and homeostasis. The present studies used metallothionein transgenic mice (overexpressing) and metallothionein knockout mice (no expression of metallothionein-1 or metallothionein-2) to examine directly the effects of metallothionein on zinc absorption, independent of secondary effects that could be caused by metallothionein inducers. Zinc absorption was examined by administering a single oral zinc dose (0.5 mmol/kg) by feeding tube to metallothionein transgenic and metallothionein knockout mice and measuring the serum zinc concentration. Two hours after the dose, the serum zinc concentration was 2.3 times higher in metallothionein knockout mice than in their control strain. Conversely, the concentration was elevated only one third as much in the metallothionein transgenic mice as in their controls after the zinc dose. We found that the serum zinc concentration was inversely related to the level of metallothionein protein. The intestinal zinc content was higher in the metallothionein knockout mice, however, suggesting that metallothionein did not reduce zinc absorption by simply sequestering zinc in the mucosa. The expression of the zinc transporter ZnT-1 was directly related to the serum zinc level and was independent of the level of metallothionein. These results further support metallothionein as an important component for reducing the efficiency of zinc absorption at elevated zinc intakes.


Circular dichroism studies on conformational changes in protein molecules upon adsorption on ultrafine polystyrene particles.
The conformational changes in well-characterized model proteins [bovine ribonuclease A (RNase A), horseradish peroxidase, sperm-whole myoglobin, human hemoglobin, and bovine serum albumin (BSA)] upon adsorption on ultrafine polystyrene (PS) particles have been studied using circular dichroism (CD) spectroscopy. These proteins were chosen with special attention to molecular flexibility. The ultrafine PS particles were negatively charged and have average diameters of 20 or 30 nm. Utilization of these ultrafine PS particles makes it possible to apply the CD technique to determine the secondary structure of proteins adsorbed on the PS surface. Effects of protein properties and adsorption conditions on the extent of the changes in the secondary structure of protein molecules upon adsorption on ultrafine PS particles were studied. The CD spectrum changes upon adsorption were significant in the "soft" protein molecules (myoglobin, hemoglobin, and BSA), while they were insignificant in the "rigid" proteins (RNase A and peroxidase). The soft proteins sustained a marked decrease in alpha-helix content upon adsorption. Moreover, the native alpha-helix content, which is given as the percentage of the alpha-helix content in the free proteins, of adsorbed BSA was found to decrease with decreasing pH and increase with increasing adsorbed amount. These observations confirm some well-known hypotheses for the confirmational charges in protein molecules upon adsorption.


[Physical activity and sports in heart failure due to myocarditis and dilated cardiomyopathy].
Sudden cardiac death of suspected healthy young athletes is a rare, but deeply moving event. Usually, the affected person has been completely free of symptoms. Commonly, unrecognized inflammatory, hypertrophic or dilated cardiomyopathies are the most frequent causes. All therapeutic principles of angiotensin-converting-enzyme (ACE) inhibition, beta-blockade, and diuretics in heart failure aim to unload the heart. During physical activity increased sympathetic tonus and loading conditions for the heart point into the opposite direction. This raises the question to what extent physical activity in patients with myocarditis, dilated cardiomyopathy or heart failure in general is tolerable. Several experimental studies revealed disadvantages of physical exercise during acute myocarditis leading to an increase in mortality. On the other hand, several small trials in men demonstrate an improvement of physical fitness and quality of life attributed to controlled supervised exercise training in patients with heart failure without assessment of mortality. Dilated cardiomyopathy was diagnosed in one third of these patients. There was no biopsy confirmation of these conditions. The other two thirds of patients suffered from ischemic heart diseases. Since the borderline between inflammatory heart disease and noninflammatory or postinflammatory dilated cardiomyopathy is difficult to determine, abstention from physical training during and shortly after inflammatory heart disease is recommended, because it is known that viral persistence or autoimmune processes could last for several months.


PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling.
Centromeres provide a pivotal function for faithful chromosome segregation. They serve as a foundation for the assembly of the kinetochore complex and spindle connection, which is essential for chromosome biorientation. Cells lacking Polo-like kinase 1 (PLK1) activity suffer severe chromosome alignment defects, which is believed primarily due to unstable kinetochore-microtubule attachment. Here, we reveal a previously undescribed mechanism named 'centromere disintegration' that drives chromosome misalignment in PLK1-inactivated cells. We find that PLK1 inhibition does not necessarily compromise metaphase establishment, but instead its maintenance. We demonstrate that this is caused by unlawful unwinding of DNA by BLM helicase at a specific centromere domain underneath kinetochores. Under bipolar spindle pulling, the distorted centromeres are promptly decompacted into DNA threadlike molecules, leading to centromere rupture and whole-chromosome arm splitting. Consequently, chromosome alignment collapses. Our study unveils an unexpected role of PLK1 as a chromosome guardian to maintain centromere integrity for chromosome biorientation.


New developments in radiochromic film dosimetry.
NIST has been a pioneer in the use of radiochromic film for medical dosimetry applications. Beginning in 1988 with experiments with (90)Sr/Y ophthalmic applicators, this work has continued into the present. A review of the latest applications is presented, which include high activity low-energy photon source dosimetry and ultra-high resolution film densitometry for dose enhancement near stents and microbeam radiation therapy dosimetry. An exciting recent development is the availability of a new radiochromic emulsion which has been developed for IMRT dosimetry. This emulsion is an order of magnitude more sensitive than was previously available. Measurements of the sensitivity and uniformity of samples of this new film are reported, using a spectrophotometer and two scanning laser densitometers. A unique feature of the new emulsion is that the peak of the absorbance spectrum falls at the wavelength of the HeNe lasers used in the densitometer, maximising sensitivity. When read at a wavelength of 633 nm, sensitivities on the order of 900 mAU Gy(-1) were determined for this new film type, compared with about 40 mAU Gy(-1) for type HS film, 20 mAU Gy(-1) for type MD-55-2 film, and 3 mAU Gy(-1) for type HD-810. Film uniformities were found to be good, on the order of 6% peak to peak. However, there is a strong polarisation effect in the samples examined, requiring care in film orientation during readout.


Risk of fatigue among anesthesia residents in Saudi Arabia.
To quantify fatigue risk and sleepiness among anesthesia residents in Saudi Arabia (SA). Methods: Between April 2014 and April 2015, all anesthesia residents training in western, central, and eastern regions in SA were invited to fill a survey. We conducted a cross-sectional self-reporting survey that included demographic data, the Epworth sleepiness scale (ESS), and 2 other scales to assess fatigue risk: a Checklist for Individual Strength (CIS) and a predefined comprehensive fatigue risk assessment previously developed by the Australian Medical Association (AMA). Results: We received 102 responses, and more than half of the individuals in the sample were at elevated risk of fatigue according to both fatigue scales. Approximately 70% reported being excessively sleepy during the day. Conclusion: All 3 scales used in our survey suggested that local anesthesia residents in SA are sleepy and at risk of becoming fatigued. This could be multifactorial, explained by long shifts, or cultural and lifestyle habits.


Single amino acid residues in a synthetic peptide of influenza haemagglutinin, HA 1 177-199, distinguish I-Ad- and I-Ed-restricted T-cell epitopes.
A majority of Iad-restricted, CD4+ T-cell clones, derived from BALB/c mice infected with X31 (H3N2) influenza virus and specific for the HA 1 subunit of the viral haemagglutinin (HA), has previously been shown to recognize the synthetic peptide HA 1 177-199, corresponding to the primary amino acid sequence of a major antibody binding site. Here it is demonstrated that both I-Ad- and I-Ed-restricted T-cell clones recognize HA 1 177-199, and that inter- and intra-allelic differences in Iad-restricted recognition are defined by single amino acid residues. A panel of truncated HA 1 synthetic peptides defined three distinct but overlapping CD4+ epitopes within the common antigenic site (HA 1 177-199): two I-Ad-restricted epitopes mapped within HA 1 186-198 and HA 1 177-199, and peptide HA 1 178-195 identified an I-Ed-restricted epitope. Moreover, fine specificity differences in the recognition of synthetic peptides, truncated at the carboxy terminus of HA 1 177-199, identified residues HA 1 A 198 and HA 1 S 199 as being critical for defining inter- and intra-allelic differences, respectively, in the Iad-restricted T-cell recognition of HA.


Intervention studies on Mediterranean diet and cardiovascular risk.
The traditional Mediterranean diet, as studied in the 1950s to 1960s in the South of Europe, is characterized by moderate energy intake, low animal fat, high olive oil, high cereals, high legumes, nuts and vegetables, and regular and moderate wine. A Mediterranean-type diet is being developed to mimic the traditional one and fit with present life style. While numerous epidemiological studies have supported the concept that adherence to the traditional Mediterranean diet is beneficial for health and particularly protects against cardiovascular disease, the limited number of intervention studies in this field have not yet provided major support. Nevertheless, the dietary interventions performed until now have demonstrated that adoption of a Mediterranean-type diet reduces several cardiovascular risk factors in subjects at risk (primary prevention) and/or cardiovascular events or mortality in patients after a first cardiac event (secondary prevention). Among numerous foodstuffs characterizing the Mediterranean diet, virgin olive oil has been shown to display beneficial effects on a wide range of risk factors.


A sensitive tissue factor activity assay determined by an optimized thrombin generation method.
Tissue factor (TF) is the principal activator of the coagulation system, but an increased concentration in the blood in cancer and inflammatory diseases has been suggested to play a role increasing the risk of venous thromboembolism. However, measurement of the TF concentration is difficult, and quantitation of activity is the most valid estimation. The objective of this study was to establish a sensitive method to measure TF activity based on thrombin generation. The assay is based on thrombin generation (TG) measured on the Calibrated Automated Thrombogram (CAT). Various low concentrations of TF were prepared from reagents containing 1 pM TF and 4 μM phospholipid (PPL), and no TF and 4 μM PPL, and a calibration curve was produced from Lagtime vs TF concentration. TF in blood samples was measured after isolation and resuspension of extracellular vesicles (EVs) in a standard plasma from which EVs had been removed. The same standard plasma was used for the calibrators. Contact activation of the coagulation system was avoided using CTI plasma samples in Monovette tubes. EVs contain procoagulant phospholipids but addition of PPL only reduced lagtime slightly at very low concentrations of TF resulting in overestimation to a lesser extent at 10 fM but no interference at 30 fM or higher. Addition of EVs to the TG analysis induced a small unspecific TF-independent activity (i.e., an activity not inhibited by antibodies against TF) which also may result in a smaller error in estimation of TF activity at very low levels but the effect was negligible at higher concentrations. It was possible to measure TF activity in healthy controls which was found to be 1-6 fM (EVs were concentrated, i.e. solubilized in a lower volume than the original volume plasma). Coefficient of variation (CV) was below 20% at the low level, and below 10% at a level around 100 fM TF. However, the step with isolation of EVs have a higher inherent CV. A sensitive and rather precise one-stage TG-based method to measure TF activity has been established.


[Severe reversible dysphagia caused by herniation of the cerebellar ectopia].
A 58-year-old woman developed headaches and increasingly severe dysphagia over two years, which made her dependent on a nasogastric tube. Other symptoms were an unsteady gait and paraesthesias in the face, hands and feet. MR scanning of the craniospinal junction showed cerebellar ectopia with protrusion into the foramen magnum (Chiari I malformation). The patient recovered completely following surgical decompression. Previous reports show that this reversible cause of dysphagia is often not recognised until at a late stage.


Controlled release of tebuconazole from a polymer matrix microparticle: release kinetics and length of efficacy.
Preparation and characterization of microencapsulated tebuconazole, its release kinetics in water, and the bioefficacy of these formulations in controlling wheat rust in spring wheat is described herein. Controlled-release (CR) formulations based on matrix microparticles were prepared by the oil-in-water emulsion process. Polymer-based matrix was prepared from poly(methyl methacrylate) (PMMA) and poly(styrene-co-maleic anhydride) (PSMA). Modification of the matrix was achieved by the use of different low molecular weight or polymeric additives. These additives were found to lower the glass transition temperature of the matrix and enhance the release rate of tebuconazole in water, under infinite sink conditions. Release of tebuconazole from matrix microparticles was found to be diffusion controlled. CR formulations were found to be very efficacious in controlling wheat rust. Soil-applied CR formulations prepared from a PMMA or PSMA matrix, modified with poly(vinyl acetate), were as effective in controlling wheat rust (Puccinia recondita) as foliar-applied tebuconazole, Raxil, from Bayer AG. Results suggest that CR formulations with a systemic fungicide, such as tebuconazole, applied as either a soil or seed treatment, may provide control of foliar diseases, possibly eliminating or reducing the need for traditional foliar applications.


Uptake of gas-phase nitric acid to ice at low partial pressures: evidence for unsaturated surface coverage.
The adsorption of gas-phase nitric acid onto water-ice surfaces at temperatures between 200 and 239 K has been studied over short time scales using a coated-wall flow tube coupled to a chemical ionization mass spectrometer. The nitric acid partial pressures used were between 10(-8) hPa and 10(-6) hPa, making this the first systematic study under partial pressure conditions present in the upper troposphere. Whereas previous findings using this technique have shown that the surface coverages are saturated at 2 to 3 x 10(14) molecules cm(-2) (referenced to the geometric surface area of the ice film) when partial pressures are larger than about 10(-7) hPa, the principal finding from this study is that the surface coverages are in the unsaturated regime at lower partial pressures. A conventional Langmuir adsorption isotherm describes the uptake in a quantitative manner while dissociative Langmuir isotherms that have been used in the past to model this process do not. The unsaturated surface coverages are strongly temperature dependent, in agreement with a number of field measurements of the nitric acid (or NOy) component of cirrus cloud particles. These laboratory results match those in the field better than do those measured at significantly higher partial pressures but, nevertheless, they still indicate somewhat greater uptake, particularly at higher temperatures.


Comparison study of passive acoustic mapping and high-speed photography for monitoring in situ cavitation bubbles.
The spatiotemporal accuracy of passive acoustic mapping (PAM) for monitoring in situ cavitation bubbles has not been assessed directly via optical means. Here, the cavitation bubbles are monitored from two image sequences obtained simultaneously with PAM and high-speed photography (HSP). The temporal accuracy of PAM for detecting cavitation nucleation and the spatial resolution for cavitation localization are compared with those measured from HSP. The results show that PAM has a temporal accuracy of 20 μs. Mean differences in the spatial locations of PAM and HSP are as small as 10.0 and 30.5 μm along the lateral and axial directions, respectively.


[Did Napoleon suffer from sleep apnea syndrome?].
Napoleon would sleep very little. He frequently woke up during night and worked. Brief sleeping time in day repaired his fatigue. He had also a short and thick neck. In the last fourth of his life he progressively suffered from obesity, daily involuntary sleepiness and his intellectual capabilities undoubtedly decreased. Our experience of 48 cases of sleep apnea syndrome diagnosed by mean of polysomnography allow no to think that Napoleon suffered from this disease. Historical consequences of this pathology is discussed.


Real-time contributions of auditory feedback to avian vocal motor control.
Songbirds and humans both rely critically on hearing for learning and maintaining accurate vocalizations. Evidence strongly indicates that auditory feedback contributes in real time to human speech, but similar contributions of feedback to birdsong remain unclear. Here, we assessed real-time influences of auditory feedback on Bengalese finch song using a computerized system to detect targeted syllables as they were being sung and to disrupt feedback transiently at short and precisely controlled latencies. Altered feedback elicited changes within tens of milliseconds to both syllable sequencing and timing in ongoing song. These vocal disruptions were larger when feedback was altered at segments of song with variable sequence transitions than at stereotyped sequences. As in humans, these effects depended on the feedback delay relative to ongoing song, with the most disruptive delays approximating the average syllable duration. These results extend the parallels between speech and birdsong with respect to a moment-by-moment reliance on auditory feedback. Moreover, they demonstrate that song premotor circuitry is sensitive to auditory feedback during singing and suggest that feedback may contribute in real time to the control and calibration of song.


Elevated positive end-expiratory pressure decreases cardiac index in a rhesus monkey model.
Clinicians are often concerned that higher positive end-expiratory pressure (PEEP) will decrease cardiac index (CI). PEEP affects CI through multiple inter-related mechanisms. The adult Rhesus monkey is an excellent model to study cardiopulmonary interaction due to similar pulmonary and chest wall compliances to human infants. Our goal was to examine the impact of increasing PEEP on CI in Rhesus monkeys as a model for critically ill children. Prospective, experimental animal study. Nine healthy anesthetized, intubated Rhesus monkeys were allowed to breathe spontaneously at a PEEP of 0, 5, 10, and 15 cm H2O while CI was measured with an ultrasonic Doppler (USCOM). Cardiac index decreased between PEEP levels of 5 and 15 cm H2O. The mean decrease in CI for the entire cohort of monkeys was 18% (p < 0.01) with a range of -11 to 49%. Stroke volume and oxygen delivery also decreased between PEEP levels of 5 and 15 cm H2O (p < 0.01). Between PEEP levels of 5 and 15 cm H2O, there was a decrease in CI, stroke volume, and oxygen delivery in intubated Rhesus monkeys. A plausible mechanism is that over-distention of normally compliant lungs at increased PEEP resulted in decreased preload to the right ventricle, outweighing the potentially beneficial decrease in left ventricular afterload or pulmonary vascular resistance. Further investigation is warranted, particularly in children with lung injury, who have historically benefited from increased PEEP levels without over-distention.


Combining activities and group psychotherapy in the treatment of chronic schizophrenics.
The author reviews literature relating to the use of activities in the treatment of chronic schizophrenia, citing several programs that combined activities and psychotherapy to produce effective modes of treatment. He also describes a program in which he used collage-making to help a group of schizophrenic women improve interpersonal relationships, reality-testing, and self-image as well as to help them express problems and develop feelings of autonomy. The author believes that such combined programs help meet the basic needs of schizophrenic patients and alleviate their tendencies to withdraw from their surroundings.


The Roles of Carcinoembryonic Antigen in Liver Metastasis and Therapeutic Approaches.
Metastasis is a highly complicated and sequential process in which primary cancer spreads to secondary organic sites. Liver is a well-known metastatic organ from colorectal cancer. Carcinoembryonic antigen (CEA) is expressed in most gastrointestinal, breast, and lung cancer cells. Overexpression of CEA is closely associated with liver metastasis, which is the main cause of death from colorectal cancer. CEA is widely used as a diagnostic and prognostic tumor marker in cancer patients. It affects many steps of liver metastasis from colorectal cancer cells. CEA inhibits circulating cancer cell death. CEA also binds to heterogeneous nuclear RNA binding protein M4 (hnRNP M4), a Kupffer cell receptor protein, and activates Kupffer cells to secrete various cytokines that change the microenvironments for the survival of colorectal cancer cells in the liver. CEA also activates cell adhesion-related molecules. The close correlation between CEA and cancer has spurred the exploration of many CEA-targeted approaches as anticancer therapeutics. Understanding the detailed functions and mechanisms of CEA in liver metastasis will provide great opportunities for the improvement of anticancer approaches against colorectal cancers. In this report, the roles of CEA in liver metastasis and CEA-targeting anticancer modalities are reviewed.


Down-regulation of the filamentous actin cross-linking activity of cortactin by Src-mediated tyrosine phosphorylation.
Cortactin, a prominent substrate for pp60(c-src), is a filamentous actin (F-actin) binding protein. We show here that cortactin can promote sedimentation of F-actin at centrifugation forces under which F-actin is otherwise not able to be precipitated. Electron microscopic analysis after negative staining further revealed that actin filaments in the presence of cortactin are cross-linked into bundles of various degrees of thickness. Hence, cortactin is also an F-actin cross-linking protein. We also demonstrate that the optimal F-actin cross-linking activity of cortactin requires a physiological pH in a range of 7.3-7.5. Furthermore, pp60(c-src) phosphorylates cortactin in vitro, resulting in a dramatic reduction of its F-actin cross-linking activity in a manner depending on levels of tyrosine phosphorylation. In addition, pp60(c-src) moderately inhibits the F-actin binding activity of cortactin. This study presents the first evidence that pp60(c-src) can directly regulate the activity of its substrate toward the cytoskeleton and implies a role of cortactin as an F-actin modulator in tyrosine kinase-regulated cytoskeleton reorganization.


FLOW-CYTOMETRIC ANALYSES OF NUCLEAR DNA CONTENT IN FOUR FAMILIES OF NEOTROPICAL BATS.
Flow-cytometric analyses of 29 species of microchiropteran bats representing four families and 20 genera revealed that bats possess only 79% (5.43 pg) of the DNA content of a "typical" mammal (e.g., Mus musculus strain C57BL; 7 pg). Chiroptera, the second largest order of mammals, is thus an exception to the prevailing view that mammals possess a minimum nuclear DNA content of 7 pg. Limitations on cell size resulting from a high metabolic rate may have constrained evolution of DNA content and could explain why the extensive heterochromatic additions that are common in some groups of mammals are absent in bats. Chromosomes of bats have been well studied; detailed chromosomal banding data are available for nearly all the species used in this investigation. However, no significant correlations were found between DNA content and karyotypic characteristics such as 2n, fundamental number, and rate or pattern of chromosomal evolution.


Disorders in executive control functions among aphasic and other brain-damaged patients.
Four experimental procedures for assessing disorders of executive control (Nonverbal Continuous Performance, Graphic Pattern Generation, Sequence Generation Test, and Tower of Hanoi) were administered to 22 left-brain-damaged aphasic patients, 19 right-brain-damaged nonaphasic patients, and 49 healthy controls. Aphasic patients with frontal-lobe lesions were significantly more impaired on these tasks than aphasics with retrorolandic or mixed lesions in the left hemisphere. Patients with right-hemisphere lesions, especially those with frontal-lobe lesions, showed even greater impairments on these visual/spatial tasks. The results suggest that aphasics' impairments in executive control are independent of their linguistic and visuospatial deficits and are specific to lesions in left frontal and prefrontal regions. The clinical utility of the experimental procedures is discussed.


Evolution of aminobenzoate synthases: nucleotide sequences of Salmonella typhimurium and Klebsiella aerogenes pabB.
p-Aminobenzoate synthase (PS) and anthranilate synthase (AS) are structurally related enzymes that catalyze similar reactions and produce similar products, para- and ortho-aminobenzoate (anthranilate). Each enzyme is composed of two non-identical subunits: a glutamine amidotransferase subunit (CoII) and a subunit that produces an aminobenzoate product (CoI). Nucleotide sequence comparisons of the Escherichia coli genes encoding each of the subunits suggest a common evolutionary origin for both subunits of the enzyme complexes. We report here the nucleotide sequences of the pabB genes that encode Salmonella typhimurium and Klebsiella aerogenes PS CoI. Comparative sequence information suggests that pabB is encoded as the first gene in a multicistronic transcript. Comparison of deduced amino acid sequences of PS CoI genes indicates that the majority of sequence identity occurs in the C-terminal two-thirds of the proteins. Similarly, identities in an alignment of eight PS and AS CoI sequences are confined to the C-terminal segments of the proteins. Secondary-structure predictions for the nine sequences suggest considerable similarity in the folding of the C-terminal portions of the aminobenzoate synthases.


Kinetics of cellular trafficking and cytotoxicity of 9.2.27-gelonin immunotoxins targeted against the high-molecular-weight melanoma-associated antigen.
The high-molecular-weight melanoma-associated antigen (HMW-MAA) is expressed on a large majority of melanoma tissues but not on most normal or other neoplastic tissues. Monoclonal antibody 9.2.27 binds with high affinity and specificity to the HMW-MAA, making it an attractive choice as an agent for targeting toxins or chemotherapeutic agents specifically towards melanomas. To characterize the interactions between 9.2.27 and melanoma cells more carefully, data on the kinetics of binding, internalization, and degradation of 9.2.27 by SK-MEL-2 cells were collected. Binding of 9.2.27 to SK-MEL-2 cells was rapid, and followed by slow loss of surface-bound antibody, probably because of loss of surface antigen caused by degradation and/or shedding. A small fraction (approx. 5%) of surface-bound 9.2.27 was internalized and degraded. A mathematical model describing these interactions was developed, and equilibrium and kinetic constants were fitted to the data. To evaluate the utility of 9.2.27 as a toxin-targeting agent, 9.2.27-gelonin immunotoxins were constructed and tested in protein synthesis inhibition assays. The dependence of the toxicity data for 9.2.27-gelonin on time and concentration was quantitatively related to the accumulated intracellular exposure to 9.2.27-gelonin by a relatively simple equation. This equation had been previously validated for immunotoxins targeted against the transferrin receptor, for which the trafficking kinetics are quite dissimilar from those of the HMW-MAA. The success of the approach here suggests that this method may be widely applicable for analysis of immunotoxin efficacy.


Correlation of four potential biomarkers of liver fibrosis with liver function and grade of hepatic fibrosis in a neonatal cholestatic rat model.
The present study investigated the correlation between four serum biomarkers of liver fibrosis, liver function and pathological hepatic fibrosis grade in neonatal cholestatic rats. A total of 38 Sprague‑Dawley rats, aged 3 weeks, were randomly assigned to the experimental group (EG), control group (CG) and the blank control group (BCG). EG received intragastric administration of 1% α‑naphthylisothiocyanate, 75 mg/kg, to induce acute cholestasis liver injury, CG and BCG were set as control groups. Blood samples from all groups were collected 48 h following the procedure. The levels of liver function markers, and four biomarkers of liver fibrosis in serum, were measured and sections of liver tissue were stained for pathological analysis. The results of the present study demonstrated that the degree of hepatic fibrosis in EG, in the serum levels or by pathological analysis, was markedly more evident compared with the CG. Several indices of four biomarkers for liver fibrosis in serum were identified and correlated with the levels of liver function markers. The pathological hepatic fibrosis grade was correlated with γ‑glutamyl transferase (γ‑GT) and Hyaluronic acid (HA). Therefore, HA and γ‑GT were positively correlated with the grade of hepatic fibrosis, indicating their efficacy as biomarkers of infantile cholestatic hepatic fibrosis.


Mentalization as a common process in treatments for borderline personality disorder: Commentary on the special issue on mentalization in borderline personality disorder.
Chapman and Dixon-Gordon were invited to write this commentary, they were concerned that they did not know enough about mentalization to make coherent comments on this interesting series. As it turns out, they were among a shrinking minority, as the past decade has witnessed a surge research on mentalization. Work in this field has been pioneered, in no small part, by the authors of the present issue. Collectively, this set of articles provides a useful summary of the state of mentalization research for the uninitiated and makes a compelling case for mentalization as a key translational construct, particularly with regard to borderline personality disorder (BPD). Mentalization deserves attention in further translational research as well as in treatment refinement for BPD and other clinical problems. Future work should also involve the development of effective, objective ways to assess mentalization. Ultimately, the use of translational constructs to loosen the boundaries between evidence-based treatment approaches may help us move toward more refined, accessible, and effective treatment for BPD and other complex mental health problems.


Long-lived 1H singlet spin states originating from para-hydrogen in Cs-symmetric molecules stored for minutes in high magnetic fields.
Nuclear magnetic resonance (NMR) is a very powerful tool in physics, chemistry, and life sciences, although limited by low sensitivity. This problem can be overcome by hyperpolarization techniques dramatically enhancing the NMR signal. However, this approach is restricted to relatively short time scales depending on the nuclear spin-lattice relaxation time T(1) in the range of seconds. This makes long-lived singlet states very useful as a way to extend the hyperpolarization lifetimes. Para-hydrogen induced polarization (PHIP) is particularly suitable, because para-H(2) possesses singlet symmetry. Most PHIP experiments, however, are performed on asymmetric molecules, and the initial singlet state is directly converted to a NMR observable triplet state decaying with T(1), in the order of seconds. We demonstrate that in symmetric molecules, a long-lived singlet state created by PHIP can be stored for several minutes on protons in high magnetic fields. Subsequently, it is converted into observable high nonthermal magnetization by controlled singlet-triplet conversion via level anticrossing.


[Surface analysis of Bio-Sinter ceramic specimens using Rutherford backscattering spectrometry following subcutaneous implantation].
The formation of a calcium and phosphorous containing surface-layer is one of the essential suppositions of bioactive materials for the replace of bone. In the submitted study on sintered Bio-Vitro-ceramic specimens, which where explanted from the subcutaneous tissues of rats after 20, 40, 90 and 180 days, a relative increase of calcium content, and an absolute increase of phosphorous content of the direct surface of the specimens (approximately 0.01 micron) could be demonstrated. In contrast to not implanted specimens the values of silicat were 90% lower. After 180 days of implantation the distribution of elements at the surface of all types of sintered specimens had been stabilized 1.6 (Ap40KS15), 7.1 (Ap40KS30), 2.3 (Ap40SV).


Adenolipoma of the breast.
We here report a patient with an adenolipoma of the breast. The radiological features appeared to be characteristic. On mammography the mass was surrounded by a radiolucent ring and on ultrasonography the lesion was revealed as a well-defined, hypoechoic, lobulated and solid mass.


Building on the life-span perspective: a model for infusing geriatric social work.
The growth in the older adult population and the demand for better trained geriatric social workers challenge the existing curricula of social work programs. The Geriatric Enrichment Grant funded by the John A. Hartford foundation has provided financial support for curricular reform. Curriculum reform is a challenging undertaking at any level. Each program and educational institution experiences the process of curriculum reform in unique ways. This paper describes one program's experience of curriculum reform for the purpose of infusing geriatric content.


Epidemiology of Creutzfeldt-Jakob disease in England and Wales.
Some aspects of the epidemiology of Creutzfeldt-Jakob disease in England and Wales in the decade 1964-73 were studied with the object of detecting evidence of natural transmission of this slow virus encephalopathy. Some geographical clustering and possibility of contact between cases was found.


Comprehensive Assessment of Genotype Imputation Performance.
Genotype imputation is a process of estimating missing ge-notypes from the haplotype or genotype reference panel. It can effectively boost the power of detecting single nucleotide polymorphisms (SNPs) in genome-wide association studies, integrate multi-studies for meta-analysis, and be applied in fine-mapping studies. The performance of genotype imputation is affected by many factors, including software, reference selection, sample size, and SNP density/sequencing coverage. A systematical evaluation of the imputation performance of current popular software will benefit future studies. Here, we evaluate imputation performances of Beagle4.1, IMPUTE2, MACH+Minimac3, and SHAPEIT2+ IM-PUTE2 using test samples of East Asian ancestry and references of the 1000 Genomes Project. The result indicated the accuracy of IMPUTE2 (99.18%) is slightly higher than that of the others (Beagle4.1: 98.94%, MACH+Minimac3: 98.51%, and SHAPEIT2+IMPUTE2: 99.08%). To achieve good and stable imputation quality, the minimum requirement of SNP density needs to be > 200/Mb. The imputation accuracies of IMPUTE2 and Beagle4.1 were under the minor influence of the study sample size. The contribution extent of reference to genotype imputation performance relied on software selection. We assessed the imputation performance on SNPs generated by next-generation whole genome sequencing and found that SNP sets detected by sequencing with 15× depth could be mostly got by imputing from the haplotype reference panel of the 1000 Genomes Project based on SNP data detected by sequencing with 4× depth. All of the imputation software had a weaker performance in low minor allele frequency SNP regions because of the bias of reference or software. In the future, more comprehensive reference panels or new algorithm developments may rise up to this challenge.


In vitro anti-inflammatory and skin protective properties of Virgin coconut oil.
Virgin coconut oil (VCO) has been traditionally used as moisturizer since centuries by people in the tropical region. Clinical studies have revealed that VCO improves the symptoms of skin disorders by moisturizing and soothing the skin. However, the mechanistic action of VCO and its benefits on skin has not been elucidated in vitro. The cytotoxicity (CTC50) of VCO was 706.53 ± 2.1 and 787.15 ± 1.1 μg/mL in THP-1 (Human monocytes) and HaCaT (Human keratinocytes) cells respectively. VCO inhibited TNF-α (62.34 ± 3.2 %), IFN-γ (42.66 ± 2.9 %), IL-6 (52.07 ± 2.0 %), IL-8 (53.98 ± 1.8 %) and IL-5 (51.57 ± 2.6 %) respectively in THP-1 cells. Involucrin (INV) and filaggrin (FLG) content increased by 47.53 ± 2.1 % and 40.45 ± 1.2 % respectively in HaCaT cells. VCO increased the expression of Aquaporin-3 (AQP3), involucrin (INV) and filaggrin (FLG) and showed moderate UV protection in HaCaT cells. In vitro skin irritation studies in Reconstructed human epidermis (RHE) and NIH3T3 cells showed that VCO is a non skin irritant (IC50 > 1000 μg/mL) and non phototoxic (PIF < 2). Our study demonstrated the anti inflammatory activity of VCO by suppressing inflammatory markers and protecting the skin by enhancing skin barrier function. This is the first report on anti-inflammatory and skin protective benefits of VCO in vitro. Overall, the results warrant the use of VCO in skin care formulations.


Bilateral internal carotid to anterior cerebral artery anastomosis with anterior communicating artery aneurysm: technical case report.
The present case report is the first one to report a bilateral anastomotic artery between the internal carotid artery and the anterior communicating artery in the presence of a bilateral A1 segment, fenestrated anterior communicating artery (AComA), and associated aneurysm of the AComA, which was discovered by magnetic resonance angiography and treated surgically. A 38-year-old man who was previously in good health experienced a sudden onset of nuchal headache, vomiting, and confusion. Computed tomography revealed a subarachnoid hemorrhage. Magnetic resonance angiography and four-vessel angiography documented an aneurysm of the AComA and two anastomotic vessels of common origin with the ophthalmic artery, between the internal carotid artery and AComA. A fenestrated clip, introduced by a left pterional craniotomy, leaving in its loop the left A1 segment, sparing the perforating and hypothalamic arteries, excluded the aneurysm. The postoperative course was uneventful, with complete recovery. Follow-up angiograms documented the successful exclusion of the aneurysm. Defining this particular internal carotid-anterior cerebral artery anastomosis as an infraoptic anterior cerebral artery is not appropriate because there is already an A1 segment in its habitual localization. Therefore, it is also thought that, embryologically, this anomaly is not a misplaced A1 segment but the persistence of an embryological vessel such as the variation of the primitive prechiasmatic arterial anastomosis. The favorable outcome for our patient suggests that surgical treatment may be appropriate for many patients with this anomaly because it provides a complete and definitive occlusion of the aneurysm.


Nonsuicidal Self-Injury Thoughts and Behavior in Adolescents: Validation of SITBI-NSSI.
The lack of knowledge about Nonsuicidal Self-Injury (NSSI) in Spanish adolescents, especially NSSI thoughts may be due to the paucity of NSSI assessment instruments with validity evidence in this sample. The aim of this study was to assess NSSI thoughts and behavior. In addition, the study examined the association between various NSSI features and suicidal behavior and included a preliminary validation of the new Self-Injurious Thoughts and Behaviors Interview - Non-Suicidal Self-Injury (SITBI-NSSI). 685 Spanish adolescents between 13 and 18 years old (M = 15.58, SD = 1.08; 60.9% girls) completed measures of NSSI features and suicidal behavior. Among adolescents, 19% thought about self-injury, and 16.8% presented NSSI behaviors. The girls had higher levels of NSSI, as well as greater frequency, number of functions, methods, and suicidal thoughts and desire. Some of the functions, methods, and precipitants differed by sex. Those with ANS had a higher risk of suicidal behavior than the comparison group. The association of SITBI-NSSI with other measures supports the validity of the data. Most features of NSSI are similar to those found in Spanish and internationally. The SITBI-NSSI could facilitate the evaluation of NSSI in Spanish adolescents.


Kinase dysfunction and kinase inhibitors.
With recent advances in molecular biology, abnormalities in cancer cells that contribute to dysregulation of cell survival and proliferation are being characterized with greater precision. Through this process, key abnormalities in cancer cells involving proteins that regulate signal transduction, migration, mitosis and other critical processes have been identified. Such abnormalities often involve a class of proteins called kinases that act to phosphorylate other proteins in the cell, resulting in activation of these proteins in the absence of appropriate stimulation/regulation. Given their role in tumour biology, substantial effort has been directed at blocking the function of these proteins. Several approaches have been used, including monoclonal antibodies and small molecule inhibitors. While antibodies are primarily directed at cell surface proteins, small molecule inhibitors, also known as kinase inhibitors, target proteins throughout the cell. A variety of kinase inhibitors have been approved for the treatment of human cancers. In some instances, these inhibitors have exhibited significant clinical efficacy, and it is likely that their biological activity will be further enhanced as combination regimens with standard treatment modalities are explored. The use of kinase inhibitors in dogs and cats is relatively recent, although two inhibitors, toceranib (Palladia; Pfizer Animal Health, Madison, NJ, USA) and masitinib (Kinavet; Catalent Pharma Solutions, Somerset, NJ, USA) have been approved by the Federal Drug Administration (USA) for use in dogs. This article reviews the biology of protein kinase dysfunction in human and animal cancers, and the application of specific kinase inhibitors to veterinary cancer patients.


Communication Apprehension About Death, Religious Group Affiliation, and Religiosity: Predictors of Organ and Body Donation Decisions.
Communication willingness has previously been identified as an important communication factor in influencing individuals' decisions to become an organ donor. Missing from this conversation is the role of communication apprehension about death and its impact on donation decisions. The purpose of this study was to examine the relationships between communication apprehension about death, religiosity, religious affiliation, and donation decisions. Three hundred and thirty-three individuals participated in an online survey. Findings suggest that communication apprehension about death, especially communication avoidance about death, negatively impact donation decisions. In addition, religiosity and affiliation with a specific religion also negatively impact donation decisions. These variables were also predictors of organ and body donation. The findings show a need for more research on what prevents conversations about donation. In addition, the stark difference between organ donation likelihood and body donation likelihood underscores the need for communication scholars to examine communication about body donation.


Effect of multisource feedback on resident communication skills and professionalism: a randomized controlled trial.
To determine whether augmenting standard feedback on resident performance with a multisource feedback intervention improved pediatric resident communication skills and professionalism. Randomized controlled trial. Children's Hospital Medical Center, Cincinnati, Ohio, from June 21, 2004, to July 7, 2005. Thirty-six first-year pediatric residents. Residents assigned to the multisource feedback group (n = 18) completed a self-assessment, received a feedback report about baseline parent and nurse evaluations, and participated in a tailored coaching session in addition to receiving standard feedback. Residents in the control group (n = 18) received standard feedback only. The control group and their residency directors were blinded to parent and nurse evaluations until the end of the study. Residents' specific communication skills and professional behaviors were rated by parents and nurses of pediatric patients. Both groups were evaluated at baseline and after 5 months. Scores were calculated on each item as percentage in the highest response category. Both groups had comparable baseline characteristics and ratings. Parent ratings increased for both groups. While parent ratings increased more for the multisource feedback group, differences between groups were not statistically significant. In contrast, nurse ratings increased for the multisource feedback group and decreased for the control group. The difference in change between groups was statistically significant for communicating effectively with the patient and family (35%; 95% confidence interval, 11.0%-58.0%), timeliness of completing tasks (30%; 95% confidence interval, 7.9%-53.0%), and demonstrating responsibility and accountability (26%; 95% confidence interval, 2.9%-49.0%). A multisource feedback intervention positively affected communication skills and professional behavior among pediatric residents.


[Anesthetic Management of Two Patients with Chilaiditi Syndrome].
Chilaiditi syndrome is assosiated with hepatodiaphragmatic interposition of the colon and the small intestines. We anesthetized 2 patients with Chilaiditi syndrome. A 62-year-old woman with interposition of the intestine was scheduled for right femoral fibrosarcoma resection. She had been medicated for schizophrenia. Total intravenous anesthesia was induced and maintained. Another patient an 81-year-old man with interposition of the colon, was scheduled for transurethral resection of a bladder tumor. He was anesthetized with spinal anesthesia. In both cases, there was no cardiovascular complication or digestive disorder during the perioperative period.


Prepartation of soluble chromatin and specific chromatin fractions with restriction nucleases.
By digestion of rat liver nuclei with EndoR HaeIII, EndoR EcoRI, and EndoR Bam and subsequent lysis of the nuclei approx. 90%, 40%, and 45%, respectively, of the chromatin were solubilized. The plateau values of solubilization are in agreement with a model in which the chromatin strands are crosslinked and/or attached to a supporting structure. The distribution of DNA lengths in the soluble and insoluble chromatin fractions were determined. According to digestion experiments with restriction nucleases rat liver DNA contains highly repetitive sequences, some of which are arranged in tandem repeats of 95 and 380 nucleotide pairs, respectively. With EndoR EcoRI chromatin containing the repetitive RNA was preferentially solubilized and, by subsequent sucrose gradient centrifugation, purified to about 90%. The useful properties of chromatin prepared by the specific action of restriction nucleases are discussed.


Impact of informed-choice invitations on diabetes screening knowledge, attitude and intentions: an analogue study.
Despite concerns that facilitating informed choice would decrease diabetes screening uptake, 'informed choice' invitations that increased knowledge did not affect attendance (the DICISION trial). We explored possible reasons using data from an experimental analogue study undertaken to develop the invitations. We tested a model of the impact on knowledge, attitude and intentions of a diabetes screening invitation designed to facilitate informed choices. 417 men and women aged 40-69 recruited from town centres in the UK were randomised to receive either an invitation for diabetes screening designed to facilitate informed choice or a standard type of invitation. Knowledge of the invitation, attitude towards diabetes screening, and intention to attend for diabetes screening were assessed two weeks later. Attitude was a strong predictor of screening intentions (β = .64, p = .001). Knowledge added to the model but was a weak predictor of intentions (β = .13, p = .005). However, invitation type did not predict attitudes towards screening but did predict knowledge (β = -.45, p = .001), which mediated a small effect of invitation type on intention (indirect β = -.06, p = .017). These findings may explain why information about the benefits and harms of screening did not reduce diabetes screening attendance in the DICISION trial.


Auxin depletion from leaf primordia contributes to organ patterning.
Stem cells are responsible for organogenesis, but it is largely unknown whether and how information from stem cells acts to direct organ patterning after organ primordia are formed. It has long been proposed that the stem cells at the plant shoot apex produce a signal, which promotes leaf adaxial-abaxial (dorsoventral) patterning. Here we show the existence of a transient low auxin zone in the adaxial domain of early leaf primordia. We also demonstrate that this adaxial low auxin domain contributes to leaf adaxial-abaxial patterning. The auxin signal is mediated by the auxin-responsive transcription factor MONOPTEROS (MP), whose constitutive activation in the adaxial domain promotes abaxial cell fate. Furthermore, we show that auxin flow from emerging leaf primordia to the shoot apical meristem establishes the low auxin zone, and that this auxin flow contributes to leaf polarity. Our results provide an explanation for the hypothetical meristem-derived leaf polarity signal. Opposite to the original proposal, instead of a signal derived from the meristem, we show that a signaling molecule is departing from the primordium to the meristem to promote robustness in leaf patterning.


Copper(II)-Catalyzed Selective Reductive Methylation of Amines with Formic Acid: An Option for Indirect Utilization of CO2.
A copper-catalyzed protocol for reductive methylation of amines and imine with formic acid as a C1 source and phenylsilane as a reductant is reported for the first time, affording the corresponding methylamines in good to excellent yields under mild conditions. This protocol offers an alternative method for indirect utilization of CO2, as formic acid can be readily obtained from hydrogenation of CO2.


MYB transcription factors regulate glucosinolate biosynthesis in different organs of Chinese cabbage (Brassica rapa ssp. pekinensis).
In this study, we investigated the expression of seven MYB transcription factors (a total of 17 genes that included Dof1.1, IQD1-1, MYB28, MYB29, MYB34, MYB51, and MYB122 and their isoforms) involved in aliphatic and indolic glucosinolate (GSL) biosynthesis and analyzed the aliphatic and indolic GSL content in different organs of Chinese cabbage (Brassica rapassp. Pekinensis). MYB28 and MYB29 expression in the stem was dramatically different when compared with the levels in the other organs. MYB34, MYB122, MYB51, Dof1.1, and IQD1-1 showed very low transcript levels among different organs. HPLC analysis showed that the glucosinolates (GSLs) consisted of five aliphatic GSLs (progoitrin, sinigrin, glucoalyssin, gluconapin, and glucobrassicanapin) and four indolic GSLs (4-hydroxyglucobrassicin, glucobrassicin, 4-methoxygluco-brassicin, and neoglucobrassicin). Aliphatic GSLs exhibited 63.3% of the total GSLs content, followed by aromatic GSL (19.0%), indolic GSLs (10%), and unknown GSLs (7.7%) in different organs of Chinese cabbage. The total GSL content of different parts (ranked in descending order) was as follows: seed > flower > young leaves > stem > root > old leaves. The relationship between GSLs accumulation and expression of GSLs biosynthesis MYB TFs genes in different organs may be helpful to understand the mechanism of MYB TFs regulating GSL biosynthesis in Chinese cabbage.


Staining of bladder tumor cell dehydrogenase.
The author tried enzyme staining for several types of dehydrogenase in transitional cell cancer of the urinary bladder. High activity of lactic dehydrogenase, malic dehydrogenase and aldolase was observed in tumor cells, but succinic dehydrogenase activity was not so high.


The breastfeeding case study: a model for educating nursing students.
Due to several national initiatives and recommendations from professional organizations, more women may be encouraged to breastfeed. However, they will not achieve improvement in breastfeeding duration if their health care providers lack knowledge about breastfeeding or are not easily accessible in some areas. Nurses who work with families with children are responsible for a great deal of patient education and can affect women's decisions to initiate and continue breastfeeding. Therefore, it is critical that nurse educators find a way to address this knowledge gap, especially in already overburdened curricula. This article describes a successful model for doing so.


Thermosensitive porphyrin-incorporated hydrogel with four-arm PEG-PCL copolymer (II): doxorubicin loaded hydrogel as a dual fluorescent drug delivery system for simultaneous imaging tracking in vivo.
Visualization of a drug delivery system could reveal the pharmacokinetic properties, which is essential for the design of a novel drug delivery system. In vivo optical imaging offers an advanced tool to monitor the drug release process and the therapeutic effect by the combination of fluorescence imaging and bioluminescence imaging. Multispectral fluorescence imaging can separate the drug and the carrier without interference. Herein, a dual fluorescent anti-tumor drug delivery system was monitored with the doxorubicin-loaded hydrogel to further explore the application of the porphyrin-incorporated hydrogel with four-arm PEG-PCL copolymer as a drug carrier, based on the beneficial fluorescence and good biocompatibility of the porphyrin incorporated hydrogel. Using nude mice bearing luciferase expressed hepatic tumor as models, the whole process from the drug delivery to the tumor therapeutic effects were real time visualized simultaneously after administration at interval from 0 to 18 d. The imaging results suggest that the fluorescence signals of the drug and the carrier can be separated and unmixed from the drug-loaded hydrogel successfully, avoiding the interference of the fluorescence signals. The tumor growth or inhibition can be real time tracked and analyzed quantitatively by bioluminescence imaging. Noninvasive continuous tracking the in vivo drug delivery process simultaneously is a potential trend for the precise drug delivery and treatment.


Techno-economic analysis of extraction-based separation systems for acetone, butanol, and ethanol recovery and purification.
Dual extraction, high-temperature extraction, mixture extraction, and oleyl alcohol extraction have been proposed in the literature for acetone, butanol, and ethanol (ABE) production. However, energy and economic evaluation under similar assumptions of extraction-based separation systems are necessary. Hence, the new process proposed in this work, direct steam distillation (DSD), for regeneration of high-boiling extractants was compared with several extraction-based separation systems. The evaluation was performed under similar assumptions through simulation in Aspen Plus V7.3® software. Two end distillation systems (number of non-ideal stages between 70 and 80) were studied. Heat integration and vacuum operation of some units were proposed reducing the energy requirements. Energy requirement of hybrid processes, substrate concentration of 200 g/l, was between 6.4 and 8.3 MJ-fuel/kg-ABE. The minimum energy requirements of extraction-based separation systems, feeding a water concentration in the substrate equivalent to extractant selectivity, and ideal assumptions were between 2.6 and 3.5 MJ-fuel/kg-ABE, respectively. The efficiencies of recovery systems for baseline case and ideal evaluation were 0.53-0.57 and 0.81-0.84, respectively. The main advantages of DSD were the operation of the regeneration column at atmospheric pressure, the utilization of low-pressure steam, and the low energy requirements of preheating. The in situ recovery processes, DSD, and mixture extraction with conventional regeneration were the approaches with the lowest energy requirements and total annualized costs.


Teleconference and videotape as teaching tools for multi-university instruction.
The combination of several existing technologies and application of them in a regional inter-university series of training programs is described. Using teleconference and videotape, the Central Conference of University Training Programs in Developmental Disabilities has provided its 15 member centers with a set of training materials that would be unavailable to them on an individual basis. Six program series have been produced and a seventh is being planned. The developmental process and the techniques employed are discussed.


Identification of Desiccation Stress-Inducible Antioxidative and Antiglycative Ultraviolet-Absorbing Oxylipins, Saclipin A and Saclipin B, in an Edible Cyanobacterium Aphanothece sacrum.
Aphanothece sacrum, a freshwater cyanobacterium, is an edible cyanobacterial strain. We identified two compounds belonging to the oxylipin family that possess UV-absorbing abilities and accumulate in the dried sample of A. sacrum. The compounds, named saclipin A and saclipin B, exhibited strong UV-absorption properties with the absorption maxima at 316 and 319 nm, respectively, and the molar extinction coefficients of 26,454 and 30,555 M-1 cm-1, respectively. The chemical structures of saclipins A and B have been elucidated, revealing that they have an all-E and a 12Z isomeric relationship within the triene structure. The saclipins could be isomerized by photoirradiation, with the cis-form saclipin B proving to be more stable in methanol, ethanol, or acetonitrile. Under drought stress conditions, the accumulation of saclipins A and B in A. sacrum was found to be increased 20- and 10-fold, respectively. Purified saclipins from A. sacrum showed biocompatibility and valuable bioactivities. Specifically, saclipins exhibited radical scavenging activity, maintaining their activity even 40 min after the reaction began. Additionally, they demonstrated inhibitory activity against glycation of elastin and collagen, which are constituents of dermal tissue. Notably, saclipins showed higher activity than the well-known glycation inhibitor aminoguanidine against collagen glycation.


Protein kinase C-mediated regulation of matrix metalloproteinase and tissue inhibitor of metalloproteinase production in a human retinal müller cells.
Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix (ECM) proteins in the retina. Breakdown of ECM proteins results in neovascularization and tractional retinal detachment, which eventually lead to the symptoms of proliferative diabetic retinopathy. Müller cells are reported to be one of the MMP-producing cells in the retina. However, the molecular mechanism of MMP production derived from Müller cells remains to be fully elucidated. The human retinal Müller cell line (MIO-M1) was continuously-subcultured in high glucose (25 mM) condition. After the cells reached confluence, they were treated for 24 h with phorbol ester and/or a protein kinase C (PKC) inhibitor, GF109203X in high (25 mM) or low (5 mM) glucose condition. Gelatinase activities in conditioned medium were assessed using gelatin zymography. RT-PCR was performed to analyze the mRNA expression level of MMP-9. Western blot analysis used to detect the protein expression of tissue inhibitors of metalloproteinases (TIMPs). Electrophoresis mobility shift assay was conducted to examine transcription factors involved in MMP-9 transcription. We demonstrated the protein kinase C (PKC)-mediated regulation of proMMP-9 transcription and protein expression through the action of phorbol ester, an activator of PKC. Moreover, we demonstrated the expression of TIMPs, known as natural inhibitors of MMPs at the protein level in a human retinal Müller cell line for the first time, and report that production of these proteins was also regulated in a PKC-dependent manner. Our results suggest that imbalance between MMP and TIMP proteins may promote neovascularization by PKC activation in retinal Müller cells. In addition, the development of novel compounds with regulatory action on MMP and TIMP production through inhibiting PKC activity in retinal Müller cells may lead to new therapeutic approaches for the treatment and prevention of diabetic retinopathy.


A parallel adaptive quantum genetic algorithm for the controllability of arbitrary networks.
In this paper, we propose a novel algorithm-parallel adaptive quantum genetic algorithm-which can rapidly determine the minimum control nodes of arbitrary networks with both control nodes and state nodes. The corresponding network can be fully controlled with the obtained control scheme. We transformed the network controllability issue into a combinational optimization problem based on the Popov-Belevitch-Hautus rank condition. A set of canonical networks and a list of real-world networks were experimented. Comparison results demonstrated that the algorithm was more ideal to optimize the controllability of networks, especially those larger-size networks. We demonstrated subsequently that there were links between the optimal control nodes and some network statistical characteristics. The proposed algorithm provides an effective approach to improve the controllability optimization of large networks or even extra-large networks with hundreds of thousands nodes.


Peptic ulceration in children.
An analysis of 84 children with peptic ulcer disease seen at The Hospital for Sick Children, in London, revealed only 30 primary ulcers over a period of 30 years. While most of these responded to conservative measures, it is recognized that a significant proportion may ultimately require surgical treatment for recurrence of the disease in adult life. Secondary ulcers occurred with almost twice the frequency of primary disease. Hemorrhage was the first sign of the ulceration in 55 per cent of these seriously ill children and could be controlled with conservative measures in 14 of 17 patients. Only three patients required surgical treatment for uncontrolled hemorrhage. Secondary ulceration was largely a terminal event and despite intensive resuscitation carried a high mortality (77.7 per cent).


Astrocytic modulation of neuronal excitability through K+ spatial buffering.
The human brain contains two major cell populations, neurons and glia. While neurons are electrically excitable and capable of discharging short voltage pulses known as action potentials, glial cells are not. However, astrocytes, the prevailing subtype of glia in the cortex, are highly connected and can modulate the excitability of neurons by changing the concentration of potassium ions in the extracellular environment, a process called K+ clearance. During the past decade, astrocytes have been the focus of much research, mainly due to their close association with synapses and their modulatory impact on neuronal activity. It has been shown that astrocytes play an essential role in normal brain function including: nitrosative regulation of synaptic release in the neocortex, synaptogenesis, synaptic transmission and plasticity. Here, we discuss the role of astrocytes in network modulation through their K+ clearance capabilities, a theory that was first raised 50 years ago by Orkand and Kuffler. We will discuss the functional alterations in astrocytic activity that leads to aberrant modulation of network oscillations and synchronous activity.


Biochemical and chemical characterization of trifluoromethylglyoxal bis(guanylhydrazone), a close analog of the antileukemic drug mitoguazone.
In order to study the structure-activity relationships of bis(guanylhydrazone) type polyamine antimetabolites, trifluoromethylglyoxal bis(guanylhydrazone) (CF3-GBG), a close analog of the antileukemic drug methylglyoxal bis(guanylhydrazone) (mitoguazone, MGBG) was synthesized according to a novel modification of previous methods, yielding single crystals. Single-crystal X-ray crystallography revealed the presence of an isomer different from the one detected in the case of MGBG and all other bis(guanylhydrazones) so far studied. In contrast to MGBG, CF3-GBG was shown to be a very weak inhibitor of yeast adenosylmethionine decarboxylase, being thus devoid of value as a polyamine antimetabolite. In addition, the compound did not have antiproliferative activity against mouse L1210 leukemia cells in vitro. As long as analogous isomers of the two compounds are not available, no conclusions can be drawn about the reasons lying behind the drastical differences between their biological properties.


Ebola virus disease in health care workers--Sierra Leone, 2014.
Health care workers (HCWs) are at increased risk for infection in outbreaks of Ebola virus disease (Ebola). To characterize Ebola in HCWs in Sierra Leone and guide prevention efforts, surveillance data from the national Viral Hemorrhagic Fever database were analyzed. In addition, site visits and interviews with HCWs and health facility administrators were conducted. As of October 31, 2014, a total of 199 (5.2%) of the total of 3,854 laboratory-confirmed Ebola cases reported from Sierra Leone were in HCWs, representing a much higher estimated cumulative incidence of confirmed Ebola in HCWs than in non-HCWs, based on national data on the number of HCW. The peak number of confirmed Ebola cases in HCWs was reported in August (65 cases), and the highest number and percentage of confirmed Ebola cases in HCWs was in Kenema District (65 cases, 12.9% of cases in Kenema), mostly from Kenema General Hospital. Confirmed Ebola cases in HCWs continued to be reported through October and were from 12 of 14 districts in Sierra Leone. A broad range of challenges were reported in implementing infection prevention and control measures. In response, the Ministry of Health and Sanitation and partners are developing standard operating procedures for multiple aspects of infection prevention, including patient isolation and safe burials; recruiting and training staff in infection prevention and control; procuring needed commodities and equipment, including personal protective equipment and vehicles for safe transport of Ebola patients and corpses; renovating and constructing Ebola care facilities designed to reduce risk for nosocomial transmission; monitoring and evaluating infection prevention and control practices; and investigating new cases of Ebola in HCWs as sentinel public health events to identify and address ongoing prevention failures.


Cancer risks in a population-based study of agricultural workers: results from the Taiwan's Farmers and Health Cohort study.
The purpose of this study was to assess cancer risk among agricultural workers compared to the general population. The study utilized data from Farmers' Health Insurance (FHI) in Taiwan, which enrolled agricultural workers (N=1 175 149). The enrolled workers were matched to a general population (N=1 175 149) of the same age, gender, township, and enrollment year. The study population was linked to the National Cancer Registry to identify new cancer cases between 2000 and 2018. The Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval for outcomes. During the study period, 136 913 new cancers among agricultural workers were identified. The study found that male farmers had an increased cancer risk, including lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma (NHL), oral cancer, lip cancer, esophagus cancer, rectum and rectosigmoid junction cancer, liver and intrahepatic bile duct cancer, lung cancer, trachea and bronchi cancer, and other non-melanoma skin cancer, even when considering the latency period. Female farmers had an elevated risk of multiple myeloma and other non-melanoma skin cancer. Moreover, only lymphoma, NHL, other lymphoid, and multiple myeloma, were both found to occur at different insurance periods. This study provides farmer cancer patterns and risk, adding to the evidence that farmers are at increased risk of certain types of cancer, especially for hematological cancers. As exposure varies by farm operation type, individual farmer exposure may vary widely. Further understanding of the complex relationship between occupational exposure, environmental factors, and lifestyle factors is needed.


Total Syntheses of (+)-Gabosine P, (+)-Gabosine Q, (+)-Gabosine E, (-)-Gabosine G, (-)-Gabosine I, (-)-Gabosine K, (+)-Streptol, and (-)-Uvamalol A by a Diversity-Oriented Approach Featuring Tunable Deprotection Manipulation.
A new diversity-oriented approach to C7-cyclitols, which possess a broad spectrum of biological activities, is developed. The key polyoxygenated intermediates with different O-protecting groups were accessed by an intramolecular aldol-cyclization of a diketone derived from δ-d-gluconolactone. The versatile intermediates can be easily transformed into structurally different carbasugars based on control of deprotection manipulation. The utility of the robust approach is illustrated by the first syntheses of (+)-gabosines P and Q, as well as the syntheses of several other gabosines and related analogues viz. (+)-gabosine E, (-)-gabosine G, (-)-gabosine I, (-)-gabosine K, (+)-streptol, and (-)-uvamalol A. In addition, the absolute configuration of (-)-uvamalol A is assigned by its total synthesis.


Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles.
Rivastigmine hydrogen tartrate (RHT), one of the potential cholinesterase inhibitors, has received great attention as a new drug candidate for the treatment of Alzheimer's disease. However, the bioavailability of RHT from the conventional pharmaceutical forms is low because of the presence of the blood brain barrier. The main aim of the present study was to prepare positively charged Eudragit RL 100 nanoparticles as a model scaffold for providing a sustained release profile for RHT. The formulations were evaluated in terms of particle size, zeta potential, surface morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Drug entrapment efficiency and in vitro release properties of lyophilized nanoparticles were also examined. The resulting formulations were found to be in the size range of 118 nm to 154 nm and zeta potential was positive (+22.5 to 30 mV). Nanoparticles showed the entrapment efficiency from 38.40 ± 8.94 to 62.00 ± 2.78%. An increase in the mean particle size and the entrapment efficiency was observed with an increase in the amount of polymer. The FTIR, XRD, and DSC results ruled out any chemical interaction between the drug and Eudragit RL100 polymer. RHT nanoparticles containing low ratio of polymer to drug (4:1) presented a faster drug release and on the contrary, nanoparticles containing high ratio of polymer to drug (10:1) were able to give a more sustained release of the drug. The study revealed that RHT nanoparticles were capable of releasing the drug in a prolonged period of time and increasing the drug bioavailability.


Interobserver variation in histopathological assessment of Helicobacter pylori gastritis.
Because the presence or absence of H pylori infection has important implications for therapeutic decisions based on histological assessment, the reproducibility of Sydney system is important. The study was designed to test the reproducibility of features of Helicobacter pylori gastritis, using the updated Sydney classification. Gastric biopsies of 40 randomly selected cases of H pylori gastritis were scored semiquantitatively by three pathologists. Variables analysed included chronic inflammation, inflammatory activity, atrophy, intestinal metaplasia, H pylori, surface epithelial damage. Kappa values below 0.5 represented poor, those between 0.5 and 0.75 good and values over 0.75 excellent interobserver agreement. The best interobserver agreement (kappa=0.62) was present for intestinal metaplasia. The agreement was the poorest for evaluating atrophy (kappa=0.31). Although the results of this study were in accordance with some previous studies, an excellent agreement could not be reached for any features of H pylori gastritis. This low degree of concordance is assumed to be due to the personal evaluation differences in grading the features, the lack of standardized diagnostic criteria, and the ignorance to reach a consensus about the methods to be used in grading the features of H pylori gastritis before initiating the study.


The P.F.C. sigma RP-F total knee arthroplasty: designed for improved performance.
The new P.F.C. Sigma RP-F (rotating-platform high-flexion) knee has been designed to permit 155 degrees of flexion after total knee arthroplasty (TKA) without compromising wear, polyethylene contact stresses, patellofemoral tracking, or stability. The purpose of this article is to describe the design features of the P.F.C. Sigma RP-F TKA. It is our belief that future primary posterior-stabilized TKA will incorporate many of the design features of the RP-F knee for improved performance.


Monofocal Chronic Nonbacterial Osteomyelitis in the Mandible Accompanied With Mucocutaneous Disease.
Chronic nonbacterial osteomyelitis (CNO) is a bone disease with nonbacteria osteitis of unknown etiology. Symptoms, including pain, swelling, fever, etc, always result in misdiagnosis and wrong therapy. This study aims to introduce the clinical features and the therapy of patients with CNO accompanied with mucocutaneous disease. The authors retrospectively reviewed the patients who presented to our hospital from 2000 to 2016, the final sample including 3 patients with CNO accompanied with mucocutaneous disease, who presented repeated severe pain of bone, swelling, tenderness, and fever during attack stage with no evidence of bacterial infections. One patient underwent surgery, and all of them took the therapy of nonsteroidal anti-inflammatory drugs and immunosuppressive agents. There was no significant effect after taken surgery, but good results with drugs. The study suggested us that medical therapy sometimes better than surgery in CNO accompanied with mucocutaneous disease.


Real-time in situ detection of the local air pollution with laser-induced breakdown spectroscopy.
The smoke of burning mosquito-repellent incense was taken as an example for the local air pollution to be detected and analyzed in situ and in real time. And the spectra of the ambient air, human breathing, and smoke were detected in situ with the LIBS technique. There are some additional spectral lines being found in human breathing, such as the C, Hβ line, and the CN molecular bands. Some characteristic peaks of the elements Fe, Ca, Ti, Sr, and Cr have been observed in the smoke. Moreover, the vibrational and rotational temperature of the CN molecule were calculated. The mosquito-repellent incense was dipped into the solutions containing Mn and Pb to simulate heavy metal pollution in the atmosphere.


Still a role for surgery as first-line therapy of splenic marginal zone lymphoma? Results of a prospective observational study.
Assessment of hematologic improvement, survival and peri-operative morbidity after first-line splenectomy for splenic marginal zone lymphoma (SMZL). Forty-three patients undergoing open splenectomy were prospectively analyzed. Perioperative clinical course, overall and progression-free survival (OS-PFS) were evaluated. Risk factors analyzed were gender, age, ASA-grade, ECOG performance status, presence of B-symptoms, body mass index, steroidal treatment, serum albumin concentration, IIL-score, operative time, spleen size and weight. The median follow-up was 31 months (IQR 15-76; range 24-154). Anemia and thrombocytopenia resolved in 80% of patients at 6 months; in 60% at 2 years. The 5-year and 10-year PFS were 35% and 13% respectively, with a median of 35 months (shorter in patients with ECOG performance status ≥2 and B-symptoms). Nineteen cases (44.2%) had a progression of disease within 2 years. Of these, 14 (32.6%) received adjuvant chemotherapy (mainly R-FC or R-CVP). Progression was attributed to high-grade B lymphoma in 7 (16.3%) patients. The median time between diagnosis and progression to aggressive lymphoma was 25.5 months (range 18.8-81.8). The median time to next treatment was 83.5 months (95% CI 49-118). The 5-year and 10-year OS were 75% and 53% respectively. Mortality was due to disease progression and histological transformation in high-grade B lymphoma in 50% of cases, myelodisplastic syndrome in 15%, recurrence of hemolytic anemia in 15%, Hodgkin lymphoma in 7% and to infections (mainly pulmonary) in the remaining 13% of cases. Post-operative morbidity was 2.3% (1 patient with grade-3 complication). Overall grade ≥2 complication rate was 32.5% (mainly hemorrhagic and pulmonary complications). Spleen weight was the only independent risk factor for morbidity. Mortality was nil. Splenectomy is safe and effective as regards cytopenia resolution and OS, although disease progression is frequently observed at follow-up. Such results are strictly linked to accurate pre- and post-operative clinical management and optimal anesthesiologic approach.


Cerebrovascular disease at young age is related to mother's health during the pregnancy-The Northern Finland Birth Cohort 1966 study.
For prevention of cerebrovascular diseases at younger age, it is important to understand the risk factors occurring early in life. We investigated the relationship between mothers' general health during pregnancy and the offspring's risk of cerebrovascular disease in age of 15 to 52 years. Within the population-based prospective Northern Finland Birth Cohort 1966, 11,926 persons were followed from antenatal period to 52 years of age. Information on their mother's ill health conditions, i.e., hospitalizations, chronic diseases, medications, vitamin or iron supplement, fever, anemia, mood, and smoking was collected from 24th gestational week onwards. Ischemic and hemorrhagic cerebrovascular diseases of the offspring were identified from national registers in Finland. Cox proportional hazard models were used to estimate the association of mother's health conditions with incidence of cerebrovascular disease in the offspring, with adjustments for potential confounders. During 565,585 person-years of follow-up, 449 (2.8%) of the offspring had a cerebrovascular disease. Hospitalization during pregnancy was associated with an increased risk of cerebrovascular disease in the offspring (hazard ratio (HR) = 1.49; 95% confidence interval (CI) 1.06-2.08) after adjustment for confounders, as was having more than three ill health conditions (HR = 1.89; CI 1.14-3.11). Not using vitamin or iron supplement was associated with increased risk for cerebrovascular disease in the offspring (HR = 1.39; CI 1.01-1.89). The results suggest that the risk of cerebrovascular disease may start as early as during the antenatal period, and the health characteristics of mothers during pregnancy may play a role in cerebrovascular disease risk of the offspring.


The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats.
Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood-brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day.


[Positive psychotherapy in work with hospice patients].
A special psychosocial programme is described conducted in Arkhangelsk hospice. The programme is based on the approaches and methods of positive psychotherapy, intended for the patients, their relatives and medical staff of the hospice. Two years of the program implementation showed its high effectiveness for all the groups observed.


Total Syntheses of Pyroclavine, Festuclavine, Lysergol, and Isolysergol via a Catalytic Asymmetric Nitro-Michael Reaction.
A catalytic enantioselective construction of vicinal stereocenters is reported. The reaction takes advantage of thiourea-catalyzed intramolecular nitronate addition onto α,β-unsaturated ester to afford exceptional levels of enantioselectivity (up to 97 % ee) with moderate diastereoselectivity (up to 4:1). Using this method, a cross-conjugated ester was synthesized in few steps, from which a 6-endo-trig cyclisation led to the formation of all required functionalities for total syntheses of ergot alkaloids. The strategy not only offers first total syntheses of ergot alkaloids, festuclavine (1 c), and pyroclavine (1 e), and but also an efficient and general approach to other congeners such as, lysergol (1 b), and isolysergol (1 d).


Analysis of Wavefront Data Obtained With a Pyramidal Sensor in Pseudophakic Eyes Implanted With Diffractive Intraocular Lenses.
To investigate the clinical validity of using wavefront measurements obtained with a recently available pyramidal aberrometer to assess the optical quality of eyes implanted with diffractive intraocular lenses (IOLs). Individual biometric data were used to create models of pseudophakic eyes implanted with two diffractive IOLs. Their synthetic wavefronts were calculated by ray-tracing with near infrared wavelength (0.85 μm). Comparisons of the through-focus visual acuity of 12 pseudophakic eyes were obtained with three different methods: clinical defocus curves; simulated defocus curves calculated from ray-tracing in the customized model eyes; and through-focus simulated defocus curves calculated from the wavefront data measured with a pyramidal aberrometer. Image quality calculated from wavefront data obtained by ray-tracing with 0.85 μm wavelength, without scaling the phase to 0.55 μm, resulted in a significantly different through-focus curve compared to the reference values. Even so, after scaling of the wavefront data to 0.55 μm, the defocus curves calculated from the wavefronts measured with the pyramidal aberrometer did not match the shape and the depth of field of the clinical defocus curves or the theoretical expected values. Correcting for the longitudinal chromatic aberration of the eye when measuring the wavefront of eyes implanted with diffractive IOLs under near infrared light only accounts for the best focus shift due to the longitudinal chromatic aberration, but not for the wavelength dependence of the diffractive element. The pyramidal sensor does not seem to properly sample the slopes of a wavefront measured from a pseudophakic eye implanted with a presbyopia-correcting diffractive IOL to a clinically acceptable level. [J Refract Surg. 2023;39(7):438-444.].


Cirrhosis has no impact on therapeutic responses of entecavir for chronic hepatitis B.
As the efficacy of a direct antiviral agent is reduced in cirrhotic chronic hepatitis C patients, prolonged duration of treatment or addition of ribavirin is recommended to improve the rates of sustained virological response. However, the impact of cirrhosis on the efficacy of antiviral treatment for chronic hepatitis B (CHB) remained unclear. This retrospective cohort study screened entecavir (ETV)-treated CHB patients in Taipei Tzu Chi Hospital from January 2007 till October 2014. The diagnosis of cirrhosis was made on the basis of clinical/imaging or histologic findings. The primary endpoints were hepatitis B e antigen (HBeAg) loss in HBeAg-positive patients and undetectable hepatitis B virus (HBV) DNA in the overall study population. Initial virological response is defined as undetectable HBV DNA at 1-year ETV treatment. A total of 381 (262 men; mean age: 49.6±12.9 years) CHB patients were recruited for the final analysis. Of these, 138 were cirrhotic. In 143 HBeAg-positive patients, there was no difference in the rates of 1- and 2-year HBeAg loss between cirrhotic and noncirrhotic patients (P=0.226 and 0.729, respectively). In the overall population, the rate of 1-year undetectable HBV DNA was higher in patients with cirrhosis than those without cirrhosis (76.1 vs. 64.2%, P=0.016). The rate of 2-year undetectable HBV DNA was not different between these two groups. Using multivariate logistic regression analysis, baseline HBV DNA levels (P=0.006) and HBeAg status (P=0.007), were associated with initial virological response, but not cirrhosis. Therapeutic responses of ETV are not decreased in cirrhotic CHB patients. Thus, cirrhotic CHB patients can be treated with ETV without the need for dose adjustment.


Subcellular compartments and protein topogenesis.
A cell is surrounded by a plasma membrane. It contains various organelles, most of which are enclosed by limiting membranes. The intracellular space is thus divided into a number of subcellular compartments. Structurally, a cell is composed of membranes and the spaces enclosed by those membranes. In order to classify these compartments, the extracellular space has been designated S1 and whenever a unit membrane structure is crossed to arrive at the next space, one is added to term; the cytoplasmic space becomes S2, the intraluminal space of the endoplasmic reticulum and the intermembrane space of the mitochondria S3, and the matrix space of the mitochondria S4. Similarly, the plasma membrane is M1, the outer membrane of the mitochondria M2, and the inner counterpart M3. This classification of the subcellular compartments is useful in understanding a number of complicated cellular structures and functions. The intracellular transport of newly synthesized protein (protein topogenesis) and the probable development of subcellular organelles during phylogenesis of eukaryotic cells is discussed in terms of these subcellular compartments.


MMP proteolysis of the human extracellular matrix protein aggrecan is mainly a process of normal turnover.
Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS1 region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less-active role in aggrecan degradation during knee injury and OA.


Bilateral focal ablation of prostate tissue using low-energy direct current (LEDC): a preclinical canine study.
To evaluate side-effects, erectile function and capability to preserve adjacent tissues of bilateral focal prostate ablation using low-energy direct current (LEDC) in a canine model. In all, 12 male Beagle dogs underwent bilateral focal prostate ablation using the NanoKnife™ LEDC system. Three 19 G monopolar electrodes were transperineally placed on each side of the prostate under transrectal ultrasonographic (TRUS) guidance using a triangular probe array. Intra- and postoperative side-effects were recorded. Erectile function was evaluated at baseline and 4-5 and 26-27 days after ablation. The dogs were killed humanely at 7 (six) and 30 days (six) for gross and microscopic evaluation of the prostate and adjacent organs. The median (range) prostate volume on TRUS was 12.1 (8.9-17.2) mL. The electrodes were placed at a median distance of 0.55-0.66 cm from the capsule, urethra and rectum. All procedures were completed successfully and recovery was uneventful. There were no episodes of urinary retention. All the dogs were able to achieve erections after ablation. Pathological analyses revealed inflammatory changes in the ablation zone at 7 days and replacement by fibrosis at 30 days. On microscopic examination no histological injury to the capsule, urethra, rectal wall or nervous structures was identified. In this study, bilateral focal prostate ablation using LEDC was safe and had a favourable side-effects profile limited to transient minor events. LEDC ablation effectively spared adjacent structures as well as physiological functions in all the dogs.