Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma.
In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.


Different enzyme classes associated with human natural killer cells may mediate disparate functions.
Previous studies have shown that degradation of the acute phase reactant serum amyloid A (SAA) is mediated by enzymes on the plasma membrane of lymphocytes and monocytes. The responsible enzymes had properties of neutral elastases. The present investigations were conducted to explore whether human NK cells enriched by Percoll gradient centrifugation have similar activity and if so, whether the same or different enzyme classes are responsible for proteolysis as well as for tumor cell lysis. Accordingly, human NK cells were enriched on discontinuous Percoll gradients after which the cells were incubated either with SAA or with [3H] proline-labeled melanoma cells at various effector to target cell ratios. When SAA degradation was followed by SDS-polyacrylamide gel electrophoresis, NK fractions proved to be as effective in digesting the protein as unfractionated mononuclear leukocytes. To characterize the enzymes that may be involved in cytotoxicity on the one hand, and SAA degradation on the other, the NK fractions were treated with the following inhibitors: diisopropylfluorophosphate (DFP), soybean trypsin inhibitor, N-p-tosyl-L-lysine chloromethylketone (TLCK), the elastase inhibitors elastatinal, Ac-Ala-Ala-Pro-Val-CH2Cl, Meo-Suc-Ala-Ala-Pro-Val-CH2Cl, and an inhibitor of aryl sulfatase, Na2SO4. Preincubation of the cells with DFP or elastase inhibitors abolished their ability to hydrolyze SAA but did not affect their ability to kill tumor cells. On the other hand TLCK, a potent inhibitor of cytotoxicity, did not bring about any reduction in the proteolysis of SAA. DFP and Na2SO4 diminished cytotoxicity partially. Elimination of NK cells by sorting after incubation of lymphocytes with the monoclonal antisera Leu-7 and Leu-11 abolished cytotoxicity as well as proteolysis. The observations are compatible with the concept that NK cells carry several enzymes with different substrate specificities that may be involved in disparate cellular functions.


[The influence of miR-16 on proliferation and angiogenesis of U87MG in vivo].
To explore the proliferation inhibition of miR-16 to U87MG in vivo. The miR-16 over-expression U87MG cells were obtained by infecting U87MG with lentivirus-hsa-GFP-miR-16. The models of subcutaneous transplantation and orthotopic brain glioma were obtained by injecting cells into flank and brains of nude mouse separately. Untransfected U87MG, negative control U87MG and miR-16 over-expression U87MG were separatively cultured and injected into brains of balb/c-nu mice for establishing an orthotopic model of brain glioma. Tumor growth curve was calculated for subcutaneous tumor. The brains were sectioned and stained with hematoxylin & eosin (H&E) and immunohistochemistry for CD31 and cyclinD1. The miR-16 over-expression U87MG cells formed no apparent tumors while the negative control U87MG grew into large tumors. HE stain of brains showed that gliomas of miR-16 over-expression U87MG (0.11 ± 0.04 mm³) were smaller than those of negative control U87MG (6.50 ± 1.41 mm³) and untransfected (6.41 ± 0.91 mm³) in murine brains. Immunohistochemistry showed that cyclinD1 staining was less in gliomas of miR-16 over-expression U87MG than the other two groups. CD31 immunohistochemistry also yielded the similar results. The mean microvascular density (MVD) of gliomas of miR-16 over-expression U87MG (4.50 ± 1.58/× 200) was smaller than negative control (30.40 ± 6.57/× 200) and untransfected (29.40 ± 4.93/× 200) (P < 0.05). miR-16 can significantly inhibit the in vivo growth of U87MG glioma. This is probably the results of cell proliferation inhibition and angiogenesis suppression.


Determination of testis temperature rhythms and effects of constant light on testicular function in the domestic fowl (Gallus domesticus).
There is a wide range of opinions regarding the operating temperature of the testis in the domestic fowl. We used physiological monitoring techniques to investigate testis and body temperature over daily periods and under various light regimes to elucidate body temperature gradients in the fowl. We confirm that the operating temperature of the adult fowl's testes is equivalent to core body temperature (40-41 degrees C). Long-term continuous temperature monitoring showed that there was no difference between the temperature of the testis, liver, and peritoneum during a 24-h period either in a normal light:dark cycle or under constant light conditions. However, there was a slight decrease in all temperatures at subjective night in each case, a decrease that does not appear to be sufficient to influence spermatogenesis. Birds maintained under constant light throughout two cycles of the seminiferous epithelium (28 days) still exhibited normal testis function and structure, even when "nightly" testis temperature decrease was the lowest. Thus, by undergoing spermatogenesis at an elevated temperature, the domestic fowl system is unique among the homeothermic animal systems studied to date.


[A nondestructive method to measure the oxygen binding and releasing properties of biodegradable polymers microcapsules intented for blood substitutes].
P50 is an important parameter reflecting the binding and releasing oxygen properties of blood substitutes. In this study, based on the strong penetrating property of near infrared light and the mechanism involved in the pulsatile oxygen meter in clinic as well as on the ability for penetrating biodegradable polymers and detecting bovine hemoglobin encapsulated within the microcapsules, we have made an airproof and equilibrium apparatus to measure oxygen saturation and oxygen partial pressure. Subsequently, we have obtained the oxygen dissociation curve and P50 of the microcapsules loaded bovine hemoglobin in the light of oxyHemoglobin and deoxyHemoglobin with different spectrum in the near infrared region. The above-mentioned apparatus and method are not destructive to the microcapsules, and the process is simple and nondestructive. So it is practical to take in-situ measurements of the oxygen binding and releasing property of biodegradable polymer microcapsules intented for the blood substitute.


Effectiveness of physical training on motor performance and fall prevention in cognitively impaired older persons: a systematic review.
To determine whether older cognitively impaired people benefit from physical training with regard to motor performance or fall risk reduction and to critically evaluate the methodologic approach in identified randomized controlled intervention trials. Published randomized controlled intervention trials from 1966 through 2004 were identified in PubMed, CINAHL, Gerolit, and the Cochrane Central Register of Controlled Trials according to predefined inclusion criteria and evaluated by two independent reviewers using a modified rating system for randomized controlled intervention trials developed by the Cochrane Library. There were 11 randomized controlled intervention trials that met the predefined inclusion criteria. There was a large heterogeneity regarding methodology, sample size, type of intervention, study outcomes, and analyses. We found conflicting evidence regarding the effect of physical training on motor performance and falls in older people with cognitive impairment. However, a considerable number of the studies had methodologic limitations, which hampered the evaluation of the effectiveness of training. The randomized controlled intervention trials showed only limited effectiveness of physical training in patients with cognitive impairment. More studies with adequate sample size, sensitive and validated measurements, and higher specificity for the types of intervention targeting subgroups of patients with different degrees of cognitive impairment are required to give evidence-based recommendations.


The doubly-bonded ditungsten anion [W2Cp2(μ-PPh2)(NO)2](-): an entry to the chemistry of unsaturated nitrosyl complexes.
Complex [W2Cp2(μ-I)(μ-PPh2)(NO)2] was prepared by reacting [W2Cp2(μ-I)(μ-PPh2)(CO)2] with NO at 233 K followed by decarbonylation in refluxing toluene. It was reduced by Na(Hg) in acetonitrile to give Na[W2Cp2(μ-PPh2)(NO)2], the first anionic nitrosyl complex featuring a metal-metal double bond (computed W-W = 2.580 Å). Reactions of the latter anion with (NH4)PF6 and [AuCl{P(p-tol)3}] gave the hydride [W2Cp2(μ-H)(μ-PPh2)(NO)2] and the cluster [AuW2Cp2(μ-PPh2)(NO)2{P(p-tol)3}] respectively, also featuring multiple W-W bonding (experimental W-W ca. 2.75 Å), and its reaction with S8 yielded the electron-precise derivative Na[W2Cp2(μ-PPh2)(μ-S)(NO)2], which was methylated by Me2SO4 to give the thiolate complex [W2Cp2(μ-PPh2)(μ-SMe)(NO)2].


Scale-free ferroelectricity induced by flat phonon bands in HfO2.
Discovery of robust yet reversibly switchable electric dipoles at reduced dimensions is critical to the advancement of nanoelectronics devices. Energy bands flat in momentum space generate robust localized states that are activated independently of each other. We determined that flat bands exist and induce robust yet independently switchable dipoles that exhibit a distinct ferroelectricity in hafnium dioxide (HfO2). Flat polar phonon bands in HfO2 cause extreme localization of electric dipoles within its irreducible half-unit cell widths (~3 angstroms). Contrary to conventional ferroelectrics with spread dipoles, those intrinsically localized dipoles are stable against extrinsic effects such as domain walls, surface exposure, and even miniaturization down to the angstrom scale. Moreover, the subnanometer-scale dipoles are individually switchable without creating any domain-wall energy cost. This offers unexpected opportunities for ultimately dense unit cell-by-unit cell ferroelectric switching devices that are directly integrable into silicon technology.


Ultrastructure of melanin formation in Verticillium dahliae with (+)-scytalone as a biosynthetic intermediate.
Transmission and scanning electron microscopy showed that melanin of wild-type Verticillium dahliae occurred as granules in microsclerotial cell walls and in a fibrillar network encapsulating the walls. An albino microsclerotial mutant and a brown microsclerotial mutant of V. dahliae did not form melanin granules. When albino microsclerotia were treated with (+)-scytalone (a metabolite that the brown mutant accumulates), they formed melanin granules and turned black. These granules were similar in appearance and distribution to those in the wild type. Melanin granules of the wild-type isolate and the scytalone-treated albino mutant were formed at a maximum rate in microsclerotia from 5- to 8-day-old cultures. These observations suggest that scytalone is a natural intermediate of melanin synthesis in V. dahliae.


Dysregulation of Cells Cycle and Apoptosis in Human Induced Pluripotent Stem Cells Chondrocytes Through p53 Pathway by HT-2 Toxin: An in vitro Study.
Kashin-Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene-environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.


Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue.
This study is significant because it demonstrates an attempt to design a scaffold specifically for small intestine using a novel fabrication method, resulting in an architecture that resembles intestinal villi. In addition, we use the versatile polymer poly(glycerol sebacate) (PGS) for artificial intestine, which has tunable mechanical and degradation properties that can be harnessed for further fine-tuning of scaffold design. Moreover, the utilization of PGS allows for future development of growth factor and drug delivery from the scaffolds to promote artificial intestine formation.


Simple Model of the Effect of Solution Conditions on the Nucleation of Amyloid Fibrils.
It is well known that peptide and protein fibrillation is strongly affected by the solution conditions, but a fundamental understanding of how amyloid fibril nucleation depends on solution pH, salt concentration, and solvent is absent. Here, we use expressions from Debye-Hückel theory to describe the interactions between charged amino acids in combination with our recently developed nonstandard nucleation theory to predict the concentration dependence of the fibril nucleation rate under different solvent conditions. The general rule that emerges from these considerations is that changes in solution pH, salt concentration, and solvent that increase the bonding energy between the fibril building blocks decrease the fibril solubility and promote fibril nucleation, in line with experimental observations. The simple analytical relations among the nucleation rate, fibril solubility, and binding energies provide a tool to controlling and understanding amyloid fibril formation by changing the solution conditions.


Feasibility studies for assessing internal exposure to 233U.
The potential internal occupational exposure encountered as a consequence of the 232Th-233U fuel cycle are likely to arise predominantly from the inhalation of 232Th, 233U and (232Th + 233U) compounds of absorption Types M and S. In the past, although direct and indirect methods for assessments of internal exposure to 232Th and its daughters were developed, standardised and employed, no such attempts have been made with regard to 233U and 233U + 232Th. Therefore, feasibility studies for assessing internal exposure to 233U have been conducted using three methods: urine bioassay, in vivo counting and measurement of thoron gas in the exhaled breath of a worker. This paper describes details of these studies and discusses the results obtained.


The Cortical Bone Trajectory Screw Technique Assisted by the Mazor Renaissance Robotic System as a Salvage Strategy for Failed Lumbar Spine Surgery: Technical Note and Case Series.
The objective of this study was to describe the Mazor Renaissance robotic system-assisted CBT (cortical bone trajectory) screw technique as a salvage strategy for failed lumbar spine surgery. Between January 2018 and June 2022, 7 patients underwent salvage surgery with the CBT screw fixation technique assisted by the Mazor Renaissance robot system in our institution. Intraoperative observations were recorded for blood loss, duration of operation, and fluoroscopy time. Complications related to CBT screws were also recorded. The accuracy of CBT screws was recorded in accordance with the modified Gertzbein-Robbins classification. The JOA (Japanese Orthopedic Association) score for low back pain was used to evaluate surgical outcomes. A total of 26 CBT screws were placed in 7 patients, including 4 females and 3 males. Three patients underwent ASD (adjacent segment disease) and four patients underwent lumbar union failure with loose or compromised PSs (pedicle screws). The mean operation time was 129.29 ± 32.97 minutes, the mean blood loss was 180 ± 52.60 mL, and the mean intraoperative fluoroscopy time was 14.29 ± 3.15 s. All screws were clinically acceptable according to the Gertzbein-Robbins classification. There were no complications related to CBT screws in any of the cases. The JOA scores for low back pain of all patients were significantly improved at the final follow-up. The CBT screw fixation technique supplemented the traditional PS fixation technique, which can be performed as a salvage strategy for failed lumbar spine surgery and achieved good clinical results. The spinal robot was very helpful in evaluating pedicle size and determining CBT screw direction, especially in a previously instrumented lumbar pedicle.


Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect.
1 2-aminoethoxydiphenyl borate (2-APB) has been widely used to examine the roles of inositol 1,4,5-trisphosphate receptors (IP3Rs) and store-operated Ca2+ entry and is an emerging modulator of cationic channels encoded by transient receptor potential (TRP) genes. 2 Using Ca2+-indicator dye and patch-clamp recording we first examined the blocking effect of 2-APB on human TRPC5 channels expressed in HEK-293 cells. 3 The concentration-response curve has an IC50 of 20 microM and slope close to 1.0, suggesting one 2-APB molecule binds per channel. The blocking effect is not shared by other Ca2+ channel blockers including methoxyverapamil, nifedipine, N-propargylnitrendipine, or berberine. 4 In whole-cell and excised membrane patch recordings, 2-APB acts from the extracellular but not intracellular face of the membrane. 5 Block of TRPC5 by 2-APB is less at positive voltages, suggesting that it enters the electric field or acts by modulating channel gating. 6 2-APB also blocks TRPC6 and TRPM3 expressed in HEK-293 cells, but not TRPM2. 7 Block of TRP channels by 2-APB may be relevant to cell proliferation because 2-APB has a greater inhibitory effect on proliferation in cells overexpressing TRPC5. 8 Our data indicate a specific and functionally important binding site on TRPC5 that enables block by 2-APB. The site is only available via an extracellular route and the block shows mild voltage-dependence.


Temporal patterns of body temperatures in the acute stage of stroke.
The present study aimed to describe the day-by-day temporal patterns of body temperatures in acute stroke and to delineate the differences in serial daily changes in body temperatures between intracerebral hemorrhage (ICH) and cerebral infarct (CI). We retrospectively enrolled 90 patients (32 with ICH and 58 with CI), admitted within 12 hours after the onset of stroke. Body temperatures were measured as the tympanic temperatures during the initial 6 days of hospitalization. Patients with clinical infections were excluded. The severity of stroke was assessed by Scandinavian Stroke Scale (SSS). SSS score < or = 30 was defined as severe stroke, and SSS score >30 as mild-to-moderate stroke. Mean body temperature was significantly higher in patients with ICH than those with CI in 0 approximately 12 hours; 12 approximately 24 hours, 24 approximately 48 hours, and 48 approximately 72 hours (all p<0.05) after the onset of stroke. Among patients with ICH, the body temperature was significantly higher in the severe group than the mild-to-moderate group during 24 approximately 48 hours and 48 approximately 72 hours (both p<0.05) after the onset of stroke. No significant difference in body temperatures was observed between patients with severe stroke and patient with mild-to-moderate CI. The serial time course of body temperature in the acute stage of stroke differs between ICH and CI. This study showed that, in ICH but not in CI, the elevation of body temperature has significant association with the stroke severity. Our results may help in the management of hyperthermia during acute stroke.


[History of the term "tan" (phlegm) (I) - Studies of the term "tan" described in classical Chinese translations of Buddhist literature].
We traced the origin of the term "tan" (phlegm) in Chinese traditional medicine. This term itself is not found in early works but is represented by the terms of tuo (saliva) and xian (drivel). However, in the theory of tri-dosa of Indian traditional medicine, phlegm is an important element. Our studies of classical Chinese translations of Buddhist literature showed that the concept of tan in Buddhist medicine was introduced into China through Buddhism.


Transcriptome Analysis of Storage Roots and Fibrous Roots of the Traditional Medicinal Herb Callerya speciosa (Champ.) ScHot.
Callerya speciosa (Champ.) ScHot is a woody perennial plant in Fabaceae, the roots of which are used medicinally. The storage roots of C. speciosa are derived from fibrous roots, but not all fibrous roots can develop into storage roots. To detect key genes involved in storage roots formation, we performed Illumina sequencing of the C. speciosa storage roots and fibrous roots. De novo assembly resulted in 161,926 unigenes, which were subsequently annotated by BLAST, GO and KEGG analyses. After expression profiling, 4538 differentially expressed genes were identified. The KEGG pathway enrichment analysis revealed changes in the biosynthesis of cytokinin, phenylpropanoid, starch, sucrose, flavone and other secondary metabolites. Transcription factor-related differentially expressed genes (DEGs) were also identified, including such gene families as GRAS, COL, MIKC, ERF, LBD, and NAC. The DEGs related to light signaling, starch, sugar, photohormones and cell wall-loosening might be involved in the formation of storage roots. This study provides the first transcriptome profiling of C. speciosa roots, data that will facilitate future research of root development and metabolites with medicinal value as well as the breeding of C. speciosa.


Assessment of potential factors associating with costs of hospitalizing cardiovascular diseases in 141 hospitals in Guangxi, China.
The rising cost of healthcare is of great concern in China, as evidenced by the media features negative reports almost daily. However there are only a few studies from well-developed cities, like Beijing or Shanghai, and little is known about healthcare costs in rest of the country. In this study, we use hospitalization summary reports (HSRs) from admitted cardiovascular diseases patients in Guangxi hospitals during 2013-2016, and we investigate temporal trends of healthcare costs and associated factors. By generalized additive model, we compute temporal trends of cost per stay (CPS), cost per day (CPD) and others. We then use generalized linear models to assess which factors associate with CPS and CPD. Using a total of 760,000 HSRs, we find that CPS appears to be stabilized around $1040 until the middle of year 2015, before exhibiting a downward trend. Similarly, CPD exhibits similar stable pattern. Meanwhile, surgery-specific CPS showed an increase in year 2013-2014, and then stabilized. Drug costs account for over 1/3 of CPS, but they are gradually declining. Costs associated with physicians' and nurses' services represent less than 5% of CPS. We found that age, sex, marital status, occupation and payment methods are significantly associated with CPS or CPD. Interestingly, we found no association between patient ethnicity and these costs. However, we did find that minority patients use more secondary hospitals than Han patients. Healthcare costs in Guangxi are stable, contrary to the rise portrayed by Chinese mass media. Several factors can be associated with healthcare costs, and these may be useful for developing evidence-based policies. In particular, there is a need to encourage more Han patients to seek care in primary and secondary hospitals.


The importance of subfragment 2 and C-terminus of myosin heavy chain for thick filament assembly in skeletal muscle cells.
In skeletal muscle cells, myofibrillar proteins are highly organized into sarcomeres in which thick filaments interdigitate with thin filaments to generate contractile force. The size of thick filaments, which consist mainly of myosin molecules, is strictly controlled. However, little is known about the mechanisms by which myosin molecules assemble into thick filaments. Here, we assessed the ability of each domain of myosin heavy chain (Myh) to form thick filaments. We showed that exogenously expressed subfragment 2 (S2) + light meromyosin (LMM) of Myh was efficiently incorporated into thick filaments in muscle cells, although neither solely expressed S2 nor LMM targeted to thick filaments properly. In nonmuscle COS7 cells, S2+LMM formed more enlarged filaments/speckles than LMM. These results suggest that Myh filament formation is induced by S2 accompanying LMM. We further examined the effects of Myh C-terminus on thick filament assembly. C-terminal deletion mutants were incorporated not into entire thick filaments but rather into restricted regions of thick filaments. Our findings suggest that the elongation of myosin filaments to form thick filaments is regulated by S2 as well as C-terminus of LMM.


Giving birth in America, 1988.
Advances in medical science have improved the prospects for pregnant women to deliver safely and for childless women to become pregnant. However, the picture is not as positive as it may seem. The liability crisis that is driving many obstetricians out of practice is likely to persist, limiting women's access to obstetric care. Reliance on cesarean delivery has risen to unacceptable levels, in part as a result of excessive use of electronic fetal monitoring. Pregnancy complications, prematurity and perinatal morbidity and mortality continue to be serious problems. U.S. perinatal mortality data do not compare favorably with those of many other developed nations, and the rate of prematurity will probably exceed that 1990 target of five percent set by the U.S. government. Prematurity and pregnancy complications are rooted in the associated social factors of poverty, welfare dependence and limited education, and they will not be eliminated until those problems are eased. There also is little hope that obstetric outcomes can be improved without reducing the extent of smoking, drug use and alcohol consumption during pregnancy. Infertility also can be caused or worsened by social factors that defy easy resolution. For the next 20 years, dealing with these societal problems should be a top priority.


Chemical Kinetics of Hydrogen Atom Abstraction from Propargyl Sites by Hydrogen and Hydroxy Radicals.
Hydrogen atom abstraction from propargyl C-H sites of alkynes plays a critical role in determining the reactivity of alkyne molecules and understanding the formation of soot precursors. This work reports a systematic theoretical study on the reaction mechanisms and rate constants for hydrogen abstraction reactions by hydrogen and hydroxy radicals from a series of alkyne molecules with different structural propargyl C-H atoms. Geometry optimizations and frequency calculations for all species are performed at M06-2X/cc-pVTZ level of theory and the hindered internal rotations are also treated at this level. The high-level W1BD and CCSD(T)/CBS theoretical calculations are used as a benchmark for a series of DFT calculations toward the selection of accurate DFT functionals for large reaction systems in this work. Based on the quantum chemistry calculations, rate constants are computed using the canonical transition state theory with tunneling correction and the treatment of internal rotations. The effects of the structure and reaction site on the energy barriers and rate constants are examined systematically. To the best of our knowledge, this work provides the first systematic study for one of the key initiation abstraction reactions for compounds containing propargyl hydrogen atoms.


Nonquantum entanglement resolves a basic issue in polarization optics.
The issue raised in this Letter is classical, not only in the sense of being nonquantum, but also in the sense of being quite ancient: which subset of 4x4 real matrices should be accepted as physical Mueller matrices in polarization optics? Nonquantum entanglement or inseparability between the polarization and spatial degrees of freedom of an electromagnetic beam whose polarization is not homogeneous is shown to provide the physical basis to resolve this issue in a definitive manner.


Probabilistic Transformations of Quantum Resources.
The difficulty in manipulating quantum resources deterministically often necessitates the use of probabilistic protocols, but the characterization of their capabilities and limitations has been lacking. We develop a general approach to this problem by introducing a new resource monotone that obeys a very strong type of monotonicity: it can rule out all transformations, probabilistic or deterministic, between states in any quantum resource theory. This allows us to place fundamental limitations on state transformations and restrict the advantages that probabilistic protocols can provide over deterministic ones, significantly strengthening previous findings and extending recent no-go theorems. We apply our results to obtain a substantial improvement in bounds for the errors and overheads of probabilistic distillation protocols, directly applicable to tasks such as entanglement or magic state distillation, and computable through convex optimization. In broad classes of resources, we strengthen our results to show that the monotone completely governs probabilistic transformations-it serves as a necessary and sufficient condition for state convertibility. This endows the monotone with a direct operational interpretation, as it can exactly quantify the highest fidelity achievable in resource distillation tasks by means of any probabilistic manipulation protocol.


The role of chronic peer difficulties in the development of children's psychological adjustment problems.
A longitudinal investigation was conducted to explicate how the confluence of early behavioral dispositions, relational histories, and cognitive representations of the self and others contributes to internalizing problems, externalizing problems, and loneliness. One-hundred and ninety three girls, and 206 boys were assessed annually from age 5 (kindergarten) to age 10 (Grade 4). Early aggressive behavior was related to Grade 4 maladjustment directly and indirectly through subsequent relational stressors. Significant associations emerged between chronic friendlessness and rejection and later adaptation not accounted for by concurrent relational difficulties. Self- and peer beliefs partially mediated the relation between peer difficulties and internalizing problems and loneliness. The results highlight the utility of child-by-environment models as a guide for the investigation of processes that antecede psychosocial maladjustment.


Cyclic AMP-mediated increase in L-type calcium current (ICa,L) by nitroglycerin in guinea-pig ventricular myocytes.
The effects of nitroglycerin (NG) on the L-type Ca2+ current (ICa,L) were investigated in guinea-pig ventricular myocytes. NG did not affect the basal ICa,L significantly. The ICa,L was increased by NG when the ICa,L was augmented by the pre-treatment with isoproterenol (Iso), and this increase was abolished by the pretreatment with methylene blue (MB), a guanylate cyclase inhibitor. NG also increased ICa,L in the myocytes undergoing the pretreatment with isobutylmethylxanthine (IBMX). The NG-induced increase in ICa,L was also observed in the myocytes intracellularly dialyzed with cyclic adenosine monophosphate (cAMP). The order of the Iso-induced increase in ICa,L was Iso, IBMX and cAMP. Relatively a lower concentration of the extracellularly applied 8bromo-cyclic guanosine monophosphate (8Br-cGMP) increased ICa,L in the myocytes dialyzed with cAMP, whereas the higher concentration of 8Br-cGMP decreased ICa,L. NG produced a marked increase in cGMP levels, and a slight increase in cAMP levels in the ventricular tissues. These results suggest that the stimulatory effect of NG on the ICa,L is due to an inhibition of cGMP-inhibitable cAMP-phosphodiesterase (PDE) and a possible activation of cGMP-dependent protein kinase via the NG-induced increase in cGMP levels in guinea-pig ventricular myocytes.


Calcium-dependent self-association of the C-type lectin domain of versican.
Versican is a large (1-2 x 10(6) Da) chondroitin-sulfate proteoglycan that can form large aggregates by means of interaction with hyaluronan and also binds to a series of other extracellular matrix proteins, chemokines and cell-surface molecules. Versican is a multifunctional molecule with roles in cell adhesion, matrix assembly, cell migration and proliferation. Characterization of the binding interactions mediated by the various domains of versican is a first step towards understanding the functions of versican and interacting molecules in the extracellular matrix. In this study we investigated a recombinant construct corresponding to the C-type lectin domain of versican and demonstrated a calcium-dependent self-association of this region by blot overlay and plasmon surface resonance assays. Electron microscopy provided further evidence of the relevance of the binding reaction by demonstrating a mixture of monomers, dimers and complex aggregates of recombinant versican C-type lectin domain. This binding reaction could contribute to the ability of versican to organize formation of the proteoglycan extracellular matrix by inducing binding of individual versican molecules or by modulating binding reactions to other matrix components.


NF-Protocadherin Regulates Retinal Ganglion Cell Axon Behaviour in the Developing Visual System.
Cell adhesion molecules play a central role in mediating axonal tract development within the nascent nervous system. NF-protocadherin (NFPC), a member of the non-clustered protocadherin family, has been shown to regulate retinal ganglion cell (RGC) axon and dendrite initiation, as well as influencing axonal navigation within the mid-optic tract. However, whether NFPC mediates RGC axonal behaviour at other positions within the optic pathway remains unclear. Here we report that NFPC plays an important role in RGC axonogenesis, but not in intraretinal guidance. Moreover, axons with reduced NFPC levels exhibit insensitivity to Netrin-1, an attractive guidance cue expressed at the optic nerve head. Netrin-1 induces rapid turnover of NFPC localized to RGC growth cones, suggesting that the regulation of NFPC protein levels may underlie Netrin-1-mediated entry of RGC axons into the optic nerve head. At the tectum, we further reveal a function for NFPC in controlling RGC axonal entry into the final target area. Collectively, our results expand our understanding of the role of NFPC in RGC guidance and illustrate that this adhesion molecule contributes to axon behaviour at multiple points in the optic pathway.


[Comparison of the antilipemic effect of bezafibrate with that of piperazine-sultosilate (A 585). A crossed double-blind study].
In 20 patients suffering from primary hyperlipoproteinaemia the action of sultosilic acid piperazine salt (A-585) was compared with bezafribrate. In a double-blind cross-over study parameters of the lipoprotein metabolism, as well as of fibrinolysis and of platelet function were examined. Both drugs significantly diminished total cholesterol, triglycerides, beta- and pre-beta cholesterol whilst alpha-cholesterol increased. Moreover, both drugs caused a significant shortening of the euglobulin lysis time and a diminution of platelet adhesiveness. In patients under oral anticoagulants the thrombotest levels were not influenced by A-585, but were depressed by bezafibrate. A slightly elevated gamma-GT normalized during bezafibrate therapy but was not influenced by A-585.


Genome analysis of Clostridium perfringens isolates from healthy and necrotic enteritis infected chickens and turkeys.
Clostridium perfringens causes gastrointestinal diseases in both humans and domestic animals. Type A strains expressing the NetB toxin are the main cause of necrotic enteritis (NE) in chickens, which has remarkable impact on animal welfare and production economy in the international poultry industry. Three pathogenicity loci NELoc-1, -2 and -3 and a collagen adhesion gene cnaA have been found to be associated with NE in chickens, whereas the presence of these has not been investigated in diseased turkeys. The purpose was to investigate the virulence associated genome content and the genetic relationship among 30 C. perfringens isolates from both healthy and NE infected chickens and turkeys, applying whole-genome sequencing. NELoc-1, -3, netB and cnaA were significantly associated with NE isolates from chickens, whereas only NELoc-2 was commonly observed in both diseased turkeys and chickens. A putative collagen adhesion gene that encodes a von Willebrand Factor (vWF) domain was identified in all diseased turkeys and designated as cnaD. The phylogenetic analysis based on single nucleotide polymorphisms showed that the isolates generally were not closely related. These results indicate that virulence factors and pathogenicity loci associated with NE in chickens are not important to the same extent in diseased turkeys except for NELoc-2. A putative collagen adhesion gene which potentially could be of importance in regard to the NE pathogenesis in turkeys was identified and need to be further investigated. Thus, the pathogenesis of NE in turkeys appears to be different from that of broiler chickens.


A systematic review of economic evaluations of population-based sodium reduction interventions.
To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of 'excellent' reporting quality, five studies fell into the 'very good' quality category and one into the 'good' category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new interventions to be evaluated in the field using strong study designs and parallel economic evaluations.


Multi-task learning models for predicting active compounds.
The computational drug discovery methods can find potential drug-target interactions more efficiently and have been widely studied over past few decades. Such methods explore the relationship between the structural properties of compounds and their biological activity with the assumption that similar compounds tend to share similar biological targets and vice versa. However, traditional Quantitative Structure - Activity Relationship (QSAR) methods often do not have desired accuracy due to insufficient data of compound activity. In this paper, we focus on building Multi-Task Learning (MTL)-based QSAR models by considering multiple similar biological targets together and make shared information transfer across from one task to another, thereby improving not only the learning efficiency, but also the prediction accuracy. This paper selects 6 assay groups with similar biological targets from PubChem and builds their QSAR models with MTL simultaneously. According to the experiment results, our MTL-based QSAR models have better performance over traditional prominent machine learning algorithms and the improvements are even more obvious when other baseline models have low accuracy. The superiority of our models is also proved by Student's t-test with level of significance 5%. Moreover, this paper also explores three different assumptions on the underlying pattern in the dataset and finds that the joint feature MTL models further improve the performance of the QSAR models and are more suitable for building QSAR models for multiple similar biological targets.


Robust face recognition via adaptive sparse representation.
Sparse representation (or coding)-based classification (SRC) has gained great success in face recognition in recent years. However, SRC emphasizes the sparsity too much and overlooks the correlation information which has been demonstrated to be critical in real-world face recognition problems. Besides, some paper considers the correlation but overlooks the discriminative ability of sparsity. Different from these existing techniques, in this paper, we propose a framework called adaptive sparse representation-based classification (ASRC) in which sparsity and correlation are jointly considered. Specifically, when the samples are of low correlation, ASRC selects the most discriminative samples for representation, like SRC; when the training samples are highly correlated, ASRC selects most of the correlated and discriminative samples for representation, rather than choosing some related samples randomly. In general, the representation model is adaptive to the correlation structure that benefits from both l1-norm and l2-norm. Extensive experiments conducted on publicly available data sets verify the effectiveness and robustness of the proposed algorithm by comparing it with the state-of-the-art methods.


Increasing Educational Attainment in Adolescents with Sickle Cell Disease.
Adolescents with sickle cell disease (SCD), a chronic condition primarily impacting African Americans, experience challenges graduating high school. Understanding demographic, educational, and community-level correlates of disease is critical to creating effective interventions for these youths. This study aimed to examine 1) educational attainment for adolescents with SCD, 2) neighborhood correlates of their education, and 3) feasibility of a pilot to increase General Education Diploma (GED) class enrollment. Findings suggest demographic characteristics influence educational attainment. Improving educational attainment in adolescents with SCD requires understanding risk beyond disease severity. Identifying risk and protective neighborhood-level factors can inform interventions to improve educational attainment. Feasibility of programming to increase GED enrollment should be further investigated.


Analysis of dental arch relationships in Swedish unilateral cleft lip and palate subjects: 20-year longitudinal consecutive series treated with delayed hard palate closure.
To evaluate the dental arch relationships for a consecutive series from Goteborg, Sweden, who had delayed hard palate closure. Retrospective study. Sahlgrenska University Hospital, Goteborg, Sweden. The dental study models of 104 consecutive unilateral cleft lip and palate subjects. The study cohort was born between 1979 and 1994. Longitudinal records were available at ages 5 (n = 94), 10 (n = 97), 16 (n = 59), and 19 years (n = 46). Five assessors rated models according to the GOSLON Yardstick on two separate occasions each. These patients had been operated upon according to the Goteborg protocol of delayed hard palate closure (at age 8 years). 85% of subjects were rated in groups 1 and 2 (excellent or very good outcome), 12% were rated in group 3 (satisfactory), and 3% were assigned to group 4 (poor). No patients presented in Group 5 (very poor). Weighted kappa statistics for double determination of Yardstick allocation for five assessors demonstrated values between .65 and .90 for interrater agreement (good/very good) and between .70 and .90 for intrarater agreement (very good). Delayed hard palate closure as practiced in Goteborg since 1979 has produced the best GOSLON Yardstick ratings in a consecutive series of patients ever recorded worldwide, since the Yardstick was first used in 1983. However, it is noteworthy that a new protocol has been introduced in Goteborg since 1994, in which hard palate closure is done at 3 years due to concerns regarding speech.


[Effect of jian yan ling on serum lipids, apoprotein and lipoprotein-a].
Effect of Jian Yan Ling (JYL, mainly consisted of Succinum, Pteria margaritifers and Astragalus membranaceus etc.) on serum lipids was studied by double-blind method in 128 hyperlipemia patients. Patients were divided randomly into two groups, the test groups (64 cases) treated with JYL, while the other 64 cases treated with placebo as control for 3 months. Serum total cholesterol (TC), triglyceride (TG), TC-high density lipolipid-cholesterol (TC-HDL-C), apoproteins were observed before and after treatment. Results showed that the TC, TG, apoproteins and lipoprotein-a of test group were all dropped significantly after JYL treatment (P < 0.01). The results suggested that JYL could regulate the blood lipids and could also exert an effect of antiatherosclerosis through reducing blood lipoprotein-a level. It is worth while to use JYL as an antihyperlipemic agent clinically.


[Control of cardiac rhythm by stimulation of the vagus nerve in bursts in the rat].
Burst stimulation of the vagus nerve in rats made it possible to obtain the ranges of the heart rate regulation. The increase of the number of impulses in a burst from 1 to 16 leads to a consistent decrease in the range of regulation from respectively 72.1 and 66.7% to 30.4 and 25% of the initial rate. The maximal range (10.1% of the initial rate) is reached with 4 impulses in a burst. The phenomenon of the regulation is reversed by atropine.


Physiological regulation and infantile anorexia: a pilot study.
To examine whether infantile anorexia is associated with physiological dysregulation. This study included eight toddlers with infantile anorexia and eight healthy eaters matched for age, race, socioeconomic status, and gender. Physiological measures of heart period and respiratory sinus arrhythmia were assessed across three different situations: mother-toddler interaction, toddler-stranger interaction, and toddler left alone with a toy while mother and stranger talked to each other at the other side of the room. Across all three situations, toddlers with infantile anorexia showed significantly shorter heart periods (i.e., faster heart rates) than controls (p <.05). In addition, as social demand decreased from episode 2 to episode 3, control toddlers exhibited an increase in respiratory sinus arrhythmia, whereas toddlers with infantile anorexia showed a decrease in respiratory sinus arrhythmia (p <.001). Toddlers with infantile anorexia showed consistently shorter heart periods and were less adaptive in their physiological regulation than controls. Such physiological dysregulation may constitute a tendency for less optimal internal homeostatic regulation of feeding in toddlers with infantile anorexia.


[Bariatric surgery : psychiatric issues before and after surgery].
Bariatric surgery is currently the most effective therapy for the treatment of severe obesity (BMI ≥ 35 kg/m2). This article addresses psychiatric issues preceding and following this surgery, considering that weight loss is not the only criterion to be considered in assessing the quality of the postoperative course. Quality of life, the evolution of psychiatric and somatic comorbidities, compliance and long-term postoperative complications and possible interventions to optimize the psychological and psychiatric care for these patients are discussed.


Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back-Looking Forward to Next-Generation Innovation.
Idiosyncratic drug-induced hepatotoxicity is a formidable challenge for rational drug discovery and development, as well as the science of personalized medicine. There is evidence that hereditary factors, in part, contribute to drug toxicity. This expert analysis and review offer the insights gained, and the challenges ahead, for genome-wide association studies (GWASs) of idiosyncratic drug-induced hepatotoxicity. Published articles on genome-wide and subsequent replication studies were systematically searched in the PubMed electronic database. We found that the genetic risk variants that were identified genome-wide, and replication confirmed, are mainly related to polymorphisms in the human leukocyte antigen (HLA) region that include HLA-DQB1*06:02 for amoxicillin-clavulanate, HLA-B*57:01 for flucloxacillin, HLA-DRB1*15:01 for lumiracoxib, and HLA-DRB1*07:01 for lapatinib and ximelagatran-induced hepatotoxicity. Additionally, polymorphisms in ST6 β-galactosamide α-2, 6-sialyltranferase-1 (ST6GAL1), which plays a role in systemic inflammatory response, and variants in intron of family with sequence similarity-65 member-B (FAM65B) that play roles in liver inflammation displayed association with flucloxacillin and antituberculosis drug-induced hepatotoxicity, respectively. Taken together, these GWAS findings offer molecular leads on the central role that the immune system plays in idiosyncratic drug-induced hepatotoxicity. We conclude the expert review with a brief discussion of the salient challenges ahead. These include, for example, the need for discursive discovery paradigms that incorporate alternating GWASs and candidate gene studies, as well as the study of the environtome, the entire complement of environmental factors, including science and innovation policies that enact on global society and the human host, and by extension, on susceptibility for idiosyncratic drug-induced hepatotoxicity.


Retrospective Analysis of Outcomes of Patients with Relapsed, Refractory and Metastatic Sarcomas who have received Metronomic Chemotherapy.
Paediatric soft tissue sarcoma treatments and outcomes have improved significantly in the last few decades. However, a significant number of patients still succumb to the disease. In low-middle income countries there are dual problems of advanced disease at presentation and financial burden leading to poor compliance to therapy. Hence, we designed a low-cost oral metronomic chemotherapy protocol for these patients and studied the responses and toxicities to therapy in a tertiary referral hospital. This is retrospective, single institutional, observational study. We retrospectively reviewed data of patients with relapsed, refractory or metastatic soft tissue sarcoma (STS) [ Ewing Sarcoma (ES); Rhabdomyosarcoma (RMS) or other STS] who were treated with the metronomic protocol of oral Tamoxifen, Etoposide and Cyclophosphamide (TEC) during the period April 1998 to September 2013, at the Tata Memorial Hospital, Parel, Mumbai. Patients with ES and RMS were primarily treated on our Institutional protocols. The patients included in the analysis were those who had relapsed after the primary protocols and then treated with metronomic TEC protocol; or those with primary refractory or metastatic disease (RMS, ES) and received metronomic TEC therapy. 49 patients were enrolled. Among the 49 patients, 32 were diagnosed ES, 13 RMS and 4 other STS. For the whole cohort response rates (RR) were 59% and clinical benefit rate (CBR) was 79%. Patients in the study were grouped into the following subgroups. Systemic recurrent/relapsed disease (N=24), metastatic disease at presentation (N=15) and local disease (refractory/recurrent) (N=10). None of the patients required blood or platelet support or admission for supportive care. The PFS for the above groups were 16.8 months, 12.5 months and 126.68 months respectively. This compares favorably with other historical cohorts in a similar setting. This study provides a preliminary evidence efficacy and tolerability of metronomic chemotherapy in poor risk ES and RMS. It also demonstrates that with this low-cost low risk treatment few patients could go into long term remissions despite high disease burden.


Interaction of phenolic uncouplers in binary mixtures: concentration-additive and synergistic effects.
The uncoupling activities of 14 binary mixtures of substituted phenols and of 4 binary mixtures of phenols and anisols were investigated at different pH values. Experiments were performed with time-resolved spectroscopy on membrane vesicles (chromatophores) of the photosynthetic bacteria Rhodobacter sphaeroides. Phenols are known to destroy the electrochemical proton gradient in energy-transducing membranes by a protonophoric mechanism. Anisols do not have protonophoric activity but disturb membrane structure and functioning as a nonspecific baseline toxicant. It was postulated in the literature that, for certain substituted phenols, the formation of a dimer between the phenoxide and the neutral phenol may contribute significantly to the overall protonophoric activity. In 13 of 14 mixtures of substituted phenols but in none of the mixtures of phenols with anisols, such a dimer appears to be formed between two different mixture partners. An extended shuttle mechanism of uncoupling, which includes a term for the contribution of such a mixed dimer, provided a good description of all experimental data. Opposite speciation favors interaction and ortho substituents abate interaction, which adds evidence for the dimerformation via a hydrogen bond between the phenol-OH and the phenoxide. These findings are significant not only regarding the mechanism of protonophoric action but also for the risk assessment process of chemical mixtures in the environment. When assessing the effect of mixtures, concentration addition is regarded as a reference X concept to estimate effects of similarly acting compounds. The substituted phenols in this work act according to the same action mechanism of uncoupling. Nevertheless, the overall effect of four of the investigated mixtures, which exhibit stronger dimer formation as compared to the single compounds or for which the resulting dimer is intrinsically more active, exceeded the effect calculated according to concentration addition considerably. In future work, this synergistic effect observed in-vitro has to be validated in-vivo to deduce its implications for the risk assessment process.


[The serological diagnosis of gastrointestinal nematode infections in cattle].
Ostertagia ostertagi and Cooperia oncophora are widely distributed and are the most important parasites affecting young bovine livestock. Therefore, there is a substantial need for sensitive and specific parameters in support of their diagnosis, especially for sub-clinical disease correlated to production loss. In this review, the value and the application as a diagnostic tool of pepsinogen, gastrin and antibody response are discussed. An increase in pepsinogen or gastrin reflects mucosal damage caused by an Ostertagia infection. Some controversy exists about the level of pepsinogen and gastrin, which may be considered indicative for the diagnosis of clinical and sub-clinical ostertagiasis. Pepsinogen levels between 3,000 tot 4,000 mU tyrosine are regarded indicative for subclinical disease, values in excess of 5,000 mU tyrosine are considered significant for diagnosing clinical disease. For gastrin, it is suggested that based on group means, values of 400 pg/ml are indicative for subclinical parasitic disease in calves with reduced daily weight gain, while threshold levels of > or = 1000 pg/ml gastrin are representative for clinical ostertagiasis. Antibody responses to Ostertagia and Cooperia can be assessed using the enzyme immunoassay (EIA). Until now, mainly crude worm extracts have been used as antigen source in the EIA. They are not species-specific as discussed experiments provide evidence of a close relationship between the onset of parasitic disease and the evolution of the group mean parameters. However, data demonstrate serious variations between animals, which impede a reliable individual diagnosis. For longitudinal epidemiological studies especially pepsinogen and gastrin have proven their value, exhibiting fast fluctuations induced by infection or as a result of treatment. Conversely antibody levels were found to be more stable and therefore are useful in large cross-sectional studies, enabling a rough assessment of the degree of infection.


Capsular formation surrounding hepatocellular carcinoma.
In Japan, it is well known that most cases of hepatocellular carcinoma occur in the cirrhotic liver and this fact is regarded as a pathologic characteristic of hepatocellular carcinoma. Capsule formation surrounding the tumor is also a characteristic of hepatocellular carcinoma and it may be related to the developmental mode of hepatocellular carcinoma, to the clinical manifestation of symptoms and to the prognosis of the disease. The formation of the capsule can often be detected by means of modern imaging diagnostic procedures as well as sonography-guided or laparoscopy-guided needle biopsy of the liver. This paper reports the results of an investigation on the incidence of capsular formation surrounding hepatocellular carcinoma and its clinicopathological consideration in hepatocellular carcinoma in its early stage occurring in liver cirrhosis.


The crossover design to evaluate the efficacy of plaque removal in tooth-brushing studies.
To evaluate the crossover clinical trial design to assess plaque removal efficacy of the Sonicare Elite. A single-cohort, 12-week, two-treatment, single-blind, crossover clinical trial recruited 45 subjects. Plaque was recorded using the modified Quigley and Hein index plaque index (PI). After screening, subjects used the toothbrush for 2 weeks and were reminded to abstain from tooth cleaning 12-18 h prior to appointments. At visit two, subjects were randomized to 2 or 2(1/2) min. brushing time. PIs was recorded pre- and post-brushing. Subjects brushed for the allocated time for a further 2 weeks. At visit 3, PIs were recorded pre- and post-brushing. Two weeks later, at visit 4, the subjects crossed over and the protocol was repeated. There was no evidence of a learning effect within each arm of the crossover. A significant period effect was detected; however, no significant treatment by period effect was found. 2(1/2) min. brushing removed more plaque at full mouth (p=0.037), smooth (p=0.012) and lingual (p=0.002) sites compared with 2 min. The crossover design is a valid model for assessing plaque removal efficacy in tooth-brushing studies where no carry-over effect is clinically plausible.


Valproate-associated hyperammonemic encephalopathy.
The use of valproic acid (VPA) (also known as Depakote, Depakene, and others) frequently results in elevated plasma ammonia. In some people, hyperammonemia may be clinically significant, resulting in hyperammonemic encephalopathy, which may be severe. Valproic acid-induced hyperammonemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels of VPA. We describe 2 cases of valproic acid-induced hyperammonemic encephalopathy in patients with supratherapeutic VPA levels, although the condition has been described in people with normal VPA levels. With the increasing indications and off-label uses of VPA, family physicians should be aware of this potential complication of VPA and check ammonia levels in patients taking VPA who present with alterations in mental status. Treatment with L-carnitine may be beneficial in reducing ammonia levels.


Preventive magnesium supplement protects the inner ear against noise-induced impairment of blood flow and oxygenation in the guinea pig.
We have recently demonstrated in the guinea pig that preventive dietary magnesium supplement can significantly reduce hearing loss caused by acute impulse noise exposure. To elucidate the underlying protective mechanisms of magnesium, the present study examined its effect on noise-induced impairment of cochlear blood flow (CoBF) and perilymphatic oxygen partial pressure (pO2) in two groups of guinea pigs maintained on optimal or suboptimal dietary magnesium status. While laser Doppler flowmetry was used to determine CoBF, perilymphatic pO2 was measured polarographically using micro-coaxial platinum needle electrodes. Auditory function was tested by recording compound action potentials. Animals were exposed to a selected high-intensity impulse noise series (L(peak) 167 dB, 1/s, 38 min). In the low magnesium groups, the noise exposure resulted in a mean decrease of CoBF and perilymphatic PO2 by about 10 and 35 per cent of the initial value, respectively. In contrast, in the high magnesium groups, neither parameter displayed any noise-induced decreases, and there was even a tendency to a slight increase. Magnesium also reduced the hearing loss significantly by 10 to 35 dB over the frequency range (2-16 kHz) tested. Both the CoBF and the perilymphatic pO2 were found to correlate with the serum magnesium. The piesent findings show that in the guinea pig preventive dietary magnesium supplement can protect the inner ear against noise-induced impairment of blood flow and oxygenation, which may partly be responsible for noise-induced hearing loss.


Altered function of nitrergic nerves inhibiting sympathetic neurotransmission in mesenteric vascular beds of renovascular hypertensive rats.
Neuronal nitric oxide (NO) has been shown to modulate perivascular adrenergic neurotransmission by inhibiting noradrenaline release from terminals in rat mesenteric arteries. This study was conducted to investigate changes in the inhibitory function of NO-containing nerves (nitrergic nerves) in mesenteric vascular beds of 2-kidney, 1-clip renovascular hypertensive rats (2K1C-RHR). Rat mesenteric vascular beds without endothelium were perfused with Krebs solution and the perfusion pressure was measured. In preparations from sham-operated rats (control) and 2K1C-RHRs, vasoconstriction induced by periarterial nerve stimulation (PNS; 2-8 Hz), but not vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0 nmol), was markedly facilitated in the presence of a nonselective NO synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) (100 microM). The facilitatory effect of L-NAME in preparations from 2K1C-RHR was smaller than that in control preparations. L-NAME augmented PNS-evoked noradrenaline release, which was smaller in 2K1C-RHRs than in controls. The expression of neuronal NO synthase (nNOS) measured by western blotting in mesenteric arteries from 2K1C-RHRs was significantly decreased compared with control arteries. Immunohistochemical staining of mesenteric arteries showed dense innervation of nNOS-immunopositive nerves that was significantly smaller in arteries from 2K1C-RHR than that in control arteries. Mesenteric arteries were densely innervated by tyrosine hydroxylase-immunopositive nerves, which coalesced with nNOS-immunopositive nerves. These results suggest that the inhibitory function of nitrergic nerves in adrenergic neurotransmission is significantly decreased in 2K1C-RHRs. This functional alteration based on the decrease in nNOS expression and nitrergic innervation leads to enhanced adrenergic neurotransmission and contributes to the initiation and development of renovascular hypertension.


Automated Delineation of Lung Tumors from CT Images Using a Single Click Ensemble Segmentation Approach.
A single click ensemble segmentation (SCES) approach based on an existing "Click&Grow" algorithm is presented. The SCES approach requires only one operator selected seed point as compared with multiple operator inputs, which are typically needed. This facilitates processing large numbers of cases. Evaluation on a set of 129 CT lung tumor images using a similarity index (SI) was done. The average SI is above 93% using 20 different start seeds, showing stability. The average SI for 2 different readers was 79.53%. We then compared the SCES algorithm with the two readers, the level set algorithm and the skeleton graph cut algorithm obtaining an average SI of 78.29%, 77.72%, 63.77% and 63.76% respectively. We can conclude that the newly developed automatic lung lesion segmentation algorithm is stable, accurate and automated.


5-Methyl-3-(3-methyl-phen-yl)-7-phenyl-1,2,4-triazolo[4,3-c]pyrimidine.
The title compound, C(19)H(16)N(4), is one of the few known 3,7-diaryl-1,2,4-triazolo[4,3-c]pyrimidines. The triazolopyrimidine unit is essentially planar (r.m.s. deviation = 0.048 Å). The phenyl ring and the heterocyclic core subtend a dihedral angle of only 15.09 (6)°, whereas the m-tolyl ring is twisted by 71.80 (6)° out of the plane of the triazole ring. Two C-H⋯N hydrogen bonds and π-π stacking inter-actions [centroid-centroid distance = 3.7045 (8) Å] stabilize the crystal packing.


Surgical advancement of the larynx (laryngeal tie-forward) as a treatment for dorsal displacement of the soft palate in horses: a prospective study 2001-2004.
Correct placement of sutures ('laryngeal tie-forward') in experimentally created dorsal displacement of the soft palate (DDSP) has been observed to replace the function of the thyrohyoideus muscles and prevent DDSP. The 'laryngeal tie-forward' procedure would prevent or delay the occurrence of DDSP during exercise in horses with naturally occurring DDSP and therefore improve performance. A clinical population (n = 116), mainly of racehorses was presented for treatment of naturally occurring exercise-induced DDSP. All horses underwent the 'laryngeal tie-forward' procedure. The relative position of the thyroid and cricoid cartilage in relation to the caudal aspect of the basihyoid bone was recorded; follow-up was obtained by telephone communication with trainers, owners and/or referring veterinarians. In addition, a performance index and earnings were determined using race records. Preoperatively, the median distance between the caudal aspect of the basihyoid bone and rostral aspect of the thyroid cartilage was 3.5 cm. Post operatively, the thyroid cartilage was moved a median distance of 4 cm rostrally and the larynx was shown to be in a position more rostral and dorsal than in preoperative radiographs. Of 98 horses for which follow-up was available, the performance of 87% was classified as improved, 12% as unchanged and 2% as worse. In 20 horses in which the diagnosis had been confirmed by treadmill videoendoscopy, 80% had a significantly increased performance index and earnings (P = 0.007). For the entire population, there was a significant improvement in performance index and earnings after surgery (82%) (P = 0.0001). Placing the larynx in a more rostral and dorsal position may have improved the performance in 80-82% of the horses affected with naturally-occurring DDSP. 'Laryngeal tie-forward' is a surgical technique that has a measurable effect on the position of the larynx and offers an alternative therapy for treating horses affected with DDSP. More experience may be needed with this technique prior to its widespread use in horses with a clinical diagnosis of DDSP.


Expression of B7 Homolog 1 (B7H1) Is Associated with Clinicopathologic Features in Urothelial Bladder Cancer.
BACKGROUND B7 homolog 1 (B7H1) plays an important role in regulating tumor immunity. The purpose of this study was to probe the relationship between B7H1 expression and clinical outcomes in urothelial bladder cancer. MATERIAL AND METHODS We investigated 110 urothelial bladder cancer cases. The expressions of B7H1 in tumors were analyzed by immunohistochemistry and RT-PCR. The correlation between B7H1 expression and survival rate was analyzed by log-rank test. RESULTS B7H1 expression was significantly increased in cancerous tissues compared to normal tissues (p<0.05). B7H1 expression was not associated with sex, age, diameter, or the combination of these factors (p>0.05). The positive expression of B7-H1 was positively correlated with grade, stage, recurrence, and metastasis (p<0.05). The RT-PCR results were consistent with the immunohistochemistry outcomes. Furthermore, the expression of B7H1 in tumors was highly correlated with the survival rate (p<0.05). CONCLUSIONS Expression of B7H1 is correlated with clinicopathologic features in bladder cancer. Up-regulation of B7H1 can result in progression and recurrence of urothelial bladder cancer.


Identification of a novel subgroup 16SrII-U phytoplasma associated with papaya little leaf disease.
Papaya is an important fruit crop cultivated in tropical and subtropical regions. Papaya little leaf (PLL) disease was observed in China. The phytoplasma 16S rRNA gene was detected from symptomatic papaya trees via PCR using phytoplasma universal primers P1/P7 followed by R16F2n/R16R2. No amplification products were obtained from templates of asymptomatic papaya trees. These results indicated a direct association between phytoplasma infection and PLL disease. Comparative and phylogenetic analyses of 16S rRNA gene sequences indicated that the papaya-infecting phytoplasmas under study belonged to the peanut witches' broom phytoplasma group (16SrII). Genotyping through use of computer-simulated RFLP analysis of 16S rRNA genes and coefficients of RFLP pattern similarities (0.97) reveal that the PLL phytoplasma was placed in a new subgroup. In this article, we describe the molecular characterization of a new phytoplasma associated with PLL disease and propose that the PLL phytoplasma be considered as a novel subgroup, 16SrII-U.


Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1.
The dynamins represent a superfamily of proteins that have been shown to function in a wide range of membrane fusion and fission events. An increasing number of mutations in the human classical dynamins, Dyn-1 and Dyn-2 has been reported, with diseases caused by these changes ranging from Charcot-Marie-Tooth disorder to epileptic encephalopathies. The budding yeast, Saccharomyces cerevisiae expresses a single dynamin-related protein that functions in membrane trafficking, and is considered to play a similar role to Dyn-1 and Dyn-2 during scission of endocytic vesicles at the plasma membrane. Large parts of the dynamin protein are highly conserved across species and this has enabled us in this study to select a number of disease causing mutations and to generate equivalent mutations in Vps1. We have then studied these mutants using both cellular and biochemical assays to ascertain functions of the protein that have been affected by the changes. Specifically, we demonstrate that the Vps1-G397R mutation (Dyn-2 G358R) disrupts protein oligomerization, Vps1-A447T (Dyn-1 A408T) affects the scission stage of endocytosis, while Vps1-R298L (Dyn-1 R256L) affects lipid binding specificity and possibly an early stage in endocytosis. Overall, we consider that the yeast model will potentially provide an avenue for rapid analysis of new dynamin mutations in order to understand the underlying mechanisms that they disrupt.


Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation.
Mesotheliomas occur in occult serous cavities after chronic exposure of mesothelial cells to asbestos fibres. Molecular events that contribute to the development of this cancer are therefore not readily accessible for study. We have used in vitro culture systems to study and compare induced and spontaneous transformation events in primary mouse mesothelial cells. Mouse mesothelial cells were cultivated until small populations of proliferating cells emerged from senescing cultures. Spontaneously transformed cultures of cells were characterized and compared to malignantly transformed cells. Human mesothelial cells had a finite lifespan of 10-15 population doublings when cultured in vitro; mouse mesothelial cells typically exhibit this same pattern. Here, we show that mouse mesothelial cells can be cultured for extended periods and that these cells can transform spontaneously. Lines of spontaneously transformed cells generated in this study are immortal and growth factor-independent. They display the salient characteristic features of transformation, including increased proliferation rate, lack of contact inhibition, aneuploidy and ability to grow in anchorage-independent conditions. A subset of these cell lines developed into tumours in syngeneic mice. Comparative gene expression analysis demonstrated that spontaneously transformed cell lines were more closely related to neoplastic cells than to primary cells. These findings have implications for interpretation of in vitro transformation studies, demonstrating broad similarity between spontaneous and induced genetic changes.


In vitro transport of methotrexate by Drosophila Multidrug Resistance-associated Protein.
Methotrexate (MTX) is a widely used chemotherapeutic agent, immune suppressant and antimalarial drug. It is a substrate of several human ABC proteins that confer multidrug resistance to cancer cells and determine compartmentalization of a wide range of physiological metabolites and endo or xenobiotics, by their primary active transport across biological membranes. The substrate specificity and tissue distribution of these promiscuous human ABC transporters show a high degree of redundancy, providing robustness to these key physiological and pharmacological processes, such as the elimination of toxins, e.g. methotrexate from the body. A similar network of proteins capable of transporting methotrexate has been recently suggested to exist in Drosophila melanogaster. One of the key players of this putative network is Drosophila Multidrug-resistance Associated Protein (DMRP). DMRP has been shown to be a highly active and promiscuous ABC transporter, capable of transporting various organic anions. Here we provide the first direct evidence that DMRP, expressed alone in a heterologous system lacking other, potentially functionally overlapping D. melanogaster organic anion transporters, is indeed able to transport methotrexate. Our in vitro results support the hypothesized but debated role of DMRP in in vivo methotrexate excretion.


NT157 Inhibits HCC Migration via Downregulating the STAT3/Jab1 Signaling Pathway.
The high fatality-to-case ratio of hepatocellular carcinoma is directly related to metastasis. The signal transducer and activator of transcription-3 is a key mediator of the cytokine and growth factor signaling pathways and drives the transcription of genes responsible for cancer-associated phenotypes. However, so far, no specific inhibitor for signal transducer and activator of transcription-3 has been used in clinical practice. Therefore, targeting the signal transducer and activator of transcription-3 for cancer therapy is highly desired to improve outcomes in patients with hepatocellular carcinoma. Using the small-molecule inhibitor NT157, the effect of signal transducer and activator of transcription-3 inhibition on cell migration was tested in hepatocellular carcinoma cell lines and a lung metastasis model of the disease. NT157 significantly inhibited the migration of hepatocellular carcinoma cell lines in vitro and lung metastasis of hepatocellular carcinoma in vivo. Mechanistically, it inhibited the phospho-signal transducer and activator of transcription-3 in a dose- and time-dependent manner. Furthermore, NT157 treatment suppressed the c-Jun activation domain-binding protein-1 levels in the nucleus but no significant decrease was observed in its expression in the cytoplasm. Finally, high mRNA expression levels of signal transducer and activator of transcription-3 and c-Jun activation domain-binding protein-1 in hepatocellular carcinoma were associated with significantly low survival rates. NT157 inhibits hepatocellular carcinoma migration and metastasis by downregulating the signal transducer and activator of transcription-3/c-Jun activation domain-binding protein-1 signaling pathway and targeting it may serve as a novel therapeutic strategy for the clinical management of hepatocellular carcinoma in the future.


[Effect of glutamic acid on the anaerobic formation of ATP in the heart muscle].
The effect of exogenous glutamic acid on nitrogenous and energetic metabolism of isolated perfused heart of the rat was studied under anoxia. Addition of 5 mM glutamic acid to the perfusate significantly increased the ATP level in anoxic heart. Perfusion of anoxic heart with 5 mM glutamic acid recovered the glutamate and aspartate tissue content and caused augmented production of alanine and succinate, while lactate formation did not change. In the presence of glutamic acid, the glutamine and asparagine contents in the heart-perfusate system markedly increased; however, the ammonia content did not reduce significantly. The effect on glutamic acid was reproduced by its transamination products, 5 mM aspartic and 5 mM alpha-ketoglutaric acids, and was totally eliminated by 2 mM aminooxyacetic acid, an inhibitor of transaminases. These data suggest that the glutamate-induced protective effect of ATP is probably related to the stimulation of substrate phosphorylation in mitochondria, resulting in succinate synthesis that is coupled with glutamate transamination.


Pathogenic mechanisms and experimental models of multiple sclerosis.
Multiple sclerosis (MS) is a devastating autoimmune disease that affects more than 1 million people worldwide and severely compromises motor and sensory function through demyelination and axonal loss. This review covers current therapies, lessons learned from failed clinical trials, genetic susceptibility, key cell types involved, animal models, gene expression, and biomarker information. The current first-line therapies for MS include the type I interferons (IFN-I) and glatiramer acetate (GA) but because of their limited effectiveness new therapeutic modalities are required. Tysabri is an anti very late antigen-4 antibody that antagonizes the migration of multiple cell types and appears more efficacious as compared to the IFNs or GA. Tysabri blocks the transmigration of T cells and monocytes, which indicates that blocking multiple cell types may increase the effectiveness of the therapy. However, this therapy may increase the risk of progressive multifocal leukoencephalopathy. The major cell types hypothesized to be pathogenic include T cells and antigen-presenting cells, including B cells. The correlation of the animal model experimental autoimmune encephalomyelitis (EAE) of MS and its predictive value to determine efficacy in the clinic appears limited. However, all current therapies do demonstrate efficacy in EAE models. There are also examples of mechanisms that have worked in EAE but have failed in the clinic, such as the TNFα antagonists and anti-p40 (a subunit of IL-12 and IL-23). The MS field would benefit if clinical biomarkers were available to monitor clinical efficacy. The etiology of MS remains elusive but additional understanding of mechanisms involved in the pathogenesis of MS may guide us to more effective treatment and management of this autoimmune disease.


Soluble diazaiptycenes: materials for solution-processed organic electronics.
The synthesis and characterization of soluble azaiptycenes is reported. Optical and physical properties were studied and compared with those of the structurally consanguine azaacenes. Electrochemical experiments and quantum-chemical calculations revealed the electronic structure of the iptycene derivatives. Their crystallization behavior was examined. A highly fluorescent amorphous diazatetracene derivative was integrated into a simple organic light-emitting diode, showing enhanced performance compared with that of previously reported, structurally similar tetracenes.


Depression and sexual functioning in minority women: current status and future directions.
Despite the increasing number of non-Caucasians in the United States, the overwhelming majority of research into both depression and sexuality has been conducted with European-American (Caucasian) samples. Sexual dysfunction and depression often co-occur, impacting relationship satisfaction, quality of life, and treatment adherence. These issues may be particularly salient for African-American, Hispanic, and Asian-American women, yet this area of research has been relatively unexplored. Cultural factors may shape women's response to sexual dysfunction, resulting from the depression itself as well as antidepressant medication. Further research emphasizing gender and culture is needed to elucidate the prevalence, impact, and treatment of sexual dysfunction in specific groups of depressed minority women.


Polysaccharide-Based Edible Coatings Containing Cellulase for Improved Preservation of Meat Quality during Storage.
The objectives of this study were to optimize the composition of edible food coatings and to extend the shelf-life of pork meat. Initially, nine meat samples were coated with solutions containing chitosan and hydroxypropyl methylcellulose at various cellulase concentrations: 0%, 0.05%, and 0.1%, stored for 0, 7, and 14 days. Uncoated meat served as the controls. The samples were tested for pH, water activity (aw), total number of microorganisms (TNM), psychrotrophs (P), number of yeast and molds (NYM), colour, and thiobarbituric acid-reactive substances (TBARS). The pH and aw values varied from 5.42 to 5.54 and 0.919 to 0.926, respectively. The reductions in the TNM, P, and NYM after 14 days of storage were approximately 2.71 log cycles, 1.46 log cycles, and 0.78 log cycles, respectively. The enzyme addition improved the stability of the red colour. Significant reduction in TBARS was noted with the inclusion of cellulase in the coating material. Overall, this study provides a promising alternative method for the preservation of pork meat in industry.


Monocytes give rise to mucosal, but not splenic, conventional dendritic cells.
The mononuclear phagocyte (MP) system is a body-wide macrophage (MPhi) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, and immune defense. The in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified MPhi/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral MPhis and DCs. We show that MDPs are in vivo precursors of BM and blood monocytes. Interestingly, grafted Gr1high "inflammatory" blood monocytes shuttle back to the BM in the absence of inflammation, convert into Gr1low monocytes, and contribute further to MP generation. The grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCs in the spleen, which develop during homeostasis from MDPs without a monocytic intermediate.


Lipoma arborescens of the hip.
Lipoma arborescens is a rare intra-articular lesion characterized by extensive villous proliferation of the synovial membrane and hyperplasia of subsynovial fat. Although it has been described as arising from traumatic, inflammatory, rheumatologic, developmental, and neoplastic causes, its etiology remains unknown. This article describes in detail--for the first time in the orthopedic literature-a case of lipoma arborescens of the hip. Clinical presentation, histologic and radiographic findings, and treatment of this rare lesion are discussed. Based on clinical, radiologic, and surgical evaluation, differential diagnosis for this lesion should include other conditions that cause synovial thickening, proliferation, and joint effusion--for example, synovial chondromatosis, pigmented villonodular synovitis, synovial hemangiomatosis, and rheumatoid arthritis. Description of this case covers the full radiologic evaluation, including magnetic resonance imaging (MRI), diagnostic pathologic description, and minimum 24-month follow-up. Although lipoma arborescens of the hip is a rare condition, it should be considered in the differential diagnosis of patients with its characteristic clinical prodrome and MRI findings confirming a periarticular fatty mass.


[The analysis of hepatitis B virus genetic characterization and ratio of mutation in low-age group of HuNan].
In order to investigate the characterization of mutation and genotype distributing in the younger group which was under the universal vaccination. The sequence of HBV was analyzed to offer the information to control and prevention in the area. Young person's sera with positive HBsAg are collected, and the Large S sequence of HBV including preS and S gene are amplified and sequenced. The genotype and serotype were determined by clastwal with the standard genotype sequence. And one virus complete genome is amplified. The virus gene are successful amplified from the 33 sera. The sequence result indicate the 30 of 33 (90.9%) HBV genotype is B and 3 of 33 (9.0%) is C. The HBV serotype including ayw (1), adr (3), adw (29), 5 of 33 mutated in the "a" dominant of HBV, and the percentage is 15.2% . The HBV full length gene of serum number of 5856 is amplified and sequenced. Its genotype is B, serotype is adw and length is 3215 base. The dominant genotype of HuNan is B, and the dominant serotype is adw.


Abnormal plasma ceramides refine high-risk patients with worsening heart failure.
Worsening heart failure (WHF) is a heterogeneous clinical syndrome with poor prognosis. More effective risk stratification tools are required to identify high-risk patients. Evidence suggest that aberrant ceramide accumulation can be affected by heart failure risk factors and as a driver of tissue damage. We hypothesized that specific ceramide lengths and ratios serve as biomarkers for risk stratification in WHF patients by reflecting pathological changes of distinct organ dysfunctions. We measured seven plasma ceramides using liquid chromatography-mass spectrometry (LC-MS) in 1,558 patients, including 1,262 participants in retrospective discovery set and 296 WHF patients in prospective validation set in BIOMS-HF study (Registry Study of Biomarkers in Heart Failure). Univariable and multivariable logistic regression models were constructed to identify associations of ceramides with organ dysfunctions. We constructed three ceramide-based scores linked independently to heart, liver, and kidney dysfunction, with ceramides and ratios included in each score specifying systemic inflammation, chronic metabolic disorder, and water-sodium retention. The combined ceramide heart failure score (CHFS) was independently associated with adverse outcomes [Hazard Ratio, 2.80 (95% CI: 1.78-4.40; P < 0.001); 2.68 995% CI: 1.12-6.46; P = 0.028)] and improved the predictive value of Acute Decompensated Heart Failure National Registry score and BNP [net reclassification index, 0.34 (95% confidence interval, CI: 0.19-0.50); 0.42 (95% CI: 0.13-0.70)] in the discovery and validation set, respectively. Lower BNP levels, but higher CHFS had the highest hazard of future adverse events in WHF patients. Abnormal plasma ceramides, associated with heart and peripheral organ dysfunctions, provide incremental prognostic information over the ADHERE score and brain natriuretic peptide concentration for risk stratification in WHF patients. This may facilitate the reclassification of high-risk patients in need of aggressive therapeutic interventions.


Low coordinate iron derivatives stabilized by a β-diketiminate mimic. Synthesis and coordination chemistry of enamidophosphinimine scaffolds to generate diiron dinitrogen complexes.
In an effort to mimic N-diaryl-β-diketiminate ligands (Nacnac), we have converted N-arylimine phosphine ligands to enamine-phosphinimines via the Staudinger reaction. By varying the aryl azide, one can access enamine-phosphinimine ligands with the same or different N-aryl substituents on both the enamine and phosphinimine units, which allows this intrinsically unsymmetrical bidentate donor set to present variable steric effects at the metal center. The enamine-phosphinimine was deprotonated and used in metathetical reactions with Fe(ii) bromide precursors to generate low coordinate complexes of the empirical formula [(CY5)NpN(Ar,Ar')]FeBr (where CY5 = cyclopentenyl; Ar,Ar' = 2,6-diisopropylphenyl, 2,6-dimethylphenyl, 2,4,6-trimethylphenyl). Depending on the substituents, these bromide derivatives can be monomeric or dimeric via bromide bridges. Reduction under dinitrogen using potassium graphite generates the dinitrogen complexes ([(CY5)NpN(Ar,Ar')]Fe)2(μ-N2) for Ar,Ar' = 2,6-diisopropylphenyl, and Ar = 2,6-dimethylphenyl, Ar' = 2,4,6-trimethylphenyl. However, for the former, a unsymmetrical side product can be isolated that has a bridging N-2,6-diisopropylphenylimide unit with one enamido-phosphine ligand bound to one iron and the other iron stabilized with an intact enamido-phosphinimine. When the steric bulk is reduced on both nitrogen donors, a complicated product mixture is obtained after reduction from which a small amount of [(CY5)NpN(Ar,Ar')]Fe[(CY5)NP(Ar)] (Ar,Ar' = 2,6-dimethylphenyl) could be isolated. All of these complexes are paramagnetic and have been characterized by elemental analysis, magnetic studies and X-ray crystallography.


Reliability of ultrasound in predicting uterine leiomyoma volume.
Recently ultrasound has been used to size and track individual myoma volumes for patients undergoing medical therapy. However, little is known about the specific performance characteristics and limitations of this technique with respect to volume measurements. We performed and prospectively interpreted serial ultrasound examinations on myoma patients and confirmed the location, size and number of myomas in the surgical specimens. The smallest detectable tumor was 2.7 cm in diameter. The specificity was 94%; reproducibility had a 14% coefficient of variation for tumors with diameters greater than 6 cm. We conclude that ultrasound is suitable for imaging and sizing myomas provided that the diagnosis is otherwise certain and the tumors tracked are large.


Chitinimonas arctica sp. nov., isolated from Arctic tundra soil.
A Gram-stain-negative, rod-shaped, green-pigmented, aerobic and motile bacterium, strain R3-44T, was isolated from Arctic tundra soil. Stain R3-44T clustered closely with members of the genus Chitinimonas, which belongs to the family Burkholderiaceae, and showed the highest 16S rRNA sequence similarity to Chitinimonas naiadis AR2T (96.10%). Strain R3-44T grew optimally at pH 7.0, 28 °C and in the presence of 0-0.5 % (w/v) NaCl. The predominant respiratory isoprenoid quinone of strain R3-44T was identified as ubiquinone Q-8. The polar lipids consisted of phosphatidylglycerol, phosphatidylethanolamine, unidentified aminolipid and unidentified phospholipid. The main fatty acids were summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c, 40.6 %) and C16 : 0 (29.3 %). The DNA G+C content of strain R3-44T was 60.8 mol%. On the basis of the evidence presented in this study, strain R3-44T represents a novel species of the genus Chitinimonas, for which the name Chitinimonas arctica sp. nov. is proposed, with the type strain R3-44T (=CCTCC AB 2010422T=KCTC 72602T).


Echocardiographic abnormalities and disease severity in Fabry's disease.
Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase A, which leads to the pathologic deposition of neutral glycosphingolipids in lysosomes of the vascular endothelium of the heart, brain and kidney. The disease is progressive in hemizygous male patients, with increasing involvement of the major organs leading to death. Because cardiac involvement is a constant feature, echocardiograms were performed on 35 patients with Fabry's disease, 23 hemizygotes (aged 28.6 +/- 14 years) and 12 heterozygotes (aged 31.6 +/- 6 years), to determine whether cardiac involvement could be detected noninvasively. The results demonstrated that hemizygous male patients had a greater aortic root diameter, thicker interventricular septum and greater ventricular mass than did heterozygous female patients. Left ventricular mass per square meter of body surface area correlated well with clinical disease severity (r = 0.68, p less than 0.05), suggesting progressive glycosphingolipid deposition. Older heterozygotes (greater than 25 years old) had more severe evidence of cardiac disease than did younger male patients. Although mitral valve prolapse was identified in 12 (54%) of 23 male hemizygotes and in 7 (58%) of 12 female heterozygotes its presence did not correlate with clinical disease severity or other echocardiographic variables. Therefore, echocardiographic evidence of Fabry's disease appears to correlate with age-related disease severity and may be a useful noninvasive marker to follow disease progression and possible regression when appropriate therapy becomes available.


A neuromorphic system for video object recognition.
Automated video object recognition is a topic of emerging importance in both defense and civilian applications. This work describes an accurate and low-power neuromorphic architecture and system for real-time automated video object recognition. Our system, Neuormorphic Visual Understanding of Scenes (NEOVUS), is inspired by computational neuroscience models of feed-forward object detection and classification pipelines for processing visual data. The NEOVUS architecture is inspired by the ventral (what) and dorsal (where) streams of the mammalian visual pathway and integrates retinal processing, object detection based on form and motion modeling, and object classification based on convolutional neural networks. The object recognition performance and energy use of the NEOVUS was evaluated by the Defense Advanced Research Projects Agency (DARPA) under the Neovision2 program using three urban area video datasets collected from a mix of stationary and moving platforms. These datasets are challenging and include a large number of objects of different types in cluttered scenes, with varying illumination and occlusion conditions. In a systematic evaluation of five different teams by DARPA on these datasets, the NEOVUS demonstrated the best performance with high object recognition accuracy and the lowest energy consumption. Its energy use was three orders of magnitude lower than two independent state of the art baseline computer vision systems. The dynamic power requirement for the complete system mapped to commercial off-the-shelf (COTS) hardware that includes a 5.6 Megapixel color camera processed by object detection and classification algorithms at 30 frames per second was measured at 21.7 Watts (W), for an effective energy consumption of 5.45 nanoJoules (nJ) per bit of incoming video. These unprecedented results show that the NEOVUS has the potential to revolutionize automated video object recognition toward enabling practical low-power and mobile video processing applications.


Myocardial Infarction With Nonobstructive Coronary Arteries Assessed by 11C-Acetate Cardiac PET.
C-acetate PET can quantify myocardial blood flow and oxidative metabolism (kmono) with a single imaging study. We present a 63-year-old man with myocardial infarction with nonobstructive coronary arteries due to vasospasm, who underwent C-acetate PET after antispastic medication. By quantifying myocardial blood flow and kmono, C-acetate PET could detect the initial ischemic insult by vasospasm and sufficient amount of remaining viable myocardium, while excluding significant inducible ischemia. We suggest that C-acetate PET can be a clinically valuable tool for assessing the pathophysiology of myocardial infarction with nonobstructive coronary arteries.


Atherosclerosis: The Culprit and Co-victim of Vascular Dementia.
Vascular dementia (VD), a cerebrovascular disease which causes cognitive impairment, is one of the significant factors that affects the quality of senectitude. Atherosclerosis (AS) is a chronic inflammatory syndrome and closely associated with VD. Analyzing the role of AS in VD contribute greatly to its early detection and prevention, but their relationship has not been integrated into a complete network. This review summarizes AS biomarkers as VD predictors for the first time and describes the direct mechanisms of AS causing VD from five aspects: vascular morphogenesis, hemodynamic change, neurovascular unit damage (NVU), oxidative stress, and microRNA (miRNA). Finally, it discriminates the relationship between AS and VD in common risk factors which can be disease or some molecules. In particular, these data imply that the role of AS in VD is not only a pathogenic factor but also a comorbidity in VD. This review aims to bring new ideas for the prediction and treatment of VD.