The combination of astragalus injection and ambroxol hydrochloride in the adjuvant treatment of COPD: a systematic review and meta-analysis.
Chronic obstructive pulmonary disease (COPD) is a severe condition that leads to premature mortality and places a significant financial burden on healthcare systems. An adjunctive therapy in COPD includes the simultaneous administration of astragalus injection and ambroxol hydrochloride. Despite its widespread use, the effectiveness of this combined approach in COPD treatment has not been systematically evaluated. Thus, we conducted a systematic review and meta-analysis to assess the efficacy of combining astragalus injection with ambroxol hydrochloride as an adjuvant treatment for COPD. Six electronic databases were used to search for relevant randomized controlled trials, and data analysis was conducted using Review Manager 5.4. A total of 14 randomized controlled trials were included, involving 1070 patients who met the criteria. The results of the meta-analysis indicated that the combination of astragalus injection with ambroxol hydrochloride as an adjuvant treatment can improve various clinical parameters in patients with COPD compared to conventional treatment alone. These parameters include the clinical effective rate (OR = 5.44, 95% CI 3.51-8.43, I2 = 0%), partial pressure of oxygen in artery (MD = 1.12, 95% CI 0.87-1.36, I2 = 5%), partial pressure of carbon dioxide in artery (MD = - 1.43, 95% CI - 1.65 to - 1.21, I2 = 0%), forced expiratory volume in one second (MD = 0.30, 95% CI 0.18-0.42, I2 = 0%), percentage of forced expiratory volume in one second (MD = 16.18, 95% CI 12.60-19.76, I2 = 82%), forced vital capacity (MD = 0.33, 95% CI 0.21-0.45, I2 = 36%), hemoglobin (MD = - 16.17, 95% CI - 20.84 to - 11.51, I2 = 29%), and the ratio of forced expiratory volume in one second to forced vital capacity (MD = 2.51, 95% CI - 0.05 to 5.06, I2 = 0%). The combination of astragalus injection and ambroxol hydrochloride could be a selection of COPD patients as an adjuvant treatment. However, further validation is required to evaluate the effectiveness of combining astragalus injection and ambroxol hydrochloride as an adjunctive treatment for patients with COPD.


Ovarian follicles of new-born Merino lambs from genetic lines which differ in fecundity.
Ovaries were obtained from 78 new-born lambs (12 singletons, 25 twins, 28 triplets, 10 quadruplets and 3 quintuplets) from flocks selected for (T902, T903 and Booroola) or against (O) multiple births. Sections of the ovaries were examined with a projection microscope and the numbers of all types of follicles were estimated. There were no differences between genetic lines in the number of primordial follicles, after adjustment for litter size and sire; however, there were significantly more of these follicles in single-born lambs than in lambs born in litters of two or more within genetic lines. The number of vesicular follicles was lower in Booroola than in O lambs.


Photography in Dermatologic Surgery: Selection of an Appropriate Lighting Solution for a Particular Clinical Application.
Lighting is an important component of consistent, high-quality dermatologic photography. There are different types of lighting solutions available. To evaluate currently available lighting equipment and methods suitable for procedural dermatology. Overhead lighting, built-in camera flashes, external flash units, studio strobes, and light-emitting diode (LED) light panels were evaluated with regard to their utility for dermatologic surgeons. A set of ideal lighting characteristics was used to examine the capabilities and limitations of each type of lighting solution. Recommendations regarding lighting solutions and optimal usage configurations were made in terms of the context of the clinical environment and the purpose of the image. Overhead lighting may be a convenient option for general documentation. An on-camera lighting solution using a built-in camera flash or a camera-mounted external flash unit provides portability and consistent lighting with minimal training. An off-camera lighting solution with studio strobes, external flash units, or LED light panels provides versatility and even lighting with minimal shadows and glare. The selection of an optimal lighting solution is contingent on practical considerations and the purpose of the image.


HlyA hemolysin of Vibrio cholerae O1 biotype E1 Tor. Identification of the hemolytic complex and evidence for the formation of anion-selective ion-permeable channels.
Hemolysin (HlyA) was concentrated from supernatants of different Vibrio cholerae O1 biotype E1 Tor strains by ammonium sulfate precipitation. The concentration of the toxin in the supernatants and in the precipitates was quantified using its hemolytic activity. The toxin formed a high molecular-mass band (about 220 kDa) on SDS/PAGE while the toxin monomer had a molecular mass of 60 kDa when it was heated. The addition of the E1 Tor hemolysin oligomers, but not that of the monomers, to the aqueous phase bathing lipid bilayer membranes resulted in the formation of ion-permeable channels, which had long lifetimes at small voltages. The hemolysin channel had a single-channel conductance of 350 pS in 1 M KCl. These results defined hemolysin (HlyA) from V. cholerae as a channel-forming component with properties similar to other cytolytic toxins. The long lifetime of the channel suggested that the channel-forming oligomer did not show a rapid association/dissociation reaction. At voltages larger than 50 mV, the hemolysin channel was voltage dependent in an asymmetric fashion dependent on the side of its addition. The single-channel conductance of the hemolysin (HlyA) from V. cholerae O1 biotype E1 Tor channel was a linear function of the bulk aqueous conductance, which suggested that the toxin forms aqueous channels with an estimated minimum diameter of about 0.7 nm. The hemolysin channel of V. cholerae was found to be moderately anion-selective. The pore-forming properties of hemolysin (HlyA) from V. cholerae O1 biotype E1 Tor were compared with those of aerolysin of Aeromonas sobria and alpha-toxin from Staphylococcus aureus. All these cytolytic toxins must probably oligomerize for activity in biological and artificial membranes and form anion-selective channels.


Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice.
Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety. We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling. We then use quantitative complementation to show that Rgs2 is a quantitative trait gene. This combined genetic and functional approach should be applicable to the analysis of any quantitative trait.


[Importance of adenosine A2A receptors in resistance to complete global cerebral ischemia].
Selective A2A agonists (CGS 21680 and DPMA) produce a moderate neuroprotector effect with respect to the complete global cerebral ischemia (GCI). At the same time, selective A2A antagonists 8-(3-chlorostyrylcaffeine (CSC) and ZM 241385 somewhat reduce the brain resistance to complete GCI, completely prevent the neuroprotector effect of CGS 21680, partly suppress the neuroprotector activity of adenosine and 5'-N-ethylcarboxamidoadenosine (NECA), and do not affect (CSC) or potentiate (ZM 241385) the neuroprotector effect of N6-cyclopentyladenosine. The A2A-receptors are probably mediating in the neuroprotector activity of CGS 21680 and participating in the natural brain stability with respect to complete GCI, as well as in the effects of NECA and adenosine.


Multiple plasmon excitations in adsorbed two-dimensional systems.
Using monolayer graphene as a model system for a purely two-dimensional (2D) electron gas, we show by energy electron loss spectroscopy, highly resolved both in energy and momentum, that there is a significant probability for the excitation of not only one but two dispersing losses. The appearance of both losses is independent of the substrate (we tested graphene on the Si face of 6H-SiC(0001), and on Ir(111) without and with an intercalated Na layer), and the ratio of the slope in the dispersion curves varies between 1.4 (SiC) and 2. While the lower dispersion curve can be attributed to the excitation of the sheet plasmon, in agreement with theoretical model calculations, the upper dispersion branch has not been identified before for plasmonic excitations in a 2D electron gas, and we assign it tentatively to the excitation of a multipole sheet plasmon.


Concentration dynamics of polychlorinated biphenyls and organochlorine pesticides in blood of growing Grey heron (Ardea cinerea) chicks in the wild.
Organochlorine contaminants (OCs) - organochlorine pesticides (OCPs) and industrial products and byproducts - are included in different monitoring programmes and surveys, involving various animal species. Fish-eating birds are suitable indicator species for OCs. Adult birds may be difficult to capture, but chicks can be sampled more easily. Blood of birds is a potentially suitable non-destructive matrix for analysis, as OC levels in blood reflect their concentrations in the body. The study was aimed at investigating how age of fast-growing Grey heron (Ardea cinerea) chicks affects contaminant levels in their blood and thus how important is sampling at exact age for biomonitoring purposes. In 1999 on Lake Engure in Latvia whole blood samples of heron chicks were collected at three different time points, with seven and nine days in between the first and second and second and third sampling points, respectively. Twenty-two chicks were sampled at all three times. In total, 102 samples were analysed for 19 polychlorinated biphenyl (PCB) congeners, DDT metabolites - DDE and DDD, hexachlorobenzene (HCB), α-, β-, γ-hexachlorocyclohexane (HCH), and trans-nonachlor. Total PCB concentrations averaged around 2000 ng/g dry extracted matter (EM). DDE was the dominant individual contaminant (ca. 800 ng/g EM), followed by CB-153, -138, and -118. Most of the other analysed OCs were below 100 ng/g EM. No significant (p > 0.05) differences in OC concentrations were found between the three sampling occasions, except for trans-nonachlor. This means that blood can safely be sampled for biomonitoring purposes during the 17 days' time window. The analysed legacy contaminants may serve as model substances for other persistent organic pollutants.


Genome merger: from sequence rearrangements in triticale to their elimination in wheat-rye addition lines.
Genetic and epigenetic modifications resulting from different genomes adjusting to a common nuclear environment have been observed in polyploids. Sequence restructuring within genomes involving retrotransposon/microsatellite-rich regions has been reported in triticale. The present study uses inter-retrotransposon amplified polymorphisms (IRAP) and retrotransposon microsatellite amplified polymorphisms (REMAP) to assess genome rearrangements in wheat-rye addition lines obtained by the controlled backcrossing of octoploid triticale to hexaploid wheat followed by self-fertilization. The comparative analysis of IRAP and REMAP banding profiles, involving a complete set of wheat-rye addition lines, and their parental species revealed in those lines the presence of wheat-origin bands absent in triticale, and the absence of rye-origin and triticale-specific bands. The presence in triticale x wheat backcrosses (BC) of rye-origin bands that were absent in the addition lines demonstrated that genomic rearrangement events were not a direct consequence of backcrossing, but resulted from further genome structural rearrangements in the BC plant progeny. PCR experiments using primers designed from different rye-origin sequences showed that the absence of a rye-origin band in wheat-rye addition lines results from sequence elimination rather than restrict changes on primer annealing sites, as noted in triticale. The level of genome restructuring events evaluated in all seven wheat-rye addition lines, compared to triticale, indicated that the unbalanced genome merger situation observed in the addition lines induced a new round of genome rearrangement, suggesting that the lesser the amount of rye chromatin introgressed into wheat the larger the outcome of genome reshuffling.


Unprecedented head-to-head conformers of d(GpG) bound to the antitumor active compound tetrakis (mu-carboxylato)dirhodium(II,II).
The N7/O6 equatorial binding interactions of the antitumor active complex Rh(2)(OAc)(4)(H(2)O)(2) (OAc(-) = CH(3)CO(2)(-)) with the DNA fragment d(GpG) have been unambiguously determined by NMR spectroscopy. Previous X-ray crystallographic determinations of the head-to-head (HH) and head-to-tail (HT) adducts of dirhodium tetraacetate with 9-ethylguanine (9-EtGH) revealed unprecedented bridging N7/O6 guanine nucleobases that span the Rh-Rh bond. The absence of N7 protonation at low pH and the notable increase in the acidity of N1-H (pK(a) approximately 5.7 as compared to 8.5 for N7 only bound platinum adducts), suggested by the pH dependence titrations of the purine H8 (1)H NMR resonances for Rh(2)(OAc)(2)(9-EtG)(2) and Rh(2)(OAc)(2-)[d(GpG)],are consistent with bidentate N7/O6 binding of the guanine nucleobases. The pK(a) values estimated for N1-H (de)protonation, from the pH dependence studies of the C6 and C2 (13)C NMR resonances for the Rh(2)(OAc)(2)(9-EtG)(2) isomers, concur with those derived from the H8 (1)H NMR resonance titrations. Comparison of the (13)C NMR resonances of C6 and C2 for the dirhodium adducts Rh(2)(OAc)(2)(9-EtG)(2) and Rh(2)(OAc)(2)[d(GpG)] with the corresponding resonances of the unbound ligands [at pH 7.0 for 9-EtGH and pH 8.0 for d(GpG)], shows substantial downfield shifts of Deltadelta approximately 11.0 and 6.0 ppm for C6 and C2, respectively; the latter shifts reflect the effect of O6 binding to the dirhodium centers and the ensuing enhancement in the acidity of N1-H. Intense H8/H8 ROE cross-peaks in the 2D ROESY NMR spectrum of Rh(2)(OAc)(2)[d(GpG)] indicate head-to-head arrangement of the guanine bases. The Rh(2)(OAc)(2)[d(GpG)] adduct exhibits two major right-handed conformers, HH1 R and HH2 R, with HH1 R being three times more abundant than the unusual HH2 R. Complete characterization of both adducts revealed repuckering of the 5'-G sugar rings to C3'-endo (N-type), retention of C2'-endo (S-type) conformation for the 3'-G sugar rings, and anti orientation with respect to the glycosyl bonds. The structural features obtained for Rh(2)(OAc)(2))[d(GpG)] by means of NMR spectroscopy are very similar to those for cis-[Pt(NH(3))(2))[d(GpG)]] and corroborate molecular modeling studies.


Modeling the self-assembly of lipids and nanotubes in solution: forming vesicles and bicelles with transmembrane nanotube channels.
Via dissipative particle dynamics (DPD), we simulate the self-assembly of end-functionalized, amphiphilic nanotubes and lipids in a hydrophilic solvent. Each nanotube encompasses a hydrophobic stalk and two hydrophilic ends, which are functionalized with end-tethered chains. With a relatively low number of the nanotubes in solution, the components self-assemble into stable lipid-nanotube vesicles. As the number of nanotubes is increased, the system exhibits a vesicle-to-bicelle transition, resulting in stable hybrid bicelle. Moreover, our results reveal that the nanotubes cluster into distinct tripod-like structures within the vesicles and aggregate into a ring-like assembly within the bicelles. For both the vesicles and bicelles, the nanotubes assume trans-membrane orientations, with the tethered hairs extending into the surrounding solution or the encapsulated fluid. Thus, the hairs provide a means of regulating the transport of species through the self-assembled structures. Our findings provide guidelines for creating nanotube clusters with distinctive morphologies that might be difficult to achieve through more conventional means. The results also yield design rules for creating synthetic cell-like objects or microreactors that can exhibit biomimetic functionality.


Function of Delta4 gene and its effects on 32D cell differentiation.
Notch activation leads to transcriptional suppression of lineage-specific genes, inhibiting differentiation in response to inductive signals. The Notch signal system contains three parts: Notch molecules, Notch ligands and effectors. Delta4 is a newly-discovered Notch ligand which has received the attention of few detailed studies. This study sought to explore the biological function of Delta4 and observe its effects on 32D cell differentiation. Delta4-expressing vector pTracer.CMV.Delta4.FLAG was constructed using molecular biological techniques. CHO cells stably transfected with pTracer.CMV.Delta4.FLAG were confirmed to have a Delta4 protein band via Western blotting. High-expression Delta4-CHO clones were selected for the following functional studies. Notch1-CHO and Notch2-CHO were used as host cells. After transiently transfecting with transition protein 1 (TP1), Delta4 activity was compared in both cell lines by means of luciferase analysis. CHO cells were incubated with Notch1-32D cells that had been transfected with Notch1 and were observed for granulocyte colony-stimulating factor (G-CSF)-induced differentiation. Jagged2-CHO and Delta4-CHO cells transfected with the Notch ligands Jagged2 and Delta4, respectively, were incubated with Notch1-32D cells to observed inhibition of Notch on G-CSF-induced differentiation. The vector pTracer.CMV.Delta4.FLAG was constructed successfully. CHO cells were stably transfected with the vector pTracer.CMV.Delta4.FLAG. Two CHO cell lines expressing Delta4 at high levels were selected for use in the study. Delta4 was found to induce signal activity via both Notch1 and Notch2 and the induction of signaling activity was stronger in Notch2 cells than in Notch1 cells. Compared with other Notch ligands, Delta4 was slightly weaker than Jagged2, but stronger than Delta1 and Jagged1 in terms of Notch1 ligands. In terms of Notch2, Delta4 had a strong signaling activity, but was weaker than Delta1, Jagged1, and Jagged2. Jagged2 could inhibit Notch1-32D cell differentiation induced by G-CSF, but Delta4 could not. Delta4 induces both Notch1 and Notch2 activity and is a ligand for both of them. The effect of Delta4 is stronger on Notch2 than that on Notch1. Jagged2 can inhibit Notch1-32D cell differentiation induced by G-CSF, but Delta4 cannot.


Establishing an esketamine clinic in Australia: Practical recommendations and clinical guidance from an expert panel.
Major depressive disorder (MDD) can have severe impacts on function and quality of life. Up to one third of patients will have an inadequate response to their first line of treatment, with subsequent lines of therapy associated with lower remission rates and higher relapse rates. Recently esketamine has become available for Australian patients, and this agent provides an additional treatment option for those with MDD who have had an inadequate response to two or more antidepressant therapies during the current moderate to severe depressive episode. This paper provides an expert panel's practical recommendations and clinical guidance for establishing esketamine clinics in Australia. An expert panel (n = 11) comprising psychiatrists, mental health care nurses, pharmacists, and individuals with experience establishing esketamine clinics was convened in Sydney. The panel developed practical recommendations and clinical guidance, which were then further refined. Five key areas were identified: practical considerations for esketamine clinic set-up, including multidisciplinary care considerations; patient selection; administering esketamine; adverse event management and long-term follow-up. Guidance presented in this paper should assist Australian clinicians to set up an esketamine clinic, and provide practical advice on the infrastructure and clinical requirements for treatment of patients with this agent.


Acute myeloid leukaemia presenting with mediastinal myeloid sarcoma: report of three cases and review of literature.
Although myeloid sarcomas (MS) are frequently associated with acute myeloid leukaemia (AML), the occurrence of mediastinal MS is a much rarer event. The authors describe a distinct group of three AML patients with mediastinal MS and complex cytogenetics presenting at their centre over a 7-year period. Clinical features consistent with superior vena caval obstruction were noted at presentation in two of the three patients. Mediastinal mass was detected on routine chest radiography, and biopsies confirmed the diagnosis of MS. One patient relapsed after consolidation chemotherapy and died from progressive disease. Two patients underwent allogeneic haemopoietic stem cell transplant, but succumbed to transplant related complications. Review of mediastinal MS over the last 20 years shows that a significant proportion of patients have complex cytogenetic abnormalities and a poor long-term prognosis. Early and accurate diagnosis is essential and patients should be managed along the lines of high risk AML.


Induction of differentiation in human hepatocarcinoma cells by isoverbascoside.
Isoverbascoside, a phenylethanoid glycoside, was isolated from Chinese folk medicine herb Pedicularis striata Pall. Here we report that isoverbascoside is capable of inducing differentiation in human hepatocellular carcinoma (HCC) cell line SMMC-7721. When treated with isoverbascoside, the proliferation of SMMC-7721 cells was markedly inhibited in a dose- and time-dependent manner, and the average cell population doubling time was delayed. Exposure of cells to 20 micromol/l isoverbascoside led to the decline of colony formation efficiency on soft agar, induced G0/G1 arresting, and resulted in the decrease of gamma-glutamyltransferase (gamma-GT) activity and the increase of tyrosine aminotransferase (TAT) activity, two marker enzymes, respectively, representing HCC malignance and differentiation stage. These results suggest that isoverbascoside possess the activity of inducing differentiation in SMMC-7721 cells.


Inflammation and insulin resistance: an old story with new ideas.
Years before insulin was discovered, anti-inflammatory sodium salicylate was used to treat diabetes in 1901. Intriguingly for many years that followed, diabetes was viewed as a disorder of glucose metabolism, and then it was described as a disease of dysregulated lipid metabolism. The diabetes research focused on the causal relationship between obesity and insulin resistance, a major characteristic of type 2 diabetes. It is only within the past 20 years when the notion of inflammation as a cause of insulin resistance began to surface. In obesity, inflammation develops when macrophages infiltrate adipose tissue and stimulate adipocyte secretion of inflammatory cytokines, that in turn affect energy balance, glucose and lipid metabolism, leading to insulin resistance. This report reviews recent discoveries of stress kinase signaling involving molecular scaffolds and endoplasmic reticulum chaperones that regulate energy balance and glucose homeostasis. As we advance from a conceptual understanding to molecular discoveries, a century-old story of inflammation and insulin resistance is re-born with new ideas.


Postinduction requirement of NMDA receptor activation for late-phase long-term potentiation of developing retinotectal synapses in vivo.
Spaced patterns of repetitive synaptic activation often result in a long-lasting, protein synthesis-dependent potentiation of synaptic transmission, known as late-phase long-term potentiation (L-LTP) that may serve as a substrate for long-term memory. Behavioral studies showed that posttraining blockade of NMDA subtype of the glutamate receptor (NMDAR) impaired long-term memory, although NMDAR activation is generally known to be required during LTP induction. In this study, we found that the establishment of L-LTP in vivo requires NMDAR activation within a critical time window after LTP induction. In the developing visual system of Xenopus laevis tadpole, L-LTP of retinotectal synapses could be induced by three episodes of theta burst stimulation (TBS) of the optic nerve with 5 min spacing ("spaced TBS"), but not by three TBS episodes applied en masse or spaced with intervals ≥10 min. Within a time window of ∼30 min after the spaced TBS, local perfusion of the tectum with NMDAR antagonist d-AP5 or Ca(2+)-chelator EGTA-AM impaired the establishment of L-LTP, indicating the requirement of postinduction activation of NMDAR/Ca(2+) signaling. Moreover, inhibiting spontaneous spiking activity in the tectum by local application of tetrodotoxin (TTX) prevented L-LTP when TTX was applied for 15 min immediately after the spaced TBS but not 1 h later, whereas the same postinduction TTX application in the retina had no effect. These findings offer new insights into the synaptic basis for the requirement of postlearning activation of NMDARs and point to the importance of postlearning spontaneous circuit activity in memory formation.


Classical Estrogen Signaling in Ciliated Epithelial Cells of the Oviduct Is Nonessential for Fertility in Female Mice.
Ciliary action performs a critical role in the oviduct (Fallopian tube) during pregnancy establishment through sperm and egg transport. The disruption of normal ciliary function in the oviduct affects oocyte pick-up and is a contributing factor to female infertility. Estrogen is an important regulator of ciliary action in the oviduct and promotes ciliogenesis in several species. Global loss of estrogen receptor α (ESR1) leads to infertility. We have previously shown that ESR1 in the oviductal epithelial cell layer is required for female fertility. Here, we assessed the role of estrogen on transcriptional regulation of ciliated epithelial cells of the oviduct using single-cell RNA-sequencing analysis. We observed minor variations in ciliated cell genes in the proximal region (isthmus and uterotubal junction) of the oviduct. However, 17β-estradiol treatment had little impact on the gene expression profile of ciliated epithelial cells. We also conditionally ablated Esr1 from ciliated epithelial cells of the oviduct (called ciliated Esr1d/d mice). Our studies showed that ciliated Esr1d/d females had fertility rates comparable to control females, did not display any disruptions in preimplantation embryo development or embryo transport to the uterus, and had comparable cilia formation to control females. However, we observed some incomplete deletion of Esr1 in the ciliated epithelial cells, especially in the ampulla region. Nevertheless, our data suggest that ESR1 expression in ciliated cells of the oviduct is dispensable for ciliogenesis and nonessential for female fertility in mice.


Hyphessobrycon platyodus (Teleostei: Characiformes), a new species from the Rio Madeira basin, Brazil, with comments on how multicuspid teeth relate to feeding habits in Characidae.
A new species of Hyphessobrycon is described from the Rio Juma, a tributary of the lower Rio Aripuanã-Rio Madeira basin, Amazonas, Brazil. Hyphessobrycon platyodus can be distinguished from its congeners by the: presence of an elongated dorsal fin in adult males, 25-28 branched anal-fin rays and absence of dark blotches from the dorsal fin and caudal peduncle. The presence of multicuspid teeth in species of Characidae and its relation with feeding habits are briefly commented on.


Escape from floral herbivory by early flowering in Arabidopsis halleri subsp. gemmifera.
Natural selection on flowering phenology has been studied primarily in terms of plant-pollinator interactions and effects of abiotic conditions. Little is known, however, about geographic variation in other biotic factors such as herbivores and its consequence for differential selection on flowering phenology among populations. Here, we examine selection by floral herbivores on the flowering phenology of Arabidopsis halleri subsp. gemmifera using two adjacent populations with contrasting herbivory regimes. Intensive floral herbivory by the leaf beetle Phaedon brassicae occurs in one population, while the beetle is absent in another population. We tested the hypothesis that the two populations experience differential selection on flowering time that is attributable to the presence or absence of floral herbivory. A two-year field study showed that early flowering was favoured in the population under intensive floral herbivory, whereas selection for early flowering was not found in one year in the population where floral herbivory was absent. Selection for early flowering disappeared when the abundance of floral herbivores was artificially decreased in a field experiment. Thus, the heterogeneous distribution of P. brassicae was a major agent for differential selection on flowering time. However, flowering time did not differ between the two populations when plants were grown in the laboratory. The lack of genetic differentiation in flowering time may be explained by ongoing gene flow or recent invasion of P. brassicae. This study illustrates that the role of floral herbivory in shaping geographic variation in selection on flowering phenology may be more important than previously thought.


An acid-free microwave approach to prepare highly luminescent boron-doped graphene quantum dots for cell imaging.
Boron-doped graphene quantum dots (B-GQDs) are prepared via a one-pot acid-free microwave approach with graphene oxide as the carbon source and borax as the boron source. Boron atoms are incorporated into the graphene framework by attacking the defects in the graphene structure, deriving an atomic percentage of 1.44% in the final product. Boron atom doping into the graphene structure and restoration of defects in the graphene structure bring the obtained B-GQDs favorable photoluminescence behaviors. The as-prepared B-GQDs exhibit excitation-independent photoluminescence behaviors with an excitation/emission maximum at 320/430 nm, and a fluorescence quantum yield of 21.1%. Moreover, stable photoluminescence is observed within a wide range of pH 3.0-11.0. A tolerance to an external ionic strength of up to 2.0 mol L-1 KCl along with an excellent anti-photobleaching capability is achieved. The standard MTT assay suggests that the B-GQDs are of low cytotoxicity with favorable biocompatibility, and a cell viability of 87% could be achieved at 4.0 mg mL-1 of B-GQDs. The practical application of B-GQDs in bio-analysis is demonstrated by bio-imaging of HeLa cells.


Apathy is associated with activities of daily living ability in Parkinson's disease.
Neuropsychiatric symptoms and impairment in performing activities of daily living (ADL) in patients with Parkinson's disease (PD) are strong predictors of the overall caregiver burden and they increase the risk for nursing home admission of the patients. The purpose of the present study was to assess the association of neuropsychiatric symptoms and ADL functions in PD. A total of 73 community-dwelling PD patients were studied. The mean age of the patient group was 65 years and the mean disease duration was 9 years. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and ADL abilities were measured by the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The prevalence of neuropsychiatric symptoms in patients with PD was 73%. The most common symptoms were depression, anxiety, irritability, apathy and agitation. ADL ability correlated significantly with apathy (p < 0.002) even when adjusted for motor symptoms. Apathy was significantly associated with ADL in PD. The result indicates that more attention should be paid to identifying apathy and targeting therapeutic interventions.


Tumor-associated macrophage promotes tumor progression via STAT3 signaling in hepatocellular carcinoma.
Signal transducer and activator of transcription 3 (STAT3) is activated in hepatocellular carcinoma (HCC), and tumor-associated macrophage plays an important role in tumor progression. Therefore, we examined STAT3 activation, cytokine expression and infiltration of tumor-associated macrophages in resected HCCs as well as the alteration of cell growth and migration by cytokine stimulation in HCC cell lines. Immunohistochemical staining of phosphorylated STAT3 (pSTAT3), CD163, interleukin (IL)-6, Ki-67 and Bcl-XL was performed for 101 cases of resected HCC, and correlations between pSTAT3 staining and clinicopathological findings were analyzed. In HCC cell lines (PLC/PRF/5 and Huh7), cell proliferation and migration by IL-6 stimulation and S3I-201 (STAT3 inhibitor) treatment were analyzed. In HCC specimens, the pSTAT3-positive group showed high levels of α-fetoprotein (p = 0.0276), large tumor size (p = 0.0092), frequent intrahepatic metastasis (p = 0.0214), high Ki-67 (p = 0.0002) and Bcl-XL (p = 0.0001), poor prognosis (p = 0.0234), and high recurrence rate (p = 0.0003). CD163-positive cells were frequently observed in the pSTAT3-positive group (p = 0.0013). In two HCC cell lines, IL-6 stimulation promoted cell proliferation and migration via the STAT3 phosphorylation, and S3I-201 inhibited this activation. STAT3 activation was correlated with aggressive behavior of HCC and may be mediated via tumor-associated macrophage. We expect that STAT3 signaling and tumor-associated macrophages can be attractive therapeutic targets in HCC patients.


Nanotechnologies in glycoproteomics.
Protein glycosylation, as an important post-translational modification, is implicated in a number of ailments. Applying proteomic approaches, including mass spectrometry (MS) analyses that have played a significant role in biomarker detection and early diagnosis of diseases, to the study of glycoproteins or glycopeptides will facilitate a deeper understanding of many physiological functions and biological pathways involved in cancer, inflammatory and degenerative diseases. The abundance of glycopeptides and their ionization potential are relatively lower compared to those of non-glycopeptides; therefore, sample enrichment is necessary for glycopeptides prior to MS analysis. The application of nanotechnology in the past decade has been rapidly penetrating into many diverse scientific research disciplines. Particularly in what we now refer to as the "glycoproteomics area", nanotechnologies have enabled enhanced sensitivity and specificity of glycopeptide detection in complex biological fluids, which are critical for disease diagnosis and monitoring. In this review, we highlight some recent studies that combine the capabilities of specific nanotechnologies with the comprehensive features of glycoproteomics. In particular, we focus on the ways in which nanotechnology has facilitated the detection of glycopeptides in complex biological samples and enhanced their characterization by MS, in terms of intensity and resolution. These studies reveal an increasingly important role for nanotechnology in helping to overcome certain technical challenges in biomarker discovery, in general, and glycoproteomics research, in particular.


The use of the wavelet transform to describe embolic signals.
A number of methods to detect cerebral emboli and differentiate them from artefacts using Doppler ultrasound have been described in the literature. In most, Fourier transform-based (FT) spectral analysis has been used. The FT is not ideally suited to analysis of short-duration embolic signals due to an inherent trade-off between temporal and frequency resolution. An alternative approach that might be expected to describe embolic signals well is the wavelet transform. Wavelets are ideally suited for the analysis of sudden short-duration signal changes. Therefore, we have implemented a wavelet-based analysis and compared the results of this with a conventional FFT-based analysis. The temporal resolution, as measured by the half-width maximum, was significantly better for the continuous wavelet transform (CWT), mean (SD) 8.40 (8.82) ms, compared with the 128-point FFT, 12.92 (9.70) ms, and 64-point FFT, 10.80 (5.69) ms. Time localization of the CWT for the embolic signal was also significantly better than the FFT. The wavelet transform appears well suited to the analysis of embolic signals offering superior time resolution and time localization to the FFT.


Repeated peritoneal dialysis-associated peritonitis: a multicenter registry study.
Determinants and outcomes of peritoneal dialysis (PD)-associated peritonitis occurring within 4 weeks of completion of therapy of a prior episode caused by the same (relapse) or different organism (recurrence) recently have been characterized. However, determinants and outcomes of peritonitis occurring more than 4 weeks after treatment of a prior episode caused by the same (repeated) or different organism (nonrepeated) are poorly understood. Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. All Australian PD patients between October 1, 2003, and December 31, 2007, with first episodes of repeated or nonrepeated peritonitis. Repeated versus nonrepeated peritonitis, according to International Society of PD (ISPD) criteria. Relapse, hospitalization, catheter removal, hemodialysis transfer, and death. After a peritonitis episode, the probability that a subsequent episode represented repeated rather than nonrepeated peritonitis was highest in the second month (41%), then progressively decreased to a stable level of 14% from 6 months onward. When first episodes of repeated (n = 245) or nonrepeated peritonitis (n = 824) were analyzed, repeated peritonitis was predicted independently by a shorter elapsed time from the prior episode (adjusted OR per day elapsed, 0.91; 95% CI, 0.88-0.94). Staphylococcus aureus and coagulase-negative staphylococcus were isolated more frequently in repeated peritonitis, whereas Gram-negative, streptococcal, and fungal organisms were recovered more frequently in nonrepeated peritonitis. Using multivariate logistic regression, repeated peritonitis was associated independently with higher relapse (OR, 5.41; 95% CI, 3.72-7.89) and lower hospitalization rates (OR, 0.63; 95% CI, 0.46-0.85), but catheter removal, hemodialysis transfer, and death rates similar to nonrepeated peritonitis. Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Repeated and nonrepeated peritonitis episodes are caused by different spectra of micro-organisms and have different outcomes. Study findings suggest that the ISPD definition for repeated peritonitis should be limited to 6 months.


Custom-built moments for edge location.
We present a general construction of functions whose moments serve to locate and parametrize step edges within an image. Previous use of moments to locate edges was limited to functions supported on a circular region, but our method allows the use of "custom-designed" functions supported on circles, rectangles, or any desired shape, and with graphs whose shape may be chosen with great freedom. We present analyses of the sensitivity of our method to pixelization errors or discrepancy between the image and an idealized edge model. The parametric edge description yielded by our method makes it especially suitable as a component of wedgelet image coding.


Effects of salvianolic acids on endothelial cells against damage induced by cholestane-3beta-5alpha-6beta-triol.
To investigate the effects of salvianolic acids on human umbilical vein endothelial cells (HUVEC) against damage induced by cholestane-3beta-5alpha-6beta-triol (chol-triol). The viability of HUVEC was measured by MTT method. The apoptosis of HUVEC induced by chol-triol was detected by flow cytometry and TUNEL assay. The production of malondialdehyd (MDA) in HUVEC was tested by thiobarbaturic acid (TBA) assay. The viability of HUVEC treated with chol-triol 100 micro mol/L decreased by 39.8% while salvianolic acids 100 micro g/ml increased by 27.9%. The apoptotic rate of HUVEC measured by PI staining increased from 6% - 8% to 17% - 20% after chol-triol treatment for 12 h. Salvianolic acids 100 micro g/ml reduced the apoptotic rate to 10% - 14% after treatment HUVEC for 1 h prior to chol-triol treatment. In another experiment, chol-triol increased the number of TUNEL-positive cells 5 times, but salvianolic acids 10 micro g/ml and 100 micro g/ml reduced the number of TUNEL-positive cells by 36.9% and 61.2%, respectively. The production of MDA in HUVEC increased by 120.7% after chol-triol treatment for 12 h. Salvianolic acids 10 micro g/ml and 100 micro g/ml also decreased the concentration of MDA by 28.7% and 39.8%, respectively. Salvianolic acids has protective effect on endothelial cells against damage induced by chol-triol.


[Descriptive study of 21,804 ENT emergencies in a third level hospital].
We present a descriptive study about 21.804 emergency patients (ENT Department) treated in our hospital between 1994 and 2000. We have seen about 260 patients every month being the otologic pathology (35.63%) the most frequent one, followed by the nasosinusal (26.65%). Individually, the epistaxis where the 13% of all cases attended. The nasal traumas (contusions and fractures) where about a 10% of the total and in a third place, the external otitis (6.84%). We estimate in more than a 60% of the patients with a simple pathology (not urgent) and in a 3% of the patients without ENT pathology when they came to emergency. We believe, like other consulted authors, that there is a high patients index coming to the Hospital, for other reasons, without a justifiable ENT emergency. That contributes to different levels, with other specialities, to the collapse of the emergencies services.


The safety of long-acting beta-agonists: more evidence is needed.
There is controversy regarding the possibility that long-acting beta-agonists (LABA) may paradoxically contribute adversely to asthma mortality. While studies and meta-analyses indicate increased risk, epidemiological data indicate a slow fall in asthma mortality since the introduction of LABA. Advocates for LABA propose that mandatory simultaneous use of inhaled corticosteroids satisfactorily reduce any potential risk. In the face of lingering doubts, others propose that LABA should be withdrawn from use. In this pro-con article, Kazani et al. provide the rationale for a modified randomized controlled trial that would define the level of risk more clearly, and provide the basis for a clear judgment to be made. Sears argues that current knowledge about the risks associated with LABA, especially when prescribed as monotherapy, provides sufficient evidence for clinicians and licensing authorities alike, and that the logistics and likely outcomes for a large prospective study are unjustified.


The Frontal Behavioral Inventory in the differential diagnosis of frontotemporal dementia.
A personality and behavioral disorder is an important and defining feature of frontal lobe dementia (FLD) or frontotemporal degeneration (FTD). The diagnosis usually depends on the progressive development of various behavioral symptoms rather than a set of neuropsychological measures. Quantification of the personality-behavior disorder is important for standardizing the diagnosis. An inventory was constructed to capture the major positive and negative behaviors and personality change, and it was administered prospectively to caregivers of 108 patients in a cognitive neurology clinic, at the time of first diagnostic assessment. The prevalence and extent of behavioral abnormality was quantitated in the clinic population of FLD, vascular dementia (VaD), Alzheimer's disease (AD), primary progressive aphasia (PPA), and depressive disorder (DD) patients. The mean scores of FLD patients were significantly above all other groups. Scores in VaD were also higher than in AD, PPA, and DD. Interrater reliability (Cohen's kappa of .90) and item consistency (a Cronbach alpha of .89) were both high. Perseveration, indifference, inattention, inappropriateness, and loss of insight rated highest in FLD, significantly different from all other groups. Apathy, aspontaneity, inflexibility, disorganization, impulsivity, personal neglect, and poor judgment were also significantly higher in FLD. Discriminant function correctly classified 92.7% versus all other patients (NON-FLD) in the study. A total of 18.8% of VaD patients were misclassified as FLD. Indifference, alien hand, and inappropriateness were the highest discriminant functions. Perseveration and verbal apraxia were important discriminatory items for FLD and PPA, respectively. The FBI is a standardized behavioral inventory useful to diagnose FLD, to differentiate it from other dementias, and to quantify the behavior disorder.


Rates and risks for prolonged grief disorder in a sample of orphaned and widowed genocide survivors.
The concept of Prolonged Grief Disorder (PGD) has been defined in recent years by Prigerson and co-workers, who have developed and empirically tested consensus and diagnostic criteria for PGD. Using these most recent criteria defining PGD, the aim of this study was to determine rates of and risks for PGD in survivors of the 1994 Rwandan genocide who had lost a parent and/or the husband before, during or after the 1994 events. The PG-13 was administered to 206 orphans or half orphans and to 194 widows. A regression analysis was carried out to examine risk factors of PGD. 8.0% (n = 32) of the sample met criteria for PGD with an average of 12 years post-loss. All but one person had faced multiple losses and the majority indicated that their grief-related loss was due to violent death (70%). Grief was predicted mainly by time since the loss, by the violent nature of the loss, the severity of symptoms of posttraumatic stress disorder (PTSD) and the importance given to religious/spiritual beliefs. By contrast, gender, age at the time of bereavement, bereavement status (widow versus orphan), the number of different types of losses reported and participation in the funeral ceremony did not impact the severity of prolonged grief reactions. A significant portion of the interviewed sample continues to experience grief over interpersonal losses and unresolved grief may endure over time if not addressed by clinical intervention. Severity of grief reactions may be associated with a set of distinct risk factors. Subjects who lose someone through violent death seem to be at special risk as they have to deal with the loss experience as such and the traumatic aspects of the loss. Symptoms of PTSD may hinder the completion of the mourning process. Religious beliefs may facilitate the mourning process and help to find meaning in the loss. These aspects need to be considered in the treatment of PGD.


Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas.
More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891).


Categorization and recommendations for outcome measures for lower limb absence by an expert panel.
Understanding the psychometric strengths and limitations of outcome measures for use with people with lower limb absence (LLA) is important for selecting measures suited to evaluating patient outcomes, answering clinical and research questions, and informing health care policy. The aim of this project was to review the current psychometric evidence on outcome measures in people with LLA to determine which measures should be included in a stakeholder consensus process. An expert panel was assembled, and a 3-stage review process was used to categorize outcome measures identified in a systematic literature review into 3 distinct categories (recommended for measures with better than adequate psychometric properties; recommended with qualification; and unable to recommend). Panelists were asked to individually categorize measures based on results of a systematic review of identified measures' psychometric properties. Each measure's final categorization was based on ≥70% agreement by all panelists. No outcome measure attained the ≥70% consensus threshold needed to achieve a rating of "recommend." Hence, panelists suggested combining "recommend" and "recommend with qualifications" into a single category of "recommend with qualifications." Using this approach, consensus was reached for 59 of 60 measures. Consensus could not be reached on 1 outcome measure (socket comfort score). Thirty-six outcome measures were categorized as "unable to recommend" based on available evidence; however, 23 (12 patient-reported measures and 11 performance-based measures) demonstrated adequate psychometric properties in LLA samples and were thus rated as "recommend with qualification" by the expert panel. The panel of experts were able to recommend 23 measures for inclusion in the subsequent stakeholder review. A key strength of this process was bringing together international researchers with extensive experience in developing and/or using LLA outcome measures who could assist in identifying psychometrically sound measures to include in a subsequent stakeholder consensus process. The above categorizations represent the current state of psychometric evidence on outcome measures for people with LLA and hence may change over time as additional research becomes available. The results will be used to achieve wider consensus from clinicians, health policymakers, health clinic managers, researchers, and end users (i.e., individuals with LLA) on outcome measures for the International Society of Prosthetics and Orthotics lower limb Consensus Outcome Measures for Prosthetic and Amputation ServiceS.


Successful closure of transcatheter aortic valve replacement-induced Gerbode defect with valve-in-valve technique: A case report.
We present the first documented case of a successful closure of a transcatheter aortic valve replacement (TAVR)-induced Gerbode defect using a valve-in-valve approach. A 90-year-old female with severe aortic stenosis underwent TAVR. Following post-dilatation, the patient experienced hemodynamic deterioration and collapse due to tamponade and sub-annular rupture leading to hemodynamic deterioration and the development of a Gerbode defect with communication between the left ventricle and right atrium. Hemodynamic stabilization was achieved through pericardiocentesis, followed by the low implantation of a second valve, effectively sealing the rupture. This case showcases a valuable alternative for managing rare challenging complications during TAVR procedures.


Early steroid withdrawal in solitary pancreas transplantation results in equivalent graft and patient survival compared with maintenance steroid therapy.
Although steroid withdrawal in simultaneous kidney pancreas transplantation has been shown to be feasible, the results of early steroid withdrawal in immunologically solitary pancreas transplantation are not well known. This study evaluated an early steroid withdrawal protocol in this group. The results of steroid withdrawal at 21 d post-transplant in solitary pancreas transplant recipients was compared with a control group consisting of solitary pancreas transplant recipients maintained on steroids (MG). Additional immunosuppression consisted of rabbit anti-thymocyte globulin induction followed by tacrolimus and mycophenolate mofetil in both groups. The withdrawal group (WG, n = 22) consisted of 11 pancreas transplant alone (PTA), six pancreas after kidney (PAK), and five simultaneous cadaveric pancreas living kidney (SPLK) recipients. The steroid maintenance group (MG, n = 32) consisted of 8 PTA, 11 PAK, and 13 SPLK recipients. Recipient and donor demographic characteristics were similar. Seventy eight percent of MG patients had infection-related complications in the first year compared with 50% of the WG patients (p = 0.04). The one-yr rejection, pancreas graft, and patient survival rates were 27.3% 95.5%, and 100% in the WG, and 37.5%, 81.3%, and 93.8% in the MG respectively and not significantly different. We conclude that early corticosteroid withdrawal in isolated pancreas transplantation results in fewer infections and can be achieved without an increased risk of rejection or graft loss over the first year.


[The Mycoplasma genome].
A review is presented of the available data on the nature of chromosomal and extrachromosomal DNA of Mollicutes (mycoplasmas)--the smallest and simplest procaryotic organisms.


Identification of a novel synthetic lethality of combined inhibition of hedgehog and PI3K signaling in rhabdomyosarcoma.
We previously reported that aberrant HH pathway activation confers a poor prognosis in rhabdomyosarcoma (RMS). Searching for new treatment strategies we therefore targeted HH signaling. Here, we identify a novel synthetic lethality of concomitant inhibition of HH and PI3K/AKT/mTOR pathways in RMS by GLI1/2 inhibitor GANT61 and PI3K/mTOR inhibitor PI103. Synergistic drug interaction is confirmed by calculation of combination index (CI < 0.2). Similarly, genetic silencing of GLI1/2 significantly increases PI103-induced apoptosis. GANT61 and PI103 also synergize to induce apoptosis in cultured primary RMS cells emphasizing the clinical relevance of this combination. Importantly, GANT61/PI103 cotreatment suppresses clonogenic survival, three-dimensional sphere formation and tumor growth in an in vivo model of RMS. Mechanistic studies reveal that GANT61 and PI103 cooperate to trigger caspase-dependent apoptosis via the mitochondrial pathway, as demonstrated by several lines of evidence. First, GANT61/PI103 cotreatment increases mRNA and protein expression of NOXA and BMF, which is required for apoptosis, since knockdown of NOXA or BMF significantly reduces GANT61/PI103-induced apoptosis. Second, GANT61/PI103 cotreatment triggers BAK/BAX activation, which contributes to GANT61/PI103-mediated apoptosis, since knockdown of BAK provides protection. Third, ectopic expression of BCL-2 or non-degradable phospho-mutant MCL-1 significantly rescue GANT61/PI103-triggered apoptosis. Fourth, GANT61/PI103 cotreatment initiate activation of the caspase cascade via apoptosome-mediated cleavage of the initiator caspase-9, as indicated by changes in the cleavage pattern of caspases (e.g. accumulation of the caspase-9 p35 cleavage fragment) upon addition of the caspase inhibitor zVAD.fmk. Thus, combined GLI1/2 and PI3K/mTOR inhibition represents a promising novel approach for synergistic apoptosis induction and tumor growth reduction with implications for new treatment strategies in RMS.


A Comparison of Platelet Count and Enrichment Percentages in the Platelet Rich Plasma (PRP) Obtained Following Preparation by Three Different Methods.
Platelet rich plasma (PRP) represents an easily accessible and rich source of autologous growth factors. Different manual methods for the preparation of PRP have been suggested. Lacuna in knowledge exists about the efficacy of PRP preparation by these different manual methods. This study was performed to determine the effects of centrifugation rate revolutions per minute (RPM) and time on the platelet count and enrichment percentages in the concentrates obtained following the three different manual methods of PRP preparation. In vitro experimental study. This was an experimental study in which platelet concentration was assessed in the PRP prepared by three different protocols as suggested by Marx R (method 1), Okuda K (method 2) and Landesberg R (method 3). A total of 60 peripheral blood samples, (n=20 per method) were obtained from healthy volunteers. Baseline platelet count was assessed for all the subjects following which PRP was prepared. The platelet count in the PRP was determined using coulter counter (Sysmex XT 2000i). The mean of the platelet count obtained and their enrichment percentage were calculated and intergroup comparison was done (Tukey's HSD test). The number of platelets and enrichment percentage in PRP prepared by method 1 was higher compared to method 2 and method 3; this difference in platelet concentrates was found to be statistically significant (p < 0.05). The centrifugation rate and time appear to be important parameters, which influence the platelet yield. Method 1 which had lower centrifugation rate and time yielded a greater platelet count and enrichment percentage.


Atypical and delayed de Winter electrocardiograph pattern: A case report.
de Winter electrocardiograph (ECG) pattern signifies proximal left anterior descending coronary artery (LAD) occlusion and extensive anterior myocardial infarction, and it is found in about 2% of patients with proximal LAD occlusion. However, it is often unrecognized by physicians. In this case report, we present a patient with chest pain but showing an atypical and delayed de Winter ECG pattern. A previously healthy 61-year-old man attended our emergency department with chest pain radiating to the left arm and back for 4 hours, who was without serious cardiovascular risk factors. ECG at emergency department showed no significant changes. High-sensitivity cardiac troponin I (hs-cTnI) was within normal limit. At 5 hours after onset, ECG showed significant upsloping ST depression at J point in precordial leads V3 to V6, slight ST elevation in aVR and depression in inferior leads, and hs-cTnI peaked at 2.610 μg/L. The diagnosis of de Winter ECG pattern was confirmed by coronary angiography with an occlusion of the proximal LAD. A stent was implanted through percutaneous coronary intervention. The patient's chest pain was relieved without further increase of hs-cTnI. ECG after procedure showed ST segment back to baseline in leads V4 to V6, but persistent ST elevation in V1 to V3 with QS or Q wave. Timely diagnosis of de Winter ECG pattern is very important, especially the atypical and delayed ECG changes. It should be treated as ST elevation myocardial infarction equivalent and deserves emergent revascularization therapy.


[57Co-bleomycetin distribution in the body of experimental animals with hyperglycemia].
Distribution of 57Co-bleomycetin in organs and tissues of rats with experimental short-term hyperglycemia was studied. Hyperglycemia was induced by intraperitoneal administration of 40 per cent glucose solution in doses of 1 to 10.4 g/kg. The labeled antitumor antibiotic was also administered intraperitoneally (0.2-0.8 MBq per animal). The data on both the external radiometry in the area under the animal limb and the radiometry of separate organs and tissues showed that hyperglycemia markedly altered pharmacokinetics of the labeled antibiotic and retarded its elimination. With respect to the lungs it even increased the drug tropism and accumulation. This information may be useful in radionuclide diagnosis and therapy in particular of lung cancer. The time course of glucose concentration in blood was not an adequate criterion of hyperglycemia influence since the influence of hyperglycemia on retarding the drug elimination was also observed when the level of glucose in blood did not differ from the initial one.


Ultrasound pregnancy dating leads to biased perinatal morbidity and neonatal mortality among post-term-born girls.
Ultrasound assessment of gestational length is based on the assumption that fetuses of the same gestational age have equal size at the time of investigation. However, there are detectable sex differences in fetal size by the end of the first trimester. We examined whether ultrasound dating introduces sex differences in risks of adverse perinatal outcomes related to post-term birth. We used the Swedish Medical Birth Register to compare male and female newborns during 1973-1978, when gestational age was based on the last menstrual period, and 1995-2007, when gestational age was based on ultrasound. We included singleton births from 39 to 43 gestational weeks. During the first time period, the newborn male-to-female ratio by gestational age at delivery was constant around 1.0, but in the later time period it consistently increased by gestational age, reaching 1.60 at 43 weeks. In the first time period, post-term females had reduced risk for adverse perinatal outcomes compared with post-term males. After the introduction of ultrasound, post-term females had higher risks of stillbirth (odds ratio = 1.60 [95% confidence interval = 1.11 to 2.30]) and meconium aspiration (1.39 [1.10 to 1.75]), compared with post-term males. One-third of stillbirths among post-term girls today might be due to incorrect calculation of gestational age. Introduction of ultrasound for the estimation of gestational age may be associated with increased risks of adverse perinatal outcomes among females classified as post-term compared with their male counterparts.


Direct Fabrication of Functional Ultrathin Single-Crystal Nanowires from Quasi-One-Dimensional van der Waals Crystals.
Micromechanical exfoliation of two-dimensional (2D) van der Waals materials has triggered an explosive interest in 2D material research. The extension of this idea to 1D van der Waals materials, possibly opening a new arena for 1D material research, has not yet been realized. In this paper, we demonstrate that 1D nanowire with sizes as small as six molecular ribbons, can be readily achieved in the Ta2(Pd or Pt)3Se8 system by simple micromechanical exfoliation. Exfoliated Ta2Pd3Se8 nanowires are n-type semiconductors, whereas isostructural Ta2Pt3Se8 nanowires are p-type semiconductors. Both types of nanowires show excellent electrical switching performance as the channel material for a field-effect transistor. Low-temperature transport measurement reveals a defect level inherent to Ta2Pd3Se8 nanowires, which enables the observed electrical switching behavior at high temperature (above 140 K). A functional logic gate consisting of both n-type Ta2Pd3Se8 and p-type Ta2Pt3Se8 field-effect transistors has also been successfully achieved. By taking advantage of the high crystal quality derived from the parent van der Waals bulk compound, our findings about the exfoliated Ta2(Pd or Pt)3Se8 nanowires demonstrate a new pathway to access single-crystal 1D nanostructures for the study of their fundamental properties and the exploration of their applications in electronics, optoelectronics, and energy harvesting.


Concurrent comparison of endoluminal versus open repair in the treatment of abdominal aortic aneurysms: analysis of 303 patients by life table method.
The aim of this study was to compare the outcome of consecutive patients with abdominal aortic aneurysm (AAA) treated concurrently by open operation and endoluminal intervention by the same surgeons during a defined interval. Between May 1992 and May 1996, 362 consecutive patients with AAA underwent repair. Fifty-three patients who underwent open operations for ruptured AAA plus two patients who underwent endoluminal repair of false AAA and four patients who underwent secondary endoluminal repair of AAA were excluded, leaving 303 patients who underwent elective repair of true AAA in the study. The elective operations were conventional open repair (OR) in 195 patients (151 men, 44 women; mean age, 69 years) and endoluminal repair (ER) in 108 patients (100 men, 8 women; mean age, 70 years). The decision to perform ERwas based on comorbidities that precluded open repair (n = 48) and patient choice (n = 60). Graft configuration in the open repair group was tubular (n = 180) and bifurcated (n = 15), and in the ER group tubular (n = 48), aortoiliac/femoral (n = 25), and bifurcated (n = 35). All procedures were performed in the operating department, and radiographic guidance was used in the ER group. Follow-up was by interview, examination, and telephone. In addition, contrast-enhanced computed tomography was performed within the first 10 days after operation, 6 months and 12 months after operation, and then annually thereafter in the ER group. Outcome measures were successful exclusion of the aneurysm sac from the general circulation and survival. Data were analyzed by the life table method. Other outcome measures were length of hospital stay, length of intensive care unit stay, and operative blood loss. No significant difference was found between the perioperative mortality rate for OR (11 deaths [5.6%] in 195 patients) and ER (six deaths [5.6%] in 108 patients). Three of the six deaths in the latter group occurred in patients with successful ER, and three occurred in 18 patients with failed ER who were converted to OR. Similarly, no significant difference was seen in the survival rate between the endoluminal and open repair groups when analyzed by the log-rank test (p = 0.14). The rate of graft failure, however, was significantly higher in the ER group than in the OR group (Fisher's exact test, p < 0.001). Success in the ER group was defined as continuing graft function without endoleak or conversion to open repair. Kaplan-Meier curve for graft failure times for the endoluminal group revealed a 3-year graft success probability of 70%. This study suggests that ER is safe, sharing the same perioperative mortality risk as OR despite 44% of the ER group being rejected as unfit for OR. Conventional open repair is the most reliable method of successfully managing AAA. The endoluminal method, however, results in shorter length of hospital stay, shorter length of intensive care unit stay, and less blood loss than the open method. Patients who opt for the endoluminal method of repair should be made aware that the minimally invasive technique carries the disadvantage of a higher failure rate.


Cortical field potentials preceding visually initiated hand movements and cerebellar actions in the monkey.
Cortical field potentials preceding hand movements initiated by a visual stimulus were recorded with chronically implanted electrodes in premotor, motor and somatosensory cortices of monkeys, and the influences of cerebellar hemispherectomy on cortical potentials as well as reaction time of movements were examined. As reported previously, early surface-positive, depth-negative (2.5-3 mm depth from the cortical surface) premovement potentials emerged at about 40 ms latency after onset of the light stimulus bilaterally in premotor and forelimb motor areas. Early potentials in the forelimb motor area contralateral to the moving hand were followed at about 120 ms latency by surface-negative, depth-positive late premovement potentials which are considered to be mainly composed of superficial thalamo-cortical (T-C) responses. Unilateral hemispherectomy of the cerebellum contralateral to the motor area immediately eliminated the surface-negative, depth-positive potentials. Reaction time from onset of the light stimulus to the hand movement was prolonged by 90-250 ms after cerebellar hemispherectomy. If the dentate and interpositus nuclei were also lesioned, disappearance of the late potentials and delay of the movement continued for many months. However, if the interpositus was spared, there was earlier recovery of reaction time with simultaneous reappearance of the late premovement potentials in the motor cortex. The conclusion is drawn that the cerebellar hemisphere (neocerebellum) activates the motor cortex via superficial T-C projections and participates directly in the initiation of reaction movements in response to an external stimulus.


Cognitive deficits in familial Alzheimer's disease associated with M239V mutation of presenilin 2.
The neuropsychological assessment of non-demented subjects with gene mutation of familial Alzheimer's disease (AD) provides a model for exploring the early cognitive features of the disease. We evaluated 1 patient and 6 non-demented subjects belonging to a family with AD with M239V mutation of the presenilin 2 gene, aiming to verify the contribution of specific cognitive patterns to the characterization of familial AD. One patient, 3 non-demented subjects with M239V mutation and 3 subjects without mutation from the same family underwent neuropsychological testing. The patient's cognitive profile was characterized by anosognosia, visuospatial agnosia, apraxia and fluent aphasia. Of the 3 non-demented subjects with mutation, 1 showed no deficits, another constructive apraxia and the third spatial perception and memory deficits. The 3 subjects without mutation showed normal abilities. The cognitive deficits of the non-demented subjects with mutations indicate focal dysfunction of the posterior cortical areas, resembling the more extended parieto-occipito-temporal dysfunction of the demented patient. Such grading of visuospatial, praxis, and language impairments highlights a distinctive pattern related to the M239V mutation of the presenilin 2 gene.


The Incidence of Blindness Due to Idiopathic Intracranial Hypertension in the UK.
To determine the incidence of blindness secondary to idiopathic intracranial hypertension (IIH) in the United Kingdom. New cases of blindness occurring secondary to IIH were identified prospectively through the British Ophthalmological Surveillance Unit (BOSU) from October 2005 to November 2006. Only idiopathic cases of intracranial hypertension and those meeting the World Health Organisation`s definition of blindness were included. Cases that were already blind or had already been blind registered before the study period were excluded. There were 24 new cases of registerable blindness secondary to IIH reported during the 12 month period. Questionnaires were completed for 19 cases. Of these 19 cases, 3 were not truly idiopathic and 3 cases did not fulfil the strict criteria for blindness. One case was a duplicate report. There were 12 definite cases of blindness secondary to IIH giving a UK incidence of blindness secondary to IIH of 0.6-2% (assuming a UK population of 63.2 million and an incidence of IIH of 1-3/100,000). If the 5 cases reported as blind but without a completed questionnaire are assumed to be true cases then the incidence of blindness would be 1-3%. The results of this study suggest that approximately 1-2% of new cases of IIH are likely to become blind in a given year. This contrasts with rates of between 4-10% reported previously in hospital-based studies, but may be a more accurate figure for the population as a whole. Under-ascertainment and improving standards of care may also have contributed to the lower figure than previously reported.


Myeloid lineage-specific deletion of antioxidant system enhances tumor metastasis.
Oxidative stress accelerates the pathogenesis of a number of chronic diseases including cancer growth and its metastasis. Transcription factor NF-E2-related factor-2 (Nrf2), which regulates the cellular defense system against oxidative stress, elicits essential protection against chemical-induced carcinogenic insults. We recently demonstrate that the systemic deletion of Nrf2 leads to an increased susceptibility to cancer metastasis, which is associated with aberrant reactive oxygen species (ROS) accumulation in myeloid-derived suppressor cells (MDSC). However, it remains elusive whether cellular antioxidant defense system in the myeloid lineage cells plays indispensable roles for metastatic cancer progression. We herein found that myeloid lineage-specific Nrf2-deficient mice exhibited an increased susceptibility to pulmonary metastasis of the mouse Lewis lung carcinoma cells, and ROS level was more highly elevated in MDSCs of cancer-bearing Nrf2-deficient mice. Similarly, myeloid lineage-specific deletion of selenocysteine-tRNA gene (Trsp), which is essential for synthesis of antioxidant selenoenzymes, resulted in increased number of metastatic nodules along with ROS accumulation in MDSCs of cancer-bearing mice. These results thus indicate that the antioxidant systems directed by Nrf2 and selenoenzymes contribute to the clearance of ROS in MDSCs, efficiently preventing cancer cell metastasis. Consistent with this notion, a synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im), a potent Nrf2 inducer, attenuated the ROS production in MDSCs, and thereafter reduced metastatic nodules. Taken together, this study provides compelling lines of evidence that Nrf2 inducer retains therapeutic efficacy against cancer cell metastasis.


Source and background threshold values of potentially toxic elements in soils by multivariate statistics and GIS-based mapping: a high density sampling survey in the Parauapebas basin, Brazilian Amazon.
A high-density regional-scale soil geochemical survey comprising 727 samples (one sample per each 5 × 5 km grid) was carried out in the Parauapebas sub-basin of the Brazilian Amazonia, under the Itacaiúnas Basin Geochemical Mapping and Background Project. Samples were taken from two depths at each site: surface soil, 0-20 cm and deep soil, 30-50 cm. The ground and sieved (< 75 µm) fraction was digested using aqua regia and analyzed for 51 elements by inductively coupled plasma mass spectrometry (ICPMS). All data were used here, but the principal focus was on the potential toxic elements (PTEs) and Fe and Mn to evaluate the spatial distribution patterns and to establish their geochemical background concentrations in soils. Geochemical maps as well as principal component analysis (PCA) show that the distribution patterns of the elements are very similar between surface and deep soils. The PCA, applied on clr-transformed data, identified four major associations: Fe-Ti-V-Sc-Cu-Cr-Ni (Gp-1); Zr-Hf-U-Nb-Th-Al-P-Mo-Ga (Gp-2); K-Na-Ca-Mg-Ba-Rb-Sr (Gp-3); and La-Ce-Co-Mn-Y-Zn-Cd (Gp-4). Moreover, the distribution patterns of elements varied significantly among the three major geological domains. The whole data indicate a strong imprint of local geological setting in the geochemical associations and point to a dominant geogenic origin for the analyzed elements. Copper and Fe in Gp-1 were enriched in the Carajás basin and are associated with metavolcanic rocks and banded-iron formations, respectively. However, the spatial distribution of Cu is also highly influenced by two hydrothermal mineralized copper belts. Ni-Cr in Gp-1 are highly correlated and spatially associated with mafic and ultramafic units. The Gp-2 is partially composed of high field strength elements (Zr, Hf, Nb, U, Th) that could be linked to occurrences of A-type Neoarchean granites. The Gp-3 elements are mobile elements which are commonly found in feldspars and other rock-forming minerals being liberated by chemical weathering. The background threshold values (BTV) were estimated separately for surface and deep soils using different methods. The '75th percentile', which commonly used for the estimation of the quality reference values (QRVs) following the Brazilian regulation, gave more restrictive or conservative (low) BTVs, while the 'MMAD' was more realistic to define high BTVs that can better represent the so-called mineralized/normal background. Compared with CONAMA Resolution (No. 420/2009), the conservative BTVs of most of the toxic elements were below the prevention limits (PV), except Cu, but when the high BTVs are considered, Cu, Co, Cr and Ni exceeded the PV limits. The degree of contamination (Cdeg), based on the conservative BTVs, indicates low contamination, except in the Carajás basin, which shows many anomalies and had high contamination mainly from Cu, Cr and Ni, but this is similar between surface and deep soils indicating that the observed high anomalies are strictly related to geogenic control. This is supported when the Cdeg is calculated using the high BTVs, which indicates low contamination. This suggests that the use of only conservative BTVs for the entire region might overestimate the significance of anthropogenic contamination; thus, we suggest the use of high BTVs for effective assessment of soil contamination in this region. The methodology and results of this study may help developing strategies for geochemical mapping in other Carajás soils or in other Amazonian soils with similar characteristics.


[Heterogenicity of hypertension: the various effects of electrolyte intake].
Nonpharmacologic approaches to patients with hypertension are a worthwhile avenue to treatment as well as a laudable public health goal. Reduced salt intake has been the primary dietary measure. However, recently attention has also been directed at potassium, calcium, magnesium, and the anions accompanying these cations. Further, the importance of total caloric intake and confounding dietary variables such as alcohol consumption have been appreciated. It is important to recognize that nutrients are not ingested in isolation, but rather as interactive constituents of a total diet. This principle may account for some of the heterogeneity of the human blood pressure response to variations of individual electrolyte intake. Moreover, failure to appreciate this heterogeneity and interactive effects may result in other than the desired effect in the population at risk.


Bevacizumab in age-related macular degeneration: a randomized controlled trial on the effect of injections every 4 weeks, 6 weeks and 8 weeks.
Several clinical trials have established the efficacy of ranibizumab therapy administered every 4 weeks to treat exudative age-related macular degeneration (ARMD). Bevacizumab appears to be a cost-effective alternative to ranibizumab, although an optimal injection schedule has not yet been determined. In this study, we set out to determine whether bevacizumab treatment in exudative ARMD every 6 or 8 weeks is non-inferior to bevacizumab treatment every 4 weeks. A total of 191 patients with exudative ARMD were randomly assigned to a 1-year continuous regimen of intravitreal bevacizumab every 4 (n = 64), 6 (n = 63) or 8 weeks (n = 64). The primary outcome was visual acuity change after 1 year of treatment. In all three treatment groups, visual acuity improved between baseline and 1 year. There was no statistically significant difference in the mean change of visual acuity score at 1 year for bevacizumab administered every 4 (1.96 ± 13.70), 6 (1.60 ± 10.98) or 8 weeks (5.98 ± 8.88). Reduction in central retinal thickness was observed in all three study groups. At 1 year, the mean decrease in central foveal thickness ranged from 86 ± 97 μm in the every 6 weeks group to 109 ± 90 μm in the group every 8 weeks group (p = 0.30). At 1 year, bevacizumab administered every 6 or 8 weeks was not inferior to therapy administered every 4 weeks.


DNA content of heterochromatin and euchromatin in tomato (Lycopersicon esculentum) pachytene chromosomes.
Lycopersicon esculentum (tomato) has a small genome (2C = 1.90 pg of DNA) packaged in 2n = 2x = 24 small acrocentric to metacentric chromosomes. Like the chromosomes of other members of the family Solanaceae, tomato chromosomes have pericentromeric heterochromatin. To determine the fraction of the tomato genome found in euchromatin versus heterochromatin, we stained pachytene chromosomes from primary microsporocytes with Feulgen and analyzed them by densitometry and image analysis. In association with previously published synaptonemal complex karyotype data for tomato, our results indicate that 77% of the tomato microsporocyte genome is located in heterochromatin and 23% is found in euchromatin. If heterochromatin is assumed to contain few active genes, then the functional genes of the tomato must be concentrated in an effective genome of only 0.22 pg of DNA (1C = 0.95 pg x 0.23 = 0.22 pg). The physical segregation of euchromatin and heterochromatin in tomato chromosomes coupled with the small effective genome size suggests that tomato may be a more useful subject for chromosome walking and gene mapping studies than would be predicted based on its genome size alone. Key words : tomato, Lycopersicon esculentum, genome size, heterochromatin, euchromatin, pachytene chromosomes, synaptonemal complex.


Lipid phase separation correlates with activation in platelets during chilling.
When human platelets are chilled below 22 degrees C, they spontaneously activate, a phenomenon that severely limits their storage life. It has previously been proposed that there is a correlation between cold-induced platelet activation and passage of the membranes through a liquid-crystalline to gel phase transition. Because animal models are essential for developing methods for cold storage of platelets, it is necessary to investigate such a correlation in animal platelets. In this work, horse platelets were used as a model, and it was found that cold-induced morphological activation is related to the lipid phase transition. Using fluorescence microscopy with the lipophilic fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil-C18), and Fourier transform infrared spectroscopy (FTIR), it was found that lipid phase separation occurs during cooling and low temperature storage. Furthermore, removal of cholesterol from the plasma membrane also induced a phase separation, possibly between specific phospholipid classes. Steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-DPH (TMA-DPH) were compared in cells and multilamellar vesicles (MLV) composed of platelet lipids. Cholesterol depletion led to a decrease in the fluorescence anisotropy of the two probes, which can be explained by changes in the order of the phospholipid molecules. In addition, the lipid composition and fatty acid profile of the cellular phospholipids were determined. Based of the similarities between horse and human platelets, it is suggested that horse platelets may be used as a model for studying cold-stored platelets. The results are discussed in relation to the possible role of phase separation during cell signalling.


Electrochemical Characterization of a Complex FeFe Hydrogenase, the Electron-Bifurcating Hnd From Desulfovibrio fructosovorans.
Hnd, an FeFe hydrogenase from Desulfovibrio fructosovorans, is a tetrameric enzyme that can perform flavin-based electron bifurcation. It couples the oxidation of H2 to both the exergonic reduction of NAD+ and the endergonic reduction of a ferredoxin. We previously showed that Hnd retains activity even when purified aerobically unlike other electron-bifurcating hydrogenases. In this study, we describe the purification of the enzyme under O2-free atmosphere and its biochemical and electrochemical characterization. Despite its complexity due to its multimeric composition, Hnd can catalytically and directly exchange electrons with an electrode. We characterized the catalytic and inhibition properties of this electron-bifurcating hydrogenase using protein film electrochemistry of Hnd by purifying Hnd aerobically or anaerobically, then comparing the electrochemical properties of the enzyme purified under the two conditions via protein film electrochemistry. Hydrogenases are usually inactivated under oxidizing conditions in the absence of dioxygen and can then be reactivated, to some extent, under reducing conditions. We demonstrate that the kinetics of this high potential inactivation/reactivation for Hnd show original properties: it depends on the enzyme purification conditions and varies with time, suggesting the coexistence and the interconversion of two forms of the enzyme. We also show that Hnd catalytic properties (Km for H2, diffusion and reaction at the active site of CO and O2) are comparable to those of standard hydrogenases (those which cannot catalyze electron bifurcation). These results suggest that the presence of the additional subunits, needed for electron bifurcation, changes neither the catalytic behavior at the active site, nor the gas diffusion kinetics but induces unusual rates of high potential inactivation/reactivation.


Alpha-1-antichymotrypsin and oxidative stress in the peripheral blood from patients with probable Alzheimer disease: a short-term longitudinal study.
To evaluate the stability and reproducibility of selected peripheral oxidative stress markers and their possible relation to cognitive performance, three different blood samples were taken at 7- to 10-day intervals from 11 patients with probable Alzheimer disease (AD) and 11 nondemented controls. Blood samples were also collected once from 6 patients with vascular dementia (VD). Alpha-1-antichymotrypsin (ACT), C-reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactoferrin (LTF), and total lipid peroxidation (LPO) were then measured. Blood levels of ACT and GSH-Px were increased in AD patients but not in patients with VD. Levels of LTF, CRP, and LPO were comparable between AD patients and controls. Erythrocyte SOD activity was increased in AD patients. Blood levels of ACT negatively correlated with LPO levels and positively correlated with scores of the Global Deterioration Scale of AD patients. ACT might be implicated in controlling oxidative damage of blood lipids and their turnover during the progression of AD.


Effects of different depths of gap on healing of surgically created coronal defects around implants in dogs: a pilot study.
This study investigated the bone growth pattern in surgically created coronal defects with various depths around implants in dogs. Four mongrel dogs were used. All mandibular premolars were extracted under general anesthesia and left to heal for 2 months. After ostectomy, bony defects were prepared in test sites, using a stepped drill with a diameter of 6.3 mm and two depths: 2.5 mm (test sites 1 [T1]) and 5.0 mm (test sites 2 [T2]). In the control sites, the implants were placed after ostectomy without any coronal defects. T1, T2, and control sites were prepared in the right and left sides of the mandible. Six implants, 3.3 mm in diameter and 10 mm in length, were placed in each dog; the implants were submerged completely. Two dogs were sacrificed 8 weeks after surgery, and the other two dogs were sacrificed 12 weeks after surgery. The stability of all implants was measured with a resonance frequency analyzer after placement and after sacrifice. All sites were block-dissected for ground sectioning and histologic examination. After 12 weeks of healing, only T2 were not filled fully with bone. At week 8, the mean bone-to-implant contact (BIC) was 47.7% for control, 43.6% for T1, and 22.2% for T2. At week 12, the control BIC was 56.7% and the 2.5-mm defect had a greater BIC (58.8%). However, in the 5-mm defect, the BIC was 35.1%. At insertion, stability was reduced at sites with a greater defect depth. Similar stability was noted in all specimens after 8 and 12 weeks of healing. Bone healing between an implant and marginal bone was compromised at sites with a deeper defect when the width of the bone defect was 1.5 mm.


Approach for energy saving and pollution reducing by fueling diesel engines with emulsified biosolution/ biodiesel/diesel blends.
The developments of both biodiesel and emulsified diesel are being driven by the need for reducing emissions from diesel engines and saving energy. Artificial chemical additives are also being used in diesel engines for increasing their combustion efficiencies. But the effects associated with the use of emulsified additive/biodiesel/diesel blends in diesel engines have never been assessed. In this research, the premium diesel fuel (PDF) was used as the reference fuel. A soy-biodiesel was selected as the test biodiesel. A biosolution made of 96.5 wt % natural organic enzyme-7F (NOE-7F) and 3.5 wt % water (NOE-7F water) was used as the fuel additive. By adding additional 1 vol % of surfactant into the fuel blend, a nanotechnology was used to form emulsified biosolution/soy-biodiesel/PDF blends for fueling the diesel engine. We found that the emulsified biosolution/soy-biodiesel/PDF blends did not separate after being kept motionless for 30 days. The above stability suggests that the above combinations are suitable for diesel engines as alternative fuels. Particularly, we found that the emulsified biosolution/soy-biodiesel/PDF blends did have the advantage in saving energy and reducing the emissions of both particulate matters (PM) and polycyclic aromatic hydrocarbons (PAHs) from diesel engines as compared with PDF, soy-biodiesel/PDF blends, and emulsified soy-biodiesel/ PDF blends. The results obtained from this study will provide useful approaches for reducing the petroleum reliance, pollution, and global warming. However, it should be noted that NO(x) emissions were not measured in the present study which warrants the need for future investigation.


A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group.
The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia (AML) induction and consolidation therapy was assessed in this prospective double-blind, randomized, placebo-controlled, multicenter trial. A total of 521 consecutive de novo AML patients aged 16 or more years were randomized to receive filgrastim (5 microg/kg/d subcutaneously) or placebo after standard induction as well as consolidation chemotherapy. Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was >/=1.0 x 10(9)/L for 3 consecutive days. The overall complete remission rate was 68%. After a median follow-up of 24 months (range 5 to 40) the median disease-free survival was 10 months (95% confidence interval [CI], 8.7 to 10.8) and the median overall survival was 13 months (95%CI, 12.2 to 14.6). These did not differ between treatment groups. Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo (P < .0001). This was accompanied by reductions in the duration of fever (7 v 8.5 days; P = .009), parenteral antibiotic use (15 v 18.5 days; P = .0001), and hospitalization (20 v 25 days; P = .0001). Similar reductions were seen after induction 2 and the consolidation courses. There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment (34% v 43%; P = .04). In conclusion, filgrastim is safe in that it had no negative impact on the prognosis of the AML patients. In addition, it effectively reduced the duration of neutropenia, leading to significant clinical benefits by reducing the duration of fever; requirement for parenteral anti-infectives, specifically amphotericin B; and the duration of hospitalization.


Autoinhibition of casein kinase I epsilon (CKI epsilon) is relieved by protein phosphatases and limited proteolysis.
Casein kinase I epsilon (CKI epsilon) is a member of the CKI gene family, members of which are involved in the control of SV40 DNA replication, DNA repair, and cell metabolism. The mechanisms that regulate CKI epsilon activity and substrate specificity are not well understood. We report that CKI epsilon, which contains a highly phosphorylated 123-amino acid carboxyl-terminal extension not present in CKI alpha, is substantially less active than CKI alpha in phosphorylating a number of substrates including SV40 large T antigen and is unable to inhibit the initiation of SV40 DNA replication. Two mechanisms for the activation of CKI epsilon have been identified. First, limited tryptic digestion of CKI epsilon produces a protease-resistant amino-terminal 39-kDa core kinase with several-fold enhanced activity. Second, phosphatase treatment of CKI epsilon activates CKI epsilon 5-20-fold toward T antigen. Similar treatment of a truncated form of CKI epsilon produced only a 2-fold activation. Notably, this activation was transient; reautophosphorylation led to a rapid down-regulation of the kinase within 5 min. Phosphatase treatment also activated CKI epsilon toward the novel substrates I kappa B alpha and Ets-1. These mechanisms may serve to regulate CKI epsilon and related forms of CKI in the cell, perhaps in response to DNA damage.


Decrease of prothrombin level during thrombolysis in acute myocardium infarction.
Previously, the direct interactions of Bβ26-42 fibrin residues with prothrombin were demonstrated. It was also shown that forming prothrombin complexes with E- or DDE-fragments causes non-enzymatic prothrombin activation. The direct measuring of the prothrombin level in the blood plasma of patients with acute myocardial infarction (AMI) allowed us to find a situation where such an activation can occur in vivo. Blood coagulation parameters in the blood plasma of patients with AMI were measured at 2 hours, three days, and seven days after the thrombolysis by streptokinase accompanied with intravenous administration of anticoagulants: unfractionated high molecular weight heparin (HMWH) and low-molecular-weight heparin (LMWH). The prothrombin level in the blood plasma of patients with AMI was normal before thrombolytic therapy and substantially decreased after streptokinase administration. This effect was prominent in the case of concomitant anticoagulant therapy with LMWH and was not observed when HMWH was applied. It can be explained by the fact that LMWH preferentially inhibits factor Xa, while the HMWH is an effective inhibitor of both factor Xa and thrombin. This observation suggested that the prothrombin level decrease was caused by the thrombin-like activity and possible autolysis of prothrombin by thrombin. Also, thrombolytic therapy with streptokinase caused the accumulation of fibrin degradation products (FDPs), some of which were able to bind prothrombin. The dramatic decrease of prothrombin level in the blood plasma of patients with AMI during thrombolysis allowed us to conclude the non-enzymatic prothrombin activation with the following autolysis of prothrombin that contributes to the pathology.


Dynamic Semicrystalline Networks of Polypropylene with Thiol-Anhydride Exchangeable Crosslinks.
Thermoplastic polyolefins (TPOs) crosslinked by dynamic covalent bonds (xTPOs) have the potential to be the most utilized class of polymer in the world, with applications ranging from household and automotive to biomedical devices and additive manufacturing. xTPO combines the benefits of thermoplastics and thermosets in a "single material" and potentially avoids their shortcomings. Here, we describe a new two-stage reaction extrusion strategy of TPOs with a backbone consisting of inert C-C bonds (polypropylene, PP), and thiol-anhydride, to dynamically crosslink PP through thiol-thioester bond exchange. The degree of PP crosslinking determines the rubber plateau modulus above the melting point of the plastic: the modulus at 200 °C increases from zero in the melt to 23 kPa at 6% crosslinking, to 60 kPa at 20%, to 105 kPa at 40%. The overall mechanical strength of the solid xTPO plastic is 25% higher compared to the original PP, and the gel fraction of xTPO reaches 55%. Finally, we demonstrate that the crosslinked xTPO material is readily reprocessable (recycled, remolded, rewelded, and 3D printed).


Time to depression treatment in primary care among HIV-infected and uninfected veterans.
Multiple factors, including patient characteristics, competing demands, and clinic type, impact delivery of depression treatment in primary care. Assess whether depression severity and HIV serostatus have a differential effect on time to depression treatment among depressed patients receiving primary care at Infectious Disease or General Medicine clinics. Multicenter prospective cohort, (Veterans Aging Cohort Study), comparing HIV-infected to uninfected patients. The total cohort consisted of 3,239 HIV-infected and 3,227 uninfected patients. Study inclusion criteria were untreated depressive symptoms, based on a Patient Health Questionnaire (PHQ-9) score of greater than 9, and no antidepressants or mental health visits in the 90 days prior to PHQ-9 assessment. Treatment was defined as antidepressant receipt or mental health visit within 90 days following PHQ-9 assessment. Depression severity based on PHQ-9 scores was defined as mild-moderate (greater than 9 to 19) and severe (20 or greater). Kaplan-Meier curves were used to estimate time to treatment by depression severity and HIV serostatus. Cox proportional hazards methods adjusted for covariates were used. Overall, 718 (11%) of the cohort met inclusion criteria, 258 (36%) of whom received treatment. Median time to treatment was 7 days [95% confidence interval (CI) = 4, 13] and was shortest for severely depressed HIV-infected patients (0.5 days; 95% CI = 0.5, 6, p = 0.04). Compared to mildly-moderately depressed uninfected patients, severely depressed HIV-infected patients were significantly more likely to receive treatment [adjusted hazard ratio (HR) 1.67, 95% CI = 1.07, 2.60), whereas mildly-moderately depressed HIV-infected patients (adjusted HR 1.10, 95% CI = 0.79, 1.52) and severely depressed uninfected patients (adjusted HR 0.93, 95% CI = 0.60, 1.44) were not. In this large cohort, time to primary care treatment of depression was shortest among severely depressed HIV-infected patients. Regardless of HIV serostatus, if depression was not treated on the assessment day, then it was unlikely to be treated within a 90-day period, leading to the majority of depression being untreated.