Extensive Epidermoid Cyst and Breathing Difficulty.
Epidermoid cysts are common cystic lesions in the skin, ovaries, and testicles, but their occurrence in the oral cavity is uncommon. They consist of cysts delimited by a fibrous capsule without cutaneous annexes and are lined by stratified squamous epithelium. The differential diagnosis includes ranula, dermoid cysts, and lingual thyroid. Despite their benign presentation, these cysts can cause functional limitations, requiring special clinical attention for extensive lesions located in regions that preserve vital structures. This paper aims to report a case of epidermoid cyst in patient with swallowing and breathing difficulty, highlighting the clinical and surgical planning.


Types and three-dimensional distribution of neuronal ectopias in the brain of mice prenatally subjected to X-irradiation.
The types and three-dimensional distribution of neocortical ectopias following prenatal exposure to X-irradiation were studied by a histological examination and computer reconstruction techniques. Pregnant ICR mice were subjected to X-irradiation at a dose of 1.5 Gy on embryonic day 13. The brains from 30-day-old mice were serially sectioned on the frontal plane at 15 microns, stained with HE and observed with a microscope. The image data for the sections were input to a computer, and then reconstructed to three-dimensional brain structures using the Magellan 3.6 program. Sectional images were then drawn on a computer display at 240 microns intervals, and the positions of the different types of neocortical ectopias were marked using color coding. Three types of neocortical ectopias were recognized in the irradiated brains. Neocortical Lay I ectopias were identified as small patches in the caudal occipital cortex, and were located more laterally in the neocortex in caudal sections than in the rostral sections. Periventricular ectopias were located more rostrally than Lay I ectopias, and were found from the most caudal extent of the presumed motor cortex to the most caudal extent of the lateral ventricle. Hippocampal ectopias appeared as continuous linear bands, and were frequently associated with the anterior parts of the periventricular ectopias.


Comparative evaluation of two newly developed devices for capillary viscometry.
Viscometry is an often applied method in clinical chemistry. A variety of studies demonstrate an association of parameters related to blood viscosity with human pathology of varying origin. Whole blood and plasma viscosity are considered to be clinically useful indicators in the diagnostic workup and therapy monitoring of certain diseases. In this study, we compare the "Waegeviskosimeter" (WV) described in previous publications with a newly developed device, the "Reverse Flow Viscometer" (RFV). Both viscometers are capillary flow viscometers. Both overcome the disadvantage of common viscometers of the Ubbelohde and Cannon-Fenske type which require large amounts of plasma and which can be only applied to Newtonian fluids. The accuracy of the measurements of both viscometers, requiring less than 1.0 ml sample volume, is superior to most conventional methods. The major distinction in the functionality of the WV and the RFV is that the WV measures the kinematic viscosity whereas the RFV directly estimates dynamic viscosity without the requirement of additional density measurement. We found good reproducibility of viscosity with coefficient of variation CV < or =1.1% for both viscometers. Quality assurance measures have been carried out. Because no quality assurance scheme according to the guidelines proposed by the German Medical Association exists for plasma or whole blood viscosity, we tested reference material Lyphochek Unassayed Chemistry Control Level 1 and Level 2 (Bio-Rad Laboratories). We determined the viscosities 1.40 mPa s and 1.08 mPa s (37 degrees C) and the between-run precision from daily quality control runs with CV of 1.4% and 1.2% for the WV, and 1.7% and 1.4% for the RFV. For direct comparison reasons, we determined the viscosity in seventy human plasma and serum samples by both methods. Using the regression analysis described by Passing-Bablok, the RFV and the WV methods are highly correlated and show only little variations (r = 0.990, tau = 0.896). The regression equation is y(WV) = 1.035x(RFV) - 0.056 with a mean deviation of 0.4+/-3.6%. We conclude that both new devices for viscosity assessment fulfill all quality requirements as prescribed for clinical chemical laboratories. One advantage RFV is to measure the dynamic viscosity directly.


Adsorption Profile of Basic Dye onto Novel Fabricated Carboxylated Functionalized Co-Polymer Nanofibers.
Acrylonitrile-Styrene co-polymer was prepared by solution polymerization and fabricated into nanofibers using the electrospinning technique. The nanofiber polarization was enhanced through its surface functionalization with carboxylic acid groups by simple chemical modification. The carboxylic groups' presence was dedicated using the FT-IR technique. SEM showed that the nanofiber attains a uniform and porous structure. The equilibrium and kinetic behaviors of basic violet 14 dye sorption onto the nanofibers were examined. Both Langmuir and Temkin models are capable of expressing the dye sorption process at equilibrium. The intraparticle diffusion and Boyd kinetic models specified that the intraparticle diffusion step was the main decolorization rate controlling the process.


Macrophage colony-stimulating factor stimulates growth progression of the G1-phase fraction and induces monocytic differentiation of the G2/M-phase fraction in human myeloid leukemia cells.
The human myeloid leukemia cell line (NKM-1) proliferates in response to exogenous macrophage colony-stimulating factor (M-CSF) in serum-free medium. This CSF alone, however, does not induce any feature of cell differentiation in NKM-1 cells. We showed that terminal monocytic differentiation is partially observed only when NKM-1 cells are sequentially treated with 1,25-dihydroxyvitamin D3 and M-CSF, as evaluated by cell morphology, analysis of surface antigens, and phagocytic function. To determine whether there might be an association between the actions of M-CSF and special phases of the cell cycle, we separated D3-treated cells into cycle-specific fractions by centrifugal elutriation. G1-enriched cells were mostly stimulated for growth progression with M-CSF. On the other hand, G2/M-enriched cells were significantly induced into monocytic differentiation. The cell percentage in the G2/M phase has clearly correlated with that of terminally differentiated cells by M-CSF. These results suggest that two distinct actions of M-CSF to stimulate cell proliferation and differentiation could work on different phases of the cell cycle: cell growth in the G1 phase and cell differentiation in the G2/M phase.


Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer.
In this study, poly(lactic-co-glycolic acid) (PLGA) was used as a carrier to construct disulfiram-loaded porous microparticle through the emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The microparticle possessed highly porous surface, suitable aerodynamic diameter for inhalation (8.31±1.33 µm), favorable drug loading (4.09%±0.11%), and sustained release profile. The antiproliferation effect of release supernatant was detected through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using non-small-cell lung cancer A549 as a model, with only 13.3% of cell viability observed for the release supernatant at 7 days. The antiproliferation mechanism was elucidated to be associated with the enhanced induction of cell apoptosis and cell cycle arrest at S phase through flow cytometry and Western blotting analysis. Finally, wound healing and transwell migration assay showed that they could efficiently inhibit the cell migration. These results demonstrated that disulfiram-loaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.


Effects of creatine monohydrate and polyethylene glycosylated creatine supplementation on muscular strength, endurance, and power output.
The purpose of this study was to examine the effects of a moderate dose of creatine monohydrate (CM) and two smaller doses of polyethylene glycosylated (PEG) creatine on muscular strength, endurance, and power output. Fifty-eight healthy men (mean +/- SD: age, 21 +/- 2 years; height, 176 +/- 6 cm; body mass [BM], 75 +/- 14 kg) volunteered and were randomly assigned to 1 of 4 groups: (a) placebo (PL; 3.6 g of microcrystalline cellulose; n = 15), (b) CM (5 g of creatine; n = 13), (c) small-dose PEG creatine (1.25 g of creatine: PEG1.25; n = 14), or (d) moderate-dose PEG creatine (2.50 g of creatine: PEG2.50; n = 16). Testing was conducted before (pre-) and after (post-) a 30-day supplementation period. Measurements included body mass, countermovement vertical jump (CVJ) height, power output during the Wingate test (peak power [PP] and mean power [MP]), 1 repetition maximum bench press (1RMBP), 1RM leg press (1RMLP) strength, and repetitions to failure at 80% of the 1RM for bench press (REPBP) and leg press (REPLP). BM and MP (W) increased (p <or= 0.05) from pre- to postsupplementation for the CM group only, whereas 1RMBP and 1RMLP increased (p <or= 0.05) for the CM, PEG1.25, and PEG2.50 groups. CVJ height (cm and cm.kg), MP (W.kg), PP (W and W.kg), REPBP, and REPLP increased (p <or= 0.05) for all groups. These findings indicated that the recommended safe dose of 5 g.d of CM increased BM and improved muscle strength (1RMBP and 1RMLP). Smaller doses of PEG creatine (1.25 and 2.50 g.d) improved muscle strength (1RMBP and 1RMLP) to the same extent as 5 g.d of CM, but did not alter BM, power output, or endurance. When compared to the PL group, neither CM nor PEG creatine supplementation improved peak power output (CVJ or PP), MP, or muscle endurance (REPBP or REPLP). Thus, PEG creatine may have ergogenic effects that are comparable to those of CM, but with a smaller dose of creatine.


Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis.
The KIT D816V mutation is found in >80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. Therefore, KIT D816V represents a prime therapeutic target for SM. Here, we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM and mast cell leukemia to develop a patient-specific SM disease model for mechanistic and drug-discovery studies. KIT D816V iPSCs differentiated into neoplastic hematopoietic progenitor cells and MCs with patient-specific phenotypic features, thereby reflecting the heterogeneity of the disease. CRISPR/Cas9n-engineered KIT D816V human embryonic stem cells (ESCs), when differentiated into hematopoietic cells, recapitulated the phenotype observed for KIT D816V iPSC hematopoiesis. KIT D816V causes constitutive activation of the KIT tyrosine kinase receptor, and we exploited our iPSCs and ESCs to investigate new tyrosine kinase inhibitors targeting KIT D816V. Our study identified nintedanib, a US Food and Drug Administration-approved angiokinase inhibitor that targets vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, as a novel KIT D816V inhibitor. Nintedanib selectively reduced the viability of iPSC-derived KIT D816V hematopoietic progenitor cells and MCs in the nanomolar range. Nintedanib was also active on primary samples of KIT D816V SM patients. Molecular docking studies show that nintedanib binds to the adenosine triphosphate binding pocket of inactive KIT D816V. Our results suggest nintedanib as a new drug candidate for KIT D816V-targeted therapy of advanced SM.


Novel Spiroplasma sp. Isolated From CWD Is an Extreme Bacterial Thermoacidophile That Survives Autoclaving, Boiling, Formalin Treatment, and Significant Gamma Irradiation.
Rapid spreading of chronic wasting disease (CWD) in wildlife and captive cervid populations has exposed lack of progress in dealing with the transmissible spongiform encephalopathies (TSE) of man and animals. Since the TSE transmissible agent was resistant to extremes in environmental and chemical treatments, focus was on an unconventional agent including the prion theory. Recent breakthrough research has revealed consistent isolation of a novel Spiroplasma sp. from TSE-affected tissues that propagates in cell-free media and on agar. Here, we developed a live culture assay to test whether the CWD spiroplasma isolate possessed unconventional biologic properties akin to those of the transmissible agent of TSE. The CWD spiroplasma isolate survived boiling for 1 hour, standard liquid autoclaving, 10% formalin treatment overnight, and gamma irradiation of 20 kGy. The CWD spiroplasma isolate is an acidophile, growing best at pH 2. The biologic resistance of the CWD spiroplasma isolate may be due to unusual phage-like viruses found in the bacterial pellet or to DNA-protein binding. Because the CWD spiroplasma isolate has biologic properties consistent with the causal agent of the TSEs, TSE research focus should be redirected to development of diagnostic tests and preventive vaccines for control of CWD based upon the bacterium.


Iron status of very-low-birth-weight infants during the first 15 months of infancy.
The adequacy of iron stores in infants of very low birth weight (defined as less than 1500 g) in Canada is unknown. We monitored the iron status of 81 such infants at 3, 6, 9, 12 and 15 months of age. All of the infants were fed formula fortified with iron (13 mg/L) for at least 6 months, starting at 2 months of age. The plasma ferritin level decreased after the formula was no longer used. Although 90% of the infants were given cereal fortified with iron (30 mg of iron per 100 g) by 9 months of age, the plasma ferritin level continued to decrease. The level was less than 10 micrograms/L in 54% of the infants at 12 months of age and in 74% at 15 months; this indicated depleted iron stores. Because of delayed development very-low-birth-weight infants eat small amounts of cereal and therefore require iron-fortified formula throughout infancy.


Transcriptional regulation of storage protein synthesis during dicotyledon seed filling.
Seeds represent a major source of nutrients for human and animal livestock diets. The nutritive value of seeds is largely due to storage products which accumulate during a key phase of seed development, seed filling. In recent years, our understanding of the mechanisms regulating seed filling has advanced significantly due to the diversity of experimental approaches used. This review summarizes recent findings related to transcription factors that regulate seed storage protein accumulation. A framework for the regulation of storage protein synthesis is established which incorporates the events before, during and after seed storage protein synthesis. The transcriptional control of storage protein synthesis is accompanied by physiological and environmental controls, notably through the action of plant hormones and other intermediary metabolites. Finally, recent post-genomics analyses on different model plants have established the existence of a conserved seed filling process involving the master regulators (LEC1, LEC2, ABI3 and FUS3) but also revealed certain differences in fine regulation between plant families.


[The role of clock gene BMAL1 in exercise-induced skeletal muscle injury recovery].
Objective: To investigate the role of clock gene BMAL1 in exercise-induced skeletal muscle injury recovery. Methods: Two hundred and eight 8-week-old SD rats were randomly divided into the control group (Group C, n=104) and the exercise group (Group E, n=104). Group E performed a 90-minute downhill run on the treadmill. After exercise, the gastrocnemius muscle of 8 rats in Group C and Group E were collected at 0 h, 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h, 66 h and 72 h. The expression of skeletal muscle core clock gene, BMAL1 was measured by real-time fluorescence quantitative PCR. The parameters of fitting cosine curve were obtained by cosine analysis software circacompare (R package), and the change trend of rhythmic oscillation was analyzed. The ultrastructure of skeletal muscle fibers was observed by transmission electron microscope. The expressions of skeletal muscle BMAL1 and DESMIN were detected by Western blot; Immunofluorescence was used to observe the localization and contents of BMAL1 and DESMIN. Results: In Group C, three complete circadian rhythm cycles of mRNA BMAL1 were observed within 72 hours; in Group E, the circadian rhythm of BMAL1 mRNA disappeared at 0 h~24 h. Compared with Group C, the expression level of BMAL1 mRNA was significantly increased at 0 h, 6 h, 12 h, and 18 h after exercise in Group E (P<0.05), and the expression of BMAL1 protein was significantly increased at 0 h and 12 h after exercise(P<0.05), and recovered to the level of that in Group C from 24 h to 72 h(P>0.05). The expression of DESMIN protein was decreased at 0 h and 12 h after exercise(P<0.05), gradually increased at 24 h, increased significantly at 48 h(P<0.01), and recovered to the control level at 72 h (P>0.05). In Group E, BMAL1 and DESMIN were co-localized at 0 h, 12 h, and 24 h after exercise; the colocalization at 0 h~24 h showed a trend of first decreasing and then increasing, and the fluorescence intensity at 24 h reached the highest value. Conclusion: The post-exercise clock gene BMAL1 may be involved in the enhanced synergy of regulating the cytoskeletal protein DESMIN, it is thus related to the promotion of muscle fiber structure recovery.


A review of post-traumatic stress disorder. Part I: Historical development and classification.
This paper describes the history of the development of understanding of psychological responses to traumatic life-events and their treatment. One major response, post-traumatic stress disorder (PTSD), is a recognized condition which has appeared relatively recently in diagnostic manuals. PTSD is a condition of major significance, not only to mental health professionals, but also to trauma surgeons and allied professionals. This paper focuses on the current definition of PTSD in the International Classification of Diseases (ICD-10, 1992, World Health Organization) and the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV, 1994). PTSD first appeared as an operational diagnosis in DSM-III (1980) and was revised in DSM-III-R (1987) and DSM-IV (1994). It made its first appearance in the ICD system later, in 1992. This paper seeks to increase awareness of PTSD across the broad spectrum of trauma management professionals, to emphasize the practical value of identifying the disorder and to encourage optimism for its treatment. This paper is in two parts. The first part deals with historical development and classification. The second part (to appear in the next issue of Injury) deals with treatment.


Elongation factor SII contacts the 3'-end of RNA in the RNA polymerase II elongation complex.
Elongation factor SII (also known as TFIIS) is an RNA polymerase II binding protein that allows bypass of template arrest sites by activating a nascent RNA cleavage reaction. Here we show that SII contacts the 3'-end of nascent RNA within an RNA polymerase II elongation complex as detected by photoaffinity labeling. Photocross-linking was dependent upon the presence of SII, incorporation of 4-thio-UMP into RNA, and irradiation and was sensitive to treatment by RNase and proteinase. A transcriptionally active mutant of SII lacking the first 130 amino acids was also cross-linked to the nascent RNA, but SII from Saccharomyces cerevisiae, which is inactive in concert with mammalian RNA polymerase II, failed to become photoaffinity labeled. SII-RNA contact was not detected after a labeled oligoribonucleotide was released from the complex by nascent RNA cleavage, demonstrating that this interaction takes place between elongation complex-associated but not free RNA. This shows that the 3'-end of RNA is near the SII binding site on RNA polymerase II and suggests that SII may activate the intrinsic RNA hydrolysis activity by positioning the transcript in the enzyme's active site.


Laparoscopic-assisted modified Kugel herniorrhaphy for obturator hernia: a case report.
Obturator hernia (OH) is a relatively rare disease and there are various surgical procedures for treating it. We report the case of a patient with an OH who underwent laparoscopic-assisted modified Kugel herniorrhaphy. The patient was a 74-year-old woman admitted to our hospital with nausea and abdominal distension. A diagnosis of intestinal obstruction was made because abdominal computed tomography revealed incarcerated right OH. No apparent strangulation findings were observed, and reduction was performed under ultrasound guidance. Laparoscopic-assisted modified Kugel herniorrhaphy for OH was performed. There were no signs of the bowel necrosis. Pneumoperitoneum was temporarily discontinued, and the OH was repaired by the modified Kugel herniorrhaphy. Laparoscopy confirmed that the direct Kugel patch was placed at the appropriate position. Laparoscopic-assisted modified Kugel herniorrhaphy is considered to be safe and useful for patients with OH and is considered as one of the treatment options.


Self-targeting, zwitterionic micellar dispersants enhance antibiotic killing of infectious biofilms-An intravital imaging study in mice.
Extracellular polymeric substances (EPS) hold infectious biofilms together and limit antimicrobial penetration and clinical infection control. Here, we present zwitterionic micelles as a previously unexplored, synthetic self-targeting dispersant. First, a pH-responsive poly(ε-caprolactone)-block-poly(quaternary-amino-ester) was synthesized and self-assembled with poly(ethylene glycol)-block-poly(ε-caprolactone) to form zwitterionic, mixed-shell polymeric micelles (ZW-MSPMs). In the acidic environment of staphylococcal biofilms, ZW-MSPMs became positively charged because of conversion of the zwitterionic poly(quaternary-amino-ester) to a cationic lactone ring. This allowed ZW-MSPMs to self-target, penetrate, and accumulate in staphylococcal biofilms in vitro. In vivo biofilm targeting by ZW-MSPMs was confirmed for staphylococcal biofilms grown underneath an implanted abdominal imaging window through direct imaging in living mice. ZW-MSPMs interacted strongly with important EPS components such as eDNA and protein to disperse biofilm and enhance ciprofloxacin efficacy toward remaining biofilm, both in vitro and in vivo. Zwitterionic micellar dispersants may aid infection control and enhance efficacy of existing antibiotics against remaining biofilm.


Functional activities and immunoglobulin variable regions of human and murine monoclonal antibodies specific for the P1.7 PorA protein loop of Neisseria meningitidis.
The meningococcal PorA protein is considered a promising vaccine candidate. Although much is understood regarding the structure of PorA proteins, little is known about the structure-function relationships of PorA antibodies. The aim of this study was to compare the functional and molecular characteristics of a human monoclonal antibody (MAb) and three murine MAbs specific for the PorA P1.7 serosubtype. Murine MAbs 207,B-4 (immunoglobulin G2a [IgG2a]) and MN14C11.6 (IgG2a) were both bactericidal and opsonophagocytic for P1.7-expressing meningococci, whereas human MAb SS269 (IgG3) and murine MAb 208,D-5 (IgA) initiated neither effector function. Epitope mapping with synthetic peptides revealed that MAbs 207,B-4 and 208,D-5 recognized the sequence ASGQ, which is the same specificity motif that a previous study had established for SS269 and MN14C11.6. Nucleotide and amino acid sequence analyses of the variable regions of the four MAbs showed that the SS269 V(H) region belonged to the VH3 family and was approximately 70% homologous to those of the murine MAbs which were all from the 7183 family, whereas the SS269 V(L) region belonged to the Vlambda1-b family and was less than 40% homologous to those of the murine MAbs which were all members of the Vkappa1 family. The Fab fragment of SS269 was cloned and expressed in Escherichia coli and was shown by enzyme-linked immunosorbent assay analyses to bind as well as intact SS269 MAb to P1.7,16 serosubtype group B strain 44/76. We conclude that distinct differences exist in the effector function activities and variable region gene sequences of human and murine P1.7-specific MAbs despite their recognition of similar epitopes.


Genomic analysis to screen potential genes and mutations in children with non-syndromic early onset severe obesity: a multicentre study in Turkey.
Obesity is a complex genetic-based pediatric disorder which triggers life-threatening conditions. Therefore, the understanding the molecular mechanisms of obesity has been a significant approach in medicine. Computational methods allow rapid and comprehensive pathway analysis, which is important for generation of diagnosis and treatment of obesity. Aims of our study are to comprehensively investigate genetic characteristics of obesity in children with non-syndromic, early-onset (< 7 years), and severe obesity (BMI-SDS > 3) through computational approaches. First, the mutational analyses of 41 of obesity-related genes in 126 children with non-syndromic early-onset severe obesity and 76 healthy non-obese controls were performed using the next generation sequencing (NGS) technique, and the NGS data analyzed by using bioinformatics methods. Then, the relationship between pathogenic variants and anthropometric/biochemical parameters was further evaluated. Obtained results demonstrated that the 15 genes (ADIPOQ, ADRB2, ADRB3, IRS1, LEPR, NPY, POMC, PPARG, PPARGC1A, PPARGC1B, PTPN1, SLC22A1, SLC2A4, SREBF1 and UCP1) which directly related to obesity found linked together via biological pathways and/or functions. Among these genes, IRS1, PPARGC1A, and SLC2A4 stand out as the most central ones. Furthermore, 12 of non-synonymous pathogenic variants, including six novels, were detected on ADIPOQ (G90S and D242G), ADRB2 (V87M), PPARGC1A (E680G, A477T, and R656H), UCP1 (Q44R), and IRS1 (R302Q, R301H, R301C, H250P, and H250N) genes. We propose that 12 of non-synonymous pathogenic variations detected on ADIPOQ, ADRB2, PPARGC1A, UCP1, and IRS1 genes might have a cumulative effect on the development and progression of obesity.


Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling.
Reactive oxygen species (ROS) and nitric oxide (NO) are important participants in signal transduction that could provide the cellular basis for activity-dependent regulation of neuronal excitability. In young rat cortical brain slices and undifferentiated PC12 cells, paired application of depolarization/agonist stimulation and oxidation induces long-lasting potentiation of subsequent Ca(2+) signaling that is reversed by hypoxia. This potentiation critically depends on NO production and involves cellular ROS utilization. The ability to develop the Ca(2+) signal potentiation is regulated by the developmental stage of nerve tissue, decreasing markedly in adult rat cortical neurons and differentiated PC12 cells.


Non-human primate regulatory T cells: current biology and implications for transplantation.
Regulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human primate Treg and prospects for their evaluation in allotransplantation and xenotransplantation.


Use of a proteome strategy for tagging proteins present at the plasma membrane.
A plasma membrane (PM) fraction was purified from Arabidopsis thaliana using a standard procedure and analyzed by two-dimensional (2D) gel electrophoresis. The proteins were classified according to their relative abundance in PM or cell membrane supernatant fractions. Eighty-two of the 700 spots detected on the PM 2D gels were microsequenced. More than half showed sequence similarity to proteins of known function. Of these, all the spots in the PM-specific and PM-enriched fractions, together with half of the spots with similar abundance in PM fraction and supernatant, have previously been found at the PM, supporting the validity of this approach. Extrapolation from this analysis indicates that (i) approximately 550 polypeptides found at the PM could be resolved on 2D gels; (ii) that numerous proteins with multiple locations are found at the PM; and (iii) that approximately 80% of PM-specific spots correspond to proteins with unknown function. Among the later, half are represented by ESTs or cDNAs in databases. In this way, several unknown gene products were potentially localized to the PM. These data are discussed with respect to the efficiency of organelle proteome approaches to link systematically genomic data to genome expression. It is concluded that generalized proteomes can constitute a powerful resource, with future completion of Arabidopsis genome sequencing, for genome-wide exploration of plant function.


Metabolic neutrality in nitrendipine therapy.
There is evidence that hypertensive patients frequently have other metabolic disorders, such as hyperlipidemia and diabetes mellitus. It is also known that the reduction in high blood pressure alone, disregarding the other cardiovascular risk factors, is unable to reduce mortality to the level of the general population. Moreover, the occurrence of metabolic side effects with some antihypertensive drugs deserves particular attention in the treatment of hypertension. Calcium antagonists seem to be devoid of untoward metabolic effects. In particular, several studies have shown that nitrendipine does not deteriorate glucose tolerance. We have evaluated the effects of nitrendipine on insulin response to i.v. glucose load: no change was observed after 2 months of treatment in both serum insulin levels and glucose percent removal rate in comparison to pretreatment values. No unfavorable change was detectable in the studies aimed at investigating the effects of nitrendipine on lipid metabolism parameters. We observed a 22% increase of the percent removal rate of a lipid emulsion (Intralipid) after nitrendipine (3.11 +/- 1.0 vs. 3.80 +/- 1.0%/min, p less than 0.03). This finding suggests a favorable effect of nitrendipine on triglyceride catabolism, possibly mediated by an interference with lipoprotein lipase activity. The metabolic neutrality of nitrendipine, therefore, leads to considering the usefulness of this drug in an antihypertensive treatment that should not disregard the global risk profile.


Use of negative pressure wound therapy after vulvar carcinoma: case studies.
Surgery is widely used to treat vulvar cancer. However, postoperative complications after a vulvectomy can occur in 26-85 % of the cases. Here, the authors describe a complete radical vulvectomy with bilateral inguinal lymph node dissection performed in two patients. Both patients developed infection and wound breakdown postoperatively. Due to failure of local care, negative pressure wound therapy (NPWT) was started to reduce bacterial rates and tension on wound edges. Accelerated tissue healing was observed in both cases, as well as an improvement in the patients' quality of life.


Stress kinases and heat shock proteins in the pancreas: possible roles in normal function and disease.
Mitogen-activated protein kinases (MAPKs) and heat shock proteins (Hsps) are ubiquitous proteins that function in both normal and stress-related pathophysiological states of the cell. Recent advances in the study of such Hsps and their interaction with signaling kinase cascades, including the cloning of new members, has helped to define their physiological roles in various tissues. In the pancreas, three major MAPKs, ERKs, JNKs, and p38, have been demonstrated. While intracellular signals involved in the ERK cascade have been most extensively investigated, only a few upstream regulators and downstream effector proteins of the JNKs and p38 MAPK are known in the pancreas. Similarly, a number of Hsps have been identified in pancreas, including Hsp27, Hsp60, and Hsp70. Although the activation of various MAPKs and the induction of Hsp expression have clearly been demonstrated following experimental exposure of rodent pancreas to stress conditions, it remains to be determined whether Hsps have a protective or detrimental effect during acute pancreatitis or at the onset of pancreatic carcinoma. This review will summarize current knowledge of the regulation and function of stress-activated kinases and stress proteins in the pancreas.


[Video-guided retrosternoscopy: a new approach in retrosternal esophagoplasty].
In this study, the authors described a new videoscopically guided approach for tunneling in esophagoplasty and insertion of an esophageal prosthesis.


Reductive borylene-CO coupling with a bulky arylborylene complex.
Partial metal-boron bond cleavage and coupling of a borylene with two CO ligands was observed upon reduction of a new bulky arylborylene complex. Both the borylene precursor and dianionic product were structurally and spectroscopically characterized. In contrast, reduction of an aminoborylene complex led to complete loss of the borylene ligand and classical Hieber reduction. A rationale for these differences based on DFT methods is presented.


Association between angiotensin II type I receptor polymorphism and resting hemodynamics in black and white youth.
An angiotensin II type I receptor polymorphism (AGTR1/A1166C) was previously found to be associated with hypertension. The purpose of this study was to investigate the relationship between this polymorphism and resting measures of hemodynamics in normotensive youth. Subjects were 41 Whites (mean +/- SD: 18 +/- 3 y old, 26 males) and 73 Blacks (19 +/- 2 y old, 55 males) with a positive family history of hypertension. Hemodynamic measures included resting systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Allele frequencies were significantly different (chi2 = 14.10, P < or = .001) between Whites and Blacks (.23 vs .06 for the C allele, respectively). For all subsequent analyses, subjects were categorized into two genotype groups, carriers and non-carriers of the C allele, because only two Whites and no Blacks were homozygous for the C allele. Genotype frequencies were significantly different (chi2 = 12.66, P < or = .0011) between Whites and Blacks (.41 vs .12 for the carriers, respectively). Among Whites, univariate analyses of covariance, using body mass index and age as covariates, indicated that carriers of the C allele compared to non-carriers, had a higher DBP (61.6 +/- 6.7 vs 57.8 +/- 6.2 mm Hg, P < or = .05) and HR (68.0 +/- 10.5 vs 61.1 +/- 8.1, P < or = .05). Genotype was not associated with resting hemodynamic measures in Blacks (all P values > .05). These results are consistent with findings that have typically involved White adults, and demonstrate that the renin system does not seem to play as great a role in BP control in Blacks as it does in Whites.


Population dynamics of feline immunodeficiency virus within cat populations.
A deterministic model was constructed for studying the circulation of Feline Immunodeficiency Virus (FIV), a feline retrovirus homologous to Human Immunodeficiency Virus (HIV), within populations of domestic cats. The model has been tested with data generated by a long-term study of several natural cat populations. Simulations and a study of stability show that once introduced, the retrovirus is maintained within the population, with a stable equilibrium stage reached by both numbers of susceptible and infected individuals. An estimation of parameters indicates that the transmission rate is low and depends on the structure of the population. In addition, FIV has a low impact on the population in that the total number of cats at equilibrium when this virus is present is almost always equal to the habitat carrying capacity in the absence of the virus. Those results, in agreement with other observations, suggest that FIV originally arose in the distant past.


The effects of episode spacing on adult's reports of a repeated event.
Witnesses' reports of repeated events have been the focus of much research; however, the spacing interval between each episode of the event has differed greatly. The aim of the current study was to determine whether spacing interval affects participants' memory reports. Adults (N = 217) watched one (n = 52) or four videos depicting workplace bullying. The repeated event participants watched the four videos all in one day (n = 55), one per day over four consecutive days (n = 60), or one every three days over 12 days (n = 50). One week after the last (or only) video, participants reported on that video and answered some reflective questions about the procedure. Repeated-event participants also reported on what usually happens across the videos. Single-event participants reported proportionally more accurate information about the target video than repeated-event participants, and spacing interval did not affect repeated event participants' accuracy. However, accuracy scores were close to ceiling while errors rates were at floor levels, preventing us from drawing strong conclusions. We found some evidence that episode spacing affected participants' perceptions of their memory performance. Overall, spacing may have a minimal effect on adults' memory for repeated events, but further research is required.


Pharmacological and physical prevention and treatment of no-reflow after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction.
After successful primary percutaneous coronary intervention in ST-segment elevation myocardial infarction, adequate myocardial reperfusion is not achieved in up to 50% of patients. This phenomenon of no-reflow is associated with a poor in-hospital and long-term prognosis. Four main factors are thought to contribute to the occurrence of no-reflow: ischaemic injury; reperfusion injury; distal embolization; susceptibility of the microcirculation to injury. This review evaluates the literature, and in particular the clinical trials, concerned with pharmacological and physical methods for prevention and treatment of no-reflow. A number of drugs may improve no-reflow experimentally and clinically, but some have not yet been associated with conclusive improvements in clinical outcome. The complex interacting factors in no-reflow make it unlikely that any single agent will be effective for all patients. Confirmed methods known to be beneficial in the prevention of no-reflow (such as aspirin therapy, chronic statin therapy, blood glucose control, thrombus aspiration in patients with a high thrombus burden and ischaemic preconditioning) should be offered to patients as often as possible, to prevent and treat no-reflow.


MiR-206 improves intervertebral disk degeneration by targeting GJA1.
A large amount of evidence suggested that miRNA was involved in the progression of intervertebral disk degeneration (IDD). The purpose of our study was to explore the function and potential mechanism of miR-206/GJA1 axis in IDD. IDD nucleus pulposus (NP) cell model was established through treatment of LPS. IDD rat model was established by annulus fibrosus puncture. The expression of miR-206 and GJA1 was detected by RT-PCR, apoptosis was evaluated by flow cytometry or TUNEL, inflammatory factors were tested by ELISA, extracellular matrix related protein expression was detected by western blot, and HE and safranin-O staining were used to assess the pathological changes of IDD. GJA1 was found to be highly expressed in IDD tissues and LPS-induced NP cells. Down regulation of GJA1 reduced inflammatory factors, inhibited apoptosis and enhanced extracellular matrix in LPS-induced NP cells. MiR-206 was downregulated in IDD tissues and directly targeted GJA1, and the expression of miR-206 was negatively correlated with the expression of GJA1 in IDD tissues. Further, it was demonstrated that overexpression of miR-206 could attenuate LPS-induced NP cell injury by targeting GJA1. In vivo, the upregulation of miR-206 improved IDD and reduced NP cell apoptosis. Our study showed that miR-206 reduced the level of inflammatory factors, restrained NP cell apoptosis and increases extracellular matrix by targeting GJA1. These data suggested that miR-206/GJA1 might be potential therapeutic targets for IDD.


The global impact of COVID-19 on drug purchases: A cross-sectional time series analysis.
The drug supply chain is global and at risk of disruption and subsequent drug shortages, especially during unanticipated events. Our objective was to determine the impact of coronavirus disease 2019 (COVID-19) on drug purchases overall, by class, and for specific countries. A cross-sectional time series analysis of country-level drug purchase data from August 2014 to August 2020 from IQVIA MIDAS was conducted. Standardized units per 100 population and percentage increase in units purchased were assessed from 68 countries and jurisdictions in March 2020 (when the World Health Organization declared COVID-19 a pandemic). Analyses were compared by United Nations development status and drug class. Autoregressive integrated moving average models tested the significance of changes in purchasing trends. Before COVID-19, standardized medication units per 100 population ranged from 3990 to 4760 monthly. In March 2020, there was a global 15% increase in units of drugs purchased to 5309.3 units per 100 population compared with the previous year; the increase was greater in developed countries (18.5%; P < 0.001) than in developing countries (12.8%; P < 0.0001). After the increase in March 2020, there was a correction in the global purchase rate decreasing by 4.7% (April to August 2020 rate, 21,334.6/100 population; P < 0.001). Globally, we observed high purchasing rates and large changes for respiratory medicines such as inhalers and systemic adrenergic drugs (March 2020 rate, 892.7/100 population; change from 2019, 28.5%; P < 0.001). Purchases for topical dermatologic products also increased substantially (42.2%), although at lower absolute rates (610.0/100 population in March 2020; P < 0.0001). Interestingly, purchases for systemic anti-infective agents (including antiviral drugs) increased in developing countries (11.3%; P < 0.001), but decreased in developed countries (1.0%; P = 0.06). We observed evidence of global drug stockpiling in the early months of the COVID-19 pandemic, especially among developed countries. Actions toward equitable distribution of medicines through a resilient drug supply chain should be taken to increase global response to future unanticipated events, such as pandemics.


Intracranial metastases from malignant pleural mesothelioma. Report of three autopsy cases and review of the literature.
We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall.


Levels of high-mobility group box-1 in gingival crevicular fluid in nonsmokers and smokers with chronic periodontitis.
High-mobility group box-1 (HMGB1), a proinflammatory cytokine, plays a role in inflammatory disorders. Smoking is a well-established risk factor for periodontal disease. The aim of this study was to compare the levels of HMGB1 in the gingival crevicular fluid from periodontally healthy nonsmokers, chronic periodontitis nonsmokers, and chronic periodontitis smokers. Furthermore, the relationship between levels of HMGB1 and periodontal parameters was examined. Periodontal parameters of 17 nonsmokers with chronic periodontitis, nine smokers with chronic periodontitis, and nine periodontally healthy nonsmokers were examined. Gingival crevicular fluid samples were collected, and the levels of HMGB1 were analyzed using the enzyme-linked immunosorbent assay. The median level of HMGB1 was statistically significantly higher in chronic periodontitis nonsmokers (37.5 ng/mL) than in chronic periodontitis smokers (9.5 ng/mL) and periodontally healthy nonsmokers (3.7 ng/mL). There was no significant difference in the levels of HMGB1 between chronic periodontitis smokers and periodontally healthy nonsmokers. Levels of HMGB1 were positively correlated with plaque index, gingival index, probing depth, and clinical attachment level of nonsmokers. However, no significant correlations were found between levels of HMGB1 and all periodontal parameters examined in chronic periodontitis smokers. Chronic periodontitis nonsmokers had elevated levels of HMGB1 in gingival crevicular fluid. Moreover, the levels of HMGB1 were correlated with severity of periodontitis. Chronic periodontitis smokers exhibited lower levels of HMGB1 than chronic periodontitis nonsmokers. Further research is needed for understanding the role of HMGB1 in smoking and pathogenesis of periodontitis.


Anisotropy Influences on the Drug Delivery Mechanisms by Means of Joint Invariant Functions.
In the frame of Higuchi's type functionality, this paper presents the anisotropy influences on the drug delivery mechanisms through the joint invariant functions to the simultaneous actions of the two SL(2R) isomorphic groups. Then, a new equation for drug delivery mechanism, independent of the type of polymer matrix and/or drug, is proposed.


Multifunctional PEGylated Niosomal Nanoparticle-Loaded Herbal Drugs as a Novel Nano-Radiosensitizer and Stimuli-Sensitive Nanocarrier for Synergistic Cancer Therapy.
Nowadays, radiotherapy is one of the most effective treatments for breast cancer. In order to overcome the radioresistance of cancer cells, radio-sensitizing agents can be used combined with irradiation to increase the therapeutic efficiency. Curcumin can enhance the radiosensitivity of cancer cells and decrease their viability by the accumulation of these cells in the G2 phase. The encapsulation of curcumin in a nanoniosomal delivery system increases aqueous solubility and bioavailability, resulting in increased radio sensitivity. The present study aimed to enhance the radio-sensitizing effect of the curcumin-containing nanoniosome (Cur-Nio) when combined with irradiation. Thus, curcumin (0.5 mg ml-1) was loaded on a PEGylated nanoniosome containing Tween 60, cholesterol, DOTAP, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (at ratios of 70:30:10:5, respectively) by the thin-film hydration method. The particle size, zeta potential, entrapment efficiency, and drug-release rate of formulated nanoniosomes were determined. In order to assess cytotoxicity and apoptosis, different doses of irradiation along with various concentrations of free curcumin and Cur-Nio (single or in combination with irradiation) were treated with breast cancer cells. The particle size and zeta potential of Cur-Nio were reported to be 117.5 nm and -15.1 mV, respectively. The entrapment efficiency (EE%) and loading capacities were 72.3% and 6.68%, respectively. The drug-release rate during 6 h was 65.9%. Cell survival in the presence of curcumin at doses of 1 and 3 Gy showed a significant reduction compared with cells irradiated at 48 h and 72 h (p < 0.000). Also, the rate of cytotoxicity and apoptosis was significantly higher in cells treated with the combination of curcumin-containing nanoniosomes and irradiation in comparison with those treated with free curcumin. These findings indicate that the efficacy of pre-treatment with Cur-Nio as a radiosensitizer during radiotherapy enhances irradiation-induced breast cancer cell apoptosis and is a useful strategy to increase the effectiveness of breast cancer therapy.


From one solution of a 3-satisfiability formula to a solution cluster: frozen variables and entropy.
A solution to a 3-satisfiability (3-SAT) formula can be expanded into a cluster, all other solutions of which are reachable from this one through a sequence of single-spin flips. Some variables in the solution cluster are frozen to the same spin values by one of two different mechanisms: frozen-core formation and long-range frustrations. While frozen cores are identified by a local whitening algorithm, long-range frustrations are very difficult to trace, and they make an entropic belief-propagation (BP) algorithm fail to converge. For the BP algorithm to reach a fixed point, the spin values of a tiny fraction of variables (chosen according to the whitening algorithm) are externally fixed during the iteration. From the calculated entropy values, we infer that, for a large random 3-SAT formula with constraint density close to the satisfiability threshold, the solutions obtained by the survey-propagation or WALKSAT algorithms belong neither to the most dominating clusters of the formula nor to the most abundant clusters. This work indicates that a single-solution cluster of a random 3-SAT formula may have further community structures.


Changing nucleosome positions through modification of the DNA rotational information.
The effects of the rotational information of DNA in determining the in vitro localization of nucleosomal core particles (ncps) have been studied in the Saccharomyces cerevisiae 5S rRNA repeat gene. We have altered the distribution of the phased series of flexibility signals present on this DNA by inserting a 25-bp tract, and we have analyzed the effects of this mutation on the distribution and on the frequencies of ncps, as compared with the wild type and a reference 21-bp insertion mutant. The variation of the standard free energy of nucleosome reconstitution was determined. The results show that the DNA rotational information is a major determinant of ncps positioning, define how many rotationally phased signals are required for the formation of a stable particle, and teach how to modify their distribution through the alteration of the rotational signals.


Pd(II)-catalyzed enantioselective C-H olefination of diphenylacetic acids.
Pd(II)-catalyzed enantioselective C-H olefination of diphenylacetic acid substrates has been achieved through the use of monoprotected chiral amino acid ligands. The absolute configuration of the resulting olefinated products is consistent with that of a proposed C-H insertion intermediate.


Changes in reciprocal herkogamy during the tristyly-distyly transition in Oxalis alpina increase efficiency in pollen transfer.
Although the spatial separation of sexual organs within a flower (herkogamy) has been interpreted as a mechanism that promotes efficient pollen transfer, there have been few attempts to relate variation in herkogamy to probabilities of pollen flow. Here, we used a heterostylous species with variation in reciprocal herkogamy to test this hypothesis. We measured legitimate and illegitimate pollen flow with fluorescent dyes in four selected populations of Oxalis alpina corresponding to the extremes of a previously reported evolutionary gradient from tristyly to distyly. After the breakdown of tristyly, the observed increment in reciprocal herkogamy between the long and short morphs was associated with a 30% increase in the proportion of dye received from compatible illegitimate pollinations. In all populations, the most likely effective pollen vectors were two Heterosarus bee species. Our results support the adaptive value of reciprocal herkogamy in promoting efficient pollen transfer in heterostylous species.


Sarcoidosis: challenging diagnostic aspects of an old disease.
Over the past few years, there have been substantial advances in our understanding of sarcoidosis immunopathogenesis. Conversely, the etiology of the disease remains obscure for a number of reasons, including heterogeneity of clinical manifestations, often overlapping with other disorders, and insensitive and nonspecific diagnostic tests. While no cause has been definitely confirmed, there is increasing evidence that one or more infectious agents may cause the disease, although the organism may no longer be viable. Here we present 2 cases, in which sarcoidosis preceded tuberculosis and non-Hodgkin lymphoma. Development of new lesions in a patient with chronic/remitting sarcoidosis should be looked at with suspicion and promptly investigated in order to rule out an alternative/concomitant diagnosis. In such cases, tissue confirmation from the most accessible site, and bone marrow biopsy-if lymphoma is in the differential diagnosis-should be performed. In conclusion, we strongly advise that physicians be ready to reconsider the diagnosis of sarcoidosis in the presence of atypical manifestations or persistent/progressive disease despite conventional therapy.


[Theoretical and clinical aspects of the use of prostaglandins in glaucoma therapy].
In the first part of the article the main information and recent research on the uveoscleral outflow pathway, including its morphology and physiology were presented. The structure of extracellular matrix of ciliary muscle and the changes of it, that are induced by prostaglandins, resulting in decreasing intraocular pressure were emphasized. In the second part biochemical characteristics of prostaglandin analogues, using nowadays were presented. Their efficacy in reducing intraocular pressure and safety profile were described.


Tension at the surface: which phase is more important, liquid or vapor?
Tension at the surface is a most fundamental physicochemical property of a liquid surface. The concept of surface tension has widespread implications in numerous natural, engineering and biomedical processes. Research to date has been largely focused on the liquid side; little attention has been paid to the vapor--the other side of the surface, despite over 100 years of study. However, the question remains as to whether the vapor plays any role, and to what extent it affects the surface tension of the liquid. Here we show a systematic study of the effect of vapor on the surface tension and in particular, a surprising observation that the vapor, not the liquid, plays a dominant role in determining the surface tension of a range of common volatile organic solutions. This is in stark contrast to results of common surfactants where the concentration in the liquid plays the major role. We further confirmed our results with a modified adsorption isotherm and molecular dynamics simulations, where highly structured, hydrogen bonded networks, and in particular a solute depletion layer just beneath the Gibbs dividing surface, were revealed.


Expression and purification of the HIV type 1 Rev protein produced in Escherichia coli and its use in the generation of monoclonal antibodies.
We have developed a simple and rapid procedure for the purification of large amounts of Rev protein overexpressed in E. coli. The purification method, which does not require denaturation of the protein, takes advantage of the positively charged nature of Rev and the ability of Rev to interact with nucleic acids. The purified protein was used to develop three novel murine monoclonal antibodies against Rev. Using fusion proteins between glutathione S-transferase (GST) and various fragments of the Rev protein, we mapped the specificity of these antibodies to different regions of the Rev protein. One antibody, 3H6, is directed against the nucleolar localization/RRE-binding domain of Rev between amino acids 38 and 44. Another antibody, 3G4, recognizes an epitope between amino acids 90 and 116 of Rev. A third antibody, 2G2, does not recognize any of the fusion proteins, and may be directed against a conformational epitope. All three antibodies are able to detect Rev on Western blots and to immunoprecipitate Rev under native conditions. However, only 3H6 and 3G4 immunoprecipitate Rev under denaturing conditions and are able to detect Rev expressed in transfected cells by indirect immunofluorescence. These antibodies should prove useful in further studies of Rev function.


Vertically Aligned Graphene-Carbon Fiber Hybrid Electrodes with Superlong Cycling Stability for Flexible Supercapacitors.
Graphene electrode-based supercapacitors are in high demand due to their superior electrochemical characteristics. A major bottleneck of using the supercapacitors for commercial applications lies in their inferior electrode cycle life. Herein, a simple and facile method to fabricate highly efficient supercapacitor electrodes using pristine graphene sheets vertically stacked and electrically connected to the carbon fibers which can result in vertically aligned graphene-carbon fiber nanostructure is developed. The vertically aligned graphene-carbon fiber electrode prepared by electrophoretic deposition possesses a mesoporous 3D architecture which enabled faster and efficient electrolyte-ion diffusion with a gravimetric capacitance of 333.3 F g-1 and an areal capacitance of 166 mF cm-2 . The electrodes displayed superlong electrochemical cycling stability of more than 100 000 cycles with 100% capacitance retention hence promising for long-lasting supercapacitors. Apart from the electrochemical double layer charge storage, the oxygen-containing surface moieties and α-Ni(OH)2 present on the graphene sheets enhance the charge storage by faradaic reactions. This enables the assembled device to provide an excellent gravimetric energy density of 76 W h kg-1 with a 100% capacitance retention even after 1000 bending cycles. This study opens the door for developing high-performing flexible graphene electrodes for wearable energy storage applications.


Top-down then automatic: Instructions can continue to influence visual search when no longer actively implemented.
The present study investigated the automaticity of top-down instructions in visual search when the instruction was no longer actively implemented. To do so, we exploited the Priming of Pop-out (PoP) effect, a selection history phenomenon that reflects faster responses when the target and distractor colors are repeated than switched across trials of singleton search. We then had participants perform a color singleton search task where they implemented the instruction of imagining the opposite color of the previous target, which put the target colors underlying PoP and the imagery instruction in opposition. To assess automaticity, on some trials participants were instructed to stop implementing the imagery instruction. When the imagery instruction was implemented, responses were faster when the target and distractor colors switched (i.e., imagery congruent) than repeated (i.e., imagery incongruent) across search displays - a pattern of results opposite to the PoP effect. When participants were to not implement this instruction, the PoP effect was absent, indicating the imagery instruction had a lingering influence on visual search. This remained true even when participants reported successfully not implementing the instruction, and only when the imagery abandonment instruction was supplanted by a different top-down task was the lingering influence removed such that the PoP effect returned. Overall, the present study demonstrates that top-down instructions can continue to influence visual search despite the will of the observer.


Reconstruction of the diet of the Middle Woodland Amerindian population at Abbott Farm by bone trace-element analysis.
In order to reconstruct the diet of various occupations of Middle Woodland Amerindians at Abbott Farm, New Jersey, nine different trace-element analyses were performed on bone specimens from the site. Contemporary bone specimens were also used as controls. Specimens of human bone from the site exhibited lower strontium levels and strontium-to-calcium ratios than deer specimens from the same site, reinforcing paleodemographic evidence that the human populations that inhabited this site included substantial amounts of meat in their diets. Strong evidence for diagenetic enrichment of strontium was also found. Copper levels were not affected by diagenesis, but dietary discrimination was not clear for this element. The results for lead were too inconsistent to permit conclusions. Magnesium levels were clearly depleted by diagenesis, suggesting that this element is less useful than others in dietary reconstruction studies. Manganese concentrations were greatly enriched by diagenesis, rendering this element useless in dietary reconstruction. Molybdenum was absent from virtually every specimen. Excellent dietary discrimination was found for sodium, despite significant leaching. Zinc was not affected by diagenesis, but interpretation of results was hampered by its complex metabolism in mammals. The results also suggest that the Middle Woodland aboriginal residents of Abbott Farm ate little seafood and utilized grain or other plants that contain phytate as a food source.


Does l-Tryptophan supplementation reduce chewing deficits in an experimental model of cerebral palsy?
Children with cerebral palsy commonly present with feeding difficulties that result from multiple orofacial sequelae, especially deficits in mastication. A previous study demonstrated that perinatal protein undernutrition accentuated the chewing impact in an experimental model of cerebral palsy. Therefore, the present study investigated whether nutritional manipulation reversed or minimized the chewing sequelae in cerebral palsy. We emphasized the relevance of evaluating the therapeutic potential of nutrients, especially tryptophan supplementation, to reduce the chewing deficits that are typical of this syndrome. Clarification of the role of nutrients may help in the development of new treatment strategies for these children.


pS2 immunostaining of colorectal carcinoma.
This study was aimed at assessing the significance of pS2 immunostaining in colorectal adenocarcinoma and adjacent tissue. Paraffin sections of 63 surgically resected colorectal adenocarcinomas were stained with a pS2 specific monoclonal antibody using the avidin-biotin complex immunoperoxidase technique. Several tumor sections also included adjacent nonneoplastic mucosa. Six tubular adenomas and five hyperplasic polyps found in the resected bowels were also examined. Focal staining for pS2 was seen in 32 tumors (51%). In all but one case, less than 10% of the tumor cells were stained. pS2 staining was more common in right-sided than in left-sided tumors (p < 0.05), and was more prevalent in Dukes C than combined Dukes A and B tumors (p < 0.05). No significant relationship was found between pS2 positivity and the degree of tumor differentiation, patients' sex, or outcome of the disease as judged by the development of recurrence or metastasis. Strong pS2 positivity was seen in hyperplastic polyps and in nonneoplastic mucosa adjacent to many tumors. Tubular adenomas were either negative or showed focal superficial staining. It is concluded that pS2 immunostaining in colorectal adenocarcinoma does not seem to have prognostic significance, but may reflect developmental differences between the right and left side of the colon. The presence of pS2 staining in adjacent nonneoplastic mucosa and in hyperplastic polyps suggests that the epithelium in these areas is of a regenerative or reactive nature.


Incentivizing Drug Development in Serious Mental Illness.
Serious mental illness (SMI) imposes a significant burden on individuals and society. Individuals living with SMI have worse expected health, education, and career outcomes during their lifetime. Although treatments exist, pharmaceutical innovation in this area has lagged many other disease areas, despite an important need for new treatments. This report describes barriers that have hindered innovation and the development of new drugs for SMI, including science and research, regulatory, and health system barriers. To address these barriers, this report presents policies that may incentivize investment in this area.


A Carbon Foam with Sodiophilic Surface for Highly Reversible, Ultra-Long Cycle Sodium Metal Anode.
Sodium metal anodes combine low redox potential (-2.71 V versus SHE) and high theoretical capacity (1165 mAh g-1), becoming a promising anode material for sodium-ion batteries. Due to the infinite volume change, unstable SEI films, and Na dendrite growth, it is arduous to achieve a long lifespan. Herein, an oxygen-doped carbon foam (OCF) derived from starch is reported. Heteroatom doping can significantly reduce the nucleation resistance of sodium metal; combined with its rich pore structure and large specific surface area, OCF provides abundant nucleation sites to effectively guide the nucleation and subsequent growth of sodium metal, and the nature of this foam can accommodate the deposited sodium. Furthermore, a more uniform, robust, and stable SEI layer is observed on the surface of OCF electrode, so it can maintain ultra-high reversibility and excellent integrity for a long time without dendritic growth. As a result, when the current density is 10 mA cm-2, the electrode can maintain stable 2000 cycles and the coulombic efficiency can reach to 99.83%. Na@OCF||Na3V2(PO4)3 full cell also has extremely high capacity retention of about 97.53% over 150 cycles. These results provide a simple but effective method for achieving the safety and commercialization of sodium metal anode.


Effects of dextromethorphan on glial cell function: proliferation, maturation, and protection from cytotoxic molecules.
Dextromethorphan (DM), a sigma receptor agonist and NMDA receptor antagonist, protects neurons from glutamate excitotoxicity, hypoxia and ischemia, and inhibits microglial activation, but its effects on differentiation and protection of cells in the oligodendroglial lineage are unknown. It is important to protect oligodendroglia (OL) to prevent demyelination and preserve axons, and to protect oligodendroglial progenitors (OPC) to optimize myelination during development and remyelination following damage. Enriched glial cultures from newborn rat brain were used 1-2 days or 6-8 days after shakeoff for OPC or mature OL. DM had large effects on glial proliferation in less mature cultures in contrast to small variable effects in mature cultures; 1 μM DM stimulated proliferation of OPC by 4-fold, microglia (MG) by 2.5-fold and astroglia (AS) by 2-fold. In agreement with increased OPC proliferation, treatment of OPC with DM for 3 days increased the % of OPC relative to OL, with a smaller difference by 5 days, suggesting that maturation of OPC to OL was "catching up" by 5 days. DM at 2 and 20 μM protected both OL and OPC from killing by glutamate as well as NMDA, AMPA, quinolinic acid, staurosporine, and reactive oxygen species (ROS). DM did not protect against kynurenic acid, and only modestly against NO. These agents and DM were not toxic to AS or MG at the concentrations used. Thus, DM stimulates proliferation of OPC, and protects both OL and OPC against excitotoxic and inflammatory insults.


Gender differences in the relationship between shiftwork and work injury: examining the influence of dependent children.
To examine the relationship between shiftwork and work injury among men and women, taking into account the presence of dependent children. An analysis of respondents to the 2009-2010 Multipurpose Household Survey (n = 6927 women and 7340 men). Logistic regression models examined the work injury risk, adjusting for various covariates. The risk of work injury associated with shiftwork was higher for women than for men. Nevertheless, gender differences were present only among respondents with dependent children. Shiftworking women with children also had a greater risk of work injury than shiftworking women without children. This previously noted elevated risk of injury associated with shiftwork among women compared with that in men may be a product of increased household responsibilities or other factors particular to female shiftworkers with dependent children.


Why have attitudes to industry funding of research changed?
This paper discusses the history of the changing relationship between research and industrial funding, using the tobacco industry as its example. It seeks to explain why funding which was once acceptable is now unacceptable. The hypotheses advanced include: the changing nature of the industry's interest in research and the role of marketing; the rise of the 'new public health' alliance focused on abstention rather than on harm minimization; the role of government funding and control of research; and the changing meaning of tobacco and especially nicotine.


Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression.
Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex diseases, but mechanistic insights are impeded by a lack of understanding of how specific risk variants functionally contribute to the underlying pathogenesis. It has been proposed that cis-acting effects of non-coding risk variants on gene expression are a major factor for phenotypic variation of complex traits and disease susceptibility. Recent genome-scale epigenetic studies have highlighted the enrichment of GWAS-identified variants in regulatory DNA elements of disease-relevant cell types. Furthermore, single nucleotide polymorphism (SNP)-specific changes in transcription factor binding are correlated with heritable alterations in chromatin state and considered a major mediator of sequence-dependent regulation of gene expression. Here we describe a novel strategy to functionally dissect the cis-acting effect of genetic risk variants in regulatory elements on gene expression by combining genome-wide epigenetic information with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in human pluripotent stem cells. By generating a genetically precisely controlled experimental system, we identify a common Parkinson's disease associated risk variant in a non-coding distal enhancer element that regulates the expression of α-synuclein (SNCA), a key gene implicated in the pathogenesis of Parkinson's disease. Our data suggest that the transcriptional deregulation of SNCA is associated with sequence-dependent binding of the brain-specific transcription factors EMX2 and NKX6-1. This work establishes an experimental paradigm to functionally connect genetic variation with disease-relevant phenotypes.


A new embryonic stem cell line from DBA/1lacJ mice allows genetic modification in a murine model of human inflammation.
The development of embryonic stem (ES) cells and their capacity to generate mice with mutations at specific loci has provided a powerful resource for functional analysis of genes in pathological processes. However, the ability to combine this technology with the large number of existing murine models of human genetic disease has been complicated by the inability to routinely generate ES cell lines from strains other than 129. Here, we report the production of a novel ES cell line derived from an inbred mouse, DBA/1lacJ. This new ES cell line undergoes homologous recombination and efficient colonization of the germline of male chimeric offspring with ES cell microinjection into C57B1/6 embryos. The DBA/1lacJ mouse is a murine model of human inflammation, therefore genetic modifications in the DBA ES cells will allow evaluation of the target gene's role in the inflammatory process.


Luminescent terbium(III) complexes with pendant crown ethers responding to alkali metal ions and aromatic antennae in aqueous solution.
The luminescence lifetime of TbL2 with a pendant 15-crown-5 increased by 65% to 2.95 ms with an [Na+] concentration of 0.13 M in aqueous solution; the maximum amplification of the luminescence intensity of TbL1 containing aza-15-crown-5 reached a factor of 47 upon addition of the aromatic antenna p-chlorobenzoate 1.


Murine coronavirus spike glycoprotein mediates degree of viral spread, inflammation, and virus-induced immunopathology in the central nervous system.
The mouse hepatitis virus (MHV) spike glycoprotein is a major determinant of neurovirulence. We investigated how alterations in spike affect neurovirulence using two isogenic recombinant viruses differing exclusively in spike. S(4)R, containing the MHV-4 spike gene, is dramatically more neurovirulent than S(A59)R, containing the MHV-A59 spike gene (J. J. Phillips, M. M. Chua, E. Lavi, and S. R. Weiss, 1999, J. Virol. 73, 7752-7760). We examined the contribution of differences in cellular tropism, viral spread, and the immune response to infection to the differential neurovirulence of S(4)R and S(A59)R. MHV-4 spike-mediated neurovirulence was associated with extensive viral spread in the brain in both neurons and astrocytes. Infection of primary hippocampal neuron cultures demonstrated that S(4)R spread more rapidly than S(A59)R and suggested that spread may occur between cells in close physical contact. In addition, S(4)R infection induced a massive influx of lymphocytes into the brain, a higher percentage of CD8(+) T cells, and a higher frequency of MHV-specific CD8(+) T cells relative S(A59)R infection. Despite this robust and viral-specific immune response to S(4)R infection, infection of RAG1-/- mice suggested that immune-mediated pathology also contributes to the high neurovirulence of S(4)R.


Off-Label Medication in Children: Responsibilities of Pediatrician and Neonatologist.
Use of drug in pediatrics and neonatology should be rational. There are clinical situations when the use of unlicensed medicines or use of medicines outside the terms of license (i.e., 'off-label') may be judged by prescriber in the best interest of the patient. Off-label prescribing is clinically appropriate when the benefits outweigh the potential risks. Such practice is particularly common in pediatrics and neonatology where development of age-appropriate formulations is difficult. Before going to prescribe a drug on off-label basis, the clinician should be satisfied that an alternative medicine would not meet the patient's needs. The clinician should be satisfied that there is sufficient evidence base safety and efficacy on off-label drug use. Communication with legal guardian with sufficient information about proposed treatment is needed. The clinician has a responsibility to monitor the off-label use of drug. He should submit a report on suspected adverse drug reactions if he observes to the authorized body.


Naturally Derived Heme-Oxygenase 1 Inducers and Their Therapeutic Application to Immune-Mediated Diseases.
Heme oxygenase (HO) is the primary antioxidant enzyme involved in heme group degradation. A variety of stimuli triggers the expression of the inducible HO-1 isoform, which is modulated by its substrate and cellular stressors. A major anti-inflammatory role has been assigned to the HO-1 activity. Therefore, in recent years HO-1 induction has been employed as an approach to treating several disorders displaying some immune alterations components, such as exacerbated inflammation or self-reactivity. Many natural compounds have shown to be effective inductors of HO-1 without cytotoxic effects; among them, most are chemicals present in plants used as food, flavoring, and medicine. Here we discuss some naturally derived compounds involved in HO-1 induction, their impact in the immune response modulation, and the beneficial effect in diverse autoimmune disorders. We conclude that the use of some compounds from natural sources able to induce HO-1 is an attractive lifestyle toward promoting human health. This review opens a new outlook on the investigation of naturally derived HO-1 inducers, mainly concerning autoimmunity.


[Percutaneous angioscopy in the diagnosis of arteriopathies of the lower limbs].
Because of the poor specificity of the arteriography, the authors have performed a percutaneous angioscopy before every angioplasty of the arteries of lower limbs for nearly 3 years. They define the angioscopy and describe materials and technique. The percutaneous route without surgery and without anesthesia underlines the originality of the technique. The great difficulty is to counter-pulse the arterial inflow. The rate of saline irrigation and all the means of arterial blockade are described. In the second part, the "elementary images" are classified. The authors insist on the specificity of the angioscopy in the interpretation of arterial obstructions. Because of this specificity, the right treatment can be applied to any type of lesion. Angioscopy permits to foresee endoluminal surgery technique.


The SMARxT Media Literacy Program: Improving Evidence-Based Prescribing among Medical Students.
Media literacy may help medical trainees optimize evidence-based decision-making. Many prescriptions written are not evidence-based, resulting in unnecessary morbidity and mortality. In this study, we aimed to assess feasibility, acceptability, and initial efficacy of a media literacy prescribing program. We recruited 30 medical students, who completed animated video modules about pharmaceutical marketing and prescribing. We used a process evaluation and open-ended items to assess feasibility and acceptability, and knowledge tests before and after the intervention to assess efficacy. The program was feasible to implement and well-accepted by participants. After the educational intervention, knowledge and attitude targets around evidence-based prescribing and drug marketing improved.


Diagnosis of flea allergy dermatitis: comparison of intradermal testing with flea allergens and a FcepsilonRI alpha-based IgE assay in response to flea control.
The objective of this study was to evaluate the accuracy of in vivo and in vitro tests in the diagnosis of flea allergy dermatitis in comparison with history, clinical signs and response to flea control. Intradermal testing using four different sources of flea allergens and FcepsilonRIalpha-based immunoglobulin (Ig)E assays were performed in 15 flea-allergic dogs, 15 atopic dogs and 15 dogs infested with fleas but showing no clinical signs of skin disease. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were calculated for all five tests and results varied greatly. Sensitivity, specificity and overall accuracy were 27, 83 and 64%, respectively, for one extract (Isotec), 67, 90 and 82% for another extract (Greer), 93, 90 and 91% for flea saliva, 40, 90 and 73% for the recombinant Cte f 1 both produced by Heska Corp. and 87, 53 and 64% for a FcepsilonRIalpha-based IgE assay. These results indicate that intradermal testing with flea extracts is more accurate in the diagnosis of flea allergy dermatitis than in vitro tests. Moreover, pure flea saliva used as a reagent for intradermal testing provided the best results in terms of sensitivity, specificity and overall accuracy although the Greer extract, a whole body flea extract, also allowed a good correlation between intradermal testing results and clinical approach to flea allergy dermatitis diagnosis.


Mobilization of intracellular copper stores by the ctr2 vacuolar copper transporter.
Copper plays an essential role in processes including signaling to the transcription and protein trafficking machinery, oxidative phosphorylation, iron mobilization, neuropeptide maturation, and normal development. Whereas much is known about intracellular mobilization of ions such as calcium, little information is available on how eukaryotic cells mobilize intracellular copper stores. We describe a mechanism by which the Saccharomyces cerevisiae Ctr2 protein provides bioavailable copper via mobilization of intracellular copper stores. Whereas Ctr2 exhibits structural similarity to the Ctr1 plasma membrane copper importer, microscopic and biochemical fractionation studies localize Ctr2 to the vacuole membrane. We demonstrate that Ctr2 mobilizes vacuolar copper stores in a manner dependent on amino acid residues conserved between the Ctr1 and Ctr2 copper transport family and that ctr2 Delta mutants hyper-accumulate vacuolar copper. Furthermore, a Ctr2 mutant that is mislocalized to the plasma membrane stimulates extracellular copper uptake, supporting a direct role for Ctr2 in copper transport across membranes. These studies identify a novel mechanism for copper mobilization and suggest that organisms cope with copper deprivation via the use of intracellular vesicular stores.


Post-translational modification of host proteins in pathogen-triggered defence signalling in plants.
Microbial plant pathogens impose a continuous threat to global food production. Similar to animals, an innate immune system allows plants to recognize pathogens and swiftly activate defence. To activate a rapid response, receptor-mediated pathogen perception and subsequent downstream signalling depends on post-translational modification (PTM) of components essential for defence signalling. We discuss different types of PTMs that play a role in mounting plant immunity, which include phosphorylation, glycosylation, ubiquitination, sumoylation, nitrosylation, myristoylation, palmitoylation and glycosylphosphatidylinositol (GPI)-anchoring. PTMs are rapid, reversible, controlled and highly specific, and provide a tool to regulate protein stability, activity and localization. Here, we give an overview of PTMs that modify components essential for defence signalling at the site of signal perception, during secondary messenger production and during signalling in the cytoplasm. In addition, we discuss effectors from pathogens that suppress plant defence responses by interfering with host PTMs.


Molecular Cloning of NELIN, a Putative Human Cytoskeleton Regulation Gene.
For searching cardiovascular-associated genes and investigating their expression profiles, human adult heart and aorta cDNA libraries were constructed, and a novel gene from adult heart cDNA library was isolated based on large-scale ESTs(expressed sequence tags) sequencing(GenBank accession number AF114264). The 2 736 bp clone contains one 1 344 bp open reading frame extending from 412 to 1 755. We named it NELIN (nexilin-like protein) because it shares high similarity with the rat nexilin. NELIN was expression-restricted in heart, skeletalmuscle, artery and vein by Northern blot and RT-PCR analyses, and mapped to chromosome 1p31-1p32 by database analyses. Based on domain structure, NELIN could regulate the formations of stress fibers,focal adhesion and its signaling complex, and even participates in the signal transduction in FAs(focal adhesions).


The sweating responses of athletes trained on land and in water.
In order to examine whether different sweating responses of athletes trained on land and in water may be ascribed to changes in the central sudomotor mechanisms and/or those of the peripheral mechanisms of sweat glands, we measured the local sweating rate at the left forearm (mswf) and the left scapula (msws), the frequence of sweat expulsion (Fsw) and body temperatures (mean skin temperature and rectal temperature: Tre) in six runners and five soccer players (R group) and six swimmers (S group) during progressive thermal stress at rest (2 degrees C increase in ambient temperature every 15 min from 35 to 45 degrees C RH = 30-40%). Tre and heart rate at the end of experiment did not differ significantly between the groups (37.31 +/- 0.04 degrees C, 74.5 +/- 7.9 beats.min-1 in the S group and 37.27 +/- 0.07 degrees C, 71.1 +/- 9.0 beats.min-1 in the R group, respectively). The msws and mswf at any given mean body temperature (Tb) were greater in the S group than in the R group. Although the regression line showing the relationship between Fsw and Tb in the S group was shifted to the left of that in the R group, there was no significant difference in the slope of the lines. The msws-Fsw or mswf-Fsw regression line was not different between the two groups. These results indicate that the higher sweating rate in the S group may be ascribed to a difference in the centrally derived sudomotor neural activity, but not to that in the peripheral mechanisms of sweat gland activity.


[Umbilicus metastasis in patients with epithelial ovarian cancer : clinical features of 21 patients].
To analyze the clinical features, treatments and prognosis of patients with Sister Mary Joseph's nodule of umbilicus (SMJN) from epithelial ovarian cancer (EOC) patients. Among a total of 2642 pathologically diagnosed EOC cases, 21 cases with SMJN were histopathologically diagnosed and had an age range of 40-66 years at Sun Yat-sen University Cancer Center between January 1991 and January 2011. Their clinical data were retrospectively analyzed. The incidence of SMJN in EOC was 0.79 %. The 1, 2 and 5-year survival rates were 61.8%, 26.8% and 9.5% respectively. The diagnosis was confirmed via local excision biopsy, fine-needle aspiration biopsy or gross pathological diagnosis. Univariate analysis showed that patients with progressive disease or relapsing with umbilical metastasis after treatment had worse prognosis than those diagnosed at pre-treatment (22 vs 6 months, P < 0.01) . Patients with suboptimal cytoreductive surgery and/or less than 6 circles of chemotherapy or palliative treatment had worse prognosis than those with optional cytoreductive surgery during 6-8 circles of chemotherapy (21 vs. 4 months). Multivariate analysis showed that the time to diagnose and treatment regimen were independent predictors of survival (relative risk = 41.28, P < 0.01). SMJN is a rare manifestation of EOC. Improving the diagnostic vigilance, optimal debulking surgery plus regular chemotherapy and other new individualized postoperative treatments may arrest the progression of EOC and prolong patient survival.


Direct and indirect effects of regional and local climatic factors on trophic interactions in the Arctic tundra.
Climate change can impact ecosystems by reshaping the dynamics of resource exploitation for predators and their prey. Alterations of these pathways could be especially intense in ecosystems characterized by a simple trophic structure and rapid warming trends, such as in the Arctic. However, quantifying the multiple direct and indirect pathways through which climate change is likely to alter trophic interactions and their relative strength remains a challenge. Here, we aim to identify direct and indirect causal mechanisms driven by climate affecting predator-prey interactions of species sharing a tundra food web. We based our study on relationships between one Arctic predator (Arctic fox) and its two main prey - lemmings (preferred prey) and snow geese (alternate prey) - which are exposed to variable local and regional climatic factors across years. We used a combination of models mapping multiple causal links among key variables derived from a long-term dataset (21 years). We obtained several possible scenarios linking regional climate factors (Arctic oscillations) and local temperature and precipitation to the breeding of species. Our results suggest that both regional and local climate factors have direct and indirect impacts on the breeding of foxes and geese. Local climate showed a positive causal link with goose nesting success, while both regional and local climate displayed contrasted effects on the proportion of fox breeding. We found no impact of climate on lemming abundance. We observed positive relationships between lemming, fox and goose reproduction highlighting numerical and functional responses of fox to the variability of lemming abundance. Our study measures causal links and strength of interactions in a food web, quantifying both numerical response of a predator and apparent interactions between its two main prey. These results improve our understanding of the complex effects of climate on predator-prey interactions and our capacity to anticipate food web response to ongoing climate change.


A valuable improvement of adult height prediction methods in short normal children.
The potential benefit of growth hormone (GH) administration to increase adult height of normal children of short stature might be blurred by the accuracy and the precision of the prediction methods used to estimate final height before onset of therapy. The aim of the present study was to evaluate three prediction methods: Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT) and Tanner-Whitehouse Mark II (TW2) and to improve their accuracy and precision by exploring their correlation with various parameters obtained in peripubertal children with poor predicted adult height. Accuracy and precision of the prediction methods were evaluated retrospectively by comparing predicted adult heights estimated in 62 boys at 13.7 +/- 0.9 years and in 28 girls at 12.1 +/- 0.9 years of age, with their adult heights measured respectively at 20.7 +/- 2.6 years and 18.8 +/- 2.8 years. At the time of prediction, the height for chronological age was -2.07 +/- 0.68 standard deviation scores for boys and -2.15 +/- 0.6 years for girls. Measured adult heights were significantly lower than target heights (165.1 +/- 5.1 vs. 169.4 +/- 4.8 cm for boys; p < 0.001 and 153.1 +/- 3.9 vs. 156.3 +/- 5.0 cm for girls; p = 0.001). For boys, the BP method was the most accurate and also the most convenient with a predicted adult height of 164.7 +/- 5.0 cm and a small underestimation of 0.4 +/- 3.5 cm. For girls, the TW2 method was the most accurate with a predicted height of 152.4 +/- 3.7 cm with a little underestimation of 0.7 +/- 3.5 cm. There were no important differences between the precision of these methods. The use of a correction factor derived from the bone age delay at the time of prediction in boys and from the chronological age at the time of prediction in girls improved the accuracy of the predicted adult height. The use of a factor correcting the accuracy of the BP method in boys and of the TW2 method in girls should be valuable in assessing the potential benefit of GH therapy to increase adult height in short normal children.


Human placental hydrolysate promotes the long-term culture of hepatocyte-like cells derived from canine bone marrow.
Long-term culture of canine artificial hepatocytes has not been established. We hypothesized that human placental hydrolysate (hPH) may support the long-term culture of differentiated hepatocyte-like cells. Canine bone marrow cells were cultured using modified hepatocyte growth medium supplemented with hPH. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical analysis for albumin, qualitative RT-PCR for cytochrome P450 1A1 (CYP1A1), hepatocyte growth factor (HGF), Cytokeratin 7 (CK7), CD90, CD44, and CD34, and functional analyses of CYP450 activity and low-density lipoprotein (LDL) uptake were performed. Cultured hepatocyte-like cells were able to maintain hepatocyte characteristics, including morphology, albumin synthesis, CYP450 activity, and LDL uptake for 80 days. Thus, hPH may be a potential facilitator for the long-term culture of hepatocyte-like cells. Clinicopathologically, this culture protocol of artificial hepatocytes will contribute to liver function evaluation.


The role of astragaloside in regeneration of the peripheral nerve system.
The aim of this study was to evaluate peripheral nerve regeneration across a 15-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve guide filled with different concentrations of astragaloside (0, 50, 100, and 200 microM). Collagen was also filled in the chambers to prevent the astragaloside from leakage. At the end of 8 weeks, animals from the group treated with astragaloside, especially at the concentration of 50 microM, had a higher rate of successful regeneration across the wide gap, a significantly larger number of myelinated axons, and a greater evoked action potential than the control group. However, the high-dose astragaloside (200 microM) completely reversed this positive effect of growth-promoting capability and inhibited nerve regeneration. Thus, astragaloside plays a dual role in anastomosis, being salutary in aiding the growth of axons in peripheral nerve but also detrimental, terminating the nerve regenerative processes if improperly applied.


Elimination of the lag period in chloroplast development in a chlorophyll mutant of peanuts.
The mutation of a nuclear gene in peanut (Arachis hypogaea L.) plants results in a reduced light-dependent development of chloroplast fine structure, soluble protein, ribulose-1, 5-diP carboxylase, NADP-glyceraldehyde-3-P dehydrogenase, fructose-1, 6-diP aldolase, glycerate-3-P kinase, phosphoenolpyruvate carboxylase, malate dehydrogenase, and dark respiration during the 72-hour lag period of chlorophyll synthesis in dark-grown leaves exposed to continuous light. The mutation has pleiotropic affects. Kinetic analysis shows there is also a 72-hour lag period in the light-dependent development of NADP-glyceraldehyde-3-P dehydrogenase and fructose-1, 6-diP aldolase in the mutant leaves, whereas there is no lag in the development of NAD-malate dehydrogenase and dark respiration. There is minimal development of the chloroplast during the 72-hour mutationally induced lag period, but there is pronounced cytoplasmic and mitochondrial activity during this phase. There is a 24-hour lag period in the light-dependent enlargement of the mutant leaves. At the completion of leaf enlargement, chloroplast differentiation is initiated. The mutation does not result in any chloroplast deletions, it only affects the timing of the synthesis of these components.Elimination of the lag period in leaf enlargement and chloroplast development (potentiation) requires a preliminary 72- to 96-hour dark period before exposing the dark-grown leaves to continuous light. There is extensive development of the etioplasts during this dark period. These results establish that the nuclear gene mutation affects the early stages of plastid development and not the light-dependent synthesis of plastid components. The nuclear gene may code for the regulation of the synthesis of a component (nutrient) in the dark (or during the lag phase in the light) which is essential for the development of mesophyll cells and plastids. Although, the chloroplast is a semi-autonomous organelle, nuclear gene control of chloroplast differentiation may not be independent of cellular growth.


[Early use of gemfibrozil in patients with non ST Elevation acute coronary syndrome. Changes of markers of inflammation and von Willebrand factor].
It is not known whether PPAR-alpha agonist gemfibrozil is able to exert rapidly its lipid modulating, potential antiinflammatory and antithrombotic effects in patients with non-ST elevation acute coronary syndrome (NSTEACS), as some other lipid lowering drugs e.g. statins do. We randomized 44 patients with NSTEACS to open gemfibrozil (n=22, 600 mg b.i.d for 90 days) or no gemfibrozil (controls, n=22) within 24 hours after pain onset. Semiquantitative C-reactive protein (CRP) latex test was used at baseline for exclusion of patients with overt inflammation. All patients received dalteparin or enoxaparin for >48 hours and oral aspirin (125 mg/day) and were treated noninvasively. Lipids, high sensitive CRP, soluble CD40 ligand (CD40L) and von Willebrand factor (vWF) activity were assessed on days 1 (baseline), 4, 7, 14, 30 and (except CD40L) 90. Gemfibrozil use was associated with significant lowering of triglycerides by day 30, however it did not prevent acute significant decline of high density lipoprotein cholesterol (HDL-C), which was similar in both groups. CD40L level significantly increased while CRP levels decreased by day 30 in both groups. Moreover, selection of a subgroup with baseline HDL-C <1.0 mmol/l did not reveal any difference in changes of CRP or CD40L between gemfibrosil treated and control patients. vWF activity did not change in controls and significantly increased in gemfibrozil group by days 7, 14, but from lower baseline level. In patients with NSTEACS early administration of gemfibrozil was not associated with positive changes of CRP and CD40L levels or vWF activity compared with control group.


Physical activity in young adults with autism spectrum disorder: Parental perceptions of barriers and facilitators.
The importance of physical activity in persons with disabilities is well known, yet the prevalence of inactivity remains high. The physical activity behaviors among adults on the autism spectrum are largely unexplored. It is presumed that sedentary behavior and obesity are a greater health issue among young adults on the autism spectrum who no longer receive Individuals with Disabilities Education Act services and supports such as school-based physical education. Using a phenomenology approach, the parents of eight young adults on the autism spectrum were interviewed about their perceptions of the barriers and facilitators to getting their young adults on the autism spectrum physically active. The purpose of this study was to investigate parent's perspective of physical activity barriers and facilitators of their adult children on the autism spectrum. Common themes of both physical activity barriers and facilitators included parents, behaviors associated with autism spectrum disorder, and access and opportunities.