Effects of grass jelly on glycemic control: hydrocolloids may inhibit gut carbohydrase.
The aim of this study was to investigate (1) the hydrocolloid properties of grass jelly on reducing glycaemic response, (2) the impact of phenolic compounds in Mesona chinensis L. on glycaemic response. A total of 15 healthy Chinese men were recruited to this study. On each visit, subjects consumed one of the following three treatments, i.e. glucose solution (T1), grass jelly (Mesona chinensis L.) solution with glucose (T2) or grass jelly gel with glucose (T3). Capillary blood glucose and venous plasma insulin were analysed over a period of 180 min. The incremental area under the curve for capillary glucose and venous plasma insulin for glucose group, grass jelly solution group and grass jelly gel was found to be statistically not significant (p>0.05). In a previous study the co-ingestion of grass jelly with complex carbohydrate was found to reduce glycaemic response. The key difference between the two studies was the use of monosaccharide glucose in the present study, compared to complex carbohydrates in the other. The present study suggests that the glycaemic lowering effect of grass jelly may be dependent on the inhibition of carbohydrase enzymes. The co-ingestion of Mesona chinensis L. appears to reduce glycaemic response of only complex carbohydrates through the inhibition of carbohydrase. This conclusion was arrived at by the lack of any effect of Mesona chinensis L. on the monosaccharide glucose.


[Investigation of the Interaction between 1,3-Dimethylurea and Solvent by Raman Methods].
Urea family plays significant role in the bio-science area. Because of the unique frame, they can form Hydrogen bond with water as well as other substance. Hydrogen bonds are normal weak interactions in the system of bio-molecules. A Raman spectrum is the most powerful method to obscure the Hydrogen bond interaction between molecules. Initially, we measure the Raman spectra of DMU crystal, and then use density function theory with a B3LYP/6-311G* * basis set to optimize the geometry structure and calculate the vibrational frequency of gas phase DMU, which assigns the Raman pecks. Then, measure the solvent. When dissolving DMU in water, the interaction between DMU-DMU will replaced by the interaction between water-DMU. The orbital hybridization of nitrogen atoms changes from the solid-state the sp' orbital hybridization to sp3. So, the frame of this molecule goes from in-planet to out of plant during this process.


The Complement System in Flavivirus Infections.
The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses.


beta-Adrenoreceptors reactivate Kaposi's sarcoma-associated herpesvirus lytic replication via PKA-dependent control of viral RTA.
Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication is mediated by the viral RTA transcription factor, but little is known about the physiological processes controlling its expression or activity. Links between autonomic nervous system activity and AIDS-associated Kaposi's sarcoma led us to examine the potential influence of catecholamine neurotransmitters. Physiological concentrations of epinephrine and norepinephrine efficiently reactivated lytic replication of KSHV in latently infected primary effusion lymphoma cells via beta-adrenergic activation of the cellular cyclic AMP/protein kinase A (PKA) signaling pathway. Effects were blocked by PKA antagonists and mimicked by pharmacological and physiological PKA activators (prostaglandin E2 and histamine) or overexpression of the PKA catalytic subunit. PKA up-regulated RTA gene expression, enhanced activity of the RTA promoter, and posttranslationally enhanced RTA's trans-activating capacity for its own promoter and heterologous lytic promoters (e.g., the viral PAN gene). Mutation of predicted phosphorylation targets at RTA serines 525 and 526 inhibited PKA-mediated enhancement of RTA trans-activating capacity. Given the high catecholamine levels at sites of KSHV latency such as the vasculature and lymphoid organs, these data suggest that beta-adrenergic control of RTA might constitute a significant physiological regulator of KSHV lytic replication. These findings also suggest novel therapeutic strategies for controlling the activity of this oncogenic gammaherpesvirus in vivo.


Neuroendocrine neoplasms of the mediastinum.
Neuroendocrine neoplasms of the mediastinum form part of a family of tumors characterized by genotypic, immunophenotypic, and functional properties of neuroendocrine differentiation. Although rare, these tumors have been the source of much attention and controversy in the literature. Their nomenclature and classification, in particular, have continued to evolve over the years. Such tumors comprise lesions derived from neuroendocrine elements within the thymus, from paraganglionic rests, or from misplaced embryonal structures within the mediastinum. The most common neuroendocrine neoplasms of this anatomic region, however, correspond to neuroendocrine carcinomas of the thymus. The light microscopic, immunohistochemical, and ultrastructural features of these tumors are reviewed along with the advances in our understanding of these lesions and current trends in nomenclature and terminology.


Effects of histamine precursor and (R)-alpha-methylhistamine on the avoidance response in rats.
The aim of this work is to clarify the role of histamine in learning and memory processes. In order to do this, the effect of administration of the histamine precursor, L-histidine (HIS) and of the agonist of the H(3) receptor, (R)-alpha-methylhistamine (RAMH), on active avoidance response in rats is studied. Treatment with RAMH (10 mg/kg i.p.) increased the number of avoidance responses produced during acquisition and retention of the learning. In contrast, administration of L-his (500 mg/kg i.p.) impairs performance in the shuttle-box. These results are consistent with a role for histamine in cognitive processes and suggest that a increase in cerebral histamine levels impair the acquisition of avoidance response, whereas reduced levels facilitate this acquisition.


Evaluation of the Venom Ex apparatus in the treatment of Egyptian cobra envenomation. A study in rabbits.
The Venom Ex cutting and suction apparatus for the initial treatment of snakebite was evaluated. Rabbits were injected with radioactive Egyptian cobra venom, and treatment with the Venom Ex followed. The fluid obtained by suction was analysed. All 8 control animals died within 4 hours; Venom Ex treatment resulted in the recovery of 7 out of 8 rabbits, after double the lethal dose of venom, providing treatment was started early. However, if treatment was delayed or if the dose of venom was high, there was a marked increase in the mortality. The amount of venom extracted was insufficient to account for the recovery of the animals. In one group of rabbits trauma was applied to the injection site without lacerating the skin and without removal of venom. About half of these animals recovered. However, this was less efficient than the Venom Ex treatment. Trauma apparently retards absorption of venom and increases survival. The possible reasons for this novel finding are discussed.


EEG based image encryption via quantum walks.
An electroencephalogram (EEG) based image encryption combined with Quantum walks (QW) is encoded in Fresnel domain. The computational version of EEG randomizes the original plaintext whereas QW can serve as an excellent key generator due to its inherent nonlinear chaotic dynamic behavior. First, a spatially coherent monochromatic laser beam passes through an SLM, which introduces an arbitrary EEG phase-only mask. The modified beam is collected by a CCD. Further, the intensity is multiply with the QW digitally. EEG shows high sensitivity to system parameters and capable of encrypting and transmitting the data whereas QW has unpredictability, stability and non-periodicity. Only applying the correct keys, the original image can be retrieved successfully. Simulations and comparisons show the proposed method to be secure enough for image encryption and outperforms prior works. The proposed method opens the door towards introducing EEG and quantum computation into image encryption and promotes the convergence between our approach and image processing.


[Influence of maternal weight on pregnancy outcome in Cotonou (Benin)].
To evaluate prevalence of obesity in pregnant women in Cotonou and to study the influence of obesity on pregnancy outcome, we analysed retrospectively obstetrical reports of 323 women delivered at the university clinic of gynecology and obstetrics during the year 1999. Prevalence of obesity was 18% among pregnant women and 30.6% of them were overweight. Medical complications of pregnancy were more frequent in obese women than in women with normal weight since obese women showed higher frequency of proteinuria (241% versus 10,5%, p<0.05) and high blood pressure (25.9% versus 4.5%, p<0.001). Diabetes mellitus was only present in obese women with a frequency of 5,2%. Compared with normal weight women, the obese ones showed a tendency to higher frequency of cesarean delivery (34.5% versus 21%), this difference being not statistically significant. Although there was a slightly higher number of reanimated infants in obese women, the difference was not significant. Six percent hypotrophic infants were observed in obese mothers versus 13.1% in mothers with normal weight (non significant) but it can be noticed that lean mothers showed statistically higher frequency of hypotrophic infants than normal weight mothers (33.3% versus 13.1%, p<0.01). This study shows that obesity in women represents, even in developing country, an obstetrical risk factor leading to high frequency of complications during pregnancy and needs the development of preventive actions.


Ligand binding and functional selectivity of L-tryptophan metabolites at the mouse aryl hydrocarbon receptor (mAhR).
The aryl hydrocarbon receptor (AhR) is a nuclear receptor regulating a wide range of biological and toxicological effects. Metabolites of L-tryptophan are able to bind and activate AhR, providing a link between tryptophan catabolism and a novel mechanism of protective tolerance, referred to as "disease tolerance". The notion that pharmacologic modulation of genes associated with endotoxin tolerance would be beneficial in clinical settings dominated by acute hyperinflammatory responses to infection thrusts AhR into the limelight as an interesting druggable target. Combining homology modeling, docking studies, and molecular dynamic simulations with mutagenesis experiments and gene profiling, in this work we report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and two different L-tryptophan metabolites, namely L-Kynurenine and FICZ (6-formylindolo[3,2-b]carbazole), are able to bind to mAhR, exploiting different key interactions with distinct set of fingerprint residues. As a result, they stabilize different conformations of mAhR that, in turn, selectively regulate downstream signaling and transcription of specific target genes. Collectively, these results open new avenues for the design and development of selective AhR modulators that, by targeting specific receptor conformations associated with specific AhR functions, may offer novel therapeutic opportunities in infectious diseases and other morbidity that may be associated with the receptor.


Dopamine signaling tunes spatial pattern selectivity in C. elegans.
Animals with complex brains can discriminate the spatial arrangement of physical features in the environment. It is unknown whether such sensitivity to spatial patterns can be accomplished in simpler nervous systems that lack long-range sensory modalities such as vision and hearing. Here we show that the nematode Caenorhabditis elegans can discriminate spatial patterns in its surroundings, despite having a nervous system of only 302 neurons. This spatial pattern selectivity requires touch-dependent dopamine signaling, including the mechanosensory TRP-4 channel in dopaminergic neurons and the D2-like dopamine receptor DOP-3. We find that spatial pattern selectivity varies significantly among C. elegans wild isolates. Electrophysiological recordings show that natural variations in TRP-4 reduce the mechanosensitivity of dopaminergic neurons. Polymorphic substitutions in either TRP-4 or DOP-3 alter the selectivity of spatial patterns. Together, these results demonstrate an ancestral role for dopamine signaling in tuning spatial pattern preferences in a simple nervous system.


Genetic variation among Clonorchis sinensis isolates from different hosts and geographical locations revealed by sequence analysis of mitochondrial and ribosomal DNA regions.
The present study examined genetic variability among Clonorchis sinensis isolates from four different geographical localities (Guangzhou, Nanning, Jiamusi and Daqing) and host species (cats, dogs, human and rabbits) in Mainland China by sequence analyses of two mitochondrial DNA (mtDNA) genes, namely NADH dehydrogenase subunits 2, 5 (nad2 and nad5) and ribosomal internal transcribed spacer 1 (ITS1). A portion of the ITS1, nad2 (pnad2) and nad5 (pnad5) was amplified by polymerase chain reaction separately from adult C. sinensis individuals and the amplicons were subjected to sequencing from both directions. The length of the sequences of ITS1, pnad2 and pnad5 was 643, 666 and 771 bp, respectively. The intraspecific sequence variations within C. sinensis were 0-1.7% for ITS1, 0-1.4% for pnad2 and 0-0.9% for pnad5. The interspecific sequence variations within other zoonotic trematodes, which were published previously, were 4.5-84.9% for ITS1, 21.9-43.6% for pnad2 and 19.2-48.9% for pnad5. The A+T contents of the sequences were 45.26-45.88% (ITS1), 62.91-63.51% (pnad2) and 58.24-58.63% (pnad5). Phylogenetic analyses using ribosomal and mitochondrial sequence data set, with three different computational algorithms (Bayesian inference, maximum parsimony and maximum likelihood), all revealed distinct groups with high statistical support. These findings demonstrated the existence of low-level intraspecific variations in ribosomal DNA (rDNA) and mtDNA sequences among C. sinensis isolates from four different regions and hosts in China and elucidated that mtDNA sequences and rDNA sequences provided reliable genetic markers for phylogenetic studies of zoonotic trematodes.


The maize α-zein promoter can be utilized as a strong inducer of cellulase enzyme expression in maize kernels.
Expression of recombinant proteins in plants is a technology for producing vaccines, pharmaceuticals and industrial enzymes. For the past several years, we have produced recombinant proteins in maize kernels using only the embryo, primarily driving expression of foreign genes with the maize globulin-1 promoter. Although strong expression is obtained, these lines use only 10-12% of the seed tissue. If strong embryo expression could be combined with strong endosperm expression, much more recombinant protein could be recovered from a set amount of seed biomass. In this study, we tested three endosperm promoters for expression of a cellulase gene. Promoters tested were rice globulin and glutelin promoters and a maize 19 kDa α-zein promoter. The rice promoters were used in two tandem expression constructs as well. Although the rice promoters were active in producing stable amounts of cellulase, the α-zein promoter was by far the most effective: as much as 9% of total soluble protein was recovered from seed of several independent events and plants. One or two inserts were detected by Southern blot in several lines, indicating that copy number did not appear to be responsible for the differences in protein accumulation. Tissue print analysis indicated that expression was primarily in the endosperm.


The use of primed synthesis by DNA polymerase I to study an intercistronic sequence of phiX-174 DNA.
A decadeoxynucleotide complementary to ten nucleotides in the major ribosome-protected fragment of phiX-174 plus-strand DNA has been chemically synthesized and used as a primer for DNA polymerase I on phiX-174 plus-strand DNA as template. The sequence of the first 40 nucleotides incorporated onto the decadeoxynucleotide has been determined. This sequence extends further the sequence of the intercistronic region preceding gene G and shows the presence of another termination codon. The sequence was determined by using manganese as the activating cation for DNA polymerase I which allows ribonucleotides to be incorporated as well as deoxyribonucleotides. The ribo-substituted product was then cleaved specifically at the ribonucleotide residues to generate a series of overlapping ribo-terminated fragments whose sequences were sufficient to determine the complete sequence of the first 40 nucleotides. No evidence for misincorporation by DNA polymerase I in the presence of manganese was detected.


Conformational analysis of r(CGCGCG) in aqueous solution: an A-type double helical conformation studied by two-dimensional nuclear Overhauser effect spectroscopy.
The conformation of the hexanucleoside pentaphosphate r( CGCGCG ) in aqueous solution was studied by circular dichroism, 1H- and 31P-NMR spectroscopy. The base-, H1'- and H2'-proton resonances were assigned by means of 2D-NOE spectroscopy. The base- and H1'-proton chemical shifts were studied as a function of temperature. Proton-proton distances are computed in A- and A'-RNA as well as in A-, B- and Z-DNA. A qualitative interpretation of the observed 2D-NOE intensities shows that r( CGCGCG ) adopts a regular A-type double helical conformation under our experimental conditions. The CD- and 31P-NMR experiments described in this paper are in agreement with this structure both under low- and high-salt conditions.


Anasarca, Fever, Thrombocytopenia, Organomegaly, and Multiorgan Failure in a 24-Year-Old Pregnant Woman.
TAFRO syndrome is a distinct idiopathic multicentric Castleman disease characterized by the association of thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We report the first case occurring in a Caucasian pregnant woman. At 34 weeks of gestation, our patient presented with all clinical and biological symptoms compatible with a TAFRO syndrome. Tough quick cesarean section was performed as symptoms got worse with onset of multiorgan failure requiring mechanical ventilation for acute respiratory distress, continuous renal replacement, and vasopressors. Nine days after ICU admission, steroid boluses were started and allowed spectacular clinical and biological improvement. As systemic inflammatory manifestations are important, TAFRO syndrome can be mistaken with severe autoimmune diseases, systemic infections, hematological malignancies, or hemophagocytic lymphohistiocytosis.


Structure of human des(1-45) factor Xa at 2.2 A resolution.
The structure of a large molecular fragment of factor Xa that lacks only a Gla (gamma-carboxyglutamic acid) domain (N-terminal 45 residues) has been solved by X-ray crystallography and refined at 2.2 A resolution to a crystallographic R-value of 0.168. The fragment identity was clearly established by automated Edman degradation. X-ray structure analysis confirmed the biochemical characterization and also revealed that the N-terminal epidermal growth factor (EGF)-like domain is flexibly disordered in crystals. The second EGF module, however, is positionally ordered making contacts with the catalytic domain. The overall folding of the catalytic domain is similar to that of alpha-thrombin, excluding the insertion loops of the latter with respect to simpler serine proteinases. The C-terminal arginine of the A-chain interacts in a substrate-like manner with the S1 specificity site of the active site of a crystallographically neighboring molecule. Based on this interaction and the structure of D-PheProArg methylene-thrombin, a model of the commonly used dansylGluGlyArg methylene inhibitor-factor Xa interaction is proposed. The region of factor Xa corresponding to the fibrinogen recognition site of thrombin has a reversed electrical polarity to the anion binding fibrinogen recognition site of thrombin but possesses a site similar to the Ca2+ binding site of trypsin and other serine proteinases. The structure of the C-terminal EGF domain of factor Xa is the first to be determined crystallographically. Its folding has been comprehensively compared with similar domains determined by NMR. Although the A-chain makes 44 contacts at less than 3.5 A with the catalytic domain, only 16 involve the EGF module. In addition, the A-chain makes 30 intermolecular contacts with a neighboring catalytic domain.


Adhesion-Induced Discontinuous Transitions and Classifying Social Networks.
Transition points mark qualitative changes in the macroscopic properties of large complex systems. Explosive transitions, exhibiting properties of both continuous and discontinuous phase transitions, have recently been uncovered in network growth processes. Real networks not only grow but often also restructure; yet common network restructuring processes, such as small world rewiring, do not exhibit phase transitions. Here, we uncover a class of intrinsically discontinuous transitions emerging in network restructuring processes controlled by adhesion-the preference of a chosen link to remain connected to its end node. Deriving a master equation for the temporal network evolution and working out an analytic solution, we identify genuinely discontinuous transitions in nongrowing networks, separating qualitatively distinct phases with monotonic and with peaked degree distributions. Intriguingly, our analysis of empirical data indicates a separation between the same two forms of degree distributions distinguishing abstract from face-to-face social networks.


Transthoracic resection versus non-transthoracic resection for gastroesophageal junction cancer: a meta-analysis.
The aim of this meta-analysis is to evaluate the impact of transthoracic resection on long-term survival of patients with GEJ cancer and to compare the postoperative morbidity and mortality of patients undergoing transthoracic resection with those of patients who were not undergoing transthoracic resection. Searches of electronic databases identifying studies from Medline, Cochrane Library trials register, and WHO Trial Registration etc were performed. Outcome measures were survival, postoperative morbidity and mortality, and operation related events. Twelve studies (including 5 RCTs and 7 non-RCTs) comprising 1105 patients were included in this meta-analysis, with 591 patients assigned treatment with transthoracic resection. Transthoracic resection did not increase the 5-y overall survival rate for RCTs and non-RCTs (HR = 1.01, 95% CI 0.80- 1.29 and HR = 0.89, 95% CI 0.70- 1.14, respectively). Stratified by the Siewert classification, our result showed no obvious differences were observed between the group with transthoracic resection and group without transthoracic resection (P>0.05). The postoperative morbidity (RR = 0.69, 95% CI 0.48- 1.00 and OR = 0.55, 95% CI 0.25- 1.22) and mortality (RD = -0.03, 95% CI -0.06- 0.00 and RD = 0.00, 95% CI -0.05- 0.05) of RCTs and non-RCTs did not suggest any significant differences between the two groups. Hospital stay was long with thransthoracic resection (WMD = -5.80, 95% CI -10.38- -1.23) but did not seem to differ in number of harvested lymph nodes, operation time, blood loss, numbers of patients needing transfusion, and reoperation rate. The results of sensitivity analyses were similar to the primary analyses. There were no significant differences of survival rate and postoperative morbidity and mortality between transthoracic resection group and non-transthoracic resection group. Both surgical approaches are acceptable, and that one offers no clear advantage over the other. However, the results should be interpreted cautiously since the qualities of included studies were suboptimal.


Trait-Emotional Intelligence and the Tendency to Emotionally Manipulate Others Among Grandiose and Vulnerable Narcissists.
This study builds on previous findings regarding emotional intelligence among narcissists by considering the maladaptive aspects of emotional manipulation and distinguishing between grandiose and vulnerable narcissism. Trait-emotional intelligence and emotional manipulation capabilities of grandiose narcissists, vulnerable narcissists, and non-narcissists were compared. A convenience sample of 584 undergraduates from the University of Florence (Italy) with a mean age of 22.61 (SD = 2.19) was recruited. A two-way ANOVA showed that vulnerable narcissists scored significantly lower than grandiose narcissists and non-narcissists in all the Bar-On EI dimensions, while grandiose narcissists scored higher than non-narcissists in Intrapersonal intelligence and the General Mood Bar-On scales. The two-way ANOVA also showed that both grandiose and vulnerable narcissists are prone to emotionally manipulate others in order to reach their aims.


Cyclooxygenase-2 inhibition and gastric cancer.
Epidemiological evidences suggest that chronic use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) might be associated with a reduced risk of gastrointestinal cancers, including gastric cancer. The pre-cancerous gastric lesions and gastric cancers over-expressed cyclooxygenase (COX)-2. This overexpression not only is associated with Helicobacter pylori infection, but also maybe due to exposure to carcinogens. Targeted inhibition of COX, especially the COX-2 isoform, can lead to growth inhibition and apoptosis of gastric cancer in vitro. Various mechanisms, including COX-dependent and COX-independent pathways, have been identified and will be discussed in this article. Animal xenograft models have confirmed the tumor suppressing effects of COX-2 inhibitors. Human studies are underway to examine the use of COX-2 inhibitor in the treatment of pre-cancerous lesions. COX-2 inhibitors have a promising role in the prevention and treatment of gastric cancer.


Treatment of epidemic Kaposi's sarcoma with a combination of interferon-alpha 2b and etoposide.
A prospective clinical trial of concomitant interferon-alpha 2b and etoposide was conducted in 24 previously untreated patients with epidemic Kaposi's sarcoma. Eight of 21 evaluable patients (38%) achieved either a complete response (1 patient) or a partial response (7 patients). None of the responders had a prior history of opportunistic infection. Hematologic toxicity was severe, and 8 patients developed an opportunistic infection. The combination of interferon-alpha 2b and etoposide has modest activity, but no additive or synergistic activity was evident in the dose and schedule utilized in this study. The exact role for interferon-alpha in epidemic Kaposi's sarcoma, both as a single agent and in combinations, remains to be determined.


Visualization of Lymph Nodal and Hepatic Metastases of Medullary Thyroid Carcinoma on 18F-Fluoride PET/CT.
F-fluoride uptake in soft tissue metastases has been previously described. Herein, we report a case of F-fluoride uptake in lymph nodal and hepatic metastases of medullary thyroid carcinoma. Simultaneous CT showed calcified lesions in these regions.


Distinct Neisseria gonorrhoeae transmission networks among men who have sex with men in Amsterdam, The Netherlands.
Molecular typing was used to elucidate Neisseria gonorrhoeae transmission networks among men who have sex with men (MSM) in Amsterdam, the Netherlands. We determined whether clusters of patients infected with specific N. gonorrhoeae genotypes were related to various epidemiological characteristics. MSM (age ≥18 years) visiting the sexually transmitted infections (STI) clinic between July 2008 and August 2009 were eligible. After STI screening, participants completed a behavioral questionnaire concerning the previous 6 months. N. gonorrhoeae cultures were genotyped using multiple-locus variable-number tandem repeat analysis typing. We obtained 278 N. gonorrhoeae-positive isolates from 240 MSM. Five large clusters (≥10 isolates), a unique sixth cluster (n = 9), and 8 smaller clusters (5-9 isolates) were identified. Prevalence of human immunodeficiency virus differed between clusters I and VI (P = .003), ranging from 27.8% to 100%. Receptive unprotected anal intercourse was frequently reported by MSM (51.8%) but did not differ significantly among clusters. Significant differences were identified concerning the participant's history of syphilis (P = .030), having met partners at a popular sex venue in Amsterdam (P = .048), and meeting partners outside Amsterdam (P = .036). Distinct N. gonorrhoeae transmission networks were present in a mixed high-risk MSM population; concordance between clusters and epidemiological characteristics was present but not marked.


Reducing the societal burden of depression: a review of economic costs, quality of care and effects of treatment.
Depression is a highly prevalent condition that results in substantial functional impairment. Advocates have attempted in recent years to make the 'business case' for investing in quality improvement efforts in depression care, particularly in primary care settings. The business case suggests that the costs of depression treatment may be offset by gains in worker productivity and/or reductions in other healthcare spending. In this paper, we review the evidence in support of this argument for improving the quality of depression treatment. We examined the impact of depression on two of the primary drivers of the societal burden of depression: healthcare utilisation and worker productivity. Depression leads to higher healthcare utilisation and spending, most of which is not the result of depression treatment costs. Depression is also a leading cause of absenteeism and reduced productivity at work. It is clear that the economic burden of depression is substantial; however, critical gaps in the literature remain and need to be addressed. For instance, we do not know the economic burden of untreated and/or inappropriately treated versus appropriately treated depression. There remain considerable problems with access to and quality of depression treatment. Progress has been made in terms of access to care, but quality of care is seldom consistent with national treatment guidelines. A wide range of effective treatments and care programmes for depression are available, yet rigorously tested clinical models to improve depression care have not been widely adopted by healthcare systems. Barriers to improving depression care exist at the patient, healthcare provider, practice, plan and purchaser levels, and may be both economic and non-economic. Studies evaluating interventions to improve the quality of depression treatment have found that the cost per QALY associated with improved depression care ranges from a low of 2519 US dollars to a high of 49,500 US dollars. We conclude from our review of the literature that effective treatment of depression is cost effective, but that evidence of a medical or productivity cost offset for depression treatment remains equivocal, and this points to the need for further research in this area.


Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis.
Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.


Endogenous bioelectric fields: a putative regulator of wound repair and regeneration in the central nervous system.
Studies on a variety of highly regenerative tissues, including the central nervous system (CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric fields (EF) that are 100-fold increased in intensity over that measured for uninjured tissue. In vitro and in vivo experiments have convincingly demonstrated that these electric fields (by their orientation, intensity and duration) can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Additionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.


Broadband SnS/Te photodetector to long-wavelength infrared: breaking the spectrum limit through alloy engineering.
Materials based on group IV chalcogenides, are considered to be one of the most promising materials for high-performance, broadband photodetectors due to their wide bandgap coverage, intriguing chemical bonding and excellent physical properties. However, the reported photodetectors based on SnS are still worked at relatively narrow near-infrared band (as far as 1550 nm) hampered by the nonnegligible bandgap of 1.1-1.5 eV. Here, a novel photodetector based on Te alloyed SnS thin film was demonstrated with an ultra-broadband response up to 10.6 µm. By controlling the Te alloyed concentration in SnS increasing to 37.64%, the bandgap narrows to 0.23 eV, exhibiting a photoresponse potential at long-wavelength infrared excitation. Our results show Te-alloying can remarkably enhance the detection properties of SnS/Te photodetectors. The photoresponsivity and detectivity of 1.59 mA/W and 2.3 × 108 Jones were realized at 10.6 µm at room temperature. Moreover, the nonzero photogain was observed generated by nonlinearly increased photocurrent density, resulting in a superlinear dependency between photoresponsivity and light intensity. Our studies successfully broaden photoresponse spectrum of SnS toward the mid-infrared range for the first time. It also suggests that alloying is an effective technique for tuning the band edges of group IV chalcogenides, contributing deep implications for developing future optoelectronic applications.


Comparative genomic study of gastric epithelial cells co-cultured with Helicobacter pylori.
To identify genes potentially involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis. GES-1 cells were co-cultured with H. pylori strains isolated from patients with gastric carcinoma (GC, n = 10) or chronic gastritis (CG, n = 10) for in vitro proliferation and apoptosis assays to identify the most and least virulent strains. These two strains were cagA-genotyped and used for further in vivo carcinogenic virulence assays by infecting Mongolian gerbils for 52 wk, respectively; a broth free of H. pylori was lavaged as control. Genomic profiles of GES-1 cells co-cultured with the most and least virulent strains were determined by microarray analysis. The most differentially expressed genes were further verified using quantitative real-time polymerase chain reaction in GES-1 cells infected with the most and least virulent strains, and by immunohistochemistry in H. pylori positive CG, precancerous diseases, and GC biopsy specimens in an independent experiment. GC-derived H. pylori strains induced a potent proliferative effect in GES-1 cells in co-culture, whereas CG-derived strains did not. The most (from a GC patient) and least (from a CG patient) virulent strains were cagA-positive and negative, respectively. At week 52, CG, atrophy, metaplasia, dysplasia, and GC were observed in 90.0%, 80.0%, 80.0%, 90%, and 60.0%, respectively, of the animals lavaged with the most virulent strain. However, only mild CG was observed in 90% of the animals lavaged with the least virulent strain. On microarray analysis, 800 differentially expressed genes (49 up- and 751 down-regulated), involving those associated with cell cycle regulation, cell apoptosis, cytoskeleton, immune response, and substance and energy metabolisms, were identified in cells co-cultured with the most virulent strain as compared with those co-cultured with the least virulent strain. The six most differentially expressed genes (with a betweenness centrality of 0.1-0.2) were identified among the significant differential gene profile network, including JUN, KRAS, BRCA1, SMAD2, TRAF1, and HDAC6. Quantitative real-time polymerase chain reaction analyses verified that HDAC6 and TRFA1 mRNA expressions were significantly more up-regulated in GES-1 cells co-cultured with the most virulent strain than in those co-cultured with the least virulent strain. Immunohistochemistry of gastric mucosal specimens from H. pylori-positive patients with CG, intestinal metaplasia (IM), dysplasia, and GC showed that moderately positive and strongly positive HDAC6 expression was detected in 21.7% of CG patients, 30.0% of IM patients, 54.5% of dysplasia patients, and 77.8% of GC patients (P < 0.001). The up-regulation of TRAF1 expressions was detected in 34.8%, 53.3%, 72.7%, and 88.9% specimens of CG, IM, dysplasia, and GC, respectively (P < 0.001). The overexpression of HDAC6 and TRAF1 in GES-1 cells co-cultured with the GC-derived strain and in H. pylori-positive dysplasia and GC suggests that HDAC6 and TRAF1 may be involved in H. pylori-induced gastric carcinogenesis.


Neuroticism, marital violence, and the moderating role of stress and behavioral skills.
Do high levels of neuroticism predict intimate partner violence (IPV)? Although neuroticism may predispose partners to increased risks of IPV perpetration, the extent to which it predicts such perpetration is likely to depend on the broader context of the relationship. Consistent with this prediction, the current longitudinal study of 169 community couples revealed that the effects of neuroticism on IPV perpetration over the first 4 years of marriage were moderated by observations of problem-solving behavior and objective ratings of chronic stress. Specifically, although husbands and wives who scored higher on a measure of neuroticism at the outset of marriage engaged in more IPV throughout the marriage on average, those who possessed more effective problem-solving skills or experienced lower levels of stress were significantly less likely to engage in IPV. Results highlight the importance of considering the broader relationship context when examining predictors of specific interpersonal processes.


Stage IV breast cancer: clinical course and survival of patients with osseous versus extraosseous metastases at initial diagnosis. The GOCS (Grupo Oncológico Cooperativo del Sur) experience.
The medical records of 414 patients with metastatic breast carcinoma treated between 1978 and 1986 were reviewed and 44 women were identified as having stage IV disease when the primary breast lesion was detected. Of these 44 women, 25 had metastatic disease limited to the skeleton while 19 had extraosseous lesions only. The clinical features, response to therapy, and survival were analyzed and compared for both groups. The median survival of those patients with bone-only metastases was 52 months as compared with 13 months for those with extraskeletal lesions (p = 0.0025). The response rate to first-line systemic therapy was similar for both groups (47% for bone metastases and 44% for extraosseous metastases). The median duration of response was 14 months (range, 3-55 months) for patients with bone disease and 8 months (range, 4-43 months) for those with extraskeletal lesions. We conclude that patients with metastatic breast cancer confined to the skeleton at initial diagnosis tend to follow an indolent, chronic course with prolonged survival. Therefore the increase in response rate with aggressive chemotherapy should be balanced against its higher morbidity. Further studies are needed to confirm whether the better prognosis of these patients is determined by the anatomical confinement of the disease to the skeleton or merely reflects the influence of other prognostic factors.


Zebrin II compartmentation of the cerebellum in a basal insectivore, the Madagascan hedgehog tenrec Echinops telfairi.
The mammalian cerebellum is histologically uniform. However, underlying the simple laminar architecture is a complex arrangement of parasagittal stripes and transverse zones that can be revealed by the expression of zebrin II/aldolase C. The cerebellar cortex of rodents, for example, is organized into four transverse zones: anterior, central, posterior and nodular. Within the anterior and posterior zones, parasagittal stripes of Purkinje cells expressing zebrin II alternate with those that do not. Zonal boundaries appear to be independent of cerebellar lobulation. To explore this model further, and to broaden our understanding of the evolution of cerebellar patterning, zebrin II expression has been studied in the cerebellum of the Madagascan hedgehog tenrec (Echinops telfairi), a basal insectivore with a lissiform cerebellum with only five lobules. Zebrin II expression in the tenrec reveals an array of four transverse zones as in rodents, two with homogeneous zebrin II expression, two further subdivided into stripes, that closely resembles the expression pattern described in other mammals. We conclude that a zone-and-stripe organization may be a common feature of the mammalian cerebellar vermis and hemispheres, and that zonal boundaries and cerebellar lobules and fissures form independently.


Up-regulating relaxin expression by G-quadruplex interactive ligand to achieve antifibrotic action.
Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.


Assessing the Amount of Spontaneous Real-World Spoken Language in Aphasia: Validation of Two Methods.
The purpose of this article is to present the results of a study evaluating the psychometric properties of 2 new measures that exclusively assess the amount of real-world spoken language in patients with aphasia. Forty individuals with aphasia were evaluated on several measures of spoken language in real-world settings. The Verbal Activity Log (VAL; Johnson et al., 2014) has participants, aided by caregivers, indicate current amount and quality of real-world spoken language compared with before stroke. In addition, digital voice recorders objectively measured the amount of real-world spoken language. The Communicative Effectiveness Index (Lomas et al., 1989), a previously validated measure of functional communication, was used as a comparison measure. Nineteen participants received follow-up assessment ≥ 3 weeks later. Validity was supported by Pearson correlations between spoken language recordings and the VAL, r(38) = .70, p < .001. Likewise, correlation with the Communicative Effectiveness Index was strong, r(38) = .73, p < .001. Test-retest reliability for both VAL and audio recording was high, with intraclass correlations ≥ .96 and .90, respectively. These results present preliminary evidence for the reliability and validity of the VAL and spoken language recording for assessment of the amount of real-world spoken language in aphasia. As a simple patient-reported outcome, the VAL may assist diverse therapies for aphasia.


[An unusual complication of perforated sigmoid diverticulitis: gas in the portal vein with miliary liver abscesses].
A patient presented with gas in the portal vein and miliary liver abscesses due to perforation of a sigmoid diverticulitis abscess. The outcome was favorable after surgical treatment. Gas in the portal vein, a sign of extreme seriousness, is generally the result of intestinal necrosis from ileo-mesenteric artery infarction, responsible for more than 75% of deaths. Diagnosis of this exceptional complication, suggested from a straight abdominal film, was confirmed by hepatic ultrasound and scan imaging. Urgent surgical intervention can hopefully, as in the present case, result in the patient's survival.


Mental illness and creative activity in female writers.
This study addressed three questions. Are female writers more likely to suffer from mental illness than members of a matched comparison group? If so, does a familial basis exist for their psychopathology and creativity? What factors predict overall creativity in women? Questionnaire and interview data were obtained on 59 female writers and 59 members of a matched comparison group. These data were used to assess overall creativity and to identify psychiatric disorders in subjects and their first-degree relatives. Female writers were more likely than members of the comparison group to suffer not only from mood disorders but from drug abuse, panic attacks, general anxiety, and eating disorders as well. The rates of multiple mental disorders were also higher among writers. Although there was evidence for the familial transmission of psychopathology, physical or sexual abuse during childhood also loomed as a potential contributor to later psychological difficulties. Creativity also appeared to run in families. The cumulative psychopathology scores of subjects, their reported exposure to sexual or physical abuse during childhood, mental difficulties in their mothers, and the combined creativity scores of their parents represented significant predictors of their overall creativity. The high rates of certain emotional disorders in female writers suggested a direct relationship between creativity and psychopathology. But the relationship was not necessarily a simple one. As the results of the predictive analysis indicated, familial and environmental factors also appeared to play an important role.


Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis.
Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.


The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled.
The eukaryotic translation initiation factor eIF4E is a potent oncogene. Although eIF4E has traditional roles in translation initiation in the cytoplasm, it is also found in the nucleus, suggesting that it has activities beyond its role in protein synthesis. The road less traveled has been taken to study these nuclear activities and to understand their contribution to the oncogenic potential of eIF4E. The molecular features and biological pathways underpinning eIF4E's nuclear mRNA export are described. New classes of eIF4E regulators have been identified and their relevance to cancer shown. The studies presented here reveal the molecular, biophysical, and structural bases for eIF4E regulation. Finally, recent clinical work targeting eIF4E in acute myeloid leukemia patients with ribavirin is discussed. In summary, these findings provide a novel paradigm for eIF4E function and the molecular basis for targeting it in leukemia patients.


Epidemiology of injuries in competition taekwondo: a meta-analysis of observational studies.
This paper aims to review and collate the epidemiological data of injuries in competition taekwondo as reported in the literature, make recommendations, and suggest further research. The electronic databases AMED, AusportMed, CINAHL, MEDLINE, PubMed, and SPORTDiscus were searched from inception to March 2008. Fourteen prospective cohort studies reporting the incidence of injuries in taekwondo were included. Two reviewers independently extracted data and assessed trial quality using the STROBE statement. Homogenous studies were combined in a pooled analysis using a Poisson random effects regression model. Poisson regression showed an overall mean injury rate of 79.3 per 1000 athlete-exposures (95% confidence interval 22.8, 275.4). Neither age, gender nor level of play were significant in the analysis. The most common injury location and type were found to be the lower limb and contusion, respectively, and were invariably associated with contact. Although taekwondo players are exposed to a substantial risk of sustaining injuries, the majority of injuries appeared to be of minimal severity. Modifications to the competition rules and protective equipment may be warranted. Future studies should adhere to recommended operational definitions, utilise a standardised injury classification system, and report injury rates using multiple denominators in order to facilitate inter- and cross-sport comparisons.


Comparison of Exit-Site Infection Frequency in Continuous Ambulatory Peritoneal Dialysis and Automated Peritoneal Dialysis Patients: A Single-Center Experience.
Catheter exit-site infection (ESI) is generally caused by skin flora. Continuous ambulatory peritoneal dialysis (CAPD) patients have more contact with their catheters than automated peritoneal dialysis (APD) patients as a result of performing multiple exchanges per day. The aim of the present study was to compare the frequency of ESIs between these 2 peritoneal dialysis (PD) modalities. PD patients from 2001 to 2015 were enrolled in the study. Patients transferred from CAPD to APD were excluded. All of the data were collected retrospectively. The rate of ESI occurrence and culture results in the CAPD and APD groups were compared. The data of 280 patients were evaluated. APD patients represented 23.2% of the study cohort. Prevalence of peritonitis was 87.6% if a patient had an ESI and 50.7% if there was no ESI (p=0.000). The frequency of ESI was similar between the 2 peritoneal dialysis modalities (p=0.343). There was a statistically significant difference in the causative organism of infection between the 2 groups (p=0.021). The ESI rate was similar in the CAPD and APD patients though CAPD requires more exchanges, and therefore there is more contact with the catheter. All PD patients, regardless of the treatment modality used, are expected to perform exchanges according to standard rules for connecting the catheter to the PD solution bag. As long as patients observe these guidelines, there would appear to be no increased ESI risk related specifically to the modality.


Ablation of atrial flutter: block (isthmus conduction) or not a block, that is the question?
It is important to identify residual slow conduction and minimize the chance of resumption of conduction after right atrial isthmus ablation to reduce the chance of recurrence of atrial flutter (AFL). The aim of this article is to discuss the best possible way of confirming a bi-directional isthmus conduction (BIC) block after ablation of an isthmus-dependent AFL. A combination of activation and double potential mapping seems to be the most practical way of acutely confirming the BIC block.


SucStruct: Prediction of succinylated lysine residues by using structural properties of amino acids.
Post-Translational Modification (PTM) is a biological reaction which contributes to diversify the proteome. Despite many modifications with important roles in cellular activity, lysine succinylation has recently emerged as an important PTM mark. It alters the chemical structure of lysines, leading to remarkable changes in the structure and function of proteins. In contrast to the huge amount of proteins being sequenced in the post-genome era, the experimental detection of succinylated residues remains expensive, inefficient and time-consuming. Therefore, the development of computational tools for accurately predicting succinylated lysines is an urgent necessity. To date, several approaches have been proposed but their sensitivity has been reportedly poor. In this paper, we propose an approach that utilizes structural features of amino acids to improve lysine succinylation prediction. Succinylated and non-succinylated lysines were first retrieved from 670 proteins and characteristics such as accessible surface area, backbone torsion angles and local structure conformations were incorporated. We used the k-nearest neighbors cleaning treatment for dealing with class imbalance and designed a pruned decision tree for classification. Our predictor, referred to as SucStruct (Succinylation using Structural features), proved to significantly improve performance when compared to previous predictors, with sensitivity, accuracy and Mathew's correlation coefficient equal to 0.7334-0.7946, 0.7444-0.7608 and 0.4884-0.5240, respectively.


Spasticity and intrathecal baclofen.
Severe spastic tone and/or spastic hypertonia can be the most disabling consequences of a neurologic insult, resulting from an excess of muscle tone. Baclofen, a GABA-B agonist, is one of the most widely used drugs in treating abnormal or disabling spastic tone. However, the effectiveness of baclofen taken orally is often limited by its systemic side effects, including sedation, confusion, and lethargy. Intrathecal baclofen (ITB) delivered by an implanted catheter can work directly at the spinal cord level to reduce spastic tone through presynaptic inhibition. Several decades after Penn and Kroin (1984) proved that continuous infusion of intrathecal baclofen reduced spinal cord spasticity, numerous studies have demonstrated the benefits of ITB therapy and proven its effectiveness in modulating and reducing spastic tone. In this article the authors review current methods of management with ITB therapy; summarize the current knowledge, controversies, and available scientific literature; illustrate through different clinical cases treatment strategies and their outcomes; and lastly, provide a synopsis of current clinical practice in ITB therapy with insights into new therapeutic developments.


The Impact and Detection of Uniform Differential Item Functioning for Continuous Item Response Models.
Psychometricians have devoted much research and attention to categorical item responses, leading to the development and widespread use of item response theory for the estimation of model parameters and identification of items that do not perform in the same way for examinees from different population subgroups (e.g., differential item functioning [DIF]). With the increasing use of computer-based measurement, use of items with a continuous response modality is becoming more common. Models for use with these items have been developed and refined in recent years, but less attention has been devoted to investigating DIF for these continuous response models (CRMs). Therefore, the purpose of this simulation study was to compare the performance of three potential methods for assessing DIF for CRMs, including regression, the MIMIC model, and factor invariance testing. Study results revealed that the MIMIC model provided a combination of Type I error control and relatively high power for detecting DIF. Implications of these findings are discussed.


Intermediate state dependence of the photoelectron circular dichroism of fenchone observed via femtosecond resonance-enhanced multi-photon ionization.
The intermediate state dependence of photoelectron circular dichroism (PECD) in resonance-enhanced multi-photon ionization of fenchone in the gas phase is experimentally studied. By scanning the excitation wavelength from 359 to 431 nm, we simultaneously excite up to three electronically distinct resonances. In the PECD experiment performed with a broadband femtosecond laser, their respective contributions to the photoelectron spectrum can be resolved. High-resolution spectroscopy allows us to identify two of the resonances as belonging to the B- and C-bands, which involve excitation to states with 3s and 3p Rydberg character, respectively. We observe a sign change in the PECD signal, depending on which electronic state is used as an intermediate, and are able to identify two differently behaving contributions within the C-band. Scanning the laser wavelength reveals a decrease of PECD magnitude with increasing photoelectron energy for the 3s state. Combining the results of high-resolution spectroscopy and femtosecond experiment, the adiabatic ionization potential of fenchone is determined to be IPaFen=(8.49±0.06) eV.


Cutaneous Radiation-associated Breast Angiosarcoma: Radicality of Surgery Impacts Survival.
Cutaneous radiation therapy (RT)-associated breast angiosarcoma (AS) is a rare consequence of breast RT associated with poor outcomes. Previous small case series have documented high recurrence rates and poor survival. We reviewed our experience and focused on the impact of conservative versus radical resections. Data for patients with RT-associated breast AS evaluated at our institution from 1993 to 2015 who underwent surgery were reviewed. Seventy-six women were diagnosed with RT-associated breast AS at a median 85 months from surgery for invasive breast carcinoma or ductal carcinoma in situ. Thirty-eight underwent mastectomy/wide excision with partial skin resection ("conservative") and 38 underwent resection of all or nearly all previously irradiated skin plus mastectomy ("radical"). The radical group (vs the conservative group) more often had multifocal disease (80% vs 56%, P = 0.04), chemotherapy for AS (58% vs 22%, P < 0.01), margin-negative resection (100% vs 73%, P < 0.01), reconstructive surgery (100% vs 13%, P < 0.01), and re-operation (16% vs 3%, P = 0.04). Five-year crude cumulative incidences of local recurrence and distant metastasis for radical versus conservative groups were 23% versus 76% (P < 0.01) and 18% versus 47% (P = 0.02), respectively. Five-year disease-specific survival (DSS) for radical versus conservative groups was 86% versus 46% (P < 0.01), respectively. On multivariable analysis, age, radicality of surgery, and margin were predictive of DSS. For patients with RT-associated breast AS, radical resection was associated with reduced recurrence rates and improved DSS. Although margin was predictive of DSS, multifocality calls into question the reliability of negative margin assessment.


The Sachs report: Investing in Health for Economic Development--or increasing the size of the crumbs from the rich man's table? Part I.
The Commission on Macroeconomics and Health report (Sachs report) of 2001 has been heralded as inspiring and groundbreaking and is being adopted as the blueprint for global health policymaking. This article argues that the report is deeply conservative and unoriginal. It encourages medico-technical solutions to public health problems; it ignores macroeconomic determinants and other root causes of both poor health and poverty; it reverses public health logic and history; it is based on a set of flawed assumptions; it reflects one particular economic perspective to the exclusion of all others; and it recommends greater amounts of charity while preserving the status quo of a deeply unjust and irrational international economic order. A set of assumptions deriving from a neoliberal approach to health underlies the report. The author proposes an alternative set of assumptions deriving from a social justice and human rights-based approach to health.


Global and local diffusion in the standard map.
We study the global and the local transport and diffusion in the case of the standard map, by calculating the diffusion exponent μ. In the global case, we find that the mean diffusion exponent for the whole phase space is either μ=1, denoting normal diffusion, or μ=2 denoting anomalous diffusion (and ballistic motion). The mean diffusion of the whole phase space is normal when no accelerator mode exists and it is anomalous (ballistic) when accelerator mode islands exist even if their area is tiny in the phase space. The local value of the diffusion exponent inside the normal islands of stability is μ=0, while inside the accelerator mode islands it is μ=2. The local value of the diffusion exponent in the chaotic region outside the islands of stability converges always to the value of 1. The time of convergence can be very long, depending on the distance from the accelerator mode islands and the value of the nonlinearity parameter K. For some values of K, the stickiness around the accelerator mode islands is maximum and initial conditions inside the sticky region can be dragged in a ballistic motion for extremely long times of the order of 10^{7} or more but they will finally end up in normal mode diffusion with μ=1. We study, in particular, cases with maximum stickiness and cases where normal and accelerator mode islands coexist. We find general analytical solutions of periodic orbits of accelerator type and we give evidence that they are much more numerous than the normal periodic orbits. Thus, we expect that in every small interval ΔK of the nonlinearity parameter K of the standard map there exist smaller intervals of accelerator mode islands. However, these smaller intervals are in general very small, so that in the majority of the values of K the global diffusion is normal.


PREDICTING MICROEVOLUTIONARY RESPONSES TO DIRECTIONAL SELECTION ON HERITABLE VARIATION.
Microevolution of quantitative traits in the wild can be predicted from a knowledge of selection and genetic parameters. Testing the predictions requires measurement of the offspring of the selected group, a requirement that is difficult to meet. We present the results of a study of Darwin's finches on the Galápagos island of Daphne Major where this requirement is met. The study demonstrates microevolutionary consequences of natural selection.


Spray-dried porcine plasma added to diets contaminated with aflatoxins and fumonisins shows beneficial effects to piglet health.
This study was aimed to analyze the effects of spray-dried porcine plasma (SDPP) on the health of post weaning piglets challenged with diets contaminated with aflatoxins and fumonisins. Fifty-six male piglets (7.15 ± 0.61 kg) were allocated in four groups: CTL group received a regular diet; SDPP group received a regular diet and 6% SDPP; MYC group received a diet containing 300 µg/kg aflatoxins and 8,000 µg/kg fumonisins; group MYC+SDPP received 300 µg/kg aflatoxins, 8,000 µg/kg fumonisins and 6% SDPP. The animals that received the experimental diet containing mycotoxins (MYC group) had lower weight gain at the end of the experiment compared to the other treatments. Animals receiving SDPP showed decreased urea levels throughout the experiment (P<0.05). Animals from MYC group presented an increased on reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels and decreased catalase activity (P<0.05). In contrast, SDPP prevented the increase of ROS and TBARS and stimulated superoxide dismutase activity (P<0.05). In conclusion, diet contaminated with mycotoxins (group MYC) caused subclinical intoxication in the piglets, as observed by the increase on free radical's production and lipid peroxidation. Conversely, SDPP presented a protective effect, minimizing the effects of oxidative stress caused by aflatoxins and fumonisins ingestion.


Surface Properties and MC3T3-E1 Cell Response of Cortical Bone Allografts Modified with Low-Concentration Phosphoric Acid.
This experimental study aimed to evaluate the effect of low-concentration phosphoric acid on the surface structure of cortical allografts. Allogenic cortical bones were obtained from femurs and tibias of New Zealand white rabbits. The bones were modified by treatment with various concentrations of phosphoric acid (10%, 20% or 30%) for 10, 30 or 60 minutes, then evaluated by the following methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and LIVE/DEAD assay, alkaline phosphatase (ALP) assay, biomechanical properties testing, contact angle detection, quantitative real-time polymerase chain reaction (Q-PCR), western blotting and scanning electron microscopy (SEM). Compared with the other groups, the group modified with 10% H3PO4 for 10 minutes had lower cytotoxicity according to MTT and LIVE/DEAD assays, higher hydrophilicity in the contact angle detection test and greater stability in the biomechanical properties test. Moreover, an up-regulation of osteopontin (OPN) in bones modified with 10% H3PO4 was observed by Q-PCR and western blotting. In addition, ALP assay and SEM showed that surface porosity and osteoinductivity were increased in the group modified with 10% H3PO4. Low-concentration phosphoric acid may be a potential method for surface modification of cortical allografts. Further animal experiments and animal infection model studies are required to validate the efficacy of surface-modified cortical allografts to repair large segmental bone defects.


The effects of platelet-activating factor and platelet-derived compounds on bovine luteal cell progesterone production.
This study was conducted to characterize bovine platelets with respect to serotonin (5-HT) concentration and platelet-activating factor (PAF)-activation and to examine the in vitro effects of PAF and platelet-derived compounds on bovine luteal progesterone (P4) production. The concentration of 5-HT in platelets, as determined by high-performance liquid chromatography, was 538.8 +/- 40.83 ng/1 x 10(8) platelets. Based on a circulating platelet concentration range of 2.3 x 10(8) 5.8 x 10(8) platelets/ml, the circulating concentration of 5-HT would be approximately 1239-3125 ng/ml of blood. Bovine platelets were found to aggregate in response to PAF (1-40 ng/0.5 ml), with maximal aggregation occurring at 20-40 ng/0.5 ml. Coincubation of luteal cells with platelets (1 x 10(7)-4 x 10(8] enhanced luteal P4 production (p less than 0.05). Addition of the 5-HT receptor antagonist mianserin blocked the platelet-induced increases in P4 (p less than 0.05). Preincubation of platelets with indomethacin did not alter the production of P4 (p greater than 0.05), nor did the addition of propranolol (p greater than 0.05). Platelet-derived growth factor at 8 and 16 ng/ml enhanced basal P4 production (p less than 0.05) but had no effect on the responsiveness of luteal cells to luteinizing hormone (LH) (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Visualisation of the rectoanal inhibitory reflex with a modified contrast enema in children with suspected Hirschsprung disease.
Patients with Hirschsprung disease lack the normal rectoanal inhibitory reflex, which can be studied with anorectal manometry or US. To see whether the rectoanal inhibitory reflex could be visualised with a modified contrast enema, thereby increasing the diagnostic accuracy of the contrast enema and reducing the number of rectal biopsies. Fifty-nine boys and 42 girls (median age, 12 months) with suspected Hirschsprung disease were examined with a modified contrast enema, supplemented with two injections of cold, water-soluble contrast medium, to induce the reflex. Two paediatric radiologists evaluated the anonymised examinations in consensus. The contrast enema findings were correlated with the results of rectal biopsy or clinical follow-up. Five boys and one girl (median age, 7.5 days) were diagnosed with Hirschsprung disease. The negative predictive value of the rectoanal inhibitory reflex was 100%. A contrast enema with signs of Hirschsprung disease in combination with an absent rectoanal inhibitory reflex had the specificity of 98% and sensitivity of 100% for Hirschsprung disease. The modified contrast enema improves the radiological diagnosis of Hirschsprung disease. By demonstrating the rectoanal inhibitory reflex in children without Hirschsprung disease, we can reduce the proportion of unnecessary rectal biopsies.


Heavy metals in cigarettes for sale in Spain.
The aim of the present study was to determine the concentrations of eight metals (Al, Cd, Co, Cr, Mn, Ni, Pb, Sr) in 33 cigarette brands for sale in Spain. Samples were analysed by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Mean values obtained were 428 µg Al/g, 0.810 µg Cd/g, 0.558 µg Co/g, 1.442 µg Cr/g, 112.026 µg Mn/g, 2.238 µg Ni/g, 0.602 µg Pb/g and 82.206 µg Sr/g. Statistically significant differences were observed with respect to concentrations of Co (0.004), Cr (0.045), Mn (0.005) and Sr (0.005) between black and blond tobacco and between levels of Mn (0.027) among manufacturers. Considering a Cd inhalation rate of 10% and a Cd absorption rate of 50%, absorption of Cd for smokers of 30 cigarettes/day was estimated at 0.75 µg Cd/day. An inhalation rate of 2-6% and an absorption rate of 86% were considered for Pb, Pb absorption in smokers of 30 cigarettes/day was therefore 0.18-0.54 μg/day. In view of the significant toxic effects of these metals, quantification and control of their concentrations in this drug are of the utmost importance.


Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they?
Serum IgG autoantibodies against the myelin oligodendrocyte glycoprotein (MOG) are present in atypical demyelinating disorders such as neuromyelitis optica spectrum disorders (NMOSD) or acute disseminated encephalomyelitis. Whereas the role of aquaporin-4 antibodies as diagnostic markers for NMOSD is meanwhile well established, the role of MOG antibodies is less clear. Initial studies suggested that MOG antibodies are associated with a more benign disease course than aquaporin-4antibodies. However, recent findings challenged this view. Data from the two largest cohorts of adult MOG antibody-positive patients with the longest clinical follow-up published so far indicate that the majority of patients develop a recurrent disease course with optic neuritis as the most frequent symptom, particularly in women. Frequent attacks are often associated with accumulating damage and functional impairment. The clinical spectrum of acquired demyelinating syndromes associated with MOG antibodies seems to be broader as anticipated in prior studies, with only a third of patients fulfilling the current diagnostic criteria for NMOSD. MOG antibodies are associated with an increasing spectrum of age and sex-dependent clinical phenotypes, only partly overlapping with NMOSD and multiple sclerosis and with a high risk of a recurrent disease course.


Simultaneous liver and renal transplantation in man.
Advanced chronic renal failure has been thought of as a contraindication to liver transplantation. We present here seven cases of simultaneous kidney-liver transplant performed for combined end-organ failure. Six of the seven patients are alive with functioning grafts with follow-up of from 6 weeks to 32 months. In one case, the patient chronically rejected his liver graft (treated with successful retransplant) while maintaining good function in his kidney. The rate of acute rejection in the liver transplant was only 37.5% compared with 59.3% in the patients undergoing liver transplant only. There were no obvious rejections observed in the kidney transplants. These cases demonstrate the utility of simultaneous kidney-liver transplant in patients with combined kidney and liver failure. Advanced chronic renal failure should no longer be considered a contraindication to liver transplantation.


Trajectory of Short- and Long-Term Recovery of Tibial Shaft Fractures After Intramedullary Nail Fixation.
To determine the trajectory of recovery after tibial shaft fracture treated with intramedullary nail over the first 5 years and to evaluate the magnitude of the changes in functional outcome at various time intervals. Prospective cohort study. A Level 1 trauma center. One hundred thirty-two patients with tibial shaft fracture (OTA 42-A, B, C) were enrolled into the Center's prospective orthopaedic trauma database between January 2005 and February 2010. Functional outcome data were collected at baseline, 6 months, 1 year, and 5 years. Enrolled patients were treated acutely with intramedullary nailing of their tibia. Evaluation was performed using the Short Form-36 and Short Musculoskeletal Function Assessment (SMFA). Mean SF-36 physical component scores improved between 6 and 12 months (P = 0.0008) and between 1 and 5 years (P = 0.0029). Similarly, mean SMFA dysfunction index scores improved between 6 and 12 months (P = 0.0254) and between 1 and 5 years (P = 0.0106). In both scores, the rate or slope of this improvement is flatter between 1 and 5 years than it is between 6 and 12 months. Furthermore, SF-36 and SMFA scores did not reach baseline at 5 years (SF-36 P < 0.0001, SMFA P = 0.0026). A significant proportion of patients were still achieving a minimal clinically important difference in function between 1 and 5 years (SF-36 = 54%, SMFA = 44%). The trajectory of functional recovery after tibial shaft fracture is characterized by an initial decline in function, followed by improvement between 6 and 12 months. There is still further improvement beyond 1 year, but this is of flatter trajectory. The 5-year results indicate that function does not improve to baseline by 5 years after injury. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Docetaxel-induced fatal interstitial pneumonitis in a patient with castration-resistant prostate cancer.
A 69-year-old man with castration-resistant prostate cancer (CRPC) received docetaxel and a corticosteroid. After the third cycle of docetaxel administration, he presented with dyspnea, cough, sputum, and fever of 39.2℃. The chest X-ray and chest computed tomography (CT) revealed a diffuse reticulonodular shadow in both lungs, which suggested interstitial pneumonitis. Initially, we used empiric broad-spectrum antibiotics and high-dose corticosteroids. However, his condition progressively became worse and he was transferred to the intensive care unit, intubated, and placed on mechanical ventilation. He died 4 days after hospital admission. Here we report this case of fatal interstitial pneumonitis after treatment with docetaxel for CRPC. We briefly consider docetaxel-induced pneumonitis to make physicians aware of the possibility of pulmonary toxicity so that appropriate treatment can be begun as soon as possible.


Socioeconomic status is associated with global diabetes prevalence.
The incidence of diabetes is increasing globally. We investigated the relationship between diabetes prevalence and patient socioeconomic status across multiple countries. We searched PubMed to identify population-based surveys reporting diabetes prevalence between 1990 and May 2016. Search results were filtered, and Human Development Index (HDI) values from the United Nations Development Programme were used to assess socioeconomic status for a given nation. Our analysis included 45 national surveys from 32 countries. Diabetes prevalence was positively correlated with national HDI (r = 0.421 P = 0.041) in developing countries, and negatively correlated with HDI (r = -0.442 P = 0.045) in developed countries. Diabetes prevalence trends were the same in women and men, although men were associated with increased diabetes risk in developed countries (r = 0.459 P = 0.048). Thus, diabetes prevalence rises with increasing HDI in developing countries, and this is reversed in developed countries. Ours is the first study to investigate the relationship between diabetes and socioeconomic status at global level using HDI values. These results will aid in evaluating global diabetes prevalence and risk with respect to patient socioeconomic status, and will be useful in the development of policies that help reduce disease incidence.


Ambulatory care patient classification.
Efficient, cost-effective use of resources is important in every aspect of health care. As ambulatory care continues to grow, it becomes an increasingly important area for managerial attention. Few tools which are specific to the outpatient environment have been developed. This paper has suggested an approach to developing a specific instrument to assist in controlling costs in the ambulatory unit: the ambulatory patient classification system.


Effects of vitamin supplementation on PCB (Aroclor 1254)-induced changes in ventral prostatic androgen and estrogen receptors.
The objective of this study was to determine the impact of the polychlorinated biphenyl (PCB) Aroclor 1254 and vitamin C and E on ventral prostatic testosterone and estradiol receptor concentration. A group of 30 rats were treated with Aroclor 1254 [2 mg/kg body weight (bwt) /day/ip] for 30 days; 10 rats were treated as Aroclor 1254 control. The remaining 20 rats were subdivided into the following two subgroups of 10 animals each. One group was given vitamin C (500 mg/kg bwt/day/oral) for 10 days, whereas the other group was given vitamin E (50 mg/kg bwt/day/oral) for 10 days. Separate controls were also maintained. Ventral prostatic androgen and estrogen receptor concentration in all the groups were quantified. Serum hormonal profiles such as total T3, T4, TSH, testosterone, and estradiol were also estimated in all the groups. Ventral prostatic zinc content and serum zinc concentration were also determined in all the groups. Aroclor 1254 exposure decreased the concentration of both receptors. Decreased serum total T3, T4, testosterone, estradiol, and increased TSH were observed after Aroclor 1254 exposure. Serum and tissue zinc levels were also decreased. Administration of vitamin C or E restored both the receptor concentration and the serum hormone levels with the exception of estradiol. Administration of vitamin C or E restored zinc levels. Vitamin E was more sensitive on ventral prostatic androgen receptors and zinc levels, including serum, in PCB-exposed rats.


The role of Toll-like receptor polymorphisms in acute pancreatitis occurrence and severity.
Toll-like receptors (TLRs) are damage-associated molecular patterns receptors, which are essential in the activation of the inflammasome cascade, required for the initiation of inflammation. We hypothesized that changes in the function of these receptors caused by genetic polymorphisms in their encoding genes could determine acute pancreatitis (AP) incidence or severity. Two hundred sixty-nine patients and 269 controls were included. Acute pancreatitis diagnosis criteria were abdominal pain, increased serum amylase levels, and positive findings on abdominal imaging. The patients were observed until discharge. Blood samples were obtained, determining the following TLRs: TLR1 rs5743611, TLR2 rs5743704, TLR3 rs3775291, TLR3 rs5743305, TLR4 rs4986790, TLR4 rs4986791, TLR5 rs5744174, TLR6 rs5743795, TLR7 rs2302267, TLR9 rs352140, and TLR10 rs4129009. No TLR polymorphism was related to AP incidence. Regarding severity, CC genotype patients in TLR3 rs3775291 had an increased risk for severe pancreatitis (CC odds ratio [OR], 2.426; P = 0.015). In addition, TLR6 rs5743795 GG genotype patients had a lower risk for severe AP (GG OR, 0.909; P < 0.05). Intensive care unit admission was related to TLR5 rs5744174 homozygote TT carriers (TT OR, 3.367; P = 0.036). Our article points to genetic polymorphisms in TLR3 and TLR6 as having a plausible role in the occurrence of severe AP.


Tyrosine Kinase-Dependent Defense Responses Against Herbivory in Arabidopsis.
Tyrosine (Tyr) phosphorylation (TP) is important for promotion of plants' signaling. Arabidopsis calcium-dependent protein kinase related protein kinases (CRK2 and CRK3) phosphorylate Tyr residues of a subset of transcription factors (TFs), including herbivory-responsive ethylene response factor 13 (ERF13), but the in vivo functions of these kinases in plant defense responses and development remain to be clarified. We show that when CRKs were coexpressed with ERF13 in Arabidopsis leaf protoplasts, the transcription activity regulated via ERF13 was elevated by CRK2 but not CRK3 or their kinase-dead form mutants. Moreover, this elevation was abolished when a Tyr-phosphorylation mutant of ERF was coexpressed with CRK2, indicating that CRK2 serves as an effector of ERF13 mediated by Tyr-phosphorylation. Moreover, CRK2 and CRK3 acted as effectors of RAP2.6 and WRKY14, respectively. CRK-overexpressing lines and knockout mutants of Arabidopsis plants showed increased and decreased expression levels of the defensin gene PDF1.2 in leaves, respectively, conferring on the plants modulated defense properties against the generalist herbivore Spodoptera litura. However, these lines did not show any obvious developmental defects, indicating that CRKs play a role in defense responses but not in the ordinary growth or development of plants. Transcription of both CRK2 and CRK3 was positively regulated by jasmonate signaling and abscisic acid (ABA) signaling upon herbivory. Our findings suggest that these phytohormone-responsive CRKs work coordinately for plant defense responses via Tyr phosphorylation of herbivory-responsive regulators.


Cultural values and cross-cultural video consumption on YouTube.
Video-sharing social media like YouTube provide access to diverse cultural products from all over the world, making it possible to test theories that the Web facilitates global cultural convergence. Drawing on a daily listing of YouTube's most popular videos across 58 countries, we investigate the consumption of popular videos in countries that differ in cultural values, language, gross domestic product, and Internet penetration rate. Although online social media facilitate global access to cultural products, we find this technological capability does not result in universal cultural convergence. Instead, consumption of popular videos in culturally different countries appears to be constrained by cultural values. Cross-cultural convergence is more advanced in cosmopolitan countries with cultural values that favor individualism and power inequality.


Two-photon laser-scanning microscopy for single and repetitive imaging of dorsal and lateral spinal white matter in vivo.
We developed appropriate surgical procedures for single and repetitive multi-photon imaging of spinal cord in vivo. By intravenous anesthesia, artificial ventilation and laminectomy, acute experiments were performed in the dorsal and lateral white matter. By volatile anesthesia and minimal-invasive surgery, chronic repetitive imaging up to 8 months were performed in the dorsal column through the window between two adjacent spines. Transgenic mouse technology enabled simultaneous imaging of labeled axons, astrocytes and microglia. Repetitive imaging showed positional shifts of microglia over time. These techniques serve for investigations of cellular dynamics and cell-cell interactions in intact and pathologically changed spinal tissue.


A Quantitative Analysis of Weight Gain Following Mandibular Distraction Osteogenesis in Robin Sequence.
Mandibular distraction osteogenesis (MDO) is an effective treatment modality for children suffering from upper airway obstruction from Robin Sequence (RS). Mandibular distraction osteogenesis has been shown to have positive effects on oral feeding and for relieving respiratory obstruction, but its effects on postoperative weight gain are poorly understood. This study quantitatively analyzes weight gain following MDO. A retrospective chart review identified 22 RS children who underwent MDO. Patient weight data, feeding methods pre- and postoperatively, and polysomnography data pre- and postoperatively were collected. Each patient's weight plotted over time was then compared with his or her closest standardized growth curve, and linear regression analysis was utilized to quantify patient growth by calculating actual and expected average daily weight gain (g/d). Percentile changes were analyzed as well. Children gained significantly less weight than expected from birth to time of MDO and significantly more weight than expected from MDO to device removal, MDO to 6 months postoperatively, and MDO to 12 months postoperatively. The average growth percentile for the cohort was 37.3 at birth, declined to 22.7 by MDO, and increased to 28.5 and 33.5 at device removal and 6 months postoperatively, respectively. More than 70% of children were exclusively orally fed within 6 months of MDO. Children with isolated Robin Sequence had superior weight gain than children with syndromic Robin Sequence following surgery. In conclusion, MDO helps improve weight gain following surgery, particularly for infants with isolated Robin Sequence, and has positive effects on oral feeding and respiration.


Imaging mass spectrometry for accessing molecular changes during burn wound healing.
The spatiotemporal analysis of the proteomic profile during human wound healing is a critical investigative step that can establish the complex interplay of molecular events that comprise the local response to burn injury. Partial-thickness wound samples with adjacent "normal" skin were collected from twenty-one patients with burn wounds and examined across a time spectrum ranging from the acute injury period at 3, 6, 11 days to the later hypertrophic scar period at 7 and 15 months. The techniques used for histology-directed tissue analyses highlighted inflammatory protein markers at the early time points after injury with diminished expression as burn wounds progressed into the proliferative phase. The datasets show the usefulness of MALDI MS and imaging mass spectrometry as discovery approaches to identify and map the cutaneous molecular sequence that is activated in response to the unique systemic inflammatory response following burn trauma. This information has the potential to define the unique factors that predispose human burn victims to disfiguring hypertrophic scar formation.


Hydrogel-Nanoparticles Composite System for Controlled Drug Delivery.
Biodegradable poly(ethylene glycol)-block-poly(-lactic acid) (PEG-b-PLA) nanoparticles (NPs) were prepared by nanoprecipitation with controlled dimension and with different electric charges, as monitored by dynamic light scattering (DLS). Then NPs were loaded within hydrogels (HG) developed for biomedical applications in the central nervous system, with different pore sizes (30 and 90 nm). The characteristics of the resulting composite hydrogel-NPs system were firstly studied in terms of ability to control the release of small steric hindrance drug mimetic. Then, diffusion-controlled release of different charged NPs from different entangled hydrogels was studied in vitro and correlated with NPs electric charges and hydrogel mean mesh size. These studies showed different trends, that depend on NPs superficial charge and HG mesh size. Release experiments and diffusion studies, then rationalized by mathematical modeling, allowed us to build different drug delivery devices that can satisfy different medical needs.


Chapparvoviruses occur in at least three vertebrate classes and have a broad biogeographic distribution.
Chapparvoviruses are a highly divergent group of parvoviruses (family Parvoviridae) that have recently been identified via metagenomic sampling of animal faeces. Here, we report the sequences of six novel chapparvoviruses identified through both metagenomic sampling of bat tissues and in silico screening of published vertebrate genome assemblies. The novel chapparvoviruses share several distinctive genomic features and group together as a robustly supported monophyletic clade in phylogenetic trees. Our data indicate that chapparvoviruses have a broad host range in vertebrates and a global distribution.


The relationship between separation time and genetic distance based on angular transformations of gene frequencies.
Expressions are constructed for the theoretical expectation and the variance of the statistic chord2 used in connection with the genetic distances introduced by Cavalli-Sforza and Edwards. The gene frequency probability distribution is taken from Kimura's solution of the diffusion equation for pure random drift. The expression for the expectation is used for discussing whether distances are independent of original gene frequencies, and whether they are proportional to separation times. A modified method for estimating such separation times is proposed, and an example is given with cattle breeds. The accuracy of procedures based on genetic distances is evaluated using the variance of chord2.


Shifts in frog size and phenology: Testing predictions of climate change on a widespread anuran using data from prior to rapid climate warming.
Changes in body size and breeding phenology have been identified as two major ecological consequences of climate change, yet it remains unclear whether climate acts directly or indirectly on these variables. To better understand the relationship between climate and ecological changes, it is necessary to determine environmental predictors of both size and phenology using data from prior to the onset of rapid climate warming, and then to examine spatially explicit changes in climate, size, and phenology, not just general spatial and temporal trends. We used 100 years of natural history collection data for the wood frog, Lithobates sylvaticus with a range >9 million km2, and spatially explicit environmental data to determine the best predictors of size and phenology prior to rapid climate warming (1901-1960). We then tested how closely size and phenology changes predicted by those environmental variables reflected actual changes from 1961 to 2000. Size, phenology, and climate all changed as expected (smaller, earlier, and warmer, respectively) at broad spatial scales across the entire study range. However, while spatially explicit changes in climate variables accurately predicted changes in phenology, they did not accurately predict size changes during recent climate change (1961-2000), contrary to expectations from numerous recent studies. Our results suggest that changes in climate are directly linked to observed phenological shifts. However, the mechanisms driving observed body size changes are yet to be determined, given the less straightforward relationship between size and climate factors examined in this study. We recommend that caution be used in "space-for-time" studies where measures of a species' traits at lower latitudes or elevations are considered representative of those under future projected climate conditions. Future studies should aim to determine mechanisms driving trends in phenology and body size, as well as the impact of climate on population density, which may influence body size.


Effect of budesonide on TGF-beta1-enhanced VEGF production by lung fibroblasts.
VEGF (vascular endothelial growth factor) is a potent proangiogenic cytokine, and vascular change is one of the characteristic features of airway remodelling. Since the glucocorticoids have shown antifibrosis properties, we sought to investigate whether budesonide, a widely used glucocorticoid in clinical practice, could attenuate TGF-beta1 (transforming growth factor-beta1)-induced VEGF production by HFL-1 (human lung fibroblasts). HFL-1 fibroblasts were treated with various concentrations of budesonide (10(-11) M, 10(-9) M and 10(-7) M) in the absence or presence of TGF-beta1. Postculture media were collected for ELISA of VEGF at the indicated times. The cell lysates were subjected to Western blotting analysis to test TGF-beta1/Smad and MAP (mitogen-activated protein) kinase signalling activation, respectively. The results suggested that budesonide pretreatment reduced the significant increase of VEGF release induced by TGF-beta1 in HFL-1 fibroblasts in a dose-dependent manner, and suppressed the increase of phospho-Smad3 and phosphor-ERK (extracellular signal-regulated kinase) protein levels. In conclusion, budesonide may reduce TGF-beta1-induced VEGF production in the lung, probably through the Smad/ERK signalling pathway and, thus, may provide new sight into the molecular mechanism underlying glucocorticoid therapy for airway inflammatory diseases.