Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.
Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.


[Intraoperative treatment for atrial fibrillation using bi-polar radiofrequency ablation system: a clinical report of 91 cases].
To observe the short and mid-term therapeutic effects of Bi-polar ablation systems for intraoperative treatment of atrial fibrillation (AF). From March 2005 to January 2007, 91 patients received intraoperative treatment of atrial fibrillation with Bi-polar ablation systems, including 5 cases of paroxysmal atrial fibrillation and 86 persistent/permanent cases. The main concomitant heart diseases were rheumatic mitral valve diseases. Atricure Dry Ablation System was used for 37 cases and Cardioblate Irrigated Ablation System for 54 cases. The ablation lesion patterns included Cox-maze III, Modified Cox Mini-maze and Left-sided Maze. Mean ablation time was (14.1+/-6.7) min. No ablation-related complications occurred. Three patients died perioperatively. Two patients had permanent pacemaker implantation 3 months after operation. One case suffered from stroke and lower limb thrombosis 2.5 years after operation. Follow-up lasted for 6 to 29 months. The none-AF rhythm were 62.5%, 85.2%, 79.0% and 74.5% at discharge, 3 months, 6 months, and>or=12 months respectively. Compared to Uni-polar Ablation therapy group, the restoration of sinus rhythm in Bi-polar group were significantly higher at 6 months and>or=12 months postoperatively. The latest follow-up results indicated that 100% of preoperative paroxysmal atrial fibrillation patients restored sinus rhythm and 75.3% of persistent/permanent patients were free from atrial fibrillation. The none-AF rhythm of Atricure group (81.1%) showed no difference from the Cardioblate (77.5%). Meanwhile there were no significant differences among the three ablation lesion groups. Intraoperative radiofrequency ablation with Bi-polar systems is a feasible, safe and highly effective surgical option compared to the Uni-polar ablation technique.


Factors associated with sexually transmissible infection testing practices among men who have sex with men in Jamaica: results from a cross-sectional, tablet-based survey.
Background Men who have sex with men (MSM) are at elevated risk for sexually transmissible infection (STI) acquisition globally. Yet, limited research has explored STI testing practices among MSM in contexts where same-sex practices are criminalised, such as in Jamaica. A cross-sectional, tablet-based survey with MSM in Kingston, Ocho Rios and Montego Bay, Jamaica, was conducted. Multivariable logistic regression analyses were conducted to determine the adjusted risk ratio for lifetime STI testing and lifetime STI diagnosis. Multinomial logistic regression analyses were conducted to determine the relative odds of having had an STI test 3-5 months ago and 6-12 months ago in comparison with <3 months ago. Three-quarters (74.8%) of the 556 participants reported receiving an STI test (44% <3 months ago; 32% 3-5 months ago; 13% 6-12 months ago; 10% >12 months ago); 12.1% reported ever receiving an STI diagnosis. In adjusted multivariable analyses, STI testing was associated with sociodemographic (education, location), individual (depression, perceived risk), social (relationship status, sexual stigma) and structural (healthcare provider access) factors. In multinomial analysis, reporting a less recent STI test (>3 months ago) versus <3 months ago was associated with increased likelihood of sexual stigma and food insecurity. Lifetime STI diagnosis was associated with sociodemographic (location), individual (HIV infection) and social (lower social support) factors. Findings document associations between structural factors and delayed timing of STI testing. Further research is necessary to explore how to address social ecological factors in sexual health interventions with MSM in Jamaica.


Translocation of histone proteins across lipid bilayers and Mycoplasma membranes.
We show that the three core histones H2A, H3 and H4 can transverse lipid bilayers of large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In contrast, the histone H2B, although able to bind to the liposomes, fails to penetrate the unilamellar and the multilamellar vesicles. Translocation across the lipid bilayer was determined using biotin-labeled histones and an ELISA-based system. Following incubation with the liposomes, external membrane-bound biotin molecules were neutralized by the addition of avidin. Penetrating biotin-histone conjugates were exposed by Triton treatment of the neutralized liposomes. The intraliposomal biotin-histone conjugates, in contrast to those attached only to the external surface, were attached to the detergent lysed lipid molecules. Thus, biotinylated histone molecules that were exposed only following detergent treatment of the liposomes were considered to be located at the inner leaflet of the lipid bilayers. The penetrating histone molecules failed to mediate translocation of BSA molecules covalently attached to them. Translocation of the core histones, including H2B, was also observed across mycoplasma cell membranes. The extent of this translocation was inversely related to the degree of membrane cholesterol. The addition of cholesterol also reduced the extent of histone penetration into the MLVs. Although able to bind biotinylated histones, human erythrocytes, erythrocyte ghosts and Escherichia coli cells were impermeable to them. Based on the present and previous data histones appear to be characterized by the same features that characterize cell penetrating peptides and proteins (CPPs).


A Consumer Segmentation Study of Nutrition Information Seeking and Its Relation to Food Consumption in Beijing, China.
The aim of this study is to identify consumer groups based on nutrition information-seeking behavior and how it relates to food consumption. Although the Chinese public can now access nutrition information through different channels, research on the segmentation of homogeneous consumer groups seeking nutrition information is lacking. This study closes this research gap and, in doing so, also shows how information seeking is related to dietary behavior. A questionnaire was sent out to a stratified random sample in Beijing, resulting in 448 responses. A cluster analysis using hierarchical methods was conducted, identifying four distinct consumer groups: Multi-Channel (27.43%), Mass Media (20.57%), Moderate (27.88%), and Uninterested (24.12%). The four segments differed significantly concerning food consumption frequencies, food literacy, and sociodemographic characteristics. Consumers who were more involved in nutrition information tended to eat healthier. Our findings indicate that nutrition information is worth promoting, but this kind of intervention is not a cure-all. Targeted interventions should focus on uninterested populations by providing non-informational nudging strategies to promote healthy eating behaviors. This study contributes to the identification of meaningful profiles for targeted interventions, particularly as regards uninterested or unreached consumers.


The in cis compound EGFR mutations in Chinese advanced non-small cell lung cancer patients.
Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had EGFR mutation; among them, 15 patients (1.2%) harboring in cis compound EGFR mutations, with 10 patients carrying EGFR L858R in combination with a rare mutation and five patients carrying two rare EGFR mutations. No patient with EGFR 19del was observed. Interestingly, no in trans configuration was identified in this cohort. All of the patients harboring in cis compound EGFR mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with in cis compound EGFR mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating EGFR mutation. This observation was further supported by in silico molecular modeling analyses which demonstrated in cis compound mutations do not alter the ATP-binding pocket of EGFR, thus having no effect on the interaction between gefitinib and EGFR.


Dietary fat stimulates pancreatic cancer growth and promotes fibrosis of the tumor microenvironment through the cholecystokinin receptor.
The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat to aid in digestion, and plasma CCK levels are elevated with the consumption of high-fat diets. CCK is also a trophic peptide for the pancreas and has also been shown to stimulate growth of pancreatic cancer. In the current investigation, we studied the influence of a diet high in saturated fat on the growth of pancreatic cancer in syngeneic murine models before the mice became obese to exclude the confounding factors associated with obesity. The high-fat diet significantly increased growth and metastasis of pancreatic cancer compared with the control diet, and the stimulatory effect was blocked by the CCK-receptor antagonist proglumide. We then selectively knocked out the CCK receptor on the pancreatic cancer cells using clustered regularly interspaced short palindromic repeats technology and showed that without CCK-receptors, dietary fat was unable to stimulate cancer growth. We next demonstrated that dietary fat failed to influence pancreatic cancer xenograft growth in genetically engineered CCK peptide knockout mice. The tumor-associated fibrosis that is so prevalent in the pancreatic cancer microenvironment was significantly decreased with CCK-receptor antagonist therapy because fibroblasts also have CCK receptors. The CCK-receptor antagonist proglumide also altered tumor metalloprotease expression and increased tumor suppressor genes by a PCR array. Our studies confirm that a diet high in saturated fat promotes growth of pancreatic cancer and the action is mediated by the CCK-receptor pathway. NEW & NOTEWORTHY Diets high in long-chain saturated fats promote growth of pancreatic cancer independent of obesity. The mechanism through which dietary fat promotes cancer is mediated through the cholecystokinin (CCK) receptor pathway. Therapy with a CCK-receptor antagonist altered the tumor microenvironment by reducing fibrosis, increasing cluster of differentiation 8+ lymphocytes, increasing tumor suppressor genes, and thus decreasing metastases. Use of CCK-receptor antagonist therapy with standard chemotherapy for pancreatic cancer may improve response by altering the tumor microenvironment.


Infrared multiphoton dissociation and electron capture dissociation of high-mannose type glycopeptides.
The combination of electron capture dissociation (ECD) and infrared multiphoton dissociation (IRMPD) for the structural characterization of high-mannose type glycopeptides is explored in depth for the first time. Contrary to previous applications to other glycan types, our analyses reveal that IRMPD does not necessarily selectively induce glycan cleavage in high-mannose type glycopeptides; rather peptide backbone cleavage can effectively compete with glycosidic cleavage. Poor glycan cleavage with IRMPD is due to a higher gas-phase stability of mannose-linking glycosidic bonds. This reasoning also explains mannose cleavage patterns observed for a xylose type glycopeptide with IRMPD. In addition, extensive peptide backbone cleavage is observed for a >6 kDa glycopeptide with ECD, to our knowledge the largest glycopeptide examined with this technique to date.


Ethnic medicine: from fundamental studies to practice of health preservation of the indigenous peoples in the North.
We carry out social-hygienic and medical examinations of the indigenous population of the Russian northern territories. Mobile medical teams examined the population of the most of settlements of the Nenets autonomous area. The study of the peculiarities of the public health state of the indigenous people. The studies allowed us to work out normative indices of physical development, functional state of the systems of hemopoiesis, blood circulation, immunity, exchange of microelements and electrolytes, to reveal the region's peculiarities of functional indices of a number of life supporting systems and their influence on the character of pathology course, the regional structure of morbidity, to work out schemes of their correction rational under these conditions. The results of the carried out long-term scientific and practical work on the study and preservation of health of the northern indigenous peoples small in number have led to conclusion about the need in organization of a new direction in medicine, i.e., ethnical medicine.


Mismatch and G-stack modulated probe signals on SNP microarrays.
Single nucleotide polymorphism (SNP) arrays are important tools widely used for genotyping and copy number estimation. This technology utilizes the specific affinity of fragmented DNA for binding to surface-attached oligonucleotide DNA probes. We analyze the variability of the probe signals of Affymetrix GeneChip SNP arrays as a function of the probe sequence to identify relevant sequence motifs which potentially cause systematic biases of genotyping and copy number estimates. The probe design of GeneChip SNP arrays enables us to disentangle different sources of intensity modulations such as the number of mismatches per duplex, matched and mismatched base pairings including nearest and next-nearest neighbors and their position along the probe sequence. The effect of probe sequence was estimated in terms of triple-motifs with central matches and mismatches which include all 256 combinations of possible base pairings. The probe/target interactions on the chip can be decomposed into nearest neighbor contributions which correlate well with free energy terms of DNA/DNA-interactions in solution. The effect of mismatches is about twice as large as that of canonical pairings. Runs of guanines (G) and the particular type of mismatched pairings formed in cross-allelic probe/target duplexes constitute sources of systematic biases of the probe signals with consequences for genotyping and copy number estimates. The poly-G effect seems to be related to the crowded arrangement of probes which facilitates complex formation of neighboring probes with at minimum three adjacent G's in their sequence. The applied method of "triple-averaging" represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested.


Social Media Burnout and Internet Addiction: The Role of Extroversion and Social Self-Concept in a Brazilian Sample.
The aim of this study was to examine the role played by the extroversion and social self-concept in the relationship between internet addiction and social media burnout. 200 individuals from the Brazilian general population between the ages of 18 and 45 participated and responded to the Compulsive Internet Use Scale, the Social Media Burnout Scale, the Multidimensional Self-Concept Scale, and a scale of reduced markers for personality assessment. The data were analyzed with the SPSS software. Results showed positive and statistically significant correlations between internet addiction and social media burnout, as well as negative correlations between both variables with social self-concept and extroversion. Furthermore, social self-concept had a significant indirect effect on the relationship between Internet addiction and social media burnout by appearing to mediate this relationship. This study contributes to the endorsement of the literature on the subject and prompts consideration of interventions needed by psychologists to promote social skills and appropriate internet use.


Exploring tree-habitat associations in a Chinese subtropical forest plot using a molecular phylogeny generated from DNA barcode loci.
Elucidating the ecological mechanisms underlying community assembly in subtropical forests remains a central challenge for ecologists. The assembly of species into communities can be due to interspecific differences in habitat associations, and there is increasing evidence that these associations may have an underlying phylogenetic structure in contemporary terrestrial communities. In other words, by examining the degree to which closely related species prefer similar habitats and the degree to which they co-occur, ecologists are able to infer the mechanisms underlying community assembly. Here we implement this approach in a diverse subtropical tree community in China using a long-term forest dynamics plot and a molecular phylogeny generated from three DNA barcode loci. We find that there is phylogenetic signal in plant-habitat associations (i.e. closely related species tend to prefer similar habitats) and that patterns of co-occurrence within habitats are typically non-random with respect to phylogeny. In particular, we found phylogenetic clustering in valley and low-slope habitats in this forest, indicating a filtering of lineages plays a dominant role in structuring communities in these habitats and we found evidence of phylogenetic overdispersion in high-slope, ridge-top and high-gully habitats, indicating that distantly related species tended to co-occur in these high elevation habitats and that lineage filtering is less important in structuring these communities. Thus we infer that non-neutral niche-based processes acting upon evolutionarily conserved habitat preferences explain the assembly of local scale communities in the forest studied.


Multimodal communication by male mantled howler monkeys (Alouatta palliata) in sexual contexts: a descriptive analysis.
We analyzed continuously sampled focal and ad libitum data of male mantled howler monkeys (Alouatta palliata) observed in random order. Males resided in two groups in a Costa Rican tropical dry forest environment (riparian habitat group: 3 males, 15 females, 402 h observation; deciduous habitat group: 2 males, 8 females, 114 h observation). Samples were limited to sexual contexts, in particular, the 60-min periods before and after each copulation observed within each group for each male. Time samples for each male were distributed equally before and after their own copulations. Before statistical analyses were conducted, data were corrected for differences in time sampled for males within each group. Four types of multimodal signaling were resolved: (1) audiovisual, (2) olfactory-visual, (3) olfactory-visual-tactile and (4) tactile-gustatory. Olfactory and tactile signals were never observed in combination with auditory signals. Consistent with expectation for a Neotropical, arboreal species, audiovisual signals were the most frequently observed type of multimodal communication in both groups (riparian habitat group: n = 139; deciduous habitat group: n = 66). Our evidence strongly suggests that unimodal signals may be combined and recombined to form complex, multimodal signals. Subordinate males in each group were more likely than dominant males to emit audiovisual signals before their own copulations. Male dyads were compared to assess the relative rate of audiovisual signaling by one male before another male's copulations. On average, the subordinate male of the riparian habitat group exhibited audiovisual signals at a higher rate before his own copulations compared to the rate of audiovisual signaling by his dominant challengers. The same comparisons are not significant for males in the deciduous habitat group. The pattern of male response that we report whereby subordinates emit some complex signals at a higher rate than dominants supports the 'terminal investment hypothesis' predicting that organisms should increase reproductive effort with age since, in mantled howlers, age correlates negatively with dominance rank. Additional, qualitative observations suggested that subordinates in both groups were most likely to obtain copulations when they increased rates of complex signaling and/or escalated interactions with their male challengers. Group differences were apparent, however, and we suggest factors that may account for these patterns. We assessed responses by female receivers of complex signals emitted by males in sexual contexts. In general, higher-ranking males are more attractive to females and are more successful at monopolizing them. Findings for other, less frequently displayed, multimodal signals (olfactory-visual, olfactory-visual-tactile and tactile-gustatory) are presented and discussed. We conclude with the suggestion that howlers may be a robust model for the investigation of complex signals in Neotropical primates, including research on functionally referential communication and context-dependent syntax.


Second derivative synchronous fluorescence determination of avanafil in the presence of its acid-induced degradation product aided by powerful Lean Six Sigma tools augmented with D-optimal design.
In this work, the quantitative determination of an erectile dysfunctional drug avanafil in the presence of its acid-induced degradation product was achieved via the application of a pre-optimized novel spectrofluorimetric method. The fluorescence emission wavelength was recorded at 370 and 407 nm, after being excited at 268 and 271 nm for avanafil and its acid-induced degradation product, respectively. Direct determination of avanafil based on its native fluorescence is restricted because the emission spectra of both components are heavily overlapped. Therefore, to overcome this constraint, a novel second derivative synchronous fluorescence method was evolved to eliminate this overlapping. The ideal determination wavelength was found to be 377 nm. Augmentation of lean six sigma (LSS) with response surface methodology (RSM) play a significant role in the development of robust specifications to ensure quality at the six sigma level with a high level of statistical confidence and targeted performance. All of the experimental conditions were optimized using D-optimal design as a RSM to select the optimal parameters. In addition, this work includes a graphical representation of the relationships between various variables that can greatly affect the results and the intensity of the synchronous fluorescence.


pp60(c-src) modulates microvascular endothelial phenotype and in vitro angiogenesis.
The tyrosine kinase c-src associates with the platelet-derived growth factor (PDGF) receptor. Overexpression of wild-type c-src, a kinase-negative c-src mutant, and v-src in microvascular endothelial cells modulated the mitogenic effect of PDGF, suggesting that c-src kinase activity inhibits PDGF signals. Analyses of cell morphology in two-dimensional culture revealed changes in cell shape and size induced by the overexpression of c-src proteins. Investigations in three-dimensional culture unveiled a modulatory role of c-src during in vitro angiogenesis. Overexpression of c-src resulted in an increased diameter of tube-like structures, and the number of branching segments was decreased. Expression of the kinase-negative c-src mutant resulted in abortive tube formation consisting of disconnected multicellular fragments. These results indicate that the c-src tyrosine kinase exerts regulatory effects on endothelial proliferation, size, and cytoskeletal organization in two-dimensional culture and on the formation of a differentiated multicellular network in three-dimensional culture.


Host cell-surface proteins as substrates of gingipains, the main proteases of Porphyromonas gingivalis.
Gingipains are extracellular cysteine proteases of the oral pathogen Porphyromonas gingivalis and are its most potent virulence factors. They can degrade a great variety of host proteins, thereby helping the bacterium to evade the host immune response, deregulate signaling pathways, trigger anoikis and, finally, cause tissue destruction. Host cell-surface proteins targeted by gingipains are the main focus of this review and span three groups of substrates: immune-regulatory proteins, signaling pathways regulators and adhesion molecules. The analysis of published data revealed that gingipains predominantly inactivate their substrates by cleaving them at one or more sites, or through complete degradation. Sometimes, gingipains were even found to initially shed their membrane substrates, but this was mostly just the first step in the degradation of cell-surface proteins.


Practicing what we preach: developing a data sharing policy for the Journal of the Medical Library Association.
Providing access to the data underlying research results in published literature allows others to reproduce those results or analyze the data in new ways. Health sciences librarians and information professionals have long been advocates of data sharing. It is time for us to practice what we preach and share the data associated with our published research. This editorial describes the activity of a working group charged with developing a research data sharing policy for the Journal of the Medical Library Association.


Microstructure Evolution of Graphene and the Corresponding Effect on the Mechanical/Electrical Properties of Graphene/Cu Composite during Rolling Treatment.
Rolling enables the directional alignment of the reinforcements in graphene/Cu composites while achieving uniform graphene dispersion and matrix grain refinement. This is expected to achieve a breakthrough in composite performance. In this paper, the process parameters of rolling are investigated, and the defects, thickness variations of graphene and property changes of the composite under different parameters are analyzed. High-temperature rolling is beneficial to avoid the damage of graphene during rolling, and the prepared composites have higher electrical conductivity. The properties of graphene were investigated. Low-temperature rolling is more favorable to the thinning and dispersion of graphene; meanwhile, the relative density of the composites is higher in the low-temperature rolling process. With the increase of rolling deformation, the graphene defects slightly increased and the number of layers decreased. In this paper, the defect states of graphene and the electrical conductivity with different rolling parameters is comprehensively investigated to provide a reference for the rolling process of graphene/copper composites with different demands.


Aberrant methylation and decreased expression of the RIZ1 gene are frequent in adult acute lymphoblastic leukemia of T-cell phenotype.
Retinoblastoma protein-interacting zinc finger, RIZ1, is a tumor suppressor gene that is inactivated in various solid tumors. However, the role of the RIZ1 gene has not been well examined in adult acute lymphoblastic leukemia (ALL). We analyzed the expression and promoter methylation status of the RIZ1 gene in patients with newly diagnosed ALL by quantitative real-time reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR, respectively. RIZ1 expression in 67 cases of ALL (mean 1.043) was decreased compared with that in normal bone marrow (mean 1.471) (p = 0.030). Methylation was detected in 11 of 71 patients (15.5%) but not in healthy controls. Methylation was associated with decreased RIZ1 expression in many ALL cases examined, but this was not statistically significant. In T-ALL, RIZ1 methylation was more frequent (63.6%) than in B-ALL (6.7%) (p < 0.0001) and the decrease of RIZ1 expression was more significant than in B-ALL (p = 0.045). 5-Aza-2'-deoxycytidine treatment of MOLT-4 cells with RIZ1 methylation induced demethylation of RIZ1 and restoration of expression. Forced RIZ1 expression in T-ALL cell lines suppressed cell growth accompanied by G2/M arrest and apoptosis. No mutations were found by PCR-single strand conformation polymorphism analysis in hotspots of the gene. These results suggest that RIZ1 is inactivated in adult ALL, and this inactivation is associated with methylation in T-ALL.


Influence of the arterial input function on absolute and relative perfusion-weighted imaging penumbral flow detection: a validation with ¹⁵O-water positron emission tomography.
Perfusion-weighted imaging maps are used to identify critical hypoperfusion in acute stroke. However, quantification of perfusion may depend on the choice of the arterial input function (AIF). Using quantitative positron emission tomography we evaluated the influence of the AIF location on maps of absolute and relative perfusion-weighted imaging to detect penumbral flow (PF; <20 mL/100 g/min on positron emission tomography(CBF)) in acute stroke. In 22 patients with acute stroke the AIF was placed at 7 sites (M1, M2, M3 ipsi- and contralateral and internal carotid artery-M1 contralateral to the infarct). Comparative (15)O-water positron emission tomography and AIF-dependent perfusion-weighted imaging (cerebral blood flow, cerebral blood volume, mean transit time, and time to maximum) were performed. A receiver operating characteristic curve analysis described the threshold independent performance (area under the curve) of the perfusion-weighted maps for all 7 AIF locations and identified the best AIF-dependent absolute and relative thresholds to identify PF. These results were compared with AIF-independent time-to-peak maps. Quantitative perfusion-weighted imaging maps of cerebral blood flow and time to maximum performed best. For PF detection, AIF placement did significantly influence absolute PF thresholds. However, AIF placement did not influence (1) the threshold independent performance; and (2) the relative PF thresholds. AIF placement in the proximal segment of the contralateral middle cerebral artery (cM1) was preferable for quantification. AIF-based maps of cerebral blood flow and time to maximum were most accurate to detect the PF threshold. The AIF placement significantly altered absolute PF thresholds and showed best agreement with positron emission tomography for the cM1 segment. The performance of relative PF thresholds, however, was not AIF location-dependent and might be along with AIF-independent time-to-peak maps, more suitable than absolute PF thresholds in acute stroke if detailed postprocessing is not feasible.


Laser processed TiN reinforced Ti6Al4V composite coatings.
The purpose of this first generation investigation is to evaluate fabrication, in vitro cytotoxicity, cell-material interactions and tribological performance of TiN particle reinforced Ti6Al4V composite coatings for potential wear resistant load bearing implant applications. The microstructural analysis of the composites was performed using scanning electron microscope and phase analysis was done with X-ray diffraction. In vitro cell-material interactions, using human fetal osteoblast cell line, have been assessed on these composite coatings and compared with Ti6Al4V alloy control samples. The tribological performance of the coatings were evaluated, in simulated body fluids, up to 1000 m sliding distance under 10 N normal load. The results show that the composite coatings contain distinct TiN particles embedded in α+β phase matrix. The average top surface hardness of Ti6Al4V alloy increased from 394±8 HV to 1138±61 HV with 40 wt% TiN reinforcement. Among the composite coatings, the coatings reinforced with 40 wt% TiN exhibited the highest wear resistance of 3.74×10(-6) mm(3)/Nm, which is lower than the wear rate, 1.04×10(-5) mm(3)/Nm, of laser processed CoCrMo alloy tested under identical experimental conditions. In vitro biocompatibility study showed that these composite coatings were non-toxic and provides superior cell-material interactions compared to Ti6Al4V control, as a result of their high surface energy. In summary, excellent in vitro wear resistance and biocompatibility of present laser processed TiN reinforced Ti6Al4V alloy composite coatings clearly show their potential as wear resistant contact surfaces for load bearing implant applications.


Flow reversals in low-Prandtl-number Rayleigh-Bénard convection controlled by horizontal circulations.
We performed numerical simulations of Rayleigh-Bénard convection of an electrically conductive low-Prandtl-number fluid under a uniform horizontal magnetic field. We reproduced the flow reversals observed in laboratory experiments previously reported by us. The flow pattern is moderately constrained, as the axes of convection rolls tend to align in the direction of the horizontal magnetic field. The flow reversals occur when the intensity of horizontal circulation in a vessel exceeds a certain value, which induces bending and reconnection of convection rolls and causes rearrangement of these rolls. The wave number selection mechanism is responsible for the instability leading to the flow reversals. The total heat flow drastically decreases at the occurrences of reversal, reflecting the reduction of roll flow velocity. The irregularity of the reversal sequence and the change in symmetry in the flow pattern during the reversals are consistent with that in cessation-led flow reversals.


Tree Visualization By One Table (tvBOT): a web application for visualizing, modifying and annotating phylogenetic trees.
tvBOT is a user-friendly and efficient web application for visualizing, modifying, and annotating phylogenetic trees. It is highly efficient in data preparation without requiring redundant style and syntax data. Tree annotations are powered by a data-driven engine that only requires practical data organized in uniform formats and saved as one table file. A layer manager is developed to manage annotation dataset layers, allowing the addition of a specific layer by selecting the columns of a corresponding annotation data file. Furthermore, tvBOT renders style adjustments in real-time and diversified ways. All style adjustments can be made on a highly interactive user interface and are available for mobile devices. The display engine allows the changes to be updated and rendered in real-time. In addition, tvBOT supports the combination display of 26 annotation dataset types to achieve multiple formats for tree annotations with reusable phylogenetic data. Besides several publication-ready graphics formats, JSON format can be exported to save the final drawing state and all related data, which can be shared with other users, uploaded to restore the final drawing state for re-editing or used as a style template for quickly retouching a new tree file. tvBOT is freely available at: https://www.chiplot.online/tvbot.html.


Dietary n-3 and n-6 polyunsaturated oils and airway contractility.
Recent reports suggest modulation of chronic obstructive pulmonary disease by dietary polyunsaturated fatty acids. In the present study, we re-examined this possibility by using an established animal model of pulmonary sensitisation. Adult guinea pigs were fed diets supplemented (10% w/w) with either olive, canola or safflower oil for 4 weeks before sensitising with ovalbumin and continuing on various diets for a further 6 week period. Neither the contraction following ovalbumin challenge, nor the responses to histamine, carbachol and various eicosanoid mediators - prostaglandin F(2 alpha), leukotriene C(4), thromboxane mimetic U44619 - of isolated segments of airway tissue were altered (P>0.05, ANOVA) by the dietary lipid treatment. Lipid analysis showed changes in membrane linoleic acid (18:2n-6) and alpha -linolenic acids (alpha 18:3n-3) in lung phospholipids consistent with dietary intakes. However, no significant further desaturation/elongation of these dietary precursors was evident. Ovalbumin induced contraction was fully reversed by the lipoxygenase inhibitor esculetin whilst indomethacin resulted in a slight increase possibly due to the inhibition of bronchodilator prostanoids. Results confirm that under the conditions employed airway function was not influenced by the variable dietary intakes of n-3 and n-6 PUFA.


[Orthostatic low blood pressure in patient suffering from hypertension, in external cardiology consultation].
This work was aimed to describe the epidemiological, clinical, biological and electrical aspects of orthostatic low blood pressure (LBP) within patients with high blood pressure (HBP) in the cardiology department of the Kati University Hospital. This was a prospective cross-sectional study conducted between June 1st, 2012 and May 31st, 2013. It included all the patients with HBP regularly assessed for at least a month, following their treatment and having no other treatments which can induce a orthostatic LBP. With a total of 300 subjects with high blood pressure, 42 subjects presented an orthostatic LBP with or without suggestive clinical demonstrations, among which 16 men and 26 women, with an average age of 55 year. In the HBP population, the orthostatic LBP had a 14% frequency (42/300), the sex ratio was 0.61. Most of the patients were 55 years old or more. The HBP was not controlled in 66.7% of cases. Twelve percent of the patients with orthostatic LBP were diabetics. The number of antihypertensive drug used did not appear to influence the appearance of an orthostatic LBP. Monotherapy was associated with an orthostatic LBP in 47.6% of cases and this monotherapy used the calcic inhibitors in 62% of the cases. Orthostatic low blood pressure is frequent within patient with HBP undergoing treatment. It must be systematically looked for, especially in the uncontrolled HBP, among older subjects, the diabetics, and those with a personal history of neurological disease.


[Modified pedicled cranial periosteum compound flap to reconstruct the defect of anterior cranial fossa complicated with cerebrospinal fluid leakage].
To explore the effect of modified pedicled cranial periosteum compound flap in reconstructing the defect of anterior cranial fossa complicated with cerebrospinal fluid leakage. Seven nasal and sinus tumor cases with defects and CSF were undertaken reconstructing surgery with the flap, of which 1 was benign and the others were malignancies. The transferred flap pedicled with the frontal branch of the superficial temporal artery and complemented with ipsilateral supraorbital and/or supratraochlear artery. All cases healed without failure, one case with adjuvant radiotherapy experienced partial free frontal bone necrosis and healed by ways of drainage through temporal incision. The inner surface of the flap in the nasal cavity was smooth. Frontal cranial periosteum compound flap have some advantages, such as adequate quantity, good blood supply and easily making,so it can be choose as an important method to reconstruct the defects of anterior cranial fossa and CSF leakage.


Retinoids induce cellular senescence in breast cancer cells by RAR-β dependent and independent pathways: Potential clinical implications (Review).
Most studies on cellular senescence (CS) have been performed in vitro by employing cytotoxic agents, irradiation, chromatin and telomerase modulators or by activating certain oncogenes. All these approaches usually lead to DNA damage, gene instability and/or chromatin alterations that primarily affect p53-p21 signaling. Little is known on whether retinoids and rexinoids, which are cell differentiation agents, can also induce CS in vitro and in vivo, and which molecular mechanisms are involved in promoting the senescent phenotype. We reviewed the recent publications on CS induced by retinoids and rexinoids in ER+ and ER- breast cancer cell lines and in corresponding animal models of mammary carcinogenesis which simulate those of human breast cancer. The role of retinoic acid receptors β2 and 5 (RARβ2 and RARβ5) and of receptor independent genes involved in mediating the senescence program of retinoids and rexinoids in ER+ and ER- breast cancer cells is discussed. Potential strategists for clinical implication of CS as biomarker of prognosis and of response to treatment with retinoids, rexinoids and with other cell differentiation and antitumor agents are outlined.


[Medical counselling of the hypertensive patient (author's transl)].
The diagnosis of arterial hypertension cannot be in doubt with repeated high blood pressure readings (140/90 under 40 years and over 40 years 160/95). In particular it will be easier to reconcile a patient who has no symptoms and who is not motivited by complaints to the understanding of a usually lifelong therapy by an exhaustive discussion. The patient must know that the risk of secondary cardiac diseases increases continuously with the level of the average arterial pressure (both systolic and diastolic) and that this average pressure includes all values of the excessive range of fluctuation of the blood pressure in hypertensive disease (stress peaks, resting values). The diagnostic program leads to a causal (surgical) therapy only in isolated cases (1 to 2%). For symptomatic therapy the general measures "adjustment of the way of living" and "diet" are the decisive basis for effective treatment.


Ischemia and reperfusion during intermittent coronary occlusion in man. Studies of electrocardiographic changes and CPK release.
The course of 357 balloon inflations performed during 38 angioplasties for single-vessel coronary artery disease was prospectively studied using continuous ECG recording. Ischemic ECG changes appeared during 91 percent of the inflations at a mean of 20 +/- 8 seconds after inflation and resolved in 97 percent of those at a mean of 11 +/- 5 seconds after deflation. Elevation of the plasma CPK level was found in six patients who had ischemic ECG changes for at least 7.8 minutes. The duration of ischemia did not exceed 5.4 minutes in any of the patients without CPK elevation. Resolution of the ischemic changes was delayed in patients with CPK elevation and in last vs initial inflations. We conclude that in patients with noninfarcted myocardium, ECG changes follow coronary occlusion and reflow very rapidly, detecting these coronary events with a high sensitivity. Lack of rapid regression predicts lack of reperfusion, and persistence of ischemia for more than 7.8 minutes is sufficient to cause myocardial necrosis.


Synthesis of Terpineol from Alpha-Pinene Catalyzed by α-Hydroxy Acids.
We report the use of five alpha-hydroxy acids (citric, tartaric, mandelic, lactic and glycolic acids) as catalysts in the synthesis of terpineol from alpha-pinene. The study found that the hydration rate of pinene was slow when only catalyzed by alpha-hydroxyl acids. Ternary composite catalysts, composed of AHAs, phosphoric acid, and acetic acid, had a good catalytic performance. The reaction step was hydrolysis of the intermediate terpinyl acetate, which yielded terpineol. The optimal reaction conditions were as follows: alpha-pinene, acetic acid, water, citric acid, and phosphoric acid, at a mass ratio of 1:2.5:1:(0.1-0.05):0.05, a reaction temperature of 70 °C, and a reaction time of 12-15 h. The conversion of alpha-pinene was 96%, the content of alpha-terpineol was 46.9%, and the selectivity of alpha-terpineol was 48.1%. In addition, the catalytic performance of monolayer graphene oxide and its composite catalyst with citric acid was studied, with acetic acid used as an additive.


Characterization of a novel isoflavone glycoside-hydrolyzing β-glucosidase from mangrove soil metagenomic library.
For the beneficial pharmacological properties of isoflavonoids and their related glycoconjugates, there is increasingly interest in their enzymatic conversion. In this study, a novel β-glucosidase gene isolated from metagenomic library of mangrove sediment was cloned and overexpressed in Escherichia coli BL21(DE3). The purified recombination β-glucosidase, designated as r-Bgl66, showed high catalytic activity for soy isoflavone glycosides. It converted soy isoflavone flour extract with the productivities of 0.87 mM/h for daidzein, 0.59 mM/h for genistein and 0.42 mM/h for glycitein. The kcat/Km values for daidzin, genistin and glycitin were 208.73, 222.37 and 288.07 mM-1 s-1, respectively. In addition, r-Bgl66 also exhibited the characteristic of glucose-tolerance, and the inhibition constant Ki was 471.4 mM. These properties make it a good candidate in the enzymatic hydrolysis of soy isoflavone glycosides. This study also highlights the utility of metagenomic approach in discovering novel β-glucosidase for soy isoflavone glycosides hydrolysis.


Commonly available outcome measures for use in Indian boys with Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder. It is still an incurable disease and many clinical trials are going on to find the cure for this disease. There is a need for sensitive and reliable measures for detecting the disease progression. This manuscript focuses on reviewing the different outcome measures which can be used in the Indian DMD patients.


A2-A1-D-A1-A2 Type Non-Fullerene Acceptors with 2-(1,1-Dicyanomethylene)rhodanine as the Terminal Groups for Poly(3-hexylthiophene)-Based Organic Solar Cells.
2-(1,1-Dicyanomethylene)rhodanine (RCN) is an important electron-deficient terminal unit to build non-fullerene acceptors (NFAs) having been realized high power conversion efficiency (PCE) beyond 12% with complicated p-type polymer as electron donor. However, the photovoltaic properties of RCN-based NFAs are unsatisfied when paired with the classic p-type polymer poly(3-hexylthiophene) (P3HT). In order to make a contribution in this regard, we designed two RCN-based small molecular acceptors with A2-A1-D-A1-A2 structure, BT3 and BTA3, where benzothiadiazole (BT) and benzotriazole (BTA) are bridged A1 segments, respectively, to modulate the optoelectronic properties. As a result, P3HT:BTA3 solar cell exhibits a promising PCE of 5.64%, with a VOC of 0.90 V and a fill factor (FF) of 0.65, which is obviously much better than that of P3HT:BT3 (PCE = 2.55%, VOC = 0.72 V, FF = 0.61). The higher electron mobility of P3HT:BTA3 film indicates BTA3 tends to form a continuous pathway for electron transport even at a lower weight ratio of 1:0.3 than 1:0.5 for P3HT:BT3 film. Our results indicate that introducing a weak electron-withdrawing building block BTA is an effective strategy compared with the BT counterpart to improve the performance of RCN-based NFA devices.


Voltage-gated proton channels find their dream job managing the respiratory burst in phagocytes.
The voltage-gated proton channel bears surprising resemblance to the voltage-sensing domain (S1-S4) of other voltage-gated ion channels but is a dimer with two conduction pathways. The proton channel seems designed for efficient proton extrusion from cells. In phagocytes, it facilitates the production of reactive oxygen species by NADPH oxidase.


Periodic Functionalization of Surface-Confined Pores in a Two-Dimensional Porous Network Using a Tailored Molecular Building Block.
We present here the periodic functionalization of a two-dimensional (2D) porous molecular network using a tailored molecular building block. For this purpose, a dehydrobenzo[12]annulene (DBA) derivative, 1-isoDBA, having an isophthalic acid unit connected by an azobenzene linker to a C12 alkyl chain and five C14 chains, was designed and synthesized. After the optimization of monolayer preparation conditions at the 1,2,4-trichlorobezene (TCB)/graphite interface, scanning tunneling microscopy (STM) observation of the self-assembled monolayer of 1-isoDBA revealed the formation of extended domains of a porous honeycomb-type molecular network, which consists of periodically located nanowells each functionalized by a cyclic hexamer of hydrogen-bonded isophthalic acid units and those without functional groups. This result demonstrates that the present strategy based on precise molecular design is a viable route to site-specific functionalization of surface-confined nanowells. The nanowells of different size can be used for guest coadsorption of different guests, coronene COR and hexakis[4-(phenylethynyl)phenylethynyl]benzene HPEPEB, whose size and shape match the respective nanowells. STM observation of a ternary mixture (1-isoDBA/COR/HPEPEB) at the TCB/graphite interface revealed the site-selective immobilization of the two different guest molecules at the respective nanowells, producing a highly ordered three-component 2D structure.


Genetic structure among 50 species of the northeastern Pacific rocky intertidal community.
Comparing many species' population genetic patterns across the same seascape can identify species with different levels of structure, and suggest hypotheses about the processes that cause such variation for species in the same ecosystem. This comparative approach helps focus on geographic barriers and selective or demographic processes that define genetic connectivity on an ecosystem scale, the understanding of which is particularly important for large-scale management efforts. Moreover, a multispecies dataset has great statistical advantages over single-species studies, lending explanatory power in an effort to uncover the mechanisms driving population structure. Here, we analyze a 50-species dataset of Pacific nearshore invertebrates with the aim of discovering the most influential structuring factors along the Pacific coast of North America. We collected cytochrome c oxidase I (COI) mtDNA data from populations of 34 species of marine invertebrates sampled coarsely at four coastal locations in California, Oregon, and Alaska, and added published data from 16 additional species. All nine species with non-pelagic development have strong genetic structure. For the 41 species with pelagic development, 13 show significant genetic differentiation, nine of which show striking FST levels of 0.1-0.6. Finer scale geographic investigations show unexpected regional patterns of genetic change near Cape Mendocino in northern California for five of the six species tested. The region between Oregon and Alaska is a second focus of intraspecific genetic change, showing differentiation in half the species tested. Across regions, strong genetic subdivision occurs more often than expected in mid-to-high intertidal species, a result that may reflect reduced gene flow due to natural selection along coastal environmental gradients. Finally, the results highlight the importance of making primary research accessible to policymakers, as unexpected barriers to marine dispersal break the coast into separate demographic zones that may require their own management plans.


Management of inherited thrombophilia: guide for genetics professionals.
Venous thromboembolism (VTE) is a common source of morbidity and mortality in developed countries. Heritable risk factors for VTE (thrombophilias) can be identified in 30-50% of affected patients. Factor V Leiden, prothrombin 20210G>A, and deficiencies of antithrombin, protein C and protein S increase the risk of a first VTE. However, an individual's thrombotic risk is determined by a complex interplay of genetic, acquired and circumstantial risk factors. At least 50% of VTE events in thrombophilic individuals are provoked by predisposing factors such as immobility, surgery, trauma, cancer, hormonal therapy and pregnancy. Non-modifiable risk factors such as advancing age and family history also increase thrombotic risk. An evidence-based risk factor evaluation is an essential step in VTE prevention. This review will educate genetics professionals about inherited and acquired risk factors for VTE and discuss recommendations for management of asymptomatic individuals with thrombophilia.


Digital scan over dental dam: workflow for successful clinical outcome.
Although the use of intraoral scanners is becoming more popular, dental professionals are still presented with the challenge of obtaining precise imaging of the preparation margins. Deep preparation margins, saliva contamination, or bleeding during the scanning procedures can impair the accuracy of the digital scan. Dental dam placement can significantly improve the quality and efficiency of the digital scan, while simultaneously providing a clean restorative field and serving as a barrier to the spread of infections for the protection of dental professionals. This article describes a technique of intraoral scanning by using dental dam isolation to ensure maximum accuracy of the digital scan of the dental preparations.


Prenatal Prediction of Difficult Intubation in Periviable Neonates Using Standard Fetal Biometric Parameters.
To assess whether standard fetal biometric parameters can be used to predict difficult intubations in periviable neonates undergoing resuscitation. This is a retrospective case-control study of periviable neonates delivered at 23 to 256/7 weeks at an academic hospital during a 5-year period in whom intubation was attempted. Standard fetal biometric measurements were included if they were taken within 7 days of delivery. Primary outcome was intubation in one attempt and was compared with more than one attempt. Data were also collected for fetal gestational age at delivery, neonatal birth weight, estimated fetal weight, head circumference, biparietal diameter, and abdominal circumference. Parametric and nonparametric statistical tests used p < 0.05 as significant. In total, 93 neonates met the inclusion criteria. The mean estimated fetal weight was 675 g (standard deviation [SD] ± 140), and the mean neonatal birth weight was 706 g (SD ± 151). The median interval between fetal ultrasound and delivery was 3 days (range: 0-7 days). A total of 45 neonates (48.3%) required more than one intubation attempt. The median number of intubation attempts was 1 (range: 1-10). There was no association between intubation difficulty and fetal abdominal circumference, biparietal diameter, head circumference, gestational age, estimated fetal weight, and neonatal birth weight (all p > 0.05). Standard biometry in periviable neonates does not predict intubation difficulty.


African American dietary patterns at the beginning of the 20th century.
Early field studies in human nutrition documented the eating habits of African Americans living in a variety of circumstances. We compare the results of these investigations. Our analysis shows systematic differences along a continuum reaching from remote, rural communities in the South toward increasingly metropolitan locations. On the latter end of the continuum, we find diets richer in protein, composed of a wider variety of foods and containing fewer of what we now call "soul foods." Greater market involvement and access to low cost alternatives to more traditional foods help explain these developments.


Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1.
Insulin receptor substrate-1 (IRS-1) is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases; it has an apparent relative molecular mass of 160-190,000 (M(r), 160-190K) on SDS polyacrylamide gel. Tyrosine-phosphorylated IRS-1 binds the 85K subunit of phosphatidylinositol 3-kinase which may be involved in the translocation of glucose transporters and the abundant src homology protein (ASH)/Grb2 which may be involved in activation of p21ras and MAP kinase cascade. IRS-1 also has binding sites for Syp and Nck and other src homology 2 (SH2) signalling molecules. To clarify the physiological roles of IRS-1 in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, IGF-1 and IGF-2. These data suggest the existence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs.


Pseudomonas huaxiensis sp. nov., isolated from hospital sewage.
A novel Gram-negative, obligate aerobic, rod-shaped, motile by one or two polar flagella, non-spore-forming bacterial strain, WCHPs060044T, was isolated from the wastewater treatment plant at West China Hospital in Chengdu, PR China. Analysis of its 16S rRNA gene sequence showed that strain WCHPs060044T belonged to the genus Pseudomonas with the highest similarity to Pseudomonas alkylphenolica KL28T (99.73 %), Pseudomonas donghuensis HYST (99.52 %) and Pseudomonas wadenswilerensis CCOS 846T (99.38 %). Phylogenomic analysis based on 107 core gene sequences demonstrated that WCHPs060044T was a member of the Pseudomonas putida group but was distant from all closely related species. Whole-genome comparisons, using average nucleotide identity based on blast (ANIb) and in silico DNA-DNA hybridization (isDDH), confirmed low genome relatedness to its close phylogenetic neighbours [below the recommended thresholds of 95 % (ANIb) and 70 % (isDDH) for species delineation]. Phenotypic characterization tests showed that the utilization of l-arginine, l-fucose, d-galacturonic, d-glucuronic acid, inositol and sorbitol in combination could distinguish this strain from other related species of the genus Pseudomonas. Therefore, based on genetic and phenotypic evidence, strain WCHPs060044T represents a novel species, for which the name Pseudomonas huaxiensis sp. nov. is proposed. The type strain is WCHPs060044T (GDMCC 1.1396T=JCM 32907T=CCTCC AB 2018120T=CNCTC 7663T).


Unusual bilateral sensory innervation of the dorsum of hand by lateral antebrachial cutaneous nerve: a case report.
A 68-year-old male cadaver showed bilateral variation in the sensory innervation of the dorsum of hand. On the dorsum of right hand, first digit and lateral half of second digit were supplied by lateral antebrachial cutaneous nerve (LABCN); medial side of second digit and lateral side of third digit were supplied by superficial branch of radial nerve (SBRN) and medial side of third digit, the fourth and fifth digits were supplied by dorsal cutaneous branch of ulnar nerve (DBUN). On the dorsum of the left hand, lateral side of first digit was supplied by LABCN, medial side of first digit, the second and third digits as well as the lateral side of fourth digit were supplied by SBRN; medial side of fourth digit and fifth digit were supplied by DBUN. These variations would be helpful in understanding peripheral neuropathy, in interpretation of conduction velocity studies and in reconstructive surgery of hand.


Evaluating appropriateness of treatment for Crohn's disease: feasibility of an explicit approach.
Situations where practical therapeutic decisions differ from guidelines in the management of patients with Crohn's disease (CD) have been described through opinion surveys. The feasibility of actually documenting these situations using an explicit approach has not been examined. The aim of this study was to evaluate the feasibility of a retrospective application of appropriateness criteria to a population of CD patients. Medical records of a cohort of patients diagnosed with CD were systematically reviewed. We used appropriateness criteria for treatment of CD that had been developed by the European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT). First we evaluated the level of precision of the elements abstracted from medical records needed in order to be able to apply these criteria. We then assessed the appropriateness of treatment for different CD categories. Only participants with at least one physician encounter during the preceding 6 months were included. 260 patient medical records were reviewed on site at 22 gastroenterologists' offices over a 2-month period in 2005. 116 (44%) patients were excluded because they had not had at least one medical visit at their referred gastroenterologist during the preceding 6 months. Medical records for 8 additional patients (3%) were not accessible. 136 (53%) medical records including 148 encounters were available for analysis. Overall, elements necessary to determine the appropriateness of treatment were available in 94% (139/148) of encounters. These elements were available in more than 90% of cases for all CD categories except for mild-moderate luminal active CD where 66% were available. Among those with all necessary elements available, 18% of treatments were judged as appropriate, 29% inappropriate, 38% uncertain according to the EPACT criteria, and for the other 15%, appropriateness had not been rated by the EPACT panel. The information necessary to assess the appropriateness of treatment of major types of CD was generally both present and precise in medical records. Therefore, in addition to the intended prospective use of these criteria, retrospective evaluation of the appropriateness of CD treatment using medical records is also feasible with the EPACT criteria.


Role of vasopressin V1a receptor in ∆9-tetrahydrocannabinol-induced cataleptic immobilization in mice.
Cannabis is a widely used illicit substance. ∆9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to cause catalepsy in rodents. Recent studies have shown that vasopressin V1a and V1b receptors are widely distributed in the central nervous system and are capable of influencing a wide variety of brain functions such as social behavior, emotionality, and learning and memory. The present study was designed to examine the possible involvement of V1a and V1b receptors in THC-induced catalepsy-like immobilization. The induction of catalepsy following treatment with THC (10 mg/kg, i.p.) or haloperidol (1 mg/kg, i.p.) was evaluated in wild-type (WT), V1a receptor knockout (V1aRKO), and V1b receptor knockout (V1bRKO) mice. The effect of treatment with the selective 5-hydroxytryptamine1A receptor antagonist WAY100635 (0.1 mg/kg, i.p.) on THC-induced catalepsy was also evaluated in V1aRKO mice. Moreover, the effects of the V1a receptor antagonist VMAX-357 and the V1b receptor antagonist ORG-52186 on THC-induced catalepsy were evaluated in ddY mice. THC and haloperidol markedly caused catalepsy in V1bRKO mice as well as in WT mice. However, V1aRKO mice exhibited a reduction in catalepsy induced by THC but not by haloperidol. WAY100635 dramatically enhanced THC-induced catalepsy in V1aRKO mice. Although VMAX-357 (10 mg/kg, p.o.) but not ORG-52186 significantly attenuated THC-induced catalepsy, it had no significant effect on the enhancement of THC-induced catalepsy by WAY100635 in ddY mice. These findings suggest that V1a receptor regulates THC-induced catalepsy-like immobilization.


Characteristics of the killing mechanism of human natural killer cells against hepatocellular carcinoma cell lines HepG2 and Hep3B.
Unlike normal hepatocytes, most hepatocellular carcinomas (HCCs) are quite resistant to death receptor-mediated apoptosis when the cell surface death receptor is cross linked with either agonistic antibodies or soluble death ligand proteins in vitro. The resistance might play an essential role in the escape from the host immune surveillance; however, it has not been directly demonstrated that HCCs are actually resistant to natural killer (NK) cell-mediated death. Therefore, this study investigated the molecular mechanism of NK cell-mediated cytotoxicity against the HCCs, HepG2, and Hep3B, using two distinct cytotoxic assays: a 4-h (51)Cr-release assay and a 2-h [(3)H] thymidine release assay which selectively measures the extent of necrotic and apoptotic target cell death, respectively. Most of the target cells exhibited marked morphologic changes when they were co-incubated with the NK cells, and the NK cytotoxicity against these HCCs was comparable to that against K562, a NK-sensitive leukemia cell line, when the cytotoxicity was assessed by a 4-h (51)Cr release assay. The NK cells also induced significant apoptotic cell death in the Hep3B targets, but not in the HepG2 targets, when the cytotoxicity was assessed by a 2-h [(3)H]-thymidine release assay. In agreement with these results, procaspase-3 was activated in the Hep3B targets, but not in the HepG2 targets. Interestingly, mildly fixed NK cells had no detectable activity in the 4-h (51)Cr release assay against both HepG2 and Hep3B targets, while they were similarly effective as the untreated NK cells in the 2-h [(3)H]-thymidine release assay, suggesting that the level of apoptotic cell death of the Hep3B targets is granule independent and might be primarily mediated by the death ligands of the NK cells. This study found that a tumor necrosis factor (TNF)-related apoptosis-inducing ligand TRAIL)/TRAIL receptor interaction is involved in the NK cell-mediated apoptotic death of the Hep3B targets, but a Fas/Fas ligand (FasL) interaction is not.


The effect of exercise on prescription on physical activity and wellbeing in a multi-ethnic female population: A controlled trial.
In Western countries, individuals from multi-ethnic disadvantaged populations are less physically active than the Western population as a whole. This lack of physical activity (PA) may be one of the factors explaining disparities in health. Exercise on Prescription" (EoP), is an exercise program to which persons are referred by primary care. It has been developed to suit the needs of physically inactive women from diverse ethnic backgrounds living in deprived neighborhoods in the Netherlands. The effectiveness of this program has however, not yet been proven. A total of 514 women from diverse ethnic backgrounds were included in this study (192 EoP, 322 control group). Women in the EoP group participated in 18 sessions of supervised PA. The control group received care as usual. At baseline, 6 and 12 months the women attended an interview and a physical examination. Outcome measures were PA, BMI, weight circumference, fat percentage, oxygen uptake, mental well-being, subjective health and use of care. Of the participants 59% had a low educational level and 90% of the women were overweight or obese. Compliance was high, only 14% dropped out during the course of the program. Total PA did not change, PA during leisure time increased at 6 and at 12 months and PA during household activities increased at 12 months (PEoPvsControl < 0.05). EoP had no significant effect on the other outcome variables. EoP was successful in recruiting its target population and compliance was high. The effect of EoP on PA, health and mental well-being was limited. In this format EoP does not seem to be effective for increasing PA and the health status of non-Western migrant women. Dutch Trial register: NTR1294.


High sensitivity troponin: Does the 50% delta change alter clinical outcomes in chest pain presentations to the emergency room?
The National Heart Foundation (NHF) and Cardiac Society of Australia and New Zealand (CSANZ) Acute Coronary Syndrome (ACS) guidelines recommend the use of a high sensitivity troponin assay (hsTrop) in the assessment of patients presenting with ACS. A troponin delta of 50% compared with the previously recommended 20% is advocated by the guidelines to aid in the clinical diagnosis of ACS. We sought to determine the clinical impact of the updated recommendation to use 50% troponin delta for patients presenting with chest pain to the emergency department. We retrospectively collected data for all patients >18 years presenting with chest or abdominal pain with a hsTrop test performed between January-June 2012. Patients with a STEMI, lacked serial hsTrop, were on dialysis or had trauma-related pain were excluded. Of the 1054 eligible patients, 422 (40%) with serial hsTrop had at least one abnormal troponin (>14 ng/ml). 73 (6.9%) fell within 20-50%. Twenty-seven had clinical or ECG evidence suggestive of ACS and were referred for further cardiac investigations. Of the remainder, five patients were medically managed for ACS, 38 patients with non-cardiac chest pain had no further tests. At 1 year follow-up, of the patients that did not undergo further investigations, 6 patients represented with ACS; there was no cardiac mortality. Our data showed a number of patients that would be potentially missed with the implementation of a 50% troponin. However, this loss of sensitivity was mitigated by the use of clinical acumen.


The Protective Role of Gallic Acid Pretreatment On Renal Ischemia-reperfusion Injury in Rats.
Renal ischemia-reperfusion injury (RIR) occurs when there is a temporary restriction of blood flow to the kidneys followed by an influx of blood, re-oxygenating the tissues. This occurs as a severe complication of major surgery. This process causes significant damage to the tissues and is responsible for the development of acute kidney injury (AKI), a life-threatening condition with high mortality rates. Here, we evaluated the potential protective effects of the antioxidant, gallic acid (GA), on RIR in an in vivo rat model. Adult male Sprague Dawley rats were randomly divided into three groups: group 1 (control, n = 8), group 2 (Ischemia-reperfusion (IR) with no-treatment, n = 7), and group 3 (IR + daily GA 100 mg/kg i.p, n = 7). The abdomens of the rats in the control group were opened during the surgical procedure, then sutured closed. GA pretreatment began daily 15 days prior to inducing RIR. To induce RIR, the umbilical arteries were obstructed on both sides and clamped with mild pressure for 45 min. Following the 45 min ischemia, the clamps were removed to allow for the induction of reperfusion. The reperfusion phase was 24 hours. Following IR, the serum levels of urea and creatinine significantly increased compared to the controls. Pretreatment with GA was observed to reduce urea and creatinine levels following IR. However, this decrease was not statistically significant. The serum and renal levels of malondialdehyde (MDA) in the IR group was significantly elevated compared to the control group. Conversely, glutathione (GSH) levels and the activity of glutathione peroxidase (GPX) significantly decreased in the IR group compared to controls. Our findings show GA pretreatment to significantly improve the levels of renal MDA, serum GSH, and GPX activity following RIR. Our findings highlight the protective role for GA in mitigating the damage caused by RIR and its applications as a potential treatment.


Antimicrobial and Antioxidant Activities and Phytochemical Analysis of Rosmarinus officinalis L. Pod and Thymus vulgaris L. Leaf Ethanolic Extracts on Escherichia coli Urinary Isolates.
The indiscriminate use of antibacterial agents has resulted in one of the largest recent global health problems, which is the emergence of bacterial resistance. This study aimed to examine the antimicrobial and antioxidant activities of ethanolic extracts of the two medicinal plants; Rosmarinus officinalis pods and Thymus vulgaris leaves on Escherichia coli urinary isolates. Both plants were extracted by absolute ethanol, and various concentrations (100, 50, 25, and 12.5 mg/ml) of the ethanolic extracts were prepared and tested against 53 urinary isolates of E. coli. An antibiotic susceptibility test was performed using chloramphenicol, gentamycin, amoxicillin, ceftriaxone, and ciprofloxacin against isolated bacteria. The antioxidant activity was measured using the DPPH method. The chemical analysis of both extracts was determined using gas chromatography-mass spectrometry (GC/MS) technique. The results showed that 88.7% of the isolated bacteria were sensitive to chloramphenicol and 87% were sensitive to gentamycin, while all isolates were resistant to amoxicillin, 13% of E. coli isolates were found to be multidrug-resistant (MDR). The inhibitory zone of R. officinalis extract against E. coli ranged between 8 and 23 mm and for T. vulgaris extract ranged between 8 and 20 mm at concentrations between 25, 50, and 100 mg/ml. The MIC of both extracts against isolates is between 12.5 and 50 mg/ml, while the MBC is between 50 and 100 mg/ml. The DPPH radical scavenging potential of T. vulgaris was 83.09%, followed by R. officinalis (81.26%). The chemical analysis by GC-MS of R. officinalis showed that the most active compounds were: eucalyptol (18.57%), bicycloheptan (10.01%), and octahydrodibenz anthracene (7.44%) and for T. vulgaris the most active compounds were: thymol (5.7%), phytol (7.92%), and hexadecanoic acid (18.51%). R. officinalis and T. vulgaris ethanolic extracts possessed antimicrobial and antioxidant activities and were found to be rich natural sources of active constituents used as traditional medicine.


Effects of blood donation on arterial blood pressure in retired racing Greyhounds.
The purpose of this study was to evaluate changes in systolic arterial blood pressure (SABP) immediately after collection of blood for transfusion in retired racing Greyhounds. We prospectively evaluated 19 blood donor Greyhounds before and after the collection of a unit (450 mL) of blood. The SABP was measured with Doppler in the right forearm after the dogs had been in the blood collection room for a few minutes (PRE-FLOOR) and again 5-10 minutes after the dogs were placed on the table where they would be bled (PRE-TABLE). A total of 3-5 minutes after completing the blood collection, the SABP was measured again while the dogs were still in lateral recumbency on the table (POST-TABLE) and once more 60-90 minutes later, when the dogs were on the floor after completing the donation (POST-FLOOR). All dogs were monitored for clinical signs of hypotension, including depression, weakness, collapse, and pallor, for a minimum of 2 hours after donation. There was a significant difference in SABP for the group between PRE-FLOOR and POST-TABLE (P = .02) and between PRE-TABLE and POST-TABLE determinations (P = .01). There were no significant differences for any of the other time points; there were no adverse events. Therefore, we conclude that the collection of 450 mL of blood from normal Greyhounds results in a short-lived yet significant decrease in SABP, but the likelihood of adverse events is negligible.


The role of the membrane confinement in the surface area regulation of cells.
We propose a new in vitro system to study the mechanics of surface area regulation in cells, which takes into an account the spatial confinement of the cell membrane. By coupling a lipid bilayer to the strain-controlled deformation of an elastic sheet, we show that upon straining the supported lipid bilayer expands its surface area by absorbing adherent lipid vesicles and upon compression decreases its area by expelling lipid tubes out of its plane. The processes are reversible and closely resemble in vivo observations on shrinking cells. Our results suggest that the mechanics of the area regulation in cells is controlled primarily by the membrane tension and the effects of the membrane confinement.


[Memory dysfunction of spinocerebellar degeneration].
We evaluated Rey's auditory verbal learning test (AVLT) and Wechsler adult intelligence scale (WAIS) in 29 patients with spinocerebellar degeneration (SCD) younger than 65 years old. They showed a significant impairment in the recall subtest of AVLT. However in the recognition subtest, there was no significant impairment in the recall subtest of AVLT. However in the recognition subtest, there was no significant difference between the patients and the control subjects. The patients with SCD also showed a significant decrement in both VIQ and PIQ. The disturbance of recall memory did not correlate with the disturbance of VIQ. The disturbance of recall memory without that of recognition memory is considered to be a characteristic of subcortical dementia. Therefore we concluded that the patients with SCD may develop subcortical dementia and that the localization of the disturbance of recall memory and that of the disturbance of VIQ might be different.


Asymmetries in blue-yellow color perception and in the color of 'the dress'.
The perception of color poses daunting challenges, because the light spectrum reaching the eye depends on both the reflectance of objects and the spectrum of the illuminating light source. Solving this problem requires sophisticated inferences about the properties of lighting and surfaces, and many striking examples of 'color constancy' illustrate how our vision compensates for variations in illumination to estimate the color of objects (for example [1-3]). We discovered a novel property of color perception and constancy, involving how we experience shades of blue versus yellow. We found that surfaces are much more likely to be perceived as white or gray when their color is varied along bluish directions, compared with equivalent variations along yellowish (or reddish or greenish) directions. This selective bias may reflect a tendency to attribute bluish tints to the illuminant rather than the object, consistent with an inference that indirect lighting from the sky and in shadows tends to be bluish. The blue-yellow asymmetry has striking effects on the appearance of images when their colors are reversed, turning white to yellow and silver to gold, and helps account for the variation among observers in the colors experienced in 'the dress' image that recently consumed the internet. Observers variously describe the dress as blue-black or white-gold, and this has been explained by whether the dress appears to be in direct lighting or shade (for example [5]). We show that these individual differences and potential lighting interpretations also depend on the special ambiguity of blue, for simply reversing the image colors causes almost all observers to report the lighter stripes as yellowish.


Knotting of a nasogastric feeding tube in a child with head injury: A case report and review of literature.
Nasogastric intubation is one of the most common routine nonoperative procedures available for the hospital care of patients. The insertion and removal of this tube is associated with many complications. The complications include trauma, nasal septal abscess and inadvertent entry into the cranial cavity and trachea, ulceration, bleeding from varices and perforation. Knotting of the nasogastric tube is one of the very rare complications of nasogastric intubation particularly in children. To the best of our knowledge there are very few reported cases in children. The technique used in the patient was the application of a steady tug which allows the lower oesophageal sphincter to open, therefore enabling the removal of the nasogastric tube. The possible predispositions to knotting of a nasogastric tube include small bore tubes, excess tube length and gastric surgery. We postulate that reduced gastric tone is another possible predisposing factor with head injury being the most likely reason in the index patient. We also challenge the fact that the small sized stomach is a risk factor for knotting of a feeding tube if the functional status and tone are normal, because of the rarity in children.


Performance of stair negotiation in patients with cerebral palsy and stiff knee gait.
Due to the limited knee range of motion, achieving adequate foot clearance while walking on level ground constitutes a major problem for patients with cerebral palsy and stiff knee gait. Stair negotiation as an activity of daily life requires a considerably higher knee range of motion than level ground walking, but little is known yet as to whether such patients are able to walk stairs. The aim of this study was to investigate how patients with a limited knee range of motion negotiate stairs. Do they increase their peak knee flexion and use the same pattern as in walking on level ground? How do the muscles act during stair negotiation? In this explorative study, 17 adults with bilateral, spastic cerebral palsy and stiff knee gait and 25 healthy subjects were examined. 3D motion analysis, including electromyography, was performed while walking on level ground, upstairs, and downstairs. A linear mixed model was used for between- and within-group comparisons. Walking upstairs and downstairs, patients increased their peak knee flexion by around 30° compared to level walking. Thus, increased knee flexion may be seen as the main mechanism for maintaining foot clearance on stairs. An increased pelvic obliquity (elevation) and hip flexion were also found and involved subjects showed a slight increase in rectus femoris activity when walking on stairs compared to level walking within the phases of high knee flexion. This study showed that patients with cerebral palsy and stiff knee gait are able to flex their knees more than would be required for level walking. Hence, the patients are able to adapt their rectus activity to stair walking to some extent. Therefore, further investigations might help to open up new therapeutic options to facilitate level walking and stair negotiation in patients with stiff knee gait.


[Advances in serological systems for diagnosis of systemic fungal infections, particularly those caused by Candida and Aspergillus].
Invasive fungal infections have emerged as important causes of morbidity and mortality in neutropenicand some other immunocompromised hosts; Candida and Aspergillus are among the major pathogens in this patient population. The clinical diagnosis of these infections is not specific and the traditional mycological methods for them not sensitive, with limits in the early detection of the pathogen. The potential additives or complements to the laboratory diagnosis of invasive candidiasis and aspergillosis are two non-culture-based methods, serodiagnostic methods and molecular ones. The former methods include the detection of pathogen-specific antigens, antibodies, metabolites and cell wall components. Several have already become standard laboratory tools and some others are under active investigation for developing new, more accurate detection systems. In this review, I will discuss the current status and future potential of serodiagnostic methods, highlighting both their technical and clinical implications.


In vitro transactivation potencies of black-footed albatross (Phoebastria nigripes) AHR1 and AHR2 by dioxins to predict CYP1A expression in the wild population.
Our previous studies have detected high levels of dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins (PCDDs), furans (PCDFs), and coplanar PCBs (Co-PCBs) in the black-footed albatross (BFA), Phoebastria nigripes, from the North Pacific region. We have also cloned two aryl hydrocarbon receptors, AHR1 and AHR2, of the BFA. To evaluate the sensitivity to DRCs in the BFA and to assess the status of cytochrome P450 1A (CYP1A) induction in the wild population, this study investigated the mRNA expression levels of BFA AHR1 and AHR2 and also the transactivation potencies of each AHR by 15 selected DRC congeners. Quantitative real-time PCR of BFA AHR mRNAs showed that hepatic AHR1 is more highly expressed than AHR2. Transactivation by graded concentrations of individual DRCs was measured in COS-7 cells, where BFA AHR1 or AHR2 was transiently transfected. For congeners that exhibited AHR-mediated dose-dependent activities, 50% effective concentration (EC(50)) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) were estimated. Based on the estimates of the REPs, TCDD induction equivalency factors (IEFs) were determined. For BFA AHR1, PeCDF was equipotent to TCDD, but other congeners exhibited lower IEFs. For BFA AHR2, PCDD/F congeners except OCDD/F showed IEFs ≥ 1.0. Using BFA AHR1- or AHR2-IEFs and hepatic concentrations of DRCs in North Pacific BFAs, TCDD induction equivalents (IEQs) were calculated. We further constructed nonlinear regression models on the relationships between BFA AHR1- or AHR2-IEF derived total IEQ or WHO-TEF derived total TEQ and ethoxyresorufin-O-deethylase activity (EROD) in the liver of wild BFAs. The results indicated that the relationships of BFA AHR1- and AHR2-based IEQs and EROD were predictable from BFA AHR1- and AHR2-mediated transactivation by TCDD, respectively. Collectively, these results suggest that the in vitro assay incorporating the AHR of species of concern would be a useful tool to predict the sensitivity to DRCs in the species and CYP1A induction in the wild population.


Crystal structure and mechanism of human carboxypeptidase O: Insights into its specific activity for acidic residues.
Human metallocarboxypeptidase O (hCPO) is a recently discovered digestive enzyme localized to the apical membrane of intestinal epithelial cells. Unlike pancreatic metallocarboxypeptidases, hCPO is glycosylated and produced as an active enzyme with distinctive substrate specificity toward C-terminal (C-t) acidic residues. Here we present the crystal structure of hCPO at 1.85-Å resolution, both alone and in complex with a carboxypeptidase inhibitor (NvCI) from the marine snail Nerita versicolor The structure provides detailed information regarding determinants of enzyme specificity, in particular Arg275, placed at the bottom of the substrate-binding pocket. This residue, located at "canonical" position 255, where it is Ile in human pancreatic carboxypeptidases A1 (hCPA1) and A2 (hCPA2) and Asp in B (hCPB), plays a dominant role in determining the preference of hCPO for acidic C-t residues. Site-directed mutagenesis to Asp and Ala changes the specificity to C-t basic and hydrophobic residues, respectively. The single-site mutants thus faithfully mimic the enzymatic properties of CPB and CPA, respectively. hCPO also shows a preference for Glu over Asp, probably as a consequence of a tighter fitting of the Glu side chain in its S1' substrate-binding pocket. This unique preference of hCPO, together with hCPA1, hCPA2, and hCPB, completes the array of C-t cleavages enabling the digestion of the dietary proteins within the intestine. Finally, in addition to activity toward small synthetic substrates and peptides, hCPO can also trim C-t extensions of proteins, such as epidermal growth factor, suggesting a role in the maturation and degradation of growth factors and bioactive peptides.


Time dependent pharmacokinetic interaction between phenylpropanolamine and chlorpheniramine maleate in human subjects.
The influence of time of administration on the serum levels of phenylpropanolamine when administered alone and in combination with chlorpheniramine maleate at two different times of a day was studied in healthy human volunteers in a randomized 4 x 4 Latin square crossover design with a washout period of ten days. Blood samples were collected at predetermined time intervals and serum samples were analysed for unchanged phenylpropanolamine using high performance liquid chromatography. The various pharmacokinetic parameters of phenylpropanolamine were calculated using model independent methods. There was a significant (P < 0.05) decrease in the rate of absorption of phenylpropanolamine following its administration in combination with chlorpheniramine maleate at 2200 hours. However, such a change was not observed for treatment at 1000 hours. The observed change may be due to the time dependent gastrointestinal effect of these drugs.


New Insights into Calorie Restriction Induced Bone Loss.
Caloric restriction (CR) is now a popular lifestyle choice due to its ability in experimental animals to improve lifespan, reduce body weight, and lessen oxidative stress. However, more and more emerging evidence suggests this treatment requires careful consideration because of its detrimental effects on the skeletal system. Experimental and clinical studies show that CR can suppress bone growth and raise the risk of fracture, but the specific mechanisms are poorly understood. Reduced mechanical loading has long been thought to be the primary cause of weight loss-induced bone loss from calorie restriction. Despite fat loss in peripheral depots with calorie restriction, bone marrow adipose tissue (BMAT) increases, and this may play a significant role in this pathological process. Here, we update recent advances in our understanding of the effects of CR on the skeleton, the possible pathogenic role of BMAT in CR-induced bone loss, and some strategies to mitigate any potential side effects on the skeletal system.


[Ocular involvement due to the juice of Dieffenbachia plants (author's transl)].
Upon breaking the stem or the branches of a Dieffenbachia plant juice is released in an explosive manner and may thus involve the eye. A myriad of fine calcium-oxalate crystals penetrate into all layers of the cornea, and an iritis can develop. The latter ceases within 6 days, the corneal cristals vanish within about three weeks.


Assessment of the cataractogenic potential of cyclohexanone in guinea pigs and rabbits.
The cataractogenic potential of cyclohexanone administered intravenously (0.5 and 5.0 mg/kg) and percutaneously (0.5 ml) was assessed in guinea pigs and rabbits. The negative control article was 0.9% sodium chloride. Positive control articles for guinea pigs were iv galactose and percutaneous dimethyl sulfoxide (DMSO), and for rabbits, iv poly(I) X poly(C) and percutaneous DMSO. An untreated group of guinea pigs was used as a sham control. Animals were treated three times a week for 3 consecutive weeks. Ophthalmic examinations performed monthly for 6 months for treated animals and 7 months for untreated animals revealed the presence of anterior subcapsular vacuoles in guinea pigs in all groups. These lesions consisted of swollen lens fibers that progressed to fiber disruption and protein liquefaction. There was no statistical difference in the incidence and severity of the lesions among treatment groups. No lenticular alterations were noted in any of the rabbits treated with cyclohexanone or any other chemical. It was concluded that these alterations are, apparently, an inherent characteristic of the guinea pig, making that animal an unsuitable model for the assessment of cataractogenic potential of xenobiotics.


Ceftriaxone normalizes nucleus accumbens synaptic transmission, glutamate transport, and export following cocaine self-administration and extinction training.
Decreased basal glutamate levels are observed in the rat nucleus accumbens (NA) core following cocaine self-administration. This disruption of glutamate homeostasis arises from a reduction in the export of glutamate via system x(C)(-) and is accompanied by a decrease in expression of xCT, the catalytic subunit of system x(C)(-). A second hallmark of disrupted homeostasis is a decrease in expression and function of the major glutamate transporter, GLT-1. We have previously shown that chronic treatment with the antibiotic ceftriaxone restores xCT and GLT-1 expression following cocaine self-administration and attenuates both cue- and cocaine-primed reinstatement. Here we used a (3)H-glutamate uptake assay and microdialysis to test the hypothesis that ceftriaxone restores the function of both GLT-1 and xCT (glutamate reuptake and export, respectively) in the NA core following cocaine self-administration. We also used electrophysiology to investigate the ability of ceftriaxone to normalize measures of synaptic plasticity following cocaine. We found that 5 d of ceftriaxone treatment following cocaine self-administration restores basal glutamate levels in the accumbens core, likely through an upregulation of system x(C)(-) function. We also found that ceftriaxone restores glutamate reuptake and attenuates the increase in synaptically released glutamate that accompanies cocaine-primed reinstatement. Ceftriaxone also reversed the cocaine-induced synaptic potentiation in the accumbens core, evidenced by normalized spontaneous EPSC amplitude and frequency and evoked EPSC amplitude. These data indicate that ceftriaxone normalizes multiple aspects of glutamate homeostasis following cocaine self-administration and thus holds the potential to reduce relapse in human cocaine addicts.


Forces and pressures in DNA packaging and release from viral capsids.
In a previous communication (Kindt et al., 2001) we reported preliminary results of Brownian dynamics simulation and analytical theory which address the packaging and ejection forces involving DNA in bacteriophage capsids. In the present work we provide a systematic formulation of the underlying theory, featuring the energetic and structural aspects of the strongly confined DNA. The free energy of the DNA chain is expressed as a sum of contributions from its encapsidated and released portions, each expressed as a sum of bending and interstrand energies but subjected to different boundary conditions. The equilibrium structure and energy of the capsid-confined and free chain portions are determined, for each ejected length, by variational minimization of the free energy with respect to their shape profiles and interaxial spacings. Numerical results are derived for a model system mimicking the lambda-phage. We find that the fully encapsidated genome is highly compressed and strongly bent, forming a spool-like condensate, storing enormous elastic energy. The elastic stress is rapidly released during the first stage of DNA injection, indicating the large force (tens of pico Newtons) needed to complete the (inverse) loading process. The second injection stage sets in when approximately 1/3 of the genome has been released, and the interaxial distance has nearly reached its equilibrium value (corresponding to that of a relaxed torus in solution); concomitantly the encapsidated genome begins a gradual morphological transformation from a spool to a torus. We also calculate the loading force, the average pressure on the capsid's walls, and the anisotropic pressure profile within the capsid. The results are interpreted in terms of the (competing) bending and interaction components of the packing energy, and are shown to be in good agreement with available experimental data.


Gene therapy for lung cancer. An introduction.
Incremental progress will likely continue to be made in the treatment of lung cancer using the conventional treatment modalities. However, there is now hope that the development of noncross-resistant modalities that can be accomplished using the technology of gene transfer may hasten the progress made in this disease. Although significant progress has been made, the practical application of the various strategies to the treatment of cancer patients in clinical trials has yielded only very limited results. For the strategies of introducing suicide genes, replacing defective tumor-suppressor genes, and inactivating oncogenes, considerable progress will need to be made particularly with regard to the ability of vectors to selectively and efficiently target tumor cells in order for many of these strategies to become effective. With regard to the application of gene therapy to immunotherapy, major responses are not likely at this time since these innovative therapies are being developed in patients with advanced disease. However, it is very likely that these pioneering clinical trials will provide important clinical and immunological information that will be the basis for future attempts to effectively harness the immune system against lung cancer.


Addressing pedestrian safety: a content analysis of pedestrian master plans in North Carolina.
To systematically examine the content of pedestrian master plans in North Carolina in order to assess whether and how these plans were designed to improve pedestrian safety. All current pedestrian master plans in North Carolina through 2008 were gathered and examined using content analysis. A safety quality index was developed to assess the thoroughness with which a plan addressed safety issues in four categories: (1) goal statement, (2) analysis of current conditions, (3) policy proposals, and (4) program proposals. Plans were also compared according to the implementation guidelines included and on the recent pedestrian accident history of the municipalities in which they were developed. Forty-six plans were developed in North Carolina through 2008, either at the municipal or regional level. Almost all pedestrian master plans in North Carolina described improving safety as one of their goals. The majority attempted to do so by improving the built environment through engineering projects, including building new sidewalks, trails, or greenways and by upgrading existing facilities. Regional plans tended to propose fewer policies and programs, as well as less specific proposals, than did municipal plans. Although most plans contained multiple proposals to address pedestrian safety, few plans identified a group accountable for implementation, a timeline of implementation actions, or the resources necessary to make implementation possible. Municipalities with a recent history of pedestrian injuries were more likely to develop plans than those with fewer pedestrian injuries. Plans developed by municipalities with a recent history of pedestrian fatalities tended to more thoroughly addressed safety. Safety was a major component of nearly every pedestrian master plan in North Carolina. Most plans contained multiple proposals to address pedestrian safety. These findings lay the foundation for future research evaluating both the implementation and the impact of these planning documents on the safety of pedestrians.