Health coaching interventions for persons with chronic conditions: a systematic review and meta-analysis protocol.
Chronic conditions are increasingly more common and negatively impact quality of life, disability, morbidity, and mortality. Health coaching has emerged as a possible intervention to help individuals with chronic conditions adopt health supportive behaviors that improve both quality of life and health outcomes. We planned a systematic review and meta-analysis of the contemporary health coaching literature published in the last decade to evaluate the effect of health coaching on clinically important, disease-specific, functional, and behavioral outcomes. We will include randomized controlled trials or quasi-experimental studies that compared health coaching to alternative interventions or usual care. To enable adoption of effective interventions, we aim to explore how the effect of intervention is modified by the intervention components, delivering personnel (i.e., health professionals vs trained lay or peer persons), dose, frequency, and setting. Analysis of intervention outcomes will be reported and classified using an existing theoretical framework, the Theory of Patient Capacity, to identify the areas of patients' capacity to access and use healthcare and enact self-care where coaching may be an effective intervention. This systematic review and meta-analysis will identify and synthesize evidence to inform the practice of health coaching by providing evidence on components and characteristics of the intervention essential for success in individuals with chronic health conditions. PROSPERO CRD42016039730.


Antioxidant and hepatoprotective effects of silymarin phytosomes compared to milk thistle extract in CCl4 induced hepatotoxicity in rats.
Milk thistle extract is a well-known hepatoprotectant with low bioavailability (20-50%). The objective of the present study is to prepare and characterize silymarin phytosomes and to test the hepatoprotective effect of the phytosomes in CCl4 induced liver injury in rats compared to milk thistle extract. Phytosomes were prepared using lecithin from soybeans and from egg yolk. The prepared phytosomes were examined using scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy (H(1)NMR). The loading efficiency was >85% in all phytosomal formulations. Formula P2 (with the molar ratio of soybean lecithin to silybin 1:1) and P4 (with the molar ratio of egg-yolk lecithin to silybin 0.25:1) exhibited significantly (p < 0.05) faster release than milk thistle extract. The in vivo study revealed that phytosomes significantly (p < 0.05) decreased glutamic pyruvic transaminase and super oxide dismutase activities compared to milk thistle extract.


Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: directed apoptotic events in vascular endothelial cells.
The serine protease granzyme B (GrB; 25 kDa) is capable of inducing apoptosis through both caspase-dependent and caspase-independent mechanisms. We designed a novel vascular-targeting fusion construct designated as GrB/vascular endothelial growth factor (VEGF)121, which is composed of a non-heparin-binding isoform of VEGF and the proapoptotic pathway enzyme GrB fused via a short, flexible tether (G4S). The chimeric fusion gene was then cloned into a bacterial vector, and the protein was expressed in Escherichia coli and purified by nickel-NTA metal affinity chromatography. Western blotting confirmed incorporation of both VEGF121 and GrB proteins into the construct. GrB/VEGF121 specifically bound (ELISA) to porcine aortic endothelial (PAE)/FLK-1 cells overexpressing the FLK-1/KDR receptor but not to cells overexpressing the FLT-1 receptor. Immunofluoresence studies showed that the GrB moiety of GrB/VEGF121 was delivered efficiently and rapidly into the cytosol of PAE/FLK-1 cells but not into that of PAE/FLT-1 cells after 4 h treatment with GrB/VEGF121. Treatment of cells with GrB/VEGF121 showed that the IC50 was approximately 10 nM against PAE/FLK-1 cells; however, there were no cytotoxic effects observed on PAE/FLT-1 cells at doses up to 200 nM. GrB/VEGF121 induced apoptotic events specifically on PAE/FLK-1 as assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay, DNA laddering, and cytochrome c release from mitochondria. In addition, the fusion construct mediated the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase in target endothelial cells within 4 h after treatment. In conclusion, delivery of the human proapoptotic pathway enzyme GrB to tumor vascular endothelial cells or to tumor cells may have significant therapeutic potential and represents a potent new class of targeted therapeutic agents with a unique mechanism of action.


MUC5AC and MUC5B expression in canine gallbladder mucocele epithelial cells.
Gallbladder mucocele (GBM) is one of the most common gallbladder diseases in dogs. Its pathogenesis has not yet been clarified, but excessive accumulation of a secretory gel-forming mucin, MUC5AC in the gallbladder has been reported. This study aimed to ascertain if MUC5AC overproduction resulted in mucus accumulation in the gallbladder during GBM development. Eleven dogs undergoing cholecystectomy who were pathologically diagnosed with GBM were included, and the expression level of mucins, particularly MUC5AC and MUC5B, in their gallbladder epithelial cells was compared with those in normal gallbladder epithelial cells. On reverse transcription-quantitative polymerase chain reaction screening, there was a significant difference (P<0.05) in the mRNA expression level of MUC1, but not of other mucins including MUC5AC and MUC5B, between mucocele and normal gallbladder epithelial cells. Protein expression levels were also evaluated for MUC5AC and MUC5B using immunohistochemistry. There was little immunoreactivity for MUC5AC, whereas MUC5B showed definitive staining in gallbladder epithelial cells. There was no difference in MUC5AC and MUC5B protein expression levels between mucocele and normal gallbladder epithelial cells. These data suggest that excessive production of mucin, especially MUC5AC and MUC5B, does not occur in canine GBM, and that abnormal mucus excretion, rather than excessive mucus production, may be the cause of GBM development.


New organ-based tube current modulation method to reduce the radiation dose during computed tomography of the head: evaluation of image quality and radiation dose to the eyes in the phantom study.
A new organ-based tube current modulation (NOB-TCM) method was designed with the intent to decrease tube current by 30% over a prescribed 90° radial arc across the anterior aspect of the radiosensitive organ, without increasing tube current in the remaining radial arc. We compared a reference scan and five other dose-reducing methods with regard to effects on dose, practicality, and image quality to determine the most effective method for the reduction of the radiation dose to the eyes during CT examinations of the head. We compared the radiation doses to the eyes and physical image quality in different regions of interest for TCM and shielding scans. Three types of TCM scans were performed: longitudinal TCM, angular TCM, and NOB-TCM. A bismuth sheet and lead goggles were each applied for the shielding scan. Relative to the reference scan, the dose to the eye was reduced to 25.88% with NOB-TCM, 44.53% with lead goggles, and 36.91% with a bismuth shield. Relative to the reference scan, the mean signal-to-noise ratio (SNR) was decreased to 8.02% with NOB-TCM, 28.36% with lead goggles, and 32.95% with the bismuth shield. The SNR of the anterior region of interest was decreased to 11.89% with NOB-TCM and 87.89% with the bismuth shield. The average figure of merit was increased by 11.7% with longitudinal TCM and 13.39% with NOB-TCM, compared with the reference scan. NOB-TCM is a superior solution for head CT, including the orbital area, due to the reduction in radiation exposure without significant loss in image quality.


Gastric and intestinal ethanol toxicity in the rat. Effect on glutathione level and role of alcohol and acetaldehyde metabolisms.
This study investigated the dose- and time-dependent effect of ethanol on gastric and intestinal glutathione and protein oxidative state in the rat. Rats received 1 or 4 g/kg of 25% ethanol solution orally or isocaloric glucose. Some rats received diethylmaleate, cimetidine or cyanamide before ethanol (1 g/kg). Glutathione, carbonyl proteins and histological damage were evaluated in the gastric and intestinal mucosa 6 hours after treatment. An increase in glutathione was observed 2 to 6 hours after 1 g/kg of ethanol both in the gastric and intestinal mucosa, whereas 4 g/kg decreased glutathione. The rise in glutathione after ethanol was associated with increased levels of its oxidized form; however, the total/oxidized ratio was significantly decreased only in the intestinal tract. Diethylmaleate depleted mucosal glutathione, while the subsequent ingestion of ethanol increased it. Unlike stomach, intestine showed a significant increase in carbonyl proteins and marked histological lesions after ethanol ingestion. Cimetidine and cyanamide inhibited by 50% the activity of alcohol dehydrogenase and by 80% aldehyde dehydrogenase, respectively, in the gastric and intestinal mucosa. Cyanamide significantly enhanced ethanol-induced protein oxidation and mucosal injury in the stomach. No such effect was observed in the intestine. The increase of glutathione after ingestion of low amounts of ethanol appears to be an adaptive mechanism against ethanol toxicity. Depletion of glutathione increased protein oxidation and the extent of histological damage in ethanol-treated rats. At gastric level, the effects of ethanol are exaggerated by the inhibition of acetaldehyde metabolism; while intestinal damages appear to be ascribed to ethanol itself.


Activin A-Mediated Regulation of XT-I in Human Skin Fibroblasts.
Fibrosis is a fundamental feature of systemic sclerosis (SSc) and is characterized by excessive accumulation of extracellular matrix components like proteoglycans (PG) or collagens in skin and internal organs. Serum analysis from SSc patients showed an increase in the enzyme activity of xylosyltransferase (XT), the initial enzyme in PG biosynthesis. There are two distinct XT isoforms-XT-I and XT-II-in humans, but until now only XT-I is associated with fibrotic remodelling for an unknown reason. The aim of this study was to identify new XT mediators and clarify the underlying mechanisms, in view of developing putative therapeutic anti-fibrotic interventions in the future. Therefore, we used different cytokines and growth factors, small molecule inhibitors as well as small interfering RNAs, and assessed the cellular XT activity and XYLT1 expression in primary human dermal fibroblasts by radiochemical activity assays and qRT-PCR. We identified a new function of activin A as a regulator of XYLT1 mRNA expression and XT activity. While the activin A-induced XT-I increase was found to be mediated by activin A receptor type 1B, MAPK and Smad pathways, the activin A treatment did not alter the XYLT2 expression. Furthermore, we observed a reciprocal regulation of XYLT1 and XYLT2 transcription after inhibition of the activin A pathway components. These results improve the understanding of the differential expression regulation of XYLT isoforms under pathological fibroproliferative conditions.


Questions about gonococcal pilus phase- and antigenic variation.
Pathogenic organisms inhabit one of several defined locations within a host where temperature, pH, and nutrients are relatively constant. While the microorganism must adapt to different environments within the host, the host immune system is the most formidable predator that can limit the growth of a pathogen. Neisseria gonorrhoeae (the gonococcus, Gc) is the causative agent of gonorrhoea, and has evolved several systems for varying the antigenicity of different surface antigens, presumably to help evade the effects of the human immune system. The On/Off/On phase variation of surface structure expression also alters the antigenic characteristics of the bacterial cell surface. Antigenic variation of the major subunit of the pilus, pilin, occurs by unidirectional, homologous recombination between a silent locus and the expression locus. The silent loci lie from 1 to 900 kb from the expression locus in the chromosome yet all can donate their sequences to the expression locus. The genetic composition of the pilin loci of two Gc strains has been elucidated, and the types of changes that lead to altered forms of the pilus have been extensively characterized. However, little is known about the precise molecular mechanisms used to allow high-frequency, non-reciprocal, chromosomal recombination between pilin loci or about what regulates the process of maintaining chromosome fidelity.


Isolation and characterization of fourteen novel putative and nine known target genes of the p53 family.
p53, a transcription factor, exerts its tumor suppressor activity by regulating a diverse array of genes involved in the control of the cell cycle, apoptosis, differentiation, and DNA repair. Previously, we and others have found that p53 contains multiple separate functional domains, each of which has a unique contribution to the activity of p53 in inducing cell cycle arrest and apoptosis, probably via differential regulation of target genes. We and others have also found that the p53 family members, that is, p53, p63, and p73, are all capable of inducing cell cycle arrest and apoptosis and regulate both common and unique target genes. Here, we used Affymetrix GeneChip assay and Northern blot analysis to determine whether some known target genes are regulated by various p53 mutants, which are active in inducing cell cycle arrest, apoptosis, or both, and to identify novel target genes regulated by the p53 family. We found that various p53 functional domains control the induction of a target gene, which may be responsible for the unique activity of a given functional domain in inducing cell cycle arrest or apoptosis. In addition, we identified fourteen potential novel target genes that are differentially regulated by various p53 family members. Therefore, the regulation of a known target gene by a defined p53 mutant can be used to classify the role of the target gene in p53 tumor suppression and the identification of these fourteen potential novel target genes of the p53 family can lead to uncover the signaling pathway to which a p53 family member functions in tumor suppression (p53) and in development (p63 and p73).


Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation.
Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.


Hyperactive Response of Direct Pathway Striatal Projection Neurons to L-dopa and D1 Agonism in Freely Moving Parkinsonian Mice.
Dopamine (DA) profoundly stimulates motor function as demonstrated by the hypokinetic motor symptoms in Parkinson's disease (PD) and by the hyperkinetic motor side effects during dopaminergic treatment of PD. Dopamine (DA) receptor-bypassing, optogenetics- and chemogenetics-induced spike firing of striatal DA D1 receptor (D1R)-expressing, direct pathway medium spiny neurons (dSPNs or dMSNs) promotes movements. However, the endogenous D1R-mediated effects, let alone those of DA replacement, on dSPN spike activity in freely-moving animals is not established. Here we show that using transcription factor Pitx3 null mutant (Pitx3Null) mice as a model for severe and consistent DA denervation in the dorsal striatum in Parkinson's disease, antidromically identified striatonigral neurons (D1R-expressing dSPNs) had a lower baseline spike firing rate than that in DA-intact normal mice, and these neurons increased their spike firing more strongly in Pitx3Null mice than in WT mice in response to injection of L-dopa or the D1R agonist, SKF81297; the increase in spike firing temporally coincided with the motor-stimulating effects of L-dopa and SKF81297. Taken together, these results provide the first evidence from freely moving animals that in parkinsonian striatum, identified behavior-promoting dSPNs become hyperactive upon the administration of L-dopa or a D1 agonist, likely contributing to the profound dopaminergic motor stimulation in parkinsonian animals and PD patients.


New density estimates of a threatened sifaka species (Propithecus coquereli) in Ankarafantsika National Park.
Propithecus coquereli is one of the last sifaka species for which no reliable and extensive density estimates are yet available. Despite its endangered conservation status [IUCN, 2012] and recognition as a flagship species of the northwestern dry forests of Madagascar, its population in its last main refugium, the Ankarafantsika National Park (ANP), is still poorly known. Using line transect distance sampling surveys we estimated population density and abundance in the ANP. Furthermore, we investigated the effects of road, forest edge, river proximity and group size on sighting frequencies, and density estimates. We provide here the first population density estimates throughout the ANP. We found that density varied greatly among surveyed sites (from 5 to ∼100 ind/km2) which could result from significant (negative) effects of road, and forest edge, and/or a (positive) effect of river proximity. Our results also suggest that the population size may be ∼47,000 individuals in the ANP, hinting that the population likely underwent a strong decline in some parts of the Park in recent decades, possibly caused by habitat loss from fires and charcoal production and by poaching. We suggest community-based conservation actions for the largest remaining population of Coquerel's sifaka which will (i) maintain forest connectivity; (ii) implement alternatives to deforestation through charcoal production, logging, and grass fires; (iii) reduce poaching; and (iv) enable long-term monitoring of the population in collaboration with local authorities and researchers.


Conductance enlargement in picoscale electroburnt graphene nanojunctions.
Provided the electrical properties of electroburnt graphene junctions can be understood and controlled, they have the potential to underpin the development of a wide range of future sub-10-nm electrical devices. We examine both theoretically and experimentally the electrical conductance of electroburnt graphene junctions at the last stages of nanogap formation. We account for the appearance of a counterintuitive increase in electrical conductance just before the gap forms. This is a manifestation of room-temperature quantum interference and arises from a combination of the semimetallic band structure of graphene and a cross-over from electrodes with multiple-path connectivity to single-path connectivity just before breaking. Therefore, our results suggest that conductance enlargement before junction rupture is a signal of the formation of electroburnt junctions, with a picoscale current path formed from a single sp(2) bond.


Simultaneous occurrence of terminal deoxynucleotidyl transferase and myeloperoxidase in individual leukemia blasts.
Cases of acute leukemia showing both terminal deoxynucleotidyl transferase (TdT) and myeloperoxidase (MPO) activities are usually classified as acute myelogenous leukemia (AML). Although some reports have implied overlap of TdT and MPO based on population percentages, direct evidence for simultaneous expression of TdT and MPO by a leukemic blast is lacking. By use of a simple new technique developed in our laboratory for identifying TdT and MPO in individual cells by light microscopy, we examined three cases of acute leukemia with both TdT and MPO positivity and found that the incidence of cells positive for both TdT and MPO was 0%, 1%, and 23%. Cytogenetic analysis showed a single leukemic clone in all patients, providing additional evidence that these leukemias arose from a single cell capable of expressing both MPO and TdT. These findings have implications for understanding the relation between MPO and TdT expression in leukemia.


International criteria for the diagnosis of diabetes and impaired glucose tolerance.
International agreement on classification and criteria for the diagnosis of diabetes is highly desirable. Two systems promulgated in 1979-80 and widely used today are those of the NIH National Diabetes Data Group (NDDG) and of the World Health Organization (WHO). Although these systems are similar in many ways, certain discrepancies between them result in different classifications of oral glucose tolerance test (OGTT) results and different estimates of prevalence of the various glucose tolerance groups. Analysis of 3704 OGTTs performed during a survey of a national probability sample of U.S. residents without known diabetes and aged 20-74 yr shows that the two systems agreed in classification of 87.7% of OGTTs. For the remainder, the NDDG and WHO classifications differed, primarily because nondiagnostic OGTTs occur in the NDDG system but not in the WHO system. The differences resulted in the prevalence of impaired glucose tolerance (IGT) using WHO criteria (11.6%) being more than twice that using NDDG criteria (4.9%), although prevalence rates of diabetic OGTTs were similar in both systems (3.6%, 3.4%). The WHO system represents a simpler, inclusive classification scheme, and there is insufficient evidence from longitudinal studies of prognostic differences that would justify the more complicated NDDG diagnostic criteria. In situations where multiple venipunctures or retesting are not possible, the venous plasma glucose concentration at 2 h after 75 g glucose appears to be the most appropriate single value to use to designate whether a person has diabetes, IGT, or neither. The use of this value alone placed 97% of diabetic subjects and all other subjects, in the same class they were in when the full WHO criteria were used.


Comparison of gene coverage of mouse oligonucleotide microarray platforms.
The increasing use of DNA microarrays for genetical genomics studies generates a need for platforms with complete coverage of the genome. We have compared the effective gene coverage in the mouse genome of different commercial and noncommercial oligonucleotide microarray platforms by performing an in-house gene annotation of probes. We only used information about probes that is available from vendors and followed a process that any researcher may take to find the gene targeted by a given probe. In order to make consistent comparisons between platforms, probes in each microarray were annotated with an Entrez Gene id and the chromosomal position for each gene was obtained from the UCSC Genome Browser Database. Gene coverage was estimated as the percentage of Entrez Genes with a unique position in the UCSC Genome database that is tested by a given microarray platform. A MySQL relational database was created to store the mapping information for 25,416 mouse genes and for the probes in five microarray platforms (gene coverage level in parenthesis): Affymetrix430 2.0 (75.6%), ABI Genome Survey (81.24%), Agilent (79.33%), Codelink (78.09%), Sentrix (90.47%); and four array-ready oligosets: Sigma (47.95%), Operon v.3 (69.89%), Operon v.4 (84.03%), and MEEBO (84.03%). The differences in coverage between platforms were highly conserved across chromosomes. Differences in the number of redundant and unspecific probes were also found among arrays. The database can be queried to compare specific genomic regions using a web interface. The software used to create, update and query the database is freely available as a toolbox named ArrayGene. The software developed here allows researchers to create updated custom databases by using public or proprietary information on genes for any organisms. ArrayGene allows easy comparisons of gene coverage between microarray platforms for any region of the genome. The comparison presented here reveals that the commercial microarray Sentrix, which is based on the MEEBO public oligoset, showed the best mouse genome coverage currently available. We also suggest the creation of guidelines to standardize the minimum set of information that vendors should provide to allow researchers to accurately evaluate the advantages and disadvantages of using a given platform.


[The action of 232Th separately and in combination with heavy and alkaline metal salts on Tradescantia (clone 02)].
The action of 232Th-nitrate in concentration 0.09, 0.18 and 0.36 mg/l (counting on 232Th ion) on water cultures of Tradescantia (clone 02) was investigated. It was found that all investigated concentrations of 232Th showed statistically significant genotoxic effect and increased level of morphological abnormal cells in the stamen hairs of Tradescantia in the absence of modifying action of other metal ions. Synergistic toxic interaction was found between the 232Th in concentration 0.18 mg/l and metal ions for all samples of thawed water. Synergistic genotoxic effect of the combined action of these factors was revealed only at the low total contents of ions of heavy and alkaline metals in thawed water samples. The observed synergistic effects of the combined action of 232Th and metal ions should be taken into account when controlling the radionuclide level in the environment.


Induced infectious bovine keratoconjunctivitis: vaccination with whole cell bacterins of Moraxella bovis mixed with Freund's incomplete adjuvant.
Our studies on vaccination against infectious bovine keratoconjunctivitis were extended to include the use of adjuvant bacterins. Seventeen calves were given 2 doses of killed Moraxella bovis mixed with Freund's incomplete adjuvant; 15 calves were given 2 doses of whole cell bacterin without adjuvant. Four weeks later, all vaccinated and non-vaccinated (control) calves were challenge exposed by the conjunctival administration of virulent M bovis. The incorporation of Freund's incomplete adjuvant did not enhance the immunogenicity of M bovis bacterin for protection of calves against infectious bovine keratoconjunctivitis. Results indicated that the use of Freund's incomplete adjuvant does not compensate for a reduction in the number of doses which are required for protective vaccination of cattle.


Initial Surgery in Tailoring Treatment for Children With Stage II and III Wilms' Tumor: An Experience From Resource Challenged Settings.
Although Wilms' tumor (WT) is ranked first among primary childhood's renal neoplasm, controversy still exists regarding the best approach for its management. The study aimed at evaluating the role of initial surgery in treatment of stage II and III pediatric WT as a part of the short administration schedule as in National Wilms' Tumor Study (NWTS)-4 and evaluating its effectiveness compared to the long administration schedule. The study included 30 children who were primarily diagnosed as stage II and III WT. They were divided into two equal groups. Group I (n = 15) included those children who had undergone neoadjuvant chemotherapy followed by surgery and postoperative chemotherapy, while group II (n = 15) included those children who had undergone primary surgery as an initial management followed by chemotherapy. After a mean postoperative follow-up period of 14 ± 5 months, clinical and radiological evaluation was performed to all patients. In group I, 10 patients were preoperatively diagnosed as stage II and five patients as stage III while in group II, 11 patients were proved to be stage II and four patients were stage III. After a follow-up period, clinical and radiological evaluation using CT was performed to all patients. In patients with stage II, evidence of recurrence was noted in three patients of group I whereas no patient showed any evidence of recurrence in group II. In patients with stage III, rebound increase in size was seen in two patients in group I and only one patient in group II. Initial surgical intervention with appropriate adjuvant therapy has better outcomes than the neoadjuvant chemotherapy and delayed surgery for children primarily diagnosed as stage II and III WT. Moreover, it may act as a short administration schedule for the treatment as it is not less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.


The diffusion of innovation: factors influencing the uptake of telehealth.
The actual use of telehealth, particularly for clinical consultations, has in many cases been less than anticipated. The literature identifies a number of factors or barriers. These include legal issues, technical difficulties, time and convenience, cost and training/familiarity with the equipment. No single factor has been identified as being consistently present. Rogers' diffusion of innovation theory suggests that organizational structures and cultures will affect health professionals' perceptions of telehealth. The introduction of telehealth services affects existing work practices and workflows. We believe that it is necessary to develop strategies for the introduction of telehealth applications which take into account the idiosyncrasies of the health service sector, and the particular structures and cultures of individual organizations within that sector.


[Testing of one of the hypotheses of the inheritance of human fingerprints].
A hypothesis claiming that the total phenotypes of finger patterns are controlled by three independent two-allele loci A, L and W with the complete dominance in each was analysed in this work. By means of the population genetics methods, non-accordance of the hypothesis examined to the observed distributions of total phenotypes A, L, W, AL, LW, ALW was revealed on the material of five populations (3060 men). On the basis of the segregation analysis method applied to 210 complete families (the total number of children-532), the hypothesis of one-locus heredity with the complete dominance of total phenotypes A and W was rejected, the reliability of this conclusion being 0.999 and 0.95, respectively. The hypothesis of the L pattern being genetically controlled by one locus with the complete dominance gave, when examined, the contradictory results, due to monomorphism of the character.


Building and Sustaining Community Partnerships: An Organizational Network Analysis in a Low-resource Neighborhood.
Launched in 2012, the Claremont Healthy Village Initiative (CHVI) is a partnership focused on fostering community collaboration, addressing the social determinants of health, and reducing health disparities. Partners include local community centers, schools, after-school programs, health care providers, a health insurer, city agencies, tenant associations, resident leaders, elected officials, and other stakeholders. To understand the development and value of collaboration within the CHVI from the perspective of multiple partners. Using a community-based participatory research approach, we worked collaboratively with the CHVI leaders, we used paper-and web-based surveys grounded in social network theory were administered in 2017 and 2018. Questions focused on relationships between organizations that are part of the coalition. Our analysis included responses from organizations that participated in the survey at both points in time. Network measures such as density, degree centrality, and node characteristics were used to understand information sharing, referral, and collaboration among the participating organizations. Additional data included stake-holder interviews. Coalition partners increased connectedness with one another over the course of the study, with significantly greater density of relationship and bi-directional partnerships in the follow-up survey. Of the three types of interactions, referrals showed a trend for highest density change. Trust levels were highest among organizations with a local physical presence. Social network analysis provided visual and quantitative information that helped reinforce relationships and identify opportunities to improve connectedness and collaboration among diverse community partners, helping to support the coalition's goals and objectives.


Left-ventricular performance in man during breath-holding and simulated diving.
We measured left-ventricular (LV) systolic time intervals (STI) to determine whether breath-holding and simulated diving evoke a depression of LV performance in man similar to that previously demonstrated in natural divers. Records of STI were obtained by a noninvasive procedure in 15 adult males who had breath-holding diving experience during supine rest, at 30 and 60 s of simple breath-holding (BH) and at 30 and 60 s of BH combined with cold, wet facial stimulation (FS). Changes in both BP and HR during FS reflected cardiovascular behavior typical of simulated diving. The isovolumic contraction period increased 13% and 31% after 60 s of BH and FS, respectively. LV ejection time shortened by 30 ms during BH and by 37 ms during FS. These measurements of STI represent the first description of cardiac cycle components during the human diving response. The alterations in STI suggest that a reduction in LV performance, as seen by a decreased rate of preejection pressure development and a diminished stroke volume, had occurred during the apneic maneuvers. In addition, there was a trend in these measures indicating that FS potentiated the response over that which occurred during BH. Thus, it appears that man exhibits a depression of LV performance during simulated diving similar to that found in natural divers.


Endocytoscopy: technology and clinical application in upper gastrointestinal tract.
Over the past few years, the innovative field of magnifying endoscopy has been expanding with various cutting-edge technologies, one of which is endocytoscopy, to facilitate improvement in the detection and diagnosis of gastrointestinal lesions. Endocytoscopy is a novel ultra-high magnification endoscopic technique enabling high-quality in-vivo assessment of lesions found in the gastrointestinal tract with the use of intraprocedural stains. The main scope of this review article is to offer a closer look at the latest endocytoscopic technology and its clinical application in the upper gastrointestinal tract, especially in the esophagus and stomach, as well as to introduce readers to our simplified and up-to-date endocytoscopic classification, specifically developed for the esophagus and stomach, for the in-vivo assessment and diagnosis of esophageal and gastric lesions. Despite the good accuracy of endocytoscopy in the diagnosis of esophageal and gastric lesions in recent studies, some challenges still remain (e.g., staining method and standardized endocytoscopic classification). Through continuous evaluation and improvement of methods and skills, these challenges may be overcome thus establishing current techniques and classification, paving the way for further advances in the field of endocytoscopy and magnifying endoscopy. In all, endocytoscopy seems to aid in the in-vivo diagnosis of gastrointestinal tract lesions and may, in the future, revolutionize the field of in-vivo endoscopic diagnosis of gastrointestinal cancer, representing another step towards the so-called optical biopsy.


Yoga during pregnancy: The effects on labor pain and delivery outcomes (A randomized controlled trial).
To investigate the effects of an antenatal yoga program on perceived maternal labor pain and delivery outcomes. This randomized control trial was conducted with sixty primiparous women, aged 18-35 years old, who were randomly assigned to either an antenatal yoga program or control groups. Labor pain and discomfort level of the participants were measured using a Visual Analogue Scale at cervical dilatation of 3-4 c and at 2 and 4 h after the initial measurement. Demographic and obstetrical information were collected. The antenatal yoga program consisted of a 1-h supervised yoga class, three times a weekly, starting at 26 weeks gestation. . Participants in control group reported higher pain intensity compared to experimental group at 3-4 cm of dilatation (p = 0.01) and at 2 h after the first and the second measurements (p = 0.000). Mothers in the antenatal intervention group that completed the yoga class required a decreased frequency of labor induction in comparison with control group (p = 0.008). In addition, mode of delivery of the intervention group resulted in a lower percentage of cesarean section than control group (p = 0.002). Lastly, the intervention group experienced a shorter duration of the second and third stages of labor. Interval level data was analyzed by using an independent t-test and chi-square. Yoga during pregnancy may contribute to a reduction pain of labor and improved adequacy of childbirth.


Assessment of data quality and reporting systems for underserved populations: the case of integrated community case management programs in Nigeria.
Decision makers are searching for reliable data and best practices to support the implementation and scale-up of the integrated community case management (iCCM) programs in underserved areas to reduce under-five mortality in low-income countries. This study assesses data quality and reporting systems of the World Health Organization supported Rapid Access Expansion program implementing iCCM in Abia and Niger States, Nigeria. This cross-sectional study used data from 16 primary health facilities in both states. Data were collected through review of registers and monthly summary reports of 140 community-oriented resource persons (CORPs), assessments of the five dimensions of the data reporting systems and 46 key informant interviews with stakeholders. Data quality was assessed by availability, completeness and consistency. Each component of the reporting system was assessed on a 3-point scale (weak, satisfactory and strong). Results show that both the structure, functions and capabilities, as well as data collection and reporting tools dimensions of the reporting system were strong, scoring (2.80, 2.73) for Abia and (2.88, 2.75) for Niger, respectively. Data management processes and links with national reporting system components scored low 2 s, indicating fair strength. Data availability, completeness and consistency were found to be good, an indication of adequate training and supervision of CORPs and community health extension workers. Indicator definitions and reporting guidelines were the weakest dimension of the system due to lack of data reporting guidelines in both states. In conclusion, the results indicate satisfactory data reporting systems and good quality data during early implementation of iCCM programs in the two states. Hence, countries planning to adopt and implement iCCM programs should first develop structures, establish national standardized tools for collecting and reporting data, provide for adequate training and supervision of community health workers and develop reporting guidelines for all reporting levels to ensure data quality.


Actions of annatto-extracted tocotrienol supplementation on obese postmenopausal women: study protocol for a double-blinded, placebo-controlled, randomised trial.
Obesity is a major health concern in postmenopausal women, and chronic low-grade inflammation contributes to the development of obesity. Cellular studies and high-fat-diet-induced obese mouse model mimicking obesity show the antiobesity effect of annatto-extracted tocotrienols (TT) with antioxidant capability. We aim to assess the safety and efficacy of TT consumption for lipid-related parameters in obese postmenopausal women. Eligible obese postmenopausal women will be randomly assigned to placebo group (430 mg olive oil) and TT group (DeltaGold Tocotrienol 70%) for 24 weeks. In the present study, the primary outcome is total/regional fat mass and visceral adipose tissue. The secondary outcomes include lipid profile in serum, mRNA expression of fatty acid synthase and carnitine palmitoyltransferase 1A in fat tissue, oxylipins and endocannabinoids in plasma and adipose tissue, abundance and composition of intestinal microbiome in faeces, high-sensitivity C-reactive protein (hs-CRP) in serum and leptin in serum. Every participant will be evaluated at 0 (prior to starting intervention) and 24 weeks of intervention, except for serum lipid profile and hs-CRP at 0, 12 and 24 weeks. 'Intent-to-treat' principle is employed for data analysis. Hierarchical linear modelling is used to estimate the effects of dietary TT supplementation while properly accounting for dependency of data and identified covariates. To our knowledge, this is the first randomised, placebo-controlled, double-blinded study to determine dietary TT supplementation on an obese population. If successful, this study will guide the future efficacy TT interventions and TT can be implemented as an alternative for obese population in antiobesity management. This study has been approved by the Bioethics Committee of the Texas Tech University Health Sciences Center, Lubbock. An informed consent form will be signed by a participant before enrolling in the study. The results from this trial will be actively disseminated through academic conference presentation and peer-reviewed journals. NCT03705845.


Vesicular stomatitis virus modified with single chain IL-23 exhibits oncolytic activity against tumor cells in vitro and in vivo.
Viruses are potentially attractive agents for development as novel oncolytic agents. Reverse genetic approaches allow for the attenuation of candidate viruses and can enhance their ability to exploit inherent cellular and molecular properties of tumors, including deficiencies in interferon (IFN) signaling. Vesicular stomatitis virus (VSV) is a promising oncolytic agent for exactly these reasons. VSV infection of immunocompetent mice is usually rapidly cleared due to the virus' sensitivity to type I IFN responses. However, in tumors that are unable to activate the IFN response, VSV is able to replicate without inhibition, resulting in cell destruction. Unfortunately, when VSV is introduced into mice intranasally or systemically via therapeutic doses into tumor-bearing rodents, hosts may develop fatal encephalitis. We have previously found that a recombinant VSV expressing the pro-inflammatory cytokine interleukin-23 (IL-23) is significantly attenuated in the central nervous system (CNS). As a result of this, we hypothesized that attenuation in the CNS is partially a result of enhanced NO response as a result of IL-23 signaling. Infection of the CNS with this virus (designated VSV23) is characterized by decreased viral replication, morbidity, and mortality. We have now extended those studies which reveal that VSV23 maintains oncolytic capacity in vitro in multiple cell lines including NB41A3 neuroblastomas, L929 adipose-derived cells, immortalized BHK-21 cells, and the murine mammary derived JC cells. Additionally, in vivo VSV23 infection results in JC tumor destruction and induces enhanced memory responses against tumor cells.


Treatment of Cutaneous Leishmaniasis with Sodium Stibogluconate and Allopurinol in a Routine Setting in Ethiopia: Clinical and Patient-Reported Outcomes and Operational Challenges.
Cutaneous leishmaniasis (CL) is common in Ethiopia, but the national guideline does not offer specific treatment recommendations. Consequently, different treatment regimens are used in the country, without quality evidence. In Boru Meda Hospital, sodium stibogluconate (SSG) is routinely used in combination with allopurinol for systemic CL treatment, although evidence on its effectiveness is limited. An observational cohort study was carried out to document clinical treatment outcomes in patients receiving SSG/allopurinol at the end of each 28-day treatment cycle and after 180 days. Patient-reported outcomes were assessed by asking patients to rate lesion severity, and by the dermatological life quality index. A total of 104 patients were included. After one treatment cycle, only four patients were clinically cured, although patient-reported outcomes significantly improved. The majority (88) of patients were appointed for a second treatment cycle, of whom only 37 (42%) attended. Among the 36 patients who came for final outcome assessment, 50% were cured. Follow-up and treatment were severely affected by conflict; drug stock-outs and insufficient ward capacity for treatment were additional challenges. The treatment outcomes of SSG/allopurinol were relatively poor, and most patients required more than one cycle of treatment. Shortages of drugs and beds indicate the existing gaps in providing CL treatment in Ethiopia.


Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia.
This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results. The working group found sufficient evidence to support a recommendation to use CSF AD biomarkers as a supplement to clinical evaluation, particularly in uncertain and atypical cases, to identify or exclude AD as the cause of dementia. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Operational recommendations for the interpretation of ambiguous CSF biomarker results were also provided.


Emotional intelligence as a standard intelligence.
The authors have claimed that emotional intelligence (EI) meets traditional standards for an intelligence (J. D. Mayer, D. R. Caruso, & P. Salovey, 1999). R. D. Roberts, M. Zeidner, and G. Matthews (2001) questioned whether that claim was warranted. The central issue raised by Roberts et al. concerning Mayer et al. (1999) is whether there are correct answers to questions on tests purporting to measure EI as a set of abilities. To address this issue (and others), the present authors briefly restate their view of intelligence, emotion, and EI. They then present arguments for the reasonableness of measuring EI as an ability, indicate that correct answers exist, and summarize recent data suggesting that such measures are, indeed, reliable.


The measles virus fusion protein transmembrane region modulates availability of an active glycoprotein complex and fusion efficiency.
The glycoprotein complex of paramyxoviruses mediates receptor binding and membrane fusion. In particular, the measles virus (MV) fusion (F) protein executes membrane fusion, after receptor binding by the hemagglutinin (H) protein. Structures and single amino acids influencing fusion function have been identified in the F-protein ectodomain and cytoplasmic tail, but not in its transmembrane (TM) region. Since this region influences function of the envelope proteins of other viruses, we examined its role in the MV F protein. Alanine-scanning mutagenesis revealed that an F protein with a single mutation of a central TM region leucine (L507A) was more fusogenic than the unmodified F protein while retaining similar kinetics of proteolytic processing. In contrast, substitution of residues located near the edges of the lipid bilayer reduced fusion activity. This was true not only when the mutated F proteins were coexpressed with H but also in the context of infections with recombinant viruses. Analysis of the H-F complexes with reduced fusion activities revealed that more precursor (F(0)) than activated (F(1+2)) protein coprecipitated with H. In contrast, in complexes with enhanced fusion activity, including H-F(L507A), the F(0)/F(1+2) ratio shifted toward F(1+2). Thus, fusion activity correlated with an active F-H protein complex, and the MV F protein TM region modulated availability of this complex.


"It Has Changed My Life": An Exploration of Caregiver Experiences in Serious Illness.
Informal, unpaid caregivers shoulder much of the care burden for individuals with serious illness. As part of a project to create an innovative model of supportive care for serious illness, a series of user interviews were conducted, forming the basis for this article. To understand both individual and interpersonal aspects of caregiving for serious illness. Twelve semistructured group interviews were conducted with patients, families, and professionals as part of a larger study of late-life serious illness. Transcript data were analyzed with descriptive coding, and then coded material was analyzed to elicit major themes and subthemes. A total of 73 individuals participated in group interview sessions. Using descriptive coding, quotes were assigned to first-order codes of rewards, challenges, and a category of learnings and adaptations. Subthemes of reward included gratitude, a sense of accomplishment or mastery, and closeness in personal relationships. The most oft-cited challenges included emotional and physical stresses of caregiving and feeling unprepared or unsupported in caregiving. Reflecting on their experiences, caregivers cited new ways in which they had learned to be creative, to show assertiveness and advocacy, and to create personal balance in a demanding situation. The experience of caregiving is a life-altering journey as individuals rise to challenges and reflect on the rewards. Caregivers described intensive caregiving, often without acknowledgment or understanding of their role from the health-care system. This invisibility created its own iatrogenic caregiving challenge. The identified themes suggest avenues of meaningful caregiver support that bear further exploration.


Metal-responsive transcription factor-1 (MTF-1) selects different types of metal response elements at low vs. high zinc concentration.
Metal-responsive transcription factor-1 (MTF-1) is a zinc finger protein with a central role in heavy metal homeostasis/detoxification. MTF-1 binds to DNA sequence motifs known as metal response elements (MREs) with a core consensus TGCRCNC. Since MTF-1 is also involved in other stress responses, we tested whether it is able to recognize different types of DNA sequence motifs. To this end we selected MTF-1-binding oligonucleotides from a collection of random sequences. Since MTF-1 binds to known target sequences at relatively high zinc concentrations, oligonucleotide selection was performed in a mammalian cell nuclear extract both at high and low zinc concentrations. Irrespective of zinc concentration, we find a robust representation of MRE consensus sequences, however with specific features. Selection was most efficient at 100 microM zinc, yielding many oligonucleotides with two MRE motifs in divergent orientation of the sequence GTGTGCATCACTTTGCGCAC (core consensus underlined). Oligonucleotides selected without zinc supplement contain a single high-affinity MRE with an extended flanking sequence of consensus TTTTGCGCACGGCACTAAAT (core consensus underlined). This low-zinc MRE motif can bind MTF-1 and induce transcription in vivo, and is less dependent on zinc than the classical MREd motif from the mouse metallothionein-I promoter. At low zinc, we also found evidence for a negative role of nuclear factor-I (NF-I/CTF-I) in MTF-1-dependent transcription. Finally, a selection in the presence of cadmium yielded no specific binding site for MTF-1, strongly supporting the concept of an indirect activation of MTF-1 by cadmium within a living cell.


Evaluating the anti-biofilm and antibacterial effects of Juglans regia L. extracts against clinical isolates of Pseudomonas aeruginosa.
Pseudomonas aeruginosa, an opportunistic pathogen, can cause serious health problems and produces several virulence factors. The most important of these factors is biofilm. Many studies suggest administration of new generation of antibiotics, as P. aeruginosa biofilm has developed high resistance to antimicrobial drugs. Emergence of multidrug resistant (MDR) strains has resulted in screening biofilm inhibitors from natural products or modified from natural compounds. To test this hypothesis, we evaluated the inhibitory effects (antibacterial and antibiofilm) of Juglans regia L. extract on biofilm formation by clinical isolates of P. aeruginosa. Samples collected from burn, tracheal and urine infections of hospitalized patients (Shahid Motahari Hospital, Tehran, Iran) were identified as P. aeruginosa using traditional biochemical tests. Antibiotic susceptibility testing of isolates was performed using disk diffusion method. The microtiter plate method was used to evaluate the ability of pathogenic strains in producing biofilm. Antibacterial and antibiofilm effects of aqueous and methanol Juglans regia L. leaf extracts were determined by microtiter plate method. 46.7% of P. aeruginosa isolates (n = 50) were resistant to gentamicin and 100% of them could form a biofilm. All isolates (100%) exhibited MDR phenotype. Various concentrations of Juglans regia L. extracts exhibited significant effects on the growth and biofilm inhibition of the isolates. In addition, aqueous Juglans regia L. leaf extract had better inhibition activity on planktonic growth, and methanol extract was more effective on inhibiting biofilm of P. aeruginosa. The results of this study indicate that antibiotic-resistant strains were significantly associated with biofilm formation. The J. regia L. extract, at various concentrations, may provide an alternative to control biofilm-related infections caused by P. aeruginosa. Further analyses are needed to validate the antibiofilm activity of these medicinal plants.


Characterization of the onset of leptin effects on the regulation of energy balance.
Leptin is a hormone required for the regulation of body weight in adult animals. However, during the postnatal period, leptin is mostly involved in developmental processes. Because the precise moment at which leptin starts to exert its metabolic effects is not well characterized, our objective was to identify the approximate onset of leptin effects on the regulation of energy balance. We observed that male Lepob/ob mice started to exhibit increased body fat mass from postnatal day 13 (P13), whereas in females, the increase in adiposity began on P20. Daily leptin injections from P10 to P22 did not reduce the weight gain of WT mice. However, an acute leptin injection induced an anorexigenic response in 10-day-old C57BL/6 mice but not in 7-day-old mice. An age-dependent increase in the number of leptin receptor-expressing neurons and leptin-induced pSTAT3 cells was observed in the hypothalamus of P7, P10 and P16 mice. Leptin deficiency started to modulate the hypothalamic expression of transcripts involved in the regulation of metabolism between P7 and P12. Additionally, fasting-induced hypothalamic responses were prevented by leptin replacement in 10-day-old mice. Finally, 12-day-old males and females showed similar developmental timing of axonal projections of arcuate nucleus neurons in both WT and Lepob/ob mice. In summary, we provided a detailed characterization of the onset of leptin's effects on the regulation of energy balance. These findings contribute to the understanding of leptin functions during development.


PITUITARY DEFICIENCY FOLLOWING TRAUMATIC BRAIN INJURY IN EARLY CHILDHOOD: A REVIEW OF THE LITERATURE.
AIMS OF REVIEW: the intent of the current manuscript is to critically review the studies on pituitary gland dysfunction in early childhood following traumatic brain injury (TBI), in comparison with those in adults. Search of the literature: The MEDLINE database was accessed through PubMed in April 2015. Results were restricted to the past 15 years and English language of articles. Both transient and permanent hypopituitarisms are not uncommon after TBI. Early after the TBI, pituitary dysfunction/s differ than those occurring after few weeks and months. Growth hormone deficiency (GHD) and alterations in puberty are the most common. After the one to more years of TBI, pituitary dysfunction tends to improve in some patients but may deteriorate in others. GH deficiency as well as Hypogonadism and thyroid dysfunction are the most common permanent lesions. Many of the symptoms of these endocrine defects can pass unnoticed because of the psychomotor defects associated with the TBI like depression and apathy. Unfortunately pituitary dysfunction appear to negatively affect psycho-neuro-motor recovery as well as growth and pubertal development of children and adolescents after TBI. Therefore, the current review highlights the importance of closely following patients, especially children and adolescents for growth and other symptoms and signs suggestive of endocrine dysfunction. In addition, all should be screened serially for possible endocrine disturbances early after the TBI as well as few months to a year after the injury. Risk factors for pituitary dysfunction after TBI include relatively serious TBI (Glasgow Coma Scale score < 10 and MRI showing damage to the hypothalamic pituitary area), diffuse brain swelling and the occurrence of hypotensive and/or hypoxic episodes. There is a considerable risk of developing pituitary dysfunction after TBI in children and adolescents. These patients should be clinically followed and screened for these abnormalities according to an agreed protocol of investigations. Further multicenter and multidisciplinary prospective studies are required to explore in details the occurrence of permanent pituitary dysfunction after TBI in larger numbers of children with TBI. This requires considerable organisation and communication between many disciplines such as neurosurgery, neurology, endocrinology, rehabilitation and developmental paediatrics.


Massive hemothorax secondary to metastatic renal carcinoma.
We present the case of a 78-year-old man with a past history of nephrectomy for renal cell carcinoma who was brought to the emergency room in hypovolemic shock after suddenly collapsing at home. A chest roentgenogram taken on admission showed a large pleural effusion on the right with a mediastinal shift to the left. A contrast computed tomographic scan of his chest excluded aortic dissection. An emergency right thoracotomy was performed, which revealed a chest wall tumor that was bleeding profusely. The tumor was biopsied after the bleeding was controlled. The histologic report revealed metastatic renal cell carcinoma, which is a rare cause for a spontaneous massive hemothorax.


Surface modification of droplet polymeric microfluidic devices for the stable and continuous generation of aqueous droplets.
Droplet microfluidics performed in poly(methyl methacrylate) (PMMA) microfluidic devices resulted in significant wall wetting by water droplets formed in a liquid-liquid segmented flow when using a hydrophobic carrier fluid such as perfluorotripropylamine (FC-3283). This wall wetting led to water droplets with nonuniform sizes that were often trapped on the wall surfaces, leading to unstable and poorly controlled liquid-liquid segmented flow. To circumvent this problem, we developed a two-step procedure to hydrophobically modify the surfaces of PMMA and other thermoplastic materials commonly used to make microfluidic devices. The surface-modification route involved the introduction of hydroxyl groups by oxygen plasma treatment of the polymer surface followed by a solution-phase reaction with heptadecafluoro-1,1,2,2-tetrahydrodecyl trichlorosilane dissolved in fluorocarbon solvent FC-3283. This procedure was found to be useful for the modification of PMMA and other thermoplastic surfaces, including polycyclic olefin copolymer (COC) and polycarbonate (PC). Angle-resolved X-ray photoelectron spectroscopy indicated that the fluorination of these polymers took place with high surface selectivity. This procedure was used to modify the surface of a PMMA droplet microfluidic device (DMFD) and was shown to be useful in reducing the wetting problem during the generation of aqueous droplets in a perfluorotripropylamine (FC-3283) carrier fluid and could generate stable segmented flows for hours of operation. In the case of PMMA DMFD, oxygen plasma treatment was carried out after the PMMA cover plate was thermally fusion bonded to the PMMA microfluidic chip. Because the appended chemistry to the channel wall created a hydrophobic surface, it will accommodate the use of other carrier fluids that are hydrophobic as well, such as hexadecane or mineral oils.


Reducing the risk of choking hazards: mouthing behaviour of children aged 1 month to 5 years.
Young children have a natural tendency to mouth items to explore their environment. Mouthing carries mechanical and chemical hazard potential for injury to the child, for example if they swallow an item they may choke, they may cut themselves on sharp items, and certain chemicals are present in plastic items which may pose a risk to children. Few data are available on the time that young children mouth items, how they mouth, and what they mouth. This study gathered data on 236 children aged between 1 month and 5 years to supplement and extend existing data. Findings are presented of estimated average and maximum daily mouthing times for children, how they mouth, what they mouth, and whether the items mouthed were intended to be. A validation study was carried out to determine the accuracy of the parental observation method used to gather the data. The implications of the findings of this study are discussed with respect to reducing the potential for mechanical accidents in the home.


Pronase destroys the lipopolysaccharide receptor CD14 on Kupffer cells.
CD14 is a lipopolysaccharide (LPS) receptor distributed largely in macrophages, monocytes, and neutrophils; however, the role of CD14 in activation of Kupffer cells by LPS remains controversial. The purpose of this study was to determine if different methods used to isolate Kupffer cells affect CD14. Kupffer cells were isolated by collagenase (0.025%) or collagenase-Pronase (0.02%) perfusion and differential centrifugation using Percoll gradients and cultured for 24 h before experiments. CD14 mRNA was detected by RT-PCR from Kupffer cell total RNA as well as from peritoneal macrophages. Western blotting showed that Kupffer cells prepared with collagenase possess CD14; however, it was absent in cells obtained by collagenase-Pronase perfusion. Intracellular calcium in Kupffer cells prepared with collagenase was increased transiently to levels around 300 nM by addition of LPS with 5% rat serum, which contains LPS binding protein. This increase in intracellular calcium was totally serum dependent. Moreover, LPS-induced increases in intracellular calcium in Kupffer cells were blunted significantly (40% of controls) when cells were treated with phosphatidylinositol-specific phospholipase C, which cleaves CD14 from the plasma membrane. However, intracellular calcium did not increase when LPS was added to cells prepared by collagenase-Pronase perfusion even in the presence of serum. These cells were viable, however, because ATP increased intracellular calcium to the same levels as cells prepared with collagenase perfusion. Tumor necrosis factor-alpha (TNF-alpha) mRNA was increased in Kupffer cells prepared with collagenase perfusion 1 h after addition of LPS, an effect potentiated over twofold by serum; however, serum did not increase TNF-alpha mRNA in cells isolated via collagenase-Pronase perfusion. Moreover, treatment with Pronase rapidly decreased CD14 on mouse macrophages (RAW 264.7 cells) and Kupffer cells. These findings indicate that Pronase cleaves CD14 from Kupffer cells, whereas collagenase perfusion does not, providing an explanation for why Kupffer cells do not exhibit a CD14-mediated pathway when prepared with procedures using Pronase. It is concluded that Kupffer cells indeed contain a functional CD14 LPS receptor when prepared gently.


Development of Safe and Scalable Continuous-Flow Methods for Palladium-Catalyzed Aerobic Oxidation Reactions.
The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has advanced significantly over the past decade, and these reactions have potential to address important green-chemistry challenges in the pharmaceutical industry. This potential has been unrealized, however, because safety concerns and process constraints hinder large-scale applications of this chemistry. These limitations are addressed by the development of a continuous-flow tube reactor, which has been demonstrated on several scales in the aerobic oxidation of alcohols. Use of a dilute oxygen gas source (8% O(2) in N(2)) ensures that the oxygen/organic mixture never enters the explosive regime, and efficient gas-liquid mixing in the reactor minimizes decomposition of the homogeneous catalyst into inactive Pd metal. These results provide the basis for large-scale implementation of palladium-catalyzed (and other) aerobic oxidation reactions for pharmaceutical synthesis.


Analytical strategies for large imaging genetic datasets: experiences from the IMAGEN study.
Large imaging genetic studies are becoming increasingly common in psychiatric research. In order to fully explore the collected information, analytical strategies that allow comprehensive investigations of the genetic and neural underpinnings of psychiatric disorders are needed. On the basis of our experience with the IMAGEN study, this review evaluates univariate and multivariate analytical strategies for exploring large imaging genetic datasets, with particular focus on reinforcement mechanisms in adolescents. Heritability estimates of functional and structural MRI endophenotypes are presented along with analytical strategies, ranging from those used in univariate candidate gene studies to genome-wide association studies. Finally, data reduction strategies are discussed at both the genotype level, in the form of expression SNPs and pathway analyses, and the phenotype level, as network analyses of neuroimaging data. Overall, imaging genetic studies have the potential to significantly contribute to our understanding of neurophysiological processes underlying human behavior. The analytical strategies presented here may aid in the comprehensive investigation of reinforcement and other neurobehavioral phenotypes.


Insights from impedance spectroscopy into the mechanism of thermal decomposition of M(NH2BH3), M = H, Li, Na, Li(0.5)Na(0.5), hydrogen stores.
We report the first solid-state impedance study of hydrogen-rich ammonia borane, AB, and its three alkali metal amidoborane derivatives. Temperature-dependent impedance spectra of solid M(NH(2)BH(3)) salts are predominated by ionic conductivity, which at room temperature ranges from 5.5 μS cm(-1) (M = Li) to 2.2-3.0 mS cm(-1) (Na, Na(0.5)Li(0.5)), while the activation energy for conductivity is rather high (140-158 kJ mol(-1)). Variation of conductivity with time can be used to extract information about the evolution of the system during thermal decomposition. By using a combination of impedance spectroscopy, thermogravimetric analysis, scanning calorimetry, evolved gas analysis, infrared absorption spectroscopy as well as (11)B and (1)H MAS NMR, we were able to reconfirm the complex pathway of thermal decomposition of amidoboranes postulated by two of us earlier (J. Mater. Chem. 2009, 19, 2043).


Intestinal regulation of copper homeostasis: a developmental perspective.
Stable-isotope studies in human infants and adults have shown that copper homeostasis occurs, but the contribution of the small intestine to this regulation is still not well understood. Copper first needs to be reduced to the cuprous form, most likely by Steap proteins on the apical membrane. Copper is subsequently absorbed by Ctr1 and then transferred in the enterocyte by the chaperone Atox1 to reach ATP7A for export from the cell. The role of ATP7B, shown to be present in the small intestine, is still poorly understood. In situations of high copper exposure, Ctr1 is endocytosed, metallothionein is induced, and ATP7A moves to a more basolateral localization. However, the ontogeny of regulation of copper homeostasis has received little attention. In rat pups, tissue copper and total-body (67)Cu retention decrease throughout postnatal development, whereas liver (67)Cu retention, serum copper, and ceruloplasmin activity increase. Total (67)Cu absorption decreases and intestinal (67)Cu retention increases with increased copper intake. During early infancy (day 10), copper supplementation increases intestinal copper and metallothionein gene expression, and Ctr1 protein levels increase, whereas Atp7A and Atp7B are unaffected. However, during late infancy (day 20), intestinal copper concentrations are unaffected by supplementation, but Ctr1, ATP7A, and Atp7B protein levels are higher than in controls. Thus, maturation of small intestine copper transport occurs through increased abundance and altered localization of Ctr1, Atp7A, and Atp7B. The mechanisms behind this maturation, including both transcriptional and posttranscriptional regulation, require further studies.


Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle through regulating p38 mitogen-activated protein kinase/p53/p21 pathway.
Iron is an essential nutrient that may exert toxic effects when it accumulates in tissues. Little is known regarding its effects on gonadal function. Both Fe2+ and Fe3+ could be released from iron deposition. We employed mouse nonluteinized granulosa cell for in vitro studies and human ovarian tissues for Prussian blue and immunohistochemical staining to identify the iron deposition and effect in vivo. After treatment with FeSO4-7H2O or FeCl3 in granulosa cell cultured with follicle-stimulating hormone (FSH) for 48 h, we found that Fe2+ significantly suppressed FSH-induced granulosa cell proliferation and arrested the cell cycle at the G2/M phase by cell proliferation assay and flow cytometry. Fe2+ significantly increased intracellular reactive oxygen species (ROS) and ferritin levels of mouse granulosa cells. The increases in p21 and p53 messenger RNA and protein expression facilitated by Fe2+ treatment in mouse granulosa cells were significantly suppressed by separate treatments with p53 small interfering RNA and p38 mitogen-activated protein kinase (MAPK) inhibitors. An ROS inhibitor downregulated Fe2+-induced increases in p38MAPK expression in mouse granulosa cells. Quantitative analysis of immunohistochemical staining revealed that human ovarian tissue sections with positive Prussian blue staining had lower levels of proliferating cell nuclear antigen expression, but higher levels of p21, p53, and CDC25C expression than those with negative Prussian blue staining. Conclusively, Fe2+ could directly arrest the cell cycle and inhibit granulosa cell proliferation by regulating the ROS-mediated p38MAPK/p53/p21 pathway. Therefore, iron can directly affect female gonadal function.


Inhibition of host extracellular matrix destructive enzyme production and activity by a high-molecular-weight cranberry fraction.
Periodontal diseases are a group of inflammatory disorders that are initiated by specific gram-negative bacteria and lead to connective tissue destruction. Proteolytic enzymes, including matrix metalloproteinases (MMPs) and elastase, produced by resident and inflammatory cells in response to periodontopathogens and their products, play a major role in gingival tissue destruction. The aim of this study was to investigate the effect of a high-molecular-weight fraction prepared from cranberry juice concentrate on MMP-3, MMP-9 and elastase activities, as well as on MMP production by human cells stimulated with lipopolysaccharide of Actinobacillus actinomycetemcomitans. MMP-3 and MMP-9 production by gingival fibroblasts and macrophages treated with the cranberry fraction and then stimulated with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. MMP-3, MMP-9 and elastase activities in the presence of the cranberry fraction were evaluated using colorimetric or fluorogenic substrates. The changes in expression and phosphorylation state of fibroblast intracellular signaling proteins induced by A. actinomycetemcomitans lipopolysaccharide and the cranberry fraction were characterized by antibody microarrays. The lipopolysaccharide-induced MMP-3 and MMP-9 responses of fibroblasts and macrophages were inhibited in a dose-dependent manner by the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. MMP-3, MMP-9 and elastase activities were also efficiently inhibited by the cranberry fraction, even when it was used at low concentrations. These results suggest that cranberry compounds offer promising perspectives for the development of novel host-modulating strategies for an adjunctive treatment of periodontitis.


The Wnt receptor Ryk plays a role in mammalian planar cell polarity signaling.
Wnts are essential for a wide range of developmental processes, including cell growth, division, and differentiation. Some of these processes signal via the planar cell polarity (PCP) pathway, which is a β-catenin-independent Wnt signaling pathway. Previous studies have shown that Ryk, a member of the receptor tyrosine kinase family, can bind to Wnts. Ryk is required for normal axon guidance and neuronal differentiation during development. Here, we demonstrate that mammalian Ryk interacts with the Wnt/PCP pathway. In vitro analysis showed that the Wnt inhibitory factor domain of Ryk was necessary for Wnt binding. Detailed analysis of two vertebrate model organisms showed Ryk phenotypes consistent with PCP signaling. In zebrafish, gene knockdown using morpholinos revealed a genetic interaction between Ryk and Wnt11 during the PCP pathway-regulated process of embryo convergent extension. Ryk-deficient mouse embryos displayed disrupted polarity of stereociliary hair cells in the cochlea, a characteristic of disturbed PCP signaling. This PCP defect was also observed in mouse embryos that were double heterozygotes for Ryk and Looptail (containing a mutation in the core Wnt/PCP pathway gene Vangl2) but not in either of the single heterozygotes, suggesting a genetic interaction between Ryk and Vangl2. Co-immunoprecipitation studies demonstrated that RYK and VANGL2 proteins form a complex, whereas RYK also activated RhoA, a downstream effector of PCP signaling. Overall, our data suggest an important role for Ryk in Wnt/planar cell polarity signaling during vertebrate development via the Vangl2 signaling pathway, as demonstrated in the mouse cochlea.


Adrenalectomy for solitary metastasis of Hepatocellular carcinoma post liver transplantation: Case report and literature review.
Liver transplantation (LT) is the treatment of choice for localized hepatocellular carcinoma (HCC) associated with cirrhosis. Extra hepatic metastasis is the most common cause of death in these patients. There is very little evidence regarding the natural history and treatment options for patients developing HCC recurrence after LT. Surgical resection offers a unique opportunity for solitary metastasis. We report a 61 year old male with solitary right adrenal metastasis 15 months post LT which was managed with open adrenalectomy. The patient is alive and disease free 24 months after the surgery. The case, histo-pathological findings and literature review is discussed.


CTP:phosphocholine cytidylyltransferase and protein kinase C recognize different physical features of membranes: differential responses to an oxidized phosphatidylcholine.
Protein kinase C (PKC) and CTP:phosphocholine cytidylyltransferase (CT) are two examples of enzymes that are regulated by reversible binding to membranes, and this binding is influenced by membrane physical properties. CT activation by oxidized phosphatidylcholines was recently demonstrated and was linked to the acyl chain disordering effect of the oxidized species (Biochemistry 38, 15606). In this paper, we compare the responses of PKC and CT to an oxidized PC, and investigate the physical properties of lipid bilayers that modulate the activity of these enzymes. We show that 1-palmitoyl, 2-(11,15 dihydroxy) eicosatrienoyl PC (diOH-PAPC) caused less of an increase in the temperature of the lamellar to hexagonal II transition (T(H)) of an unsaturated PE, compared to its parent, PAPC. Using a polarity-sensitive interfacial probe, we also found evidence to suggest that this oxidized PC increases interfacial packing pressure. We found that whereas diOH-PAPC activates CT, it inhibits PKC relative to the parent PAPC. The activities of both CT and PKC are known to increase in the presence of non-lamellar forming lipids. The greater activating effect of diOH-PAPC compared with PAPC, is consistent with a stimulation of the activity of CT by negative curvature strain. However, this is not the case with PKC, for which we suggest that surface packing pressure is of prime importance.


Protein folding triggered by electron transfer.
Rapid photochemical electron injection into unfolded ferricytochrome c titrated with 2.3 to 4.6 M guanidine hydrochloride (GuHCL) at pH 7 and 40 degrees C produced unfolded ferrocytochrome, which then converted to the folded protein. Two folding phases were observed: a fast process with a time constant of 40 microseconds (4.6 M GuHCL), and a slower phase with a rate constant of 90 +/- 20 per second (2.3 M GuHCL). The activation free energy for the slow step varied linearly with GuHCL concentration; the rate constant, extrapolated to aqueous solution, was 7600 per second. Electron-transfer methods can bridge the nanosecond to millisecond measurement time gap for protein folding.


[Pasteurella multocida bacteremic meningitis].
Human infections by Pasteurella multocida are usually associated with bites or scratches from dogs and cats. Many of them are accompanied by other oropharyngeal microorganisms of these animals. We herein present a case of bacteremic meningitis by P. multocida in an 86-year-old woman who was living with seven cats. Even though no skin or soft tissue infection was recorded, it is possible that a mild infection had gone undetected and a subsequent bacteremia had impacted on the meninges, or that meningitis could have occurred after nasopharyngeal colonization (not demonstrated). The isolates obtained from blood cultures and cerebrospinal fluid were identified as P. multocida by API 20NE, API 20E, and Vitek 1. In agreement with findings in the literature, this strain was susceptible to penicillin, cefotaxime, levofloxacin and tetracyclines.


Compressed sensing and parallel imaging accelerated T2 FSE sequence for head and neck MR imaging: Comparison of its utility in routine clinical practice.
To directly compare the capability of compressed sensing (CS) and parallel imaging (PI) accelerated T2 FSE (Fast Spin Echo) sequence with PI for head and neck MR imaging. Thirty consecutive patients with various head and neck diseases (15 men and 15 women, mean age 53 ± 22 years) underwent MR imaging by PI with CS and by PI. Reduction factors were as follows: PI with CS, 3 and PI, 1.5. Examination times for PI with CS and PI were all recorded. For quantitative image quality assessment, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. For qualitative assessment, two investigators assessed overall image quality, artifacts and diagnostic confidence level using a 5-point scoring system, and final scores were determined by consensus of two readers. Mean examination time and all indexes were compared by means of paired t-test and Wilcoxon signed-rank test. Inter-observer agreement for each qualitative index was assessed in terms of kappa statistics. Mean examination time for PI with CS (83.5 ± 11.0 s) was significantly shorter than that for PI (173.0 ± 54.4 s, p < 0.0001). SNR and CNR of PI with CS were significantly better than those with PI (mean SNR; 11.2 ± 3.6 vs 8.9 ± 2.6, median of CNR; 7.4 vs. 6.1, p < 0.0001). All inter-observer agreements were assessed as significant and substantial (0.62 < κ < 0.81). PI with CS accelerated T2 weighted sequence performs equally well or even slightly better than its PI accelerated, conventional counterpart at reduced scan times in the context of head and neck MR imaging.


Analysis of consumers' preferences and behavior with regard to horse meat using a structured survey questionnaire.
In this study, a structured survey questionnaire was used to determine consumers' preferences and behavior with regard to horse meat at a horse meat restaurant located in Jeju, Korea, from October 1 to December 24, 2005. The questionnaire employed in this study consisted of 20 questions designed to characterize six general attributes: horse meat sensory property, physical appearance, health condition, origin, price, and other attributes. Of the 1370 questionnaires distributed, 1126 completed questionnaires were retained based on the completeness of the answers, representing an 82.2% response rate. Two issues were investigated that might facilitate the search for ways to improve horse meat production and marketing programs in Korea. The first step was to determine certain important factors, called principal components, which enabled the researchers to understand the needs of horse meat consumers via principal component analysis. The second step was to define consumer segments with regard to their preferences for horse meat, which was accomplished via cluster analysis. The results of the current study showed that health condition, price, origin, and leanness were the most critical physical attributes affecting the preferences of horse meat consumers. Four segments of consumers, with different demands for horse meat attributes, were identified: origin-sensitive consumers, price-sensitive consumers, quality and safety-sensitive consumers, and non-specific consumers. Significant differences existed among segments of consumers in terms of age, nature of work, frequency of consumption, and general level of acceptability of horse meat.


Nutritional and physiological responses of broiler chickens to dietary supplementation with de-oiled soyabean lecithin at different metabolisable energy levels and various fat sources.
A 42-d study was conducted to investigate the effects of an emulsifier supplementation (de-oiled soyabean lecithin (DSL)) of diets with different levels of metabolisable energy (ME) and various sources of fat on growth performance, nutrient digestibility, blood profile and jejunal morphology of broiler chickens. Diets were arranged factorially (2 × 2 × 2) and consisted of two concentrations of ME (normal and low), two fat sources (soyabean oil (SO) and poultry fat (PF)) and two levels of DSL supplementation (0 and 1 g/kg). A total of 800 1-d-old male broiler chickens were assigned to eight treatments with five replicates/treatment. The results showed the supplemental DSL caused improvements in the overall feed conversion ratio, fat digestibility and jejunal villus height:crypt depth ratio, but the magnitude of the responses was greater in the PF-containing diets, resulting in significant fat × DSL interactions (P<0·05). Abdominal fat percentage was also reduced by the PF-containing diet, but the response was greater in the normal ME diet, resulting in a significant ME × fat interaction (P = 0·048). Dietary DSL supplementation also increased nitrogen-corrected apparent ME values but decreased blood TAG (P = 0·041) and LDL (P = 0·049) concentrations, regardless of the source of fat used or the ME values in the diet. In conclusion, the present study suggests that the improvements in growth performance, fat digestibility and intestinal morphology that can be achieved with DSL supplementation are highly dependent on the degree of saturation of lipid incorporated into broiler chicken diets.


Comparing 1.5 T and 3.0 T MR data for 3D visualization of neurovascular relationships in the posterior fossa.
Neurovascular relationships in the posterior fossa are more frequently investigated due to the increasing availability of 3.0 Tesla MRI. For an assessment with 3D visualization, no systematic analyzes are available so far and the question arises as to whether 3.0 Tesla MRI should be given preference over 1.5 Tesla MRI. In a prospective study, a series of 25 patients each underwent MRI investigations with 3D-CISS and 3D-TOF at 1.5 and 3.0 Tesla. For both field strengths separately, blood vessel information from the TOF data was fused into the CISS data after segmentation and registration. Four visualizations were created for each field strength, with and without optimization before and after fusion, which were evaluated with a rating system and verified with the intraoperative situation. When only CISS data was used, nerves and vessels were better visualized at 1.5 Tesla. After fusion, flow and pulsation artifacts were reduced in both cases, missing vessel sections were supplemented at 3.0 Tesla and 3D visualization at 1.5 and 3.0 Tesla led to anatomically comparable results. By subsequent manual correction, the remaining artifacts were further eliminated, with the 3D visualization being significantly better at 3.0 Tesla, since the higher field strength led to sharper contours of small vessel and nerve structures. 3D visualizations at 1.5 Tesla are sufficiently detailed for planning microvascular decompression and can be used without restriction. Fusion further improves the quality of 3D visualization at 3.0 Tesla and enables an even more accurate delineation of cranial nerves and vessels.


Effects of Phytochelatin-like Gene on the Resistance and Enrichment of Cd2+ in Tobacco.
Phytochelatins (PCs) are class III metallothioneins in plants. They are low molecular-weight polypeptides rich in cysteine residues which can bind to metal ions and affect the physiological metabolism in plants. Unlike other types of metallothioneins, PCs are not the product of gene coding but are synthesized by phytochelatin synthase (PCS) based on glutathione (GSH). The chemical formula of phytochelatin is a mixture of (γ-Glu-Cys)n-Gly (n = 2-11) and is influenced by many factors during synthesis. Phytochelatin-like (PCL) is a gene-encoded peptide (Met-(α-Glu-Cys)11-Gly) designed by our laboratory whose amino acid sequence mimics that of a natural phytochelatin. This study investigated how PCL expression in transgenic plants affects resistance to Cd and Cd accumulation. Under Cd2+ stress, transgenic plants were proven to perform significantly better than the wild-type (WT), regarding morphological traits and antioxidant abilities, but accumulated Cd to higher levels, notably in the roots. Fluorescence microscopy showed that PCL localized in the cytoplasm and nucleus.


Is multiple session of intralesional bleomycin mandatory for complete resolution of macrocystic lymphatic malformation?
Intralesional bleomycin scelro-therapy has become a favored line of treatment for macrocystic lymphatic malformations. However the need for multiple sessions is a drawback associated with this treatment modality. Our aim is to document whether multiple session of intra- lesional sclero-therapy is necessary for complete resolution of cystic lymphatic malformation. Intralesional bleomycin under Ultrasound guidance was used for macrocystic lymphangioma at concentration of 3mg/ml but not exceeding the total dose (1mg/kg) body weight for single session or cumulative dose of 5mg/kg. In all cases intralesional sclerosant (ILS) was installed under proper aseptic precaution in operation theatre in general anesthesia or sedation depending on the site or size of lesion and age of the patient. Age of patients at the time of enrolment in study ranged from 3 months to 18 years. Clinical examination was the main stay of diagnosis which was supplemented by USG and/or computed tomography. Compression of the lesion site was done for few hours wherever it was possible after the ILS session. A total of 21 patients included in our study. The age ranged from 3 months to 18 years. Male to female ratio was 8:13. The most common site of involvement was neck and axilla followed by anterior chest wall and nape of the neck. Complete resolution after single session was observed in 90.5% cases where as surgery was required in 9.5% case. Major complication was observed in one patient, who had intralesional bleeding which was managed conservatively. Transient pain and fever was observed in 23.8% of cases. Only two patient required surgical intervention where one had persistent subcutaneous fibrotic nodule and other one did not respond to ILS. Intralesional bleomycin is an effective treatment for macrocystic lesion, and complete resolution may be achieved by single session of ILS if proper principle are followed.


Blood pressure regulation by the angiotensin type 1 receptor in the proximal tubule.
The renin-angiotensin system (RAS) plays a critical role in the pathogenesis of hypertension. Homeostatic actions of the RAS, such as increasing blood pressure (BP) and vasoconstriction, are mediated via type 1 (AT1) receptors for angiotensin II. All components of the RAS are present in the renal proximal tubule, which reabsorbs the bulk of the glomerular filtrate, making this segment of the nephron a location of great interest for solute handling under RAS influence. This review highlights recent studies that illustrate the key role of renal proximal tubule AT1 receptors in BP regulation. A variety of investigative approaches have demonstrated that angiotensin II signaling via AT1a receptors, specifically in the renal proximal tubule, is a major regulator of BP and sodium homeostasis. Reduction of proximal tubule AT1a receptors led to lower BPs, whereas overexpression generally caused increased BPs. AT1a receptors in the proximal tubule are critical to the regulation of BP by the kidney and the RAS. The pattern of BP modulation is associated with alterations in sodium transporters. As a key site for sodium homeostasis, the renal proximal tubule could hence be a potential target in the treatment of hypertension.


Fast fingerprint database maintenance for indoor positioning based on UGV SLAM.
Indoor positioning technology has become more and more important in the last two decades. Utilizing Received Signal Strength Indicator (RSSI) fingerprints of Signals of OPportunity (SOP) is a promising alternative navigation solution. However, as the RSSIs vary during operation due to their physical nature and are easily affected by the environmental change, one challenge of the indoor fingerprinting method is maintaining the RSSI fingerprint database in a timely and effective manner. In this paper, a solution for rapidly updating the fingerprint database is presented, based on a self-developed Unmanned Ground Vehicles (UGV) platform NAVIS. Several SOP sensors were installed on NAVIS for collecting indoor fingerprint information, including a digital compass collecting magnetic field intensity, a light sensor collecting light intensity, and a smartphone which collects the access point number and RSSIs of the pre-installed WiFi network. The NAVIS platform generates a map of the indoor environment and collects the SOPs during processing of the mapping, and then the SOP fingerprint database is interpolated and updated in real time. Field tests were carried out to evaluate the effectiveness and efficiency of the proposed method. The results showed that the fingerprint databases can be quickly created and updated with a higher sampling frequency (5Hz) and denser reference points compared with traditional methods, and the indoor map can be generated without prior information. Moreover, environmental changes could also be detected quickly for fingerprint indoor positioning.


In vitro antibacterial activity of FA103, a new quinolone derivative of C-7 position with 7-perhydrodiazepinone.
A number of new quinolone antibacterial agents such as ofloxacin, norfloxacin, ciprofloxacin and sparfloxacin have been developed and introduced to the market. They possess a broad spectrum of activity against Gram-positive and Gram-negative bacteria. Ciprofloxacin has the highest activity against Gram-positive is higher than other quinolones. The activity of these quinolones against Gram-negative bacteria is generally higher than against Gram-positive bacteria. The substitution group of quinolones at C-7 position is responsible to show similar antibacterial activity with broad spectrum and similar pharmacokinetic properties, and variety of the substituents have been synthesized in many laboratories. Most of the substituents are piperazinyl of six-membered ring or pyrrolidinyl of five-membered ring, being modified with an alkyl group or another group. The development of potent quinolones against bacteria involved in pneumonia was seemed to be useful, and we investigated structure-activity relationships of new quinolones with a stronger activity against Gram-positive bacteria. A quinolone derivative with a seven-membered ring, perhydrodiazepinone, at the C-7 position was found to be a candidate for further evaluation. No previous attempts have been made to synthesize this type of derivatives. The compound FA103, 5-amino-1-cyclopropyl-6,8-difluoro-7-(2,3,4,5,6,7-hexahydro-1 H-1,4-diazepin-5-on-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, was synthesized and evaluated. Chemical structure of FA103 is shown in Fig. 1. This is a new difluoroquinolone with a broad antibacterial spectrum and improved activity against Gram-positive bacteria. In this paper, we compare the in vitro activity of FA103 with that of ofloxacin, norfloxacin, sparfloxacin against Gram-positive and Gram-negative bacteria.


AuNP-peptide probe for caspase-3 detection in living cells by SERS.
Colloidal nanoparticles can be used as surface-enhanced Raman scattering (SERS) substrates because the very close spacing between particles existing in these colloidal systems is beneficial for the generation of extremely strong and highly spatially localized electric field enhancements. Herein, a caspase-3-specified peptide was used as a molecular cross-linker to engineer gold nanoparticle (AuNP) junctions in a controllable manner. The peptide was designed with a sequence of CCALNNPFFDVED (Cys-Cys-Ala-Leu-Asn-Asn-Pro-Phe-Phe-Asp-Val-Glu-Asp) or CCALNNKYDDVED (Cys-Cys-Ala-Leu-Asn-Asn-Lys-Tyr-Asp-Asp-Val-Glu-Asp), where the CALNN (Cys-Ala-Leu-Asn-Asn) fragment helps to stabilize AuNP suspension in aqueous media and the sequence of DVED (Asp-Glu-Val-Asp) can be cleaved by caspase-3. In addition, the PFF (Pro-Phe-Phe) or KYD (Lys-Tyr-Asp) was exposed and interacted via the hydrophobic or alternate negative and positive electro-interaction in the presence of caspase-3, inducing the aggregation of colloidal Au-peptides accompanied with the enhancement of SERS. It can be observed that the SERS-enhanced signals were correlated with the caspase-3 concentrations and the limit of detection can reach 1.5 ng mL-1. Finally, this caspase-3-specified AuNP-peptide probe has been found to be a promising candidate for its application in the analysis of caspase-3 in living cells.


Lack of association of a 9 bp insertion/deletion polymorphism within the bradykinin 2 receptor gene with myocardial infarction.
The BK (bradykinin) B2 receptor is the major cellular mediator of the effects of BK. A 9 bp deletion in the promoter of the receptor gene represents an allelic variant that is associated with enhanced mRNA expression levels. We tested whether this polymorphism is associated with the prevalence of MI (myocardial infarction) or with echocardiographically determined left ventricular function in post-MI patients. Patients with documented MI (n=484), matched controls and controls without evidence of coronary heart disease (n=1363) constituted cases and controls. MI patients and controls were carefully matched for age, gender and cardiovascular risk factors. Genotype distributions of the 9 bp insertion/deletion polymorphism were similar across the groups: -9/-9, -9/+9 and +9/+9 were 22.1, 49.5 and 28.5% in MI patients, and 23.0, 44.6 and 32.5% in matched control subjects respectively. The lack of association was also observed in selected subgroups, stratified by age, gender and cardiovascular risk factors. Furthermore, there was no relation between this polymorphism and left ventricular systolic function in post-MI patients. These findings indicate that the 9 bp insertion/deletion polymorphism of the BK B2 receptor gene is neither related to the prevalence of MI nor to left ventricular function after MI.