Effects of Resveratrol on Receptor for Advanced Glycation End Products (RAGE) Expression and Oxidative Stress in the Liver of Rats with Type 2 Diabetes.
Incidence of diabetes mellitus is dramatically growing in the world. Oxidative stress, advanced glycation end products (AGEs) and receptor for AGE (RAGE) play key role in the pathogenesis of diabetes. Little is known about resveratrol effects on the liver. We hypothesize that resveratrol may exert a hepatoprotective effect in diabetic rats. Male rats with diabetes were treated with or without resveratrol at 1, 5 and 10 mg/kg body weight for 30 days. Total AGEs and malondialdehyde (MDA) levels in liver tissues were determined by spectrofluorimetric methods. Total antioxidant capacity and total oxidant contents in the liver and glucose in plasma were measured by a colorimetric assay. Expression of RAGE was assayed in liver of all animals using quantitative polymerase chain reaction. In liver tissue extract of resveratrol-treated rats with diabetes, MDA levels, total oxidant, plasma glucose and expression of RAGE were significantly reduced compared to the untreated group. Moreover, total antioxidant levels were significantly increased in treated rats. There was no significant difference in AGE contents among all groups. These results revealed that resveratrol had beneficial effects on the liver by extenuating oxidative stress and down regulation of RAGE expression.


Improving Angular Accuracy of a Scanning Mirror Based on Error Modeling and Correction.
Scanning mirrors appear to be key components in optoelectronic systems for line-of-sight (LOS) stabilization. For improving the angular accuracy of a scanning mirror based on the eddy current displacement sensor measurement, an angular error-correction method is proposed and demonstrated. A mathematic angular error model with physical parameters was developed, and the cross-validation method was employed to determine the reasonable order of the Maclaurin series used in the error model, which increased the exactitude and robustness of the correction method. The error parameters were identified by accurately fitting the calibrated angular errors with the error model, which showed excellent error prediction performance. Based on the angular calculation model corrected by the error model, the closed-loop control system was established to obtain accurate deflection angles. Experimental results show that within the deflection angle of ±1.5 deg, the angular accuracy was improved from 0.28 deg to less than 1.1 arcsec, and the standard deviation for six measurements was less than 1.2 arcsec, which indicates that the angle correction method was effective in improving the linearity of the eddy current sensors and reducing the influence of manufacturing and installation errors.


Analysis of the methylation pattern of c-Ha-ras oncogene in human prostatic cancer.
To determine the methylation pattern of c-Ha-ras oncogene in prostatic tissue and to identify possible changes of methylation associated with cancer, high molecular weight DNA was extracted from 7 normal and 6 carcinomatous human prostates. Analysis of the samples was performed by cleaving DNA with the restriction endonucleases Msp I, Hpa II and Cfo I, and by Southern hybridizing the DNA digests with the 32P-labelled c-Ha-ras (pT24-C3) probe. Several discrete fragments were obtained with Hpa II and Cfo I digestion while the Msp I pattern showed fewer and smaller bands. Therefore, c-Ha-ras appears to be partially methylated. While a considerable polymorphism of the sequence 5'-CCGG-3' was observed at several Msp I sites in all cases, no significant differences could be evidenced in the methylation patterns of normal and neoplastic prostatic DNA samples extracted and purified from each patient.


Megalin dependent urinary cystatin C excretion in ischemic kidney injury in rats.
Cystatin C, a marker of kidney injury, is freely filtered in the glomeruli and reabsorbed by the proximal tubules. Megalin and cubilin are endocytic receptors essential for reabsorption of most filtered proteins. This study examines the role of these receptors for the uptake and excretion of cystatin C and explores the effect of renal ischemia/reperfusion injury on renal cystatin C uptake and excretion in a rat model. Binding of cystatin C to megalin and cubilin was analyzed by surface plasmon resonance analysis. ELISA and/or immunoblotting and immunohistochemistry were used to study the urinary excretion and tubular uptake of endogenous cystatin C in mice. Furthermore, renal uptake and urinary excretion of cystatin C was investigated in rats exposed to ischemia/reperfusion injury. A high affinity binding of cystatin C to megalin and cubilin was identified. Megalin deficient mice revealed an increased urinary excretion of cystatin C associated with defective uptake by endocytosis. In rats exposed to ischemia/reperfusion injury urinary cystatin C excretion was increased and associated with a focal decrease in proximal tubule endocytosis with no apparent change in megalin expression. Megalin is essential for the normal tubular recovery of endogenous cystatin C. The increase in urinary cystatin C excretion after ischemia/reperfusion injury is associated with decreased tubular uptake but not with reduced megalin expression.


Participation levels of physical activity programs for community-dwelling older adults: a systematic review.
Although many physical activity (PA) programs have been implemented and tested for effectiveness, high participation levels are needed in order to achieve public health impact. This study aimed to determine participation levels of PA programs aimed to improve PA among community-dwelling older adults. We searched five databases up until March 2013 (PubMed, PubMed publisher, Cochrane Library, EMBASE, and Web of Science) to identify English-written studies investigating the effect of PA programs on at least one component of PA (e.g. frequency, duration) among community-dwelling populations (i.e. not in a primary care setting and/or assisted living or nursing home) of persons aged 55 years and older. Proportions of participants starting and completing the PA programs (initial and sustained participation, respectively) were determined. The search strategy yielded 11,994 records of which 16 studies were included reporting on 17 PA programs. The number of participants enrolled in the PA programs ranged between 24 and 582 persons. For 12 PA programs it was not possible to calculate initial participation because the number of older adults invited to participate was unknown due to convenience sampling. Of the five remaining programs, mean initial participation level was 9.2% (±5.7%). Mean sustained participation level of all 17 programs was 79.8% (±13.2%). Understanding how to optimize initial participation of older adults in PA programs deserves more attention in order to improve the population impact of PA programs for community-dwelling older adults.


Mind wandering in reading: An embodied approach.
In the last 20 years, the study of mind wandering has attracted the attention of a growing number of researchers from fields like psychology, philosophy, and neuroscience. Mind wandering has been characterized in multiple ways: as task-unrelated, unintentional, stimulus-independent, or unguided thought processes. Those accounts have mostly focused on the identification of neurocognitive mechanisms that enable the emergence of mind-wandering episodes. Reading is one activity in which mind wandering frequently occurs, and it is widely accepted that mind wandering is detrimental for reading flow, comprehension and the capacity to make inferences based on the text. This mind wandering scepsis in reading is based on two unchallenged views: (i) that reading is a disembodied, mental activity of information processing, and (ii) that mind wandering is essentially characterized as a task-unrelated and involuntary thought process that disrupts all kinds of goal-oriented behavior. However, recent developments within cognitive science treat the mind as embodied and thus challenge both ontological and epistemological assumptions about what mind wandering is, where it is located, and how it is being studied empirically during reading. In this article we integrate embodied accounts of mind wandering and reading to show how reading benefits from nested mind wandering processes. Empirically, we investigate how a reader can move successfully in and out of different embodied processes and mesh different cognitive strategies over time, including some forms of mind wandering. While such changes in reading are frequently deemed dysfunctional, we suggest an alternative interpretation: Rather than seeking constant flow and fluency, we propose that reading is multi-actional and benefits from drawing on different cognitive strategies spanning mind wandering processes and goal-oriented behavior. In that sense, we suggest that mind wandering has a potential for enriching cognitive processes underlying reading, such as imagining and reflection. We exemplify these insights through analyses of data obtained in ethnographic and semi-experimental studies of reading practices. We conclude that to capture cognitive phenomena within an embodied framework, a richer methodology must be developed. Such a methodology must not only be capable of accounting for brains, bodies, and contexts in isolation, but must consider an overall brain-body-environment system.


How do different components of Effortful Control contribute to children's mathematics achievement?
This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children's mathematics achievement. The sample was composed of 142 children aged 9-12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent's report); math achievement was measured via teacher's report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only AF significantly contributed to the variance of children's mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children's self-regulation abilities in the context of school.


The Crossroad of Ion Channels and Calmodulin in Disease.
Calmodulin (CaM) is the principal Ca2+ sensor in eukaryotic cells, orchestrating the activity of hundreds of proteins. Disease causing mutations at any of the three genes that encode identical CaM proteins lead to major cardiac dysfunction, revealing the importance in the regulation of excitability. In turn, some mutations at the CaM binding site of ion channels cause similar diseases. Here we provide a summary of the two sides of the partnership between CaM and ion channels, describing the diversity of consequences of mutations at the complementary CaM binding domains.


Insights into the Mechanistic Perspective Effect of Insulin on the Nonamyloidogenic Component (NAC) and α-Synuclein Aggregation.
Insulin plays important functions in the brain, such as neuroprotective effects on neurons, and it is also involved in cognitive functions (e.g., attention, learning and memory). It is proposed that a lack of insulin in the brain may initiate development of neurodegenerative diseases. Herein, we examined the effect of insulin on aggregates of α-synuclein (AS), a protein that is related to Parkinson's disease (PD), and its segment nonamyloidogenic component (NAC), which is known to play a crucial role in AS aggregation. The molecular modeling tools assist us to provide insights into the molecular mechanism of the effect of insulin on fibrillation of NAC and AS. Our research leads to three conclusions. First, the preferred interactions between insulin chain B and the "zipper domain" sequence within both NAC and AS appear at the central domain across the fibril axis or at the edge of the fibril. Second, these interactions do not disrupt the cross-β structure of NAC fibril-like oligomers but disrupt the cross-β structure of AS fibril-like oligomers. Thus, insulin does not inhibit the fibrillation of NAC but may inhibit AS fibrillation. Third, some of the polymorphic NAC and AS fibril-like oligomers bind to chain A in insulin. This is the first study that demonstrates that insulin chain A can also participate in the interactions with amyloid fibril-like oligomers. Our study proposes that insulin plays a crucial role in impeding AS aggregation in the brain and consequently could inhibit the development of PD.


The sensitization phase of T-cell-mediated immunity.
Many cell-mediated immune responses appear to develop in two phases: A sensitization phase in which unprimed or memory T cells interact with dendritic cells to become active lymphoblasts, and an effector phase in which the T lymphoblasts and other presenting cells interact to eliminate the antigen. Antigen presentation is essential to both phases. Here we review several features that are pertinent to the special sensitization role of dendritic cells. First, dendritic cells from lymphoid tissues, blood, and lymph (lymphoid dendritic cells) express very high levels of class I and II MHC products, and these levels cannot be increased by exposure to cytokines such as immune interferon. Second, dendritic cells efficiently cluster antigen-specific T cells during primary responses. Other presenting cells, like macrophages and B lymphocytes, do not form clusters but do bind to sensitized T lymphoblasts. Dendritic-T-cell binding is not inhibited by mAb to CD4 and LFA-1 antigens. It is suggested that a dendritic-cell-specific molecule is required. Third, it is not yet clear if dendritic cells make a "lymphocyte activating factor." However, IL-1 is not produced, even when dendritic cells are in contact with responding T cells. Fourth, dendritic cells have the capacity to migrate from the tissues and move to T-dependent areas. Epidermal Langerhans cells represent a reservoir of tissue dendritic cells but seem to be immunologically immature. The viability and accessory function of the Langerhans cell greatly depend on a single cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF), leading to the proposal that GM-CSF is critical in mobilizing active dendritic cells at the onset of a cell-mediated immune response.


Spiking Kinematics in Volleyball Players With Shoulder Pain.
Spiking is one of the most frequently used scoring techniques in volleyball games, and around 80% of shoulder pain in volleyball players is linked with the spiking movement. To investigate the differences in glenohumeral joint, scapular, and trunk movements during the spiking motion between volleyball players with and those without shoulder pain. Cross-sectional study. University laboratory. Twenty amateur volleyball players with shoulder pain (age = 21.8 ± 1.79 years, with an average of 4.0 ± 0.92 years of volleyball experience and 6.0 ± 3.51 months of shoulder pain) and 20 sex-, age-, and experience-matched control participants. The 3-dimensional kinematics of the shoulder joint, scapula, and trunk during spiking were assessed using an electromagnetic tracking system. Compared with the control group, individuals with shoulder pain demonstrated less scapular posterior tilt ( P = .041) and more glenohumeral horizontal abduction ( P = .008) and scapular internal rotation ( P = .02) at ball contact when performing the cross-body spike. The decrease in scapular posterior tilt, along with increased glenohumeral horizontal abduction and scapular internal rotation, was associated with shoulder pain in university volleyball players. These changes should be addressed in the training and treatment of young volleyball players.


Effect of various hepatectomy procedures on circulating tumor cells in postoperative patients: a case-matched comparative study.
The objective of this study is to elucidate the prevalence of systemic circulating tumor cells (CTCs) prior to and following resection of hepatocellular carcinoma (HCC), and to compare the disparities in postoperative CTCs in terms of quantity and classifications between the open liver resection (OPEN) and laparoscopic liver resection (LAP) cohorts. From September 2015 to May 2022, 32 consecutive HCC patients who underwent laparoscopic liver resection at Southwest Hospital were retrospectively enrolled in this study. The clinicopathological data were retrieved from a prospectively collected computer database. Patients in the OPEN group matched at a 1:1 ratio with patients who underwent open liver resection during the study period on age, gender, tumor size, number of tumors, tumor location, hepatitis B surface antigen (HBsAg) positivity, alpha-fetoprotein (AFP) level, TNM and Child-Pugh staging from the database of patients to form the control group. The Can-Patrol CTC enrichment technique was used to enrich and classify CTCS based on epithelial-mesenchymal transformation phenotypes. The endpoint was disease-free survival (DFS), and the Kaplan-Meier method and multiple Cox proportional risk model were used to analyze the influence of clinicopathological factors such as total CTCs and CTC phenotype on prognosis. The mean age of the 64 patients with primary liver cancer was 52.92 years (23-71), and 89.1% were male. The postoperative CTC clearance rate was more significant in the OPEN group. The total residual CTC and phenotypic CTC of the LAP group were significantly higher than those of the OPEN group (p = 0.017, 0.012, 0.049, and 0.030, respectively), which may increase the possibility of metastasis (p = 0.042). In Kaplan-Meier analysis, DFS was associated with several clinicopathological risk factors, including Barcelona Clinical Liver Cancer (BCLC) stage, tumor size, and vascular invasion. Of these analyses, BCLC Stage [p = 0.043, HR (95% CI) =2.03(1.022-4.034)], AFP [p = 0.007, HR (95% CI) =1.947 (1.238-3.062)], the number of positive CTCs [p = 0.004, HR (95% CI) =9.607 (2.085-44.269)] and vascular invasion [p = 0.046, HR (95% CI) =0.475 (0.22-1.023)] were significantly associated with DFS. In comparison to conventional OPEN technology, LAP technology has the capacity to augment the quantity of epithelial, mixed, and mesenchymal circulating tumor cells (CTCs). Following the surgical procedure, there was a notable increase in the total CTCs, epithelial CTCs, and mixed CTCs within the LAP group, indicating a potential drawback of LAP in facilitating the release of CTCs.


A putative transcription factor LFC1 negatively regulates development and yield of winter mushroom.
Basidioma is the fruiting body of mushroom species. The deep understanding on the mechanism of basidioma development is valuable for mushroom breeding and cultivation. From winter mushroom (Flammulina velutipes), one of the top five industrially cultivated mushrooms, a novel putative Zn(II)2Cys6 transcription factor LFC1 with negative regulatory function in basidioma development was identified. The transcript level of lfc1 was dramatically decreased during basidioma development. Neither overexpression nor knockdown of lfc1 affected hyphal vegetative growth. However, knockdown of lfc1 could promote basidioma development and shorten cultivation time by 2 days, while overexpression of lfc1 delayed the optimal harvest time by 3 days. In the lfc1 knockdown strain, in which the lfc1 expression was reduced by 72%, mushroom yield and biological efficiency could be increased at least by 24%. Knockdown of lfc1 did not affect the shape of caps but significantly increased basidioma length and number, while its overexpression did not affect basidioma length but dramatically reduced basidioma number. In addition, rather than producing basidiomata with round caps as in wild type, the caps of basidiomata in the lfc1 overexpression mutants were significantly larger and the cap edge was wrinkled. RNA-seq analysis revealed that 455 genes had opposite transcriptional responses to lfc1 overexpression and knockdown. Some of them were previously reported as genes involved in basidioma development, including 3 hydrophobin encoding genes, 2 lectin encoding genes, FVFD16, an Eln2 ortholog encoding gene, and 3 genes encoding membrane components. As LFC1 homologs are widely present in mushroom species, lfc1 can be useful in mushroom breeding.Key Points• A novel transcription factor LFC1 negatively regulates fruiting in winter mushroom• LFC1 regulated transcription of more than 400 genes.• Reduction of LFC1 expression could shorten cultivation time and increase yield.• lfc1 could be a potentially useful reference gene for mushroom breeding.


Double-dose hepatitis B vaccination in cirrhotic patients on a liver transplant waiting list.
Development of immunity to hepatitis B virus in cirrhotic patients waiting for liver transplantation is highly desirable. Though a double-dose regimen is available, little is know about its effectiveness. We examined the efficacy of double-dose hepatitis B virus vaccination in cirrhotic patients waiting for liver transplantation. We studied 43 patients who were waiting for liver transplantation. They were vaccinated with three doses of 40 mg hepatitis B vaccine at 0, 1 and 6 months; the normal dose is 20 microg. Efficacy was measured based on seroconversion of anti-HBs. Global response to the primary vaccination scheme was 67.5% (29 patients). Forty-one per cent of responders had anti-HBs titers above 1,000 IU/mL. No factors were associated with response, based on multivariate analysis. The vaccination scheme of 40 microg at 0, 1 and 6 months was superior to conventional vaccination doses (20 microg) for cirrhotic patients on a waiting list for liver transplantation.


On the Charge-Transfer Excitations in Azobenzene Maleimide Compounds: A Theoretical Study.
Photoswitchable systems with charge-transfer (CT) transitions have gained much attention during the recent years because of their many emerging applications. CT transitions themselves are of fundamental importance from physical, chemical, engineering, and molecular modeling points of view because they depend on the modified intramolecular electronic structure. CT transitions in azobenzene (AB) were observed when substituted with the maleimide (MI) functional group. This work represents a systematic theoretical study of excited states of the AB-MI structures of eight azo derivatives. In addition to the two main azo transitions (π → π* and n → π*), our calculations show a CT occurring between the azo moiety as a donor and the MI group as an acceptor. The CT mechanism can be characterized based on both the number and the position of the MI fragments. MI groups in the azo structure result in low-energy transitions, changing the order of the main transitions by introducing a CT character. Calculations using both density functional theory (DFT) and high-end molecular orbital theories confirm the CT character of these derivatives, although the order of excited states was found to differ depending on the chosen level of theory. We present here the first theoretical investigation of the electronic excited states (nπ*CT and ππ*CT) and corresponding transitions for this class of compounds. The computational results showed that the CT mechanism in AB-MI derivatives can occur via two pathways: planar and twisted. Our findings are expected to be of substantial interest, especially in the area of molecular optoelectronics and in the design of responsive materials.


Fertility-sparing management of low-grade endometrial stromal sarcoma: analysis of an institutional series and review of the literature.
Low-grade endometrial stromal sarcoma (LG-ESS) is a rare malignancy, often occurring before menopause. There is no consensus regarding its optimal management. Total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women wishing to maintain their reproductive potential. However, experience of fertility-sparing management in LG-ESS is very limited. In this paper, the disease outcome is presented in six young women with LG-ESS conservatively treated by combined hysteroscopic resection and hormonal therapy. From October 2009 to February 2013, at the Gynecologic Oncology Department of the National Cancer Institute of Naples, six women, with early-stage LG-ESS aged 18-40 years who desired childbearing and/or retaining their fertility, were enrolled into a pilot study of fertility-sparing management. Diagnosis of LG-ESS was made on specimens from hysteroscopic resection performed on a presumed benign lesion. All patients were planned to be treated with adjuvant megestrol acetate for two years. Hormonal therapy was started within 6 weeks from the hysteroscopic resection, with orally megestrol acetate at 40mg daily, increasing gradually according to patient's tolerance to the recommended total dose of 160mg daily. All patients were submitted to hysteroscopic resection in a one-step procedure. Five patients started megestrol acetate within 6 weeks from the hysteroscopic resection (one patient did not start hormonal therapy because of early pregnancy after the hysteroscopic resection). Hormonal therapy was well tolerated; one patient stopped megestrol acetate after 12 months because of self-supporting strong desire to conceive; the other four patients regularly completed the hormonal therapy. To date, all patients show no evidence of disease. Although fertility-sparing management is not the current standard of care for young women with early-stage LG-ESS, our preliminary data are promising. Larger series with a longer follow-up are needed to further assess safety and efficacy of combined hysteroscopic resection and hormonal therapy.


Transient Signals and Inattentional Blindness in a Multi-object Tracking Task.
Inattentional blindness is a failure to notice an unexpected event when attention is directed elsewhere. The current study examined participants' awareness of an unexpected object that maintained luminance contrast, switched the luminance once, or repetitively flashed. One hundred twenty participants performed a dynamic tracking task on a computer monitor for which they were instructed to count the number of movement deflections of an attended set of objects while ignoring other objects. On the critical trial, an unexpected cross that did not change its luminance (control condition), switched its luminance once (switch condition), or repetitively flashed (flash condition) traveled across the stimulus display. Participants noticed the unexpected cross more frequently when the luminance feature matched their attention set than when it did not match. Unexpectedly, however, a proportion of the participants who noticed the cross in the switch and flash conditions were statistically comparable. The results suggest that an unexpected object with even a single luminance change can break inattentional blindness in a multi-object tracking task.


Recent Advances on Cellulose-Based Nano-Drug Delivery Systems: Design of Prodrugs and Nanoparticles.
Cellulose being the first abundant biopolymers in nature has many fascinating properties, including low-cost, good biodegradability, and excellent biocompatibility, which made cellulose a real potential material to create nano-drug delivery systems (nano-DDS). This review aims to present and discuss some remarkable recent advances on the drug delivery applications of cellulosebased prodrugs and nanoparticles. By searching the research literatures over last decade, a variety featured studies on cellulosebased nano-DDS were summarized and divided into prodrugs, prodrug nanoparticles, solid or derivative nanopartilces, amphiphilic copolymer nanoparticles, and polyelectrolyte complex nanoparticles. Various methods employed for the functionalization, pharmacodynamic actions and applications were described and discussed. Many types of cellulose-based nano-DDS can ensure efficient encapsulation of various drugs and then overcome the free drug molecule shortcomings. Among all the method described, cellulosebased amphiphilic nanoparticles are most frequently used. These formulations have the higher drug loading capability, a simple and flexible way to achieve multi-functional. Apart from hydrophilic or hydrophobic modification, cellulose or its derivatives can form nanoparticles with different small molecules and macromolecules, leading to a large spectrum of cellulose-based nano-DDS and providing some unexpected advantages. Thorough physicochemical characterization and profound understanding of interactions of the cellulose-based nano-DDS with cells and tissues is indispensable. Moreover, studies toward technics parameter optimization and scale up from the laboratory to production level should be undertaken. The development of intravenous and orally applicable cellulose-based nano-DDS will be an important research area, and these systems will have more commercial status in the market.


A rubidium Mx-magnetometer for measurements on solid state spins.
The detection of environmental magnetic fields is well established by optically pumped atomic magnetometers. Another focus of magnetometry can be the research on magnetic or spin-active solid-state samples. Here we introduce a simple and compact design of a rubidium-based Mx magnetometer, which allows for hosting solid-state samples. The optical, mechanical, and electrical design is reported, as well as simple measurements which introduce the ground-state spin-relaxation time, the signal-to-noise ratio of a measurement, and subsequently the overall sensitivity of the magnetometer. The magnetometer is optimized for the most sensitive operation with respect to laser power and magnetic field excitation at the Larmor frequency.


How case law impacts risk management.
Published decisions by federal and state appellate courts impact health care risk management in a number of ways, including overruling precedents, explaining and clarifying new laws and regulations, describing new and novel rules, describing new performance standards, and describing new civil rights.


Preparing nurses for the new world order: a faculty development focus.
The new world order demands nursing faculty members be as competent in teaching and coaching students as they are about the art and science of nursing. The complexity associated with classroom management requires mastery of innovative learning modalities to assist students to think critically using research-based evidence in making patient care decisions. Grand Canyon University has made faculty competence a priority to ensure quality student outcomes. The College of Nursing has embraced a systematic process for creating faculty excellence through a comprehensive faculty development initiative. Developing faculty requires university support through policy and resources that is essential to prepare nurses for the new world order and therefore closing the education practice gap.


Herbimycin A accelerates the induction of apoptosis following etoposide treatment or gamma-irradiation of bcr/abl-positive leukaemia cells.
Philadelphia chromosome (Ph)-positive leukaemia cells express the chimeric bcr/abl oncoprotein, whose deregulated protein tyrosine kinase (PTK) activity antagonizes the induction of apoptosis by DNA damaging agents. Treatment of Ph-positive K562, TOM 1 and KCL-22 cells with etoposide for 2d induced cytosolic vacuolation, but not nuclear condensation or DNA fragmentation. The bcr/abl kinase-selective inhibitor herbimycin A increased the induction of nuclear apoptosis by etoposide or gamma-radiation. The concentration of herbimycin required to synergize with etoposide was similar to that required to decrease the level of tyrosine phosphorylated proteins or of the protein tyrosine kinase activity of anti-abl immune complexes in K562 cells. The ability of herbimycin A to sensitize K562, TOM 1 or KCL-22 cells to apoptosis induction correlated with its ability to decrease the cellular content of phosphotyrosyl proteins in these Philadelphia-positive lines. Enhancement of nuclear apoptosis by herbimycin was not attributable to downregulation of the bcl-2 or bcl-XL anti-apoptotic proteins. In contrast, herbimycin protected Philadelphia-negative HL60 cells from apoptosis induction by etoposide and did not affect killing of NC37 and CEM cells. The data suggest that the induction of apoptosis is blocked in cells expressing the bcr/abl oncoprotein and that herbimycin A increases induction of programmed cell death following DNA damage. Selective PTK inhibitors may therefore be of value in securing the genetic death of Ph-positive leukaemia cells.


Modeling and Comparative Analysis of Atmospheric Pressure Anodic Carbon Arc Discharge in Argon and Helium-Producing Carbon Nanostructures.
In this work, within the framework of a unified model for the discharge gap and electrodes, a comparative numerical analysis was carried out on the effect of evaporation of graphite anode material on the characteristics of the arc discharge in helium and argon. The effect of changing the plasma-forming ion, in which the ion of evaporated atomic carbon becomes the dominant ion, is demonstrated. For an arc discharge in helium, this effect is accompanied by a jump-like change in the dependence of the current density on voltage (CVC), and smoothly for a discharge in argon. With regard to the dynamics of the ignition of an arc discharge, it is shown that during the transition from glow discharge to arc in helium, the discharge parameters are also accompanied by an abrupt change, while in argon, this transition is smooth. This is due to the fact that the ionization potentials, as well as the ionization cross sections, differ significantly for helium and carbon, and are close in value for helium and argon. For various points on the CVC, the density distributions of the charged and neutral particles of an inert gas and evaporated gases are presented.


An Assessment of Genetic Diversity and Drought Tolerance in Argan Tree (Argania spinosa) Populations: Potential for the Development of Improved Drought Tolerance.
The argan tree (Argania spinosa) occurs in a restricted area of Southwestern Morocco characterized by low water availability and high evapotranspirative demand. Despite the adaptation of the argan tree to drought stress, the extent of the argan forest has declined markedly due to increased aridity, land use changes and the expansion of olive cultivation. The oil of the argan seed is used for cooking and as the basis for numerous cosmetics. The identification of argan tree varieties with enhanced drought tolerance may minimize the economic losses associated with the decline of the argan forest and constrain the spread of desertification. In this study we collected argan ecotypes from four contrasting habitats and grew them under identical controlled environment conditions to investigate their response to drought. Leaf gas exchange analysis indicated that the argan ecotypes showed a high degree of adaptation to drought stress, maintaining photosynthetic activity at low levels of foliar water content and co-ordinating photosynthesis, stomatal behavior and metabolism. The stomata of the argan trees were highly sensitive to increased leaf to air vapor pressure deficit, representing an adaptation to growth in an arid environment where potential evapotranspiration is high. However, despite originating in contrasting environments, the four argan ecotypes exhibited similar gas exchange characteristics under both fully irrigated and water deficit conditions. Population genetic analyses using microsatellite markers indicated a high degree of relatedness between the four ecotypes; indicative of both artificial selection and the transport of ecotypes between different provinces throughout centuries of management of the argan forest. The majority of genetic variation across the four populations (71%) was observed between individuals, suggesting that improvement of argan is possible. Phenotypic screening of physiological responses to drought may prove effective in identifying individuals and then developing varieties with enhanced drought tolerance to enable the maintenance of argan production as climate change results in more frequent and severe drought events in Northern Africa.


Identification of crystallin modifications in the human lens cortex and nucleus using laser capture microdissection and CyDye labeling.
With aging, lens crystallins undergo post-translational modifications (PTMs) and these modifications are believed to play a major role in age-related cataract development. The purpose of the present study was to determine the protein profiles of crystallins and their PTMs in the cortical and nuclear regions within an aging human lens to gain a better understanding about changes in crystallins as fiber cells migrate from cortical to nuclear region. Laser capture microdissection (LCM) was used to select and capture cells from cortical and nuclear regions of 12 mum, optimum cutting temperature (OCT) compound-embedded frozen lens sections from a 69-year-old human lens. Proteins were extracted and then analyzed by 2-D difference gel electrophoresis (2-D DIGE) with sulfonated indocyanine dye (CyDye) labeling. Crystallin identities and their PTMs were then determined by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) and Electrospray Ionization Quadripole Linear Ion-Trap Liquid Chromatography (ESI-QTRAP LC-MS/MS) mass spectrometry. Crystallin fragments (M(r) <20 kDa) were present in both cortical and nuclear regions, while high molecular weight (HMW) aggregates (M(r) > 35 kDa) were mostly localized in the nuclear region. HMW complexes contained a relatively large number of truncated and modified beta-crystallins, compared to alpha- and gamma-crystallins, and two lens-specific intermediate filaments, CP49 (phakinin) and filensin. Modified alpha-crystallins were in low abundance in the nuclear region compared to the cortical region. Several PTMs, including deamidation, oxidation, phosphorylation, ethylation, methylation, acetylation, and carbamylation, were identified in virtually all crystallins and CP49. The data provide the first report of human lens crystallin profiling by a combination of LCM, 2D-DIGE, and mass spectrometric analysis. The results suggested that as the fiber cells migrate from cortical region to the nuclear region, the crystallin degradation begins in the cortical region and continues in the nuclear region. However, a greater number of the HMW complexes exist mainly in the nuclear region.


Mastocytosis: from a Molecular Point of View.
Mast cells (MCs) are physiologically activated by binding of stem cell factor (SCF) to the extracellular domains of the Kit receptor. This binding increases the proliferation and prolongs the survival of normal mature MCs, as well as intensifies the release of mediators. In mastocytosis, somatic mutations of the coding Kit gene cause autocrine dysregulation and lead to constitutive KIT activation even in the absence of its ligand SCF. Clinical symptoms are caused by MC-mediator release and/or infiltration of MCs into tissues. Aberrant KIT activation may result in increased production of MCs in the skin and extracutaneous organs. Depending on the affected organ(s), the disease can be divided into cutaneous mastocytosis (CM), systemic mastocytosis (SM), and localized MC tumors. The updated classification of WHO discriminates between several distinct subvariants of CM and SM. While the prognosis in CM and indolent SM (ISM) is excellent with (almost) normal life expectancy, the prognosis in aggressive SM (ASM) and MC leukemia (MCL) is dismal. The symptoms may comprise urticaria, angioedema, flush, pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal pain and are the results of MC infiltration and mediator release into target organs, i.e., the skin, gastrointestinal tract, liver, spleen, lymph nodes, and bone marrow. Mastocytosis differs from a lot of other hematological disorders because its pathology is not only based on the lack of normal function of a specific pathway or of a specific cell type but additionally is a proliferative disease. Currently available treatments of mastocytosis include symptomatic, antimediator and cytoreductive targeted therapies.


Negative Correlation between miR-200c and Decorin Plays an Important Role in the Pathogenesis of Colorectal Carcinoma.
Aim. To demonstrate the regulatory role of miRNA in colorectal carcinoma (CRC) and reveal the transcript markers that may be associated with CRC clinical outcomes. Method. Herein, we analyzed both mRNA and miRNA gene expression profiles of 255 CRC tumor samples from The Cancer Genome Atlas project to reveal the regulatory association between miRNA and mRNA. Also, the potential role of gene coexpression network in CRC has been explored. Results. The negative correlation between miR-200c and DCN (Decorin) was calculated in CRC, indicating that DCN could be a potential target of miR-200c. Clinical features indicated that colon polyp history and overall survival were significantly related to the expression level of miR-200c. Three coexpression networks have been constructed, and genes involved in the networks are related to cell cycle, NOTCH, and mTOR signaling pathways. Conclusion. Our result provides a new insight into cancer related mRNA coexpression network in CRC research.


Slingshot feeding of the goblin shark Mitsukurina owstoni (Pisces: Lamniformes: Mitsukurinidae).
Five striking and prey capture events of two goblin sharks were videotaped at sea for the first time, showing their extraordinary biting process. The goblin sharks swung their lower jaw downward and backward to attain a huge gape and then rapidly protruded the jaws forward a considerable distance. The jaws were projected at a maximum velocity of 3.1 m/s to 8.6-9.4% of the total length of the shark, which is by far the fastest and greatest jaw protrusion among sharks. While the jaws were being retracted, the mouth opened and closed again, which was considered a novel feeding event for sharks. Phylogenetic evidence suggested that their feeding behavior has evolved as an adaptation to food-poor deep-sea environments, possibly as a trade-off for the loss of strong swimming ability.


Nurse managers' use of a computer decision support system. Differences in nursing labor costs per patient day.
To control nursing labor cost, nurse managers (NMs) need access to productivity indicators and financial performance information on a daily basis. Labor cost and hour reports after the fact are no longer acceptable for making crucial management/labor decisions. The purpose of this study was to determine if there was a mean difference in nursing labor cost per patient day (PPD) when a nurse manager used a labor computer decision support system (CDSS) compared to an NM who did not use this system. This descriptive study was implemented on a study and comparison unit in both a psychiatric and a medical hospital. The CDSS provided the NMs with daily labor cost information on which to base labor decisions. Study findings indicate that with the use of the labor CDSS, nurse managers achieved better cost performance per patient day compared to the nurse managers who did not use the labor CDSS.


Determinants of Childhood Asthma: A Case Control Study from a Tertiary Care Hospital in Bengaluru, South India.
Childhood asthma is a common, and often serious, chronic disease with episodic exacerbations in infants and children. There is an increasing trend in the prevalence of childhood asthma in developing countries. Objectives: To identify the determinants of childhood asthma. A case control study with 30 cases of childhood asthma and 30 gender- and aged-matched controls selected from the paediatric outpatient department and paediatric ward of a tertiary hospital. The primary caregiver was interviewed to capture sociodemographic details, prenatal and birth history, and history of exposure to environmental risk factors. Odds ratios with 95% confidence intervals were calculated to determine the strength of association between childhood asthma and independent co-variates, followed by subgroup multiple logistic regression analysis. We found that children with a parental history of allergy/atopy [OR=2.88 (1.94-4.27), P<0.001], residence in houses located in industrial areas [AOR=2.72 (2.6-323.1), P<0.001], exposure to incense at home [AOR=2.03 (1.14-29.42), P<0.001], or a history of allergic rhinitis [AOR=3.09 (2.22-243.25), P<0.001] had significantly higher odds of developing childhood asthma. Our study found that having homes located in industrial areas, burning incense at home, parental history of allergy, and history of allergic rhinitis in the child are determinants of childhood asthma. The findings from our study can be used to generate awareness regarding risk factors that are linked to childhood asthma.


Walking speed and global cognition: results from the OKLAHOMA Study.
Executive functioning and processing speed have been related to physical functioning in non-demented, elderly samples; however, the relationship between walking speed and global cognition has not been examined. Six hundred and seventy-five community dwelling older adults were enrolled through their primary care physicians. Walking speed was assessed on a 50-foot course at usual pace. Global cognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale score. After adjusting for age, gender, and education, there was a strong inverse relationship between walking speed and global cognition, with slower walkers performing worse on the cognitive measures, faster walkers performing better on the cognitive measures, and the intermediate walkers performing in the middle. In these older adults, global cognition was related to walking speed.


The characteristic ultrasound features of specific types of ovarian pathology (review).
Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner's subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images.


Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice.
Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism.


Stride characteristics of horses competing in Grand Prix jumping.
An investigation was made of the stride characteristics of horses jumping 2 obstacles during a Grand Prix competition. One obstacle was a picket fence and rail 1.3 m high (fence 2), and the other was a coop and rail 1.52 m high (fence 11). Thirteen distance and 22 timing measurements of 17 horses were extracted from high-speed films, using computer-aided analysis. These data were used to compare takeoff and landing of the lead and nonlead legs, the thoracic limbs and pelvic limbs, and fence 2 and fence 11. Paired t-tests were used to compare means and a stepwise regression analysis was done for each fence, using the total horizontal distance jumped as the dependent variable. Stride timing and distance measurements did not differ (P less than 0.05) between the 2 fences . Each horse approached the fences in a moderately fast canter and, at takeoff , placed the nonlead thoracic limb earlier and farther from the fence than the lead thoracic limb (P less than 0.05). The nonlead leg stance phase lasted longer than the lead leg stance phase (P less than 0.05). The lead and nonlead pelvic limbs acted more in unison than the thoracic limbs and did not differ in their time of placement, stance phase duration, or position from the fence (P less than 0.05). The overlap of the stance phases of the pelvic limbs was greater than that of the thoracic limbs (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Anemia and hepatosplenomegaly as presenting features in a child with rickets and secondary myelofibrosis.
Anemia and hepatosplenomegaly are common reasons for referring a child to a pediatric hematologist or oncologist. Among the many causes for these findings is severe rickets, which has been shown to be associated with secondary myelofibrosis and myeloid metaplasia. The authors present the case of an infant with severe rickets and secondary myelofibrosis and review the differential diagnosis of hepatosplenomegaly from the viewpoint of the pediatric hematologist/oncologist.


Exposure assessment of epoxy fatty acids through consumption of specific foods available in Belgium.
Epoxy fatty acids (EFAs) are secondary oxidation products formed from unsaturated fatty acid hydroperoxides. Seventeen food categories were analysed for C18 monoEFAs of food products available on the Belgian market. A quantitative exposure assessment was performed based on deterministic and probabilistic approaches combining these concentration data with consumption data obtained from the Belgian National Food Consumption Survey of 2004. A preliminary evaluation of any potential risk related to the intake of the studied EFAs through the studied foods was performed by applying the threshold of toxicological concern (TTC) concept. Three food categories out of 17 foods, mayonnaise, butter-margarine and ready-to-eat meals were found to contribute most to the intake of EFAs. According to probabilistic determination, these foods had P50 intakes of 0.4085, 0.3328 and 0.2997 mg kg-1 bw day-1 respectively. They had P99.5 intakes of 3.7183, 2.7921 and 38.6068 mg kg-1 bw day-1 respectively. The intake below the TTC was from the consumption of cooked meat, smoked salmon and raw cured ham, with P50 intakes of 0.0006, 0.0007 and 0.0011 mg kg-1 bw day-1 respectively, and the other foods were above the TTC. Based on the TTC concept, a risk to human health could be identified related to the consumption of cheese, snacks foods, plant oils, French fries, dry nuts, chips, cured minced raw meat, cookies, fresh and frozen salmon and bacon.


Vibrio porteresiae sp. nov., a diazotrophic bacterium isolated from a mangrove-associated wild rice (Porteresia coarctata Tateoka).
Two facultatively anaerobic, nitrogen-fixing bacteria (strains MSSRF30(T) and MSSRF31) were isolated from a mangrove-associated wild rice (Porteresia coarctata Tateoka). These strains were determined to be nitrogen-fixers using the acetylene reduction assay and by PCR detection of a nifH gene amplicon. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the novel strains were most closely related to Vibrio fluvialis LMG 7894(T) (96.8 % gene sequence similarity), Vibrio furnissii LMG 7910(T) (96.8 % sequence similarity) and Vibrio tubiashii CIP 102760(T) (96.7 % sequence similarity). Further multilocus sequence analysis using recA, pyrH, rpoA and nifH genes also showed low levels of sequence similarities (83-93 %) with all species of the genus Vibrio with validly published names. A multigene phylogenetic tree using concatenated sequences of the four genes (16S rRNA, rpoA, recA and pyrH) showed that strains MSSRF30(T) and MSSRF31 occupied a distinct phylogenetic position, forming a long branching that was not clustered with any other recognized Vibrio species. The fatty acid profile also suggested that the novel strains belonged to the genus Vibrio. The results of physiological and biochemical tests, genomic fingerprinting and DNA-DNA hybridization analyses clearly differentiated both novel strains from their closest phylogenetic neighbours, Vibrio cholerae IID6019, Vibrio mimicus LMG 7896(T), V. fluvialis LMG 7894(T) and V. furnissii LMG 7910(T). Several phenotypic traits enabled the differentiation of strain MSSRF30(T) from other species of the genus Vibrio. The DNA G+C content of strain MSSRF30(T) was 44.4+/-3.1 mol%. Based on genotypic, phenotypic, chemotaxonomic, phylogenetic and DNA-DNA hybridization analyses, the name Vibrio porteresiae sp. nov. (type strain MSSRF30(T)=LMG 24061(T)=DSM 19223(T)) is proposed for this novel taxon.


Enhancing remediation potential of heavy metal contaminated soils through synergistic application of microbial inoculants and legumes.
Soil microorganisms play a crucial role in remediating contaminated soils in modern ecosystems. However, the potential of combining microorganisms with legumes to enhance the remediation of heavy metal-contaminated soils remains unexplored. To investigate this, we isolated and purified a highly efficient cadmium and lead-tolerant strain. Through soil-cultivated pot experiments with two leguminous plants (Robinia pseudoacacia L. and Sophora xanthantha), we studied the effects of applying this microbial agent on plant nutrient uptake of soil nutrients, heavy metal accumulation, and the dynamics of heavy metal content. Additionally, we examined the response characteristics of inter-root microbial and bacterial communities. The results demonstrated that microorganisms screened from heavy metal-contaminated soil environments exhibited strong survival and adaptability in heavy metal solutions. The use of the Serratia marcescens WZ14 strain-phytoremediation significantly increased the soil's ammonium nitrogen (AN) and organic carbon (OC) contents compared to monoculture. In addition, the lead (Pb) and cadmium (Cd) contents of the soil significantly decreased after combined remediation than those of the soil before potting. However, the remediation effects on Pb- and Cd-contaminated soils differed between the two legumes following the Serratia marcescens WZ14 inoculation. The combined restoration altered the composition of the plant inter-rhizosphere bacterial community, with the increase in the relative abundance of both Proteobacteria and Firmicutes. Overall, the combined remediation using the tolerant strain WZ14 with legumes proved advantageous. It effectively reduced the heavy metal content of the soil, minimized the risk of heavy metal migration, and enhanced heavy metal uptake, accumulation, and translocation in the legumes of S. xanthantha and R. pseudoacacia. Additionally, it improved the adaptability and resistance of both legumes, leading to an overall improvement in the soil's environmental quality. These studies can offer primary data and technical support for remediating and treating Cd and Pb in soils, as well as rehabilitating mining sites.


Relation between progression of aortic valve sclerosis and carotid intima-media thickening in asymptomatic subjects with cardiovascular risk factors.
Aortic valve sclerosis (AVS) is the early lesion of calcific aortic valve disease and may subsequently progress toward valvular stenosis. Histopathological and clinical evidence has suggested that AVS and atherosclerosis share similar mechanisms. However, little is known regarding the relation between the early AVS progression and the early atherosclerosis progression. The carotid intima-media thickness (IMT) by carotid ultrasonography has been established as the surrogate marker of the early atherosclerosis. The aim of this study was to examine the association between progression of early AVS and increase of carotid IMT. We retrospectively analyzed the data of 127 asymptomatic subjects (49 ± 8 years, 114 men) with ≥1 cardiovascular (CV) risk factors, without history of CV disease, who underwent echocardiographic and carotid ultrasonographic examinations twice ≥6 months apart. We evaluated aortic valve morphology and function and carotid IMT at the baseline and at follow-up examinations. During a follow-up of 25 ± 15 months, the number of subjects with AVS was significantly increased (34 vs. 47%, P < 0.0001) and the mean value of carotid IMT was significantly increased (1.16 ± 0.33 vs. 1.29 ± 0.41 mm, P < 0.0001). The progression of AVS was observed in 26 subjects. By logistic regression analysis, the baseline carotid IMT value was an independent predictor of AVS progression (odds ratio = 4.07, P = 0.026). In asymptomatic subjects with CV risk factors, progression of AVS and increase of carotid IMT were observed during a mean follow-up period of 25 months. Progression of AVS in asymptomatic subjects with CV risk factors was associated with carotid intima-media thickening.


Characterization and Discrimination of Oueslati Virgin Olive Oils from Adult and Young Trees in Different Ripening Stages Using Sterols, Pigments, and Alcohols in Tandem with Chemometrics.
Dynamics of squalene, sterol, aliphatic alcohol, pigment, and triterpenic diol accumulations in olive oils from adult and young trees of the Oueslati cultivar were studied for two consecutive years, 2013-2014 and 2014-2015. Data were compared statistically for differences by age of trees, maturation of olive, and year of harvesting. Results showed that the mean campesterol content in olive oil from adult trees at the green stage of maturation was significantly (p < 0.02) above the limit established by IOC legislation. However, the mean values of campesterol and Δ-7-stigmastenol were significantly (p < 0.01) above the limits in oils from young trees at the black stage of ripening. Principal component analysis was applied to alcohols, squalene, pigments, and sterols having noncompliance with the legislation. Then, data of 36 samples were subjected to a discriminant analysis with "maturation" as grouping variable and principal components as input variables. The model revealed clear discrimination of each tree age/maturation stage group.


Accuracy of retrospective pain measurement in patients with chronic pain.
The use of pain scales that refer to a past time period is thereby based on the assumption that patients accurately remember their 'average', 'greatest' and 'least' pain. The present study addresses the validity of numerical pain rating scales that refer to a past period of time (herein, the past 7 days). Routine data from 94 patients with chronic pain were retrospectively analysed. Pain questionnaire data on the greatest, least and average pain during the past week and on current pain were compared with the mean value of entries in a pain diary from the corresponding period. The retrospectively assessed average, greatest and least pain values were consistently slightly higher than the corresponding values of daily current pain measured for the studied collective of chronic pain patients. Current pain (at the time of answering the questionnaire) better represents daily currently measured pain [intraclass correlation (ICC)=0.885] than retrospective individual measurements. The greatest correlation with averaged diary data was shown by the combination of questionnaire data on average, least and current pain (ICC=0.911). The high correlations between the questionnaire and diary data support the validity of retrospective pain surveys. However, the current status influences recall. Thus, composite retrospective pain data improve with the addition of current pain.


Radiotherapy for newly diagnosed primary central nervous system lymphoma: role and perspective.
Whole brain radiotherapy (WBRT) has long been a key treatment of newly diagnosed primary central nervous system lymphoma (PCNSL). In the 1990s, the addition of high dose Methotrexate-based induction chemotherapy (HD MTX-based CT) has enabled a drastic improvement in PCNSL patients outcome. However, combined treatment has led to radiation-induced delayed neurotoxicity, especially in older patients. Alternative treatment strategies have been assessed to improve the efficacy and neurotoxicity ratio. Nowadays, in the elderly patients WBRT is widely omitted or deferred, and in younger patients WBRT is challenged by high dose chemotherapy with autologous stem cell transplant (HCT-ASCT) for consolidation treatment after HD MTX-based CT. In this setting, this review is addressed to clinicians with the aim to summarize the role of WBRT in the treatment of newly diagnosed PCNSL and its perspectives.


Comparison of 3 different methods of anesthesia before transrectal prostate biopsy: a prospective randomized trial.
Periprostatic nerve block (PNB) is the most common anesthesia technique used before prostate biopsy. However, needle punctures for anesthetic infiltration may be painful and cause higher infectious complications. We assessed whether addition of rectal lidocaine gel would improve its efficacy. We also investigated the efficacy and safety of tramadol, a codeine derivative, as a noninvasive method. A total of 300 patients who underwent prostate biopsies were randomized into 4 groups of controls, PNB, perianal/intrarectal lidocaine gel plus PNB and tramadol. Pain was assessed with a numeric analog scale. Each group consisted of 75 patients, and there was a statistically significant difference among pain scores (p = 0.001). Mean pain scores were 4.63 for controls, 2.57 for PNB, 2.03 for infiltration plus gel group and 3.11 for tramadol. Pain and discomfort were least in PNB plus gel arm. The difference of pain score between PNB alone and tramadol group did not reach statistical significance. Infectious complications were higher in the combination group, whereas there were no complications with tramadol. Any form of analgesia/anesthesia was superior to none. The combination of PNB plus gel provided significantly better analgesia compared to PNB alone or tramadol. If this can be duplicated in other trials, the combination may be accepted as the new gold standard of anesthesia for prostate biopsy. The efficacy of tramadol was similar to that of PNB, and was free of complications. Therefore, tramadol may have a role before prostate biopsy, which needs to be explored.


Management of skin infections in Pacific children prior to hospitalisation.
Hospital admissions for childhood skin infections in New Zealand (NZ) are on the increase. Pacific children make up a high number of those who are admitted. This study describes the parents of Pacific children's understanding and management of skin sores in the home prior to the sores becoming infected and requiring hospital admission. A descriptive qualitative approach combined with the Pacific research frameworks of Fa'afaletui and the Metaphor of Kakala were used to elicit parents' understanding and management of children's skin sores in the home. The semi-structured interviews were conducted in English or Samoan, and all transcribed into English. Mothers of 11 Pacific children admitted with skin infections between 2006 and 2008 were interviewed. The children's infections started with insect bites in some cases. Parents actively sought treatment to ensure children's optimal health was maintained. Initial management included a 'watch and see' approach for some, until deterioration was noted. This is the first known study in New Zealand that has captured children's experiences when sustaining a skin infection/s and the activities that took place while seeking treatment in the community. Although most of the children received medical attention in primary health care (PHC), this did not prevent the need for hospital admission. The acuteness and seriousness of children's health on admission shows that preventive efforts need to increase and the early management of infections in PHC settings needs to be better understood.


Polymeric micelle assembly for preparation of large-sized mesoporous metal oxides with various compositions.
Here we report the synthesis of mesoporous metal oxide materials with various compositions by assembly of spherical polymeric micelles consisting of triblock copolymer poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-b-PVP-b-PEO) with three chemically distinct units. The PVP block interacts strongly with the inorganic precursors for the target compositions. The hydrophobic PS block is kinetically frozen in the precursor solutions, enabling the spherical micelles to remain in a stable form. The frozen PS cores serve as templates for preparing robust mesoporous materials. The PEO corona helps the micelles to stay well dispersed in the precursor solutions, which plays a key role in the orderly arrangement of the micelles during solvent evaporation. This approach is based on assembly of the stable micelles using a simple, highly reproducible method and is widely applicable toward numerous compositions that are difficult for the formation of mesoporous structures.


Markers of increased aeration in the paranasal sinuses and along the skull base: association between anatomic variants.
There may be substantial variation in paranasal sinus pneumatization across patients and between right and left sides. Patients with extensive sinus aeration, especially of the sphenoid sinus and along the skull base, often have protrusion of critical structures into the pneumatized sinus cavities, which potentially places these structures at risk during sinus surgery. To evaluate associations between anatomic markers of increased paranasal sinus aeration along the skull base and to determine whether the presence of certain markers predicts other critical anatomic variants. Submillimeter axial computed tomography (CT) scans and associated triplanar reconstructions from 100 subjects were reviewed for the presence of 22 anatomic variants by two separate evaluators. Twelve of these variants were selected as markers of increased pneumatization. Average numbers of markers were compared with t-tests; associations between markers were evaluated by logistic regression analyses. The Holm-Bonferroni method was used to correct for multiple tests. Five anatomic variants were associated with increased paranasal sinus pneumatization, as defined by total number of markers of pneumatization: anterior ethmoid artery below the skull base, dehiscent/protruding internal carotid artery (ICA), dehiscent/protruding optic nerve (ON), pneumatized pterygoid recess, and middle turbinate (MT) concha bullosa (all p < .02). Significant associations were found between pneumatized pterygoid recesses and dehiscent or protruding ONs (odds ratio [OR] 3.06, p = .0120), dehiscent or protruding ICAs (OR 6.64, p < .0001), and anterior ethmoid arteries below the skull base (OR 2.65, p = .0189). Significant association was also found between dehiscent or protruding ONs and dehiscent or protruding ICAs (OR 3.57, p = .0047). The markers of increased pneumatization and anatomic associations identified in this study have important implications for surgeons planning and undertaking operative approaches in and around the sinuses.


High-contrast solid-state electrochromic devices of viologen-bridged polysilsesquioxane nanoparticles fabricated by layer-by-layer assembly.
Water-soluble silsesquioxane nanoparticles (NPs) incorporating viologen groups (PXV; 1,1'-bis[3-(trimethoxysilyl)propyl]-4,4'-bipyridinium iodide) have been synthesized by sol-gel polymerization. The electrochromic properties of the bulk film fabricated by layer-by-layer (LbL) assembly have been examined, along with their incorporation into solid-state devices. The orange LbL films show high thermal stability and exhibit a maximum UV-vis absorption at 550 nm. Electrochromic switching of the NPs in liquid electrolyte as well as in the solid state was evaluated by a kinetic study via measurement of the change in transmission (% T) at the maximum contrast. Cyclic voltammograms of the PXV NP LbL films exhibit a reversible reduction at -0.6 V vs Ag/AgCl in a 0.1 M NaClO4(aq) solution, revealing good electrochromic stability, with a color change from orange to dark purple-blue at applied potentials ranging from -0.7 to -1.3 V. Cathodically coloring PXV NP solid-state devices exhibit a switching time of a few seconds between the purple-blue reduced state and the orange oxidized state, showing a contrast of 50% at 550 nm and a coloration efficiency of 205 cm2/C. Their solubility and fairly fast electrochromic switching ( approximately 3 s) at low switching voltages (between 0 and 3.0 V), along with their stability under atmospheric conditions, make PXV NPs good candidates for electrochromic displays.


Specific recognition mechanism between RNA and the KH3 domain of Nova-2 protein.
The KH3 domain of Nova-2 protein can precisely recognize the sequence-specific target RNA of human glycine receptor α2. However, the recognition mechanism between the protein and its target RNA is still hotly debated. In this study, molecular dynamic simulations in explicit solvent were utilized to understand the recognition mechanism. The structural analysis and the Kolmogorov-Smirnov P-test statistics reveal that the KH3 domain might obey a conformational selection mechanism upon RNA binding. However, the induced fit mechanism could not be completely ruled out. Unfolding kinetics indicates that the folding of RNA and KH3 happens first and then the binding between RNA and KH3 follows. Principle component analysis shows that the invariant Gly-Lys-Gly-Gly loop moves toward to the RNA molecule but the C-terminal domain moves away from the RNA molecule upon binding. These specific dominant motions were hypothesized to stabilize the complex structure. The hydrophobic and hydrogen bonding interactions were found to be the driving forces for the specific recognition, in contrast to the dominant electrostatic interactions for nonspecific recognition.


Acute variation of estimated glomerular filtration rate following a half-marathon run.
The accurate estimation of glomerular filtration rate (GFR) is pivotal in sports medicine. However, there is controversial information on the acute influence of physical exercise on kidney function in healthy athletes. The estimated GFR (EGFR) was assessed by the recommended Modification of Diet in Renal Disease (MDRD) equation before a 21-km half-marathon, at the end, and 3, 6, 24 hrs thereafter on 17 trained, middle-aged males. Results were corrected for plasma volume changes. The mean EGFR at the baseline was 76 mL/min/1.73 m (2); it decreased at the end of the run (62 mL/min/1.73 m (2)) and for the following 3 hrs (68 mL/min/1.73 m (2)) and 6 hrs (70 mL/min/1.73 m (2)), though statistical significance was only achieved immediately after the run (mean decrease 16 %, p < 0.01). The frequency of athletes with EGFR below the normal threshold was higher than the baseline immediately after the race and for the following 6 hrs. Twenty-four hours after the run, the EGFR had returned to values similar and nonsignificantly different from those recorded at the baseline. These results attest that medium to high strains of running in healthy, middle-aged, trained individuals do not cause renal damage, but a limited and temporary decline in renal function.


Extracellular signalling, translational control, two repressors and an activator all contribute to the regulation of methylenomycin production in Streptomyces coelicolor.
Bioinformatic analysis of the plasmid-linked gene cluster associated with biosynthesis of methylenomycin (Mm) suggested that part of the cluster directs synthesis of a gamma-butyrolactone-like autoregulator. Autoregulator activity could be extracted from culture fluids, but differed from gamma-butyrolactones in being alkali resistant. The activity has recently been shown to comprise a series of novel autoregulator molecules, the methylenomycin furans (termed MMF). MMF autoregulator activity is shown to account for the ability of certain Mm non-producing mutants to act as 'secretors' in cosynthesis with other 'convertor' mutants. Three genes implicated in MMF biosynthesis are flanked by two regulatory genes, which are related to genes for gamma-butyrolactone-binding proteins. Genetic evidence suggests that these two genes encode components of a hetero-oligomeric repressor of MMF and Mm biosynthesis. The Mm biosynthetic genes themselves depend on the activator gene mmyB, which appears to be repressed by the putative MmyR/MmfR complex until enough MMF accumulates to release repression. The presence of TTA codons in mmyB and the main MMF biosynthetic gene causes Mm production to be dependent on the pleiotropically acting bldA gene, which encodes the tRNA for the rarely used UUA codon.


T-cell-rich B-cell lymphoma in a cat.
T-cell-rich B-cell lymphoma is a neoplasm recognized in humans in which a neoplastic proliferation of large B lymphocytes is present amid a background of reactive T lymphocytes. A 13-year-old Domestic Shorthair cat developed a mass in the region of the left parotid gland. Histologically, the mass was composed of scattered large atypical cells within a dense background of uniform small lymphoid cells. Immunohistochemically, the large cells were uniformly labeled using antiserum directed against the B-lymphocyte marker BLA.36, whereas labeling of nearly all of the small cells was limited to the T-lymphocyte marker CD3. The histomorphologic and immunohistochemical features of this unique feline neoplasm are characteristic of T-cell-rich B-cell lymphoma of humans.


Toll-like receptor 3 agonist induces impairment of uterine vascular remodeling and fetal losses in CBA x DBA/2 mice.
The objective of this study was to examine the expression of Toll-like receptor (TLR) 3 at the maternal-fetal interface and determine whether exposure to TLR3 agonist would induce an innate immune response and trigger pregnancy loss. To address this, abortion-prone male DBA/2J mated-CBA/J female mice were given polyinosinic-polycytidylic acid (poly I:C; 10 microg/g body weight, i.p.) or PBS at gestation day (gd) 6.5. All implantation sites appeared viable at gd 7.5 when endometrium was dissected for immunohistological examination. It was noted that poly I:C treatment increased fetal losses to 40.2+/-1.7% at midgestation stage compared with control animals (11.0+/-3.0%). It was observed also that the ratio of vessel to lumen area significantly increased at gd 10.5 and gd 12.5 after poly I:C treatment, indicating that the spiral artery (SA) modification was impaired. Meanwhile, 24h after poly I:C injection, expression of TLR3 was markedly elevated within decidua basalis (DB), and endometrial TNF-alpha increased 2.7-fold but IFN-gamma remained unchanged in homogenized endometrium. These results suggest that enhanced TNF-alpha expression in endometrial stroma may play a critical role in inflammatory factor production and impairment of uterine spiral artery remodeling in the pregnancy failure of CBA x DBA/2 mating.


Lack of effect of cyclandelate in peripheral arterial disease.
While cyclandelate is widely used in the therapy of peripheral arterial disease, objective evidence of its efficacy remains controversial. For this reason, 12 patients with intermittent claudication (average age of 66.8 years) received both cyclandelate 400 mg qid and placebo in a double-blind crossover trial lasting two months. During the cyclandelate and placebo periods, the following peripheral hemodynamic measurements were obtained using a plethysmograph and treadmill claudication testing: mean calf blood flow, vascular resistance and venous capacitance; finger and toe blood flow, pulsation amplitude and temperature before and after vasodilating maneuvers; arm and leg arterial pulsation amplitudes, one and ten minute calf reactive hyperemia reaction; 30 pound/30 second calf active hyperemia reactions and times of onset of claudication as measured on a treadmill. No major significant difference could be demonstrated between placebo and cyclandelate on any subjective symptom or any objective measurement. It is concluded that cyclandelate 400 mg qid for 4 weeks was of little objective value in treating this group of 12 patients with peripheral arterial disease and suffering from intermittent claudication.


Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents.
Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that beta-blocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy. We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a beta-adrenergic-receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding beta1- and beta2-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and alpha- and beta-myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (beta-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of beta-adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography. Twenty-six of 32 beta-blocker-treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [+/-SE] increase, 18.8+/-1.8). As compared with the six beta-blocker-treated patients who did not have a response (mean change, a decrease of 2.5+/-1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and alpha-myosin heavy chain mRNA and a decrease in beta-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of beta-adrenergic receptors. In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.


[Gastric bypass in incurable esophageal cancer].
Between 1977 and 1981, 70 patients were treated for esophageal carcinoma; 45 carcinomas were considered to be unresectable. In 11 of the 45, the site and stage of the tumor and the physical condition of the patient permitted palliative treatment with retrosternal gastric bypass. One patient died postoperatively. A gastric bypass enabled the remaining 10 patients to swallow normally and therefore led to significantly better quality of life. Only two patients survived for more than 1 year, the longest survival time being 15 months till now.


A Supramolecular Antidote to Macromolecular Toxins Prepared through Coassembly of Macrocyclic Amphiphiles.
Poisoning is a leading cause of admission to medical emergency departments and intensive care units. Supramolecular detoxification, which involves injecting supramolecular receptors that bind with toxins to suppress their biological activity, is an emerging strategy for poisoning treatment; it has few requirements and a broad application scope. However, it is still a formidable challenge to design supramolecular therapeutic materials as an antidote to macromolecular toxins, because the large size, flexible conformation, and presence of multiple and diverse binding sites of biomacromolecules hinder their recognition. Herein, a supramolecular antidote to macromolecular toxins is developed through the coassembly of macrocyclic amphiphiles, relying on heteromultivalent recognition between the coassembled components and toxic macromolecules. The coassembly of amphiphilic cyclodextrin and calixarene strongly and selectively captures melittin, a toxin studied herein; this imparts various therapeutic effects such as inhibiting the interactions of melittin with cell membranes, alleviating melittin cytotoxicity and hemolytic toxicity, reducing the mortality rate of melittin-poisoned mice, and mitigating damage to major organs. The use of the proposed antidote overcomes the limitation of supramolecular detoxification applicability to only small-molecular toxins. The antidote can also detoxify other macromolecular toxins as long as selective and strong binding is achieved because of the coassembling tunability.


[Iatrogenic botulism: a complication to be taken into account in the treatment of child spasticity].
During the last decades the use of botulinum toxin for management of muscular disorders and spasticity associated to cerebral palsy has become a widespread practice. A 6-years female suffering of cerebral palsy secondary to a partial agenesis of the corpus callosum who was receiving bolulinum toxin since October 2001. One week after the last dose (Dysport 46 U/kg/dose) she started high grade fever, malaise, food refusal, choking, constipation, eyelid ptosis, absence of deep tendon reflexes, and abundant mucous discharge. Such features were so progressively severe that ventilatory support became mandatory. After a previous dose five months before, she developed similar features but they were less severe and thought to be related to a respiratory infection. At the present, there are two forms of botulinum toxin commercially available: the British brand Dysport and the American brand Botox. Bio equivalences are 1 U Botox to 2 or 6 U Dysport. Dosing (U/kg per session) has been established as follows: 5 U for Botox, 35 U for Dysport. Safety limits are a wide range with a therapeutic toxic index rate of 1:10. Generalized side effects after diffusion to blood of locally injected botulinum toxin are rare.


Effects and Mechanisms of Cu Species in Fe-MOFs on Fenton-Like Catalytic Activity and Stability.
Fe-based MOFs (Fe-MOFs) are deemed promising Fenton-like catalysts due to their well-developed pores and accessible active sites. However, their inferior catalytic activity, iron leaching, and low H2O2 utilization always hinder their application as Fe-based MOF catalysts. In this work, we manipulated the structure of Fe-oxo nodes in MIL-88B(Fe) via a CuI species substitution method, affording a mixed-valence (Cu-incorporated Fe-MOFs) with highly improved Fenton-like performance. It is found that the CuI serves as a shuttle to promote transfer between FeII/FeIII, inducing the formation of a larger amount of stable FeII sites, which was proven by experimental and DFT calculation results. A linear relationship was observed for the Fenton-like performance and the amount of CuI species for the catalysts. The corresponding value of the •OH formation is 2.17 eV for Cu-incorporated MIL-88B(Fe), which is significantly lower than that of MIL-88B(Fe) (2.69 eV). Meanwhile, the enriched CuI species suppress Fe species leaching during the catalytic reaction. The Fe-ion leakage of 0.4Cu@MIL-88B is very tiny (0.01-0.03 mg/L), significantly less than that of MIL-88B (2.00-3.02 mg/L). At the same time, H2O2 utilization for 0.4Cu@ MIL-88B(Fe) is 88%, which is almost 4.4 times that of pure MIL-88B(Fe). This work provides insights into the rational design of Fe-MOFs as promising Fenton-like catalysts for wastewater treatment.


Single-crystal vanadium pentoxide nanowires.
Single-crystal V2O5 nanowires were successfully synthesized from the starting materials V6O13 powder and water. The experimental results indicate that high purity nanowires can be obtained using this simple synthetic route in absence of templates or catalysts. The diameter of the nanowires was found to be ca. 20 approximately 60 nm and the length up to several tens of micrometers, and the phases of nanowires were determined by XRD and TEM measurements.


Stable expression of the tax gene of type I human T-cell leukemia virus in human T cells activates specific cellular genes involved in growth.
Stable expression of the 40-kDa transactivator protein (Tax) from the type I human T-cell leukemia virus (HTLV-I) in Jurkat T cells leads to the activation and sustained expression of certain cellular genes that are transiently induced during normal T-cell growth. Cellular genes induced by Tax include those encoding the alpha subunit of the high-affinity interleukin 2 receptor (Tac), interleukin 2, and granulocyte/macrophage colony-stimulating factor. Tax induction of the interleukin 2 gene is synergistically amplified by mitogens that augment cytoplasmic levels of calcium. These changes in the pattern of cellular gene expression reflect a specific action of Tax, as they are undetectable in isogenically matched control cell lines expressing antisense tax cDNA. The spectrum of cellular genes regulated by Tax appears to be restricted: several other T-cell genes, either inducibly or constitutively expressed, are unaffected by this viral protein. These cell lines constitutively expressing Tax provide valuable reagents to explore the molecular basis for Tax action and to delineate the full spectrum of cellular genes regulated by this retroviral gene product.


Effect of Escherichia coli endotoxin on tissue lipoprotein lipase activities in chickens.
1. Four-week-old broiler chickens were injected intravenously with from 0.01 to 1 mg of E. coli endotoxin/kg body weight or with saline. 2. At all doses used endotoxin markedly depressed food intake and lipoprotein lipase activities in muscle and adipose tissue within 8 h. Heart lipoprotein lipase activity was significantly depressed only at doses of 0.1 mg endotoxin/kg body weight or greater. 3. Treatment of birds with 0.3 mg endotoxin/kg body weight reduced post-heparin lipoprotein lipase activity to 0.13 of that in control birds in 8 h. 4. Endotoxin generally depressed plasma very-low-density lipoprotein concentration. Plasma non-esterified fatty acid concentration was significantly elevated only in birds given 1 mg endotoxin/kg body weight. 5. Fatty acid synthetase activity in the liver of endotoxin-treated birds was significantly lower than in control birds 16 h after administration of endoxin, but not after 8 h. 6. These results show that tissue lipoprotein lipase activity in birds is very responsive to E. coli endotoxin, as in mammals. Hypertriglyceridaemia occurs only occasionally in endotoxin-treated chickens, most probably because of the particularly close relationship between food intake and hepatic lipoprotein synthesis in birds.


Giant liposome microreactors for controlled production of calcium phosphate crystals.
Calcium phosphates are among the most important biominerals in living organisms, where they play both a mechanical and a calcium storage role. Their growth in vivo is under strong biological control, and this process occurs in closed spaces. Our aim in this paper is to describe a microreactor system able to control the mineralization process within closed spaces. To this aim we produce giant liposomes containing calcium ions as active ions in the mineralization process, spermine as an activator of crystal growth, and alkaline phosphatase as a catalyst to convert phosphate esters into phosphates. These phosphate esters are provided in the form of p-nitrophenyl phosphate outside of the liposomes. It is demonstrated that these amphiphilic molecules are able to diffuse through the lipidic container and to be subsequently hydrolyzed under enzymatic catalysis into active phosphate species which interact with the already available calcium and spermine to produce calcium phosphates only in the interior of the liposomes. This opens the route to control the calcium phosphate particle size in biomimetic systems.


Successful treatment of progressive stage 4s hepatic neuroblastoma in a neonate with intra-arterial chemoembolization.
Stage 4s neuroblastoma (NB) is a unique entity seen in infants less than 1 year of age, with metastatic disease confined to liver, skin, or bone marrow. Despite metastatic spread, stage 4s NB has a favorable outcome. An exception to this is seen in neonates who present with progressive enlargement of the liver with secondary respiratory compromise and liver failure. We describe a 4-week-old neonate who presented with 4s NB, with a rapidly enlarging liver, resulting in respiratory and hepatic failure, who had a rapid, sustained, and ongoing response to chemoembolization of the hepatic artery. This approach is feasible at this age, and may be effective in improving the outcome in this group of patients.


c-FLIP is a target of the E3 ligase deltex1 in gastric cancer.
The ubiquitin E3 ligase DELTEX1 (DTX1) is specifically downregulated in gastric cancer tissues, and expression of DTX1 is linked to better prognoses and survival in gastric cancer. Cellular FLICE inhibitory protein (c-FLIP) is known for its pivotal role in the resistance of cancer cells to death receptor-induced cell death. Here, we show that DTX1 is an E3 ligase for c-FLIP in gastric cancer cells. DTX1 promoted c-FLIP downregulation. Overexpression of DTX1 sensitized gastric cancer cells to TRAIL-induced apoptosis, whereas DTX1-knockdown attenuated apoptosis induction. DTX1 binds c-FLIPL and directs it into the endosome-lysosomal pathway for proteasome-independent degradation. Moreover, induction of DTX1 in AGS cells by geldanamycin conferred susceptibility of those cells to TRAIL-induced apoptosis. Our results reveal a tumor-suppressive role for DTX1 and suggest a new approach to increasing TRAIL efficacy by raising DTX1 levels in gastric cancer therapy. DTX1 also enhanced c-FLIP degradation and FasL-induced and TRAIL-induced apoptosis in T cells, suggesting that DTX1 constitutes one of the physiological mechanisms regulating c-FLIP stability.


Changes in Dietary Intake of Major Nutrients and Food Sources among Costa Rican Adolescents in the Last 20 Years.
Adolescence offers a window of opportunity to prevent adult obesity and noncommunicable disease risk factors. With the rising prevalence of adolescent obesity over the last 20 y, identifying any changes in dietary risk factors is crucial. We aimed to assess the dietary intake of major nutrients and their food sources in Costa Rican adolescents from 1996 to 2017. Means from 3-d food records from adolescents (ages 13-18 y) living in San José (the province with the highest concentration of adolescents in Costa Rica) were obtained in 1996 (n = 276), 2006 (n = 133), and 2017 (n = 818). Differences in consumption of major nutrients and selected food groups by sex and survey period were tested using age- and area-adjusted ANOVAs. In 2017, adolescents consumed significantly (P < 0.05) less saturated and trans fats [saturated: -3.2% of total energy (TE); trans: -1.4% TE], vegetables (-24 g/d), beans (-42 g/d), and white rice (22 g/d) than in 1996. The 2017 adolescents also reported significantly higher consumption of unsaturated fatty acids (MUFAs: up from 8.2% to 15.3% TE; PUFAs: up from 5.5% to 9.5% TE; P < 0.05), sugary drinks (+134 g/d), pastries/desserts (+55 g/d), other refined starchy foods (+36 g/d), and snacks/fast foods (+26 g/d) than their 1996 counterparts. In 1996 and 2006, the main source of calories was white rice, whereas in 2017, it was sugary drinks (12% TE and 15% TE, respectively; P < 0.05). The intake ratio of beans to white rice was significantly higher in 1996 (1:1.6) than in 2017 (1:3.5). The changes in the intake of major nutrients and food sources of Costa Rican adolescents present new public health challenges for cardiometabolic risk prevention. Costa Rica should prioritize the design of comprehensive strategies that target added sugar intake while simultaneously increasing access to and promotion of healthful items.


Fluorescence tomographic imaging of sentinel lymph node using near-infrared emitting bioreducible dextran nanogels.
Sentinel lymph node (SLN) mapping is a critical procedure for SLN biopsy and its diagnosis as tumor metastasis in clinical practice. However, SLN mapping agents used in the clinic frequently cause side effects and complications in the patients. Here, we report the development of a near-infrared (NIR) emitting polymeric nanogel with hydrodynamic diameter of ~28 nm - which is the optimal size for SLN uptake - for noninvasive fluorescence mapping of SLN in a mouse. This polymeric nanogel was obtained by coupling Cy7, an NIR dye, to the self-assembled nanogel from disulfide-linked dextran-deoxycholic acid conjugate with the dextran of 10 kDa, denoted as Dex-Cy7. Fluorescence imaging analysis showed that Dex-Cy7 nanogels had an enhanced photostability when compared to Cy7 alone. After intradermal injection of Dex-Cy7 nanogel into the front paw of a mouse, the nanogels were able to migrate into the mouse's axillary lymph node, exhibiting longer retention time and higher fluorescence intensity in the node when compared to Cy7 alone. An immunohistofluorescence assay revealed that the nanogels were localized in the central region of lymph node and that the uptake was largely by the macrophages. In vitro and in vivo toxicity results indicated that the dextran-based nanogels were of low cytotoxicity at a polymer concentration up to 1,000 μg/mL and harmless to normal liver and kidney organs in mice at an intravenous dose of 1.25 mg/kg. The results of this study suggest that NIR-emitting polymeric nanogels based on bioreducible dextran-deoxycholic acid conjugates show high potential as fluorescence nanoprobes for safe and noninvasive SLN mapping.


Paediatric tympanoplasty: comparative study between patients aged 5-8 years and those aged over 14 years.
To evaluate and analyse the success rate of tympanoplasty type I in paediatric patients aged 5 to 8 years compared to a control group (patients aged over 14 years). In this prospective study, 60 patients (of either sex) with chronic suppurative otitis media inactive mucosal disease were divided into 2 groups (30 in each): group A comprised paediatric patients aged 5-8 years and group B consisted of older individuals aged over 14 years. All patients underwent tympanoplasty type I with an underlay technique using a temporalis fascia graft. Impressive surgical success rates of 87 and 90 per cent were recorded in groups A and B, respectively. Furthermore, audiological success rates of 69 and 78 per cent were achieved in groups A and B respectively. Statistical analysis of the data revealed that eustachian tube function had no impact on the outcome of tympanoplasty. Tympanoplasty type I performed in children aged five to eight years gives comparable results to those of older individuals.


Moisture sorption isotherms of grape pestil and foamed grape pestil.
Moisture sorption isotherms of grape pestil and foamed grape pestil were determined using the static gravimetric method at 10, 20 and 30 degrees C. The overall shape of the curves was typical of sugar-rich materials. The effect of temperature on moisture content in the lower aw range was not significant (P > 0.05). Four models, namely the Brunauer, Emmet and Teller (BET), the Guggenheim, Anderson and DeBoer (GAB) the Halsey and the Oswin, were evaluated to determine the best fit for the experimental data. The BET and GAB models fitted well the data of the samples in the temperature and water activity range studied. The Clausius-Clapeyron equation was used to evaluate the isosteric heats of sorption.