Dental pulp exposed to the CO2 laser beam.
Traumatic inflammation due to application of CO2 laser beam on teeth (dentin and pulp) of Beagle dogs and Macaca Monkeys, stimulate in dentino-pulpal tissue morphological phenomena studied after 5 days, 1, and 3 months by microscopy and microradiography. After a dentin exposure to a density of energy from 2 X 10(3) J/cm2, the first cell layers of the pulp tissue show a rarefaction and a cellular degeneration, followed by a neoformation of calcified dentin, of about 300 microns thick in 3 months, due to the excitation of odontoblasts or produced by pulpal cells functioning before. A density of energy of 10(3) J/cm2 order applied to the pulp beads to its partial necrosis, to various inflammatory aspects and to a quasi-constant regeneration by a neo-dentin bridge of 200 microns at 1 month. The analysis of cell activity seems able to be investigated from this method.


Analysis of Chameleonic Change of Red Cabbage Depending on Broad pH Range for Dye-Sensitized Solar Cells.
Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from red cabbage as a sensitizer. In this work, we investigated the adsorption characteristics and the electrochemical behavior for harvesting sunlight and electron transfer in red cabbage DSSCs under different solvents and pH. For the red cabbage dye-sensitized electrode adsorbed at pH 3.5, the solar cell yields a short-circuit current density (Jsc) of 1.60 mA/cm2, a photovoltage (Vcc) of 0.46 V, and a fill factor of 0.55, corresponding to an energy conversion efficiency (η) of 0.41%.


[Concentration of selected trace elements in serum and erythrocytes of children with chronic renal failure and am attempt at deficiency correction with animal blood preparation].
The results are presented of studies in 32 children with chronic renal failure treated conservatively in whom the value was evaluated of serum Mg, Zn, and Se concentration, and erythrocyte Mg, and Zn concentration. Among the patients a group of 15 children was isolated whose diet was enriched with the animal blood preparation brown Livex containing among others the studied trace elements. Significant Zn and Mg deficiency was demonstrated in the serum and Mg deficiency in the erythrocytes of the ill children which were effectively corrected after three months of supplementation with the preparation Livex.


Prostaglandin E and mitogenic stimulation of human lymphocytes in serum-free medium.
Sera used in cell cultures contain significant ammounts of prostaglandins (PGs). In order to avoid any effects of contaminating PGs, the present study employed a serum-free culture medium and confirmed the inhibitory effect of prostaglandin E (PGE) on the human lymphocyte activation which had been observed previously employing a serum-containing medium. PGE1 displayed a significantly stronger inhibitory effect on the cells than previously shown. Furthermore, reported enhancement of PGE synthesis by mitogen-activated lymphocytes could not be reproduced.


Stent Size Optimization in the Femoral Bifurcation Using a Fractal Model: A Morphological Analysis.
Stenting of common femoral artery (CFA) bifurcation lesions is complex due to harmonious asymmetric geometry between the CFA and deep or superficial femoral artery. In order to ensure an optimal flow, the stents must be implanted according to the diameter of the CFA and the diameter of the daughter vessels. The aim of this study was to validate a mathematical formula for the CFA bifurcation in order to optimize the implantation of stents in this bifurcation with a fast and efficient method. We retrospectively included all patients who underwent transcatheter aortic valve implantation and who had a healthy CFA bifurcation on the CT-scan. Diameters of the mother vessel (Dm), daughter vessels (Dl: larger vessel; Ds: smaller vessel), and the ratio between the two were calculated. According to the latter, the following linear model was proposed: [Dm = (Dm/Dl + Ds) × (Dl + Ds)] and was compared to the four existing models (Murray, HK, Flow, Finet). Finally, we calculated the relative error between the prediction of the four models and the measurements. Overall, 110 CFA bifurcations were included. Mean CFA diameter was 7.75 ± 1.67 mm. Mean Dl diameter was 5.79 ± 1.21 mm and mean Ds diameter was 5.23 ± 1.09 mm. A reduction of 25 % was seen between the CFA and the larger daughter-vessel. The mean ratio between the CFA and the daughter vessels was 0.71. Our model [Dm = 0.71× (Dl + Ds)] and the flow law were the most accurate (relative difference of 1.59 ± 11.97% and 1.01 ± 11.94%, respectively). However, Murray's law had a statistically significant deviation from the real mother-vessel diameter (P < 0.001). We developed a simple fractal ratio between CFA and daughter vessels, which could be easily used in daily practice during CFA percutaneous reconstruction to identify the optimal diameters of the diseased vessels.


Effect of guanosine triphosphate on the release of Ca2+ from intracellular store sites of saponin-treated human peripheral lymphocytes.
The effects of guanosine triphosphate (GTP) on the release and uptake of Ca2+ in nonmitochondrial intracellular store sites of human peripheral lymphocytes were examined. GTP in the presence of 3% polyethylene glycol released Ca2+ from the intracellular store sites of lymphocytes in a dose-dependent manner, and the maximal release was obtained at 10 microM GTP. GDP and 5'-GMP also enhanced the release of Ca2+. On the other hand, Ca2+ uptake in the presence of oxalate by saponin-treated lymphocytes was stimulated by GTP and this stimulation was abolished when polyethylene glycol was concomitantly present. The dose dependence of the stimulated Ca2+ uptake by GTP was much the same as that of the Ca2+ released by GTP. These results indicate that GTP has an inherent activity to release Ca2+ as well as to stimulate the uptake of Ca2+ in nonmitochondrial intracellular store sites of saponin-treated lymphocytes. The stimulatory effect of polyethylene glycol on GTP-mediated Ca2+ release may occur by inhibiting functions of the Ca2+ pump.


Response of sulfur-metabolizing biofilm to external sulfide in element sulfur-based denitrification packed-bed reactor.
Dosing sulfide into the sulfur-packed-bed (S0PB) has great potential to enhance the denitrification efficiency by providing compensatory electron donors, however, the response of sulfur-metabolizing biofilm to various sulfide dosages has never been investigated. In this study, the S0PB reactor was carried out with increasing sulfide dosages by 3.6 kg/m3/d, presenting a decreasing effluent nitrate from 14.2 to 2.7 mg N/L with accelerated denitrification efficiency (k: 0.04 to 0.27). However, 6.5 mg N/L of nitrite accumulated when the sulfide dosage exceeded 0.9 kg/m3/d (optimum value). The increasing electron export contribution of sulfide a maximum of 85.5% illustrated its competition with the in-situ sulfur. Meanwhile, over-dosing sulfide caused serious biofilm expulsion with significant decreases in the total biomass, live cell population, and ATP by 90.2%, 86.7%, and 54.8%, respectively. This study verified the capacity of dosing sulfide to improve the denitrification efficiency in S0PB but alerted the negative effect of exceeded dosing.


Fate of orthotopic corneal allografts in C57BL/6 mice.
Our aim was to determine whether corneal allografts placed in normal eyes of C57BL/6 mice enjoy immune privilege, and whether recipients of long-standing grafts acquire donor-specific ACAID. C57BL/6 mice received corneal grafts from BALB/c, C57BL/6, C3H, B10.D2 or BALB.B mice; for comparison, BALB/c mice received C3H or C57BL/6 corneal allografts. Delayed hypersensitivity and anterior chamber associated immune deviation (ACAID) induction were assessed in recipient mice at four and eight weeks after grafting. It was found that C57BL/6 mice resemble BALB/c mice in mounting more vigorous rejection reactions against minor H, rather than MHC, alloantigenic corneas, and in the acquisition of donor-specific DH within four weeks of engraftment. In addition, C57BL/6 mice with long-standing, healthy allografts display donor-specific ACAID. However, C57BL/6 mice differ from BALB/c mice in that (1) fewer allodisparate corneal grafts were accepted indefinitely; and (2) rejection in these eyes correlated with sustained donor-specific DH. It was concluded that immune privilege is less secure in the eyes of C57BL/6 mice, compared to BALB/c mice. This conclusion is discussed in terms of known polymorphic differences between these mouse strains at genetic loci governing (a) immune responsiveness, (b) alloform of Fas ligand, and (c) bias of immune response toward Th1 or Th2 phenotypes.


Cefaclor: in vitro spectrum of activity and beta-lactamase stability.
The in vitro activity of cefaclor against 556 clinical isolates of gram-positive and gram-negative bacteria was compared with that of other cephalosporins. Cefaclor had activity similar to that of cephalexin against gram-positive bacteria. It showed greater activity against Haemophilus strains than did cephalexin and inhibited beta-lactamase-producing Haemophilus isolates. Cefaclor was more active than cephalexin or cephalothin against Escherichia coli, Salmonella, and Shigella isolates but did not act against Serratia, Acinetobacter, indole-positive Proteus, or Bacteroides isolates. Cefaclor was resistant to type III (TEM) beta-lactamases but was destroyed by type I beta-lactamases and, to a lesser degree, by type IV and type V beta-lactamases.


Mechanistic insights into ball milling enhanced montmorillonite modification with tetramethylammonium for adsorption of gaseous toluene.
Montmorillonite is widely used for pollutants adsorption due to its porous structure and low price. However, the low specific surface area and small porosity limit its application in gas adsorption field. In this study, montmorillonite was organically modified using a facile dry ball milling method by tetramethylammonium bromide. The adsorption behaviour of toluene as a model VOC compound on organic montmorillonite was systematically investigated through adsorption breakthrough curves, adsorption kinetics and isotherms. After modification by ball milling, the specific surface area of ball milling with tetramethylammonium bromide for montmorillonite modification (BMTMt) was increased from 20.6 m2/g to 186.4 m2/g, and the microporosity proportion was up to 47%. Dynamic adsorption experiments showed that the best performance of BMTMt for toluene (55.9 mg/g) was 6 times higher than that of original montmorillonite (8.8 mg/g). Compared with the water bath preparation method, ball milling method promoted the intercalation of tetramethylammonium bromide into the layers of montmorillonite, resulting in a higher proportion of micropores. Density functional theory calculations indicated that the interaction between tetramethylammonium bromide and montmorillonite was mainly electrostatic forces, and the enhanced adsorption performance for toluene was mainly through microporous filling. BMTMt was proved to be a promising adsorbent for VOCs removal.


Genetics of liver disease: From pathophysiology to clinical practice.
Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients.


Impact of Dose Reduction on Efficacy: Implications of Exposure-Response Analysis of Palbociclib.
Palbociclib is indicated for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Exposure-response analyses were conducted to evaluate efficacy in Asian versus non-Asian patients and in patients with versus without dose reduction in PALOMA-2. PALOMA-2 compared palbociclib plus letrozole versus placebo plus letrozole in patients with ABC. Population pharmacokinetic analysis provided apparent palbociclib clearance (CL/F) for each patient. The time-varying exposure metric, Cavg,t, was calculated using average dose intensity and CL/F at the time of each progression-free survival (PFS) event. A Cox proportional model characterized PFS and palbociclib Cavg,t relationships. Significant prognostic factors for PFS were identified by univariate analysis, which were subsequently included in multivariate analyses, in addition to the Cavg,t effect on PFS. PFS profiles in Asian/non-Asian patients and patients with/without dose reduction were simulated and compared using observed palbociclib exposures and established exposure-response relationships. Patients (n = 421) received palbociclib plus letrozole (Asian = 64, non-Asian = 357; no dose reduction = 272, dose reduction = 149). Based on univariate analyses, significant prognostic factors were Ki67 score, age, and baseline aspartate aminotransferase (BAST), tumor size, alkaline phosphatase, and albumin levels. In multivariate analysis, only Ki67 and BAST remained significant. Palbociclib exposure did not significantly affect PFS in either univariate (P = 0.12) or multivariate (P = 0.44) analyses. This analysis suggests that palbociclib exposure has no impact on PFS when the dose reduction algorithm from palbociclib clinical trials is used. There is no difference in efficacy between Asians and non-Asians, despite the higher level of dose reductions in Asians. NCT01740427.


Restructuring ability and patterns of physics achievement.
For a sample of 24 male and 19 female college students, persons with high visualization (F1,36 = 7.60, P less than .01) and low flexibility of closure (F1,36 = 6.54, P less than .02) attained significantly higher achievement in physics than persons with low visualization or high flexibility of closure. Persons with high restructuring ability and high spatial visualization (M = 88.64, SD = 15.6) attained a significantly higher level of physics achievement than persons with high restructuring ability and low spatial visualization (M = 56.5, SD = 25.1). Flexibility of closure, spatial visualization, and the embedded figures test accounted for 23.8%, 18.4%, and 53% of the variability in physics achievement among the entire sample, among amles, and among females, respectively. The data provided moderate support for the field-dependence--independence model of psychological differentiation and for investigators who reported a possible link between field-dependence--independence, visualization, and extent of neurological lateralization.


Prevalence and determinants of maternal healthcare utilisation among young women in sub-Saharan Africa: cross-sectional analyses of demographic and health survey data.
Maternal health constitutes high priority agenda for governments across the world. Despite efforts by various governments in sub-Saharan Africa (SSA), the sub-region still records very high maternal mortality cases. Meanwhile, adequate utilization of maternal healthcare (antenatal care [ANC], skilled birth attendance [SBA], and Postnatal care [PNC]) plays a vital role in achieving improved maternal health outcomes. We examined the prevalence and determinants of maternal healthcare utilization among young women in 28 sub-Saharan African countries using data from demographic and health surveys. This was a cross-sectional study of 43,786 young women aged 15-24 years from the most recent demographic and health surveys of 28 sub-Saharan African countries. We adopted a multilevel logistic regression analysis in examining the determinats of ANC, SBA, and PNC respectively. The results are presented as adjusted Odds Ratios (aOR) for the logistic regression analysis. Statistical significance was set at p < 0.05. The prevalence of maternal healthcare utilisation among young women in SSA was 55.2%, 78.8%, and 40% for ANC, SBA, and PNC respectively with inter-country variations. The probability of utilising maternal healthcare increased with wealth status. Young women who were in the richest wealth quintile were, for instance, 2.03, 5.80, and 1.24 times respectively more likely to utilise ANC (95% CI = 1.80-2.29), SBA (95% CI = 4.67-7.20), and PNC (95% CI = 1.08-1.43) than young women in the poorest wealth quintile. Young women who indicated having a barrier to healthcare utilisation were, however, less likely to utilise maternal healthcare (ANC: aOR = 0.83, 95% CI = 0.78-0.88; SBA: aOR = 0.82, 95% CI = 0.75-0.88; PNC: aOR = 0.88, 95% CI = 0.83-0.94). While SBA utilisation was high, we found ANC and PNC utilisation to be quite low among young women in SSA with inter-country variations. To accelerate progress towards the attainment of the Sustainable Development Goal (SDG) targets on reducing maternal mortality and achieving universal health coverage, our study recommends the adoption of interventions which have proven effective in some countries, by countries which recorded low maternal healthcare utilisation. The interventions include the implementation of free delivery services, training and integration of TBAs into orthodox maternal healthcare, improved accessibility of facilities, and consistent public health education. These interventions could particularly focus on young women in the lowest wealth quintile, those who experience barriers to maternal healthcare utilisation, uneducated women, and young women from rural areas.


Intracellular processing of measles virus fusion protein.
Intracellular processing of measles virus fusion (F) protein was studied by radiolabeling and immunoprecipitation with a monoclonal antibody against F protein. The cleavage of F protein into F1 and F2 subunits was complete after 5 hours of chase during which the growth of oligosaccharide chains on the F2 domain of F protein continued. The addition of terminal sialic acid conferred a strong negative charge on the F2 subunit. F protein expressed on the cell surface was removed by a fungal semi-alkaline protease, providing a method to follow the kinetics of its transport to the cell surface. The transport of the F protein was faster than that of the hemagglutinin (HA) protein. Uncleaved F protein, as well as cleaved subunits became digestible by the protease, indicating that a portion of the F protein reaches the cell surface uncleaved. The treatment of measles virus-infected cells with tunicamycin resulted in the synthesis of unglycosylated HA (65 kilodaltons, Kd) and F (48 Kd) proteins. Unglycosylated F protein was not cleaved into smaller subunits, nor was it transported to the cell surface. Unglycosylated HA protein likewise failed to reach the cell surface.


Stapes Surgery Teaching Tool: A Simple and Stable Technique.
Stapedotomy followed by placement of a piston prosthesis is the mainstay for surgical management of otosclerosis primarily undertaken to improve hearing in patients. Although a simple and elegant procedure, prosthesis placement in stapes surgery is difficult to master. Improper surgical technique or improper placement of prosthesis may result in complications which may require revision surgery. We here describe a training technique that is simple, inexpensive, improves the skills and can be done using easily available materials such as a disposable syringe, stapler pin and micro-forceps. Regular practice with this training module minimizes surgical time and can even be done just prior to the surgery, however, this is not a substitute for temporal bone dissections.


Transepithelial dipeptide (glycylsarcosine) transport across epithelial monolayers of human Caco-2 cells is rheogenic.
Net transepithelial transport (and cellular accumulation) of the dipeptide glycylsarcosine (Gly-Sar), across the apical membrane of human intestinal Caco-2 epithelia, is driven by a proton gradient (Na(+)-free conditions) and displays saturation kinetics (Km 17.4 +/- 5.1 mM, Vmax of 92.8 +/- 15.6 nmol.cm-2.h-1). Net Gly-Sar transport is associated with the stimulation of an inward short-circuit current (Isc). This dipeptide-stimulated Isc is observed in both Na(+)-containing and Na(+)-free conditions, is stimulated by apical acidity, and displays saturation kinetics (in Na(+)-free media at apical pH 6.0, Km of 13.6 +/- 4.5 mM and a Vmax of 284.1 +/- 39.3 nmol.cm-2.h-1). The maximal capacities of Gly-Sar transport and Isc suggest a dipeptide/proton stoichiometry greater than unity (1:3).


In vitro activity of daptomycin against gram-positive European clinical isolates with defined resistance determinants.
The in vitro activity of daptomycin against 337 gram-positive European clinical isolates with known resistance genes was determined. The MIC ranges for Staphylococcus aureus, enterococci, pneunococci, and streptococci were 0.03 to 1, 0.25 to 8, 0.12 to 1, and 0.06 to 8 micro g/ml, respectively. For only one streptococcus isolate and seven enterococcus isolates was the MIC 8 micro g/ml.


Tunnelling versus open harvest technique in obtaining venous conduits for coronary bypass surgery.
The tunnelling as opposed to the open harvest technique for harvesting long saphenous vein for coronary artery bypass procedures is a less frequently used technique as it requires more handling of the vein and this may induce trauma. This study aims to compare the degree of endothelial denudation and donor site morbidity between the two different harvest techniques. Saphenous vein segments in 78 patients (45 in tunnelling versus 33 in open harvest group) undergoing coronary artery bypass procedures were examined by light microscopy and graded according to the extent of endothelial denudation varying from grade 1 (most preserved) to grade 6 (>90% endothelial denudation). Clinical parameters relating to donor site morbidity including leg wound pain and infection were also assessed. There was no statistical difference in the age, sex, macroscopic vein quality, length and time taken to harvest the veins between the two groups. The tunnelling technique always used thigh saphenous vein whereas nearly a third of veins harvested by the open harvest technique were lower leg veins (P=0.001). The tunnelling technique resulted in an endothelial score of 2.5 compared with 3.3 for the open harvest technique (P < 0.001). In addition, saphenous vein tunnelling resulted in significantly less leg wound pain (1.2 vs. 1.8, P=0.001), no leg wound infection (compared with 12.2% in open harvest group, P=0.02) and produced cosmetically more acceptable scars. Furthermore, length of hospital stay was significantly prolonged to 19.3 days in those with leg wound infection compared to 8.7 days in those without leg wound infection (P < 0.001). These results show that saphenous vein tunnelling is an attractive alternative to the open harvest technique in obtaining venous conduits for coronary artery bypass procedures.


Glucose-regulated protein 78 (GRP78) binds directly to PIP3 phosphatase SKIP and determines its localization.
Skeletal muscle and kidney-enriched inositol polyphosphate phosphatase (SKIP), a PIP3 phosphatase, has been implicated in the regulation of insulin signaling in skeletal muscle. SKIP interacts with Pak1 and glucose-regulated protein 78 (GRP78), both of which are necessary for the regulation of insulin signaling. In this study, we showed that GRP78 directly binds to the SKIP C-terminal homology (SKICH) domain of SKIP and that this binding is necessary for the localization of SKIP at the ER. In addition, in vitro binding analysis showed that GRP78 and Pak1 competitively bind to SKIP. Taken together, these findings suggest a model by which GRP78 regulates intracellular localization of SKIP and how SKIP binds to Pak1 on insulin stimulation.


Quantum-limited optical time transfer for future geosynchronous links.
The combination of optical time transfer and optical clocks opens up the possibility of large-scale free-space networks that connect both ground-based optical clocks and future space-based optical clocks. Such networks promise better tests of general relativity1-3, dark-matter searches4 and gravitational-wave detection5. The ability to connect optical clocks to a distant satellite could enable space-based very long baseline interferometry6,7, advanced satellite navigation8, clock-based geodesy2,9,10 and thousandfold improvements in intercontinental time dissemination11,12. Thus far, only optical clocks have pushed towards quantum-limited performance13. By contrast, optical time transfer has not operated at the analogous quantum limit set by the number of received photons. Here we demonstrate time transfer with near quantum-limited acquisition and timing at 10,000 times lower received power than previous approaches14-24. Over 300 km between mountaintops in Hawaii with launched powers as low as 40 µW, distant sites are synchronized to 320 attoseconds. This nearly quantum-limited operation is critical for long-distance free-space links in which photons are few and amplification costly: at 4.0 mW transmit power, this approach can support 102 dB link loss, more than sufficient for future time transfer to geosynchronous orbits.


Antileukemic activity of derivatives of 1-phenyl-2,5-dimethyl-3,4-bis(hydroxymethyl)pyrrole bis(N-methylcarbamate).
Treatment of N-aryl-N-acetylalanine derivatives, 3, with acetic anhydride-dimethyl acetylenedicarboxylate gave the dimethyl N-aryl-2,5-dimethylpyrrole-3,4-dicarboxylates, 4. Reduction of 4 and acylation of 5 gave 2a-j and 6. All of the title compounds 2a-j and 6 showed significant reproducible activity in the P388 in vivo antileukemic assay.


Label-free, multiplexed detection of bacterial tmRNA using silicon photonic microring resonators.
A label-free biosensing method for the sensitive detection and identification of bacterial transfer-messenger RNA (tmRNA) is presented employing arrays of silicon photonic microring resonators. Species specific tmRNA molecules are targeted by complementary DNA capture probes that are covalently attached to the sensor surface. Specific hybridization is monitored in near real-time by observing the resonance wavelength shift of each individual microring. The sensitivity of the biosensing platform allowed for detection down to 53 fmol of Streptococcus pneumoniae tmRNA, equivalent to approximately 3.16×10(7) CFU of bacteria. The simplicity and scalability of this biosensing approach makes it a promising tool for the rapid identification of different bacteria via tmRNA profiling.


Gammaglobulin therapy in a case of chronic relapsing dysimmune polyneuropathy.
A boy with chronic relapsing dysimmune polyneuropathy was treated with intravenous gammaglobulin injections for the fourth and fifth episodes, and showed rapid clinical improvement compared with in the three previous episodes, when he was treated by high dose steroid administration.


Rothmund-Thomson syndrome and Addison disease.
We report an 18-year-old man with the unusual combination of Rothmund-Thomson syndrome (RTS) and Addison disease. He was admitted when he was 26 months old because of short stature, dehydration, metabolic acidosis, hyperpigmentation, and typical skin lesions. Because his growth remained delayed, at age 10 years he was given a trial of recombinant growth hormone. After six years of treatment no improvement in height, bone, or sexual maturation was observed. This fact may be related to a defect in connective tissue metabolism. Chromosomal analysis of peripheral blood lymphocytes revealed increased numbers of breaks and gaps. Fibroblasts cultured from affected skin did not grow. Patients with RTS are prone to developing cancer, but no malignant disease was found in our patient. Early diagnosis and treatment of both endocrinologic and malignant complications are essential for survival of patients with this rare syndrome.


Sympathetic control of glucagon receptor mRNA levels in brown adipose tissue of cold-exposed rats.
Brown adipose tissue (BAT) is implicated in both cold-induced thermogenesis and regulation of energy expenditure and is mainly controlled by sympathetic innervation. To clarify the permissive and/or complementary roles of glucagon in cold-induced BAT activation, glucagon receptor gene expression and its modulation by sympathetic activity were investigated in rats. One pad of interscapular BAT was surgically denervated while the other pad was sham operated, then rats were either cold-exposed (CE) for 1 week at 4 degrees C or kept near thermoneutrality (25 degrees C, TN). Using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay, it was shown that cold exposure decreased (-44%) the relative abundance of BAT glucagon receptor mRNA, an effect which was prevented by unilateral surgical sympathectomy of BAT. The present results show a negative control by sympathetic nervous activity of glucagon receptor gene expression and/or of glucagon receptor mRNA stability in BAT of cold-exposed rats. The down-regulation of glucagon receptor expression during cold exposure does not support a major role of the peptide in the thermogenic control of BAT.


Student, Staff, and Faculty Perspectives on Intimate Partner and Sexual Violence on 3 Public University Campuses: Protocol for the UC Speaks Up Study and Preliminary Results.
Intimate partner and sexual violence are pervasive public health issues on college and university campuses in the United States. Research is recommended for creating and maintaining effective, relevant, and acceptable prevention programs and response services for student survivors. The University of California (UC) Speaks Up study aims to examine factors contributing to intimate partner and sexual violence on 3 UC campuses and use the findings to develop and test interventions and policies to prevent violence, promote health, and lay the groundwork for subsequent large-scale quantitative research. A mixed methods study was conducted at UC Los Angeles, UC San Diego, and UC Santa Barbara. Phase I (2017-2020) involved a resource audit; cultural consensus modeling of students' perceptions of sexual consent; in-depth interviews (IDIs) and focus group discussions with students to understand perceptions of campus environment related to experiences as well as prevention of and responses to violence; and IDIs with faculty, staff, and community stakeholders to investigate institutional and community arrangements influencing students' lives and experiences. Phase II (2020-ongoing) involves IDIs with student survivors to assess the use and perceptions of campus and community services. Qualitative content analysis is used to generate substantive codes and subthemes that emerge, using a thematic analysis approach. In January 2019, we conducted 149 free-listing interviews and 214 web-based surveys with undergraduate and graduate and professional students for the cultural consensus modeling. Between February 2019 and June 2019, 179 IDIs were conducted with 86 (48%) undergraduate students, 21 (11.7%) graduate and professional students, 34 (19%) staff members, 27 (15.1%) faculty members, and 11 (6.1%) community stakeholders, and 35 focus group discussions (27/35, 77% with undergraduate students and 8/35, 23% with graduate and professional students) were conducted with 201 participants. Since September 2020, 50% (15/30) of the planned student survivor interviews have been conducted. This segment of data collection was disrupted by the COVID-19 pandemic. Recruitment is ongoing. Data analysis and phase II data collection are ongoing. The findings will be used to develop and test interventions for preventing violence, promoting health and well-being, and ensuring that survivor services are relevant and acceptable to and meet the needs of all individuals in the campus community, including those who are typically understudied. The findings will also be used to prepare for rigorous, UC-system-wide public health prevention research. DERR1-10.2196/31189.


Intergenerational Transmission of Depression: Examining the Roles of Racism and Trauma Among Black Mothers and Youth.
Racism is a multifaceted system of oppression that disproportionately harms Black mothers and children across the lifespan. Despite reliable evidence that racism is associated with worse mental health outcomes (eg, increased depressive symptoms), less is known about potential intergenerational effects of Black mothers' experiences of racism on children's mental health, as well as how traumatic experiences influence these pathways. In this cross-sectional quantitative study, we aimed (1) to replicate the finding that maternal experiences of racism are associated with both maternal and child depression; (2) to identify whether maternal experiences of racism are indirectly associated with child depression via the effect of maternal depression; and (3) to test whether the indirect effect of racism on child depression via maternal depression is conditioned on maternal trauma. Black mothers and their children (N = 148 dyads) were recruited from an urban hospital and were interviewed about their experiences of racism, trauma, and mental health symptoms. The mothers' average age was 35.16 years (SD = 8.75) and the children's average age was 10.03 years (SD = 1.51). First, we found that maternal experiences of racism were associated with more severe maternal depression (r = 0.37, p < .01) as well as more severe child depression (r = 0.19, p = .02). Second, we found that maternal experiences of racism were indirectly associated with child depression through the effect of maternal depression (ab = 0.76, 95% CI = 0.26, 1.37). Third, we found that maternal trauma exposure moderated this indirect effect such that, at relatively lower levels of maternal trauma exposure, the indirect effect of maternal experiences of racism on child depression was nonsignificant (ωlow = -0.05, 95% CI = -0.50, 0.45), whereas at relatively higher levels of maternal trauma exposure, the indirect effect of maternal experiences of racism on child depression was statistically significant (ωhigh= .65, 95% CI = 0.21, 1.15). These findings suggest that the indirect effect of maternal experiences of racism on child depression through the effect of maternal depression depends on the degree of maternal trauma exposure. This study advances the literature by shedding light on key processes that can explain the intergenerational effects of racism as well as contextual factors that can exacerbate racism's downstream consequences across generations.


Optimization of boron neutron capture therapy for the treatment of undifferentiated thyroid cancer.
To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis (alpha,beta-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60 mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10(8) n/cm(2)/sec for 83.4 min. Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm(3) or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.


[Determination of the species specificity of interferons in the translation of the their mRNA from various cell cultures].
Interferons obtained on induction of human lymphocytes with Newcastle viruses and staphylococcal enterotoxin A and diploid fibroblast cells of human embryos with poly (I).poly (C), as well as translation products of interferon mRNA obtained from these cells were analysed serologically. It was shown that the main type of interferon produced by the cells depended on the cell culture and inductor nature. It was defined at the level of the respective gene depression. Effective translation of mRNA of the interferons of the 3 types makes possible production of cDNA and creation of bacterial plasmids coding the genetic information for the synthesis of human interferon.


Inhibition of lymphocyte protease granzyme A by antithrombin III.
T-lymphocytes contain a cytoplasmic granule associated homo-dimeric protease designated granzyme A. Upon T-cell target cell interaction, the granules undergo exocytosis and granzyme A, and other granule constituents, are released. Here we show that granzyme A secreted into plasma is immediately inactivated by antithrombin III. The rate of complex formation is enhanced 400-fold in the presence of heparin. Two different complexes are generated: granzyme A-antithrombin III and granzyme A-(antithrombin III)2, respectively, indicating that both active centers of granzyme A are functional. Thus, the proteolytic activity of lymphocyte protease granzyme A, whose physiologically relevant function is unknown, is well regulated in plasma.


On the photocycle and light adaptation of dark-adapted bacteriorhodopsin.
Pulsed Nd laser (25 ns, 530 nm) photolysis experiments were carried out at room temperature in aqueous suspensions of dark- and light-adapted fragments of the purple membrane of Halobacterium halobium. It is shown that the (50%) 13-cis isomeric component (BR13-cis) of dark-adapted bacteriorhodopsin (BRDA) undergoes a photocycle involving a characteristic transient absorbing in the neighborhood of 610 nm. At relatively high excitation intensities BR13-cis is converted to the same 410 nm (M) transient that characterized the photocycle of the all-trans isomer (BRtrans) of light-adapted bacteriorhodopsin (BRLA). This process, which competes with the generation of the "610" species, is attributed to the photo-induced conversion, during the pulse, of BR13-cis (or of its primary photoproduct "X") to a species in the BRtrans photocyte. The relationship between these observations and the mechanism of BRDA hv leads to BRLA adaptation at low excitation intensities (for which a quantum yield limit, 0 less than or equal to (3.5 +/- 0.7) X 10(-2) , is established) is discussed.


Comparison between pressure-recording analytical method (PRAM) and femoral arterial thermodilution method (FATD) cardiac output monitoring in an infant animal model of cardiac arrest.
The pressure-recording analytical method is a new semi-invasive method for cardiac output measurement (PRAM). There are no studies comparing this technique with femoral artery thermodilution (FATD) in an infant animal model. A prospective study was performed using 25 immature Maryland pigs weighing 9.5 kg. Fifty-eight simultaneous measurements of cardiac index (CI) were made by FATD and PRAM at baseline and after return of spontaneous circulation. Differences, correlation, and concordance between both methods were analyzed. The ability of PRAM to track changes in CI was explored with a polar plot. Mean CI measurements were 4.5 L/min/m(2) (95 % CI, 4.2-4.8 L/min/m(2); coefficient of variation, 27 %) by FATD and 4.0 L/min/m(2) (95 % CI, 3.6-4.3 L/min/m(2); coefficient for variation, 37 %) by PRAM (difference, 0.5 L/min/m(2); 95 % CI for the difference, 0.1-1.0 L/min/m(2); p = 0.003; n = 58). No correlation between both methods was observed (r = 0.170, p = 0.20). Limits of agreement were -2.9 to 4.0 L/min/m(2) (-69.9 to 84.9 %). Percentage error was 80.6 %. Only 26.1 % of data points lied within an absolute deviation of ±30° from the polar axis. No correlation nor concordance between both methods was observed. Limits of agreement and percentage of error were high and clinically not acceptable. No concurrence between both methods in CI changes was observed. PRAM is not a useful method for measurement of the CI in this pediatric model of cardiac arrest.


Proton NMR study of the heme environment in bacterial quinol oxidases.
The heme environment and ligand binding properties of two relatively large membrane proteins containing multiple paramagnetic metal centers, cytochrome bo3 and bd quinol oxidases, have been studied by high field proton nuclear magnetic resonance (NMR) spectroscopy. The oxidized bo3 enzyme displays well-resolved hyperfine-shifted 1H NMR resonance assignable to the low-spin heme b center. The observed spectral changes induced by addition of cyanide to the protein were attributed to the structural perturbations on the low-spin heme (heme b) center by cyanide ligation to the nearby high-spin heme (heme o) of the protein. The oxidized hd oxidase shows extremely broad signals in the spectral region where protons near high-spin heme centers resonate. Addition of cyanide to the oxidized bd enzyme induced no detectable perturbations on the observed hyperfine signals, indicating the insensitive nature of this heme center toward cyanide. The proton signals near the low-spin heme b558 center are only observed in the presence of 20% formamide, consistent with a critical role of viscosity in detecting NMR signals of large membrane proteins. The reduced bd protein also displays hyperfine-shifted 1H NMR signals, indicating that the high-spin heme centers (hemes b595 and d) remain high-spin upon chemical reduction. The results presented here demonstrate that structural changes of one metal center can significantly influence the structural properties of other nearby metal center(s) in large membrane paramagnetic metalloproteins.


Echocardiographic Biventricular Coupling Index to Predict Precapillary Pulmonary Hypertension.
Pulmonary hypertension (PH) is a frequent and detrimental condition. Right heart catheterization (RHC) is the gold standard to identify PH subtype (precapillary from postcapillary PH) and is key for treatment allocation. In this study, the novel echocardiographic biventricular coupling index (BCI), based on the ratio between right ventricular stroke work index and left ventricular E/E' ratio, was tested for the discrimination of PH subtype using RHC as the comparator. BCI was derived in 334 consecutive patients who underwent transthoracic echocardiography and RHC for all indications. BCI was then tested in a validation cohort of 1,349 patients. The accuracy of BCI to identify precapillary PH was high in the derivation cohort (area under the curve, 0.82; 95% CI, 0.78-0.88; P < .001; optimal cut point, 1.9). BCI identified patients with precapillary PH with high accuracy also in the validation cohort (area under the curve, 0.87 [95% CI, 0.85-0.89; P < .001]; subgroup with PH: area under the curve, 0.91 [95% CI, 0.89-0.93; P < .001]; cut point, 1.9; sensitivity, 82%; specificity, 89%; positive predictive value, 77%; negative predictive value, 92%). BCI outperformed both the D'Alto score (Z = 3.56; difference between areas = 0.05; 95% CI, 0.02-0.07; P < .001) and the echocardiographic pulmonary-to-left atrial ratio index (Z = 2.88; difference between areas = 0.02; 95% CI, 0.01-0.04; P = .004). BCI is a novel, noninvasive index based on routinely available echocardiographic parameters that identifies with high accuracy patients with precapillary PH. BCI may be of value in the screening workup of patients with PH.


User-centric genomics infrastructure: trends and technologies.
Genomics is both a data- and compute-intensive discipline. The success of genomics depends on an adequate informatics infrastructure that can address growing data demands and enable a diverse range of resource-intensive computational activities. Designing a suitable infrastructure is a challenging task, and its success largely depends on its adoption by users. In this article, we take a user-centric view of the genomics, where users are bioinformaticians, computational biologists, and data scientists. We try to take their point of view on how traditional computational activities for genomics are expanding due to data growth, as well as the introduction of big data and cloud technologies. The changing landscape of computational activities and new user requirements will influence the design of future genomics infrastructures.


Effect of deferasirox (ICL670) on arterial function in patients with beta-thalassaemia major.
Deferasirox (ICL670) has been shown to have rapid accessibility to intracellular labile iron. We tested the hypothesis that oral deferasirox improves arterial dysfunction in patients with beta-thalassaemia major. Nineteen thalassaemia patients, aged 23 +/- 7 years, with normal left ventricular (LV) function were treated with deferasirox at 25-35 mg/kg/d for 12 months. LV function, brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, and serum ferritin levels were determined at baseline prior to initiation, after 6 months and after 12 months of therapy. The baseline cardiovascular indices were compared with those of 17 age-matched controls. Longitudinal changes in patients during the treatment period were also determined. Compared with controls, patients had similar echocardiographic indices of LV function (all P > 0.05), while their baseline brachial FMD was reduced (P < 0.001) and carotid stiffness increased (P = 0.019). An increase in FMD (P < 0.001) and a decrease in carotid stiffness (P = 0.007) were found at 6 and 12 months follow-up. The stiffness index correlated inversely with FMD (r = -0.42, P = 0.001). Although there was an increase in ferritin level at 12 months (3303 +/- 1185 ng/ml vs. 2714 +/- 780 ng/ml at baseline, P = 0.006), no significant correlation existed between ferritin level and FMD or carotid stiffness. In conclusion, deferasirox therapy in thalassaemia patients is associated with improved arterial function.


Pneumatic compression device treatment of lower extremity lymphedema elicits improved limb volume and patient-reported outcomes.
Examine the effectiveness of an advanced pneumatic compression device (APCD) in reducing limb volume (LV), and to evaluate clinician and patient-reported outcomes. Device registry study. Data were collected prospectively for 196 lower extremity lymphedema patients prescribed an APCD. Baseline and post-treatment LVs were calculated and clinical outcomes (skin changes, pain, and function) were assessed. Patient-reported outcomes and satisfaction utilizing a pre- and post-treatment survey were also evaluated. 90% of APCD-treated patients experienced a significant reduction in LV with 35% enjoying a reduction >10%. Mean LV reduction was 1,150 mL or 8% (p < .0001). Greater baseline LV and BMI were strong predictors of LV reduction (p < .0001). Clinician assessment indicated that the majority of patients experienced improvement in skin fibrosis and function. Patient-reported outcomes showed a significant increase in ability to control lymphedema through APCD treatment, with an increase in function and a reduction in the interference of pain. 66% were "very satisfied" with the APCD treatment. APCD use is associated with consistent reductions in LV, with favorable patient-reported outcomes. Results demonstrate that reduction in LV and pain, combined with functional improvement and patient satisfaction can be achieved, providing tangible benefit for lower extremity patients.


Drug-induced Liver Injury Secondary to Herbal and Dietary Supplements.
The use of herbal and dietary supplements (HDS) is increasing in the United States and worldwide. Its significant association with liver injury has become a concern, particularly because rates of hepatotoxicity caused by HDS are increasing. There are variety of HDS available, ranging from multi-ingredient substances, to anabolic steroids for bodybuilding purposes, to individual ingredients for purposes of supplementing a diet. This article reviews the impact of liver injury cause by HDS and explores the hepatotoxic potential of such products and their individual ingredients.


VOICE: developing a new measure of service users' perceptions of inpatient care, using a participatory methodology.
Service users express dissatisfaction with inpatient care and their concerns revolve around staff interactions, involvement in treatment decisions, the availability of activities and safety. Traditionally, satisfaction with acute care has been assessed using measures designed by clinicians or academics. To develop a patient-reported outcome measure of perceptions of acute care. An innovative participatory methodology was used to involve services users throughout the research process. A total of 397 participants were recruited for the study. Focus groups of service users were convened to discuss their experiences and views of acute care. Service user researchers constructed a measure from the qualitative data, which was validated by expert panels of service users and tested for its psychometric properties. Views on Inpatient Care (VOICE) is easy to understand and complete and therefore is suitable for use by service users while in hospital. The 19-item measure has good validity and internal and test-retest reliability. Service users who have been compulsorily admitted have significantly worse perceptions of the inpatient environment. A participatory methodology has been used to generate a self-report questionnaire measuring service users' perceptions of acute care. VOICE encompasses the issues that service users consider most important and has strong psychometric properties.


Direct identification of clinical pathogens from liquid culture media by MALDI-TOF MS analysis.
We propose using MALDI-TOF MS as a tool for identifying microorganisms directly from liquid cultures after enrichment of the clinical sample in the media, to obtain a rapid microbiological diagnosis and an adequate administration of the antibiotic therapy in a clinical setting. To evaluate this approach, a series of quality control isolates were grown in thioglycollate (TG) broth and brain heart infusion (BHI) broth and extracted under four different protocols before finally being identified by MALDI-TOF MS. After establishing the best extraction protocol, we validated the method in a total of 300 liquid cultures (150 in TG broth and 150 in BHI broth) of different types of clinical samples obtained from two tertiary Spanish hospitals. The initial evaluation showed that the extraction protocol including a 5 minute sonication step yielded 100% valid identifications, with an average score value of 2.305. In the clinical validation of the procedure, 98% of the microorganisms identified from the TG broth were correctly identified relative to 97% of those identified from the BHI broth. In 24% of the samples analysed, growth by direct sowing was only successful in the liquid medium, and no growth was observed in the direct solid agar cultures. Use of MALDI-TOF MS plus the sonication-based extraction method enabled direct and accurate identification of microorganisms in liquid culture media in 15 minutes, in contrast to the 24 hours of subculture required for conventional identification, allowing the administration of a targeted antimicrobial therapy.


Pregnancy: a cloned horse born to its dam twin.
Several animal species, including sheep, mice, cattle, goats, rabbits, cats, pigs and, more recently, mules have been reproduced by somatic cell cloning, with the offspring being a genetic copy of the animal donor of the nuclear material used for transfer into an enucleated oocyte. Here we use this technology to clone an adult horse and show that it is possible to establish a viable, full-term pregnancy in which the surrogate mother is also the nuclear donor. The cloned offspring is therefore genetically identical to the mare who carried it, challenging the idea that maternal immunological recognition of fetal antigens influences the well-being of the fetus and the outcome of the pregnancy.


Emotional intelligence and professional identity formation in pharmacy education.
Considering the various professional roles of pharmacists, pharmacy students and pharmacists have had difficulty identifying with a clear professional identity. Thereby there is a need for a professional identity formation (PIF) that conveys a consistent message about the role and value of pharmacists. Having a clear professional identity may also be a driver to advance the pharmacy profession. While achieving PIF is a challenging path, one element that conceivably contributes to PIF is emotional intelligence (EI). EI is acquired through life experiences and relates to personal and social awareness and the management of emotions and relationships. EI is critical for personal and professional success. Pharmacy students are exposed to different pharmacists' professional identities. This faces them with challenges as they try to incorporate their roles and expectations into practice. Integrating the core elements of EI into pharmacy education through a variety of teaching and learning methods is essential in the PIF of pharmacy students. PIF will enable pharmacy students to better associate with the profession by "thinking, acting, and feeling like a pharmacist." Both EI and PIF need to be integrated in pharmacy curricula. However, there is paucity of literature on how to best develop, integrate and assess EI and PIF. Therefore, a collaborative comprehensive approach by the pharmacy profession is necessary to that end.


Developmental regulation of myelin basic protein expression in mouse brain.
Developmental regulation of myelin basic protein expression in mouse brain has been examined by comparing the myelin basic protein coding potential of mRNA in vitro with the accumulation of myelin basic protein-related polypeptides in vivo. In vitro translation of mRNA isolated from mouse brain generated eight myelin basic protein-related polypeptides with apparent molecular weights of 34K, 30K, 29K, 26K, 21.5K, 18.5K, 17K, and 14K. A similar set of eight myelin basic protein-related polypeptides with corresponding molecular weights was identified in vivo when total brain proteins were analyzed by immunoblotting. Each of the myelin basic protein-related polypeptides shows a characteristic developmental profile in terms of mRNA level and rate of accumulation implying a complex developmental program of myelin basic protein gene expression with regulation and modulation at several different biosynthetic levels.


The good habit of reading (El Buen Habito de la Lectura): parental reactions to an enhanced Reach Out and Read program in a clinic for the underserved.
This report describes parental reactions to a Reach Out and Read (ROR) program enhanced with a children's library in an urban clinic serving low-income immigrant families.


The effect of dehydration on the neurohypophyseal blood flow in rats with hereditary diabetes insipidus.
Neurohypophyseal blood flow increases in water-deprived rats. This increase is independent of vasopressin release, since it occurs even in rats with hereditary defect of hypothalamic vasopressin synthesis.


Characterization and fed-batch culture of hybridoma overexpressing apoptosis suppressing gene bcl-2.
Mouse hybridoma 2E3 transfected with human bcl-2 gene survived longer with increasing expression level of bcl-2 when cultured in DME medium supplemented with 9% serum. One of the transfectants, 2E3BCMGbcl-2, overexpressed bcl-2 and could maintain viable cell density higher than the initial density for more than four days at a low 0.5% serum concentration. In comparison a mock transfectant 2E3BCMG remained viable for only one day. However, both hybridomas died out within a day in serum-free medium. These results suggested that bcl-2 needed a small amount of some serum components to suppress apoptosis of the hybridoma. Overexpression of bcl-2 also suppressed apoptosis of the hybridoma induced by glutamine deprivation. When hybridoma 2E3BCMGbcl-2 was inoculated in DME medium supplemented with 9% serum and cultured for 10 d with additional 2% serum feed at day 4 of the culture, viable cell density increased 2-fold and antibody produced 3-fold, in comparison with mock transfected 2E3 cultured in the same manner. The mock transfectant with additional feed of serum at day 4 of the culture showed no difference in viable cell density and antibody production. These results suggested that the mock transfectant committed to apoptosis before day 4 of the culture and the additional serum at day 4 could not reverse the commitment.


Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression.
Porcine epidemic diarrhea virus (PEDV) is an important pathogen in swine and is responsible for substantial economic losses. Previous studies suggest that the PEDV E protein plays an important role in the viral assembly process. However, the subcellular localization and other functions of PEDV E protein still require more research. The subcellular localization and function of PEDV E protein were investigated by examining its effects on cell growth, cell cycle progression, interleukin-8 (IL-8) expression and cell survival. The results show that plenty of PEDV E protein is localized in the ER, with small quantities localized in the nucleus. The PEDV E protein has no effect on the intestinal epithelial cells (IEC) growth, cell cycle and cyclin A expression. The cells expressing PEDV E protein express higher levels of IL-8 than control cells. Further studies show that PEDV E protein induced endoplasmic reticulum (ER) stress and activated NF-κB which is responsible for the up-regulation of IL-8 and Bcl-2 expression. This study shows that the PEDV E protein is localized in the ER and the nucleus and it can cause ER stress. The PEDV E protein had no effect on the IEC growth and cell cycle. In addition, the PEDV E protein is able to up-regulate IL-8 and Bcl-2 expression.


What is the impact of outdoor pollution on children's asthma?
Outdoor pollution is a complex mix of more than 200 air contaminants. Among these pollutants, ozone, nitrogen dioxide and fine particles may generate bronchial inflammation and hyperreactivity. The hypothesis that pollution contributes to the development of asthma in children is based on epidemiological, clinical and experimental data. Many risk factors during the in utero and postnatal period have been identified in the aetiology of childhood asthma. During pregnancy, outdoor pollution was identified as a causal factor of respiratory disease in neonatal cohort studies. Several epidemiological studies also demonstrate that outdoor pollution is a trigger of asthma exacerbations. This review aims to highlight the current knowledge on outdoor pollution and asthma.


A fluorescent chemosensor for calcium with excellent storage stability in water.
This article describes the design, synthesis and characterization of an optical sensor suitable for practical measurement of ionized calcium in serum and whole blood samples. The key to the development of this sensor is the identification of a chemically very stable, nitrogen-containing, calcium selective ionophore, coupled with a fluorophore having the correct spectral and electron accepting properties. The slope of the sensor is about 34%/mM in the typical clinically significant range of 0.32-2.2mM. This sensor has been implemented into the disposable cartridge, used for commercially available OPTI CCA analyzer with precision better than +/-0.02 mM (1S.D.). The sensor displays excellent stability against hydrolysis and oxidation, leading to less than 0.02 mM measurement error after 9 months of wet storage at room temperature, up to 30 degrees C.


Effect of prebiotic carbohydrates on the growth and tolerance of Lactobacillus.
Resistance to gastrointestinal conditions is a requirement for bacteria to be considered probiotics. In this work, we tested the resistance of six different Lactobacillus strains and the effect of carbon source to four different gastrointestinal conditions: presence of α-amylase, pancreatin, bile extract and low pH. Novel galactooligosaccharides synthesized from lactulose (GOS-Lu) as well as commercial galactooligosaccharides synthesized from lactose (GOS-La) and lactulose were used as carbon sources and compared with glucose. In general, all strains grew in all carbon sources, although after 24 h of fermentation the population of all Lactobacillus strains was higher for both types of GOS than for glucose and lactulose. No differences were found among GOS-Lu and GOS-La. α-amylase and pancreatin resistance was retained at all times for all strains. However, a dependence on carbon source and Lactobacillus strain was observed for bile extract and low pH resistance. High hydrophobicity was found for all strains with GOS-Lu when compared with other carbon sources. However, concentrations of lactic and acetic acids were higher in glucose and lactulose than GOS-Lu and GOS-La. These results show that the resistance to gastrointestinal conditions and hydrophobicity is directly related with the carbon source and Lactobacillus strains. In this sense, the use of prebiotics as GOS and lactulose could be an excellent alternative to monosaccharides to support growth of probiotic Lactobacillus strains and improve their survival through the gastrointestinal tract.


Next generation sequencing and RNA-seq characterization of adipose tissue in the Nile crocodile (Crocodylus niloticus) in South Africa: Possible mechanism(s) of pathogenesis and pathophysiology of pansteatitis.
Concerted efforts to identify the pathogenesis and mechanism(s) involved in pansteatitis, (a generalized inflammation of the adipose tissue), that was attributed to the recent crocodile die off in the Olifants River and Loskop Dam in Kruger National Park, Mpumalanga, South Africa have been in the forefront of research in recent time. As part of the efforts, molecular characterization of healthy and pansteatitis adipose tissue was carried out by RNA sequencing (RNA-Seq) using Next Generation Sequencing (NGS) and de novo assembly of the adipose transcriptome, followed by differential gene expression analysis. Healthy adipose tissue consisting of fifty samples was collected from the subcutaneous, visceral, intermuscular adipose tissues and the abdominal fat body of ten 4 years old juvenile crocodiles from a local crocodile farm in Pretoria, South Africa. Ten pansteatitis samples were collected from visceral and intermuscular adipose tissues of five crocodiles that were dying of pansteatitis. Forty-two thousand, two hundred and one (42,201) transcripts were assembled, out of which 37, 835 had previously been characterized. The de novo assembled transcriptome had an N50 (average sequence) of 436 bp, percentage GC content of 43.92, which compared well with previously assembled transcripts in the saltwater crocodile. Seventy genes were differentially expressed and upregulated in pansteatitis. These included genes coding for extracellular matrix (ECM) signaling ligands, inflammatory cytokines and tumour necrosis factor alpha (TNFα) receptors, fatty acid synthase and fatty acid binding proteins, peroxisome proliferator-activated receptor gamma (PPARγ), nuclear factor and apoptosis signaling ligands, and mitogen activated protein kinase enzymes among others. Majority (88.6%) of the upregulated genes were found to be involved in hypoxia inducible pathways for activation of NFkβ and inflammation, apoptosis, Toll-like receptor pathway and PPARγ. Bicaudal homologous 2 Drosophila gene (BICD2) associated with spinal and lower extremity muscle atrophy was also upregulated in pansteatitis while Sphingosine -1-phosphate phosphatase 2 (SGPP2) involved in Sphingosine -1- phosphate metabolism was downregulated. Futhermore, Doublesex-mab-related transcription factor 1 (DMRT1) responsible for sex gonad development and germ cell differentiation was also downregulated. Thus, from the present study, based on differentially expressed genes in pansteatitis, affected Nile crocodiles might have died partly due to their inability to utilize stored triglycerides as a result of inflammation induced insulin resistance, leading to starvation in the midst of plenty. Affected animals may have also suffered muscular atrophy of the lower extremities and poor fertility.


An automated approach to salt selection for new unique trazodone salts.
The purpose of this study was to establish an automated approach to salt selection and to search for unique trazodone salts for new applications. Automated procedures were developed on a Biomek 2000 automation workstation with stacker and plate reader capabilities. Trazodone was dispensed into 96-well plates, and an automated method was set up to form 104 trazodone salts. Salts were observed under a polarized light microscope to determine crystallinity. After stepwise eliminations, the remaining salts were scaled-up and subjected to differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), hygroscopic, pH-solubility, density, surface area, and particle size analyses. Oils formed in several cases resulting in preliminary elimination of mesyl and esyl salts and four crystallizing solvents. Crystallinity was observed in 34 of 44 scaled-up trazodone salts. PXRD, DSC, and hygroscopic analyses indicated a number of new salts that were comparable in physicochemical parameters to the marketed HCl salt. Among them, the tosylate salt showed uniqueness for new applications. Automated procedures can be developed to increase the efficiency of pharmaceutical salt selection. The new tosylate salt gave a unique pH-solubility profile with low solubility over the entire pH range making it a potential candidate for a suspension or prolonged action formulation.


[Autonomic control and functional condition of suprasegmental structures of the brain in patients with heart rhythm disorders and vasculo-autonomic dystonia].
A study was made by the method of combination of electroencephalography (EEG) and variational pulsimetry in 157 patients to determine the background vegetative tone and that very tone during conducting functional tests aimed at activating of sympathetic and parasympathetic portions of the nervous system. Criteria have been established characterizing the vegetative tone. Particular features are described of changes in the power of the EEG wave spectra while conducting tests in those groups being different in their baseline vegetative tone. The percentage is estimated of the incidence rate of the cardiac rhythm disturbances in those groups being different in their vegetative tone.


Outcomes of a Series of Patients with Post-Prostatectomy Incontinence Treated with an Adjustable Transobturator Male System or Artificial Urinary Sphincter.
A prospective evaluation of outcomes in a series of patients with post-prostatectomy incontinence (PPI) treated with two different devices is presented. Consecutive patients with PPI underwent interventions with an adjustable transobturator male system (ATOMS) or artificial urinary sphincter (AUS). Decisions were based on patient preference after physician counselling. Patient characteristics and operative and postoperative parameters including dryness, satisfaction, complications, revision and device durability were evaluated. One hundred twenty-nine patients were included: 102 (79.1%) received ATOMS and 27 (20.9%) AUS. Mean follow-up was 34.9 ± 15.9 months. No difference was observed between patient age (p = 0.56), ASA score (p = 0.13), Charlson index (p = 0.57) and radiation (p = 0.3). BMI was higher for AUS (27.1 vs. 29.7; p = 0.003) and also baseline incontinence severity (7.9% mild, 44.1% moderate and 48% severe for ATOMS vs. 11.1% moderate and 88.9% severe for AUS; p = 0.0007). Differential pad test was higher for AUS (- 470 vs. - 1000 ml; p < 0.0001) and so was ICIQ-SF (15.62 vs. 18.3; p < 0.001), but total dryness (76.5 vs. 66.7%; p = 0.33), social continence (90.2 vs. 85.2%; p = 0.49) and satisfaction (92.2 vs. 88.9%; p = 0.69) were equivalent. The postoperative complication rate was similar (22.6 vs. 29.6%; p = 0.4). The surgical revision rate was higher for AUS (6.9 vs. 22.2%; p = 0.029) and also the explant rate but did not reach statistical significance (4.9 vs. 14.8%; p = 0.09). Time to explant was shorter for AUS (log-rank p = 0.021). Regression analysis revealed radiation (p = 0.003) and incontinence severity (p = 0.029) predict total dryness, while complications (p < 0.005) and type of device (p = 0.039) independently predict surgical revision. Both ATOMS and AUS are effective devices. Pad test change for AUS exceeds that of ATOMS. The revision rate is higher for AUS, and durability is superior for ATOMS. The satisfaction rate is equivalent. Larger series and longer follow-up are needed to compare both devices more appropriately. According to our experience, the AUS is not the only gold standard for PPI.


High impact of a national psoriasis telementoring clinic on medical practices for patients in underserved areas.
Argentina is a large country in which important asymmetries exist in the knowledge and management of psoriasis. For this reason, in 2015 we launched Project ECHO Psoriasis, a telementoring strategy for dermatologists aimed at providing best medical practices in this population. The main objective of this study was to explore the reasons why the physicians participating in Project ECHO Psoriasis Argentina sought remote assistance. Cross-sectional study of the consultations made by dermatologists to the panel of experts. 213 consultations, which involved 158 patients in 60 teleclinics, were analyzed. The most frequent reasons for consultation were to implement changes in ongoing treatment, to support the treating physician approach to the patient, and to choose a de novo treatment, which were observed in 63 (39.9%), 47 (29.7%) and 46 (29.1%) consultations, respectively. The experts suggested modifying the approach to the patients in two thirds of the consultations (69.6%; 95% CI 61.8-76.7). Complete and partial compliance with the suggestions were observed in 66.4% (95% CI 56.7-75.1) and in 4.5% (95% CI 1.5-10.3), respectively. The main barriers identified were adherence by the patients and health services access issues. Telementoring for psoriasis is useful in reducing asymmetries in knowledge between dermatologists and ensuring access to the best clinical practices.


CAND1-dependent control of cullin 1-RING Ub ligases is essential for adipogenesis.
Cullin-RING ubiquitin (Ub) ligases (CRLs) are responsible for ubiquitinylation of approximately 20% of all proteins degraded by the Ub proteasome system (UPS). CRLs are regulated by the COP9 signalosome (CSN) and by Cullin-associated Nedd8-dissociated protein 1 (CAND1). The CSN is responsible for removal of Nedd8 from cullins inactivating CRLs. CAND1 modulates the assembly of F-box proteins into cullin 1-RING Ub ligases (CRL1s). We show that CAND1 preferentially blocks the integration of Skp2 into CRL1s. Suppression of CAND1 expression in HeLa cells leads to an increase of the Skp2 assembly into CRL1s and to significant reduction of the cyclin-dependent kinase (CDK) inhibitor p27. In contrary, CAND1 overexpression causes elevation of p27. The observed CAND1-dependent effects and CAND1 expression are independent of the CSN as demonstrated in CSN1 knockdown cells. Increase of p27 is a hallmark of preadipocyte differentiation to adipocytes (adipogenesis). We demonstrate that the accumulation of p27 is associated with an increase of CAND1 and a decrease of Skp2 during adipogenesis of human LiSa-2 preadipocytes. CAND1 knockdown reduces p27 and blocks adipogenesis. Due to the impact of CAND1 on Skp2 control, CAND1 could represent an important effector molecule in adipogenesis, but also in cancer development.


Malpractice insurance rates reach boiling point. Physicians burned by lawyers, lawsuits and jury awards.
Costs of medical malpractice insurance are soaring. Major insurers are refusing to write policies. And doctors are struggling to pay their premiums. Find out what's behind the insurance crisis.


Evaluation of transcatheter arterial embolization therapy on hepatocellular carcinomas using contrast-enhanced harmonic power Doppler sonography: comparison with CT, power Doppler sonography, and dynamic MRI.
The aim of this study was to assess and compare the sensitivity of power Doppler sonography, contrast-enhanced sonography, plain computed tomography (CT), and dynamic magnetic resonance imaging (MRI) for detecting hepatocellular carcinoma (HCC) nodules incompletely treated with transcatheter arterial embolization (TAE). A total of 63 unresectable HCC nodules were examined in this study. The HCCs were treated with TAE. All patients underwent plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI 1 week after TAE. The sensitivity of each modality to incompletely treated HCC nodules was compared. Detection of the residual viable HCC on angiography or tumor biopsy was regarded as the gold standard for the diagnosis of incomplete treatment. Twenty-four nodules (38%) were diagnosed as incompletely treated. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these incompletely treated nodules were 42% (10/24), 46% (11/24), 88% (21/24), and 79% (19/24), respectively. Eighty percent (19 nodules) of the 24 incompletely treated nodules were located within a depth of less than 8 cm. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these superficial incompletely treated nodules were 37% (7/19), 53% (10/19), 100% (19/19), and 74% (14/19), respectively. In contrast, the sensitivities of each modality to deeply located nodules were 60% (3/5), 20% (1/5), 40% (2/5), and 100% (5/5), respectively. Plain CT and power Doppler sonography had a low sensitivity to HCC nodules incompletely treated with TAE. Except for those that were deeply located, contrast-enhanced harmonic sonography showed the highest sensitivity in detecting incompletely treated HCC nodules.


Interaction between startle and voluntary reactions in humans.
The startle reaction (SR) is usually understood as an involuntary reaction to an unexpected sensory input. However, there is evidence that the mechanisms involved in the SR contribute also to the execution of actions that we consider voluntary. We need to exert a fine control of the motor output, which usually involves inhibition of the reflex reaction but it may also imply letting the SR manifest, shaped in accordance with our willed actions. The latter occurs mainly with relatively simple ballistic movements but it has also been shown to occur in complex movements. In this review, we describe arguments published in the literature in favour of the contribution of subcortical motor tracts involved in the generation of the SR to the execution of voluntary movements. Some of these studies have brought insight on the mechanisms accounting for motor preparation and execution of voluntary movements.


Do hearing loss interventions prevent dementia?
Hearing loss has been identified as a potentially modifiable risk for dementia. This discussion paper reviews studies examining the impact of hearing loss interventions on cognitive decline and incident cognitive impairment, identified the challenges for research on the cognitive impacts of hearing interventions, and the likely benefits of hearing interventions for healthy aging and mental well-being.


Fast signaling by glucocorticoids shapes neural representations of behaviors.
Glucocorticoids are stress hormones that play central roles in the immediate and slower adaptive responses of the brain and body to new behavioral experience. The exact mechanisms by which the rapid and slow processes underlying glucocorticoid mnemonic effects unfold are under intensive scrutiny. It is possible that glucocorticoids rapidly modify memory representations in the brain by interfering with synaptic functions between inhibitory and excitatory neurons in a timing and context dependent manner. In particular, activity-dependent trans-synaptic messengers appear to have all the necessary attributes to engage in the rapid signaling by glucocorticoids and regulate the brain and behaviors. Novel frameworks for the treatment of stress-related disorders could emerge from a better characterization of the dynamic interplay between the rapid and slow signaling components by glucocorticoids on large-scale brain networks. Here I present some of the exact factors that could help reach this objective.


CaMKII: new tricks for an old dog.
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a pivotal signaling molecule in both the brain and the heart. In this issue of Cell, Erickson et al. (2008) demonstrate a mechanism for CaMKII activation by reactive oxygen species that provides a direct link between kinase activation and cardiac dysfunction.


Platinum-Catalyzed Cascade Rearrangement Reaction of 1,5-Diynyl Esters: Unusual Regioselective 1,5-Hydride Migration.
A highly regioselective sequential 1,3-acyloxy migration/pentannulation/1,5-hydride migration reaction is disclosed which provides an efficient access to (E)-2-vinyl-3-oxo-1-methyleneindenes under neutral and mild reaction conditions. The migrated hydrogen atom was derived from an unactivated alkyl group, and the long-range 1,5-H shift was confirmed through related deuterium experiments.


Correction: Predictors of death including quality of positive pressure ventilation during newborn resuscitation and the relationship to outcome at seven days in a rural Tanzanian hospital.
[This corrects the article DOI: 10.1371/journal.pone.0202641.].


A physiochemical study of azo dyes: DFT based ESIPT process.
Azo linked dye derivatives were synthesized and characterized by NMR, mass and elemental analysis. An excited state intramolecular proton transfer (ESIPT) in hydroxy Schiff base has been analyzed, and found that two distinct ground state isomers of I and II are responsible for the observed dual emission. DFT calculation on energy, dipole moment, charge distribution of the rotamers in the ground and excited states support the ESIPT process. PES calculation indicates that the energy barrier for the interconversion of two rotamers is too high in the excited state than the ground state. By varying the addition of base concentration to hydroxy Schiff base, two isobestic points were found which confirm the equilibrium among the trans enol form, anion and the cis enol form. Fluorescence quenching with metal ions reveal that hydroxy Schiff base can be used as a new fluorescence sensor to detect the Cu(2+) ion.


Minimally Invasive Parathyroidectomy Versus Bilateral Neck Exploration for Primary Hyperparathyroidism.
Primary hyperparathyroidism is a disease that is caused by excess parathyroid hormone (PTH) secretion from 1 or more of the parathyroid glands. Surgery is the only cure. Traditional surgical management consists of a 4-gland cervical exploration. Development of imaging specific to identification of parathyroid glands and application of the rapid PTH assay to operative management have made more minimal exploration possible. There are distinct advantages and disadvantages of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE). The advantages of MIP seem to outweigh those of BNE, and MIP has replaced BNE as the operation of choice by many surgeons.


Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.
Severe graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells. Mesenchymal stem cells modulate immune responses in vitro and in vivo. We aimed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation. Patients with steroid-resistant, severe, acute GVHD were treated with mesenchymal stem cells, derived with the European Group for Blood and Marrow Transplantation ex-vivo expansion procedure, in a multicentre, phase II experimental study. We recorded response, transplantation-related deaths, and other adverse events for up to 60 months' follow-up from infusion of the cells. Between October, 2001, and January, 2007, 55 patients were treated. The median dose of bone-marrow derived mesenchymal stem cells was 1.4x10(6) (min-max range 0.4-9x10(6)) cells per kg bodyweight. 27 patients received one dose, 22 received two doses, and six three to five doses of cells obtained from HLA-identical sibling donors (n=5), haploidentical donors (n=18), and third-party HLA-mismatched donors (n=69). 30 patients had a complete response and nine showed improvement. No patients had side-effects during or immediately after infusions of mesenchymal stem cells. Response rate was not related to donor HLA-match. Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin. Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response (11 [37%] of 30 vs 18 [72%] of 25; p=0.002) and higher overall survival 2 years after haemopoietic-stem-cell transplantation (16 [53%] of 30 vs four [16%] of 25; p=0.018). Infusion of mesenchymal stem cells expanded in vitro, irrespective of the donor, might be an effective therapy for patients with steroid-resistant, acute GVHD.


Characterization and comparison of lipid and PUFA production by native thraustochytrid strains using complex carbon sources.
The thraustochytrid are marine heterotrophic protists that are widely distributed in the marine world. They are characterized by producing and accumulating great amount of lipids in their cells, especially long chain polyunsaturated fatty acids (LC-PUFA), highlighting the docosahexaenoic acid (DHA, 22:6, n-3), eicosapentaenoic acid (EPA, 20:5, n-3) and arachidonic acid (ARA, 20:4, n-6), as well as pigments of interest for human health and animal nutrition, such as carotenoids. Therefore, the objective of this study was to isolate and characterize three natives isolated of thraustochytrids and assess the potential of the by-products of the manufacture of beer (RB) and protein extraction of Lupine flour (RL) as complex carbon sources to produce biomass, lipid and polyunsaturated fatty acids. Three native strains of thraustochytrid (AS5-B2, IQ81 y VAL-B1), isolated from Chilean coastal waters were morphologically and genetically identified as thraustochytrid. For the determination of biomass production cultures were quantified by gravimetry and the fatty acids quantification and identification were carried out by gas chromatography (GC-FID). Our results show that the culture with any sources of complex carbon used, increased significantly the production of both biomass and total lipids in the strains IQ81 and VAL-B1, compared to glucose as pure carbon source. On the other hand, strain AS5-B2 showed a decrease in the total production of lipids in RB compared to the pure carbon source. For the production of fatty acids, the strains IQ81 and VAL-B1 showed a significant increase in DHA when growing in RB. In conclusion strains IQ81 and VAL-B1 can be used to biotransform industrial waste, such as RB and RL, into a more valuable product such as DHA, EPA, ARA and lipids.


Further definition of lipid-lipoprotein abnormalities in children with various degrees of chronic renal insufficiency.
We characterized the lipid-lipoprotein abnormalities encountered in a series of 45 nonnephrotic uremic children with various degrees of chronic renal insufficiency. A mild hypertriglyceridemia associated with decreased serum high-density lipoprotein cholesterol levels was confirmed. The correlation between high-density lipoprotein cholesterol and creatinine clearance showed a power behavior with a marked decrease in high-density lipoprotein cholesterol below a creatinine clearance value of 40 ml/min/1.73 m2. A number of uremic children accumulate an abnormal population of very low-density lipoprotein particles in their plasma. On agarose gel electrophoresis these particles migrate as a slow moving pre-beta band and are clearly distinguished from the regular fast moving pre-beta very low-density lipoprotein band. This electrophoretic phenomenon has been called double pre-beta lipoproteinemia. The prevalence of double pre-beta lipoproteinemia increased significantly with the degree of impairment of renal function, reaching highest figures in patients on hemodialysis. Accordingly, the very low-density lipoprotein cholesterol/triglyceride ratio also was significantly increased. The double pre-beta lipoproteinemia phenomenon was not detected in any of the control, nonuremic subjects. The clinical importance of double pre-beta lipoproteinemia in uremic plasma is related to its possible atherogenic role.


Sonolysis of 4-chlorophenol in aqueous solution: effects of substrate concentration, aqueous temperature and ultrasonic frequency.
The sonolysis of 4-chlorophenol (4-CP) in O2-saturated aqueous solutions is investigated for a variety of operating conditions with the loss of 4-CP from solution following pseudo-first-order reaction kinetics. Hydroquinone (HQ) and 4-chlorocatechol (4-CC) are the predominant intermediates which are degraded on extended ultrasonic irradiation. The final products are identified as Cl-, CO2, CO, and HCO2H. The rate of 4-CP degradation is dependent on the initial 4-CP concentration with an essentially linear increase in degradation rate at low initial 4-CP concentrations but with a plateauing in the rate increase observed at high reactant concentrations. The results obtained indicate that degradation takes place in the solution bulk at low reactant concentrations while at higher concentrations degradation occurs predominantly at the gas bubble-liquid interface. The aqueous temperature has a significant effect on the reaction rate. At low frequency (20 kHz) a lower liquid temperature favours the sonochemical degradation of 4-CP while at high frequency (500 kHz) the rate of 4-CP degradation is minimally perturbed with a slight optimum at around 40 degrees C. The rate of 4-CP degradation is frequency dependent with maximum rate of degradation occurring (of the frequencies studied) at 200 kHz.


Task coordination between and within sensory modalities: effects on distraction.
Load theory predictions for the effects of task coordination between and within sensory modalities (vision and hearing or vision only) on the level of distraction were tested. Response competition effects in a visual flanker task when it was coordinated with an auditory discrimination task (between-modality conditions) or a visual discrimination task (within-modality conditions) were compared with single-task conditions. In the between-modality conditions, response competition effects were greater in the two- (vs. single-) task conditions irrespective of the level of discrimination task difficulty. In the within-modality conditions, response competition effects were greater in the two-task (vs. single-task) conditions only when these involved a more difficult visual discrimination task. The results provided support for the load theory prediction that executive control load leads to greater distractor interference while highlighting the effects of task modality.


Ocular melanoma metastasis to the cervical spine.
Ocular melanoma is a rare type of malignant melanoma. Melanoma metastatic to the spine typically arises within the vertebral column, presents with back pain, and has a poor prognosis. We present a patient with a unique disease course: ocular melanoma metastasis occurred after an extended latency period of 14 years, attained a large size within the spinal intradural space, presented with severe neurological deficits without additional central nervous system disease, and the tumor was amenable to surgical intervention. We also review the literature on melanoma spine metastasis.


Direct evidence that 17 alpha,20 beta-dihydroxy-4-pregnen-3-one functions as a goldfish primer pheromone: preovulatory release is closely associated with male endocrine responses.
This study directly tested the hypothesis that 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) is a goldfish preovulatory pheromone (pheromone released at peak levels during oocyte final maturation) which increases blood gonadotropin (GtH) and milt volume in males. During spontaneous ovulation, GtH and 17,20 beta-P in female blood and 17,20 beta-P released to the water increased dramatically 7-10 hr prior to ovulation, peaked 1-4 hr prior to ovulation, and then rapidly declined. Males held with these females, or exposed to their odors, had increased GtH levels and milt volumes at approximately the time when increased 17,20 beta-P release by ovulatory females commenced. Although these findings strongly support the hypothesis that 17,20 beta-P is a preovulatory female sex pheromone in goldfish which stimulates male GtH levels and milt production prior to spawning, the milt increases occurred earlier than predicted, suggesting either that preovulatory 17,20 beta-P release begins earlier than the data indicate or that other steroids known to have pheromonal activity are released before 17,20 beta-P.


Avian retroviral recombinant expressing foreign envelope delays tumour formation of ASV-A-induced sarcoma.
An avian recombinant retrovirus expressing subgroup A envelope glycoprotein antigenicity, RAV-0-A1, significantly delayed sarcoma induction in chickens after challenge with ASV-A. When tumours were formed, significantly smaller tumours resulted. The mechanism of protection does not appear to be interference mediated, since virus was not detected in the chickens. Protection was correlated with both neutralizing and complement-dependent cytotoxic antibodies (CDCA).


The evaluation of comprehensive cancer control efforts: useful techniques and unique requirements.
This article discusses evaluation of comprehensive cancer control efforts as developed in the United States by involved partners at all levels -- community, regional, state, tribal, territorial, and national. Evaluation of comprehensive cancer control can concern the evaluation of a program, a plan or activities from a plan. In its development, it is grounded in both theory and practice, and the results are used in program development and implementation to document activities, inform decision making, and demonstrate accountability. Various types of evaluation have been shown to be important. Challenges to evaluating comprehensive cancer control include incorporating and working with a broad group of stakeholders; developing an agreed upon plan and evaluation, ensuring the necessary infrastructure for overseeing, facilitating, and disseminating results of evaluations; conceptualizing and communicating desired changes; and potentially implementing (and evaluating) programs at the community, regional, tribal, territorial, state, or national level. Using the CDC Framework for Evaluation, selected examples of state program evaluations are presented. These examples show the use of both process and outcome evaluations to illustrate programmatic improvement and the accomplishment of proposed objectives. As evaluation of comprehensive cancer control continues to be developed and results communicated, our ability to evaluate comprehensive cancer control programs increases and the growth of comprehensive cancer control efforts are encouraged.


The level of blood thrombogenicity was not elevated in stable patients with disrupted coronary plaque.
Although extremely high blood thrombogenicity has been reported in patients with acute myocardial infarction, it has not been clarified if the increased blood thrombogenicity is a cause of acute myocardial infarction or a mere result induced by thrombus formation at the disrupted plaque. Therefore, we examined if blood thrombogenicity is extremely increased as in acute myocardial infarction patients when disrupted plaque is present in patients with stable coronary artery disease. Consecutive patients (n=38) with stable coronary artery disease who received angioscopic examination were included. Patients were divided into two groups according to presence or absence of disrupted plaque that accompanied thrombus. Blood thrombogenicity was evaluated by blood vulnerability index and compared between the patients with and without disrupted plaque. Among 38 study patients, 16 had disrupted plaque and 22 did not. Blood vulnerability index was not different between the patients with and without disrupted plaque (2395 ± 612 vs. 3013 ± 1476, p=0.12). Multivariate analysis revealed no significant association between blood vulnerability index and the presence of disrupted plaque. The presence of disrupted plaque, in comparison with its absence, was not associated with higher blood thrombogenicity evaluated by blood vulnerability index.


Characteristics of obstructive and central sleep apnea in the elderly: an interim report.
Home sleep recordings were done on 358 randomly selected elderly volunteers (mean age 72.4). When men and women were combined, 62 (17%) had predominantly obstructive sleep apnea, 21 (6%) had predominantly central sleep apnea, and 3 (1%) had mixed sleep apnea. Although the prevalence of sleep apnea in women does increase after menopause, sleep apnea was still significantly more common in older men (31%) than in older women (19%). There were no significant differences in age among groups with different types of apnea. There was a significant correlation of age with increasing apnea index within the obstructive sleep apnea group. Elderly volunteers with central sleep apnea had more midsleep awakenings. Elderly volunteers with obstructive sleep apnea had longer apneas. Unlike previous studies, we found many similarities and only modest differences in the presentations of central and obstructive sleep apnea.


Induction of a heat shock gene (hsp70) in rabbit retinal ganglion cells detected by in situ hybridization with plastic-embedded tissue.
Elevation of body temperature by 2-3 degrees C induces a 2.7 kilobase hsp70 mRNA species in the rabbit retina within 1 hr. In situ hybridization with thin sections derived from plastic-embedded tissue permitted a higher level of resolution of retinal cell types compared to procedures which involved the use of frozen tissue sections. A prominent induction of hsp70 mRNA in retinal ganglion cells was observed when an hsp70 riboprobe was utilized for in situ hybridization. These results indicate that this neuronal cell type responds rapidly to fever-like body temperatures by inducing one of the major heat shock genes.


Controlled Photoinduced Electron Transfer from InP/ZnS Quantum Dots through Cu Doping: A New Prototype for the Visible-Light Photocatalytic Hydrogen Evolution Reaction.
Photoexcited electron extraction from semiconductors can be useful for converting solar energy into useful forms of energy. Although InP quantum dots (QDs) are considered alternative materials for solar energy conversion, the inherent instability of bare InP QDs demands the use of passivation layers such as ZnS for practical applications, which impedes carrier extraction from the QDs. Here, we demonstrate that Cu-doped InP/ZnS (InP/Cu:ZnS) QDs improve the electron transfer ability due to hole capture by Cu dopants. Steady-state and time-resolved photoluminescence studies confirmed that electrons were effectively transferred from the InP/Cu:ZnS QDs to a benzoquinone acceptor by retarding the electron-hole recombination within the QD. We evaluated the photocatalytic H2 evolution performance of InP/Cu:ZnS QDs under visible light, which showed outstanding photocatalytic H2 evolution activity and stability under visible light illumination. The photocatalytic activity was preserved even in the absence of a cocatalyst.


Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications.
Certain abnormalities of autonomic function in the setting of structural cardiovascular disease have been associated with an adverse prognosis. Various markers of autonomic activity have received increased attention as methods for identifying patients at risk for sudden death. Both the sympathetic and the parasympathetic limbs can be characterized by tonic levels of activity, which are modulated by, and respond reflexively to, physiological changes. Heart rate provides an index of the net effects of autonomic tone on the sinus node, and carries prognostic significance. Heart rate variability, though related to heart rate, assesses modulation of autonomic control of heart rate and carries additional prognostic information, which in some cases is more powerful than heart rate alone. Heart rate recovery after exercise represents the changes in autonomic tone that occur immediately after cessation of exercise. This index has also been shown to have prognostic significance. Autonomic evaluation during exercise and recovery may be important prognostically, because these are high-risk periods for sudden death, and the autonomic changes that occur with exercise could modulate this high risk. These markers provide related, but not redundant information about different aspects of autonomic effects on the sinus node.