Agroinfiltration as an Effective and Scalable Strategy of Gene Delivery for Production of Pharmaceutical Proteins.
Current human biologics are most commonly produced by mammalian cell culture-based fermentation technologies. However, its limited scalability and high cost prevent this platform from meeting the ever increasing global demand. Plants offer a novel alternative system for the production of pharmaceutical proteins that is more scalable, cost-effective, and safer than current expression paradigms. The recent development of deconstructed virus-based vectors has allowed rapid and high-level transient expression of recombinant proteins, and in turn, provided a preferred plant based production platform. One of the remaining challenges for the commercial application of this platform was the lack of a scalable technology to deliver the transgene into plant cells. Therefore, this review focuses on the development of an effective and scalable technology for gene delivery in plants. Direct and indirect gene delivery strategies for plant cells are first presented, and the two major gene delivery technologies based on agroinfiltration are subsequently discussed. Furthermore, the advantages of syringe and vacuum infiltration as gene delivery methodologies are extensively discussed, in context of their applications and scalability for commercial production of human pharmaceutical proteins in plants. The important steps and critical parameters for the successful implementation of these strategies are also detailed in the review. Overall, agroinfiltration based on syringe and vacuum infiltration provides an efficient, robust and scalable gene-delivery technology for the transient expression of recombinant proteins in plants. The development of this technology will greatly facilitate the realization of plant transient expression systems as a premier platform for commercial production of pharmaceutical proteins.


Micro-shear bond strength of different surface treatments on a polymer infiltrated ceramic network.
Background: Polymer infiltrated ceramic networks, or hybrid ceramics, are a combination of infiltrating polymerizable organic monomers into a pre-sintered porous ceramic matrix. In addition to having good mechanical properties, the polymer infiltrated ceramic network must comply with the possibility of adequate bonding to the resinous cement. The surface conditioning of this hybrid material must be carefully considered due to its organic composition and ceramic network. The purpose of this research is to evaluate the effect of hydrofluoric acid and a self-etching ceramic primer, under two different application times, on the bond strength of a polymer infiltrated ceramic network. Methods: Blocks of a polymer infiltrated ceramic network were cut to obtain sheets, and these were randomized into five groups. For the group termed AAS, airborne-particle abrasion with Al 2O 3 (aluminum oxide) of 50µm was used. For groups HF2 and HF6, hydrofluoric acid was used for 20 and 60 seconds respectively, and for the groups MB2 and MB6, a self-etch ceramic primer was applied for 20 and 60 seconds respectively. A silane was applied to the groups AAS, HF2, and HF6 after the treatment. After 24-hour storage in distilled water, a micro-shear bond strength test was performed using a universal mechanical testing machine. All samples were evaluated in a stereomicroscope at 40x and 50x to determine the type of failure. Results: The highest and lowest values of bond strength were reported by groups MB6 and AAS, respectively. Groups HF2, HF6, MB6, and MB2 did not report statistically significant differences. The predominant failure pattern was a mixed failure. Conclusions: With the limitations of the present investigation, the treatments of self-etching ceramic primer and hydrofluoric acid followed by silane were reported to be statistically equal at 20 and 60 seconds.


The molecular genetics of schizophrenia: new findings promise new insights.
The high heritability of schizophrenia has stimulated much work aimed at identifying susceptibility genes using positional genetics. However, difficulties in obtaining clear replicated linkages have led to the scepticism that such approaches would ever be successful. Fortunately, there are now signs of real progress. Several strong and well-established linkages have emerged. Three of the best-supported regions are 6p24-22, 1q21-22 and 13q32-34. In these cases, single studies achieved genome-wide significance at P<0.05 and suggestive positive findings have also been reported in other samples. The other promising regions include 8p21-22, 6q21-25, 22q11-12, 5q21-q33, 10p15-p11 and 1q42. The study of chromosomal abnormalities in schizophrenia has also added to the evidence for susceptibility loci at 22q11 and 1q42. Recently, evidence implicating individual genes within some of the linked regions has been reported and more importantly replicated. The weight of evidence now favours NRG1 and DTNBP1 as susceptibility loci, though work remains before we understand precisely how genetic variation at each locus confers susceptibility and protection. The evidence for catechol-O-methyl transferase, RGS4 and G72 is promising but not yet persuasive. While further replications remain the top priority, the respective contributions of each gene, relationships with aspects of the phenotype, the possibility of epistatic interactions between genes and functional interactions between the gene products will all need investigation. The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that it is now poised to deliver crucial insights into the nature of schizophrenia.


Long distance ski racing is associated with lower long-term incidence of depression in a population based, large-scale study.
Physical activity has been proposed to be beneficial for prevention of depression, although the importance of exercise intensity, sex-specific mechanisms, and duration of the effects need to be clarified. Using an observational study design, following 395,369 individuals up to 21 years we studied whether participation in an ultralong-distance cross-country ski race was associated with lower risk of developing depression. Skiers (participants in the race) and matched non-skiers from the general population (non-participants in the race) were studied after participation (same year for non-participation) in the race using the Swedish population and patient registries. The risk of depression in skiers (n = 197,685, median age 36 years, 38% women) was significantly lower, to nearly half of that in non-skiers (adjusted hazard ratio, HR 0.53) over the follow-up period. Further, a higher fitness level (measured as the finishing time to complete the race, a proxy for higher exercise dose) was associated with lower incidence of depression in men (adjusted HR 0.65), but not in women. Our results support the recommendations of engaging in physical activity as a preventive strategy decreasing the risk for depression in both men and women. Furthermore, the exercise could reduce risk for depression in a dose-dependent matter, in particular in males.


A multi-ingredient containing carbohydrate, proteins L-glutamine and L-carnitine attenuates fatigue perception with no effect on performance, muscle damage or immunity in soccer players.
We investigated the effects of ingesting a multi-ingredient (53 g carbohydrate, 14.5 g whey protein, 5 g glutamine, 1.5 g L-carnitine-L-tartrate) supplement, carbohydrate only, or placebo on intermittent performance, perception of fatigue, immunity, and functional and metabolic markers of recovery. Sixteen amateur soccer players ingested their respective treatments before, during and after performing a 90-min intermittent repeated sprint test. Primary outcomes included time for a 90-min intermittent repeated sprint test (IRS) followed by eleven 15 m sprints. Measurements included creatine kinase, myoglobin, interleukine-6, Neutrophil; Lymphocytes and Monocyte before (pre), immediately after (post), 1 h and 24 h after exercise testing period. Overall, time for the IRS and 15 m sprints was not different between treatments. However, the perception of fatigue was attenuated (P<0.001) for the multi-ingredient (15.9±1.4) vs. placebo (17.8±1.4) but not for the carbohydrate (17.0±1.9) condition. Several changes in immune/inflammatory indices were noted as creatine kinase peaked at 24 h while Interleukin-6 and myoglobin increased both immediately after and at 1 h compared with baseline (P<0.05) for all three conditions. However, Myoglobin (P<0.05) was lower 1 h post-exercise for the multi-ingredient (241.8±142.6 ng·ml(-1)) and CHO (265.4±187.8 ng·ml(-1)) vs. placebo (518.6±255.2 ng·ml(-1)). Carbohydrate also elicited lower neutrophil concentrations vs. multi-ingredient (3.9±1.5 10(9)/L vs. 4.9±1.8 10(9)/L, P = 0.016) and a reduced (P<0.05) monocytes count (0.36±0.09 10(9)/L) compared to both multi-ingredient (0.42±0.09 10(9)/L) and placebo (0.42±0.12 10(9)/L). In conclusion, multi-ingredient and carbohydrate supplements did not improve intermittent performance, inflammatory or immune function. However, both treatments did attenuate serum myoglobin, while only carbohydrate blunted post-exercise leukocytosis.


Volatile Substances Produced by Fusarium oxysporum from Coffee Rhizosphere and Other Microbes affect Meloidogyne incognita and Arthrobotrys conoides.
Microorganisms produce volatile organic compounds (VOCs) which mediate interactions with other organisms and may be the basis for the development of new methods to control plant-parasitic nematodes that damage coffee plants. In the present work, 35 fungal isolates were isolated from coffee plant rhizosphere, Meloidogyne exigua eggs and egg masses. Most of the fungal isolates belonged to the genus Fusarium and presented in vitro antagonism classified as mutual exclusion and parasitism against the nematode-predator fungus Arthrobotrys conoides (isolated from coffee roots). These results and the stronger activity of VOCs against this fungus by 12 endophytic bacteria may account for the failure of A. conoides to reduce plant-parasitic nematodes in coffee fields. VOCs from 13 fungal isolates caused more than 40% immobility to Meloidogyne incognita second stage juveniles (J2), and those of three isolates (two Fusarium oxysporum isolates and an F. solani isolate) also led to 88-96% J2 mortality. M. incognita J2 infectivity decreased as a function of increased exposure time to F. oxysporum isolate 21 VOCs. Gas chromatography-mass spectrometry (GC-MS) analysis lead to the detection of 38 VOCs produced by F. oxysporum is. 21 culture. Only five were present in amounts above 1% of the total: dioctyl disulfide (it may also be 2-propyldecan-1-ol or 1-(2-hydroxyethoxy) tridecane); caryophyllene; 4-methyl-2,6-di-tert-butylphenol; and acoradiene. One of them was not identified. Volatiles toxic to nematodes make a difference among interacting microorganisms in coffee rhizosphere defining an additional attribute of a biocontrol agent against plant-parasitic nematodes.


Seasonal variation of relapse rate in multiple sclerosis is latitude dependent.
Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude. The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak. A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29-53.71, p = 0.028). We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere.


Efficacy of Tranexamic Acid for Hemostasis in Patients Undergoing High Tibial Osteotomy.
Extensive bone bleeding and an uncomfortable hematoma can develop due to the opening gap and space during a medial open high tibial osteotomy (HTO). Tranexamic acid (TXA) has been used in various orthopaedic surgeries to reduce bleeding and wound complications. However, no study has investigated the effect of TXA during HTO. Therefore, the purpose of this study is to evaluate the efficacy of TXA in reducing postoperative blood loss in patients undergoing HTO. The hypothesis is that topical TXA administration will reduce postoperative bleeding in patients undergoing medial opening HTO. Topical TXA (2 g in 20 mL saline) was administered at the osteotomy site in patients (n = 15) who underwent medial open HTO from November 2015 to March 2016. Patients (n = 15) who underwent medial open wedge HTO by the same surgeon from October 2014 to October 2015 were enrolled as a control group for comparison. Drainage volumes on postoperative days (PODs) 1, 2, and 3 as well as hemoglobin (Hb) level on PODs 1, 6, and 13 were measured and compared. Mean total postoperative drainage volume was 246 mL in the TXA group and 377 mL in the control group. Mean drainage volume on POD 1 was 138 mL in the TXA group and 277 mL in the control group (p < 0.05). No differences in drainage volume were detected between the groups on POD 2 or 3. Preoperative Hb levels were 13.0 g/dL in the TXA group and 12.9 g/dL in the control group, which decreased to 11.9 g/dL in the TXA group and 11.2 g/dL in the control group on POD 1. These postoperative Hb differences were significant (p < 0.05). Also, Hb levels were 11.7 and 12.0 g/dL in the TXA group and 11.4 and 11.6 g/dL in the control group on PODs 6 and 13, respectively (p > 0.05). An extensive hematoma requiring additional surgery developed in one case in the control group. No wound complications were detected in the TXA group. Topical TXA was effective for reducing postoperative bleeding after medial open HTO. The level of evidence of the study is Level 3.


Synthesis and characterization of calcium beta-diketonate complexes. X-ray crystal and molecular structures of: [{Ca(tmhd)2}2(18-crown-6)], [Ca(dpp)2(thf)2] and [Ca(dpp)2(triglyme)].
Reactions of 2,2,6,6-tetramethyl-3,5-heptanedione (Htmhd), 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (Hhfa) or 1,3-diphenyl-1,3-propanedione (Hdpp) with calcium methoxide in hexane or toluene afford the corresponding known oligomeric beta-diketonates: [Ca(3)(tmhd)(6)], [{Ca(hfa)(2)}(n)] and [{Ca(dpp)(2)}(n)]. The complexes react with tetrahydrofuran, 2,5,8,11-tetraoxadodecane (triglyme) or 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6) leading to the formation of the new mononuclear [Ca(dpp)(2)(thf)(2)], [Ca(dpp)(2)(triglyme)] and dinuclear [{Ca(dpp)(2)}(2)(18-crown-6)] and [{Ca(tmhd)(2)}(2)(18-crown-6)] adducts. The obtained complexes were characterized by elemental analyses, IR, (1)H and (13)C NMR spectroscopies; moreover, single crystal X-ray diffraction measurements were also carried out for: [{Ca(tmhd)(2)}(2)(18-crown-6)], [Ca(dpp)(2)(thf)(2)] and [Ca(dpp)(2)(triglyme)].


Dermoscopy combined with reflectance confocal microscopy as a noninvasive involvement for monitoring Cutaneous Rosai-Dorfman: A case report.
Cutaneous Rosai-Dorfman disease(CRDD) is an extremely rare entity and features histiocytic proliferation in the skin. Dermoscopy and reflectance confocal microscopy(RCM) reports on CRDD are rare. We reported a case of CRDD and summarized the dermoscopy(FotoFinder Medicare 800HD, FotoFinder-Systems GmbH, Birbach Germany) and RCM(VivaScope® 1500, V Caliber Imaging and Diagnostics) features of CRDD. The dermoscopic features of CRDD showed red-orange background with pale yellowish roundish areas similar to millet, surrounded by branched blood vessels. Sometimes the white structureless materials of CRDD could be observed by dermoscopy, which may be a hint of spontaneous regression. The RCM features of CRDD revealed dense highly refractile roundish or ovoid structures(inflammatory cells), and multiple larger structures with central low refraction and moderately refractive peripheral semicircle or circle(engulfed inflammatory cells), together with low refractive branched structures(blood vessels). Dermoscopic and RCM features of CRDD can help the dermatologists recognize and follow-up the disease in real time.


Composite measures for hospital quality using quality-adjusted life years.
Developing clinically meaningful summary measures of health-care quality is key to inferring quality of care. Current summary measures use a number of different approaches to weight their individual measures but rarely use weights based on clinical 'importance'. Such an approach would help to focus quality improvement efforts on areas likely to have the largest impact on health outcomes. Using coronary artery bypass graft (CABG) surgery as a case study, we weight and combine 11 process, complication, and survival measures to summarize differences in quality-adjusted life expectancy 1 year following surgery for a sample of hospitals. We use a fully Bayesian analysis to estimate 1-year survival outcomes using a hierarchical exponential survival model. We then estimate the expected utility of the year following surgery for each patient using complication probabilities fitted from hierarchical models and utility values from the literature. We estimate quality-adjusted life years (QALYs) for each hospital as the utility-weighted average 1-year survival probability and then estimate 'incremental QALYs' by taking the difference in QALYs for each hospital relative to a comparison group that reflects the average performance of all hospitals in the state. We illustrate our framework by estimating incremental QALYs for 14 hospitals performing CABG surgery in Massachusetts in 2003 and find that a composite measure based on QALYs can change the classification of quality outliers relative to conventional mortality measures.


Inhibitory Activity of Avicennia marina, a Medicinal Plant in Persian Folk Medicine, against HIV and HSV.
Avicennia marina (Avicenniaceae) is a species of mangrove tree used for treatment of small pox lesions in Persian folk medicine. The antiviral activity of methanol, ethanol, water, chloroform and n-hexane extracts was evaluated against HIV-1 and HSV. Methanol extract had the highest antiviral activity and the most polar fraction of this extract (fraction D) inhibited HSV with TI and SI values of 57.1 and 133; however, it showed mild activity against HIV with SI value of 6.25 (fraction 3). The anti-HSV activity of active fraction was confirmed using FLASH-PCR. Phytochemical investigation revealed that fraction D encompasses flavonoids compounds. The time-of-addition study demonstrated that fraction D disturbs viral replication after penetrating to the cell. A. marina was endowed with fragments by which found to be able to inhibit replication of HSV after entry but did not show significant potency against HIV-1. This promotes further investigation in anti-HSV drug discovery.


Intraspecific competition affects population size and resource allocation in an ant dispersing by colony fission.
Intraspecific competition is a pervasive phenomenon with important ecological and evolutionary consequences, yet its effect in natural populations remains controversial. Although numerous studies suggest that in many cases populations across all organisms are limited by density-dependent processes, this conclusion often relies on correlative data. Here, using an experimental approach, we examined the effect of intraspecific competition on population regulation of the ant Aphaenogaster senilis. In this species females are philopatric while males disperse by flying over relatively long distances. All colonies were removed from 15 experimental plots, except for one focal colony in each plot, while 15 other plots remained unmanipulated. After the first reproductive season, nest density in the experimental plots returned to a level nonsignificantly different from that in the control plots, which was not expected if the populations were indeed regulated by density-independent phenomena. In both the control plots and the experimental plots colonies remained overdispersed throughout the experiment, suggesting colony mutual exclusion. Nests outside the plots rapidly extended their foraging span, but we did not detect any significant inward migration into the experimental plots. Experimental reduction in density did not significantly affect the focal colonies' biomass, measured just before the first reproductive season. However, the ratio of males to workers-pupae biomasses was smaller in experimental plots, suggesting that colonies there had redirected part of the resources normally allocated to male production to the production instead of new workers. Microsatellite analysis indicated that, after the reproductive season, many colonies in the experimental plots were headed by a young queen that was the mother of the brood but not of the old workers, indicating that reduction in colony density stimulated fission of the remaining colonies. Finally, at the end of the experiment, 14 months after experimental reduction in density, colonies that derived from fission were smaller in the experimental than in the control plots, suggesting that the former had undergone fission at a smaller size than in control plots, which presumably allowed them to colonize the emptied areas. We conclude that colonies adjust resource allocation and colony fission to the degree of intraspecific competition.


Gradual Analytics of Starch-Interacting Proteins Revealed the Involvement of Starch-Phosphorylating Enzymes during Synthesis of Storage Starch in Potato (Solanum tuberosum L.) Tubers.
The complete mechanism behind starch regulation has not been fully characterized. However, significant progress can be achieved through proteomic approaches. In this work, we aimed to characterize the starch-interacting proteins in potato (Solanum tuberosum L. cv. Desiree) tubers under variable circumstances. Starch-interacting proteins were extracted from developing tubers of wild type and transgenic lines containing antisense inhibition of glucan phosphorylases. Further, proteins were separated by SDS-PAGE and characterized through mass spectrometry. Additionally, starch-interacting proteins were analyzed in potato tubers stored at different temperatures. Most of the proteins strongly interacting with the potato starch granules corresponded to proteins involved in starch metabolism. GWD and PWD, two dikinases associated with starch degradation, were consistently found bound to the starch granules. This indicates that their activity is not only restricted to degradation but is also essential during storage starch synthesis. We confirmed the presence of protease inhibitors interacting with the potato starch surface as previously revealed by other authors. Starch interacting protein profiles of transgenic tubers appeared differently from wild type when tubers were stored under different temperatures, indicating a differential expression in response to changing environmental conditions.


Comparative validity of the Shedler and Westen Assessment Procedure-200.
A predominant dimensional model of general personality structure is the five-factor model (FFM). Quite a number of alternative instruments have been developed to assess the domains of the FFM. The current study compares the validity of 2 alternative versions of the Shedler and Westen Assessment Procedure (SWAP-200) FFM scales, 1 that was developed on the basis of items identified by J. Shedler and D. Westen (2004) and 1 that used items identified by R. R. McCrae, C. E. Lokenhoff, and P. T. Costa (2005). The comparative validity of both measures was examined in a sample of persons who evidenced personality-related problems in living (N = 94). The McCrae et al. Neuroticism, Agreeableness, and Openness scales were superior to their respective Shedler and Westen scales. Both research teams developed comparably valid Extraversion and Conscientiousness scales. Implications of the results for future SWAP-200 research are discussed.


Dietary Green Pea Protects against DSS-Induced Colitis in Mice Challenged with High-Fat Diet.
Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2.5% DSS in drinking water for 7 days followed by a 7-day recovery period. GP supplementation ameliorated the disease activity index score in HFD-fed mice during the recovery stage, and reduced neutrophil infiltration, mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and inflammatory markers interleukin (IL)-6, cyclooxygenase-2 (COX-2), IL-17, interferon-γ (IFN-γ), and inducible nitric oxide synthase (iNOS) in HFD-fed mice. Further, GP supplementation increased mucin 2 content and mRNA expression of goblet cell differentiation markers including Trefoil factor 3 (Tff3), Krüppel-like factor 4 (Klf4), and SAM pointed domain ETS factor 1 (Spdef1) in HFD-fed mice. In addition, GP ameliorated endoplasmic reticulum (ER) stress as indicated by the reduced expression of Activating transcription factor-6 (ATF-6) protein and its target genes chaperone protein glucose-regulated protein 78 (Grp78), the CCAAT-enhancer-binding protein homologous protein (CHOP), the ER degradation-enhancing α-mannosidase-like 1 protein (Edem1), and the X-box binding protein 1 (Xbp1) in HFD-fed mice. In conclusion, GP supplementation ameliorated the severity of DSS-induced colitis in HFD-fed mice, which was associated with the suppression of inflammation, mucin depletion, and ER stress in the colon.


A Systematic Review on Cost-effectiveness Studies Evaluating Ovarian Cancer Early Detection and Prevention Strategies.
Ovarian cancer imposes a substantial health and economic burden. We systematically reviewed current health-economic evidence for ovarian cancer early detection or prevention strategies. Accordingly, we searched relevant databases for cost-effectiveness studies evaluating ovarian cancer early detection or prevention strategies. Study characteristics and results including quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were summarized in standardized evidence tables. Economic results were transformed into 2017 Euros. The included studies (N = 33) evaluated ovarian cancer screening, risk-reducing interventions in women with heterogeneous cancer risks and genetic testing followed by risk-reducing interventions for mutation carriers. Multimodal screening with a risk-adjusted algorithm in postmenopausal women achieved ICERs of 9,800-81,400 Euros/QALY, depending on assumptions on mortality data extrapolation, costs, test performance, and screening frequency. Cost-effectiveness of risk-reducing surgery in mutation carriers ranged from cost-saving to 59,000 Euros/QALY. Genetic testing plus risk-reducing interventions for mutation carriers ranged from cost-saving to 54,000 Euros/QALY in women at increased mutation risk. Our findings suggest that preventive surgery and genetic testing plus preventive surgery in women at high risk for ovarian cancer can be considered effective and cost-effective. In postmenopausal women from the general population, multimodal screening using a risk-adjusted algorithm may be cost-effective.


Imaging methods used for children with hip dysplasia.
Ultrasound has been used to examine the infant hip for more than 20 years. The Thornbury model for assessing the clinical efficacy of a diagnostic imaging procedure has been used in this review to determine what has been achieved and what remains to be learned. To accomplish the effective and efficient treatment of patients with developmental dysplasia of the hip, orthopaedic, radiologic, and pediatric organizations must collaborate in writing and revising standards of care and guidelines for treatment as our knowledge base grows.


The Psychological Capital of Left-Behind University Students: A Description and Intervention Study From China.
The migrant worker phenomenon in China has negatively impacted the psychological development of these workers' children, whom researchers have termed "left-behind children" (LC) or university students with left-behind experience (USWL). Since USWL are the best among the LC in some sense, we decided to perform two investigations to determine if they might possess unique positive psychological capital factors. Study 1 aimed to explore the development of the psychological capital of USWL, and Study 2 utilized a group intervention design to improve USWL psychological capital. A questionnaire was administered to 281 USWL and 284 control university students in study 1. The results showed that the psychological capital of USWL was moderate, and their self-efficacy, optimism, hope, and overall psychological capital were significantly lower than those with no left-behind experience. However, their psychological resilience was remarkably higher than those who were not left behind. It also suggested that some demographic factors such as gender, grade, only child status, student leadership experience, reunion frequency with parents, and relationship with guardians significantly influence the psychological capital of USWL. In Study 2, a single-factor interventional experimental design based on the psychological capital intervention theory (PCI) was conducted in 73 USWL (38 in the experimental group, 35 in the control group). There were significant post-test differences between groups. Both the pre- and post-test results differed greatly in the experimental and control groups. Overall, our findings indicate that although the left-behind experience in childhood moderately impairs psychological capital development, it also fosters resilience. The psychological intervention based on PCI is an effective "remedy scheme" to improve their psychological capital qualities.


Effects of intravenous, sternal, and humerus intraosseous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.
To determine if there were significant differences among humerus intraosseous (HIO), sternal intraosseous (SIO), and intravenous (IV) administration of 500 mL Hextend in hemodynamics or administration time in a hypovolemic swine model. Vivarium. Yorkshire swine; sample size was based on a large effect size of 0.5, an α of 0.05, and a power of 80 percent Swine were randomly assigned to one of four groups: HIO (n = 9), SIO (n = 9), IV (n = 9), and control (n = 9). Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered by either the HIO, SIO, or IV route; the control group received none. Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV among HIO, SIO, and IV groups over 8 minutes (p > 0.05). An analyses of variance determined that there was no significant difference between groups relative to time of administration (p = 0.521). When IV access is difficult, both HIO and SIO are effective techniques for rapid vascular access and the administration of Hextend for patients in hypovolemic shock.


ATP production in isolated muscle mitochondria from haemodialysis patients: effects of correction of anaemia with erythropoietin.
1. The ATP production rate in isolated skeletal muscle mitochondria was measured with a bioluminescence method, before and during erythropoietin treatment, in 21 anaemic haemodialysis patients. In addition, the concentrations of ATP, phosphocreatine and total creatine and the ratio of alkali-soluble protein to DNA were determined in skeletal muscle. Maximal oxygen uptake and maximal exercise capacity were determined on a bicycle ergometer. 2. The results unexpectedly showed a 35% higher mitochondrial ATP production rate in the patients before erythropoietin treatment than in sedentary control subjects. On the other hand, mitochondrial density, as measured by the activity of the matrix enzyme glutamate dehydrogenase, was the same in the patients as in the sedentary control group. After 1 year on maintenance erythropoietin treatment, the ATP production rate per kg of muscle decreased in five out of seven patients and reached the same level as in the sedentary control subjects. The ratio between ATP production rate and glutamate dehydrogenase activity was on average 40% higher in the patients at the start and decreased towards the control level in six out of seven patients after 1 year on maintenance erythropoietin treatment. When related to the mitochondrial protein content, a significant reduction in the ATP production rate was observed. 3. The ratio of alkali-soluble protein to DNA in skeletal muscle and the concentrations of ATP, phosphocreatine and total creatine in skeletal muscle at rest were normal in the patients and did not change during the study. The maximal aerobic power improved by 25% after the correction of anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiopulmonary reflexes and arterial pressure during rest and exercise in dogs.
Mean arterial blood pressure, heart rate, and cardiac output were monitored at rest and during exercise of two grades of severity in conscious dogs under control conditions and after progressive interruption of the baroreflexes. Aortic arch denervation and vascular isolation and pressurization of the carotid sinuses were used to interrupt arterial baroreflexes. Subsequent interruption of cardiopulmonary afferents was produced by acute bilateral cervical vagotomy. The results indicate that 1) with the cardiopulmonary receptors alone operative, the arterial blood pressure response to exercise is abnormal, 2) cardiopulmonary receptors do not contribute to the moment-to-moment modulation of arterial pressure, and 3) the carotid sinuses, aortic arch, and cardiopulmonary receptors are all involved in determining the mean level of arterial blood pressure. It is concluded that vagally innervated cardiopulmonary receptors do not have a significant role in regulating arterial blood pressure during exercise but are involved in establishing the general level of arterial blood pressure.


Quality of life theory I. The IQOL theory: an integrative theory of the global quality of life concept.
Quality of life (QOL) means a good life and we believe that a good life is the same as living a life with a high quality. This paper presents the theoretical and philosophical framework of the Danish Quality of Life Survey, and of the SEQOL, QOL5, and QOL1 questionnaires. The notion of a good life can be observed from subjective to the objective, where this spectrum incorporates a number of existing quality of life theories. We call this spectrum the integrative quality-of-life (IQOL) theory and discuss the following aspects in this paper: well being, satisfaction with life, happiness, meaning in life, the biological information system ("balance"), realizing life potential, fulfillment of needs, and objective factors. The philosophy of life outlined in this paper tries to measure the global quality of life with questions derived from the integrative theory of the quality of life. The IQOL theory is an overall theory or meta-theory encompassing eight more factual theories in a subjective-existential-objective spectrum. Other philosophies of life can stress other aspects of life, but by this notion of introducing such an existential depth into the health and social sciences, we believe to have taken a necessary step towards a new humility and respect for the richness and complexity of life.


[Possible existence of alternative secretion routes of acid phosphatase in the yeast Saccharomyces cerevisiae].
The secretion of different acid phosphatase forms into the growth medium was studied in the yeast Saccharomyces cerevisiae. The secretion of constitutive acid phosphatase highly correlated with the process of bud formation. This exoenzyme might be involved in the construction of the bud cell wall. Analysis of the rate, at which repressible acid phosphatase was excreted into the growth medium, as well as a negative correlation between its secretion and the process of bud formation were indicative of an additional route via which the repressible form of acid phosphatase was secreted. It is possible that yeast cells contain vesicles similar to "safe" vesicles in higher eukaryotic cells.


Accidental oral administration of povidone iodine in a newborn: case report.
Iodine solutions are widely used as antiseptic for treating and preventing wound infections. Povidone iodine, one of the most common topical iodine solutions in emergency kits, can lead to several abnormalities as thyroid dysfunction. Povidone iodine poisoning is unusual and previously reported effects are mainly complications of topical usage during surgical procedures. Here we present the case of a newborn that was accidentally given oral povidone iodine, showing no signs or symptoms of toxicity after ingestion.


Controlled manipulation and in situ mechanical measurement of single co nanowire with a laser-induced cavitation bubble.
The flow induced by a single laser-induced cavitation bubble is used to manipulate individual Co nanowires. The short-lived (<20 μs) bubble with a maximum size of 45 μm is created in an aqueous solution with a laser pulse. Translation, rotation, and radial motion of the nanowire can be selectively achieved by varying the initial distance and orientation of the bubble with respect to the nanowire. Depending on the initial distance, the nanowire can be either pushed away or pulled toward the laser focus. No translation is observed for a distance further than approximately 60 μm, while at closer distance, the nanowire can be bent as a result of the fast flow induced during the bubble collapse. Studying the dynamics of the shape recovery allows an estimation of the Young's modulus of the nanowire. The low measured Young's modulus (in a range from 9.6 to 13.0 GPa) of the Co nanowire is attributed to a softening effect due to structural defects and surface oxidation layer. Our study suggests that this bubble-based technique allows selectively transporting, orienting, and probing individual nanowires and may be exploited for constructing functional nanodevices.


Magnetic Field Signatures Near Galileo's Closest Approach to Gaspra.
Two large magnetic field rotations were recorded by the spacecraft Galileo 1 minute before and 2 minutes after its closest approach to the asteroid Gaspra. The timing and the geometry of the field changes suggest a connection with Gaspra, and the events can be interpreted as the result of the draping of the solar wind field around a magnetospheric obstacle. Gaspra's surface field is inferred to be within an order of magnitude of Earth's surface field, and its magnetic moment per unit mass is in the range observed for iron meteorites and highly magnetized chondrites. The location of the magnetic signatures suggests that perturbations are carried by waves in the magnetosonic-whistler mode with wavelengths between electron and ion gyro radii.


A subgroup analysis of penetrating injuries to the pancreas: 777 patients from the National Trauma Data Bank, 2010-2014.
This study is the first to analyze penetrating injuries to the pancreas within subgroups of severe traumatic brain injury (TBI), early deaths, and potential survivors. Our objectives were to identify national patterns of injury, predictors of mortality, and to validate the American Association for Surgery of Trauma Organ Injury Scale (AAST-OIS) pancreas injury grades by mortality. Secondary outcomes included hospital and intensive care unit length of stay and days on mechanical ventilation. Using the Abbreviated Injury Scale 2005 and ICD-9-CM E-codes, we identified 777 penetrating pancreatic trauma patients from the National Trauma Data Bank that occurred between 2010 and 2014. Severe TBI was identified by ICD-9-CM diagnosis codes and Glasgow Coma Score (GCS; n = 7), early deaths were those that occurred within 24 h of admission (n = 82), and potential survivors included patients without severe TBI who survived longer than 24 h following admission (n = 690). We estimated multivariable generalized linear mixed models to predict mortality to account for the nesting of potential survivors within trauma centers. Our results indicated that overall mortality decreased from 16.9% to 6.8% after excluding severe TBI and early deaths. Approximately, 11% of patients died within 24 h of admission, of whom 78% died in the first 6 h. Associated injuries to the stomach, liver, and major vasculature occurred in approximately 50% of patients; rates of associated injuries were highest in patients who died within 6 h of admission. In potential survivors, mortality increased by AAST-OIS grade: 3.5% I/II; 8.3% III; 9.6% IV; and 13.8% V. Predictors of mortality with significantly increased odds of death were patients with increasing age, lower admission GCS, higher admission pulse rate, and more severe injuries as indicated by Organ Injury Scale grade. From 777 patients, we identified national patterns of injury, predictors of outcome, and mortality by AAST-OIS grade within the subgroups of severe TBI, early deaths, and potential survivors. Because AAST-OIS is not a reported element in the National Trauma Data Bank, we correlated Abbreviated Injury Scale 2005 codes to injury grade and identified an increase in mortality. After controlling for covariance, we found that greater age, lower GCS in stab wounds, higher pulse, and presence of a grade V pancreatic injury independently predicted the likelihood of death in patients surviving beyond 24 h following penetrating injuries to the pancreas.


Sexual Experiences of Young Transgender Persons During and After Gender-Affirmative Treatment.
Early gender-affirmative treatment (GAT) of adolescents may consist of puberty suppression, use of affirming hormones, and gender-affirmative surgeries. This treatment can potentially influence sexual development. In the current study, we describe sexual and romantic development during and after treatment. The participants were 113 transgender adolescents treated with puberty suppression, affirmative hormones, and affirmative surgery who were assessed as young adults (38 transwomen and 75 transmen; mean age 20.79 years, SD 1.36) during and after their GAT. A questionnaire on sexual experiences, romantic experiences, and subjective sexual experiences was administered and compared to the experiences of a same-aged sample from a Dutch general population study (N = 4020). One year post surgery, young transgender adults reported a significant increase in experiences with all types of sexual activities: masturbation increased from 56.4% to 81.7%, petting while undressed increased from 57.1% to 78.7%, and sexual intercourse increased from 16.2% to 37.6% post surgery compared to presurgery. Young transmen and transwomen were almost equally experienced. In comparison with the general population, young transgender adults were less experienced with all types of sexual activities. Early GAT (including puberty suppression, affirmative hormones, and surgeries) may provide young transgender adults with the opportunity to increase their romantic and sexual experiences.


Combining patient reported outcomes and EHR data to understand population level treatment needs: correcting for selection bias in the migraine signature study.
Electronic health records (EHR) data can be used to understand population level quality of care especially when supplemented with patient reported data. However, survey non-response can result in biased population estimates. As a case study, we demonstrate that EHR and survey data can be combined to estimate primary care population prescription treatment status for migraine stratified by migraine disability, without and with adjustment for survey non-response bias. We selected disability as it is associated with survey participation and patterns of prescribing for migraine. A stratified random sample of Sutter Health adult primary care (PC) patients completed a digital survey about headache, migraine, and migraine related disability. The survey data from respondents with migraine were combined with their EHR data to estimate the proportion who had prescription orders for acute or preventive migraine treatments. Separate proportions were also estimated for those with mild disability (denoted "mild migraine") versus moderate to severe disability (denoted mod-severe migraine) without and with correction, using the inverse propensity weighting method, for non-response bias. We hypothesized that correction for non-response bias would result in smaller differences in proportions who had a treatment order by migraine disability status. The response rate among 28,268 patients was 8.2%. Among survey respondents, 37.2% had an acute treatment order and 16.8% had a preventive treatment order. The response bias corrected proportions were 26.2% and 11.6%, respectively, and these estimates did not differ from the total source population estimates (i.e., 26.4% for acute treatments, 12.0% for preventive treatments), validating the correction method. Acute treatment orders proportions were 32.3% for mild migraine versus 37.3% for mod-severe migraine and preventive treatment order proportions were 12.0% for mild migraine and 17.7% for mod-severe migraine. The response bias corrected proportions for acute treatments were 24.8% for mild migraine and 26.6% for mod-severe migraine and the proportions for preventive treatment were 8.1% for mild migraine and 12.0% for mod-severe migraine. In this study, we combined survey data with EHR data to better understand treatment needs among patients diagnosed with migraine. Migraine-related disability is directly related to preventive treatment orders but less so for acute treatments. Estimates of treatment status by self-reported disability status were substantially over-estimated among those with moderate to severe migraine-related disability without correction for non-response bias.


Catalytic function of DNA topoisomerase II.
Although the genetic code is defined by a linear array of nucleotides, it is the three-dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three-dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme is essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme carries out its catalytic cycle.


Autogenous and global control of the flagellar master operon, flhD, in Salmonella typhimurium.
Expression of the flagellar master operon, flhD, is known to be affected by growth conditions and by mutations in a variety of genes. In the present work, the transcriptional control of the Salmonella typhimurium flhD operon was investigated in various genetic backgrounds. First, we examined the effect of mutations in the global regulators cAMP-CRP, H-NS, OmpR and RpoS. Mutations in the cya, crp or hns gene reduced but did not eliminate flhD expression. However, expression was completely inhibited in the cya hns and crp hns double mutants. These results indicate that cAMP-CRP and H-NS independently activate the flhD operon and that maximal expression is attained in the presence of both regulators. On the other hand, the ompR and rpoS mutations did not affect either the motility phenotype or flhD expression. We next examined the expression of a chromosomal flhD-lac fusion gene in the presence of a plasmid carrying the wild-type flhD operon. It was found that under this condition the chromosomal flhD operon was repressed or activated, depending on the intracellular activity of FliA, an alternative sigma factor specific for late flagellar operons. In the absence of FliA or in the presence of both FliA and its cognate anti-sigma factor FlgM, the flhD operon was autogenously repressed, whereas in the flgM mutant background it was autogenously activated in the presence of FliA. This autoregulation was still observed in the crp or hns mutant background, indicating that the autogenous control is achieved by a mechanism that is independent of the cAMP-CRP and H-NS regulatory pathways.


Materials aspects of display devices.
For many years interest in display devices stemmed almost entirely from the needs of television receivers, oscilloscopes, and radar systems whose requirements were almost ideally satisfied by the cathode-ray tube. However, during the past two decades the proliferation of small electronic instruments with digital output has stimulated the development of a number of new display media which, because of their compact nature and low power consumption, are better suited for such applications. In view of the success achieved with these technologies a continuing effort is being directed toward increasing their information capacity to the point where they may ultimately be useful in applications now requiring cathode-ray tubes.


Palliative Care Version 1.2016.
The NCCN Guidelines for Palliative Care provide interdisciplinary recommendations on palliative care for patients with cancer. The NCCN Guidelines are intended to provide guidance to the primary oncology team on the integration of palliative care into oncology. The NCCN Palliative Care Panel's recommendations seek to ensure that each patient experiences the best quality of life possible throughout the illness trajectory. Accordingly, the NCCN Guidelines outline best practices for screening, assessment, palliative care interventions, reassessment, and after-death care.


Impaired rejection of minor-histocompatibility-antigen-disparate skin grafts and acquisition of tolerance to thymus donor antigens in allothymus-implanted, thymectomized Xenopus.
We examine whether J strain Xenopus laevis and X laevis/gilli (LG) isogeneic hybrids, thymectomized (Tx) at 7 days and implanted with larval or postmetamorphic thymus (either normal or irradiated) in late larval life, can be used to explore the role of the developing thymus in the education of minor histocompatibility (H) antigen-reactive T cells and in the acquisition of tolerance to MHC (major histocompatibility complex) antigens. Tx LG Xenopus implanted with isogeneic thymus display fully restored ability to reject both MHC-incompatible and minor H-disparate grafts. Allothymuses (both MHC- and minor-H-disparate) restore normal rejection of skin grafts with MHC incompatibility to thymus donor and Tx (J or LG) host, but reactivity to grafts with putative minor H disparity is impaired. Defective minor-H-disparate skin graft rejection occurs even when the Tx host has received a thymus of the "correct" MHC haplotype (i.e., the same MHC as the assay skin graft). This defect may be attributable to inadequate establishment of minor-H-reactive T lymphocytes, to sharing of minor antigens, or to "nonspecificity" of tolerance induction to minor antigens, since such tolerance is demonstrated here following perimetamorphic grafting of skin to control LG clones. Skin grafts from Xenopus isogeneic to the donors of the MHC-incompatible larval and adult thymus implants are always tolerated by Tx hosts. In contrast, in vitro one-way MLC (mixed leukocyte culture) reactivity of splenocytes to thymus donor MHC antigens occurs when certain donor/host combinations are used but not when others are tested. Postmetamorphic thymus implants appear to promote in vitro MLC tolerance more effectively than larval thymus implants.


Qualitative Evaluation of Evidence-Based Online Decision Aid and Resources for Osteoarthritis Management: Understanding Patient Perspectives.
To qualitatively examine the experiences with, and impact of, evidence-based online resources in self-management among Australians with osteoarthritis. Telephone interviews were conducted with 36 users of a novel osteoarthritis resource, the Osteoarthritis Awareness Hub. Rogers' 5 attributes of innovation (relative advantage, compatibility, complexity, trialability, and observability) and outcomes guided the semistructured interview and analysis. Maximum variation sampling was used, and data saturation occurred after 33 interviews. A coding scheme was agreed upon and all interview data were entered into NVivo for qualitative content analysis. Study participants had high levels of literacy and health literacy. For adoption and implementation of an innovation, the participants' narratives confirmed and underscored the fact that it was important that it come from an authoritative and trusting voice and that its perceived benefits align with participants' values and existing practices (relative advantage and compatibility). The participants also valued seeing the practical benefits of the innovation, such as its capacity to impart quality and balanced new insights and information, and to maintain and monitor their personal progress. Notably, many participants spoke about the mental and physical health benefits that they derived from engagement with the online resources. Our study findings confirm that web-based tools can be a useful adjunct to patients adopting self-management strategies. Rogers' theory provides a framework for a deeper appreciation of the how, why, and what questions concerning the adoption and implementation processes, especially among people with good technology and health literacy.


miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator.
Recent studies show that mantle cell lymphoma (MCL) express aberrant microRNA (miRNA) profiles; however, the clinical effect of miRNA expression has not previously been examined and validated in large prospective homogenously treated cohorts. We performed genome-wide miRNA microarray profiling of 74 diagnostic MCL samples from the Nordic MCL2 trial (screening cohort). Prognostic miRNAs were validated in diagnostic MCL samples from 94 patients of the independent Nordic MCL3 trial (validation cohort). Three miRNAs (miR-18b, miR-92a, and miR-378d) were significantly differentially expressed in patients who died of MCL in both cohorts. MiR-18b was superior to miR-92a and miR-378d in predicting high risk. Thus, we generated a new biological MCL International Prognostic Index (MIPI-B)-miR prognosticator, combining expression levels of miR-18b with MIPI-B data. Compared to the MIPI-B, this prognosticator improved identification of high-risk patients with regard to cause-specific, overall, and progression-free survival. Transfection of 2 MCL cell lines with miR-18b decreased their proliferation rate without inducing apoptosis, suggesting that miR-18b may render MCL cells resistant to chemotherapy by decelerating cell proliferation. We conclude that overexpression of miR-18b identifies patients with poor prognosis in 2 large prospective MCL cohorts and adds prognostic information to the MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance.


Quantitative estimation of itopride hydrochloride and rabeprazole sodium from capsule formulation.
Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C(18) column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies.


Ring expansion of a 2-rhodaoxetane: insertion chemistry with unsaturated molecules.
A 2-rhodaoxetane was found to react with unsaturated electrophiles, such as highly electron-deficient acetylene dicarboxylates, CS2 and various aldehydes, to form a series of six-membered metallacycles. These metallacycles were characterized by (1)H, (13)C and 2D NMR spectroscopic techniques, as well as HRMS and, for one complex, XRD. In some cases, the insertions were found to be reversible.


Rapid Visual Detection of Amines by Pyrylium Salts for Food Spoilage Taggant.
Amines are ubiquitous in biological world, but are toxic and harmful in nature. Detection of biogenic amines that are released from spoiled seafood, meat, or dairy products is an important task to maintain the quality and safety of these packaged foods. To this endeavor, herein we report pyrylium salts that are capable of sensing various amines by rapid change of fluorescence color or intensity. In molecular level, this change of fluorescence is rooted to the formation of pyridine or analogous product that have distinct optical property. The pyrylium salts are capable of efficiently sensing amine vapors or amine solutions both in solid state and in solution state and thus demonstrating a multiphase sensing platform. Utilizing the excellent sensing property, we have employed our pyrylium compounds as spoilage indicator for food products such as fish, meat or cheese which relies on sensing biogenic amines released from these spoiled foods and provide optical response. Prominent change in visible and luminescence color was observed within 4-18 h of packaging at room temperature (∼33 °C). Considering the rapid response for biogenic amines, these molecular sensors have great potential to be utilized for food packaging industry, medical diagnostics, or other sensory devices.


Expression of plasma membrane water channel genes under water stress in Nicotiana excelsior.
Deduced amino acid sequences encoded by the cDNAs related to the MIP gene family from Nicotiana excelsior were characterized. Phylogenetic characterization of the products of corresponding genes named NeMip1, NeMip2, and NeMip3 strongly suggested that they are water channel proteins localized in the plasma membrane. Organ specificity of the gene expression was examined in leaves, roots, and reproductive organs. NeMip1 was expressed in roots and reproductive organs; however, it was hardly detectable in leaves. Two other genes, NeMip2 and NeMip3, were expressed in all of organs examined. mRNA accumulation from the genes was investigated in leaves under salt- and drought-stresses. The results demonstrated that mRNA accumulation from all three genes increased under salt- and drought-stresses within one day. However, they showed different accumulation patterns. In addition to their up-regulation under salt- and drought-stresses, daily changes in NeMip2 and NeMip3 mRNA accumulation was observed under unstressed conditions in leaves.


Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics.
HYPOTHESIS/INTRODUCTION: A polymorphic marker within the angiotensin- converting enzyme (ACE) gene has been associated with circulating and tissue ACE activity and with a variety of forms of cardiovascular disease. Since angiotensin II (Ang II) causes pulmonary vasoconstriction and vascular and myocardial remodelling, we postulated a role for the renin-angiotensin system and the ACE DD genotype in the pathophysiology of primary pulmonary hypertension (PPH) and in the right ventricular response to pressure overload in these patients. The incidence of the ACE DD genotype was evaluated in 60 patients with severe PPH compared with two normal control populations, a group of healthy population-based controls (n=158) and subjects found suitable for cardiac organ donation (n=79). Genomic DNA extracted from peripheral leukocytes was amplified using the polymerase chain reaction to detect polymorphic markers. Haemodynamics were determined by right heart catheterisation in a subset of the PPH patients. The frequency of the ACE DD genotype was 45% in the patients with PPH, compared with 24% in the organ donors, and 28% in population-based healthy controls (p=0.01 for chi-square test). Of the 32 PPH patients with baseline haemodynamics, 12 exhibited the ACE DD genotype and 20 were non-DD. While the mean pulmonary artery pressure and the duration of symptoms attributable to pulmonary hypertension was not different between the DD and non-DD groups, cardiac output was significantly lower (3.29+0.27 vs. 5.07+0.37 L/minute, p=0.002) and the mean right atrial pressure tended to be higher (8.85+1.29 vs. 4.92+1.27 mmHg, p=0.08) in the non-DD group. The reduction in cardiac output seen in the non-DD group was not due to a difference in heart rate, but to a significant reduction in stroke volume, consistent with a decreased contractile state. In addition, non-DD patients exhibited a significantly worse functional capacity (NYHA Class 3.14+0.12 vs. 2.40+0.28, p=0.02). 1) The ACE DD genotype is significantly increased in patients with severe PPH compared with normal controls, suggesting that certain individuals may be genetically predisposed to developing pulmonary hypertension. 2) The ACE DD genotype is associated with preserved right ventricular function in PPH patients, supporting a compensatory myocardial or inotropic role for Ang II in the pressure overloaded right ventricle.


Molecular characterization of antibiotic resistant Escherichia coli isolates recovered from food samples and outpatient Clinics, KSA.
Multidrug-resistant Escherichia coli is one of the most important public health concern worldwide that can be transferred through the food of animal origin to human being causing serious infection. The genetic responsibility of such resistant genes (Plasmids, integrons, and transposons) can be easily transmitted from the resistant strain to another. Therefore, the main objectives of the study is the molecular characterization of the resistant Escherichia coli isolates recovered from food samples and human isolates collected from outpatient clinics, KSA especially the resistance strains against aminoglycoside resistance genes which are responsible for the resistance against gentamicin and the resistance caused β-lactamases genes. Examination of food samples revealed 120 Escherichia coli isolates (22.22%) (30 strains O26: K60, 28 strains O128: K67, 20 strains O111: K58, 18 strains O126: K58, 10 strains O55: K59, 9 strains O86: K61 and 5 strains O157: H7). All the strains were highly resistance to penicillin, amoxicillin-clavulanic and erythromycin with a percentage of 100%, while the resistance to gentamicin, ampicillin, oxytetracycline, chloramphenicol, norfloxacin, trimethoprim, and nalidixic acid were 83%, 75%, 65.3%, 55.8%, 36.5%, 30.7% and 26.9% respectively. On the other hand, 59.6% of tested strains were sensitive to ciprofloxacin. Positive amplification of 896 bp fragments specific for aacC2 genes were observed by PCR designated for the detection of the aminoglycoside resistance genes. Meanwhile, multiplex PCR designed to detect the ampicillin and amoxicillin-clavulanic acid resistant E. coli isolates revealed positive amplification of 516 bp fragments specific for BlaTEM gene with all the resistant strains to ampicillin and amoxicillin-clavulanic acid. Moreover, positive amplification of 392 bp fragments specific for BlaSHV resistant gene were observed with (60.52%) of E. coli isolate. While all the tested strains were negative for amplification of BlaOXA_1.


Zoonotic implications of camel diseases in Iran.
Approximately 60% of all human pathogens and 75% of emerging infectious diseases are zoonotic (of animal origin). Camel zoonotic diseases can be encountered in all camel-rearing countries. In this article, all studies carried out on camel zoonotic diseases in Iran are reviewed to show the importance of camels for public health in this country. More than 900 published documents were systematically searched to find relevant studies from 1,890 until late 2018. The collected articles were classified according to the aetiological agents. In this study, 19 important zoonotic diseases were reported among Iranian camels including listeriosis, leptospirosis, plague, Q fever, brucellosis, campylobacteriosis, tuberculosis, pasteurellosis, clostridiosis, salmonellosis, Escherichia coli infections, rabies, camelpox, Middle East respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever, echinococcosis, cryptosporidiosis, toxoplasmosis and dermatophytosis, most of which belong to bacterial, viral, parasitic and fungal pathogens, respectively. Results show that camels are one of the most important sources of infections and diseases in human; therefore, continuous monitoring and inspection programs are necessary to prevent the outbreak of zoonotic diseases caused by this animal in humans.


Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA-MB-231 and MCF-7 breast cancer cells, an in-vitro and in silico studies.
Epithelial-mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA-MB-231 and MCF-7 breast cancer cells. The apparent anticancer activity of UA on MDA-MB-231 and MCF-7 cells was evident from IC50 values of 14.98 and 15.99 μg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA-MB-231 and MCF-7 cells were treated with 20 μg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G0 /G1 phase, S phase, G2 /M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum-polarized-ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with -53.865, -48.971 and -40.617 MMGBSA (ΔGbind ) scores, respectively. The long-range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent.


The influence of the CYP3A4*22 polymorphism on serum concentration of quetiapine in psychiatric patients.
Besides dietary, hormonal, or pathological factors, mutations in cytochrome P450 enzymes are thought to be responsible for the interindividual differences in serum concentrations of cytochrome P450 (CYP450)-dependent drugs. Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of greater than 50% of the prescribed drugs. Recently, a new single-nucleotide polymorphism (SNP) was found (CYP3A4*22), which results in a decreased enzyme activity, in contrast to the other known SNPs in CYP3A4. We investigated to which degree the CYP3A4*22 SNP affects serum concentrations of patients receiving quetiapine, a drug exclusively metabolized by CYP3A4. Two hundred thirty-eight adult patients receiving quetiapine were included in this study, based on availability of DNA, serum quetiapine levels, and information on dose. Patients were genotyped for CYP3A4*22 using allele-specific polymerase chain reaction, and, as a control, restriction fragment length polymorphism analysis. Carriers of the CYP3A4*22 allele (*1/*22 and *22/*22, n = 31) had 2.5-fold higher serum levels of quetiapine than did wild-type patients (n = 207; P = 0.03) when using a comparable dose (median, 300 mg/d for both wild-type and carriers; P = 0.67). The dose-corrected serum concentration (C/D) was 67% higher in carriers than in wild-type patients (P = 0.01). The number of patients who achieved serum levels above the therapeutic range (>500 µg/L) was also higher in *22-allele carriers (16.1% vs 2.9%; P = 0.007). Being a carrier of the CYP3A4*22 allele increases the serum concentration of quetiapine at comparable doses.


[Postradiation atrophy of anophthalmic orbit after treatment of retinoblastoma. System of surgical rehabilitation].
A system of surgical treatment of patients with radiation atrophy of orbital tissues has been developed in order to attain a stable position of the prosthesis in the cavity and improve the patients' appearances. A total of 366 interventions were performed in 242 patients. The operations were as follows: formation of conjunctival cavity by autotransplants of the mucosa from the lips (242), delayed plasty of the stump (81), contour plasty of the temple and external edge of the orbit (32), correction of eyelids (11). Single-stage treatment was carried out in 156 patients and 2-7 stages in 86 patients. Positive results were attained in all cases: the depth of the vault increased, lagophthalmos decreased, falling-in defect of prosthesis, eyelids, and temple were reduced, and stable position of the prosthesis in the cavity was attained. Surgical treatment of this condition differs greatly from plastic repair for other diseases because of changes in tissues after radiotherapy. Functional and cosmetic rehabilitation of patients with postradiation atrophy of orbital tissues after treatment of retinoblastoma with good effect can be attained only by staged surgical treatment.


Determinants of health in early adulthood: what is the role of parental education, childhood adversities and own education?
Of the many studies assessing the impact of childhood living conditions on health and health inequalities in adulthood, only few have combined information on current determinants of health with detailed individual level data on different aspects of childhood living conditions and adversities. This study aims (i) to assess the role of parental education, self-reported childhood adversities and family structure as determinants of different dimensions of health in early adulthood, and (ii) to identify the role of the respondent's own education as a modifier of the association between childhood living conditions and health. The study is based on a representative sample (n = 3669; participation rate 83%) of young adults aged 18-39 years in 2000 in Finland. The main outcome measures were poor self-rated health (SRH), psychological distress (by GHQ12) and somatic morbidity. Parental education, problems in childhood and the respondent's own education were independently related to SRH and psychological distress. The impact of childhood living conditions on health varied by gender and according to the measure of health. Childhood conditions were strongly associated with poor SRH and psychological distress, whereas the connection with somatic morbidity was weaker. The associations remained relatively unchanged after controlling for the respondent's own education. Childhood living conditions and adversities are strongly associated with poor SRH and psychological distress in early adulthood. Early recognition of childhood adversities followed by relevant support measures may play an important role in preventing health problems in adulthood.


7T Brain MRS in HIV Infection: Correlation with Cognitive Impairment and Performance on Neuropsychological Tests.
Validated neuroimaging markers of HIV-associated neurocognitive disorder in patients on antiretroviral therapy are urgently needed for clinical trials. The purpose of this study was to explore the relationship between cognitive impairment and brain metabolism in older subjects with HIV infection. It was hypothesized that MR spectroscopy measurements related to neuronal health and function (particularly N-acetylaspartate and glutamate) would be lower in HIV-positive subjects with worse cognitive performance. Forty-five HIV-positive patients (mean age, 58.9 ± 5.3 years; 33 men) underwent detailed neuropsychological testing and brain MR spectroscopy at 7T. Twenty-four subjects were classified as having asymptomatic cognitive impairment, and 21 were classified as having symptomatic cognitive impairment. Single-voxel proton MR spectra were acquired from 5 brain regions and quantified using LCModel software. Brain metabolites and neuropsychological test results were compared using nonparametric statistics and Pearson correlation coefficients. Differences in brain metabolites were found between symptomatic and asymptomatic subjects, with the main findings being lower measures of N-acetylaspartate in the frontal white matter, posterior cingulate cortex, and precuneus. In the precuneus, glutamate was also lower in the symptomatic group. In the frontal white matter, precuneus, and posterior cingulate cortex, NAA and glutamate measurements showed significant positive correlation with better performance on neuropsychological tests. Compared with asymptomatic subjects, symptomatic HIV-positive subjects had lower levels of NAA and glutamate, most notably in the frontal white matter, which also correlated with performance on neuropsychological tests. High-field MR spectroscopy offers insight into the pathophysiology associated with cognitive impairment in HIV and may be useful as a quantitative outcome measure in future treatment trials.


Emerging Potential Mechanism and Therapeutic Target of Ferroptosis in PDAC: A Promising Future.
Pancreatic cancer (PC) is a devastating malignant tumor of gastrointestinal (GI) tumors characterized by late diagnosis, low treatment success and poor prognosis. The most common pathological type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for approximately 95% of PC. PDAC is primarily driven by the Kirsten rat sarcoma virus (KRAS) oncogene. Ferroptosis was originally described as ras-dependent cell death but is now defined as a regulated cell death caused by iron accumulation and lipid peroxidation. Recent studies have revealed that ferroptosis plays an important role in the development and therapeutic response of tumors, especially PDAC. As the non-apoptotic cell death, ferroptosis may minimize the emergence of drug resistance for clinical trials of PDAC. This article reviews what has been learned in recent years about the mechanisms of ferroptosis in PDAC, introduces the association between ferroptosis and the KRAS target, and summarizes several potential strategies that are capable of triggering ferroptosis to suppress PDAC progression.


Construction of a light-emitting diode fluorescence detector for high-performance liquid chromatography and its application to fluorometric determination of L-3-hydroxybutyrate.
This study employed a new light source, a light-emitting diode (LED), for fluorescence detection of high-performance liquid chromatography to measure the concentration of trace constituents in biological fluids. Using l-3-hydroxybutyrate ( l-3HB) as a tested trace compound, the function of the new system was compared with that of the current commercially available model. A detailed schematic diagram of the path of the detection rays in the LED detector is given. A voltage-stabilizer for the drive circuit was designed with an input of 10 V and an output of 8 V, and another voltage regulator was used to maintain a constant 8 V. Then the regulator was used to set the output voltage for the LED at 2.8 V by two external resistors. Replacing the xenon lamp with LED, this system provided higher photon density and a narrow spectrum at a wavelength of 491 nm. At room temperature (22.1°C), the average temperature of six places in the chamber of LED detector was 22.1°C compared with 51.1°C in the xenon detector. The spectra of the excitation light sources were measured. Compared with the xenon lamp, approximately 1.32 times higher excitation intensity was obtained by the LED source. The accuracy of detection of l-3HB in 50 μL of rat serum was 99.85-100.85%, and the intra-day and inter-day precision values were within 8.99 and 13.90%, respectively. The limit of detection of l-3HB was approximately 0.73 µM (signal-to-noise ratio 3). The sensitivity of the proposed LED detector was comparable to that of traditional fluorescence detectors using xenon arc lamps; however, the cost and operating temperature of LED lamps were far lower. This assay system could be further used to detect trace constituents in various samples.


Physical interaction between replication protein A and Rad51 promotes exchange on single-stranded DNA.
Replication protein A (RPA) is displaced from single-stranded DNA (ssDNA) by Rad51 during the initiation of homologous recombination. Interactions between these proteins have been reported, but the functional significance of the direct RPA-Rad51 interaction has yet to be elucidated. We have identified and characterized the interaction between DNA-binding domain A of RPA (RPA70A) and the N-terminal domain of Rad51 (Rad51N). NMR chemical shift mapping showed that Rad51N binds to the ssDNA-binding site of RPA70A, suggesting a competitive mechanism for the displacement of RPA from ssDNA by Rad51. A structure of the RPA70A-Rad51N complex was generated by experimentally guided modeling and then used to design mutations that disrupt the binding interface. Functional ATP hydrolysis assays were performed for wild-type Rad51 and a mutant defective in binding RPA. Rates of RPA displacement for the mutant were significantly below those of wild-type Rad51, suggesting that a direct RPA-Rad51 interaction is involved in displacing RPA in the initiation stage of genetic recombination.


A case of bupropion-induced Stevens-Johnson syndrome with acute psoriatic exacerbation.
Bupropion is a very popular medication prescribed to millions of patients globally for depression (Wellbutrin, GlaxoSmithKline, Research Triangle Park, NC) as well as an aid in smoking cessation (Zyban, GlaxoSmithKline, Research Triangle Park, NC). It has been reported to have some common dermatologic side effects, such as pruritus, urticaria and serum-sickness like reaction. The authors report a case of bupropion-induced Stevens-Johnson syndrome (SJS) with a concomitant acute psoriatic exacerbation in a 56-year-old woman, who began taking bupropion for treatment of depression. While the United States (U.S.) prescribing information for bupropion does include SJS as a rare potential side effect, it does not mention worsening of psoriasis. Physicians should be aware of the potential life-threatening adverse effects of this commonly prescribed medication as well as the risk in patients with known psoriasis.


The origins of U.S. safety standards for microwave radiation.
An analysis is made of the scientific research and values influencing the policy decisions that led to the adoption of the 1966 U.S. standard for exposure to microwave radiation. This analysis is used as a tool for understanding the problems faced by those who set standards. An effort is made to unravel the complex motivations that lay behind the adoption of the microwave standard. Based on the past record, it is suggested that standard setting remain distinct from basic scientific research and that adversary procedures be used only as a last resort in seeking consensus over a proposed standard.


In vitro protease inhibition and cytotoxicity of Aspergillus fumigatus biomolecules secreted under long-term aerated conditions.
The fatality rate of invasive aspergillosis (IA) is still very high, especially in prolonged and untreated pulmonary cases. Aspergillus fumigatus is the main causative agent of IA and investigation of its metabolites could provide valuable insight into virulence factor(s) associated with this organism. We evaluated the A. fumigatus culture filtrate (CF) products generated during short- and long-term aerated and non-aerated conditions and tested for (i) inhibition of cysteine or serine proteases and (ii) cytotoxicity. In addition, the mathematical model was determined using response surface methodology (RSM) to estimate the influence of different fermentation conditions on A. fumigatus CF characteristics, predict enzyme inhibition and make possible correlations with in vivo conditions. Biosynthesis of A. fumigatus low molecular weight proteinaceous products (from 6.4 to 15.4 kDa) was observed after 6 days of growth under aerated and alkaline conditions. Also, only these CFs showed significant reduction in cell lines survival (Caco-2 and WISH 35.6% and 54.6%, respectively). Obtained results provide solid starting point for further studies that would include: (i) detailed chemical characterization of A. fumigatus CF, (ii) activity relationships and in vivo correlation with pathogenicity of prolonged pulmonary IA and (iii) possible use of biomolecules as diagnostic or therapeutic markers.


Bioequivalence of Jusline following subcutaneous administration in healthy subjects.
The aim of the current work is to evaluate the pharmacokinetic and pharmacodynamic profile of a new human insulin preparation (jusline) following subcutaneous administration in healthy subjects, and to compare this profile with Humulin insulin. 20 healthy male subjects received a single dose of 0.2 U/kg of test (Jusline) or reference insulin (Humulin) during an euglycemic clamp keeping blood sugar constant (90 +/- 5 mg/dl) by changing the glucose infusion rate. Pharmacokinetic and pharmacodynamic measurements were taken from blood measurements of glucose, insulin, and C-peptide levels for tested insulin formulations. The mean values of the individual AUC ratios were well within the 90% confidence interval (100.5% for Regular, 101.9% for NPH, and 100.0% for Premixed Regular/NPH (30/70)). Similarly, Cmax and tmax were within the bioequivalence limit (80 - 125%). The maximum GIR were 10.20 mg/kg/min and 9.72 mg/kg/min for Jusline Regular and Humulin Regular, respectively. The maximum GIR were 7.09 mg/kg/min and 7.91 mg/kg/min for Jusline NPH and Humulin NPH, respectively. The maximum GIR and tGIRmax were 6.39 mg/kg/min and 6.63 mg/kg/ min for Jusline Premixed Regular/NPH (30/70) and Humulin Premixed Regular/NPH (30/70), respectively. Both insulin products produced similar suppression of endogenous C-peptide level (-29.76% to -50.22%). The present study demonstrated that after subcutaneous administration, there are no significant differences between Jusline and Humulin to promote peripheral glucose uptake.


Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1).
The organic anion transporter, OAT1 (SLC22A6), plays a role in the renal elimination of many drugs and environmental toxins. The goal of this study was to identify and functionally characterize OAT1 variants as a first step towards understanding whether genetic variation in OAT1 may contribute to interindividual differences in renal elimination of xenobiotics. As part of a larger study, 276 DNA samples from an ethnically diverse population were screened and 12 coding region variants of OAT1 were identified. The non-synonymous variants were then constructed and characterized in Xenopus laevis oocytes. A small family-based clinical study was conducted to determine the renal elimination of a model OAT1 substrate, adefovir (an antiviral agent) in human subjects who possessed a non-functional variant, OAT1-R454Q. Six non-synonymous variants were identified; two (OAT1-R50 H and OAT1-R293W) were present at > or = 1% in at least one ethnic population. These two variants exhibited normal uptake of p-aminohippurate, ochratoxin A and methotrexate assayed in X. laevis oocytes. One variant, OAT1-R454Q, was non-functional with respect to the above substrates. In the clinical study, there was no significant decrease in the renal secretory clearance of adefovir in family members heterozygous for OAT1-454Q in comparison to those with the reference transporter, OAT1-454R. These data indicate that the coding region of OAT1 has low genetic and functional diversity and suggest that coding region variants of OAT1 may not contribute substantially to interindividual differences in renal elimination of xenobiotics.


Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons.
Blocking the function of Stat (signal transducer and activator of transcription) proteins, which are critical for antiviral responses, has evolved as a common mechanism for pathogen immune evasion. The poxvirus-encoded phosphatase H1 is critical for viral replication, and may play an additional role in the evasion of host defense by dephosphorylating Stat1 and blocking interferon (IFN)-stimulated innate immune responses. Vaccinia virus (VACV) H1 can inhibit the phosphorylation of the transcription factor Stat1 after IFN-gamma stimulation of epithelial cells, greatly attenuating IFN-induced biological functions. In this study, we demonstrate that VACV infection is capable of inhibiting the phosphorylation of Stat1 and Stat2 after stimulation of fibroblasts or bone marrow-derived macrophages with either type I or type II IFNs, but did not inhibit the activation of Stat3 or Stat5 in either cell type. By using recombinant proteins for in vitro assays, we observe that variola virus H1 is more active than VACV H1, although it has similar selectivity for Stat targets. Differential effects of VACV infection were observed on the induction of IFN-stimulated genes, with complete inhibition of some genes by VACV infection, while others were less affected. Despite the IFN-gamma-induced expression of some genes in VACV-infected cells, IFN-gamma was unable to rescue the VACV-mediated inhibition of MHC class II antigen presentation. Moreover, VACV infection can affect the IFN-induced expression of Stat1-dependent and Stat1-independent genes, suggesting that the virus may target additional IFN-activated pathways. Thus, VACV targets multiple signaling pathways in the evasion of antiviral immune responses.


Mutational study of Streptomyces tyrosinase trans-activator MelC1. MelC1 is likely a chaperone for apotyrosinase.
The melanin operon (melC) of Streptomyces antibioticus contains two genes, melC1 and melC2 (apotyrosinase). Our previous studies indicated that MelC1 forms a transient binary complex with the downstream apotyrosinase MelC2 to facilitate the incorporation of copper ion and the secretion of tyrosinase. In this study, we investigated the role of histidine residues in the function of MelC1 by examining a series of substitution or deletion mutants. Of eight mutants only the substitution of His-117 with Asp in the mutant M-117D rendered the complete abolishment of the intracellular tyrosinase activity in both Streptomyces and Escherichia coli. Replacement of His-102 by Leu in the mutant M-102L also caused a 64-70% reduction of tyrosinase activity in Streptomyces and E. coli. These two mutations also affected the secretion of both MelC1 and MelC2 proteins. In vitro copper activation of the purified MelC1.MelC2 binary complex from these two mutants regained only 20-30% tyrosinase activity of the wild type. Biochemical characterization of the tyrosinases from these two mutants revealed that they were different in several aspects. The intracellular tyrosinase activity in M-117D, but not in M-102L, could be partially reactivated by copper ion or by the cell extract containing MelC1. The copper content and the specific activity of the tyrosinase purified from the culture supernatant from M-117D were only 40% of those in wild type and M-102L. Additionally, fast protein liquid chromatography analysis indicated that in these two mutants the copper activation process was defective, very likely due to the incompetent MelC1.MelC2 binary complex formed: reduced association in M-117D and elevated association in M-102L. Furthermore, the conformation of MelC2 in the binary complex or in the mature enzyme form in wild type could be differentiated by the proteinase K digestion pattern, and so did the conformation of MelC2 found in those of M-102L, but not in M-117D mutant. Taken together, our results demonstrate that MelC1 is indispensable in the incorporation of copper ion into MelC2 apotyrosinase via a transient, competent binary complex formation, during which a conformational transition of MelC2 has occurred. This strongly suggests that MelC1 is a chaperone for the apotyrosinase MelC2.


Effects of cinnamaldehyde on glucose-6-phosphate dehydrogenase activity, some biochemical and hematological parameters in diabetic rats.
Diabetes is a metabolic disorder related to blood insulin deficiency and high glucose level. Cinnamaldehyde is an important component of cinnamon and has an effect on blood glucose. It was aimed to investigate the the effect of cinnamaldehyde on the liver glutathione (GSH), glucose-6-phosphate dehidrogenase (G6PD) activity, blood glucose, protein, lipid and erythrocyte parameters, live weight in diabetic rats. Rat used for this research were divided 4 group as control, diabetic, cinnamaldehyde and diabetic + cinnamaldehyde group. The live weight and fasting blood glucose level, taken from tail vein were recorded every ten days. End of the trail the blood samples were taken from rats. Biochemical parameters with autoanalyzer and hematological parameters with blood cell counter were determined in blood. The activity of G6PD and GSH amounts were measured with ELISA in the liver tissues. Blood sugar, triglyceride, total cholesterol, VLDL, LDL, and urea levels increased in diabetic rats, and cinnemaldehyde significantly decreased these parameters. Cinnemaldehyde also showed a positive effect on body weight, blood total protein, and mean corpuscular volume in diabetes. A decrease in HbA1c and an increase in liver G6PD, GSH activity were found in treatment group, but these changes were not statistically significant. In conclusion, the antidiabetic, hypolipidemic and antioxidant effects of cinnamaldehyde were determined. It has also been shown to improve anaemia, ürea levels and weight loss.


[Assessment of the nutritional impact of the complementary feeding program of Panama in children under five years old].
To evaluate the nutritional impact of the Complementary Feeding Program of Panama in children under 5 years old. A retrospective cohort of children beneficiaries of the program was studied and compared with others of the same age and districts not involved in this intervention. Weight for age (W-A), height for age (H-A), and weight for height (W-H) was calculated in each control and the nutritional status determined according to Ministry of Health norms. Every beneficiary received six pounds/month of a food supplement containing cereals, legumes, calcium, iron and vitamin A (350 Kcal and 12 g of protein by 100 grams). Most of the children enter into the program in their second year of life with an average W-A and W-H of -1.5 +/- 1.2 and -0.6 +/- 0.9 respectively; both indicators were declining before the intervention (-0.6 +/- 1.2 y -0.3 +/- 1.3 respectively, p < 0.01). In 9 months of intervention an average change in W-A of 0.0 +/- 1.1 and H-A of - 0.1 +/- 1.1 was observed (NS). Weight gain was higher in children with lower W-A, in families with less children or mother with better education level (p < 0.05). In 35% of malnourished children and 24% of children at risk nutritional status improved during the intervention. Children with higher nutritional deficit at the beginning of the program have significantly better nutritional improvement (p < 0.001), encouraging the importance on focusing this program in malnourished children.


The cost of obesity in Canada.
Almost one-third of adult Canadians are at increased risk of disability, disease and premature death because of being obese. In order to allocate limited health care resources rationally, it is necessary to elucidate the economic burden of obesity. To estimate the direct costs related to the treatment of and research into obesity in Canada in 1997. The prevalence of obesity (body mass index of 27 or greater) in Canada was determined using data from the National Population Health Survey, 1994-1995. Ten comorbidities of obesity were identified from the medical literature. A population attributable fraction (PAF) was calculated for each comorbidity with data from large cohort studies to determine the extent to which each comorbidity and its management costs were attributable to obesity. The direct cost of each comorbidity was determined using data from the Canadian Institute of Health Information (for direct expenditure categories) and from Health Canada (for the proportion of expenditure category attributable to the comorbidity). This prevalence-based approach identified the direct costs of hospital care, physician services, services of other health professionals, drugs, other health care and health research. For each comorbidity, the cost attributable to obesity was determined by multiplying the PAF by the total direct cost of the comorbidity. The overall impact of obesity was estimated as the sum of the PAF-weighted costs of treating the comorbidities. A sensitivity analysis was completed on both the estimated costs and the PAFs. The total direct cost of obesity in Canada in 1997 was estimated to be over $1.8 billion. This corresponded to 2.4% of the total health care expenditures for all diseases in Canada in 1997. The sensitivity analysis revealed that the total cost could be as high as $3.5 billion or as low as $829.4 million; this corresponded to 4.6% and 1.1% respectively of the total health care expenditures in 1997. When the contributions of the comorbidities to the total cost were considered, the 3 largest contributors were hypertension ($656.6 million), type 2 diabetes mellitus ($423.2 million) and coronary artery disease ($346.0 million). A considerable proportion of health care dollars is devoted to the treatment and management of obesity-related comorbidities in Canada. Further research into the therapeutic benefits and cost-effectiveness of management strategies for obesity is required. It is anticipated that the prevention and treatment of obesity will have major positive effects on the overall cost of health care.