Factors determining conversion to laparotomy in patients undergoing total laparoscopic hysterectomy.
To identify the risk factors determining conversion to laparotomy during total laparoscopic hysterectomy (TLH) for benign diseases. We retrospectively reviewed medical records of 288 patients that underwent TLH during the first 2 years of performing TLH at Kang-Nam Sacred Heart Hospital. Twenty-three cases were converted to laparotomy. We compared patient characteristics, indications for hysterectomy, operation time, estimated blood loss, adhesion, uterine weight and postoperative complications between failed and successful groups. The rate of conversion to laparotomy was 8%. There were no differences in patient characteristics between the two groups. Independent risk factors for conversion were adhesion and uterine weight. The most common cause of the conversion to laparotomy was adhesions (p = 0.000). Uterine weight was found to be heavier in the failed group (331.5 ± 157.1 vs. 270.3 ± 132.5 g, p = 0.038). Estimated blood loss was greater in the failed group (455.6 ± 143.7 vs. 304.2 ± 45.8 ml, p = 0.047). Bladder injury occurred in the failed group more frequently than in the successful group (p = 0.024). An awareness of risk factors for conversion is important for better patient selection for TLH. Indirect measurement of uterine weight by sonography and detailed history taking is helpful in determining the appropriate hysterectomy route.


Association between malocclusion, tongue position and speech distortion in mixed-dentition schoolchildren: an epidemiological study.
Malocclusions are highly prevalent in childhood and adolescence, being considered a public health problem worldwide, in addition to be considered an important predictor in the tongue position and speech disorders. Evaluate the association of malocclusions with tongue position and speech distortion in mixed-dentition schoolchildren from the south of Brazil. This cross-sectional study was performed using a database of an epidemiological survey realized in the southern of Brazil, in 2015, for evaluating the dental and myofunctional condition of the mixed-dentition from 7-13 years' schoolchildren. The outcome variables were tongue position and speech distortion, evaluated by a trained and calibrated examiner. Characteristics regarding sociodemographic and oral health measures (Angle's classification of the malocclusion, overjet, overbite, posterior crossbite and respiratory mode) were also assessed. Poisson regression models with adjusted robust variance were used to evaluate the association among predictors variables in the outcomes. Results are presented as prevalence ratio (PR) and 95% confidence interval (95% CI). A total of 547 children were evaluated. Schoolchildren who presented anterior open bite (PR 2.36 95%CI 1.59-3.49) and having oral/oral-nasal breathing (RP 2.51 95%CI 1.70-3.71) are more likely to have altered position of the tongue. Both deep bite and being male represent protection factors for the abnormal tongue position. Regarding speech distortion, deep overbite presents a protective relationship to speech distortion (PR 0.41; 95%CI 0.24-0.71), whereas schoolchildren with posterior crossbite were more likely to present this problem (PR 1.77; 95%CI 1.09-2.88). Anterior open bite and posterior crossbite were the malocclusions related to speech distortion and/or altered tongue position. Oral/oral-nasal breathing was also related to myofunctional changes. Deep bite malocclusion was a protective factor for both speech problems and altered tongue position when compared to a normal overbite.


Protective effects of gingerol on streptozotocin-induced sporadic Alzheimer's disease: emphasis on inhibition of β-amyloid, COX-2, alpha-, beta - secretases and APH1a.
Gingerol is a major dietary compound that occurs in several plants belonging to the Zingiberaceae family. In the current study, the protective effect of gingerol on STZ-induced sporadic Alzheimer's disease (SAD) was determined. Gingerol was isolated from the seeds of Aframomum melegueta K. Schum and tested at doses of 10 and 20 mg/kgbwt for its possible effect on the SAD model in mice, using celecoxib (30 mg/kg bwt) as a reference standard. The curative effects of gingerol were assessed through measurement of β-amyloid (Aβ-42), α-, β- secretases, APH1a and COX-2 levels. In addition, improvement in the cognitive deficit in mice after treatment was confirmed using the water maze and Y-maze with intra-maze cues. Gingerol improved the cognitive and behavioral impairment and AD-like pathology in streptozotocin model mice. These beneficial effects occurred with an increase in α-secretase activity and a decrease in cerebral Aβ-42, β- secretase, APH1a activity and COX-2-linked neuro-inflammation.


The Interpersonal-Psychological Theory of Suicide in Adolescents: A Preliminary Report of Changes Following Treatment.
This study investigated change in suicide risk in the framework of the interpersonal theory of suicide. Fifty-four adolescents completed measures of interpersonal needs, acquired capability, depressive symptoms, and suicide risk at entry and exit from treatment. There was a significant drop following treatment in unmet interpersonal needs but not in acquired capability, consistent with the theory. Both change in the interaction between interpersonal needs and in depressive symptoms contributed unique prediction to change in suicide risk. These findings extend the research in understanding changes in suicide risk and inform treatment by suggesting cognitive targets for intervention.


Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: Results from a randomized phase II study in infants.
Vaccination with formulations containing pneumococcal protein antigens such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may extend serotype-related protection of pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae. This phase II, multi-center, observer-blind trial conducted in Europe (NCT01204658) assessed 2 investigational vaccines containing 10 serotype-specific polysaccharide conjugates of PHiD-CV and either 10 or 30µg of dPly and PhtD each. Infants randomized 1:1:1:1 received 4 doses of PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, or 13-valent PCV (PCV13), co-administered with DTPa-HBV-IPV/Hib, at ages ∼2, 3, 4 and 12-15months. Occurrences of fever >40.0°C following primary vaccination with PHiD-CV/dPly/PhtD vaccines compared to PHiD-CV (non-inferiority objective), dose superiority, safety and immunogenicity were assessed. 575 children received primary vaccination, and 564 booster vaccination. The non-inferiority objective was met; no fever >40.0°C causally related to vaccination was reported during primary vaccination. Incidence of adverse events appeared similar between the 3 PHiD-CV groups. Serious adverse events were reported in 13, 9, 21 (1 related to vaccination), and 17 children in the PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, and PCV13 groups, respectively. PHiD-CV/dPly/PhtD-30 was superior to PHiD-CV/dPly/PhtD-10 in terms of post-dose 3 anti-Ply and Anti-PhtD antibody levels. Anti-Ply and anti-PhtD antibody levels were higher in both PHiD-CV/dPly/PhtD groups than in controls and increased from post-primary to post-booster timepoint. Post-primary and booster vaccination, for each PHiD-CV serotype, ≥98.5% of participants in PHiD-CV/dPly/PhtD groups had antibody concentrations ≥ 0.2μg/mL, except for 6B (≥72.3%) and 23F (≥82.7%) post-primary vaccination. Similar results were observed in the PHiD-CV group. Immune responses to protein D and DTPa-HBV-IPV/Hib were within similar ranges for the 3 PHiD-CV groups. Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group.


Breastfeeding initiation, duration, and reasons for weaning in patients with systemic lupus erythematosus.
To assess breastfeeding in patients with systemic lupus erythematosus (SLE), a cross-sectional study of patients with SLE compared to a non-SLE sample was performed. Patients who had pregnancies subsequent to their diagnosis of SLE and who were followed up in the hospital were interviewed. The group of non-SLE mothers consisted of patients who had no known rheumatic disease at the time of their pregnancy, and who were approached at the hospital paediatrics service waiting room. Thirty-six pregnancies in 31 patients with SLE and the same number of non-SLE mothers were studied. The number of SLE patients who did not initiate breastfeeding was higher than that of non-SLE mothers (19.4 vs 5.6%, respectively; p 0.07). The average duration of breastfeeding in SLE patients was 6 months (SD 6 months) versus 12 months (SD 8 months) in non-SLE mothers (log rank p: 0.003). Fifty-three percent of the non-SLE mothers indicated no particular reason for weaning, and considered that they had nursed their children a suitable amount of time. Conversely, SLE patients often set weaning in motion on the grounds that they had been placed on medication (41%). However, when the treatment was analysed, in 6 out of 12 cases, it consisted of low doses of either corticosteroids or hydroxychloroquine. Patients with SLE showed reduced rates of initiating breastfeeding. They also showed reduced duration of breastfeeding, and the reason for cessation was frequently cited to be therapies which were actually of low risk. Breastfeeding duration could be optimised by improving the level of information provided to patients.


Rebirth fantasy and the psychoanalytic process.
In this paper, Jungian and Freudian perspectives on the fantasy of rebirth are explored and a brief review of the literature on the theme is used to show how that the rebirth fantasy seems to be a universal fantasy in the human mind, connected with the experience of both destruction and creation. In the psychoanalytic process the rebirth fantasy is connected with initial hopes for a better life, but is also a vehicle for creating the analytic pair and for separating from the 'totalitarian object'. An account of clinical work with a patient is given to illustrate the mutual and parallel process of rebirth in both the patient and the therapist. For the patient, the therapy was experienced as an awakening or a birth. The therapist was initially doubtful about the patient's capacity to engage in the analytic process but his involvement and interest were 'born' during the early sessions, enabling the patient to rely on him to lead her out of the claustrophobic power of the totalitarian object.


Investigating the Convergence between Actigraphy, Maternal Sleep Diaries, and the Child Behavior Checklist as Measures of Sleep in Toddlers.
The current study examined associations among actigraphy, maternal sleep diaries, and the parent-completed child behavior checklist (CBCL) sleep items. These items are often used as a sleep measure despite their unclear validity with young children. Eighty middle class families (39 girls) drawn from a community sample participated. Children (M = 25.34 months, SD = 1.04) wore an actigraph monitor (Mini-Mitter(®) Actiwatch Actigraph, Respironics) for a 72-h period, and mothers completed a sleep diary during the same period. Eighty-nine percent of the mothers and 75% of the fathers also filled out the CBCL (1.5-5). Mother and father CBCL scores were highly correlated. Overall, good correspondence was found between the CBCL filled out by mothers and sleep efficiency and duration derived from maternal sleep diaries (r between -0.39 and -0.25, p ≤ 0.05). Good correspondence was also found between the CBCL filled out by fathers and sleep efficiency as derived from maternal sleep diaries (r between -0.39 and -0.24, p ≤ 0.05), but not with sleep duration (all results were non-significant). Very few correlations between actigraphy and the CLBL scores reached statistical significance. The Bland and Altman method revealed that sleep diaries and actigraphy showed poor agreement with one another when assessing sleep duration and sleep efficiency. However, diary- and actigraphy-derived sleep durations were significantly correlated. Consistent with findings among older groups of children, this study suggests that the CBCL sleep items, sleep diaries, and actigraphy tap into quite different aspects of sleep among toddlers. The choice of which measures to use should be based on the exact aspects of sleep that one aims to assess. Overall, despite its frequent use, the composite sleep score of the CBCL shows poor links to objective measures of sleep duration and sleep efficiency.


Deep surgical site infection after ankle fractures treated by open reduction and internal fixation in adults: A retrospective case-control study.
Information on ankle fractures is limited. The purpose of this study was to investigate the incidence and risk factors for deep surgical site infection (DSSI) after open reduction and internal fixation (ORIF). Adult patients who underwent ORIF for an ankle fractures at 3 level-I centres between January 2013 and June 2017 were included. Data on demographic, injury-related, and surgery-related variables and biochemical indexes from the laboratory were collected from patients' electronic medical records. Univariate analysis and multivariate logistic regression analysis model were used to perform the data analysis through SPSS 19.0. Within 1-year postoperatively, 2.83% (74/2617) of cases developed DSSI, with the earliest occurring at the 4th and latest at 147th day. Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and methicillin-susceptible Staphylococcus aureus were the top 3 bacteria, causing 73% (37/51) of all the cases. Age (45-64 and ≥65 years), current smoking status, chronic heart disease, lower preoperative albumin level, open injury, and prolonged surgical duration were identified to be independently associated with DSSI occurrence. Preoperative active supplementation of nutrition, immediate smoking cessation, and optimisation of an operative plan for the reduction of surgical duration were feasible measures for DSSI prevention following ORIF of ankle fractures.


The minimal important difference of the King's Brief Interstitial Lung Disease Questionnaire (K-BILD) and forced vital capacity in interstitial lung disease.
Health status and forced vital capacity (FVC) are widely used outcome measures of interstitial lung disease (ILD) but there is a paucity of studies reporting the minimal clinically meaningful change in these parameters. A study was undertaken to assess the minimal important difference (MID) of an ILD specific health status questionnaire, the King's Brief ILD questionnaire (K-BILD) and that of FVC in a range of ILDs. 57 patients with ILD (17 idiopathic pulmonary fibrosis; IPF) completed the K-BILD (score range 0-100) at 2 separate clinic visits. Patients underwent spirometry at both visits. The MID was determined by a range of distribution methods (Standard error of mean: SEM and 0.3× Effect size: ES) and anchor based methods (objective: FVC and subjective: global rating of change questionnaires, GRCQ). The MID was derived by calculating an average of all methods. Health status was reduced at baseline in all patients, mean (SD) K-BILD total score 62(23). The average MID for K-BILD total score incorporating all methods was an 8 unit change (range 6-10). The average MID for FVC was a 6% change of baseline (range 4-7%). The K-BILD is a responsive patient reported outcome measure for patients with ILD. It can potentially be used to assess patients in the clinic and evaluate the response to therapy. The MID of the K-BILD total score is 8 units. The MID for FVC for a range of ILDs was 6%, similar to that reported recently for patients with IPF. Our findings will facilitate the clinical interpretation of health status and FVC data in ILD.


Application of Intelligent Intravenous Drug Dispensing Robot in Clinical Nursing.
In order to explore the application of intelligent intravenous drug dispensing robot in clinical nursing, the efficiency, residual amount, needle pushing, and pulling times, the incidence of accidental hand stab injury and the accuracy of drug dispensing were compared and observed between intelligent intravenous drug dispensing robot and manual dispensing. The study found that the sterile powder residual amount of injection is pointed out in the standard, the drug label is not equipped with ≤50 mg, and the residual limit is ≤ 15%; the lamination is 50-150 mg, the residual amount is limited to ≤10%; the marking is 150-500 mg, the residual amount is ≤ 7%; the marking is 500 mg, the residual amount is limited to ≤5%; 6 months of artificial deployment accidental stab ergonomics occur; without this phenomenon when using the drug-like robot, 6 months internal use of the pharmaceutical robot, 4 times of error occurrence, and errors occurred 60 times. During the clinical intravenous infusion dispensing process, the use of intelligent vein is used to configure the robot, improve the efficiency of the drug, reduce the incidence of drug residual, reduce the incidence of dispensing, increase the accuracy and safety of venous liquidation, and decrease to some extent professional injury caused by drug formulation for liquid nurses.


Adherence of Peptostreptococcus micros morphotypes to epithelial cells in vitro.
Peptostreptococcus micros, which is associated with oral and non-oral mixed anaerobic infections, occurs in three colony morphotypes, the smooth type, the rough type and the smooth variant of the rough type. These types differ in surface structures; the rough type expresses large fibrillar surface appendages, which are absent on the surface of both the smooth and the smooth variant of the rough type. To determine the role of these surface structures in adherence we characterized the adherence of the three morphotypes of P. micros to epithelial cells in vitro. Although all three types adhered well to epithelial cells, adhering numbers of the rough type were significantly lower than those of the smooth and the smooth variant of the rough type. Protease treatment increased the adherence of the rough type of the level of the two other types. The adherence of all three types was reduced more than 85% by treatment with 10 mM sodium periodate. Furthermore, the adherence was pH independent and could not be blocked by incubation with antisera to the bacteria. In addition, we determined the capacity to invade epithelial cells by P. micros. In an acridine orange assay such invasion could not be detected. Our results suggest that the adherence of P. micros to epithelial cells is mediated by periodate-sensitive extracellular polysaccharides and that the protruding fibril-like protein surface structures of the rough type have an obstructive effect on the adherence.


[Comparison of the effects and safety of atenolol and nifedipine in the treatment of angina pectoris].
The effects of atenolol (100 mg/day) and nifedipine (60 mg/day) on angina symptoms and exercise tolerance were compared in an open, randomized study. Twelve-week treatment period was compared with two weeks of placebo treatment in 51 patients with chronic stable angina pectoris. Mean frequency of angina attacks decreased significantly from 8.3 to 1.6 attacks per week after atenolol treatment (p < or = 0.05). Both drugs increased exercise tolerance to development of signs of ischemia on electrocardiogram (p < or = 0.05) and increased maximal exercise tolerance as well (p < or = 0.05). Mean ST segment depressions at peak exercise were significantly decreased after treatment with atenolol and nifedipine (p < or = 0.05). Both drugs also increased total exercise capacity in comparison with placebo period, stated as 100%:192% after atenolol and to 191% after nifedipine. No significant changes of heart rate and blood pressure were noted during treatment period. Twelve patients did not finished study, two of them suffered myocardial infarction with death in one of them (atenolol group, other one nifedipine group). Thus, atenolol in one daily dose is as effective as nifedipine in chronic stable angina patients when administered as single therapy.


Temporal Variance Analysis for Action Recognition.
Slow feature analysis (SFA) extracts slowly varying signals from input data and has been used to model complex cells in the primary visual cortex (V1). It transmits information to both ventral and dorsal pathways to process appearance and motion information, respectively. However, SFA only uses slowly varying features for local feature extraction, because they represent appearance information more effectively than motion information. To better utilize temporal information, we propose temporal variance analysis (TVA) as a generalization of SFA. TVA learns a linear transformation matrix that projects multidimensional temporal data to temporal components with temporal variance. Inspired by the function of V1, we learn receptive fields by TVA and apply convolution and pooling to extract local features. Embedded in the improved dense trajectory framework, TVA for action recognition is proposed to: 1) extract appearance and motion features from gray using slow and fast filters, respectively; 2) extract additional motion features using slow filters from horizontal and vertical optical flows; and 3) separately encode extracted local features with different temporal variances and concatenate all the encoded features as final features. We evaluate the proposed TVA features on several challenging data sets and show that both slow and fast features are useful in the low-level feature extraction. Experimental results show that the proposed TVA features outperform the conventional histogram-based features, and excellent results can be achieved by combining all TVA features.


Blockchain technology for improving clinical research quality.
Reproducibility, data sharing, personal data privacy concerns and patient enrolment in clinical trials are huge medical challenges for contemporary clinical research. A new technology, Blockchain, may be a key to addressing these challenges and should draw the attention of the whole clinical research community.Blockchain brings the Internet to its definitive decentralisation goal. The core principle of Blockchain is that any service relying on trusted third parties can be built in a transparent, decentralised, secure "trustless" manner at the top of the Blockchain (in fact, there is trust, but it is hardcoded in the Blockchain protocol via a complex cryptographic algorithm). Therefore, users have a high degree of control over and autonomy and trust of the data and its integrity. Blockchain allows for reaching a substantial level of historicity and inviolability of data for the whole document flow in a clinical trial. Hence, it ensures traceability, prevents a posteriori reconstruction and allows for securely automating the clinical trial through what are called Smart Contracts. At the same time, the technology ensures fine-grained control of the data, its security and its shareable parameters, for a single patient or group of patients or clinical trial stakeholders.In this commentary article, we explore the core functionalities of Blockchain applied to clinical trials and we illustrate concretely its general principle in the context of consent to a trial protocol. Trying to figure out the potential impact of Blockchain implementations in the setting of clinical trials will shed new light on how modern clinical trial methods could evolve and benefit from Blockchain technologies in order to tackle the aforementioned challenges.


Serious complications following transgression of the pleural space in drainage procedures.
Transgression of the parietal pleura may occur during placement of interventional drainage catheters into the liver and upper abdomen, and occasionally results in lethal complications. In a review of nearly 2,000 such procedures, four deaths were found to be related directly to pleural transgression from biliary drainage. Therefore, the anatomy of the pleura pertinent to abdominal needle or catheter insertion was analyzed. In 14 cadavers examined after intercostal needle insertion into the liver, needles inserted through the 9th intercostal space or higher punctured the pleura in all but one cadaver. Radiologic studies of 15 clinical cases revealed that elderly patients rarely depressed the diaphragm below the 9th intercostal space, which increases the risk of unsuspected puncture of the pleura. Review of clinical material revealed that diagnostic needle puncture through the parietal pleura carries far less risk than placement of a long-term drainage catheter. Methods to avoid puncture of the pleura, as well as the technical problems involved in such maneuvers, are given.


25-year analysis of a dental undergraduate research training program (BSc Dent) at the University of Manitoba Faculty of Dentistry.
Research in the context of the dental school has traditionally been focused on institutional/faculty accomplishments and generating new knowledge to benefit the profession. Only recently have significant efforts been made to expand the overall research programming into the formal dental curriculum, to provide students with a baseline exposure to the research and critical thinking processes, encourage evidence-based decision-making, and stimulate interest in academic/research careers. Various approaches to curriculum reform and the establishment of multiple levels of student research opportunities are now part of the educational fabric of many dental schools worldwide. Many of the preliminary reports regarding the success and vitality of these programs have used outcomes measures and metrics that emphasize cultural changes within institutions, student research productivity, and student career preferences after graduation. However, there have not been any reports from long-standing programs (a minimum of 25 years of cumulative data) that describe dental school graduates who have had the benefit of research/training experiences during their dental education. The University of Manitoba Faculty of Dentistry initiated a BSc Dent program in 1980 that awarded a formal degree for significant research experiences taking place within the laboratories of the Faculty-based researchers and has continued to develop and expand this program. The success of the program has been demonstrated by the continued and increasing demands for entry, the academic achievements of the graduates, and the numbers of graduates who have completed advanced education/training programs or returned to the Faculty as instructors. Analysis of our long-term data validates many recent hypotheses and short-term observations regarding the benefits of dental student research programs. This information may be useful in the design and implementation of dental student research programs at other dental schools.


Triboelectricity in insulating polymers: evidence for a mechanochemical mechanism.
Transfer of reaction products formed on the surfaces of two mutually rubbed dielectric solids makes an important if not dominating contribution to triboelectricity. New evidence in support of this statement is presented in this report, based on analytical electron microscopy coupled to electrostatic potential mapping techniques. Mechanical action on contacting surface asperities transforms them into hot-spots for free-radical formation, followed by electron transfer producing cationic and anionic polymer fragments, according to their electronegativity. Polymer ions accumulate creating domains with excess charge because they are formed at fracture surfaces of pulled-out asperities. Another factor for charge segregation is the low polymer mixing entropy, following Flory and Huggins. The formation of fractal charge patterns that was previously described is thus the result of polymer fragment fractal scatter on both contacting surfaces. The present results contribute to the explanation of the centuries-old difficulties for understanding the "triboelectric series" and triboelectricity in general, as well as the dissipative nature of friction, and they may lead to better control of friction and its consequences.


Developmental Studies of Maize-Infesting Picture-Winged Flies (Diptera: Ulidiidae).
Eleven species of picture-winged flies (Diptera: Ulidiidae) attack maize (Zea mays L.) in the Americas. Field and laboratory studies were used to determine developmental times on sweet corn ears for the three most common species attacking the crop in the United States, Chaetopsis massyla (Walker), Euxesta eluta Loew, and Euxesta stigmatias Loew. Egg plus larval stage developmental times were evaluated in early Spring and late Fall 2009, and late Spring 2010, by placing newly deposited eggs in protected ears in the field. Newly formed puparia were removed daily from cages and held in the laboratory to determine pupal developmental times. Developmental times were compared with flies reared on artificial diet in the laboratory. Ear- and diet-reared adults were held until their death to determine adult longevity. Developmental times, including for pupae from ear-reared larvae, were significantly affected by species and season. All three species required nearly twice as long to complete development in the late Fall compared to late Spring studies. Flies required 3-13 d longer to complete development on artificial diet than on ears. Euxesta eluta adults lived two to three times longer than the other species, and females of all species lived 10-15% longer than males. Species and seasonal developmental times are discussed in relation to ear developmental times and control strategies. It is estimated that 16-19 generations per year of all three fly species can develop in the field in the sweet corn production area of southern Florida.


[Comparative effects of 4 cephalosporins on the incorporation of tritiated diaminopimelic acid during bacterial growth].
When comparing antibiotic activities, it might be of interest to study parameters other than minimal inhibitory concentrations (MIC's). Specific activity of beta-lactams on bacterial cell wall makes it possible to determine radiolabelled diaminopimelic acid (DAP) incorporation in growing cultures. We have studied the effects of various concentrations of cefalotin , cefotaxime, latamoxef (moxalactam) and ceftiolene (42 980 RP) on DAP incorporation in 6 strains of E. coli, E. cloacae and S. aureus. Drug concentration which inhibits 90 % of radioactivity incorporation (CII 90) was found to vary from 0.1 X MIC to 3 X MIC. This fact suggests that beta-lactam action on cell wall synthesis and/or structure and MIC's are not always strictly correlated.


Prokaryotic RNA activates endothelial cells promoting neutrophil transmigration.
Endothelial cell (EC)-neutrophil (PMN) interactions are crucial in the resolution of bacterial infections. Prokaryotic RNA (pRNA) has been reported as a pathogen-associated molecular pattern that is released from bacteria upon death and is able to activate PMN. In this work, we studied the effects of pRNA on EC and investigated whether these effects could modulate EC-PMN interaction. For this purpose, we purified total pRNA from Escherichia coli and used it as a stimulus for Human Umbilical Vein Endothelial Cells (HUVEC). We found that the incubation of pRNA with HUVEC caused the increase of surface intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on HUVEC, and the secretion of IL-8 and von Willebrand factor, characteristics consistent with HUVEC activation, without causing toxic effects. Moreover, pRNA-treated HUVEC also induced PMN adhesion and the conditioned medium obtained from treated-HUVEC was chemotactic for PMN and caused their activation, as determined by CD11b upregulation. As reported previously, the degradation products of pRNA induced similar biological effects. The treatment of HUVEC with endocytosis inhibitors revealed that the entry of pRNA partially relied on a clathrin-dependent mechanism, whereas the effects of degradation products could not be inhibited by any of the inhibitors tested. Using a transwell system, we found that pRNA or degraded pRNA were also able to stimulate HUVEC when recognized from the basolateral side. Our results indicate that pRNA activates EC, resulting in the modulation of EC-PMN interaction by inducing PMN chemotaxis, adhesion and activation. In the context of infection, pRNA sensed by EC and PMN could favor bacterial clearance.


[Intraspecific variations of Paecilomyces fumosoroseus in temperature fitness and carbendazim resistance].
A total of six wild strains of fungal biocontrol agent Paecilomyces fumosoroseus were grown at 15 degrees C-35 degrees C to reveal their variations in colony growth, conidiation, and conidial viability. The results showed that the test three indices were the best at 25 degrees C, but differed significantly at different temperatures for a given strain or at a given temperature among test strains. The strains Pfr116 and Pfr6206 behaved better or more stably than other strains at 15 degrees C-35 degrees C. The sensitivities of the fungal strains to gradient concentrations of fungicide carbendazim were assayed at the optimal temperature, based on their colony growth diameters and the counts of colony forming units (CFU). The inhibitory effect of carbendazim concentration on CFU counts fitted well to a Logistic model, with high coefficients of determination being achieved for all the strains (r2 > or = 0.90). The fitted minimal inhibitory concentration (MIC) values showed a low carbendazim resistance of strains Pfr4205 and Pfr116 (MIC < or = 20.0 microg x ml(-1)), whereas the other four strains fell within medium resistance to the fungicide (20 < or = MIC < or = 100). The MIC of strain Pfr6206 (93.5 microg x ml(-1) was very close to the high resistance level of MIC > 100 microg x ml(-1). Therefore, strain Pfr6206 was satisfactory with both the temperature fitness and the carbendazim resistance, and could be considered as a candidate strain for a fungal formulation adapting to more variable crop systems against insect pests.


Statistical Challenges in Development of Prognostic Models in Diffuse Large B-Cell Lymphoma: Comparison Between Existing Models - A Systematic Review.
Based on advances in the diagnosis, classification, and management of diffuse large B-cell lymphoma (DLBCL), a number of new prognostic models have been proposed. The aim of this study was to review and compare different prognostic models of DLBCL based on the statistical methods used to evaluate the performance of each model, as well as to analyze the possible limitations of the methods. A literature search identified 46 articles that proposed 55 different prognostic models for DLBCL by combining different clinical, laboratory, and other parameters of prognostic significance. In addition, six studies used nomograms, which avoid risk categorization, to create prognostic models. Only a minority of studies assessed discrimination and/or calibration to compare existing models built upon different statistical methods in the process of development of a new prognostic model. All models based on nomograms reported the c-index as a measure of discrimination. There was no uniform evaluation of the performance in other prognostic models. We compared these models of DLBCL by calculating differences and ratios of 3-year overall survival probabilities between the high- and the low-risk groups. We found that the highest and lowest ratio between low- and high-risk groups was 6 and 1.31, respectively, while the difference between these groups was 18.9% and 100%, respectively. However, these studies had limited duration of follow-up and the number of patients ranged from 71 to 335. There is no universal statistical instrument that could facilitate a comparison of prognostic models in DLBCL. However, when developing a prognostic model, it is recommended to report its discrimination and calibration in order to facilitate comparisons between different models. Furthermore, prognostic models based on nomograms are becoming more appealing owing to individualized disease-related risk estimations. However, they have not been validated yet in other study populations.


Hard time to be parents? Sea urchin fishery shifts potential reproductive contribution of population onto the shoulders of the young adults.
In Sardinia, as in other regions of the Mediterranean Sea, sustainable fisheries of the sea urchin Paracentrotus lividus have become a necessity. At harvesting sites, the systematic removal of large individuals (diameter ≥ 50 mm) seriously compromises the biological and ecological functions of sea urchin populations. Specifically, in this study, we compared the reproductive potential of the populations from Mediterranean coastal areas which have different levels of sea urchin fishing pressure. The areas were located at Su Pallosu Bay, where pressure is high and Tavolara-Punta Coda Cavallo, a marine protected area where sea urchin harvesting is low. Reproductive potential was estimated by calculating the gonadosomatic index (GSI) from June 2013 to May 2014 both for individuals of commercial size (diameter without spines, TD ≥ 50 mm) and the undersized ones with gonads (30 ≤ TD < 40 mm and 40 ≤ TD < 50 mm). Gamete output was calculated for the commercial-size class and the undersized individuals with fertile gonads (40 ≤ TD < 50 mm) in relation to their natural density (gamete output per m2). The reproductive potential of populations was slightly different at the beginning of the sampling period but it progressed at different rates with an early spring spawning event in the high-pressure zone and two gamete depositions in early and late spring in the low-pressure zone. For each fertile size class, GSI values changed significantly during the year of our study and between the two zones. Although the multiple spawning events determined a two-fold higher total gamete output of population (popTGO) in the low-pressure zone, the population mean gamete output (popMGO) was similar in the two zones. In the high-pressure zone, the commercial-sized individuals represented approximatively 5% of the population, with almost all the individuals smaller than 60 mm producing an amount of gametes nearly three times lower than the undersized ones. Conversely, the high density of the undersized individuals released a similar amount of gametes to the commercial-size class in the low-pressure zone. Overall, the lack of the commercial-size class in the high-pressure zone does not seem to be very alarming for the self-supporting capacity of the population, and the reproductive potential contribution seems to depend more on the total density of fertile sea urchins than on their size. However, since population survival in the high-pressure zone is supported by the high density of undersized sea urchins between 30 and 50 mm, management measures should be addressed to maintain these sizes and to shed light on the source of the larval supply.


Remote Assessment of Cognitive Impairment Level Based on Serious Mobile Game Performance: An Initial Proof of Concept.
Individuals with cognitive impairments are evaluated using clinically validated cognitive assessment tools, which need to be administered by trained therapists. This serves as a major barrier for frequent and longitudinal monitoring of patients' cognitive impairment level. We introduce Neuro-World, a set of six mobile games designed to challenge visuospatial short-term memory and selective attention, which allows one to self-administer the assessment of his/her cognitive impairment level. Game performance is analyzed to estimate a widely accepted clinical measure, the mini mental state examination (MMSE), which highlights the translational impact of the system in real-world settings. We collected game-specific performance data from 12 post-stroke patients at baseline and a three-month follow-up, which were used to train supervised machine learning models to estimate the corresponding MMSE scores. The results presented herein show that the proposed approach can estimate the MMSE scores with a normalized root mean square error of 5.75%. We also validate the system's responsiveness to longitudinal changes in cognitive impairment level and demonstrate the system's positive usability in cognitively impaired individuals and their willingness to adhere to the longitudinal use. This study demonstrates that Neuro-world has great potential to be used to evaluate the cognitive impairment level and monitor its long-term change. This study enables new clinical and research opportunities for accurate, longitudinal assessment of cognitive function via mobile games.


How clinical nurse and midwifery consultants optimise patient care in a tertiary referral hospital.
To develop new insights into the phenomenon of clinical nurse/midwifery consultant clinical effectiveness in a tertiary referral hospital. International studies identify the pivotal role clinical nurse/midwifery consultants play in patient outcomes. There remains, however, a significant deficit in our knowledge of how these, or other advanced practice nurses and midwives, apply their extensive experience, ontological understandings and tacit knowledge to the enhancement of patient outcomes in complex healthcare environments. This study was underpinned by the principles of Heideggerian hermeneutic phenomenology. Recruitment involved expressions of interest distributed hospital-wide to clinical nurse/midwifery consultants. Inclusion criteria specified a minimum of three years' experience. Fifteen clinical nurse/midwifery consultants, representing a broad range of specialties, were interviewed. Preliminary descriptive analysis of transcribed data was followed by in-depth hermeneutic analysis. The findings comprise four themes: walking beside the patient, anticipating the unexpected, pushing through barriers and leading within a complex system. These themes highlight how clinical nurse/midwifery consultants significantly influence pre-existing trajectories of patient care delivery through context-appropriate strategies. This study introduces new insights into the meanings advanced practice nurses and midwives develop from their engagements with patients and how these meanings inform clinical decisions. The paper accomplishes this by drawing on Heideggerian philosophical concepts such as ontological understandings, authenticity and care. It also casts light on the participants' shared understandings of how to synergise expectations within the team. The significance of this paper lies in the uncovering of ontological understandings and tacit knowledge of how consultant nurses and midwives optimise patient care delivery in challenging situations. The findings indicate, however, that the value of these internationally established roles is yet to be fully realised. The paper concludes by recommending strategies to assist newly appointed clinical nurse/midwifery consultants transition into these demanding autonomous roles.


Viability of the antigen determines whether DNA or urocanic acid act as initiator molecules for UV-induced suppression of delayed-type hypersensitivity.
UV radiation suppresses the immune response, and UV-induced immune suppression contributes to UV-induced photocarcinogenesis. For UV-induced immune suppression to occur, electromagnetic energy (i.e. UV radiation) must be converted to a biological signal. Two photoreceptors have been identified in the skin that serves this purpose, epidermal DNA and trans-urocanic acid (UCA). Although compelling evidence exists to support a role for each pathway (UV-induced DNA damage or photoisomerization of UCA) in UV-induced immune suppression, it is not clear what determines which photoreceptor pathway is activated. To address this question, we injected UV-irradiated mice with a monoclonal antibody with specificity for cis-UCA or applied liposomes containing DNA repair enzymes to the skin of UV-irradiated mice. The effect that each had on UV-induced suppression of delayed-type hypersensitivity was measured. We asked whether the light source used (FS-40 sunlamps vs solar-simulated UV radiation) altered whichever pathway of immune suppression was activated. Different doses of UV radiation and the viability of the antigen were also considered. Neither the dose of UV nor the light source had any influence on determining which pathway was activated. Rather, we found that the viability of the antigen was the critical determinant. When live antigens were used, UV-induced immune suppression was blocked with monoclonal anti-cis-UCA but not with T4 endonuclease V-containing liposomes. The reverse was observed when formalin-fixed or killed antigens were used. Our findings indicate that antigen viability dictates which photoreceptor pathway predominates after UV exposure.


The food intake of rats during pregnancy and lactation.
Quantities of food required by Sprague-Dawley rats during gestation and lactation and in the post-lactation period were examined. Rats allowed to eat ad libitum during pregnancy consumed quantities of food only slightly greater than the amount reported to be the average intake of pregnant Sprague-Dawley rats (20 g/day). Rats delivered their pups on day 22 or day 23 of the gestation period, but regardless of the day of delivery, the food intake of each rat decreased on day 21 of pregnancy and then decreased a second time on the day of parturition. During lactation, food consumption of the rats soon exceeded the amount reported as the average intake of lactating rats (30-35 g/day). Food intake was found to escalate from 12.2 +/- 3.1 g/rat on day 0 of lactation, the lowest intake in the study, to 94.4 +/- 23.7 g on day 21 of lactation. However, in the latter part of the lactation period, the intake represented the combined food intake of dams and pups. Eight days in the post-lactation period were required for food intake of dams to return to a level near that recorded at the beginning of pregnancy.


Effect of pentoxifylline treatment on testicular perfusion and semen quality in Miniature horse stallions.
The objective was to investigate the effects of pentoxifylline (PTX) on testicular perfusion and sperm production in stallions. In a preliminary study, six mature Miniature horse stallions were given 0, 8.5, or 17.0 mg/kg of PTX orally, twice daily, for 3 d. Total Arterial Blood Flow Rate (TABFR) was higher (P < 0.05) in all treated versus control stallions during and after treatment. Two months later (during the fall and winter), the same stallions received either 0 or 17 mg/kg of PTX orally, twice daily for 60 d. Resistance and pulsatility indices (RI and PI, respectively) decreased in PTX-treated stallions between Treatment 1 and Post-treatment periods. Arterial diameter, as well as Total Arterial Blood Flow (TABF), decreased in controls between Baseline and Treatment 1 (P < 0.05). A similar decrease in arterial diameter was delayed in Group TREATED, but reached significance during Post-treatment (P < 0.05), whereas TABF did not change in this group. Furthermore, TABFR had a transient tendency to increase during Treatment 1 (P < 0.1), whereas it steadily decreased in controls and reached significance in the Post-treatment period (P < 0.05). Both RI and PI were negatively correlated with end diastolic velocity (EDV) in both groups (P < 0.0001). There were positive correlations between RI and peak systolic velocity (PSV) in treated stallions during Treatment 1 (RI: r = 0.53, P = 0.021; PI: r = 0.59, P = 0.007). Also, there were negative correlations between Time Averaged Maximum Velocity (TAMAX) and Doppler indexes in treated stallions during Treatment 2 period (RI: r = -0.49, P = 0.006; PI: r = -0.47, P = 0.008), and during Post-treatment periods (RI: r = -0.40, P = 0.049; PI: r = -042, P = 0.039). Transient hydrocele occurred in all treated stallions (a potential complication of high-dose PTX). Semen end points were not significantly affected by PTX treatment. In conclusion, PTX delayed the seasonal decrease of testicular perfusion in stallions. Sperm quality and quantity were not significantly affected; perhaps they would have been enhanced by prolonged treatment.


Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging.
The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.


Polycystic Ovary Syndrome (PCOS): A Cross-Sectional Observational Study Analyzing the Quality of Content on YouTube.
Polycystic ovary syndrome (PCOS), a chronic multifactorial disorder in women of reproductive age group, is a major public health problem. With most women resorting to platforms like "YouTube" that form a perfect source of edutainment, our aim was to analyze the quality of content available regarding the same. The aims and objectives of this study were to assess the quality and reliability of content related to PCOS on YouTube by analyzing the DISCERN score, global quality score (GQS), and video power index (VPI). It was a facility-based cross-sectional study undertaken on a single day with each author reviewing 10 videos from YouTube on PCOS using predetermined keywords. The number of likes, dislikes, views, comments, and uploader backgrounds were evaluated. DISCERN score, GQS, and VPI were also calculated for each video. While data entry was done using Microsoft Excel 2020 (Microsoft Corporation, Washington, United States), the analysis was carried out using SPSS Statistics version 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). Categorical variables were expressed as frequency and percentages, and statistical significance was determined using the Kruskal-Wallis test/one-way ANOVA. A total of 80 videos that fit the inclusion criteria were analyzed. A majority of the videos (80%) were posted a year back with no updates. Only 28.8% of the video content was posted by doctors. Though most videos (96.25%) shared information pertaining to symptomatology, only 45% spoke regarding prevention. Promotional content was noted in 28.75% of the video content. GQS and VPI were better with information being provided by doctors, hospitals, and healthcare organizations (p-value 0.033 and 0.006, respectively). With women reaching out to edutainment platforms like YouTube to clarify their concerns surrounding lifestyle diseases such as PCOS in the digital era, it becomes relevant to evaluate the quality of content available on such platforms. The findings of the study form a prototype for addressing the existing gaps in the knowledge available on YouTube. Furthermore, the findings warrant frequent monitoring of such available web-based content and delivery of such content only from qualified wellness experts.


Increased sensitivity to norepinephrine cardiac arrhythmias in the deoxycorticosterone acetate high salt rat before the onset of hypertension.
To determine whether salt loading increases the sensitivity of the myocardium to fatal arrhythmias induced by norepinephrine, four groups of Sprague-Dawley rats were studied. Group I received both saline (0.9%) as drinking water and deoxycorticosterone acetate (DOCA) (0.5 mg/kg, 3 times) for 14 days (DOCA high salt group); group II received only 0.9% saline as drinking water (high salt group); group III received DOCA in the same dose regime, but tap water to drink (DOCA group); and group IV received tap water (control). Under pentobarbital anesthesia, norepinephrine was infused and electrocardiogram and blood pressure were monitored. The DOCA high salt group developed arrhythmias significantly (p less than 0.05) earlier than at lower norepinephrine doses. The dose at which 50% mortality occurred was 20 micrograms . kg-1 . min-1 in DOCA high salt group, 37 micrograms . kg -1 . min-1 in high salt group, 40 micrograms . kg-1 . min-1 in the control, and 44 micrograms . kg-1 . min-1 in the DOCA group. The cumulative dose of norepinephrine associated with 50% mortality was 160 micrograms/kg in the DOCA high salt group, 370 micrograms/kg in the high salt group, 530 micrograms/kg in the control group, and 600 micrograms/kg in the DOCA group. The blood pressure after sodium loading before norepinephrine infusion was similar in all three groups. The blood pressure response to norepinephrine was not significantly different between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effects of early submaximal cardiopulmonary exercise test and cardiac rehabilitation for patients with acute myocardial infarction after percutaneous coronary intervention: a comparative study].
To investigate the safety and effects of early submaximal cardiopulmonary exercise test (CPET) and cardiac rehabilitation for patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). 94 patients with AMI after PCI were randomly divided into 2 groups: exercise group undergoing anaerobic rehabilitation training based on anaerobic threshold (AT) exercise prescription for 3 months, and control group, conducting exercise according to the needs of the patients themselves. Three months later, the exercise cardiopulmonary function was evaluated. In the first CPET 89 patients attained their anaerobic threshold (AT) and their heart rates were lower than their target heart rates following the exercise test. The oxygen consumption at the anaerobic threshold (VO2AT) 3 months later of the exercise group was [(12.6 +/- 2.9) ml x min(-1) x kg(1)], significantly greater and that before the exercise [(10.5 x 2.9) ml x min x kg(-1), P = 0.000]. The peak oxygen uptake (VO2 pea) 3 months of the exercise group was (20 +/- 4) ml x min(-1) x kg(-1), signficantly greater then that before exercise [(14 +/- 4) ml x min(-1) x kg(-1), P = 0.000]. The LAT 3 months of the exercise group was (42 +/- 16) J x s(-1), significantly higher than that before exercise p [(33 +/- 20) J x s(-1), P = 0.000]. The workload at peak level (Lpeak) 3 months of the exercise group was (89 +/- 14) J x s(-1) significantly greater than thatbefore exercise [(66 +/- 21) J x s(-1), P = 0.000]. And the VO2pea and Lpeak of 3 months later of the control group were [(19 +/- 4) ml x min(-l) x kg(-1)) and (80 +/- 14) J x s(-1)] respectively, both significantly higher than those before exercise [(14 +/- 4) ml x min(-1) x kg(-1) and (64 +/- 21) J x s(-1), both P = 0.000]. The early submaximal CPET and cardiac rehabilitation for patients with AMI after PCI are not only safe but also can improve their exercise capacity.


Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol.
In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.


Ability of Plasmodium falciparum to invade Southeast Asian ovalocytes varies between parasite lines.
Plasmodium falciparum, the causative agent of the most lethal form of human malaria, uses multiple ligand-receptor interactions to invade host red blood cells (RBCs). We studied the invasion of P falciparum into abnormal RBCs from humans carrying the Southeast Asian ovalocytosis (SAO) trait. One particular parasite line, 3D7-A, invaded these cells efficiently, whereas all other lines studied invaded SAO RBCs to only about 20% of the extent of normal (non-SAO) cells. This result is consistent with the clinical observation that SAO individuals can experience high-density P falciparum infections and provides an explanation for previous discrepant results on invasion of SAO RBCs. Characterization of the invasion phenotype of 3D7-A revealed that efficient invasion of SAO RBCs was paralleled by relatively efficient invasion of normal RBCs treated with either neuraminidase, trypsin, or chymotrypsin and a novel capacity to invade normal RBCs treated sequentially with both neuraminidase and trypsin. Our results suggest that only parasites able to use some particular invasion pathways can invade SAO RBCs efficiently in culture. A similar situation might occur in the field.


Associations between serum relaxin 2, aneurysm formation/size and severity of atherosclerosis: a preliminary prospective analysis.
Serum relaxin 2 (RL2) is a pleiotropic hormone that acts on various organs and systems, particularly the cardiovascular system. Although RL2 seems to upregulate the synthesis of nitric monoxide (NO) and matrix metalloproteinase (MMP)-2 and -9, current literature on its role in atherosclerosis and aneurysm formation is scarce. The aim of this study was to investigate the levels of serum RL2 in patients with an arterial aneurysm as well as in atherosclerotic patients, and correlate them with the severity of their related vascular disease. A total of 53 subjects were enrolled in this study: 37 patients were scheduled to undergo surgery: 21 patients for different forms of atherosclerotic disease (ATH), 16 patients for an arterial aneurysm (AA), 6 patients for undergoing temporal artery biopsy (TAB), and 10 healthy blood donors (HBD) served as the control groups. RL2 was measured using enzymelinked immunosorbent assay. RL2 was significantly higher in AA patients compared to ATH (P<0.01), TAB (P<0.001) and HBD (P<0.01). No significant difference was found between the ATH and TAB groups (P>0.05). In addition, ATH and AA patients were further subdivided based on the severity of their disease. Serum RL2 was progressively increased in patients with arterial aneurysms, showing a positive relationship with the size of the aneurysmatic dilatation. By contrast, the RL2 level was inversely related to the severity of the atherosclerotic disease. Studies with a larger cohort incorporating a consistent study population are warranted to verify our results and shed light on the mechanistic background of these processes.


Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains.
Transactivation by the ETS family of transcription factors, whose members share structurally conserved DNA-binding domains, is variably sensitive to methylation of their target genes. The mechanism by which DNA methylation controls ETS proteins remains poorly understood. Uncertainly also pervades the effects of hemi-methylated DNA, which occurs following DNA replication and in response to hypomethylating agents, on site recognition by ETS proteins. To address these questions, we measured the affinities of two sequence-divergent ETS homologs, PU.1 and Ets-1, to DNA sites harboring a hemi- and fully methylated CpG dinucleotide. While the two proteins bound unmethylated DNA with indistinguishable affinity, their affinities to methylated DNA are markedly heterogeneous and exhibit major energetic coupling between the two CpG methylcytosines. Analysis of simulated DNA and existing co-crystal structures revealed that hemi-methylation induced non-local backbone and groove geometries that were not conserved in the fully methylated state. Indirect readout of these perturbations was differentially achieved by the two ETS homologs, with the distinctive interfacial hydration in PU.1/DNA binding moderating the inhibitory effects of DNA methylation on binding. This data established a biophysical basis for the pioneering properties associated with PU.1, which robustly bound fully methylated DNA, but not Ets-1, which was substantially inhibited.


A quality marker study on salvianolic acids for injection.
The quality of Chinese medicine (CM) has being an active and challenging research area for CM. Prof. Chang-Xiao Liu et al first proposed the concept of quality marker (Q-Marker) for the quality evaluation and control on CM. This article describe the exploratory studies of Q-Marker in salvianolic acids for injection (SAI) based on this new concept. This study was designed to screen Q-Marker of SAI and establish its quality control method based on the concept of CM Q-Marker. Based on the concept of CM Q-Marker, the SAI was investigated for the identification of chemical components and their sources. The pharmacological effects on cerebral ischemia and reperfusion induced injury in rats were also investigated. Furthermore, the target cell extracts and pharmacokinetic studies were conducted to screen Q-Markers. Finally, the fingerprints and determination based on Q-Markers were established to assess the quality of SAI more effectively. Overall, 20 constituents in SAI were identified. It was found that salvianolic acid B (SA-B), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid D (SA-D) and salvianolic acid Y (SA-Y) are major chemical components of SAI. Based on chemical components identifications, analysis of their sources, target cell extracts and pharmacokinetic studies, four phenolic acids, namely SA-B, RA, LA and SA-D, were screened and determined as effective Q-Markers of SAI. This study demonstrated that the described method is a powerful approach for detecting Q-Markers, which can be used as control index for the quality assessment of CM.


Isolation of granulosa-like cells from the bovine secretory corpus luteum and their characterization in long-term culture.
The isolation of cells termed type 5 from the bovine corpus luteum was recently reported. Since these cells were reminiscent of immature granulosa cells, their morphological and functional relationship requires further investigation in view of the novel concept of corpus luteum growth. It suggests that putative stem cells of unknown origin supply the pool of small luteal cells. Bovine corpora lutea were mechanically dispersed, cell suspensions separated over a Percoll density gradient, and type 5 cells purified by colony transfer. Granulosa cells were harvested from small-sized antral follicles. Observations were carried out at the light and electron microscopical level. 3 beta-Hydroxy-steroid-dehydrogenase was localized histochemically in addition to intracellular lipid droplets stained with nile red. Immunolocalization was used to study Factor VIII antigen presence, the architecture of the cytoskeleton, as well as the occurrence of neuronal cell adhesion molecules, and of neuronal cadherin-like molecules. The uptake of acetylated low density lipoprotein was examined. As for progesterone concentration, cells were seeded at low density on day zero. Cell numbers and progesterone levels of supernatants were determined on day 10 in culture. Type 5 cells behaved morphologically like immature granulosa cells, yet the total cell number and the progesterone concentration differed for type 5 cells compared to granulosa cells. The addition of LH had no influence on the progesterone concentration as seen for either type 5 cells or for granulosa cells. It is concluded that type 5 cells, which were originally mistaken for microvascular endothelial cells, display similarities with immature granulosa cells. Type 5 cells may play a role in renewal of luteal cells.


[The lymphatic system of the liver in alcoholic intoxication].
Liver of men and test animals (dogs, white rats) has been studied by means of a complex of injection, histological and electron microscopical methods (179 organs). At alcoholic intoxication all elements of the lymphatic bed (capillaries, postcapillaries, lymphangions) demonstrate certain adaptive-compensatory or pathological changes. Their manifestation degree depends on duration of alcoholization (in the experiment--up to 7 months). The greatest changes are noted in the hepatic lymphatic bed of adolescents and of the first mature age. In the test animals the functional rearrangement is demonstrated as certain changes of lymph outflow via the thoracic duct, which was wider than in the control during the whole period of the experiment. A high resistivity of the lymphatic bed, activation of its function, absence of any parallelism between the morphological and functional rearrangements in the lymphatic bed have been revealed. Certain parallelism is noted in development of the morphological rearrangements between the lymphatic and circulatory links of the hepatic vascular bed and cell elements of the organ.


[Determination of levamisole in livestock products using high performance liquid chromatography].
A method is described for the determination of the anthelmintic levamisole in muscle, liver, kidney and fat of cattle, swine and poultry using high performance liquid chromatography with photodiode array detection. Levamisole was extracted from an alkaline sample with ethyl acetate and back-extracted with 0.1 mol/L hydrochloric acid. The extract was applied to an SCX solid-phase extraction column. The column was washed with water and methanol. Levamisole was eluted with a solution of ammonia in methanol. The eluate was evaporated to dryness and the residue was dissolved in the mobile phase and injected into the HPLC system. Mean recoveries from 0.01-0.10 microgram/g fortified muscle, liver, kidney and fat samples ranged from 78.3 to 99.8%. The detection limit for the assay was 0.005 microgram/g.


Increasing understanding of environmental modifications using the Virtual Dementia Experience for professional carers of people living with dementia.
Modifications to the environment can have a positive impact on the person living with dementia. The purpose of this study was to examine the effects of a virtual reality (VR) educational workshop on improving understanding of the impact of environments for people living with dementia for carers in residential aged care facilities in Australia. Participants were nonrandomly allocated to one of two conditions: a VR condition which enabled them to take the perspective of a person living with dementia as they navigate a home environment (n = 40), or to a non-VR condition, in which participants received equivalent information in a classroom without the use of VR (n = 56). Participants completed a purpose-built pictorial measure of their understanding of environmental factors that could impact on people with dementia before and after the workshop. Following education, an analysis of covariance revealed that compared to non-VR education, those who received VR education identified a significantly greater number of appropriate environmental modifications, after adjusting for practice test scores. The results from this study demonstrate the utility of VR as a promising tool to improve carers' understanding of the ways in which the environment can be modified to assist people living with dementia.


Monitoring avian influenza A(H7N9) virus through national influenza-like illness surveillance, China.
In China during March 4-April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical.


Inhibition of alpha(v)beta3 integrin reduces angiogenesis, bone turnover, and tumor cell proliferation in experimental prostate cancer bone metastases.
The growth of metastatic prostate cancer cells in the bone involves an intimate interaction between the tumor cells and various elements of the bone microenvironment, resulting in increased rate of bone turnover and rapid tumor growth. The alpha(v)beta3 integrin has been shown to play an important role in tumor growth and angiogenesis, and is known to be critical to osteoclast formation and activity. This study was designed to examine the role of alpha(v)beta3 expressed by cells native to the bone in the growth and pathogenesis of prostate cancer bone metastases. Human prostate cancer cells which do not express alpha(v)beta3 or alpha(IIb)beta3 integrins were injected directly into human bone fragments previously implanted subcutaneously in SCID mice (SCID-human-bone model). At the same time treatment with anti-beta3 antibody fragment (m7E3 F(ab')2) i.p. at 300 microg/dose 3 x per week was initiated and continued for 2 weeks. In this system, m7E3 F(ab')2 only recognizes human bone-derived alpha(v)beta3. Antibody inhibition of alpha(v)beta3 integrin in vivo resulted in a specific reduction in the proportion of antigenically-human blood vessels within tumor-bearing bone implants (from 73.5% +/- 3.93 in controls to 17.74% +/- 5.64 in treated animals). Proliferation of the alpha(v)beta3-negative tumor cells was also reduced, although the overall vessel density was maintained by compensating mouse vasculature. Blockage of human bone-derived alpha(v)beta3 also significantly reduced the recruitment of osteoclasts in response to tumor cells, as well as degradation of calcified bone tissue. Together these observations confirm the importance of alpha(v)beta3 in bone metabolism and angiogenesis, and point to the role of these processes in controlling growth of metastatic prostate cancer cells in the bone.


Applying an Integrative Framework of Executive Function to Preschoolers With Specific Language Impairment.
The first goal of this research was to compare verbal and nonverbal executive function abilities between preschoolers with and without specific language impairment (SLI). The second goal was to assess the group differences on 4 executive function components in order to determine if the components may be hierarchically related as suggested within a developmental integrative framework of executive function. This study included 26 4- and 5-year-olds diagnosed with SLI and 26 typically developing age- and sex-matched peers. Participants were tested on verbal and nonverbal measures of sustained selective attention, working memory, inhibition, and shifting. The SLI group performed worse compared with typically developing children on both verbal and nonverbal measures of sustained selective attention and working memory, the verbal inhibition task, and the nonverbal shifting task. Comparisons of standardized group differences between executive function measures revealed a linear increase with the following order: working memory, inhibition, shifting, and sustained selective attention. The pattern of results suggests that preschoolers with SLI have deficits in executive functioning compared with typical peers, and deficits are not limited to verbal tasks. A significant linear relationship between group differences across executive function components supports the possibility of a hierarchical relationship between executive function skills.


The effect of breed and diet type on the global transcriptome of hepatic tissue in beef cattle divergent for feed efficiency.
Feed efficiency is an important economic and environmental trait in beef production, which can be measured in terms of residual feed intake (RFI). Cattle selected for low-RFI (feed efficient) have similar production levels but decreased feed intake, while also emitting less methane. RFI is difficult and expensive to measure and is not widely adopted in beef production systems. However, development of DNA-based biomarkers for RFI may facilitate its adoption in genomic-assisted breeding programmes. Cattle have been shown to re-rank in terms of RFI across diets and age, while also RFI varies by breed. Therefore, we used RNA-Seq technology to investigate the hepatic transcriptome of RFI-divergent Charolais (CH) and Holstein-Friesian (HF) steers across three dietary phases to identify genes and biological pathways associated with RFI regardless of diet or breed. Residual feed intake was measured during a high-concentrate phase, a zero-grazed grass phase and a final high-concentrate phase. In total, 322 and 33 differentially expressed genes (DEGs) were identified across all diets for CH and HF steers, respectively. Three genes, GADD45G, HP and MID1IP1, were differentially expressed in CH when both the high-concentrate zero-grazed grass diet were offered. Two canonical pathways were enriched across all diets for CH steers. These canonical pathways were related to immune function. The absence of common differentially expressed genes across all dietary phases and breeds in this study supports previous reports of the re-ranking of animals in terms of RFI when offered differing diets over their lifetime. However, we have identified biological processes such as the immune response and lipid metabolism as potentially associated with RFI divergence emphasising the previously reported roles of these biological processes with respect to RFI.


Population doubling level-dependent change of secreted glycosaminoglycan in equine bone marrow-derived mesenchymal stem cells.
In regenerative medicine using transplantation of mesenchymal stem cells (MSCs), the importance of regulating the quality of MSCs has been well recognized; however, there is little information concerning the relationship between the population doubling level (PDL) and the stemness of MSCs in equine medicine. In this study, we showed that the amount of glycosaminoglycan (GAG) secreted by bone marrow-derived MSCs (BMSCs) decreases with increase of PDL. Enzymatic digestion and two-dimensional electrophoresis revealed that a main component of GAG produced by BMSCs was hyaluronan with a small amount of chondroitin sulfate. Increase of PDL downregulated the expression of MSC CD markers, including CD44, CD73, CD90, CD105, and CD146, along with loss of differentiation capacity. Thus, the effect of hyaluronan supplement to the growth medium on both expression of CD markers and the tri-lineage potential of BMSCs was evaluated. Expression of CD73 and CD90 was preserved by continuous addition of hyaluronan to the growth medium, whereas mRNA levels corresponding to CD44, CD105 and CD146 were not preserved by supplementation of hyaluronan. BMSCs subcultured with hyaluronan-supplemented growth medium to PDL-12 showed osteogenic capacity, however adipogenic and chondrogenic activities at PDL-12 were not preserved by exogenous hyaluronan. These results suggest that downregulation of CD44, CD105 and CD146 might not affect the osteogenic capacity. Taken together, the results suggested that supplementation of hyaluronan to the growth medium might be effective at maintaining the osteogenic capacity of equine BMSCs.


[Malaria in Switzerland: 1982-1986].
There has been no decrease in the number of cases of malaria brought into Switzerland. 841 cases were reported to the Federal Office of Public Health between 1982 and 1986, a figure probably below the actual number of cases. Reports were received from all cantons and the majority involve Swiss travellers. 54% of the cases were due to P. falciparum and 90% of these could be traced to a stay in tropical or subtropical Africa, particularly Kenya, where it was possible to determine the attack rate and to compare it with the risk in Thailand. An enquiry into prophylaxis disclosed how slowly the latest recommendations on preventive measures against malaria are being adopted, and the importance of keeping a close watch on regions where resistance or multiresistance has developed. Systematic reporting is essential to control and also permits the recommendation of appropriate preventive measures.


The effect of granulocyte colony-stimulating factor (G-CSF) on bacterial translocation in the splenectomized rat.
We created a study group in order to investigate the effects of splenectomy and filgrastim. Filgrastim is an immunomodulator granulocyte colony-stimulating factor (G-CSF), that affects bacterial translocation. We created 3 study groups with 30 male Sprague-Dawley rats; the first group included sham splenectomy, the second group was splenectomy, and the third group was splenectomy+ filgrastim group. The mean bacterial colony count of the cecum were 2.5 x 10(9) in group 1, 1.2 x 10(10) in group 2 and 3.5 x 10(9) in group 3. The differences between these groups were accepted as statistically significant. The mean counts of the terminal ileum were 1.1 x 10(9) in group 1, 5.5 x 10(10) in group 2 and 2.5 x 10(10) in group 3. The p values of group 1-2 were 0.036 (statistically significant) and 0.123 in groups 2-3) were not statistically significant. The mean counts of the liver were 0.2 x 10(4), 1 x 10(10) and 3.4 x 10(5), respectively. In comparison of the groups the p values of the first and last 2 groups were found to be 0.047 (statistically significant). The mean counts of the mesenteric lymph node were 0.7 x 10(3), 1 x 10(10) and 0.9 x 10(6) respectively. The p values were 0.343 for the first and the last 2 groups both. As they were above 0.05, they were not statistically significant. The degrees of liver Kupffer cell hyperplasia were (+) 40%, (+2) 50% and (+3) 10% (group 1), (+) 10%, (+2) 40% and (+3) 50% (group 2), (+2) 60% and (+3) 40% (group 3) (p = 0.0039). The rates of the absence of pathology in mesenteric lymph nodes were 70% (group 1), 90% (group 2) and 100% (group 3) (p = 0.049). These findings were statistically significant. We found that splenectomy has activated the whole predisposing factors of bacterial translocation and created the latter itself. In addition, we showed that filgrastim, a recently widespread used G-CSF, decreases bacterial translocation significantly.


Sucrose preload reduces snacking after mild mental stress in healthy participants as a function of 5-hydroxytryptamine transporter gene promoter polymorphism.
Brain serotonin (5-hydroxytryptamine, 5-HT) dysfunction is considered to promote food intake and eating-related disturbances, especially under stress or negative mood. Vulnerability for 5-HT disturbances is considered to be genetically determined, including a short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) that is associated with lower serotonin function. Since 5-HT function may be slightly increased by carbohydrate consumption, S-allele 5-HTTLPR carriers in particular may benefit from a sugar-preload due to their enhanced 5-HT vulnerability. The aim of the current study was to investigate whether a sugar-containing preload may reduce appetite and energy intake after exposure to stress to induce negative mood, depending on genetic 5-HT vulnerability. From a population of 771 healthy young male and female genotyped college students 31 S/S carriers (8 males, 23 females) and 26 long allele (L/L) carriers (9 males, 17 females) (mean ± S.D. 22 ± 1.6 years; body mass index, BMI, 18-33 kg/m(2)) were monitored for changes in appetite and snacking behavior after stress exposure. Results revealed an increased energy intake after mild mental stress (negative mood) mainly for high-fat sweet foods, which was significantly greater in S/S carriers, and only in these genotypes this intake was significantly reduced by a sucrose-containing preload. Although alternative explanations are possible, it is suggested that S/S participants may have enhanced brain (hypothalamic) 5-HT responsiveness to food that makes them more susceptible to the beneficial satiation effects of a sucrose-preload as well as to the negative effects of mild mental stress on weight gain.


Are Activity and Diet Really Important for Children's Bones?
During the last decade the focus of osteoporosis prevention moved toward understanding the importance of maximizing peak bone mass early in life. The role of nutrition, physical activity, and genetics in the attainment of peak bone mass is currently a major focus of osteoporosis research. Calcium intake and physical activity play important roles in the development of peak bone mass. Genetics also plays an important role and may interact with diet and activity in its effect on bone. Future studies on how diet, activity, and genetics interact with each other will provide important insights into the development of peak bone mass.


Photoluminescence properties of a cationic trinuclear zinc(II) complex with the tetradentate Schiff base ligand 6-methyl-2-({[(pyridin-2-yl)methyl]imino}methyl)phenolate.
Metal complexes with Schiff base ligands have been suggested as potential phosphors in electroluminescent devices. In the title complex, tetrakis[6-methyl-2-({[(pyridin-2-yl)methyl]imino}methyl)phenolato-1:2κ(8)N,N',O:O;3:2κ(8)N,N',O:O]trizinc(II) hexafluoridophosphate methanol monosolvate, [Zn3(C14H13N2O)4](PF6)2·CH3OH, the Zn(II) cations adopt both six- and four-coordinate geometries involving the N and O atoms of tetradentate 6-methyl-2-({[(pyridin-2-yl)methyl]imino}methyl)phenolate ligands. Two terminal Zn(II) cations adopt distorted octahedral geometries and the central Zn(II) cation adopts a distorted tetrahedral geometry. The O atoms of the phenolate ligands bridge three Zn(II) cations, forming a dicationic trinuclear metal cluster. The title complex exhibits a strong emission at 469 nm with a quantum yield of 15.5%.


Composition control and localization of S2- in CdSSe quantum dots grown from Li4[Cd10Se4(SPh)16].
The development of ternary nanoscale materials with controlled cross-sectional doping is an important step for the use of chemically prepared quantum dots for nanoscale engineering applications. We report cross-sectional, elemental doping with the formation of an alloyed CdSSe nanocrystal from the thermal decomposition of Li(4)[Cd(10)Se(4)(SPh)(16)]. The sulfur incorporation arises from surface-mediated phenylthiolate degradation on the growing quantum dot surface. In the alloy, we identify a pure CdSe nucleus of approximately 1.5 nm, consistent with the predictions of nucleation theory. As the particle grows, S(2-) incorporation increases until the CdSSe reaches approximately 4 nm, where a marked reduction in phenylthiolate content on the nanocrystal is observed by CP-MAS NMR spectroscopy, implying that rapid decomposition of the phenylthiolate arises with subsequent enhanced S(2-) incorporation at the level of the stoichiometry of the reaction (namely approximately 60%). The use of molecular clusters to allow controlled defect ion incorporation can open new pathways to more complex nanomaterials.


Serum Golgi protein 73 levels and liver pathological grading in cases of chronic hepatitis B.
The present study was designed to assess the correlation between serum Golgi protein 73 (GP73) and liver pathological grading and staging in patients with chronic hepatitis B (CHB). Two hundred and fifty‑three patients with chronic hepatitis B virus (HBV) infections were enrolled in the present study. All patients received a serum GP73 test, and 91 CHB patients underwent liver biopsy. GP73 expression in liver tissue was assessed by immunohistochemical analysis. The results indicated that serum GP73 levels were positively correlated with disease progression in patients with chronic HBV infection (r=0.677). There was no significant difference in serum GP73 levels between hepatitis B e antigen‑positive and ‑negative patients (P>0.05). There were also no significant differences in serum GP73 levels among specimens with varying HBV DNA contents (P>0.05). Serum GP73 levels were positively correlated with increased liver pathological grading (r=0.737) and staging (r=0.692), and immunohistochemical analysis indicated that GP73 protein expression increased concurrently with liver pathological grading and staging. In conclusion, serum GP73 was found to be correlated with liver pathological grading and staging in patients with CHB, and may be an effective indicator for the evaluation of disease progression. However, serum GP73 levels were not associated with HBV replication.


Multielement analysis and antioxidant capacity of Merlot wine clones developed in Montenegro.
The overall aim of this paper was to compare the multielement composition and antioxidant capacity of two Montenegrin Merlot wines obtained from specific vine clones (VCR1 and VCR 101) along with commercial Merlot wine throughout the consecutive vintages in 2010 and 2011. Elemental composition was analysed using inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). Additionally, antioxidant capacity was assessed by cyclic voltammetry. VCR 1 wine from 2011 stood out for its elemental composition. On the other hand, antioxidant capacity of VCR 101 wines was the highest one for the both vintages. According to the experimental data obtained, all three wines are good source of essential elements and products with a significant antioxidant activity and specific geographical origin.


Microhardness of different thicknesses of bulk fill composites.
To compare the microhardness values and bottom/top hardness ratios of different composites after being cured in 2 or 4 mm increments. Two bulk fill composites, methacrylate-based and ormocer-based, and one conventional composite were tested. 36 cylindrical discs were prepared (n=12/composite, with six for 2 mm, and six for 4 mm thickness) by pressing each composite into a mold between two glass slides covered by Mylar strips. The top and bottom surfaces of each sample were evaluated using a Buehler hardness tester for Knoop microhardness, with a 50 g static load applied for 10 seconds at three different locations of the central part of each sample. The bottom/top hardness ratio was calculated for each sample. The Knoop microhardness data and bottom/top ratio percentages were analyzed using two-way repeated measures ANOVA and Holm-Sidak post hoc test, with significance at P< 0.05. The tested methacrylate-based bulk fill had the highest overall microhardness among the three tested composites. All three composite types showed a significant difference in microhardness between the top and bottom of the 4 mm discs. The bottom/top ratio percentages differed significantly for both tested bulk fill composites across different thicknesses. Both tested bulk fill materials had a bottom/top ratio of ≥ 80% at the deepest level of a 4 mm increment. The type of material significantly affected both the bottom and top microhardness values under the experimental conditions used. While both tested bulk fill composites showed a decline in microhardness at the bottom of the 4 mm depth, they had clinically acceptable microhardness ratios at greater depths.


Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats.
High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc R(a)) under basal conditions. They also reduce insulin suppression of glc R(a) and insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 (n = 5-7/group) or 5 wk (n = 5-6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-3H]glucose was infused. In the second, a hyperglycemic period (HP), [6-3H]glucose, [6-14C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 +/- 1.5 mg/dl; HP: 172.3 +/- 1.5 mg/dl), insulin (BP: 2.5 +/- 0.2 ng/ml; HP: 4.9 +/- 0.3 ng/ml), and glucagon (BP: 81.8 +/- 1.6 ng/l; HP: 74.0 +/- 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg x kg(-1) x min(-1)) necessary to maintain arterial glucose concentrations at approximately 170 mg/dl (pooled average: 6.4 +/- 0.8 at 1 wk; 6.4 +/- 0.7 at 5 wk), percent suppression of glc R(a) (44.4 +/- 7.8% at 1 wk; 63.2 +/- 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 +/- 1.3 microg x g liver(-1) x min(-1) at 1 wk; 10.5 +/- 2.2 microg x g liver(-1) x min(-1) at 5 wk), indirect pathway glycogen synthesis (3.7 +/- 0.9 microg x g liver(-1) x min(-1) at 1 wk; 3.4 +/- 0.9 microg x g liver(-1) x min(-1) at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 +/- 0.3 microg x g muscle(-1) x min(-1) at 1 wk; 1.6 +/- 0.3 microg x g muscle(-1) x min(-1) at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.


Conjugation of glutathione with the reactive metabolites of 1, 1-dichloroethylene in murine lung and liver.
Exposure to 1,1-dichloroethylene (DCE) elicits lung and liver cytotoxicities that are manifested in bronchiolar Clara cell injury and centrilobular necrosis, respectively. The tissue damage is associated with cytochrome P450-dependent bioactivation of DCE to reactive intermediates, and is consistent with the finding that the target cells coincided with the sites of high concentrations of cytochrome P450 enzymes. The metabolites formed from DCE bind covalently to cellular macromolecules, and the extent of binding and cell damage are inversely related to the content of intracellular glutathione (GSH). Histochemical studies showed that staining for GSH in the lung is localized in the bronchiolar epithelial and alveolar septal cells, with relatively strong staining in the Clara cells. In the liver, staining is observed rather uniformly in hepatocytes distributed across the hepatic lobule. Depletion of GSH correlates with the Clara cell damage and centrilobular necrosis observed in the lung and liver, respectively. The primary metabolites of DCE formed in lung and liver microsomal incubations have been identified as DCE-epoxide, 2,2-dichloroacetaldehyde and 2-chloroacetyl chloride. All are electrophilic metabolites that form secondary reactions including conjugation with GSH. Results of our studies indicated that the DCE-epoxide is the major metabolite forming conjugates with GSH, and this reaction is likely responsible for the depletion of GSH observed in vivo. Our findings support the premise that, following depletion of intracellular GSH, metabolites of DCE including the DCE-epoxide bind to cellular proteins, a process which leads to cell damage and suggests that conjugation with the thiol nucleophile represents a-detoxification mechanism.


A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.
The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.


In vitro biocompatibility testing of biomaterials and medical devices.
Biomaterials used for medical devices must be thoroughly tested according to ISO 10993 before their introduction so that any negative effects on the body are known about and prevented. By using in vitro laboratory tests, dangers for patients and unnecessary animal experiments can be avoided. Here, in vitro tests for cell compatibility (cytotoxicity) and blood compatibility (haemocompatibility) are described.


Persistence of CTL clones targeting melanocyte differentiation antigens was insufficient to mediate significant melanoma regression in humans.
Adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) can mediate durable cancer regression in selected patients with metastatic melanoma. However, the tumor antigens associated with these favorable responses remain unclear. We hypothesized that a clinical strategy involving the iterative adoptive transfer of selected autologous antigen-specific T-cell clones could help systematically define immunologic targets associated with successful cancer therapy, without the interpretative ambiguity of transferring polyclonal populations. Here, we evaluated the clinical efficacy of CD8(+) T-cell clones specific for the melanocyte differentiation antigens (MDA), gp100 and MART-1, respectively. We conducted two consecutive phase II clinical trials involving the adoptive transfer of highly selected autologous antigen-specific CD8(+) T-cell clones against gp100 and MART-1, respectively. Fifteen patients with HLA-A2(+) treatment-refractory metastatic melanoma received highly avid MDA-specific CD8(+) T-cell clones specific for either gp100 (n = 10) or MART-1 (n = 5) with or without intravenous interleukin-2 (IL2) after a lymphodepleting myeloablative preparative regimen. Of the 15 treated patients, we observed immune-mediated targeting of skin melanocytes in 11 patients (73%) and clonal engraftment in eight patients (53%) after cell transfer. There were only transient minor tumor regressions observed, but no objective tumor responses based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria. Despite successful clonal repopulation and evidence of in vivo antigen targeting, the poor therapeutic efficacy after the adoptive transfer of autologous MDA-specific T cells raises significant concerns regarding future immunotherapy efforts targeting this class of tumor antigens.


Using Machine Learning To Predict Partition Coefficient (Log P) and Distribution Coefficient (Log D) with Molecular Descriptors and Liquid Chromatography Retention Time.
During preclinical evaluations of drug candidates, several physicochemical (p-chem) properties are measured and employed as metrics to estimate drug efficacy in vivo. Two such p-chem properties are the octanol-water partition coefficient, Log P, and distribution coefficient, Log D, which are useful in estimating the distribution of drugs within the body. Log P and Log D are traditionally measured using the shake-flask method and high-performance liquid chromatography. However, it is challenging to measure these properties for species that are very hydrophobic (or hydrophilic) owing to the very low equilibrium concentrations partitioned into octanol (or aqueous) phases. Moreover, the shake-flask method is relatively time-consuming and can require multistep dilutions as the range of analyte concentrations can differ by several orders of magnitude. Here, we circumvent these limitations by using machine learning (ML) to correlate Log P and Log D with liquid chromatography (LC) retention time (RT). Predictive models based on four ML algorithms, which used molecular descriptors and LC RTs as features, were extensively tested and compared. The inclusion of RT as an additional descriptor improves model performance (MAE = 0.366 and R2 = 0.89), and Shapley additive explanations analysis indicates that RT has the highest impact on model accuracy.