Estrogen sensitive liver transgenic zebrafish (Danio rerio) line (Tg(vtg1:mCherry)) suitable for the direct detection of estrogenicity in environmental samples.
Environmental estrogens are a serious concern worldwide due to their ubiquity and adverse ecotoxicological and health effects. Chemical structure of these substances is highly diverse, therefore estrogenicity cannot be predicted on the basis of molecular structure. Furthermore, estimation of estrogenicity of environmental samples based on chemical analytics of suspects is difficult given the complex interaction of chemicals and the impact on estrogenicity. The full estrogenic impact of an environmental sample can thus only be revealed by a series of sensitive in vitro and in vivo ecotoxicological tests. Herein we describe a vitellogenin reporter transgenic zebrafish line (Tg(vtg1:mCherry)) that enables the detection of estrogenicity in the environmentally relevant, low concentration ranges in embryonic tests that are in accordance with 3Rs and relevant animal welfare regulations. The transgene construct used for the development of Tg(vtg1:mCherry) carried a long (3.4 kbp) natural vitellogenin-1 promoter sequence with a high number of ERE sites. A test protocol was developed based on our finding that the endogenous vitellogenin and the reporter show similar spatial expression pattern and both endogenous and vitellogenin reporter is only produced in the left hepatic lobe of 5 dpf zebrafish embryos. Seven generations of Tg(vtg1:mCherry) have been established, and the estrogen responsiveness was tested with different estrogenic substances and wastewater samples. Embryos were exposed from 3 to 5 days post fertilization (dpf). Fluorescence in embryos could be detected upon treatment with 17-ß-estradiol from a concentration of 100 ng/L, 17-α-ethynilestradiol from 1 ng/L, zearalenone from 100 ng/L and bisphenol-A from 1 mg/L. In the adult stage transgene activity appeared to be more sensitive to estrogen treatment, with detectable transgene activity from 5 ng/L 17-ß-estradiol concentration. The transgenic line Tg(vtg1:mCherry) was also suitable for the direct measurement of estrogenicity in wastewater samples without sample extraction. The detection of estrogenic activity using the reporter line was confirmed by the bioluminescent yeast estrogen screen.


How Much is Too Much? Getting Children Involved, but Not Too Involved.
In the pediatric office, the summer months are filled with well-child visits and sports physicals. It is during these visits that it is important to evaluate our patients as a whole, remembering to discuss both physical and emotional concerns. It is also important to discuss the upcoming school year so concerns by both parents and children can be addressed. Extracurricular activities play a vital role in developing social skills, building a sense of community, and allowing children to discover life-long activities they truly enjoy. However, it is important to remind parents that as a family they must find a balance between a busy extracurricular activity schedule and time for rest, relaxation, and family.


Blood Transfusion Incidence, Risk Factors, and Associated Complications in Surgical Treatment of Hip Dysplasia.
Perioperative bleeding requiring blood transfusion is a known complication of hip dysplasia (HD) surgery. Here we examine rates of, risk factors for, and postoperative complications associated with transfusion during HD surgery. The National Surgical Quality Improvement Program (NSQIP) Pediatric database was queried for patients treated by an orthopaedist from 2012 to 2013. HD cases were categorized by Current Procedural Terminology codes into femoral osteotomies, acetabular osteotomies, combined femoral/acetabular osteotomies, and open reductions. Patients were grouped by comorbidities: neuromuscular (NM) disease (eg, cerebral palsy) group, non-NM with other comorbidity (Other) group, and no known comorbidity (NL) group. Patients were stratified by weight-normalized transfusion volume. Multivariate regression analysis of transfusion association with procedures, demographics, comorbidities, preoperative laboratory values, and 30-day complications was performed. A total of 1184 HD cases were included. Transfusion rates for the NL, Other, and NM groups, respectively, were 44/451 (9.8%), 61/216 (28.2%), and 161/517 (31.1%). Transfusion volumes (mean±SD) for the NL, Other, and NM groups, respectively, were 8.4±5.4, 13.9±8.8, and 15.5±10.0 mL/kg (P<0.001). Combined osteotomies had the highest transfusion rates in the NM and Other groups (35.7% and 45.8%, respectively), whereas acetabular osteotomies had the highest rate in the NL group (15.8%). Open reductions had the lowest transfusion rate (all groups). Longer operations were independently associated with transfusion (all groups, per hour increase, OR>1.5, P<0.001). Independent patient risk factors included preoperative hematocrit <31% (NM group, OR=18.42, P=0.013), female sex (NL group, OR=3.55, P=0.008), developmental delay (NM group, OR=2.37, P=0.004), pulmonary comorbidity (NM group, OR=1.73, P=0.032), and older age (NL group, per year increase: OR=1.29, P<0.001). In all groups, transfusion was associated with longer hospitalization (P<0.001). We observed a volume-dependent increase in overall complication rate within the Other group for transfusion volumes >15 mL/kg (25.0% vs. 5.4% for <15 mL/kg, P=0.048). We identified several risk factors for transfusion in HD surgery. The incidence of transfusion in HD surgery and its association with adverse outcomes warrants development of appropriate patient management guidelines. Level III-prognostic.


[Automatization of heparin determination using chronometric evaluation of anti-Xa activity of the AT III-heparin complex].
The authors describe an adaptation on a semi- automatique coagulometer KC 10 of a manual assay of anti-Xa activity of the Heparin-Antithrombin III Complex close to the technique described by Yin and al. ( Hepaclot - Stago ). The results show a good linearity and a good reproducibility, with a better sensitivity than the manuel method. Freezing has no influence. Significant differences were observed between our assay and the manuel anti-IIa assay. These last results neither depend on the administration route nor on the heparin batches.


A retrospective study of secondary bacteraemia in hospitalised adults with community acquired non-typhoidal Salmonella gastroenteritis.
The clinical significance of bacteraemia secondary to non-typhoidal Salmonella (NTS) gastroenteritis in hospitalised adults is uncertain. Adults admitted to a hospital in Liverpool, UK, with NTS gastroenteritis were identified using hospital discharge data and laboratory records. Patients with known HIV infection were excluded. Risk factors for a complicated or fatal course were determined. Between 1982 and 2006 inclusive, 633 adults were identified. Serovars causing infection included Enteritidis (46.6%), Typhimurium (27.6%) and Virchow (4.9%). A blood culture was taken in 364 (57.5%) patients who were generally sicker than those who were not cultured. Bacteraemia was detected in 63 (17.3%) patients who had blood cultures taken (63/633 (10.0%) of all patients). Bacteraemia was more common in those aged ≥ 65 years (p < 0.001) and in those aged < 65 years who had an underlying chronic disease. A complicated course occurred in 91 (25.0%) patients who had had a blood culture taken (148/633 (23.4%) of all patients). Independent factors associated with a complicated or fatal course among the patients investigated with a blood culture were bacteraemia (Adjusted Odds Ratio 5.34, 95% CI 2.86-9.95); new onset confusion or coma (AOR 4.80, 95% CI 1.91-12.07); prolonged symptoms prior to admission (AOR 2.48, 95% CI 1.44-4.27); dehydration (AOR1.90, 95% CI 1.07-3.38); and absence of fever (AOR 0.56, 95% CI 0.32-0.95). The 30 day attributable case fatality for all patients was 1.5%. In this study secondary bacteraemia, as well as other clinical factors, was independently associated with a complicated or fatal course in non-HIV infected adults admitted to hospital with NTS gastroenteritis.


Cascading training the trainers in ophthalmology across Eastern, Central and Southern Africa.
The Royal College of Ophthalmologists (RCOphth) and the College of Ophthalmology of Eastern Central and Southern Africa (COECSA) are collaborating to cascade a Training the Trainers (TTT) Programme across the COECSA Region. Within the VISION 2020 Links Programme, it aims to develop a skilled motivated workforce who can deliver high quality eye care. It will train a lead, faculty member and facilitator in 8 countries, who can cascade the programme to local trainers. In phase 1 (2013/14) two 3-day courses were run for 16/17 selected delegates, by 3 UK Faculty. In phase 2 (2015/16) 1 UK Faculty Member ran 3 shorter courses, associated with COECSA events (Congress and Examination). A COECSA Lead was appointed after the first course, and selected delegates were promoted as Facilitators then Faculty Members on successive courses. They were given appropriate materials, preparation, training and mentoring. In 4 years the programme has trained 87 delegates, including 1 COECSA Lead, 4 Faculty Members and 7 Facilitators. Delegate feedback on the course was very good and Faculty were impressed with the progress made by delegates. A questionnaire completed by delegates after 6-42 months demonstrated how successfully they were implementing new skills in teaching and supervision. The impact was assessed using the number of eye-care workers that delegates had trained, and the number of patients seen by those workers each year. The figures suggested that approaching 1 million patients per year were treated by eye-care workers who had benefited from training delivered by those who had been on the courses. Development of the Programme in Africa initially followed the UK model, but the need to address more extensive challenges overseas, stimulated new ideas for the UK courses. The Programme has developed a pyramid of trainers capable of cascading knowledge, skills and teaching in training with RCOphth support. The third phase will extend the number of facilitators and faculty, develop on-line preparatory and teaching materials, and design training processes and tools for its assessment. The final phase will see local cascade of the TTT Programme in all 8 countries, and sustainability as UK support is withdrawn.


Activation of the protein kinase p38 in the spindle assembly checkpoint and mitotic arrest.
The mitogen-activated protein kinase (MAPK) superfamily comprises classical MAPK (also called ERK), c-Jun amino-terminal or stress-activated protein kinase (JNK or SAPK), and p38. Although MAPK is essential for meiotic processes in Xenopus oocytes and the spindle assembly checkpoint in Xenopus egg extracts, the role of members of the MAPK superfamily in M phase or the spindle assembly checkpoint during somatic cell cycles has not been elucidated. The kinase p38, but not MAPK or JNK, was activated in mammalian cultured cells when the cells were arrested in M phase by disruption of the spindle with nocodazole. Addition of activated recombinant p38 to Xenopus cell-free extracts caused arrest of the extracts in M phase, and injection of activated p38 into cleaving embryos induced mitotic arrest. Treatment of NIH 3T3 cells with a specific inhibitor of p38 suppressed activation of the checkpoint by nocodazole. Thus, p38 functions as a component of the spindle assembly checkpoint in somatic cell cycles.


Hepatitis B and C virus prevalence and association with demographics: report of population screening in Nigeria.
Hepatitis B and C remain a major cause of chronic liver disease worldwide with its attendant consequences. The burden of these viral infections in sub-Saharan Africa including Nigeria rely on estimates based on small population studies in some select populations. We present the report of a population survey in Nigeria during the period 2010-2012. A total of 5,558 adults participated in the screening exercise. The minimum age recorded was 18 years, while the maximum age was 75 years. The mean ± S.D. was 36.07 ± 8.76 years. The prevalence of hepatitis B (HBsAg) among the adults screened was determined to be 6.7% while that of hepatitis C (HCV) was 0.9%. The peak prevalence for HBsAg carriage was in the third to fourth decade in keeping with childhood acquisition while of HCV antibody was in the sixth to seventh decade. Male gender was significantly associated with HBsAg carriage while we noted a higher prevalence in those within the lower socioeconomic status. Overall our findings suggest that hepatitis B is endemic in Nigeria, much less than previously reported, while the prevalence for HCV is low although reports of pockets of high prevalence exist in select populations (hospital patients including those living with HIV).


Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations.
Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.


Phytoseiid mites (Acari: Phytoseiidae) from Chile, with descriptions of three new species and a redescription of Chileseius camposi.
A total of 40 phytoseiid species has been reported from Chile, including the two species (Neoseiulus californicus (McGregor) and Phytoseiulus persimilis (Athias-Henriot) most widely used worldwide for the biological control of the two-spotted spider mite, Tetranychus urticae Koch (Tetranychidae). In this paper we report nine other species found in new collecting conducted since 1989, including three new species: Amblyseius herbicolus (Chant), Amblyseius tamatavensis Blommers, Arrenoseius robertogonzalezi Trincado Martin n. sp., Neoseiulus anonymus (Chant Baker), Neoseiulus bicaudus (Wainstein), Neoseiulus viticolus Trincado Martin n. sp., Metaseiulus (Metaseiulus) camelliae (Chant Yoshida-Shaul), Metaseiulus (Metaseiulus) neoflumenis Moraes Kreiter and Metaseiulus (Metaseiulus) relictus Trincado Martin n. sp.. Chileseius camposi Gonzalez Schuster, 1962 is redescribed, and a list of all species presently known from Chile and a key to help in their separation are given. A new name, Proprioseiopsis kargi Trincado nom. nov., is a replacement name for Proprioseiopsis globosus Karg, 1976, a junior homonym of Proprioseiopsis globosus (Gonzalez Schuster, 1962).


Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure.
Immune checkpoint inhibitors (ICIs) have become a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy. However, the prognostic factors for patients with mUC receiving ICIs are not well established. We retrospectively collected clinical and laboratory data and reviewed the survival outcomes of patients with mUC who were treated with ICIs after platinum-based chemotherapy. We used univariate and multivariable Cox proportional hazard models to identify independent prognostic factors, and the concordance index (C-index) to evaluate the performance of the new prognostic model. In addition, bootstrap analysis was employed for internal validation of the prognostic model. A total of 224 patients were included in the study. With a median follow-up of 10.5 months (interquartile range, 5.1-17.4 months), median overall survival (OS) was 13.6 months (95% confidence interval [CI], 9.7-17.3 months). In multivariable analysis, independent prognostic factors predicting adverse OS were the presence of liver metastasis (LM), hypoalbuminemia, and neutrophil-lymphocyte ratio (NLR) >5. When patients were categorized into 3 risk groups, median OS was not reached (NR) (95% CI, 17.3-NR), 9.5 months (6.8-NR), and 2.9 months (2.3-4.4) for patients with a score of 0, 1, and 2+, respectively. The C-index for the new model was 0.763 (95% CI, 0.739-0.787). A novel prognostic model, including LM, hypoalbuminemia, and NLR, was developed and validated to estimate OS in patients with platinum-refractory disease on second- or subsequent-line ICI therapy. Further investigations, including prospective validation, are needed.


Virus-Enabled Optimization and Delivery of the Genetic Machinery for Efficient Unnatural Amino Acid Mutagenesis in Mammalian Cells and Tissues.
Unnatural amino acid (UAA) mutagenesis of recombinant proteins in live mammalian cells requires coexpression of the mutant target, as well as an engineered tRNA/aminoacyl-tRNA synthetase pair. The ability to readily determine the optimal relative expression levels of these three genetic components for efficient expression of the UAA-modified target is highly desirable, but remains challenging to accomplish. Here we report a facile strategy to achieve this by taking advantage of the efficient gene-delivery by a baculovirus vector, which enables systematic variation of the expression level of each genetic component in a population-wide manner. Insights gained from this study led to the design of an optimal expression system, which can be delivered into mammalian cells by a single baculovirus vector to provide significantly improved UAA incorporation efficiency at a low virus load. Furthermore, this optimized baculovirus vector was shown to enable efficient UAA mutagenesis of proteins expressed in mouse brain tissue.


Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial.
Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 Group), MIV with AS03 (AS03 × 2 Group), unadjuvanted MIV (No Adj Group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 Group), and A/H7-naïve (Unprimed Group). Participants were randomized to receive one dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing (Neut) antibody assays. We enrolled 304 participants: 153 received the adjuvanted boost, and 151 received the unadjuvanted boost. At 21 days post vaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were: 88% and 49% in MF59 × 2 Group, 89% and 75% in AS03 × 2 Group, 59% and 20% in No Adj Group, 94% and 55% in Adjx1Group, and 9% and 11% in Unprimed Group. Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens.


Interaction of cholesterol with a docosahexaenoic acid-containing phosphatidylethanolamine: trigger for microdomain/raft formation?
Docosahexaenoic acid (DHA, 22:6) containing phospholipids have been postulated to be involved in promoting lateral segregation within membranes into cholesterol- (CHOL-) rich and CHOL-poor lipid microdomains. Here we investigated the specific molecular interactions of phospholipid bilayers composed of 1-[(2)H(31)]palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (16:0-22:6PE-d(31)) or 1-[(2)H(31)]palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (16:0-18:1PE-d(31)) with equimolar CHOL using solid-state (2)H NMR spectroscopy and low- and wide-angle X-ray diffraction (XRD). Moment analysis of (2)H NMR spectra obtained as a function of temperature reveals that the main chain melting transition and the lamellar-to-inverted hexagonal (H(II)) phase transition of 16:0-22:6PE-d(31) remain in the presence of equimolar CHOL, whereas addition of equimolar CHOL essentially obliterates the gel-to-liquid crystalline transition of 16:0-18:1PE-d(31). (2)H NMR order parameter measurements show that the addition of equimolar CHOL in the lamellar liquid crystalline phase causes a smaller increase in order for the perdeuterated sn-1 chain by 22% for 16:0-22:6PE-d(31) as opposed to 33% for 16:0-18:1PE-d(31). XRD experiments determined markedly lower solubility of 32 +/- 3 mol % for CHOL in 16:0-22:6PE bilayers in contrast to the value of approximately 51 mol % for 16:0-18:1PE. Our findings provide further evidence that cholesterol has a low affinity for DHA-containing phospholipids and that this reduced affinity may serve as a mechanism for triggering the formation of lipid microdomains such as rafts.


Changes in electric activity of masseter and temporal muscles after mandibular sagittal split osteotomy.
The functioning of the masseter and anterior temporal muscles was assessed by electromyography in 18 patients before orthognathic surgery and 6 weeks, 3 months, 1 year, and 2 years afterwards. Electromyogram (EMG) recordings were made during maximal bite in intercuspal position and chewing. The mean electric activity in the masseter and anterior temporal muscles decreased markedly 6 weeks after surgery but increased clearly for 1 year in both functions. Only a slight further increase was observed at 2-year follow-up during chewing, but not during maximal bite in intercuspidation. The mean changes in electric activity increased more clearly in patients with hyperplastic mandible than in patients with hypoplastic mandible and in those with long shift of the mandible. The same finding was also more visible in men and older patients than in women and younger patients.


The Huddle: It's Not Just for Football Anymore.
Huddles are a wonderful team-building tool to enhance team function and efficiency. The Institute of Medicine (2011) report, The Future of Nursing--Leading Change, Advancing Health, identifies the need for collaborative healthcare teams. This is based on 14 years of research and evidence. Creating a team culture is identified as being essential to delivering high-quality patient care. Huddles are easy to complete and don't cost anything but a few minutes that are well worth their while! It's not often we get an opportunity to do so much with so little. So, 1, 2, 3, Hut; let's all go Huddle!


Hyperbranched polymer mediated fabrication of water soluble carbon nanotube-metal nanoparticle hybrids.
1-Pyrenemethanol initiated hyperbranched polyglycerol (PiHP) has been synthesized and utilized to non-covalently functionalize pristine multi-walled carbon nanotubes (CNTs) through π-π stacking interactions. Mediated with the PiHP coating, a variety of metal nanoparticles (Au, Ag, Pd and Pt) were in situ generated and randomly tethered on the CNT sidewalls, producing various water-soluble CNT/PiHP/metal hybrids. Particularly, the resulting CNT/PiHP/Pt hybrids possess improved metal coverage in comparison to the reported CNT/Pt nanohybrids obtained by the use of conventional non-covalent CNT surface-modifiers. Depending on the using concentration of Pt(2+) precursor, Pt coverage in CNT/PiHP/Pt hybrids can be effectively controlled. In the meanwhile, Pt component on the CNT sidewalls can be either well isolated nanoparticles or loose "nanoclusters". To test the promising catalytic application of these obtained CNT/PiHP/Pt hybrids, a systematic investigation on their catalytic performance towards the reduction of 4-nitrophenol to produce 4-aminophenol was performed. Surprisingly, these hybrids exhibited significantly enhanced catalytic activity compared with the conventionally utilized Au and Ag nanoparticles. Moreover, they can be easily recovered and reused without significant loss in catalytic activity after running 6 circles.


Effect on postoperative analgesia of small-dose lysine acetylsalicylate added to prilocaine during intravenous regional anesthesia.
Nonsteroidal antiinflammatory drugs act largely peripherally by blocking the local synthesis of prostaglandins. The aim of this study was to evaluate whether the addition of a small dose of lysine acetylsalicylate (LA) to the prilocaine used for intravenous regional anesthesia (IVRA) would improve the quality of postoperative analgesia. Sixty patients undergoing lower extremity IVRA for foot or ankle surgery were randomly assigned to three double-blind groups: LA-IVRA where 90 mg of LA was mixed with prilocaine 0.5% for IVRA and 1 mL of 0.9% NaCl administered intravenously (IV) through the forearm catheter after tourniquet inflation; LA-IV where 1 mL of 0.9% NaCl was mixed with prilocaine and 90 mg of LA administered IV; and placebo where 1 mL of 0.9% NaCl was administered both with prilocaine for the IVRA and IV. Duration of analgesia (time elapsed between tourniquet release and first injection of morphine, expressed as mean +/- SD) was significantly longer (P < 0.05) in LA-IVRA (387 +/- 216 min) when compared with LA-IV (175 +/- 264 min) and placebo (126 +/- 201 min). Analgesic requirements remained significantly lower in LA-IVRA when compared with placebo only during the first six postoperative hours, LA-IV being in an intermediate position. Pain scores were significantly lower in LA-IVRA during the first postoperative hour when compared with LA-IV and during the first 3 postoperative hours when compared with placebo. We conclude that 90 mg of LA (corresponding to 50 mg of acetylsalicylic acid) added to prilocaine 0.5% during IVRA improves the quality of postoperative analgesia in the early postoperative period.


A novel co-existing ZCCHC8-ROS1 and de-novo MET amplification dual driver in advanced lung adenocarcinoma with a good response to crizotinib.
In non-small cell lung cancer (NSCLC), driver gene alterations, such as EGFR, ALK, MET, and ROS1, are usually mutually exclusive. Few clinical cases with co-existing ROS1 fusion and de-novo MET amplification have been reported. In addition, the efficacy of crizotinib in Chinese patients with driver co-existing alterations is uncertain. A 65-year-old female was diagnosed with lung adenocarcinoma metastatic to the brain. She had sufficient tumor tissue for detection of the target gene; however, common driver gene mutations, such as EGFR-wild and ALK-negative, were not initially detected. The patient was ultimately shown to have both ZCCHC8-ROS1 and de-novo MET gene amplification through next-generation sequencing with sensitivity to the targeted therapy of crizotinib. Unfortunately, the progression-free survival was only 6 months in length. We report here the first patient with co-existing ROS1 fusion and de-novo MET amplification to receive crizotinib in China. Treatment of our patient was effective with targeted therapy based on a precise diagnosis. Advanced or metastatic NSCLC patients with co-existing ROS1 fusion and de-novo MET amplification are sensitive to crizotinib. These uncommon driver gene mutations may be missed using the current first-generation detection assay. We must be aware of the incidence of concomitant ROS1 fusion and de-novo MET amplification because NSCLC patients could benefit from targeted therapy.


Transient Velopharyngeal Insufficiency After Calcified Stylohyoid Ligament Resection.
Elongation of the stylohyoid process or calcification of the stylohyoid ligament is known as the Eagle syndrome. Mostly, it is seen incidentally on imaging or with extreme suspicion and usually patients are asymptomatic.Surgery is the preferred method in symptomatic patients. Transcervical or transoral methods may be preferred as surgical route.A 28-year-old female patient who had formerly underwent tonsillectomy presented with throat and ear pain. A neck computed tomography was performed, and the patient was diagnosed as Eagle Syndrome. Surgery was recommended.Patient developed transient velopharyngeal insufficiency on postoperative day 4. Ventilation exercise and follow-up was recommended. Complaints of the patient decreased on the 15th day.It should be kept in mind that stylohyoid ligament may be calcified in young age group and middle age group patients with dysphagia or odynophagia, and differential diagnosis should be performed. Another issue is the condition of velofaringeal insufficiency which may occur due to the damage of the pharynx muscles by deep dissection during surgery.


Probing the Time Dependency of Cyclooxygenase-1 Inhibitors by Computer Simulations.
Time-dependent inhibition of the cyclooxygenases (COX) by a range of nonsteroidal anti-inflammatory drugs has been described since the first experimental assays of COX were performed. Slow tight-binding inhibitors of COX-1 bind in a two-step mechanism in which the EI → EI* transition is slow and practically irreversible. Since then, various properties of the inhibitors have been proposed to cause or affect the time dependency. Conformational changes in the enzyme have also been proposed to cause the time dependency, but no particular structural feature has been identified. Here, we investigated a series of inhibitors of COX-1 that are either time-independent or time-dependent using a combination of molecular dynamics simulations, binding free energy calculations, and potential of mean force calculations. We find that the time-dependent inhibitors stabilize a conformational change in the enzyme mainly identified by the rotation of a leucine side chain adjacent to the binding pocket. The induced conformation has been previously shown to be essential for the high binding affinities of tight-binding inhibitors in COX-1. The results of this work show that the structural features of the enzyme involved in both time-dependent and tight-binding inhibition are identical and further identify a structural mechanism responsible for the transition between the two enzyme-inhibitor complexes characteristic of slow tight-binding COX-1 inhibitors.


Effect of Cinnamon and Turmeric Aqueous Extracts on Serum Interleukin-17F Level of High Fructose-Fed Rats.
Studies have indicated that extraweight and obesity induce chronic inflammation, which can lead to other diseases such as cancers. To evaluate the effects of two weight-lowering and anti-inflammatory agents including cinnamon, and turmeric, on serum levels of interleukin-17 (IL-17) as a pro-inflammatory cytokine. In this study, 64 rats were designated in eight groups. The control group received normal diet. The other groups were fed with normal diet plus high cinnamon (3 mg/ml), high turmeric (3 mg/ml), high-fructose solution (30%), fructose solution with low (0.15 mg/ml) and high doses (3 mg/ml) of cinnamon and turmeric three times per week. The serum level of IL-17F was measured by enzyme-linked immunosorbent assay (ELISA). High fructose consumption led to an increase in the weight and serum level of IL-17. While, feeding with cinnamon and turmeric caused to decline weight but, surprisingly increased IL-17F levels. Although, some studies have showed that cinnamon and turmeric supplementation decreased IL-17F under the standard diet, in the presence of high fructose diet and extraweight their effects were reversed and caused an increase in serum level of IL-17F.


Discrimination of oral squamous cell carcinoma from oral lichen planus by salivary metabolomics.
This study was conducted to distinguish salivary metabolites in oral squamous cell carcinoma (OSCC) from those in oral lichen planus (OLP) to identify practical biomarkers for the discrimination of OSCC from OLP. Whole unstimulated saliva samples were collected from patients with OSCC (n = 34) and OLP (n = 26). Hydrophilic metabolites in the saliva samples were comprehensively analysed by capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC from OLP. Fourteen metabolites were found to be significantly different between the OSCC and OLP groups. Among them, indole-3-acetate and ethanolamine phosphate were used to develop the MLR model. The combination of these two metabolites showed a high area under the receiver operating characteristic curve (0.856, 95% confidential interval: 0.762-0.950; p < .001) for discriminating OSCC from OLP. We identified salivary metabolites for discerning between OSCC and OLP, which is clinically important for detecting the malignant transformation of OLP by both dentists and oral surgery specialists. Our candidate salivary metabolites show potential for non-invasive screening of OSCC versus OLP.


Posttetanic potentiation critically depends on an enhanced Ca(2+) sensitivity of vesicle fusion mediated by presynaptic PKC.
Activity-dependent enhancement of transmitter release is a common form of presynaptic plasticity, but the underlying signaling mechanisms have remained largely unknown, perhaps because of the inaccessibility of most CNS nerve terminals. Here we investigated the signaling steps that underlie posttetanic potentiation (PTP), a form of presynaptic plasticity found at many CNS synapses. Direct whole-cell recordings from the large calyx of Held nerve terminals with the perforated patch-clamp technique showed that PTP was not mediated by changes in the presynaptic action potential waveform. Ca(2+) imaging revealed a slight increase of the presynaptic Ca(2+) transient during PTP ( approximately 15%), which, however, was too small to explain a large part of PTP. The presynaptic PKC pathway was critically involved in PTP because (i) PTP was occluded by activation of PKC with phorbol esters, and (ii) PTP was largely (by approximately two-thirds) blocked by the PKC inhibitors, Ro31-8220 or bisindolylmaleimide. Activation of PKC during PTP most likely acts directly on the presynaptic release machinery, because in presynaptic Ca(2+) uncaging experiments, activation of PKC by phorbol ester greatly increased the Ca(2+) sensitivity of vesicle fusion in a Ro31-8220-sensitive manner ( approximately 300% with small Ca(2+) uncaging stimuli), but only slightly increased presynaptic voltage-gated Ca(2+) currents ( approximately 15%). We conclude that a PKC-dependent increase in the Ca(2+) sensitivity of vesicle fusion is a key step in the enhancement of transmitter release during PTP.


Overcoming the Usual Reactivity of β-Nitroenones: Synthesis of Polyfunctionalized Homoallylic Alcohols and Conjugated Nitrotriene Systems.
Herein, we report a new application of β-nitroenones as valuable building blocks for the preparation of polyfunctionalized homoallylic alcohols; they can be used as key precursors of conjugated nitrotriene systems. The synthesis of homoallylic alcohols was performed exploiting the chemoselective addition of metal allylating agents to the ketone moiety vs the nitroalkenyl group. The conversion of alcohols into nitrotrienes was achieved under Lewis-acid-promoted conditions. Both classes of compounds were obtained in good to excellent yields.


Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli.
The F16L gene of vaccinia virus (VACV) is conserved in all chordopoxviruses except avipoxviruses. The crocodile poxvirus F16 protein ortholog has highly significant similarity to prokaryotic serine recombinases and contains all amino acids that comprise the catalytic site. In contrast, F16 orthologs encoded by other poxviruses show only marginally significant similarity to serine recombinases, lack essential amino acids of the active site and are most likely inactive derivatives of serine recombinases. Nevertheless, the conservation of F16L in non-avian poxviruses suggested an important function. However, a VACV mutant with the F16L gene knocked out replicated normally in dividing and quiescent cells. The F16 protein was synthesized early after infection and detected in virus cores. When expressed in infected or uninfected cells, F16 accumulated in nucleoli depending on the level of expression and confluency of cells. Evidence was obtained that F16 forms multimers, which might regulate concentration-dependent intracellular localization.


[The evaluation of quality of implementation of preventive medical examinations of underage persons in the Russian Federation].
The analysis was implemented concerning informational statistic data characterizing health of children population of different age groups in the Russian Federation on the basis of results of dispensarization in its federal okrugs and subjects in 2014. The purpose of the study was to discover ways and modes of developing and increasing efficiency of preventive examinations of underage population. The following indices were analyzed: coverage of children population by preventive medical examinations, distribution according health groups and medical groups for physical culture involvement, level and stricture of established total and primary morbidity, rate of dispensary registration, requirements in additional consultations, examinations and treatment in out-patient condition, day hospital, day-and-night hospital and also coverage with all these medical services. In the most of the subjects of the Russian Federation a high level of coverage of underage population with preventive medical examinations is registered. The percentage of healthy children population in the Russian Federation comprises more than one third of all covered by dispensarization. The significant variations in indices of rate of healthy children and children with functional disorders and chronic diseases in subjects of the Russian Federation is determined by quality and accessibility of medical care at the regional level. The established total and primary morbidity of children population in significant percentage (more than one third) of the subjects has a level higher than a national one. The leading causes of morbidity in children are diseases of respiratory system, musculoskeletal system, nervous system. In adolescents, these causes are diseases of musculoskeletal system, eye diseases and diseases of respiratory system. Despite high prevalence of chronic pathology in children population of the Russian Federation, the guidelines concerning treatment and rehabilitation on the basis of results of preventive medical examinations were developed in inadequate scope. The regional characteristics of the results of dispensarization are established. These results made it possible to sort out the most unfavorable territories and to determine defects in its organization and absence of continuity between medeical institutions providing the given type of medical services.


Phase variation in Salmonella: analysis of Hin recombinase and hix recombination site interaction in vivo.
The bacteriophage P22-based challenge phase selection was used to characterize the binding of Salmonella Hin recombinase to the wild-type hixL and hixR recombination sites, as well as to mutant and synthetic hix sequences in vivo. Hin recombinase binds to the hixL or hixR recombination sites and represses transcription from an upstream promoter in the challenge phage system. Hin-mediated repression results from Hin associating into multimers either prior to binding or during the binding process at the hix operator sites (cooperativity). The ability of Hin multimers to repress transcription is eliminated when the hix 13-bp half-sites are rotated to opposite sides of the DNA helix by inserting 4 bp between them. Insertion of 1 bp between half-sites reduces overall repression. Hin also binds one of the hixL half-sites to repress transcription, but only when high levels of Hin protein are present in the cell. Mutations have been identified in the hix sites that impair Hin binding. Five of the 26 bp in the hix sites are critical; sites with base-pair substitutions at these five positions show greatly reduced binding. Three additional base pairs make minor contributions to binding. These results are consistent with the results of binding studies between Hin and the hix sites in vitro.


H.M. Parker lecture. Radiation protection standards: a historical perspective.
The historical development of radiation standards limiting exposure to people is given in this paper. Since its purpose was to provide information to the public, the number of units is limited to two, and mathematical expressions are avoided. Emphasis is placed on the role of the National Council on Radiation Protection and Measurements and the International Commission on Radiological Protection rather than on regulations because the recommendations of these groups have played a strong part in the formulation of regulations.


Patient-clinician mobile communication: analyzing text messaging between adolescents with asthma and nurse case managers.
With the increasing penetration of digital mobile devices among adolescents, mobile texting messaging is emerging as a new channel for patient-clinician communication for this population. In particular, it can promote active communication between healthcare clinicians and adolescents with asthma. However, little is known about the content of the messages exchanged in medical encounters via mobile text messaging. Therefore, this study explored the content of text messaging between clinicians and adolescents with asthma. We collected a total of 2,953 text messages exchanged between 5 nurse case managers and 131 adolescents with asthma through a personal digital assistant. The text messages were coded using a scheme developed by adapting categories from the Roter Interaction Analysis System. Nurse case managers sent more text messages (n=2,639) than adolescents with asthma. Most messages sent by nurse case managers were targeted messages (n=2,475) directed at all adolescents with asthma, whereas there were relatively few tailored messages (n=164) that were created personally for an individual adolescent. In addition, both targeted and tailored messages emphasized task-focused behaviors over socioemotional behaviors. Likewise, text messages (n=314) sent by adolescents also emphasized task-focused over socioemotional behaviors. Mobile texting messaging has the potential to play an important role in patient-clinician communication. It promotes not only active interaction, but also patient-centered communication with clinicians. In order to achieve this potential, healthcare clinicians may need to focus on socioemotional communication as well as task-oriented communication.


Riboswitches: natural SELEXion.
Advances in our knowledge of the structure and chemistry of RNA have been harnessed in the process known as SELEX to develop artificial RNA-based molecules that can act as enzymes and ligand binders performing a wide variety of functions. The discovery of riboswitches, natural RNA aptamers involved in genetic regulation, offers a basis of comparison between the artificial selection and the natural selection of structured RNAs for small-molecule recognition. The guanine riboswitch structural determination allows us to draw conclusions regarding the apparent increased complexity of the riboswitch aptamers compared to their in-vitro-selected cousins.


FOXO signaling pathway participates in oxidative stress-induced histone deacetylation.
High concentrations of antioxidants can exert pro-oxidative effects, elevate the level of intracellular reactive oxygen species (ROS), and cause oxidative stress in cells. We previously found that high concentrations of curcumin, a natural polyphenol antioxidant, elevated ROS levels and upregulated the expression of histone deacetylase 1 (HDAC1) in human gastric cancer cells (hGCCs); however, its potential mechanisms and subsequent functions have not been elucidated. In the present study, we treated hGCCs with high concentrations of curcumin, detected several indicators of oxidative stress, and investigated the mechanism of curcumin-treatment-mediated HDAC1 upregulation and its effect on histone acetylation. The results showed that curcumin treatment caused oxidative stress in hGCCs and upregulated HDAC1/2 expression via the forkhead box O (FOXO) signaling pathway, ultimately leading to the deacetylation of histones in hGCCs. Moreover, HDAC1/2 mediates the deacetylation of FOXOs and promotes their transcription activities, implying a positive feedback loop between FOXOs and HDAC1/2. These findings present a mechanism by which oxidative stress induces histone deacetylation in hGCCs.


Cytosol is the prime compartment of hepatitis B virus X protein where it colocalizes with the proteasome.
The hepatitis B virus X protein plays an important role in the regulation of viral genome expression and has also been implicated in the development of liver cancer associated with chronic viral infection. Several effects have been attributed to X but their biological relevance remains elusive. One of the confusing issues has been so far the uncertainty concerning its cellular location. To gain insight into the mechanism(s) how X exerts its effects, we have analysed its subcellular distribution and its dependency on the cell cycle. We used two complementary approaches namely, immunolocalization using a cell line stably expressing X, and characterization of the dynamics of X location in living cells by means of the reporter gene GFP. Our data clearly define the cytosol as the prime location of X, irrespectively of the cell cycle and show in addition the close attachment of a fraction of X to the nuclear membrane. However, X does not associate with any cytoplasmic vesicles and organelles so far tested. In contrast, our study provides strong evidence for the codistribution of X with the cytosolic fraction of proteasomes. In pulse-chase experiments, X decayed with a half-life of less than 30 min and proteasome-inhibitors did not modify its turnover, suggesting that X colocalization with the proteasome does not simply point to its degradation pathway. The proteolytic processing of the p105 precursor of the p50 subunit of the NF-kappaB transcription factor, which has been shown to be proteasome-dependent, is markedly slow down in the presence of X. These findings suggest that X modulates the processing rate of p105 by acting presumably at the level of the proteasome. Thus, targeting of proteasomes by X might be one of the pathways employed by this viral protein to subvert cellular functions.


Sarcopenia in the Elderly.
In the 21st century, life expectancy has increased and consequently so has the number of elderly people. Sarcopenia is an emerging area in geriatric medicine. The European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength and/or physical performance, associated with a risk of adverse outcomes such as physical disability, poor quality of life, and death. Sarcopenia requires diagnostic and interventional methods in order to initiate timely and appropriate treatment. Diagnosing sarcopenia requires assessments of muscle mass, muscle strength and physical performance. Management of sarcopenia involves a variety of approaches. Nutritional and exercise interventions are strongly supported.


Implant risk failure in patients undergoing postmastectomy 3-week hypofractionated radiotherapy after immediate reconstruction.
To evaluate reconstruction failure (RF) rate in patients receiving implant-based immediate breast reconstruction (IBR) and hypofractionated (HF) postmastectomy radiation therapy (PMRT). Stage II-III breast cancer patients, treated with HF-PMRT using intensity modulated radiotherapy were stratified in two groups according to IBR: single-stage direct-to-implant (DTI-group) and two-stage expander and implant (TE/I-group). Irradiated patients were matched with non-irradiated ones who underwent the same IBR during the same period. Prescription dose was 40.05 Gy/15 fractions to chest wall and infra/supraclavicular nodal region. Primary endpoint was RF defined as the need of major revisional surgery (MaRS) for implant removal or conversion to autologous reconstruction. Secondary endpoint was the rate of minor revisional surgeries (MiRS) including implant repositioning or substitution with another implant. One hundred and seven irradiated patients (62 in TE/I-group, 45 in DTI-group) were matched with 107 non-irradiated subjects. Median follow-up was 4.2 years (0.1-6.1) In the TE/I setting, MaRS was performed in 8/62 irradiated patients (12.9%) of the irradiated TE/I group compared to 1/62 (1.6%) non-irradiated subjects (p = 0.015). In the DTI setting, MaRs occurred in 3/45 irradiated patients (6.7%) compared to 1/45 non-irradiated ones (2.2%) (p = 0.35). Overall MaRS rate was 10.3% in the irradiated group. MiRS was performed in 35.6% and 31.1% of the irradiated and non-irradiated DTI-groups (p = 0.65), respectively, and in 12.9% and 8.1% of the irradiated and non-irradiated TE/I groups (p = 0.38), respectively. Compared to the non-irradiated counterparts, the TE/I group showed higher rate of RF, while no statistically significant difference was observed for the DTI group. The use of hypofractionation and IMRT to implant-based IBR did not seem to increase the risk of RF which appeared to be in line with the literature.


An in vitro adult mouse muscle-nerve preparation for studying the firing properties of muscle afferents.
Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice.


Craniofacial pain and incomplete oculomotor palsy associated with ipsilateral primitive trigeminal artery. Case report.
A case is reported of persistent primitive trigeminal artery associated with recurrent facial pain and noncomitant strabismus by partial ipsilateral oculomotor palsy. Transcranial Doppler disclosed indirectly persistent carotid-basilar anastomosis. CT and angiography allowed complete diagnosis excluding a posterior communicating artery aneurysm, a Tolosa-Hunt syndrome and an ophthalmoplegic migraine. Steroid therapy is recommended treatment. Surgery should be considered when symptoms are intractable to medical therapy.


Visible-light photochromism of triarylamine- or ferrocene-bound diethynylethenes that switches electronic communication between redox sites and luminescence.
Redox-active ferrocene- and triarylamine-terminated diethynylethene derivatives have been synthesized and their photochromic properties and switching behavior based on through-bond electronic communication between the two redox sites, as well as their emissions, have been examined. Both bis(ferrocenylethynyl)ethene 1 and bis(triarylaminoethynyl)ethene 2 show visible-light photochromism induced by donor-acceptor charge-transfer (CT) transitions from the ferrocene or triarylamine to the diethynylethene moieties. The reversibility and quantum yields of the photochromism of 2 (Phi(E-->Z)=6.1 x 10(-2), Phi(Z-->E)=1.4 x 10(-2)) are far higher than those of 1 (Phi(E-->Z)=8.6 x 10(-6), Phi(Z-->E)=2.5 x 10(-6)). The higher efficiency in 2 may be attributed to the absence of the heavy atom effect and of a low-lying (3)LF state, which are characteristic of ferrocenyl compounds. This proposition is further supported by the fact that bis(ferrocenylbuta-1,3-diynyl)ethene 3, which, unlike 1, is free from steric interference between the two ferrocenyl groups in the Z form, does not show a significant improvement in its photoisomerization quantum yields (Phi(E-->Z)=6.2x10(-5), Phi(Z-->E)=3.4 x 10(-5)). The visible-light photochromism of 1 and 2 is accompanied by a switch in the strength of the electronic communication between the two redox sites in their mixed-valence states (DeltaE(0)' values are 70 and 48 mV for (E)-1 and (Z)-1, and 74 and 63 mV for (E)-2 and (Z)-2). In the case of 2, further evaluations were carried out through intervalence charge-transfer (IVCT) band analyses and DFT calculations. We have also demonstrated that steric repulsion between the methyl ester moieties in the Z form is implicated in the reduction in the through-bond electronic communication. Compound 2 exhibits photoluminescence, which is more efficient in the E form than in the Z form, whereas 1 and 3 show no photoluminescence.


Your chance to shape the future of the RCN and the profession.
Offering you the chance to join a committee is unlikely to set your pulse racing, so let's put it another way: would you like to join a group of dynamic nurses who will help shape the future of the RCN and the wider nursing profession? If the answer is yes, then read on.


Simulation of stray laser light of Thomson scattering systems in the HL-2M tokamak.
Stray laser light is a serious problem that interrupts the measurement of electron temperature and density in Thomson scattering (TS) systems. This paper presents a ray-tracing simulation of stray laser light in HL-2M TS systems. A model including (i) a simplified laser-beam injection system, (ii) the scattered-light collection systems for central-point TS (CPTS) and edge TS (ETS), and (iii) the HL-2M vessel is built using the TracePro and CATIA software packages based on measurements of the bidirectional scattering distribution function at a wavelength of 532 nm. The simulation results show that no stray laser light reaches the injection surface of the collection lens of the CPTS system, and only a few stray laser rays of all the rays reaching the injection surface of the collection lens of the ETS system can be collected when the energy threshold per ray is 1 × 10-16. The stray laser rays that reach the scattered-light collection systems are mainly from the first and second parts of the slides of the beam dump, so decreasing the roughness of those parts could be effective in reducing the level of stray laser light.


Cobalt(III)-Catalyzed C-H Activation: Azo Directed Selective 1,4-Addition of Ortho C-H Bond to Maleimides.
Highly selective azo directed 1,4-addition of an ortho C-H bond to maleimides has been developed using Co(III) catalyst. This reaction furnishes 3-arylated succinimide derivatives in good yields with excellent selectivity. This protocol exhibits a broad substrate scope and is compatible with symmetrical and unsymmetrical azobenzene derivatives, with maleimides and maleate esters. Preliminary deuterium incorporation studies have been performed to understand the mechanism of the reaction.


Initial body temperature in ischemic stroke: nonpotentiation of tissue-type plasminogen activator benefit and inverse association with severity.
Body temperature (BT) is an important physiological factor in acute ischemic stroke. However, the relationship of initial BT to stroke severity and degree of benefit from thrombolytic therapy has been delineated incompletely. We analyzed the public data set of the 2 National Institute of Neurological Disorders and Stroke Tissue-Type Plasminogen Activator (tPA) stroke trials, comparing patients with lower (<37.0°C) and higher (≥37.0°C) presenting BT. Among 595 patients (297 placebo and 298 tPA treated) with documented initial BT, 77.1% had initial BT <37.0°C and 22.9% ≥37.0°C. Patients with higher initial BT had lower baseline stroke severity in both tPA-treated patients (the National Institute of Health Stroke Scale median, 11 versus 15; P=0.05) and placebo-treated patients (median, 13 versus 16; P<0.01). Patients with higher initial BT also had lower infarction volume on computed tomography at 3 months in both tPA-treated patients (median, 9.6 versus 16.7 cm(3); P=0.08) and placebo-treated patients (median, 13.1 versus 28.1 cm(3); P=0.02), but no clinical outcome differences. Analysis of lytic treatment effect found no heterogeneity in the degree of tPA benefit in both higher and lower BT groups (≥37.0°C: odds ratio for the modified Rankin Scale 0-1 outcome, 2.55; 95% confidence interval, 1.05-6.21 and <37.0°C: odds ratio, 2.30; 95% confidence interval, 1.38-3.84; heterogeneity P=0.83). In patients with hyperacute stroke, higher presenting temperatures are associated with less severe neurological deficits and reduced final infarct volumes. Presenting temperature does not modify the benefit of tPA on 3-month favorable outcome.


Long Noncoding RNA PVT1 as a Novel Diagnostic Biomarker and Therapeutic Target for Melanoma.
Accumulating evidences indicated that plasmacytoma variant translocation 1 (PVT1) plays vital roles in several cancers. However, the expression, functions, and clinical values of PVT1 in melanoma are still unknown. In this study we measured the expression of PVT1 in clinical tissues and serum samples and explored the diagnostic value of PVT1 for melanoma and the effects of PVT1 on melanoma cell proliferation, cell cycle, and migration. Our results, combined with publicly available PVT1 expression data, revealed that PVT1 is upregulated in melanoma tissues compared with nonneoplastic nevi tissues. Serum PVT1 level is significantly increased in melanoma patients compared with age and gender-matched nonmelanoma controls with melanocytic nevus. Receiver operating characteristic curve analyses revealed that serum PVT1 level could sensitively discriminate melanoma patients from controls. Furthermore, serum PVT1 level indicted melanoma dynamics. Functional experiments showed that overexpression of PVT1 promotes melanoma cells proliferation, cell cycle progression, and migration, while depletion of PVT1 significantly inhibits melanoma cells proliferation, cell cycle progression, and migration. Collectively, our results indicate that PVT1 functions as an oncogene in melanoma and could be a potential diagnostic biomarker and therapeutic target for melanoma.


Impact of proximity to comprehensive sickle cell center on utilization of healthcare services among children with sickle cell disease.
The impact of comprehensive care on utilization of healthcare services by children with sickle cell disease (SCD) has not been fully evaluated. We compared the medical care utilization and mortality in children less than 20 years of age with SCD in four regions in the state of Tennessee with and without a comprehensive sickle cell center (CSCC). Rates of hospitalizations, outpatient and emergency department (ED) visits, and deaths were measured in a cohort of children aged <20 years with SCD, enrolled in TennCare, from January 1995 to December 2002. TennCare data linked to Tennessee vital records were used to define the population and identify the outcomes. The patients were classified into one of four regions based on their residential address on the day of their hospitalization or outpatient visit. The cohort consisted of 1,214 children with 6,393 person-years of follow-up. Fifty-six percent of patients resided in the region with the CSCC. This region had the highest overall rates of hospitalization for all children (P < 0.001), while ED and outpatient visits were higher in other areas. The death rates ranged from 1.8 to 4.3 per 1,000 person-years in the four regions and did not represent statistically significant differences. No clear pattern of improved utilization of medical care services were identified in relation to proximity of residence to a CSCC. This cohort was not large enough to detect small differences in death rates. In addition, other outcomes that incorporate quality of life measures may be more sensitive to differences in medical care.


Dynamic Aspects of Macrophage Polarization during Atherosclerosis Progression and Regression.
It is well recognized that macrophages in many contexts in vitro and in vivo display a spectrum of inflammatory features and functional properties. A convenient system to group together different subsets of macrophages has been the M1 (inflammatory)/M2 (anti-inflammatory) classification. In addition to other sites of inflammation, it is now established that atherosclerotic plaques contain both M1 and M2 macrophages. We review results made possible by a number of recent mouse models of atherosclerotic regression that, taken with other literature, have shown the M1/M2 balance in plaques to be dynamic, with M1 predominating in disease progression and M2 in regression. The regulation of the macrophage phenotype in plaques and the functional consequences of the M1 and M2 states in atherosclerosis will also be discussed.


A review of the Generic Design Assessment (GDA) Public Dialogue Pilot (2015) for new nuclear build in the UK: lessons for engagement theory and practice.
We have discussed previously that a community-based, asset-based approach is required to achieve any sense of how social sustainability can be defined in a community setting within the context of energy developments. Our approach aims to initiate a lasting change within 'energy' communities through building social capital; focusing on community assets not deficits to define their social priorities. Through deliberation, we develop an understanding of social sustainability so that a community is well placed to enter discussions with government and industry regarding large energy developments that will directly affect them. We review the 2015 Generic Design Assessment (GDA) Public Dialogue Pilot process for potential new nuclear reactors in the UK. We examine the aims of the dialogue, giving particular attention to a comparison between the national sampling of citizens for the GDA and the local community-based, deliberative approach we have proposed previously. We find an ongoing tension between 'national' engagement processes (such as the GDA Public Dialogue Pilot process) and the specific requirements of those energy communities that live adjacent or close to energy infrastructure, manifested here by a conflict between the requirements of the convenor and those of participants regarding priority issues for discussion. We also reveal a paradox; despite participant preference for a remote, internet-based engagement process, they agreed that face to face contact is a priority to encourage trust building between participants and the convenor of the process-a desired outcome of the process. The GDA Public Dialogue Pilot process has demonstrated that stakeholders are willing to engage with and be more directly involved in local energy-related decisions that affect them directly, provided there is opportunity to discuss locally-relevant and site-specific issues in addition to those of a broader nature. There exists a disparity and conflict between 'national' engagement processes and the 'local' priorities of those energy communities that are adjacent or close to energy infrastructure. In this process and others, we have seen an imbalance between the requirements of the convenor and those of participants regarding priority issues for discussion. This continues to be a persistent challenge for those convening stakeholder engagement events where the scope and context is not primarily site-specific. However, it is encouraging that convenors and participants alike continue to be willing to work towards resolving this.


Manipulating chemoattractant and receptor genes.
Chemoattractants, including classical chemotactic factors and members of the chemokine superfamily, function as inducers of leukocyte trafficking and activation based on interactions with seven transmembrane (STM), G protein-coupled receptors. These molecules are expressed by many cell types either constitutively or upon stimulation. Considerable knowledge about the pathophysiological role of chemoattractants and their receptors has been accumulated during the past two decades. However, recent studies using transgenic and gene targeting technology have provided a better illustration of the importance and complexity of the involvement of chemoattractants and receptors in leukocyte trafficking, inflammation, infection, immune responses, development, angiogenesis/angiostasis, and malignant tumors.


Caveolin-3 deficiency decreases the gene expression level of osteopontin in mdx mouse skeletal muscle.
Caveolin-3 is a muscle-specific membrane protein that serves as a scaffold of various molecules. As previously reported, caveolin-3 deficiency causes muscle degeneration in mice. In the present study, gene expression profiles, analyzed in the skeletal muscles of caveolin-3 deficient mice using the DNA microarray technique, showed that the gene of osteopontin, a versatile regulator of inflammation and tissue repair, was significantly down-regulated. This is in contrast to mdx mice showing a markedly up-regulated osteopontin gene in their skeletal muscles. Recently, osteopontin has been reported to be important in the pathogenesis of muscular dystrophy. We examined whether up-regulated osteopontin gene expression in mdx muscles is altered by the deficiency of caveolin-3. To this end, we developed caveolin-3 and dystrophin double-deficient mice and used them for the analysis. Levels of osteopontin mRNA and protein in the double-deficient mice clearly decreased compared with those in mdx mice.


Mineral trioxide aggregate and subepithelial connective tissue graft for treatment of iatrogenic gingival recession: long-term results.
This study aimed to examine the combination of mineral trioxide aggregate (MTA) and subepithelial connective tissue grafts to treat esthetic deficiencies caused by iatrogenic tooth perforations. Three patients were treated, and clinical and histologic documentation was obtained. Connective tissue grafts were performed following standard techniques after application of MTA to seal the root perforations. Complete root coverage was obtained, significantly improving the esthetic outcomes. Histologic analysis showed the long junctional epithelium in intimate contact with the root surface. It appeared to form coronal to the perforation and extended apical to the MTA. Based on the limitations of this clinical and histologic observation, it can be concluded that MTA in conjunction with connective tissue grafts could be considered for treatment of esthetic deficiencies associated with iatrogenic tooth perforations.


High temperature microbial activity in upper soil layers.
Biomineralization at high temperatures in upper soil layers has been largely ignored, although desertification and global warming have led to increasing areas of soils exposed to high temperatures. Recent publications evidenced thermophilic bacteria ubiquity in soils as viable cells, and their role in nutrient cycling and seedling development. High temperature events, frequently observed at medium and low latitudes, locate temporal niches for thermophiles to grow in soils. There, at temperatures inhibitory for common mesophiles, thermophilic bacteria could perform biogeochemical reactions important to the soil food web. Nutrient cycling analyses in soils at medium and low latitudes would benefit from considering the potential role of thermophiles.


Attention modulates the learning of multiple contingencies.
We employed a novel version of the serial reaction time task to test the idea that human implicit learning allows the simultaneous learning of multiple independent contingencies and that this learning may proceed in the absence of attention. Using probabilistic sequences, we showed that both a primary sequence (the focus of the experimental task) and a statistically independent secondary sequence could be learned across 4,800 target localization trials, provided the perceptual load of the primary task was low. However, learning of the secondary sequence was abolished under conditions of high perceptual load. These findings suggest that there are attentional limitations on the learning of multiple contingencies.


Subcutaneoscopic excision of external angular dermoid cyst in children without conspicuous scarring.
External angular dermoid cysts are benign lesions that are excised through an incision over the eyebrow. This leaves a visible scar that may not be cosmetically acceptable. Herein, we describe a minimally invasive subcutaneoscopic technique that involves placing incisions above the hairline to avoid scarring on the face. This is a retrospective review of three consecutive cases of dermoid cysts. Each patient underwent subcutaneoscopic excision between March 2012 and September 2012. With the patient under general anesthesia, a 6-mm incision was made on the scalp above the hairline. After a wide subcutaneous tunnel was created, a 5-mm port with a 30° telescope was placed for an optical port. Insufflation was done with CO2 at pressure of 8 mmHg and flow rate of 1 L/min. Two para-optical stab incisions were used to insert a 3-mm Maryland dissector and a 3-mm hook for dissection. The cyst was excised and removed through one of the ports. All three cases underwent successful subcutaneoscopic excision without the need for conversion. The mean operative time was 42 min. There were no complications, and all patients had excellent cosmesis. Subcutaneoscopic excision of dermoid cyst is a technically feasible procedure in pediatric patients, as demonstrated by our three cases. It provides excellent cosmesis and avoids scarring on the face.


Laparoscopic aproach in post-traumatic chylous ascites.
Chylous ascites is a rare condition little reported in literature, with even more exceptional traumatic origin. Its production mechanism is not known exactly but has been attributed to hyperflexion or hyperextension of the spine leading to a rupture of lymph ducts. We present a case of post-traumatic chyloperitoneum in a young patient after abdominal blunt trauma. Conservative treatment should be the first therapeutic option, especially if the origin is traumatic, reserving more aggressive possibilities for cases that do not respond after 15 days, if debt is greater than 1.5 litres/day in adult patients or in those with metabolic complications. A laparoscopic approach is indicated to confirm the diagnosis and to rule out other associated injuries that may require other surgical procedures.


Esophageal adenocarcinoma after laparoscopic gastric band placement for obesity.
Obesity is a risk factor for the development of esophageal malignancy. We report a case of the development of esophageal adenocarcinoma after placement of an adjustable gastric band for obesity. A 66-year-old male was referred to our clinic for findings of an obstructing mass at the gastroesophageal junction after previously undergoing a laparoscopic adjustable gastric band placement. Investigations confirmed a locally advanced poorly differentiated esophageal adenocarcinoma. The patient underwent chemotherapy and gastric band removal with improvement of his dysphagia. However, his disease progressed and he died of metastatic disease. We discuss the diagnosis of esophageal carcinoma after gastric banding procedure.


Image analysis of Transwell assays in the assessment of invasion by malignant cell lines.
This study aims to determine if layering of extracellular matrix (ECM) can achieve a physiological basement membrane thickness of 8 microm and to assess the use of paraffin wax-embedded Transwell plates coupled with digital image analysis as a means of determining invasion by malignant cell lines. Layers of Matrigel, a sarcoma-derived ECM was built to a concentration of 7.4 microg/mm2 in the upper chamber of a Transwell plate invasion assay. Two cell lines from extrahepatic bile duct adenocarcinoma were tested in serum-free growth medium. Conditioned medium was added to the lower chamber to act as a chemoattractant. Following attachment, cells were incubated for 48 h and the Matrigel-coated insert cut from its holder and fixed in 10% unbuffered formalin saline. Each insert was bisected and processed to paraffin wax. Serial levels were stained by haematoxylin and eosin. A Kontron image analysis system was used to measure the mean thickness of Matrigel for each cell line and the degree of invasion was assessed by measuring the depth to which cells had degraded the Matrigel. A mean thickness of 8 microm was achieved using 5.0 microg/mm2 for the OCUCh-LM1 cell line and 7.4 microg/mm2 for the SKChA-1 cell line. No significant difference was seen in the ability of either cell line to degrade Matrigel. Immunocytochemistry for laminin and cytokeratin helped to identify ECM components and cells, respectively. In conclusion, digital image analysis of paraffin wax-embedded inserts can be used to determine the invasive capacity of various cell lines; immunocytochemistry may help to identify ECM components and cells; and the assay used to assess different cell lines and their ability to degrade Matrigel.


Molecular HLA-class II typing: advantages and clinical application.
The major histocompatibility complex (HLA system in Man) is characterized by its extensive degree of allelic polymorphism. After the serological and cellular methods, the molecular biological methods appeared to be a powerful tool in detecting HLA-class II polymorphism. Restriction fragment length polymorphism (RFLP), using restriction endonucleases, represented an efficient method of HLA-DR, DQ, and DP genotyping. Recently, the polymerase chain reaction (PCR) permitted the development of two major class II genotyping techniques: the PCR allele specific oligonucleotide typing and the PCR-RFLP typing. By these new methods, a refined and accurate determination of DRB, DQB, DQA, and DPB alleles is possible. The major application of a refined HLA class II typing is in transplantation especially for unrelated bone marrow grafts. Moreover, it permits the identification of the amino acids implicated in the cellular response which by itself is important for the fundamental immunological studies.


Structure modeling of Co-encapsulated PPI dendrimer.
Co-encapsulated PPI dendrimer with 64 functional groups (G5-generation) on periphery was synthesized. The modeled PPI dendrimer-like structure composed of 4 and 6 terminal flexible chains displays empty spaces between chains on periphery. Obtained occupation area on periphery is 1.0-3.0 nm2 where could be most probable location place of Co nanoparticle. The modeled structure displays that periphery of the PPI dendrimer is rich of oxygen atoms. The influence of oxygen on the stability of Co2O(m) and Co6O(m) (m = 1-7) clusters were studied. Calculations results demonstrate that higher oxidation rate enhances the stability of Co-O clusters.


Endothelial injury induced by thrombin or thrombi.
A variety of blood constituents was injected into an isolated segment of rabbit aorta to determine which elements might be involved in early endothelial injury. Test materials consisted of platelet-rich plasma (PRP) alone; PRP plus adenosine diphosphate (ADP); PRP plus tendon extract; PRP plus thrombin; ultrasonicated PRP alone; platelet-poor plasma alone; and thrombin in saline. Each experimental mixture was left in the aorta for 15 minutes, followed by reflow for 20 minutes. The vessel was then fixed by glutaraldehyde perfusion. Thick sections of the entire circumference of the aorta were taken for phase contrast microscopy and representative arease were selected for electron microscopy. In control PRP alone, platelet-poor plasma alone and with PRP plus ADP there were occasional subendothelial vesicles. When PRP plus thrombin and platelet-poor plasma plus thrombin were injected separately to form a thrombus or when thrombin in saline was used, there was extensive subendothelial vesiculation with focal ulceration and adherence of thrombus to endothelium. Severe injury was associated with the presence of thrombin initiating the polymerization of fibrinogen to fibrin. Electron micrographs demonstrate the earliest lesion as a disruption of the superficial fibrilliary elastica with separation of overlying endothelium.


Prevalence of skin diseases among adolescents 12--16 years of age.
A prevalence study of 8298 pupils in compulsory school grades 7--9 was performed in the county of Västerbotten (AC county) in northern Sweden. Prevalence figures for 19 skin diagnoses are presented. A female dominance was found in the prevalence of atopic dermatitis, striae distensae and plantar warts, and a male dominance in multiple pigmented naevi. A sharp drop in atopic dermatitis was found at 13 years. Acne vulgaris showed a negative correlation with atopic dermatitis, ephelides, multiple pigmented naevi and spider naevi and a positive correlation with striae distensae. Atopic dermatitis was negatively correlated to ephelides and multiple pigmented naevi as well as acne. Pronounced variations in the occurrence of plantar warts were registered between different schools. Of the 19 diagnoses registered, only hereditary palmo-plantar keratodermia has a geographical distribution compatible with an increased prevalence of the disease in the AC county. Consequently the figures presented for the other diagnoses are considered to be representative for a north European Caucasian population.


Scintigraphy with [111In]octreotide and 201Tl in a Hürthle cell thyroid carcinoma without detectable radio-iodine uptake. Report of a case and review of the literature.
To describe the visualization of recurrent disease by [111In]octreotide and 201Tl scintigraphy in a patient with Hürthle cell thyroid carcinoma, increased thyroglobulin levels, and a negative radio-iodine total-body scan. Scintigraphy with [111In]octreotide and 201Tl was performed, and a local recurrence in the thyroid bed was detected which was excised by surgery. On histology, the tumour proved to be a Hürthle cell carcinoma, and within the tumour somatostatin receptors were detected by RT-PCR. Scintigraphy with [111In]octreotide and 201Tl is an alternative imaging method for the detection of residual disease in patients with a differentiated thyroid carcinoma having increased thyroglobulin levels and a negative radio-iodine total-body scan.


Complex structural ordering of the oxygen deficiency in La0.5Ca2.5Mn2O7-δ Ruddlesden-Popper phases.
Ruddlesden-Popper oxides, (AO)(ABO3)n, occupy a prominent place in the landscape of materials research because of their intriguing potential applications. Compositional modifications to the cation sublattices, A or B, have been explored in order to achieve enhanced functionalities. However, changes to the anionic sublattice have been much less explored. In this work, new oxygen-deficient manganese Ruddlesden-Popper-related phases, La0.5Ca2.5Mn2O6.5 and La0.5Ca2.5Mn2O6.25, have been synthesized by controlled reduction of the fully oxidized n = 2 term La0.5Ca2.5Mn2O7. A complete structural and compositional characterization, by means of neutron diffraction, electron diffraction and atomically resolved scanning transmission electron microscopy and electron energy-loss spectroscopy techniques, allows the proposition of a topotactic reduction pathway through preferential oxygen removal in the [MnO2] layers along [031] and [0{\bar 1}3] directions. The gradual decrease of the Mn oxidation state, accommodated by short-range ordering of anionic vacancies, reasonably explains the breaking of ferromagnetic interactions reinforcing the emergence of antiferromagnetic ones. Additional short-range order-disorder phenomena of La and Ca cations have been detected in the reduced La0.5Ca2.5Mn2O7-δ, as previously reported in the parent compound.


Comparative Transcriptomic and Metabolic Analyses Reveal the Molecular Mechanism of Ovule Development in the Orchid, Cymbidium sinense.
Ovule development is pivotal to plant reproduction and seed development. Cymbidium sinense (Orchidaceae) has high ornamental value due to its pleasant aroma and elegant floral morphology. The regulatory mechanism underlying ovule development in orchids, especially C. sinense, is largely unknown and information on the C. sinense genome is very scarce. In this study, a combined analysis was performed on the transcriptome and non-targeted metabolomes of 18 C. sinense 'Qi Jian Hei Mo' ovule samples. Transcriptome analysis assembled gene-related information related to six growth stages of C. sinense ovules (S1-S6, equivalent to 30, 35, 42, 46, 53, and 60 days after pollination). Illumina sequencing technology was used to obtain the complete set of transcriptome sequences of the 18 samples. A total of 81,585 unigene sequences were obtained after assembly, 24,860 (30.47%) of which were functionally annotated. Using transcriptome sequencing technology, a total of 9845 differentially expressed unigenes (DEUs) were identified in C. sinense ovules that were assigned to specific metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). DEUs associated with transcription factors (TFs) and phytohormones were identified and analyzed. The TFs homeobox and MADS-box were associated with C. sinense ovule development. In particular, the phytohormones associated with DEUs such as indole-3-acetic acid (IAA), cytokinin (CK), gibberellin (GA), abscisic acid (ABA), brassinosteroid (BR), and jasmonate (JA), may have important regulatory effects on C. sinense ovule development. Metabolomic analysis showed an inconsistent number of KEGG annotations of differential metabolites across comparisons (S2_vs_S4, S2_vs_S5, and S4_vs_S5 contained 23, 26, and 3 annotations, respectively) in C. sinense ovules. This study provides a valuable foundation for further understanding the regulation of orchid ovule development and formation, and establishes a theoretical background for future practical applications during orchid cultivation.


Emotional indicators in young patients with Idiopathic Scoliosis: a study through the drawing of Human Figure.
Investigating Health Related Quality of Life (HRQL) is considered determinant in patients with Adolescent Idiopathic Scoliosis (AIS) in clinical as in research field. The aim of the present study is to explore the most relevant aspects of personality of the patients with AIS and its relationship with HRQL. 50 patients (mean age = 16 years) were given a socio-demographic data questionnaire, the Human Figure Drawing (HFD) and SRS (Scoliosis Research Society) -22. In Subtotal SRS-22, patients presented a mean value of 3.9. In HFD, half of these patients presented physical and/or emotional tensions with reference to the shoulders and almost all of them did not show any expression of aggressiveness. No relationship between personality and HRQL was confirmed. The older the patients were, the more body tension was discovered as well as the more concerns about their bodies they showed to have. There was also a correlation between growing old and a decreasing in Mental Health. Previous conservative treatment did not show any impact on personality or on HRQL. Patients with AIS suffer stress and general concern more frequently with the increase of age. We suggest an appropriate supportive treatment for this type of patients.


Environmentally Responsive Systems for Drug Delivery.
In recent decades, the development of the environmentally responsive systems for drug delivery has been well regarded, with enormous potential in different applications.

 Methods: These environmentally sensitive, smart, intelligent formulations have the ability to alter their physical properties in response to small changes in physical or chemical conditions, such as temperature, glucose, pH, ultrasound, light, electric field and redox potential with a huge potential in drug delivery systems. The use of formulations containing smart materials enables to carry the drug to the target tissue, cells and release in a triggered way. Consequently, they have demonstrated several advantages like decreased dose frequency, ease of preparation and administration, prolonged release with reduced side effects, as well as, reduced costs when compared to conventional processes for industrial applications. In this sense, many patents have deposited, displaying different pharmaceutical devices using responsive systems.

 Results: There are more than twenty-five patents deposited about thermoresponsive systems. Furthermore, a few number of patents within glucose responsive, ultrasound responsive and light responsive deposited. There also are about eight patents that are pH-responsive, four as electric-field responsive. Most of them cover more than one type of stimuli.

 Conclusion: Therefore, in this review, since 1975 to 2016, we have categorized, reviewed and discussed the patents, applications, pharmaceutical dosage forms, the importance and perspectives of this environmentally responsive approach as potentially useful therapeutic modality.


Cervical angina.
Cervical angina is defined as chest pain that resembles true cardiac angina but originates from a cervical discopathy with nerve root compression. This condition, which is also referred to as pseudoangina, most commonly results from compression of the C7 nerve root. Several simple findings from the history and the physical examination help make the diagnosis, which can then be confirmed with magnetic resonance imaging and/or discography. Coexisting coronary artery disease must always be ruled out. Treatment includes intermittent cervical traction, physical therapy, nonsteroidal anti-inflammatory drugs and muscle relaxants. If these measures fall to alleviate the patient's pain, referral to a spine surgeon may be indicated.


Bactericidal and fungicidal activities of Calia secundiflora (Ort.) Yakovlev.
Calia secundiflora (Ortega) Yakovlev (Fabaceae) is considered a medicinal plant in Mexico but has scarcely been used because of the toxicity of its quinolizidine alkaloids. Several quinolizidine alkaloids have shown bactericidal, nematicidal, and fungicidal activities. The purpose of this study was to identify the alkaloids in the seeds and evaluate the activity of the organic extract on several phytopathogenic fungi and bacteria. An in vitro bioassay was conducted with species of the following phytopathogenic fungi: Alternaria solani, Fusarium oxysporum and Monilia fructicola; and of the following bacteria Pseudomonas sp., Xanthomonas campestris and Erwinia carotovora. Cytisine, lupinine, anagyrine, sparteine, N-methylcytisine, 5,6-dehydrolupanine, and lupanine were identified by liquid chromatography-mass spectrometry in the extract of seeds; the most abundant compound of the extract was cytisine. It was observed that the crude extract of Calia secundiflora was moderately active on bacteria and more potent on phytopathogenic fungi. In contrast cytisine showed the opposite effects.


Oligonucleotide (GTG)5 as an epidemiological tool in the study of nontuberculous mycobacteria.
Analysis of restriction fragment length polymorphisms in the genome of Mycobacterium tuberculosis (DNA fingerprinting) has proved to be a useful epidemiological tool in the study of tuberculosis within populations or communities. However, to date, no similar method has been developed to study the epidemiology of nontuberculous mycobacteria (NTM). In this communication, we report that a simple oligonucleotide repeat, (GTG)5, can be used to accurately genotype all species and strains of NTM tested. We suggest that this technology is an easily applied and accurate tool which can be used for the study of the epidemiology of NTM.


Incomplete metabolism of phytoestrogens by gut microbiota from children under the age of three.
Phytoestrogens are plant-derived polyphenols with structural and functional similarities to mammalian oestrogens. The aim of this work was to study the metabolism of phytoestrogens by children's intestinal microbiota and to compare it with previous results in adults. Faecal samples of 24 healthy children were subjected to phytoestrogen fermentation assay. Only one child produced equol, while O-desmethylangolensin was found in all. Urolithin production was detected in 14 children and enterolactone in 10. Further comparison with the metabolism of phytoestrogens by adult intestinal microbiota reflected that glycitein, dihydrogenistein, urolithins D and E, enterolactone, secoisolariciresinol and arctigenin were the most important metabolites differentiating between adult and child microbial gut metabolism. Although the child intestinal microbiota showed the ability to metabolise isoflavones, ellagitannins and lignans to a certain extent, it generally showed a reduced metabolism of phytoestrogens, with a lack of 5-hydroxy equol and enterodiol, and less urolithins and enterolactone producers.


Fabrication of Thermoresponsive Nanoactinia Tentacles by a Single Particle Nanofabrication Technique.
Nanowires that are retractable by external stimulus are the key to fabrication of nanomachines that mimick actinia tentacles in nature. A single particle nanofabrication technique (SPNT) was applied over a large area to the fabrication of retractable nanowires (nanoactinia tentacles) composed of poly(N-isopropylacrylamide) (PNIPAM) and poly(vinylpyrrolidone) (PVP), which are thermoresponsive and hydrophilic polymers. The nanowires were transformed with increasing temperature from rod-like- to globule-forms with gyration radii of ∼1.5 and ∼0.7 μm, respectively. The transformation of the nanowires was reversible and reproducible under repeated cycles of heating and cooling. The reversible transformation was driven by hydration and dehydration of PNIPAM, the thermoresponsive segments, resulting in coil-to-globule transformation of the segments. The nanoactinia tentacle systems trapped the nanoparticles as a model of living cells under thermal stimulation, and the trapping was controlled by temperature. We present herein a unique nanomachine system which can be applicable to nanoparticle filtering/sensing systems and expandable to large-area functionalization and demonstrate polymer-based nanoactuators via scaling of molecular level coil-to-globule transformation into micron-sizes.


Obesity in Eastern Europe: an overview of its health and economic implications.
To assess the evolution and patterns of obesity in countries of the WHO European Region with a particular focus on the Eastern European countries, and to discuss the health and economic implications of obesity for those countries. The available data on overweight and obesity in children and adults for the countries of the WHO European countries were collated from the International Obesity TaskForce database and considered in the light of estimates for the costs of obesity-related ill health. Overweight and obesity in most countries of Europe show rising secular trends, and are predicted to continue rising if not addressed. Estimates of the costs to the health services and to economic productivity indicate that some countries may find it hard to cope with the burden of obesity: up to 6% of total health care costs and as much in indirect costs of lost productivity could be attributed to obesity and its associated illnesses. Transition, despite the many benefits it has undoubtedly conferred to the population living in the Region, has also entailed the collateral damage of a fast growing obesity challenge. Policy-makers in the new and candidate EU countries as well as other countries of the European Region can learn from the negative Western European and global experience, act now to stem the obesity epidemic from further developing and in so doing, reduce the substantial economic losses associated with obesity. Local, national and international strategies will be needed to combat the problem.


In vivo secretome sampling technology for proteomics.
Secretome is a critical mediator for cell-cell and microbe-cell interaction. Identification of secretome will endow researchers with important biomarkers and therapeutic targets as well as reinforce the current methods used in the systems biology research of cell-cell interactions. Here, we introduce an in vivo sampling technique using capillary ultrafiltration (CUF) probes that are capable of continuously collecting pure in vivo secretome from tissue microenvironments. Great benefits of CUF probes when compared with other current sampling techniques have been acknowledged. CUF probes can be designed to fit various in vivo models and they are easily adapted to different protein-detection systems including mass spectrometers. The future challenges and clinical advantages of CUF probe sampling are also highlighted in this review. Many prospective properties such as simple manipulation, dynamic sampling, pathogen clearance, online mass spectrometric coupling, and disease treatment and monitoring have made CUF probes attractive for clinical uses in the near future.


Chemical Stability of Morphine, Ropivacaine, and Ziconotide in Combination for Intrathecal Analgesia.
Pain is the most feared symptom amongst individuals living with cancer. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Intrathecal drug delivery systems may present an effective alternative for pain management. The Cancerology Center Paul Papin protocol includes an admixture of morphine, ropivacaine, and ziconotide in intrathecal preparations. These drugs are administered by a fully implantable or an external pump. Syringes or polyolefin infusion bags are prepared for refill just before use. Few centers in France use the method of intrathecal analgesia. Therefore, for those patients receiving intrathecal preparations, each filling requires that the patients be transported from their local hospital (or their home) to a referral center where the patients are monitored. They sometimes must travel up to a hundred kilometers to have a pump filled. The preparation and the analytical control of the mixture are carried out only by those centers meeting the proper criteria, which includes the proper equipment. To spare the patient this travel, a peripheral center may be subcontracted to manage the patient's pump refill. No data are available concerning the chemical stability of admixtures in syringes or polyolefin infusion bags. The aim of this study was to evaluate, with a new analytical method using ultra high-performance liquid chromatography, the chemical stability of these admixtures in syringes or in polyolefin infusion bags. Ziconotide 1 µg/mL was combined with ropivacaine (7.5 mg/mL) and morphine (3.5 mg/mL) in syringes at 5°C, 21°C, and 31°C, and in polyolefin infusion bags at 21°C. Assays were performed using ultra high-pressure liquid chromatography. In syringes stored at 21°C and 31°C, concentrations after 6 hours were not in the acceptable criterion of 10% variability. When syringes were stored at 5°C, the residual concentration of ziconotide after 3 days was 100.5% +/- 2.6% [92.7% to 108.4%]. In polyolefin infusion bags, the residual concentration of ziconotide after 14 days was 96.9% +/- 2.2% [90.1% to 103.6%]. This study demonstrates the chemical stability of this admixture in syringes stored at 5°C for 3 days and in polyolefin plastibags stored at 21°C for 14 days.


Useful landmarks in arytenoid adduction and laryngeal reinnervation surgery.
Knowledge of the location of the muscular process of the arytenoid cartilage and the recurrent laryngeal nerve is essential to performing a successful arytenoid adduction and laryngeal reinnervation surgery. We describe external landmarks useful in locating these structures. Cadaveric laryngeal dissection. Posterior laryngeal dissection was performed in 16 human larynges. The position of the muscular process of the arytenoid was measured bilaterally relative to the inferior and superior borders of the thyroid lamina. The recurrent laryngeal nerve was followed distally from slightly below the level of the cricothyroid joint to its genu where its vertical course changes to an oblique intralaryngeal course. The muscular process of the arytenoid was usually found halfway between the roots of the superior and inferior cornu of the thyroid lamina. The recurrent laryngeal nerve was found just deep to the cricothyroid joint and lateral to the posterior cricoarytenoid muscle. There were no other nerves in this area. This study finds that the superior and inferior borders of the thyroid lamina are useful intraoperative landmarks to locate the muscular process of the arytenoid. The cricothyroid joint provides a good starting point to locate the recurrent laryngeal nerve, which can be identified slightly deeper between it and the posterior cricoarytenoid muscle.


Land cover diversity increases predator aggregation and consumption of prey.
A lower diversity of land cover types is purported to decrease arthropod diversity in agroecosystems and is dependent on patterns of land use and fragmentation. Ants, important providers of ecosystem services such as biological control, are susceptible to landscape-level changes. We determined the relationships between land cover diversity and fragmentation on the within-field spatial associations of ants to pests and resulting predation events by combining mapping and molecular tools. Increased land cover diversity and decreased fragmentation increased ant abundance, spatial association to pests and predation. Land cover diversity and fragmentation were more explanatory than land cover types. Even so, specific land cover types, such as deciduous forest, influenced ant and pest diversity more so than abundance. These results indicate that geospatial techniques and molecular gut content analysis can be combined to determine the role of land use in influencing predator-prey interactions and resulting predation events in agroecosystems.