Microleakage of endodontically treated teeth restored with posts.
A fluid filtration system using 15 psi of pressure on the penetrating fluid was used to quantify the amount of microleakage of a stainless-steel post and a carbon-fiber post system, each placed with various cements. Statistical analysis showed that there was a significant difference in microleakage between the cements (p < 0.001). Zinc phosphate cement showed the most microleakage, whereas C & B Metabond cement showed the least. There was no significant difference in microleakage between the stainless-steel and carbon-fiber posts. The results of this study showed that both posts, when cemented with dentin-bonding resin cements (C & B Metabond and Panavia-21), exhibited less microleakage than when cemented with non-dentin-bonding cements (glass ionomer and zinc phosphate).


MPK38 expression is upregulated in immature T cells activated by concanavalin A.
We have previously identified a cDNA clone from a murine teratocarcinoma PCC4 cDNA library, which we have termed MPK38 for murine protein kinase 38. MPK38 is a new member of the SNF1 serine/threonine kinase family. To understand the role of the MPK38 in thymocytes, we have investigated the level of MPK38 expression by Northern blot analysis. Interestingly, incubation of thymocytes at 37 degrees C resulted in the loss of the MPK38 transcript, however the transcript could be reinduced by treatment with Con A or PHA, but not with PMA and growth factors such as IL-2, IL-7, TGF-beta, TNF-alpha, and EGF. In addition, stimulation of mature T cells from the spleen with Con A failed to reinduce the MPK38 transcript, indicating a developmental regulation of MPK38 expression, whereas non-T cell populations significantly reinduced the transcript. These results suggest that MPK38 may play a functional role as one of the signal regulators in early T cell activation and, potentially, certain lineages of hematopoietic cell activation induced by Con A.


Addressing sustainability gaps.
Widespread industrialization, rapid urbanization, and massive transport through land, waters, and air have led to catastrophes such as climate change, water pollution, resource limitation, and pandemics causing severe economic consequences, massive influences on the natural environment and pose a great threat to the life sustainability. Sustainability topic has a long history, and many policies and initiatives are in effect for a sustainable planet Earth, still gaps of varying degrees exist in almost all sectors. This article addresses the essentiality of minimising the sustainability gaps exist in diverse realms of life and citing few examples. Creating a cyclic path for production-consumption process in the economic sector through promoting circular economy, learning from the natural processes through appropriate biomimicking, and knowledge-integration from diverse disciplines and emphasizing sustainability in the educational sector are shown to lower the sustainability gaps.


Biochemical and pharmacological properties of a new proton pump inhibitor, 2-amino-4,5-dihydropyrido[1,2-a]thiazolo [5,4-g] benzimidazole (YJA20379-5).
This study was designed to determine biochemical and pharmacological properties of a newly synthesized benzimidazole derivative, 2-amino-4,5-dihydropyrido [1,2-a] thiazolo [5,4-g] benzimidazole (YJA20379-5) in vitro and in vivo. In the leaky membrane vesicles of pig gastric mucosa, YJA20379-5 inhibited the K(+)-stimulated H+,K(+)-ATPase activity in a concentration- and time-dependent manner, with IC50 values being 43 microM and 31 microM at pH 6.4 and 7.4, respectively. YJA20379-5, given intraduodenally, had a potent inhibitory effect on the gastric acid secretion in pylorus-ligated rats. The ED50 value for acid secretion was 15.4 mg/kg. YJA20379-5, administered orally, also suppressed gastric damages induced by water-immersion stress, indomethacin and ethanol, and duodenal damage induced by mepirizole in rats; the ED50 values were 17.6, 4.7, 3.0 and 18.7 mg/kg, respectively. Furthermore, repeated oral administration of YJA20379-5 accelerated the spontaneous healing of acetic acid-induced gastric ulcers in rats. It is concluded that the antisecretory activity of YJA20379-5 appears to be associated with inhibition of H+,K(+)-ATPase, while its antigastric and antiduodenal lesion activities are primarily related to the antisecretory effect.


Machine learning approaches to analyze histological images of tissues from radical prostatectomies.
Computerized evaluation of histological preparations of prostate tissues involves identification of tissue components such as stroma (ST), benign/normal epithelium (BN) and prostate cancer (PCa). Image classification approaches have been developed to identify and classify glandular regions in digital images of prostate tissues; however their success has been limited by difficulties in cellular segmentation and tissue heterogeneity. We hypothesized that utilizing image pixels to generate intensity histograms of hematoxylin (H) and eosin (E) stains deconvoluted from H&E images numerically captures the architectural difference between glands and stroma. In addition, we postulated that joint histograms of local binary patterns and local variance (LBPxVAR) can be used as sensitive textural features to differentiate benign/normal tissue from cancer. Here we utilized a machine learning approach comprising of a support vector machine (SVM) followed by a random forest (RF) classifier to digitally stratify prostate tissue into ST, BN and PCa areas. Two pathologists manually annotated 210 images of low- and high-grade tumors from slides that were selected from 20 radical prostatectomies and digitized at high-resolution. The 210 images were split into the training (n=19) and test (n=191) sets. Local intensity histograms of H and E were used to train a SVM classifier to separate ST from epithelium (BN+PCa). The performance of SVM prediction was evaluated by measuring the accuracy of delineating epithelial areas. The Jaccard J=59.5 ± 14.6 and Rand Ri=62.0 ± 7.5 indices reported a significantly better prediction when compared to a reference method (Chen et al., Clinical Proteomics 2013, 10:18) based on the averaged values from the test set. To distinguish BN from PCa we trained a RF classifier with LBPxVAR and local intensity histograms and obtained separate performance values for BN and PCa: JBN=35.2 ± 24.9, OBN=49.6 ± 32, JPCa=49.5 ± 18.5, OPCa=72.7 ± 14.8 and Ri=60.6 ± 7.6 in the test set. Our pixel-based classification does not rely on the detection of lumens, which is prone to errors and has limitations in high-grade cancers and has the potential to aid in clinical studies in which the quantification of tumor content is necessary to prognosticate the course of the disease. The image data set with ground truth annotation is available for public use to stimulate further research in this area.


Physicians' exodus: why medical graduates leave Austria or do not work in clinical practice.
Austria has the highest number of medical graduates of all Organisation for Economic Co-operation and Development (OECD) countries in relation to its population size, but over 30% choose not to pursue a career as physicians in the country. This article describes under- and postgraduate medical education in Austria and analyses reasons for the exodus of physicians. In Austria, medicine is a 5- or 6-year degree offered at four public and two private medical schools. Medical graduates have to complete training in general medicine or a speciality to attain a licence to practice. While not compulsory for speciality training, board certification in general medicine has often been regarded as a prerequisite for access to speciality training posts. Unstructured postgraduate training curricula, large amounts of administrative tasks, low basic salaries and long working hours present for incentives for medical graduates to move abroad or to work in a non-clinical setting. The scope of current reforms, such as the establishment of a new medical faculty and the implementation of a common trunk, is possibly insufficient in addressing the issue. Extensive reforms regarding occupational conditions and the structure of postgraduate medical education are necessary to avoid a further exodus of junior doctors.


The influence of oral health conditions, socioeconomic status and home environment factors on schoolchildren's self-perception of quality of life.
The objective this study was to investigate the influence of clinical conditions, socioeconomic status, home environment, subjective perceptions of parents and schoolchildren about general and oral health on schoolchildren's oral health-related quality of life (OHRQoL). A sample of 515 schoolchildren, aged 12 years was randomly selected by conglomerate analysis from public and private schools in the city of Juiz de Fora, Brazil. The schoolchildren were clinically examined for presence of caries lesions (DMFT and dmft index), dental trauma, enamel defects, periodontal status (presence/absence of bleeding), dental treatment and orthodontic treatment needs (DAI). The SiC index was calculated. The participants were asked to complete the Brazilian version of Child Perceptions Questionnaire (CPQ11-14) and a questionnaire about home environment. Questions were asked about the presence of general diseases and children's self-perception of their general and oral health status. In addition, a questionnaire was sent to their parents inquiring about their socioeconomic status (family income, parents' education level, home ownership) and perceptions about the general and oral health of their school-aged children. The chi-square test was used for comparisons between proportions. Poisson's regression was used for multivariate analysis with adjustment for variances. Univariate analysis revealed that school type, monthly family income, mother's education, family structure, number of siblings, use of cigarettes, alcohol and drugs in the family, parents' perception of oral health of schoolchildren, schoolchildren's self perception their general and oral health, orthodontic treatment needs were significantly associated with poor OHRQoL (p < 0.001). After adjusting for potential confounders, variables were included in a Multivariate Poisson regression. It was found that the variables children's self perception of their oral health status, monthly family income, gender, orthodontic treatment need, mother's education, number of siblings, and household overcrowding showed a strong negative effect on oral health-related quality of life. It was concluded that the clinical, socioeconomic and home environment factors evaluated exerted a negative impact on the oral health-related quality of life of schoolchildren, demonstrating the importance of health managers addressing all these factors when planning oral health promotion interventions for this population.


Cross-cultural adaptation and validation of the psychometric properties of the Quality from the Patient's Perspective I Questionnaire translated into Spanish.
translate the questionnaire Quality from the Patient's Perspective-Intrapartal (QPP-I) into Spanish, carrying out a cross-cultural adaptation and validation of its validity and reliability DESIGN: observational multi-centre transversal study, with transcultural adaptation and validation of a scale. the study was carried out in two public Spanish hospitals. 248 women in their postpartum period. the instrument was translated and back translated. Validity was determined in different ways: by comparing the QPP-I with an instrument which had already been validated (the COMFORTS scale); by carrying out an exploratory factor analysis by means of a principal component analysis (PCA), and by studying the relationship between the QPP-I and sociodemographic variables (level of studies, age, place of birth of the mother), clinical variables (number of children, type of childbirth, use of epidural, gestational age), positive feelings (control, pride, safety, being paid attention to) and negative feelings (failure, feeling ignored) experienced during childbirth, as well as physical and mental state as assessed by the woman. Reliability was estimated from the internal consistency, with the Cronbach's alpha (α), and the test-retest, with the intraclass correlation coefficient (ICC). eleven factors obtained an eigenvalue greater than the unit value in the PCA, explaining 70.5% of the total variance. A statistically significant association was found with the variables place of birth of the mother, level of studies, type of birth, positive and negative feelings during childbirth, and state of health of the mother. On comparing the QPP-I with the COMFORTS scale, the area under the received operating characteristic (ROC) curve was 0.824 (confidence interval of 95%, 0.764-0.884). For the total scale, the value of α was 0.96. The consistency ICC was 0.76 (CI 95%, 0.65-0.84) and the absolute agreement ICC was 0.76 (CI 95%, 0.66-0.84). the QPP-I with 39 items distributed among 11 factors seems adequate to measure women's satisfaction with the care received during childbirth in our setting. this tool can be used in both a clinical and a research setting for women to be able to evaluate the care they receive when they give birth. It is therefore a way of improving the care given to these users.


Urological complications in kidney transplantation: ureterocystostomy versus uretero-ureterostomy.
In our initial experience of kidney transplantation, we performed an extravesical uretero-cystostomy (U-C), but in 1997 we shifted to a uretero-ureterostomy (U-U) with the aim of reducing early and late urological complications. A data base was constructed to compare the incidence, donor and recipient risk factors, treatments, and outcomes of urological complications with the two techniques. From 1990 to the end of July 2004, 894 kidney transplants included 43 from living donors and 851 from cadaveric donors with 804 first and 47 second transplants. We observed 48 urinary fistulas (5.4%): 45 were successfully repaired and three were treated with a ureteral stent with two good results; and one failed at a late operation. We had 26 early stenoses (2.9%), all of which were successfully treated: 16 with surgery and 10 with a stent. Donor and recipient risk factors for fistula and early stenosis did not reach statistical significance, confirming the technical etiology of these complications. There were only six cases of late ureteral stenosis in patients operated after 1990, and in eight cases of U-C we observed vesico ureteral reflux. There were 88 urological complications, with only one kidney lost. The shift from U-C to U-U did not change the incidence of urological complications, but with U-U we observed a significant decrease in the number of postoperative urinary infections, an easier possibility to resolve ureteral stenosis with endourology and no reflux. It is now our first choice with a normal ureter.


A method for 14C and 3H double-label autoradiography.
The present study describes and validates a 3H/14C double-label autoradiographic method in which separation of the labels was obtained by sequential film exposures to film types sensitive to 14C only and to both 3H and 14C, respectively. The error in assuming a pure 14C image on the first film was 2-3%. A linear subtraction equation was developed for calculation of the 3H activity expressed in 14C equivalents as the difference in tissue activity between the second and the first film exposure. The actual 3H activity in the tissue could be obtained by multiplying the result by 25 (14C to 3H conversion factor). The subtraction procedure was validated for absolute 14C and 3H activities of 100-1,300 nCi/g and 600-11,000 nCi/g, respectively, and for relative 3H/14C activities between 5 and 10. Self-absorption of 3H in white matter was corrected for by multiplication by 1.61 (self-absorption coefficient). This factor was close to unity for 14C.


Mitochonic acid 5 rescues cardiomyocytes from doxorubicin-induced toxicity via repressing the TNF-α/NF-κB/NLRP3-mediated pyroptosis.
Doxorubicin (DOX) is an effective anti-tumor drug, but the cardiotoxicity severely limits its clinical use. Interestingly, a hypothesis has emerged suggesting an association between DOX-induced cardiotoxicity and mitochondrial disorders and oxidative stress. The mitochonic acid 5 (MA5) shows promise in alleviating mitochondrial dysfunction by promoting mitochondrial ATP synthesis and reducing reactive oxygen species (ROS) accumulation, though its potential in ameliorating DOX-induced cardiotoxicity remains elusive. Network pharmacology approach, molecular docking techniques, and molecular dynamics simulation (MDS) were used to reveal the specific drug targets and pharmaceutical mechanisms involved in the treatment of DOX-induced cardiotoxicity using MA5. For experimental verification, cardiomyocytes (H9c2) and mice were exposed to DOX in the presence or absence of MA5. Our investigation involved the assessment of echocardiographic parameters, cardiac enzymes, inflammatory factors, mitochondrial function, myocardial structure, and cardiomyocyte pyroptosis. Among the 100 core targets identified in network pharmacology, MA5 was pharmacologically active against DOX-induced cardiotoxicity via pathways implicated in cancer, prostate cancer, lipids and atherosclerosis. Molecular docking analysis confirmed that MA5 docked well with TNF-α, interleukin-6 (IL-6), and caspase-3. Furthermore, MA5 exhibited a stronger affinity toward TNF-α than IL-6 and caspase-3. Subsequent MDS revealed the stability of binding between MA5 and TNF-α. The DOX-challenged mice also displayed abnormal myocardial enzymogram, disrupted systolic and diastolic function, and elevated inflammation and cardiomyocyte pyroptosis, which could be mitigated by the administration of MA5. Similarly, H9c2 cells exposed to DOX showed increased intracellular ROS production and impaired mitochondrial function, which were relieved by MA5 treatment. Our findings suggest that MA5 attenuates DOX-induced cardiac anomalies through the TNF-α-mediated regulation of inflammation and pyroptosis. These insights offer a potential therapeutic strategy for managing DOX-induced cardiac complications, thereby improving the safety and efficacy of cancer treatments.


Propensity to seek healthcare in different healthcare systems: analysis of patient data in 34 countries.
Some people have a lower threshold to seek care for certain symptoms than others. This study aims to investigate what factors are associated with patients' propensity to seek care. In addition, this study explores whether patients' propensity to seek care is associated with their actual health care utilization. We hypothesized that higher scores for propensity to seek care will lead to more general practitioners (GP) consultations, but to lower rates of avoidable hospitalization. Propensity to seek care and GP utilization were measured by the Patient Experience Questionnaire of the QUALICOPC study, a survey among 61,931 patients that recently visited GP services in 34 countries. Propensity to seek care was estimated by two questions: one question focusing on health care seeking behavior for serious symptoms and the other question focused minor complaints. Data on country level rates of avoidable hospitalization for CHF, COPD, asthma and diabetes were obtained from the OECD health care quality indicators project. Beside patient characteristics, various organizational factors, such as better accessible and continuous primary care, and better experienced communication between patient and GPs was associated with a higher propensity to seek care for both severe and minor complaints. A higher propensity to seek care was associated with a slightly higher health care utilization in terms of GP visits, with no differences between the severity of the experienced symptoms (OR 1.08 for severe complaints and OR 1.05 for minor complaints). At country level, no association was found between propensity to seek care and rates of avoidable hospitalization for CHF, COPD, asthma and diabetes, possibly due to low statistical power at country level. The organization of primary care and patients' perceived communication with their GP were found to be highly correlated with patients' decision to seek health care for minor or severe complaints, suggesting that characteristics of healthcare systems directly influence patients' care seeking behavior, potentially leading to overuse or underuse of health services. However, we also observed that patients' propensity to seek care is only weakly associated with more GP use.


Nitric oxide releasing derivatives of tolfenamic acid with anti-inflammatory activity and safe gastrointestinal profile.
Tolfenamic acid esters with nitrooxyalcohols are synthesized. They are anti-inflammatory agents reducing carrageenan rat paw edema, with low gastrointestinal and general toxicity. In vitro, they are nitric oxide donors, inhibitors of lipoxygenase and cyclooxygenases. A two to three carbon chain between carboxylic and nitric ester groups seems optimal for activity.


Bovine pericardium: a source of pulmonary venous obstruction in the Mustard procedure.
Following Mustard's popularization of the intraatrial baffle procedure for transposition of the great arteries, debate has persisted regarding the ideal materials to use. Reports of xenograft (i.e., bovine pericardium) as a suitable prosthetic material made it an appealing choice. We report our recent experience with 2 patients in whom bovine pericardium was used for atrial augmentation, with subsequent pulmonary venous obstruction. For this reason, we have abandoned this material as an acceptable prosthetic in the Mustard procedure.


Inhibition of quorum sensing in Serratia marcescens H30 by molecular regulation.
Quorum sensing in Serratia marcescens, which uses two types of signaling molecules-N-acyl homoserine lactones and furanosyl borate diester-play important regulatory roles in the synthesis of 2,3-butanediol and prodigiosin. In the hope of understanding the effect of quorum sensing on physiologic metabolism, we established two molecular strategies, one to express acyl-homoserine lactone hydrolase to inactivate AI-1 signaling molecule using an expression vector with lactose as the inducer and the other to mutate luxS gene with a suicide plasmid pUTKm2 to inhibit the synthesis of AI-2 signaling molecule.


Ultrastructural comparison of erythrocytic stages of experimentally selected drug resistant strains of rodent malaria parasite P. berghei with its susceptible strain.
Studies on ultrastructure of drug-resistant strains of Plasmodium berghei have been mostly restricted to the experimentally selected chloroquine and pyrimethamine resistant strains. Study of the morphology of mefloquine and quinine resistant strain of P. berghei has been carried out to demonstrate some differences between normal and drug-resistant strains. The main differences are concerned with a complex physiological process i.e., food ingestion and digestion. E.M. studies reveal that in the sensitive strain of P. berghei the trophozoites possess numerous rod-shaped malarial pigment particles which lie within a vesicle. In the trophozoites of resistant parasites the malarial pigment particles are rarely visible. Trophozoites of the sensitive strain have only one large food vacuole while the trophozoite of the resistant parasite contains 2-3 smaller vacuoles.


Optimal fixation of cells for use in solid-phase ELISA.
Glutaraldehyde (GA) is commonly used to achieve the stable fixation of whole cells onto microtitre plates for use in solid-phase ELISA. Concentrations of GA greater than 0.10% (v/v) were found to result in increased levels of non-specific binding of antibodies in ELISA. However, the use of 0.05-0.025% (v/v) GA permitted the stable fixation of cells whilst minimizing the non-specific effects seen with higher GA concentrations. The binding of cells onto microtitre plates was also found to be highly variable depending on both the type of plates and the nature of the cells being used.


Methods of selection for adenoidectomy in childhood otitis media with effusion.
We have examined the implications of selecting children with otitis media with effusion (OME) for adenoidectomy using different criteria. Data were collected pre-operatively on 125 consecutive cases of OME. Ages 1-13 years, mean = 4.9 years; 68 males and 57 females. The criteria used were: (1) obstructive nasal symptoms, (with three sub-categories); (2) age: and (3) nasopharyngeal airway size. The three sub-categories of obstructive nasal symptoms were based on the clinical practices of colleagues in the UK. Thus we analysed five criterion groups in all. These were: (1) snoring; (2) snoring + mouth breathing; (3) snoring + nasal obstruction; (4) age = 4-8 years and (5) nasopharyngeal airway < 4 mm. We found that applying each criterion separately to the group of children would result in widely differing numbers of children being selected for adenoidectomy. Of the 125 children, the percentage selected by each method varied considerably, ranging from 35-70%. In addition, there was only limited overlap, (43-71%) between the composition of the groups. This helps to explain the variations in surgical rates in different centres. In the absence of any universally acceptable guidelines, therefore, the importance of individual assessment of children can not be overemphasised.


Non-enzymatic template-directed synthesis on RNA random copolymers. Poly(C, U) templates.
Poly(C, U) random copolymer templates direct the oligomerization of 2-MeImpG and 2-MeImpA, resulting in the production of a variety of oligo/(G,A)s. The efficiency of monomer incorporation into newly synthesized oligomers is greater for 2-MeImpG than for 2-MeImpA, and decreases for both monomers as the uracil content of the template increases. The relatively poor incorporation of adenine is partly due to an intrinsically less efficient incorporation reaction, and partly due to the masking of uracil sites by G X U non-complementary pairing. The efficiency of adenine incorporation can be improved by decreasing the concentration of 2-MeImpG and increasing the concentration of 2-MeImpA in the reaction mixture. The oligomeric product distribution can be characterized in detail using high-pressure liquid chromatography on an RPC-5 column. Oligomers are separated on the basis of chain length, base composition, and phospho-diester-linkage isomerism. The 3'----5' regiospecificity of monomer addition to template-bound oligomers is lower for 2-MeImpA than for 2-MeImpG. The presence of an adenine residue at the 2'(3') terminus of the acceptor strand lowers the regiospecificity of 2-MeImpA addition even further.


Changes in motor commands, as shown by changes in perceived heaviness, during partial curarization and peripheral anaesthesia in man.
1. The centrally generated ;effort' or direct voluntary command to motoneurones required to lift a weight was studied using a simple weight-matching task when the muscles lifting a reference weight were weakened. This centrally generated input to motoneurones was increased when the lifting muscles were partially paralysed with curare or decamethonium as judged by the increased perceived heaviness of a reference weight lifted by the weakened muscles.2. If subjects were asked simply to make matching isometric contractions when the lifting muscles were weakened the isometric tension produced by a weakened muscle was over-estimated.3. When subjects matched weights by flexing the distal joint of the thumb the perceived heaviness of a reference weight during a control partial curarization was compared with its perceived heaviness during a similar partial curarization when the thumb was also anaesthetized. At any level of maximal strength during curarization the perceived heaviness (which reflects the motor command to lifting motoneurones) was increased when the thumb was anaesthetized.4. This increased voluntary command to lifting motoneurones may be required because automatic reflex assistance provided by apparent servo action from the long flexor of the thumb is suppressed by anaesthesia of the thumb (Marsden, Merton & Morton, 1971, 1973, 1976a; Dyhre-Poulsen & Djørup, 1976).


Renal mitochondrial glutamine metabolism and dietary potassium and protein content.
Renal mitochondrial glutamine metabolism and dietary potassium and protein content. Glutamine distribution, glutamate accumulation, phosphate-dependent glutaminase (PDG) concentrations and intact mitochondrial ammonia production were studied in renal mitochondria from rats fed low, normal and high potassium diets and in mitochondria from rats fed high or low protein diets. The rats given a low potassium diet were potassium-depleted by 10 to 20% but in none of the groups were there any abnormalities of extracellular acid-base status. Glutamine was present in the outer space of mitochondria but could not be depleted in the matrix space in any group. In both the potassium-depleted and the high protein animals, we found increased matrix -14-C-uptake of glutamine (as -14-C-glutamate), increased intact mitochondrial ammonia production and increased concentrations of PDG. In the K+-depleted group there was a decreased matrix -14C-uptake when -14C-gamma-ketoglutarate of -14C-glutamate was present in the medium. Potassium loading produced no change in mitochondrial glutamine metabolism. Protein loading (compared with protein depletion) and potassium depletion induce an increased uptake of glutamine into the renal mitochondrial matrix space which leads to its increased deamidation. This adaption may explain the increased renal ammonia production seen in these situations when compared to their respective controls.


The value of plasma acetaminophen half-life in antidote-treated acetaminophen overdosage.
A plasma acetaminophen (INN, paracetamol) half-life of more than 4 hours has been correlated with hepatotoxicity in acetaminophen overdosing not treated with an antidote. Acetaminophen half-life has not been studied in patients receiving the antidote N -acetylcysteine. Prospectively, 112 patients with acetaminophen overdosage all treated with intravenous N -acetylcysteine were studied. A minimum of 2 plasma acetaminophen values >20 micromol/L were available for calculation of acetaminophen half-life, assuming first-order kinetics. Overall, the median acetaminophen half-life was 5.4 hours (range, 0.8-119.7 hours). Forty-eight patients with no or little hepatotoxicity (ALT <1000 U/L), 43 patients with hepatotoxicity without encephalopathy, and 21 patients with hepatotoxicity and encephalopathy had acetaminophen half-lives of 3.0 hours (range, 0.8-10.0 hours), 6.4 hours (range, 1.3-19.0 hours), and 18.4 hours (range, 4.6-119.7 hours), respectively (P <.001). An acetaminophen half-life >4 hours was observed in 71 patients, and 56 of those (79%) had hepatotoxicity (ALT >1000 U/L or coma). Thirty-three of 41 patients (81%) with an acetaminophen half-life <4 hours had no hepatotoxicity. A receiver operating characteristic curve analysis showed that an acetaminophen half-life of 5.5 hours provided better discrimination; hepatotoxicity was therefore present in 49 of 54 patients with an acetaminophen half-life >5.5 hours (positive predictive value, 91%) and in 15 of 58 patients with a half-life below this limit (negative predictive value, 74%) despite treatment with N -acetylcysteine. Acetaminophen half-life correlates well with the degree of liver damage in patients treated with the antidote N-acetylcysteine. Longer half-lives reflect a greater toxic effect on the liver.


A 5-year, randomized, open-label safety study of latanoprost and usual care in patients with open-angle glaucoma or ocular hypertension.
To investigate the incidence of latanoprost-related adverse events of the cornea, iris, and retina and the occurrence of hyperpigmentation. An open-label safety surveillance study was conducted in 14 countries. Patients on intraocular pressure (IOP)-reducing therapy other than latanoprost were eligible if they required a change in therapy. Patients were randomly assigned (2:1) to latanoprost administered once daily or to usual care (any other commercially available medication). Patients were examined at baseline and every 6 months for 5 years. In all, 5854 patients were included (latanoprost, 3936; usual care, 1918). Of those initially randomized to latanoprost, 2707 (68.8%) completed the study, and 4638 (79.2%) patients received at least one dose of latanoprost. Five-year risks were < or = 3.17% for new occurrences of corneal erosions, iritis/uveitis, or macular edema in both randomization groups. Serious adverse drug reactions were reported in 17/3936 (0.43%) latanoprost and 9/1918 (0.47%) usual care patients. In all, 87.6% of patients ever treated with latanoprost had no increased iris pigmentation; no serious adverse drug reactions were reported in patients with increased iris pigmentation. This 5-year study suggests that latanoprost as prescribed in 14 countries is a safe long-term treatment for patients with glaucoma and ocular hypertension.


Mangiferin alleviates hyperglycemia-induced endothelial impairment via Nrf2 signaling pathway.
The regulation of angiogenesis by nuclear factor erythroid 2-related factor 2 (Nrf2), a master redox transcription factor, is well established. In the present study, we aimed to activate Nrf2 by mangiferin (MG) and investigate its potential to regulate angiogenesis under a hyperglycemic (HG) environment in human endothelial cells. The mRNA expression of Nrf2 and its downstream targets HO-1, SOD-1, and CAT were observed to be decreased at 72 h of HG (33.3 mM glucose) exposure, and was ameliorated in MG (24 h) pretreated endothelial cells. ROS generation was assessed using an DCFDA assay, where we found the ROS generated at HG exposure was quenched by MG in a dose-dependent manner. The angiogenic markers HIF-1α and VEGF were also decreased in HG-induced endothelial cells, which significantly increased in the cells pretreated with MG. In addition, we have observed substantially more closed tube network formation in MG pretreated cells, which was low in HG-induced endothelial cells. The cell migration potential was monitored using a scratch assay, where the cells activated by MG showed a more significant movement than those under HG stress. Furthermore, to understand the role of Nrf2 in regulating angiogenesis, we knocked out the Nrf2 using CRISPR/Cas9 in endothelial cells. The wild-type endothelial cells exposed to MG alone showed a cytoprotective effect under a hyperglycemic environment. Our findings collectively demonstrated that MG helps regulate impaired angiogenesis under a hyperglycemic environment through Nrf2 signaling.


[Development and evolution of a balanced scorecard in primary health care: Lessons learned].
To describe the design, implementation, and monitoring of eSOAP (Primary Health Care Balanced Scorecard) and its role in the deployment of strategic objectives and clinical management, as well as to show the lessons learned during six years of follow-up. Descriptive study areas: methodology (conceptual framework, strategic matrix, strategic map, and processes map), technology and standardisation. As of December 2014, 9,046 (78%) professionals are registered in eSOAP. A total of 381 indicators were measured from 16 data sources, of which 36% were of results (EFQM model), 39.1% of clinical management, and 20% were included in the Program Centre Contract. The Balanced Scorecard has enabled to deploy all strategic lines of Primary Health Care, and has enabled the healthcare professionals to evaluate the evolution of results over time, and at patient level (e.g. 16% increase in control of diabetic patients). A total of 295,779 reports were generated and 13,080 professionals were evaluated by goals. There was an increased use of the eSOAP application by the professionals. The Balanced Scorecard was the key in deploying Primary Health Care strategies. It has helped clinical management and improved relevant indicators (health, patient experience, and costs), such as the management models that we used as references (EFQM Kaplan and Norton), and new emerging scenarios (Triple aim).


Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity.
To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37, human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418. The biological expression of rhIL-18 was tested by RT-PCR and ELISA method; nude mice were injected with Bcap37 cell with or without the hIL-18 gene. The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3+/-4.5 pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth. These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine; the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity. The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.


EHTask: Recognizing User Tasks From Eye and Head Movements in Immersive Virtual Reality.
Understanding human visual attention in immersive virtual reality (VR) is crucial for many important applications, including gaze prediction, gaze guidance, and gaze-contingent rendering. However, previous works on visual attention analysis typically only explored one specific VR task and paid less attention to the differences between different tasks. Moreover, existing task recognition methods typically focused on 2D viewing conditions and only explored the effectiveness of human eye movements. We first collect eye and head movements of 30 participants performing four tasks, i.e., Free viewing, Visual search, Saliency, and Track, in 15 360-degree VR videos. Using this dataset, we analyze the patterns of human eye and head movements and reveal significant differences across different tasks in terms of fixation duration, saccade amplitude, head rotation velocity, and eye-head coordination. We then propose EHTask - a novel learning-based method that employs eye and head movements to recognize user tasks in VR. We show that our method significantly outperforms the state-of-the-art methods derived from 2D viewing conditions both on our dataset (accuracy of 84.4% versus 62.8%) and on a real-world dataset ( 61.9% versus 44.1%). As such, our work provides meaningful insights into human visual attention under different VR tasks and guides future work on recognizing user tasks in VR.


Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.
Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT-PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan-Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC.


Contributions of mature granule cells to structural plasticity in temporal lobe epilepsy.
During the development of epilepsy in adult animals, newly generated granule cells integrate abnormally into the hippocampus. These new cells migrate to ectopic locations in the hilus, develop aberrant basal dendrites, contribute to mossy fiber sprouting, and exhibit changes in apical dendrite structure and dendritic spine number. Mature granule cells do not appear to exhibit migration defects, basal dendrites, and mossy fiber sprouting, but whether they exhibit apical dendrite abnormalities or spine changes is not known. To address these questions, we examined the apical dendritic structure of bromodeoxyuridine (Brdu)-birthdated, green fluorescent protein (GFP)-expressing granule cells born 2 months before pilocarpine-induced status epilepticus. In contrast to immature granule cells, exposing mature granule cells to status epilepticus did not significantly disrupt the branching structure of their apical dendrites. Mature granule cells did, however, exhibit significant reductions in spine density and spine number relative to age-matched cells from control animals. These data demonstrate that while mature granule cells are resistant to developing the gross structural abnormalities exhibited by younger granule cells, they show similar plastic rearrangement of their dendritic spines.


Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment?
The best therapy regimen for refractory obstetrical antiphospholipid syndrome remains to be determined. Additional treatments with steroids, plasma exchanges and immunoglobulins failed to show any beneficial effect. We present a case of a woman who had a better pregnancy outcome after the administration of hydroxychloroquine (HCQ) as additional treatment. Furthermore, we highlighted that HCQ was able to dramatically reduce the antiphospholipid antibodies levels.


A mandibular second molar with a middle mesial root canal.
The present case report describes the clinical detection and root canal management of a rare middle mesial canal of a Japanese mandibular second molar by troughing preparation using an operating microscope and cone-beam computed tomography.


Pan-cancer efficacy and safety of anlotinib plus PD-1 inhibitor in refractory solid tumor: A single-arm, open-label, phase II trial.
The combination of immunotherapy and antiangiogenic agents for the treatment of refractory solid tumor has not been well investigated. Thus, our study aimed to evaluate the efficacy and safety of a new regimen of anlotinib plus PD-1 inhibitor to treat refractory solid tumor. APICAL-RST is an investigator-initiated, open-label, single-arm, phase II trial in patients with heavily treated, refractory, metastatic solid tumor. Eligible patients experienced disease progression during prior therapy without further effective regimen. All patients received anlotinib and PD-1 inhibitor. The primary endpoints were objective response and disease control rates. The secondary endpoints included the ratio of progression-free survival 2 (PFS2)/PFS1, overall survival (OS) and safety. Forty-one patients were recruited in our study; 9 patients achieved a confirmed partial response and 21 patients had stable disease. Objective response rate and disease control rate were 22.0% and 73.2% in the intention-to-treat cohort, and 24.3% and 81.1% in the efficacy-evaluable cohort, respectively. A total of 63.4% (95% confidence interval [CI]: 46.9%-77.4%) of the patients (26/41) presented PFS2/PFS1 >1.3. The median OS was 16.8 months (range: 8.23-24.4), and the 12- and 36-month OS rates were 62.8% and 28.9%, respectively. No significant association was observed between concomitant mutation and efficacy. Thirty-one (75.6%) patients experienced at least one treatment-related adverse event. The most common adverse events were hypothyroidism, hand-foot syndrome and malaise. This phase II trial showed that anlotinib plus PD-1 inhibitor exhibits favorable efficacy and tolerability in patients with refractory solid tumor.


Role of cyclic adenosine monophosphate in amylase release from dissociated rat pancreatic acini.
1. The effect of octapeptide of cholecystokinin-pancreozymin (CCK(8)), bethanechol, cholera toxin, glucagon and vasoactive intestinal polypeptide (VIP) on amylase secretion and lactic dehydrogenase (LDH) release from isolated rat pancreatic acini was studied.2. In isolated rat pancreatic acini, in the absence of theophylline in the medium, amylase secretion was increased by 65-78% with 10(-7) and 10(-6) M-cholera toxin. In the presence of theophylline, amylase secretion was increased by 43-56% with 10(-7) and 10(-6) M-cholera toxin following a 90 min incubation. No effect was observed in the presence of theophylline at 30 and 60 min. The effect of cholera toxin was potentiated by CCK(8) at 60 and 90 min.3. In the absence of theophylline in the medium, amylase secretion was increased by 81-118% with 10(-5) and 10(-4) M-glucagon and 86% with 10(-6) M-VIP at 60 min. In the presence of theophylline in the medium, amylase secretion was increased by 53-246% with 10(-9) to 10(-6) M-glucagon and 111-158% with 10(-7) and 10(-6) M-VIP respectively. The effect of glucagon and VIP was potentiated by CCK(8).4. Potentiation of the rate of amylase release due to glucagon (10(-5) M) and VIP (10(-6) M) occurred during the first 15 min of incubation.5. Release of LDH was not increased by any of these agents.6. It is concluded that cyclic AMP rise (due to cholera toxin, glucagon and VIP effect) increased amylase secretion from rat pancreatic acinar cells. This effect is less marked than in the guinea-pig pancreas and is potentiated by agents mobilizing cellular Ca(2+) (CCK(8) and bethanechol).7. These data indicate species-specific variation in the action of cyclic AMP in the pancreas.


Severe intestinal graft versus host disease after donor lymphocyte infusion; response to extracorporeal photochemotherapy.
We present a patient with acute myelogenous leukemia who developed severe acute intestinal graft versus host disease (GVHD) after donor lymphocyte infusion (DLI) following non-myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBCT). One month after DLI, patient developed severe abdominal cramps, watery diarrhea without any signs or symptoms of the skin and liver GVHD. Treatment with steroid, cyclosporine A, tacrolimus and mycophenolat mofetil were not effective in controlling intestinal symptoms. Extracorporeal photochemotherapy (ECP), a recently used procedure in the treatment of GVHD was employed periodically and the symptoms subsided gradually. Acute GVHD after DLI may occur severely and atypically, but being limited to the intestine has rarely been reported.


S-Adenosylhomocysteine Is a Useful Metabolic Factor in the Early Prediction of Septic Disease Progression and Death in Critically Ill Patients: A Prospective Cohort Study.
A common final pathway of pathogenetic mechanisms in septic organ dysfunction and death is a lack or non-utilization of oxygen. Plasma concentrations of lactate serve as surrogates for the oxygen-deficiency-induced imbalance between energy supply and demand. As S-adenosylhomocysteine (SAH) was shown to reflect tissue hypoxia, we compared the ability of SAH versus lactate to predict the progression of inflammatory and septic disease to septic organ dysfunction and death. Using univariate and multiple logistic regression, we found that SAH but not lactate, taken upon patients' inclusion in the study close to ICU admission, significantly and independently contributed to the prediction of disease progression and death. Due to the stronger increase in SAH in relation to S-adenosylmethionine (SAM), the ratio of SAM to SAH, representing methylation potential, was significantly decreased in patients with septic organ dysfunction and non-survivors compared with SIRS/sepsis patients (2.8 (IQR 2.3-3.9) vs. 8.8 (4.9-13.8); p = 0.003) or survivors (4.9 (2.8-9.5) vs. 8.9 (5.1-14.3); p = 0.026), respectively. Thus, SAH appears to be a better contributor to the prediction of septic organ dysfunction and death than lactate in critically ill patients. As SAH is a potent inhibitor of SAM-dependent methyltransferases involved in numerous vital biochemical processes, the impairment of the SAM-to-SAH ratio in severely critically ill septic patients and non-survivors warrants further studies on the pathogenetic role of SAH in septic multiple organ failure.


Phenolic Characterization, Antioxidant Activity, and Enzyme Inhibitory Properties of Berberis thunbergii DC. Leaves: A Valuable Source of Phenolic Acids.
: Berberis species are known for their use in traditional medicine. Here, we report the phenolic composition and bioactivity of methanolic and aqueous extracts of Berberis thunbergii DC. leaves. The phenolic profiling and the quantitation of the main compounds were performed by high-performance liquid chromatography with diode array and mass spectrometry detections. The most abundant compounds in both extracts were caffeoylquinic acids (chlorogenic acid, particularly, with a concentration of 90.1-101.3 mg g-1 dried extract), followed by caffeoylglucaric acids and quercetin glycosides. Antioxidant and radical scavenging assays (phosphomolybdenum, DPPH, ABTS, CUPRAC, FRAP, metal chelating activity), as well as enzyme inhibitory assays (acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase, glucosidase, and lipase), were carried out to evaluate the potential bioactivity of B. thunbergii. The methanolic extract presented the highest antioxidant and radical scavenging values, in agreement with its higher phenolic content. Regarding enzyme inhibitory potential, the methanolic extract was also more potent than the aqueous one. Hence, B. thunbergii leaves represent a suitable candidate for the preparation of pharmaceutical or nutraceutical products.


Influence of theophylline on concentrations of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate of rat brain.
The influence of theophylline (2.5--100 mg/kg p.o.) on cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) in brain of Sprague-Dawley rats (0.5--3.0 hr after administration of theophylline) was investigated. It was found that theophylline increases cAMP and cGMP levels when administered in a dose of 25 mg/kg or higher. A significant decrease of cGMP level was observed after administration of 10 mg/kg. The results of this study suggest that the influence of theophylline on cyclic nucleotide levels of rat brain is the result of two factors: (a) inhibitory properties of theophylline on cAMP and cGMP phosphodiesterases and (b) competition of theophylline with adenosine.


The environmental footprints of the feeds used by the EU chicken meat industry.
Chicken meat production in the European Union (EU) causes environmental pressures within and beyond the EU, mostly due to feed consumption. The expected dietary shift from red to poultry meat will drive changes in the demand for chicken feeds and the associated environmental impacts, calling for a renewed attention on this supply chain. By performing a break-down analysis based on material flow accounting, this paper assesses the annual environmental burden caused within and outside of the EU by each single feed consumed by the EU chicken meat industry from 2007 to 2018. The increased feed demand required to support the growth of the EU chicken meat industry over the analyzed period caused a 17 % increase in cropland use - 6.7 million hectares in 2018. Instead, CO2 emissions linked to feed demand decreased by ~45 % over the same period. Despite an overall improvement in resource and impact intensity, chicken meat production was not decoupled from environmental burden. In 2018, 0.40 Mt. of nitrogen, 0.28 Mt. of phosphorous, and 0.28 Mt. of potassium inorganic fertilizers were implied. Our findings indicate that the sector is not yet compliant with the EU sustainability targets defined in the Farm To Fork Strategy, calling for an urgent need to fill existing policy implementation gaps. The EU chicken meat industry's environmental footprints were driven by endogenous factors such as the feed use efficiency at the chicken farming stage and the feed cultivation efficiency within the EU, as well as by exogenous factors such as the import of feed via international trade. Limitations on the use of alternative feed sources, as well as the exclusion of the imports from the EU legal framework constitute a crucial gap, which hamper fully leveraging existing solutions.


Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism.
Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.


Feedback control of the COVID-19 pandemic with guaranteed non-exceeding ICU capacity.
In this paper we investigate feedback control techniques for the COVID-19 pandemic which are able to guarantee that the capacity of available intensive care unit beds is not exceeded. The control signal models the social distancing policies enacted by local policy makers. We propose a control design based on the bang-bang funnel controller which is robust with respect to uncertainties in the parameters of the epidemiological model and only requires measurements of the number of individuals who require medical attention. Simulations illustrate the efficiency of the proposed controller.


Delayed treatment with lidocaine reduces mouse microglial cell injury and cytokine production after stimulation with lipopolysaccharide and interferon γ.
Neuroinflammation is an important pathological process for almost all acquired neurological diseases. Microglial cells play a critical role in neuroinflammation. We determined whether lidocaine, a local anesthetic with anti-inflammatory property, protected microglial cells and attenuated cytokine production from activated microglial cells. Mouse microglial cultures were incubated with or without 1 μg/mL lipopolysaccharide and 10 U/mL interferon γ (IFNγ) for 24 hours in the presence or absence of lidocaine for 1 hour started at 2, 3, or 4 hours after the onset of lipopolysaccharide and IFNγ stimulation. Lactate dehydrogenase release and cytokine production were determined after the cells were stimulated by lipopolysaccharide and IFNγ for 24 hours. Lidocaine dose-dependently reduced lipopolysaccharide and IFNγ-induced microglial cell injury as measured by lactate dehydrogenase release. This effect was apparent with lidocaine at 2 μg/mL (30.3% ± 5.8% and 23.1% ± 9.7%, respectively, for stimulation alone and the stimulation in the presence of lidocaine, n = 18, P = 0.025). Lidocaine applied at 2, 3, or 4 hours after the onset of lipopolysaccharide and IFNγ stimulation reduced the cell injury. This lidocaine effect was not affected by the mitochondrial K(ATP) channel inhibitor 5-hydroxydecanoate. Similar to lidocaine, QX314, a permanently charged lidocaine analog that usually does not permeate through the plasma membrane, reduced lipopolysaccharide and IFNγ-induced microglial cell injury. QX314 also attenuated the stimulation-induced interleukin-1β production. Delayed treatment with lidocaine protects microglial cells and reduces cytokine production from these cells. These effects may involve action site(s) on the cell surface.


Towards high performance hybrid two-dimensional material plasmonic devices: strong and highly anisotropic plasmonic resonances in nanostructured graphene-black phosphorus bilayer.
Plasmonics of two-dimensional materials have attracted increasing attention in the past few years. It provides a platform for strong light-matter interactions and enables a variety of novel applications in the infrared and terahertz ranges. In this paper, we study the plasmonic properties of a graphene-black phosphorus (G-BP) bilayer. It exhibits both strong and highly anisotropic plasmonic responses that performs beyond individual graphene and black phosphorus films. Polarization dependent, anisotropic perfect absorption can be realized in this type of two-dimensional plasmonic nanostructures with moderate doping levels. This type of hybrid architecture opens a new door for high performance two-dimensional material plasmonic devices.


The efficacy of selamectin in the treatment of naturally acquired infestations of sarcoptes scabiei on dogs.
Selamectin, a novel avermectin, was evaluated for its effect on naturally occurring infestations of Sarcoptes scabiei in 42 dogs. In two controlled and masked laboratory studies conducted in the USA and Italy, infested dogs received treatment with either selamectin (6mgkg(-1); range: 6-12mgkg(-1)) or the vehicle only (negative control). Treatments were administered topically to the skin on each animal's back at the base of the neck in front of the scapulae. Study day 0 was defined as the first day of treatment administration. Dogs were treated on days 0 and 30, and efficacy was assessed by counting viable mites recovered from skin scrapings performed on each dog on days 14, 29 or 30, 44, and 60, and by categorising the clinical signs of canine scabies on the same days. Percentage reductions in geometric mean mite counts for selamectin, compared with vehicle, on days 14, 29 or 30, 44, and 60 were > or =98.1, > or =93.5, 100, and 100%, respectively. Analysis of variance, confirmed by Savage Scores, showed that ln(mite counts+1) values for selamectin-treated dogs were significantly lower (P< or =0.0391) than those for vehicle-treated dogs on all post-treatment assessment days. Clinical signs of scabies were markedly reduced in selamectin-treated dogs, compared with vehicle-treated dogs. Topical administration to the skin in a single spot of a single unit dose of selamectin, or of two unit doses given 1 month apart, each providing at least the recommended minimum dosage of 6mgkg(-1), was highly effective against naturally acquired infestations of S. scabiei in dogs, reducing mite counts by >93% (single dose) and 100% (two doses).


Novel insights into the early histopathogenesis of immunodeficiency-associated Burkitt lymphoma: a case report of Burkitt microlymphoma arising within HIV lymphadenitis.
To report a case detailing the early histopathogenesis of Burkitt lymphoma (BL), Epstein-Barr virus (EBV) positive, in the clinical setting of HIV infection. We describe a 57 year-old woman with newly diagnosed HIV infection who presented with unilateral localized axillary lymphadenopathy. Histopathological, immunohistochemical, and flow cytometric analyses were performed and showed EBV-positive nests of Burkitt cells, including rare nests also positive for cytomegalovirus, exclusively located within hyperplastic monocytoid B-cell areas of HIV lymphadenitis. Due to positron emission tomography/computed tomography findings of persistent localized lymphadenopathy with markedly increased fludeoxyglucose avidity a core needle biopsy was performed. Histopathological, immunohistochemical, fluorescence in situ hybridization, and flow cytometric analyses confirmed BL. Early histopathogenesis of HIV-associated BL occurred as nests of EBV-positive Burkitt cells within prominent monocytoid B-cell areas in our case. The results equip the pathologist to identify a very subtle Burkitt microlymphoma which would allow for prompt and appropriate chemotherapeutic intervention and may promote research into the possible relationship between monocytoid B cells and BL.


Effects of daylength and temperature on root elongation in tundra graminoids.
Effects of soil temperature and daylength on root elongation of Carex aquatilis, Dupontia fischeri, and Eriophorum angustifolium were studied under both field and phytotron conditions. Late season decrease in root elongation rate and cessation of root elongation in Dupontia and Eriophorum are shown to be controlled by decreasing daylength. During the growing season, low temperature is not a direct factor in limiting root growth in any of the three species despite the presence of permafrost and low soil temperatures in the shallow thawed soil layer. In the phytotron, temperature-dependence of root elongation is related to experimental conditions characterized by continuous light. Plants of all three species are capable of root growth at near-freezing temperatures.


Influence of monoethanolamine on activity measurements of the isoenzymes of alkaline phosphatase.
Monethanolamine, a frequent impurity of diethanolamine, inhibits the activity of the isoenzymes of alkaline phosphatase to various extents. Isoenzymes from liver and bone, in particular, are strongly inhibited. Inhibition is stronger at lower (25 degrees C) than at higher temperatures (37 degrees C).


Characteristics of rat lateral hypothalamic neuron responses to smell and taste in emotional behavior.
Single unit activity in the lateral hypothalamus (LHA) of the rat was recorded while the animal learned to discriminate cue signals. Normally preferred potables (glucose, orange, or grape solution) or intracranial self-stimulation (ICSS) were used as rewards. Electric shock or tail pinch were used as aversive stimuli. The same behavior, licking, was the response required to either obtain the rewarding stimuli or avoid the aversive ones. For positive reinforcement a rat was rewarded with fluid or ICSS upon licking a spout presented in front of its mouth. In negative reinforcement experiments, an aversive stimulus, electric shock or tail pinch, was applied if the rat did not lick the spout. Solutions having smell only, taste only, or smell-plus-taste, were prepared from oranges or grape extract. Of 392 neurons analyzed, 256 responded differentially to rewarding and aversive stimuli, and 138 of these were tested with the 3 different solutions. Similar LHA neural responses occurred during actual drinking of the 3 kinds of solutions, as well as on recognition of the cue signal. Responses to smell only had shorter latency than responses to taste only. Neural activity in response to solutions that could be both smelled and tasted was the sum of activity in response to taste-only solutions plus that in response to smell-only solutions. Cue signal responses were rapidly acquired, usually within 2-5 trials, for both taste-only and smell-only solutions. The results indicate the integration of both taste and olfactory information by the same LHA neurons, and these neurons are involved in cue signal learning. Present results of LHA neuronal responses to taste and smell suggest that the intensity of gustation and olfaction may add together to enhance instinctive hedonic sensations. These neurons are involved in the formation of stimulus-reinforcement association in learning, and in elicitation of conditioned emotional responses.


Phenology, nectar dynamics and reproductive success of Inga vera (Leguminosae) in monospecific plantations and forest remnants in Atlantic forest: Dataset exploration.
Distinct approaches have been adopted for tropical forest restoration in the last decades. The long-term viability of these restored forests and their capacity to provide the required services demand continuous evaluation to guide future initiatives. In addition, the resilience and maintenance of plant and animals communities in restored forests in tropical regions are closely related to the recovery of animal-mediated interactions. We provide, in this article, raw data related to the reproductive ecology of Inga vera, one of the most common tree species used in forest restoration initiatives in the Brazilian northeastern Atlantic forest. Specifically, we explore data on phenology, nectar dynamics and reproductive success of I. vera in natural and planted (monospecific) populations. This data article is related to the research article "Pollination partial recovery across monospecific plantations of a native tree (Inga vera, Leguminosae) in the Atlantic forest: lessons for restoration" (Cruz-Neto et al., 2018) [1].


Predictors of technical outcome for prostatic artery embolisation using pre-procedural CT angiography.
Predicting patients that will pose procedural technical challenges in prostate artery embolisation (PAE) remains difficult, with prolonged procedural times impacting on both patient dose and resource planning. Understanding the factors that influence these parameters as well as the likelihood of technical success is therefore important in effective patient selection and procedural planning. Data were collected retrospectively for 75 consecutive patients who underwent PAE. Multiple patient predictor variables available from planning computed tomography angiography (CTA) were identified and measured objectively. The vessel angles navigated during the procedure, prostate volume, prostate artery (PA) diameter, PA origin, aortic atheroma, iliac tortuosity and baseline demographics were correlated with outcome variables (fluoroscopy time, air kerma (AK), dose area product (DAP), the number of cone beam CTs (CBCTs)) performed and whether bilateral embolisation was possible (technical success). Data were analysed using linear regression, ANOVA, t tests and chi-squared tests. Aortic atheroma severity significantly increased fluoroscopy time (p = 0.004), whilst air kerma (AK) was significantly greater in patients with smaller prostatic arteries (p = 0.009) and smaller pre-procedural prostate volumes (p = 0.038). Increased vascular tortuosity and prostatic artery origin were not shown to significantly affect fluoroscopy time or DAP. Smaller prostate artery size (p = 0.007) also increases the likelihood of either unilateral embolisation or technical failure. Pre-operative prediction of technical outcome measures in PAE remains challenging. However, vascular calcification, prostatic artery diameter and prostate volume are likely to be important factors when considering the risk/benefits of PAE. • Increased severity of atheroma and the presence of small prostate arteries increase fluoroscopy time and AK respectively during prostate artery embolisation. • Lower pre-procedural prostate volume increases the AK during procedures. • Smaller prostate artery size increases the likelihood of either unilateral embolisation or technical failure.


Operative safety and oncologic outcome of laparoscopic radical nephrectomy for renal cell carcinoma >7 cm: a multicenter study of 222 patients.
To evaluate the safety of laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) >7 cm, addressing the issue of modality and risk factors for complications and open conversion, and to assess the oncologic outcome. The data of 222 patients undergoing LRN for RCC >7 cm prospectively enrolled from 2002 to 2010 at 5 urologic centers were reviewed. Transperitoneal LRN was performed by 5 experienced laparoscopic surgeons. The Clavien-Dindo classification was used to assess complications. Multivariable analysis of factors predictive of conversions was performed. Oncologic outcomes for survival were estimated using the Kaplan-Meier method. Median tumor size was 8.5 cm, operative time was 180 minutes, and blood loss was 280 mL. Forty-two patients (19%) received a blood transfusion. Six (2.7%) patients had grade III-IV complications: 2 with postoperative bleeding requiring abdominal re-exploration and 1 each with adrenal injury, splenic injury, wound diastasis, and respiratory insufficiency. Twelve patients (5.4%) were converted to open surgery. The diameter was 11.9 in converted groups and 8.5 cm in nonconverted groups (P = .001). Multivariable analysis revealed that pathologic stage was the only independent predictor of conversion (P = .002). The 5-year overall (OS), cancer-specific (CSS), and progression-free (PFS) survival was 74%, 78%, and 66%, respectively. The 5-year stage-adjusted CSS was 89% in pT2 and 40% in pT3 patients (P <.0001). Limitations of this study were its retrospective nature and the relatively short follow-up period for oncologic outcome. LRN for large RCC is a safe operation. Stage pT3 is a risk factor for open conversion and is associated to significantly lower cancer-specific survival compared with pT2 stage.


Genuine eye contact elicits self-referential processing.
The effect of eye contact on self-awareness was investigated with implicit measures based on the use of first-person singular pronouns in sentences. The measures were proposed to tap into self-referential processing, that is, information processing associated with self-awareness. In addition, participants filled in a questionnaire measuring explicit self-awareness. In Experiment 1, the stimulus was a video clip showing another person and, in Experiment 2, the stimulus was a live person. In both experiments, participants were divided into two groups and presented with the stimulus person either making eye contact or gazing downward, depending on the group assignment. During the task, the gaze stimulus was presented before each trial of the pronoun-selection task. Eye contact was found to increase the use of first-person pronouns, but only when participants were facing a real person, not when they were looking at a video of a person. No difference in self-reported self-awareness was found between the two gaze direction groups in either experiment. The results indicate that eye contact elicits self-referential processing, but the effect may be stronger, or possibly limited to, live interaction.


Protein-anchoring strategy for delivering acetylcholinesterase to the neuromuscular junction.
Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ). Congenital defects of ColQ cause endplate AChE deficiency and myasthenic syndrome. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq(-/-) mice recovered motor functions, synaptic transmission, as well as the morphology of the NMJ. ColQ-tailed AChE was specifically anchored to NMJ and its amount was restored to 89% of the wild type. We next characterized the molecular basis of this efficient recovery. We first confirmed that ColQ-tailed AChE can be specifically targeted to NMJ by an in vitro overlay assay in Colq(-/-) mice muscle sections. We then injected AAV1-COLQ-IRES-EGFP into the left tibialis anterior and detected AChE in noninjected limbs. Furthermore, the in vivo injection of recombinant ColQ-tailed AChE protein complex into the gluteus maximus muscle of Colq(-/-) mice led to accumulation of AChE in noninjected forelimbs. We demonstrated for the first time in vivo that the ColQ protein contains a tissue-targeting signal that is sufficient for anchoring itself to the NMJ. We propose that the protein-anchoring strategy is potentially applicable to a broad spectrum of diseases affecting extracellular matrix molecules.


[Surprising mechanism of highly symptomatic tachycardia in a young patient : Diagnosis and treatment].
The diagnosis of paroxysmal tachycardia can be challenging in clinical practice because even with a typical patient history including palpitations, tachycardia, and an on/off phenomenon, 24 h Holter monitoring frequently fails to document the tachycardia. After unsuccessful 24 h Holter monitoring, we managed to document a very fast wide QRS complex tachycardia in a young patient by a mobile portable event monitor. Subsequent invasive electrophysiologic diagnostics followed by catheter ablation clarified the tachycardia mechanism and led to permanent elimination of the tachycardia.


Early experience with percutaneous balloon kyphoplasty for treatment of osteoporotic vertebral compression fracture in Nepal: A case report.
Balloon kyphoplasty is a promising treatment option for osteoporotic vertebral compression fractures with posterior cortical defect, offering pain relief, vertebral height restoration, and low risk of cement leakage. Millions of people worldwide suffer from osteoporotic vertebral compression fractures (OVCFs) annually, which cause pain and functional limitations, particularly in the elderly. Conservative treatments such as pain management, rest, and medication are frequently used, while surgical options such as vertebroplasty and kyphoplasty are considered. We present a case of 68-year-old female with vertebral compression fracture of L1 vertebra with posterior cortical defect and posterior wall retropulsion. She was treated successfully with balloon kyphoplasty. Kyphoplasty appears to be a better option than vertebroplasty in cases with posterior cortical defect due to lower chance of cement leakage.


Optimization of reduced Graphene oxide synthesis using central composite design analysis-A waste to value approach.
In recent times, reduced graphene oxide has gained more attention in various fields. In our study, a direct synthesis of reduced graphene oxide using a novel carbon-rich agro-waste from Pennisetum glaucum was used. Ferrocene acted as an oxidizing agent during thermal degradation at 300 °C for 15 and 20 min to promote graphene oxide and reduced graphene oxide formation. The X-ray diffraction peak at 2θ indicating a shift from 16.86 to 24.28°, presence of functional groups like -OH stretching, -C = C-, C = O, C-O, and C-OH by Fourier transmission infrared spectroscopy, prominent D and G bands at 1308 cm-1 and 1578 cm-1 by Raman spectra and UV-visible spectroscopy peak shift from 235 to 245 nm (π-π*, C = C bonds) confirmed the reduction of graphene oxide to reduced graphene oxide. The average particle size values 233.3 nm for graphene oxide and 63.57 nm for reduced graphene oxide illustrate the nanoscale range of our synthesized material. The negative zeta potential values in the range - 45.5 mV and - 29.5 mV for graphene oxide and its reduced forms infer the dispersion stability along with surface oxygen group presence. We have also highlighted the formation of graphene oxide quantum dots by magnetic stirring and confirmed by UV transilluminator and photoluminescence spectra. The photodegradation efficiency was optimized using central composite design for dosage, dye concentration, pH, and time for both malachite green and reactive blue dye. The kinetic studies report pseudo-first-order kinetic model for catalytic degradation and statistical Analysis of variance proved the significance of the process for p value < 0.05. Thus, the synthesized graphene materials could be used as a potential candidate for environmental applications.


Formulation of pH-responsive PEGylated nanoparticles with high drug loading capacity and programmable drug release for enhanced antibacterial activity.
In the current global crisis of antibiotic resistance, delivery systems are emerging to combat resistant bacteria in a more efficient manner. Despite the significant advances of antibiotic nanocarriers, many challenges like poor biocompatibility, premature drug release, suboptimal targeting to infection sites and short blood circulation time are still challenging. To achieve targeted drug delivery and enhance antibacterial activity, here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin (PEG-Schiff-Van) prodrug and free Van in one drug delivery system. The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition. Notably, on account of the combination of physical encapsulation and chemical conjugation of vancomycin, these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior, which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period. In addition, more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity. Using this strategy, this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites, thereby presenting prominent antibacterial therapy both in vitro and in vivo. This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles, which would be a promising class of antimicrobial materials for potential clinical translation.


Somatic cell count and milk neutrophil viability of dairy heifers with specific CXCR1 genotypes following experimental intramammary infection with Staphylococcus chromogenes originating from milk.
Previous observational studies suggest an association between polymorphism c.980A>G in the CXCR1 gene, encoding the chemokine (C-X-C motif) receptor 1, and the innate immunity and infection status of the mammary gland. Mammary glands of eight Holstein heifers were experimentally infected with a Staphylococcus chromogenes isolate originating from a chronic intramammary infection (IMI) to study differences between CXCR1 genotypes c.980AG and c.980GG. Quarters from heifers with genotypes c.980AG and c.980GG developed subclinical mastitis but showed differences in the early response at 6-18 h post challenge. Bacterial count at 18 h post challenge tended to be higher in quarters from c.980AG heifers compared to c.980GG heifers. Somatic cell count (SCC) was higher at 6 h post challenge and tended to be higher at 9 h post challenge in c.980AG heifers compared to c.980GG heifers. Milk production decreased similarly. Milk neutrophils of c.980AG heifers showed more apoptosis at 9 h post challenge and tended to show more necrosis at 6, 9 and 12 h post challenge than c.980GG heifers. Differences were less pronounced in the later stage (>18 h) of infection. The results demonstrate that CXCR1 polymorphism can influence SCC and milk neutrophil viability following experimental IMI.


Effects of Jatrorrhizine on inflammatory response induced by H2O2 in microglia by regulating the MAPK/NF-κB/NLRP3 signaling pathway.
Microglia-induced neuroinflammation is a contributing factor to neurodegenerative diseases. Jatrorrhizine (JAT), an alkaloid isolated from Huanglian, has been shown to have neuroprotective effects against various neurodegenerative diseases, but its impact on microglia-induced neuroinflammation remains unclear. In this study, we investigated the role of JAT in MAPK/NF-κB/NLRP3 signaling pathway in an H2O2-induced oxidative stress model using microglia (N9 cells). We divided cells into six groups, including control, JAT, H2O2, H2O2 + 5 μmol/L JAT, H2O2 + 10 μmol/L JAT, and H2O2 + 20 μmol/L minocycline groups. Cell viability was measured using MTT assay and TNF-α levels were detected with an ELISA Kit. Western blot was used to detect NLRP3, HMGB1, NF-κB, p-NF-κB, ERK, p-ERK, p38, p-p38, p-JNK, JNK, IL-1β, and IL-18 expressions. Our results showed that JAT intervention improved H2O2-induced cytotoxicity in N9 cells and reduced the elevated expression of TNF-α, IL-1β, IL-18, p-ERK/ERK, p-p38/p38, p-JNK/JNK, p-p65/p65, NLRP3, and HMGB1 in H2O2 group. Furthermore, treatment with ERK inhibitor SCH772984 specifically blocked ERK phosphorylation, resulting in decreased protein levels of p-NF-κB, NLRP3, IL-1β, and IL-18 in H2O2 group. These results suggest that the MAPK/NF-κB signaling pathway may regulate the protein levels of NLRP3. Overall, our study indicates that JAT may have a protective effect on H2O2-treated microglia via inhibition the MAPK/NF-κB/NLRP3 pathway and could be a potential therapeutic approach for neurodegenerative diseases.


Extracorporeal cardiopulmonary resuscitation for adult patients who underwent post-cardiac surgery.
Refractory cardiac arrest (CA) occasionally develops in patients after cardiac surgery. To examine the clinical outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) in adult patients with post-cardiotomy CA. This was a retrospective study of the 9-year experience (from January 2004 to May 2012) of the Beijing Anzhen Hospital with ECPR in adult patients with post-cardiotomy CA. At this hospital, a dedicated ECPR team is available 24/7 for emergency cases requiring ECPR. Demographic data, biochemical data, survival, morbidity, and complications were examined before, during, and after ECPR. Outcomes were compared between survivors and non-survivors. Twenty-four adult patients (19 men and 5 women; mean age: 59.3 ± 11.9 years) received ECPR support for post-cardiotomy CA. The cardiac surgery procedures included coronary artery bypass grafting (n = 20, 83.3 %), valvular surgery alone (n = 2, 8.3 %), and correction of congenital heart defects (n = 2, 8.3 %). The mean extracorporeal membrane oxygenation (ECMO) duration was 115.23 ± 70.17 h. Twenty-one patients received ECPR after intra-aortic balloon pump, and three patients received ECPR directly. The main cause of mortality was multiple system organ failure (n = 12, 50.0 %). Approximately one-half of non-survivors had severe neurologic impairments. Among 16 patients who were weaned off ECMO support, eight patients survived to hospital discharge. ECPR can be effective for partial cardiopulmonary support to resuscitate adult patients suffering from refractory CA after cardiac surgery. Improvement in outcomes of patients who received ECPR requires a multidisciplinary approach to protect organ function and limit organ injury before and during cardiac support.


[Significance of molecular-cytogenetic findings in mucoepidermoid carcinoma as an example of salivary gland tumors].
Chromosome translocations in tumors frequently give rise to fusion genes encoding proteins with oncogenic activities. Mucoepidermoid carcinomas (MEC) are characterized by a t(11;19)(q21-22;p13) translocation found in approximately 60% of the tumors. This t(11;19) translocation results in a fusion gene consisting of exon 1 of the MECT 1 gene and exons 2-5 of the MAML 2 gene. As a result of the t(11;19) a fusion protein is generated which, independent of NOTCH-ligands, activates the transcription of the NOTCH target gene HES 1. The altered function of MAML 2 causes a disruption of NOTCH signalling which suggests a novel mechanism of tumorigenesis. Pending the elucidation of the t(11;19) at the molecular level of an apparently identical chromosomal translocation in Warthin's tumor, the identification of the translocation in MEC by FISH- and/or RT-PCR-analyses may become important in diagnosis and might have prognostic relevance. Warthin's tumors are benign salivary gland neoplasms with a distinctive histomorphology and histogenesis completely different from MEC.


Peripheral tears of triangular fibrocartilage complex: results of primary repair.
In 16 patients with ulnar wrist pain, we performed primary arthroscopic or open repair of the peripheral rim tears of the triangular fibrocartilage complex (TFCC) (14 ulnar, 4 volar, and 3 radial tears). The wrist function was assessed before and 1 year after the repair using the Mayo-modified wrist score. The average pain score improved from 9.1+/-8.0 to 21.2+/-6.5, the average functional score from 5.0+/-8.1 to 20.6+/-6.3, the average motion score from 4.7+/-2.8 to 15.6+/-7.3, and the average grip point from 4.4+/-3.5 to 15.6+/-7.7, all with significant differences (P<0.01). Ten of the 17 cases had instability of the distal radioulnar joint and five had recurrent instability after repair.


Identifying Indicators to Assess and Monitor Data Integration Engines Systems.
We aimed to identify relevant indicators for end-users in integration engines for healthcare systems. The study was performed in two steps, including interviews and the identification of additional indicators from the literature. 10 interviews were performed and 90 indicators identified. Several of the indicators are difficult to calculate, nevertheless, they have the potential to improve data quality and processes in healthcare institutions and should be further explored in future studies.


Identification and Comparison of Barriers to Assessing and Combating Acute and Postoperative Pain in Elderly Patients in Surgical Wards of Polish Hospitals: A Multicenter Study.
Inadequate pain monitoring and management in hospitalized patients poses a serious clinical problem which has been extensively covered in literature for over 25 years. The purpose of the paper was to learn about and compare the existing barriers to effective analgesia controlled by nurses on surgical wards in Polish hospitals. The study was carried out upon the approval of the study protocol by the Independent Bioethics Committee for Scientific Research of the Medical University of Gdańsk. The research project was multi-center and took a year. The study was questionnaire-based. It used the Polish version of the Nurses' Perceived Obstacles to Pain Assessment and Management Practices questionnaire. The study included a total of 1300 nurses working on surgical wards. The barriers most frequently observed by the respondents were: disorganization of the healthcare system, physicians' mistrust of pain assessment by nursing staff, difficulty contacting and communicating with physicians to discuss the results of patients' pain assessments and difficulties experienced by elderly patients with completing pain assessment scales. The barriers most frequently impeding pain therapy in elderly patients are associated with the healthcare system, and they were more frequently present on the anesthesiology and intensive care ward and in the emergency department, and occurred the least frequently on the surgical ward. Patient-related problems were more frequent on the anesthesiology and intensive care wards than in the emergency department. Doctor-related problems most frequently occurred on the gynecological ward, while nurse-related problems were more frequent on the anesthesiology and intensive care ward.


T-cell proliferation and forkhead box P3 expression in human T cells are dependent on T-cell density: physics of a confined space?
T-cell proliferation rates in vitro depend on factors including initial T-cell number, dose of stimulus, culture time, and available physical space. The role of forkhead box P3 (FoxP3) in the identification of T cells with a regulatory phenotype remains controversial in humans. Through 5-carboxyfluorescein diacetate succinimidyl ester labeling of human T cells and subsequent culture of different numbers of T cells and antigen-presenting cells (APC), we studied proliferative T-cell responses and FoxP3 expression in divided T cells. T-cell proliferation rates depended on initial T-cell/APC numbers. Proliferation rates decreased when high initial T-cell numbers were increased. FoxP3 expression was expressed exclusively in virtually all divided T cells cultured at high T-cell densities, irrespective of their CD4 nature or cytokine content, and was coexpressed with T-bet. However, when T cells were cultured on larger surfaces or at lower initial numbers, FoxP3 expression was not induced in divided T cells, even when most of the cells had undergone cell division. FoxP3(+) T cells generated at high cell densities did not elicit a suppressive phenotype and FoxP3 expression was subsequently lost in time when the stimulus was removed. Therefore, caution should be observed in the use of FoxP3 expression to identify regulatory T cells in humans because its expression may be only a consequence of activation status in a restricted environment.


Detection of amino acids in artificial nectars by two tropical ants, Leptothorax and Monomorium.
Many ants forage at extrafloral nectar on plants and provide the plant with some measure of protection from herbivory. These nectars contain sugars, amino acids and, often, other compounds. The role of amino acids in attracting ants to extrafloral nectars was studied by baiting with Karo-syrup-based solutions. Control (without amino acids) and experimental (with amino acids) solutions were placed in second growth forest in Trinidad, W.I. The number of ants visiting the solutions was counted at fiveminute intervals for 45 min. In tests of solutions with only one amino acid, both Leptothorax sp. and Monomorium sp. visited solutions with alanine, arginine, serine, cysteine, methionine or aspartic acid more frequently than sugaronly controls. Monomorium preferred control solutions to tyrosine solutions; Leptothorax preferred control solutions to histidine solutions. Leptothorax did not discriminate between control and tyrosine solutions; Monomorium did not discriminate between control and histidine solutions. However, in six of eight tests of combinations of amino acids, ants visited control solutions more frequently than experimental solutions. These results suggest that ants can act as selective agents, favoring plants with particular amino acids in their nectars.


Differential gene expression in the honeybee head after a bacterial challenge.
Bidirectional interactions between the immune and nervous systems are well established in vertebrates. Insects show similar neuro-immune-behavioral interactions to those seen in vertebrates. Using quantitative real-time PCR, we present evidence that gene expression in the honeybee head is influenced by activation of the immune system 8h after a bacterial challenge with Escherichia coli. Seven genes were selected for quantitative analysis in order to cover both typical functions of the head such as exocrine secretion (mrjp3 and mrjp4) and olfactory processes (obp17) as well as more general processes such as structural functions (mlc2 and paramyosin), stress response (ERp60) and energy housekeeping (enolase). In this way, we show at the molecular level that the immune system functions as a sensory organ in insects -- as it does in vertebrates -- which signals to the head that a bacterial infection is present, and leads to regulation of expression of several genes in the head by a yet unidentified mechanism.


Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation.
The Caudal-related homeodomain transcription factor Cdx2 plays a key role in intestinal cell fate determination. Reduction of Cdx2 expression is a feature of many human colon carcinomas and inactivation of one cdx2 allele facilitates the development of invasive adenocarcinoma in the murine colon. Here, we investigated the post-translational regulation of Cdx2. We showed that various forms of Cdx2 coexist in the intestine and colon cancer cell lines, some of them being phosphorylated forms. We found that cyclin-dependent kinase 2 phosphorylated Cdx2 in vitro and in vivo. Using site-specific mutagenesis, we identified serine 281 as a new key residue for Cdx2 phosphorylation. Intriguingly, serine 281 belongs to a conserved motif of four evenly spaced serines (the 4S motif) similar to the one controlling beta-catenin degradation by the proteasome pathway. A nonphosphorylated mutant Cdx2 lacking the 4S motif (4S>A) exhibited reduced polyubiquitination upon proteasome inhibition and increased stability compared to wild-type Cdx2. In addition, we found that this mutant was less efficient to suppress colony formation than wild-type Cdx2. Thus, our data highlight a novel post-translational mechanism controlling Cdx2 degradation via phosphorylation and polyubiquitination, which may be of importance for intestinal development and cancer.


Entrapment efficiency and initial release of phenylbutazone from nanocapsules prepared from different polyesters.
Several formulations of poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) nanocapsules containing phenylbutazone were prepared according to the interfacial deposition technique. These formulations differed in the type of polymer used to form the shell of the nanocapsules. Analysis of particle size distribution and encapsulation efficiency of the nanocapsules revealed that the type and molecular weight of polyester used were the main factors influencing these properties. PLA had the highest encapsulation efficiency with the best reproducibility. From in vitro release studies, a small amount of drug release was observed at pH 7.4. However, in the gastric medium, an important burst effect occurred and was highest with the PLGAs and lowest with PCL, suggesting that drug release from these systems is affected by the type of polymer and the environmental conditions. The two formulations of phenylbutazone-loaded nanocapsules should be evaluated based on PCL and PLA in vivo in order to determine to what extent they are able to reduce the local side effects of this drug.


Quality of life in patients with facial steroid dermatitis before and after treatment.
Improper long-term, even low-dose, topical corticosteroids, especially application to the face, could induce steroid dermatitis, which was refractory and detrimental to the quality of life. To evaluate the quality of life in patients with facial steroid dermatitis before and after the treatment of doxycycline and indomethacin plus support therapy. A prospective study. Outpatients of the Department of dermatology, the Third Hospital of Hangzhou, from August 2, 2004, to April 20, 2005. Fifty consecutive outpatients completed the treatment. The intervention is doxycycline 10 mg twice a day and indomethacin 25 mg twice a day for 4 weeks, cetirizine or loratadine 10 mg daily if pruritic, topical white petroleum if feeling dry and wet dressing if burning and oedema, plus psychological support and health education. The efficacy of the treatment was quantified using a 24-point steroid clinical score. The detriment of the quality of life was quantified using a 30-point Dermatology Life Quality Index. The steroid dermatitis clinical score decreased significantly from 15.06 +/- 4.61 at baseline to 4.52 +/- 3.39 at 2 weeks after the end of treatment (week 6; P < 0.001). Twenty-one patients underwent a rebound phenomenon and the steroid dermatitis clinical score increased significantly from 13.71 +/- 4.33 at baseline (week 0) to 19.24 +/- 3.40 at 1 week after treatment (week 1; P < 0.001). Quality of life score decreased significantly from 13.76 +/- 7.68 at baseline to 3.44 +/- 2.57 at 2 weeks after the end of treatment (week 6; P < 0.001). The quality of life was profoundly affected by facial steroid dermatitis. Doxycycline and indomethacin plus support therapy might be effective in patients with facial steroid dermatitis.


A randomized controlled clinical trial of cardiac telerehabilitation with a prolonged mobile care monitoring strategy after an acute coronary syndrome.
Center-based cardiac rehabilitation (CBCR) improves health outcomes but has some limitations. We designed and validated a telerehabilitation system to overcome these barriers. We included 67 low-risk acute coronary syndrome patients in a randomized controlled trial allocated 1:1 to a 10-month cardiac telerehabilitation (CTR) program or an 8-week CBCR program. Patients underwent ergospirometry, blood tests, anthropometric measurements, IPAQ, PREDIMED, HADS, and EQ-5D questionnaires at baseline and 10 months. Data collectors were blinded to the treatment groups. The intention-to-treat analysis included 31 patients in the CTR group and 28 patients in the CBCR group. The primary outcome showed increased physical activity according to the IPAQ survey in the CTR group compared to the CBCR group (median increase 1726 METS-min/week vs. 636, p = .045). Mean VO2max increased 1.62 ml/(kg min) (95% confidence interval [CI]: 0.56-2.69, p < .004) from baseline in the CTR group, and 0.60 mL/(kg min) (p = .40) in the CBCR group. Mean apoB/apoA-I ratio decreased 0.13 (95% CI: -0.03 to 0.24, p = .017) in the CTR group, with no significant change in the CBCR group (p = .092). The median non-HDL cholesterol increased by 7.3 mg/dl (IQR: -2.4 to 18.6, p = .021) in the CBCR group, but the increase was not significant in the CTR group (p = .080). Adherence to a Mediterranean diet, psychological distress, and quality of life showed greater improvement in the CTR group than in the CBCR group. Return-to-work time was reduced with the telerehabilitation strategy. This system allows minimal in-hospital training and prolonged follow-up. This strategy showed better results than CBCR.


Recombinant phosphoprotein based single serum dilution ELISA for rapid serological detection of Newcastle disease virus.
Newcastle disease virus (NDV) is the causative agent of a highly contagious disease in avian species. All strains of NDV belong to avian paramyxovirus serotype-1. The disease is endemic in different parts of the world and vaccination is the only way to protect birds from NDV infection. The virus non-structural phosphoprotein (P) is the second most abundant protein and a major modulator of viral replication. Although P protein shows lesser evolutionary divergence among NDV isolates, it is known to be highly divergent among different avian paramyxovirus serotypes. In the present study, a recombinant P protein based single serum dilution ELISA was developed which showed better sensitivity, specificity and accuracy as compared to conventional methods for NDV detection. The recombinant P protein based ELISA could be an alternative to existing diagnostics against NDV infection in chickens.