Renal hyperfiltration revisited-Role of the individual body surface area on mortality.
Higher than normal estimated glomerular filtration rate (eGFR), i.e. renal hyperfiltration (RHF), has been associated with mortality. A population-based screening program in Finland identified 1747 apparently healthy middle-aged cardiovascular risk subjects in 2005-2007. GFR was estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation indexed for 1.73 m2 and for the actual body surface area (BSA) of the subjects. This individually corrected eGFR was calculated as eGFR (ml/min/BSA m2) = eGFR (ml/min/1.73 m2) x (BSA/1.73). BSA was calculated by the Mosteller formula. RHF was defined as eGFR of more than 1.96 SD above the mean eGFR of healthy individuals. All-cause mortality was obtained from the national registry. The higher the eGFR, the greater was the discrepancy between the two GFR estimating equations. During the 14 years of follow-up, 230 subjects died. There were no differences in mortality rates between the categories of individually corrected eGFR (p = 0.86) when adjusted for age, sex, body mass index, systolic BP, total cholesterol, new diabetes, current smoking, and alcohol use. The highest eGFR category was associated with increased standardized mortality rate (SMR) when CKD-EPI formula indexed for 1.73 m2 was used, but SMR was at the population level when individually corrected eGFR was applied. Higher than normal eGFR calculated by the creatinine-based CKD-EPI equation is associated with all-cause mortality when indexed to 1.73 m2, but not when indexed to actual BSA of a person. This challenges the current perception of the harmfulness of RHF in apparently healthy individuals.


Effect of exercise on glucose metabolism in postmenopausal women.
A cross-sectional study was conducted to examine the effect of treadmill and muscle resistance training on glucose tolerance and insulin levels in a group of 25 normal-weight, naturally menopausal women. Subjects trained 20 minutes three times per week for at least 6 months to 70% to 85% of maximum heart rate on a treadmill, or to maximum effort for all major muscle groups on Nautilus equipment. A nonexercising age-height-weight--matched group was monitored as a control. All three groups were of above-average fitness for age as measured by aerobic capacity during initial testing. The treadmill group significantly increased its maximal oxygen uptake over the training period. Glucose tolerance and insulin response, measured as areas under the curve after a 75 gm oral glucose load, were improved in both exercise groups compared with controls, with more marked improvement in the treadmill group. The only difference achieving statistical significance was the insulin levels 30 minutes or less after glucose ingestion, representing the first phase of insulin release. Long-term exercise training that increases aerobic power thus maintains normoglycemia with lower insulin values than in otherwise physically fit postmenopausal women.


Rapid estrogen actions on ion channels: A survey in search for mechanisms.
A survey of nearly two hundred reports shows that rapid estrogenic actions can be detected across a range of kinds of estrogens, a range of doses, on a wide range of tissue, cell and ion channel types. Striking is the fact that preparations of estrogenic agents that do not permeate the cell membrane almost always mimic the actions of the estrogenic agents that do permeate the membrane. All kinds of estrogens, ranging from natural ones, through receptor modulators, endocrine disruptors, phytoestrogens, agonists, and antagonists to novel G-1 and STX, have been reported to be effective. For actions on specific types of ion channels, the possibility of opposing actions, in different cases, is the rule, not the exception. With this variety there is no single, specific action mechanism for estrogens per se, although in some cases estrogens can act directly or via some signaling pathways to affect ion channels. We infer that estrogens can bind a large number of substrates/receptors at the membrane surface. As against the variety of subsequent routes of action, this initial step of the estrogen's binding action is the key.


Prevalence and factors associated with antenatal care utilization in Ethiopia: an evidence from demographic health survey 2016.
Ethiopia is one of the sub-Saharan African country with high maternal mortality ratio (MMR). According to Ethiopian demographic health survey (EDHS) 2016 report, MMR is 420 among 100,000 live births. Antenatal care utilization is a key intervention to reduce these deaths through problem detection and treatment, promotion of health seeking behavior, and preparing pregnant women for birth. Therefore, this study aimed to assess prevalence and factors associated with antenatal care service utilization in Ethiopia in 2016. Secondary data analysis was done on EDHS 2016. It was a stratified, two-stage, and cluster sampling design. Analysis has been restricted to antenatal care utilization among women who delivered at least one time in the past five years. Data were weighted to correct sampling bias. Moreover, complex data analysis was done. Bi-variate and multivariable logistic regression analyses were carried out. Adjusted odds ratio with 95% confidence interval was computed and P-value less than 0.05 considered as a statistically significance level for identification of association. Prevalence of antenatal care utilization was 62.8% [95%CI: 60.9, 64.6] in this study. Maternal educational status of primary school (AOR = 1.8,95%CI:1.2, 2.6), maternal educational status of secondary school (AOR = 4.4,95%CI: 1.1, 17.3), women who listen radio less than 1 per week (AOR = 1.9,95%CI:1.12,3.34), women who listen radio at least 1 per week (AOR = 2.6,95%CI:1.4,4.8), women in rich wealth quintile (AOR = 1.9,95%CI: 1.1, 3.2) were factors positively associated with antenatal care utilization. However, women who had traditional belief (AOR = 0.1,95%CI:0.02,0.49), and women who had five children and above (AOR = 0.6,95%CI: 0.3, 0.9) were factors associated negatively with antenatal care utilization. Prevalence of antenatal care utilization is still low in Ethiopia in 2016. Maternal higher maternal educational status, frequent radio listening, higher wealth quintile, traditional belief, and greater number of children were found to be associated significantly with antenatal care utilization. Consequently, socio-economic status should be enhanced, information should be accessed by women about antenatal care utilization and family planning service through mass media. Furthermore, intensive community education program should be designed for traditional believers to increase uptake of antenatal care by stakeholders.


The significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor activity in renal cell carcinoma.
Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PDECGF) and has angiogenic activity. Little is known about the significance of TP/PDECGF activity in patients with renal cell carcinoma (RCC). The authors examined the enzymatic activity of TP in 66 RCC specimens and investigated the association between the level of TP activity and the stage/grade status of patients with RCC. Furthermore, the authors examined the correlation between TP/PDECGF activity and prognosis. TP activity levels in nonfixed, fresh-frozen RCC specimens and in specimens of normal kidney were determined using a thin-layer chromatography assay. The activity of TP was approximately 3.5-fold greater in RCC specimens compared with normal kidney specimens. TP activity in patients with Stage III-IV RCC was 2.6-fold greater compared with TP activity in patients with Stage I-II RCC. In addition, the level of TP activity was correlated with a higher grade of RCC. Patients who had RCC with low TP activity had a longer postoperative disease-specific survival compared with patients who had RCC with high TP activity in the 5-year follow-up. The current study is the first to demonstrate a correlation between levels of TP activity and both disease progression and a higher grade of RCC. It also is the first to show that elevated TP activity in patients with RCC predicts a poor prognosis. The results suggest that high TP/PDECGF activity may be associated with the malignant potential of RCC and that TP/PDECGF may be a molecular therapeutic target in patients with RCC.


catena-Poly[[bis-(μ-2-formyl-6-meth-oxy-phenolato-1:2κO,O:O,O)copper(II)sodium]-μ-tetra-fluorido-borate-1:1'κF:F'].
In the title heterodinuclear complex, [CuNa(BF(4))(C(8)H(7)O(3))(2)](n), the Cu(II) ion is four-coordinated by four O atoms of two 2-formyl-6-meth-oxy-phenolate ligands, giving rise to a square-planar geometry. The Na(+) ion is six-coordinated by four O atoms from the two ligands and two F atoms of two tetra-fluoridoborate anions. The tetra-fluoridoborate anion links the Na(+) ions, forming a one-dimensional structure along [001]. Three F atoms of the tetra-fluoridoborate anion are disordered over two sets of sites, with an occupancy ratio of 0.790 (11):0.210 (11).


Physeal bridges: causes, diagnosis, characterization and post-treatment imaging.
The cartilaginous primary physis, or growth plate, at the end of long bones in children allows for longitudinal bone growth. A variety of insults to the physis can lead to physeal bridge formation, which in turn can lead to limb-shortening and angular deformities. This paper begins with a description of the causes, risk factors and mechanisms by which bridges form. Then it reviews the use of imaging in the diagnosis and characterization of bridges and in the evaluation of treatment and post-treatment complications. It is important for radiologists taking care of children to be aware of the indirect and direct imaging findings of physeal bridges to aid in their diagnosis, to be able to characterize bridges as part of preoperative planning, and to know the imaging finding of post-resection complications.


Stimulation of glucose transport in cultured uterine cells by rat and rabbit uterine extracts.
Estradiol-17 beta was previously shown to stimulate glucose transport (as measured by phosphorylation of 2-deoxyglucose) in rat uterine tissue in vivo (Meier, D.A. and Garner, C.W. (1987) Endocrinology 121, 1366-1374) but attempts to demonstrate this in uterine organ strips in vitro, in uterine tumor cell lines or in uterine cells in primary culture have been unsuccessful. However, aqueous uterine extracts and uterine luminal fluid did stimulate glucose transport in uterine tumor cells and uterine cells in primary culture. Estradiol in vivo and uterine extracts in vitro each increased the initial rate of glucose transport 1.5- to 3-fold. In each case, 2-3 h were required for the stimulation to be fully expressed. The stimulation was not inhibited by cycloheximide suggesting that protein synthesis was not required. Uteri from ovariectomized rats injected daily for 4 days with 10 micrograms estradiol contained 4-fold more activity than uteri from saline-injected control animals. The activity was acid- and heat-stable, inactivated by trypsin treatment but not removed by dextran-coated charcoal treatment, suggesting that the activity is (or is associated with) a protein. The activity eluted in the 6-12 kDa range upon chromatography on Sephadex G-50. Insulin (1-1000 ng/ml) and epidermal growth factor (1-100 ng/ml) stimulated glucose transport, but only less than 50% of the stimulation by extracts. The substance(s) present in the extracts, possibly a known growth factor, may be involved in the estradiol stimulation of glucose transport and other estradiol actions in vivo.


Temperature dependence of seedling establishment of a perennial, Dioscorea tokoro.
The temperature dependence of seed germination and seedling growth was analyzed in Dioscorea tokoro, an East Asian summer-green perennial. Seeds were able to germinate fully only at 11-20 degrees C. At around 17-20 degrees C the first leaf petiole of the seedling elongated and quickly set the first leaf blade at a position enabling photosynthesis. At temperatures higher than 20 degrees C petiole elongation was retarded, and seedlings formed a rhizome and established as a perennial. The rhizome size increased with temperature up to 29 degrees C. Thus, during growth immediately after germination, temperature appears to be a key factor in determining whether the plant establishes as a perennial or grows rapidly without rhizome thickening.


[Choice of the criterion and method of measuring the interference stability of the information element gates of electrocardiac signals].
The relative error of detecting ECG informative elements at the optimum threshold is suitable to consider as a quantitative criterion for noise-immunity of selectors of ECG informative elements. So, the method of measuring the noise-immunity of binary detectors using the portions of real ECG's and noise tracings as test signals should be used to measure the criterion.


Effect of the phosphate substrate on drug-inhibitor binding to human purine nucleoside phosphorylase.
The thermodynamics of the drug-inhibitors acyclovir, ganciclovir, and 9-benzylguanine binding to human purine nucleoside phosphorylase (hsPNP) were determined from isothermal titration calorimetry as a function of the substrate phosphate ion (Pi) concentration from 0 to 0.125 M and temperature from 15 degrees C to 35 degrees C. At 25 degrees C and with an increase in the Pi concentration from 0 to 50mM, acyclovir binding becomes more entropically-driven and ganciclovir binding becomes more enthalpically-driven. At 25 degrees C, the tighter 9-benzylguanine binding reaction goes from an enthalpically-driven reaction in the absence of Pi to an entropically-driven reaction at 10 mM Pi, and the enthalpically-driven nature of the binding reaction is restored at 75 mM Pi. Since the dependencies of the driving-nature of the binding reactions on Pi concentration can be simulated by Pi binding to its catalytic site, it is believed that bound Pi affects the interactions of the side-chains with the ribose catalytic site. However, the binding constants are unaffected by change in the bound Pi concentration because of enthalpy-entropy compensation. The enzymatic activity of hsPNP was determined by an ITC-based assay employing 7-methylguanosine and Pi as the substrates. The heat of reaction determined from the assay increased by 7.5 kJ mol(-1) with increase in Pi concentration from 50 to 100mM and is attributed to weak binding of the Pi to a secondary regulatory site. Although the binding constants of acyclovir and ganciclovir at 20 microM hsPNP were in agreement with the inverse inhibition constants determined from the ITC enzyme inhibition assays at 60 nM, the binding constant of 9-benzylguanine, which interacts with Phe159 from an adjacent subunit, decreased from 5.62 x 10(5) M(-1) to 1.14 x 10(5) M(-1). This reduction in the 9-benzylguanine binding affinity along with a 7-fold increase in the specific activity of hsPNP at 14.5 nM results from partial dissociation of the hsPNP trimer into monomers below the 60 nM level.


Synthesis of Sterically Congested 2,2'-Bi(Adamantyl)-Based Alcohol and Amines.
Sterically congested chiral alcohol and amines have gained tremendous attention in the design of asymmetric catalysts. Herein, the synthesis of a sterically congested bis-adamantane framework-based chiral alcohol, (1R,2S,3S,4R)-4-(2-adamantyl)adamantan-2-ol, and amine, (1R,2S,3S,4R)-4-(2-adamantyl)adamantan-2-amine, is described. Access to these sterically encumbered compounds is found via the preparation of an enantioenriched 4-adamantyladamantan-2-one intermediate, which was synthesized in 6 steps from adamantan-2-one. The key step involved enzyme-catalyzed ester hydrolysis in giving unsaturated alcohol with an enantiomeric excess of >95%. This adamantylidene adamantanol was subjected to an acid-catalyzed intramolecular [1,4] shift to give the key chiral intermediate without racemization. This ketone intermediate was transformed into the target compounds via reduction and reductive amination protocols.


Biovalorization of brewer's spent grain as single-cell protein through coupling organosolv pretreatment and fungal cultivation.
Brewer's spent grain (BSG) is a clean byproduct from the food sector, comprising 85% of the brewing process solid byproducts. BSG is mainly used as low-quality animal feed and often ends up in landfills due to its short shelf life. However, considering its abundant availability and high nutritional content, BSG holds the potential for biorefineries to produce valuable products. The recalcitrant nature of BSG poses a challenge, requiring pretreatment steps. Therefore, this study focused on valorizing BSG obtained from organosolv pretreatment by producing food- and feed-grade single-cell protein (SCP). The BSG was subject to organosolv pretreatment at 180C for 2 h with 50% v/v ethanol as solvent. Filamentous fungi N. intermedia and A. oryzae were cultivated on as-received and different fractions of organosolv-treated BSG to evaluate the effect of factors such as pretreatment, fungal strain, pretreated fraction content, and substrate loading on fungal biomass yield, biomass composition (protein content), and metabolite production. A. oryzae cultivation on all tested substrates yielded 7%-40% more biomass than N. intermedia. Cultivating A. oryzae on organosolv liquor resulted in the highest biomass protein content (44.8% ± 0.7%) with a fungal biomass concentration of 5.1 g/L. A three-fold increase in the substrate loading increased the ethanol-to-substrate yield by 50%, while protein content was decreased by 23%. Finally, a biorefinery concept was proposed to integrate the organosolv pretreatment of BSG with fungal cultivation for maximum yield of SCP while obtaining other products such as lignin and ethanol, providing a sustainable rout for managing BSG.


Giving policy some teeth: routes to reducing disparities in oral health.
Despite improvements in oral health status and clear links between oral and systemic health, oral health is not accorded the same importance in health care policy as is general health. This review of oral health disparities over the life span documents the results of this inequity. Dental concerns and unmet dental treatment needs, especially among vulnerable populations, are not well addressed in oral health policies. We offer examples of discrepancies between policy and needs and examples of successful interventions that integrate oral health care with informed policy.


Efficacy of biceps-radial-slice magnetic resonance images for the diagnosis of biceps and pulley lesions.
Injuries to the biceps reflection pulley lead to instability of the long head of the biceps tendon (LHBT). However, conventional magnetic resonance (MR) imaging (MRI) has low diagnostic accuracy for LHBT and pulley lesions. Here, we investigated the usefulness of novel biceps-radial MRI for evaluating LHBT and pulley lesions. Biceps-radial MR images of 84 patients (84 shoulders) were prospectively analyzed. The biceps-radial MRI protocol includes sequences acquired in radial planes perpendicular to the LHBT in the shoulder joint. All patients underwent shoulder arthroscopy, and the intraoperative LHBT and pulley lesion findings were compared to the preoperative evaluations. The diagnostic accuracies of the biceps-radial MR images and conventional MR images were determined. A normal LHBT was observed in 30 (31.6%) patients, partial tears in 43 (52.6%), and complete tears in 11 (15.8%). Normal LHBT stability was present in 54 (61.4%) patients, subluxation in 24 (31.6%), and dislocation in 6 (7.0%). The biceps-radial MR (kappa coefficient: 0.94) and conventional MR (kappa coefficient: 0.68) images accurately identified LHBT tears. The biceps-radial MR images excellently agreed with the arthroscopic findings (kappa coefficient: 0.91), whereas the conventional MR images poorly agreed (kappa coefficient: 0.17) regarding LHBT instability. A normal medial wall of the pulley was observed in 26 (31.0%) patients, partial tears in 30 (35.7%), and complete tears in 28 (33.3%). A normal lateral wall of the pulley was observed in 30 (35.7%) patients, partial tears in 21 (25.0%), and complete tears in 33 (39.3%). The biceps-radial MR images excellently agreed with the arthroscopic findings (kappa coefficient: 0.89), whereas the conventional MR images moderately agreed (kappa coefficient: 0.50) regarding medial pulley lesions. The biceps-radial MR images excellently agreed with the arthroscopic findings (kappa coefficient: 0.95) and the conventional MR images moderately agreed (kappa coefficient: 0.56) regarding lateral pulley lesions. Biceps-radial MRI allows for tracking of the LHBT and pulley from the supraglenoid tuberosity to the bicipital groove in the glenohumeral joint and accurate evaluations of LHBT and pulley lesions.


RNAi-mediated mortality of Culex quinquefasciatus using two delivery methods of potential field application.
With increasing reports of resistance to traditional insecticides, there is a need for innovative ways for mosquito control. RNAi is a sequence-specific molecular biology technique for gene silencing through degradation of mRNA and prevention of protein translation. Some genes are essential for insect life and their silencing can lead to insect morbidity and/or mortality. Searching for lethal genes in Culex quinquefasciatus, we found dynamin, ROP, HMGR and JHAMT to be lethal targets for RNAi in initial screening through larval soaking in dsRNA solution. Two delivery methods, chitosan nanoparticles and genetically modified yeast cells, were used in this study and proved effective in inducing high larval mortality and low adult emergence. Adult emergence after chitosan nanoparticles/dsRNA treatment was 12.67% ± 1.76 (HMGR), 17.33% ± 1.76 (dynamin), 18.67% ± 0.67 (ROP), and 35.33% ± 0.67 (JHAMT). Genetically modified yeast increased mortalities as adult emergence was 8.33% ± 1.67 (HMGR), 13.33% ± 3.33 (dynamin), and 10% ± 2.89 (JHAMT and ROP). Chitosan nanoparticles retained 75% of its biological activity whereas yeast cells retained >95% of their activities after 7 days of incubation in water. In conclusion, our results showed that these four genes are good targets for C. quinquefasciatus control using RNAi packaged in either chitosan nanoparticles or genetically modified yeast cells.


Complementary spiritual beliefs in the Latino community: the interface with psychotherapy.
A model involving a dynamic spectrum of belief by Latinos in the spiritual traditions of Santeria and Espiritismo is proposed as replacement for the more static prevalence model. The issue of clinical responsiveness to such material is examined and illustrated, and implications for research and practice are discussed.


Mortality rate of schizophrenic patients with tardive dyskinesia during 10 years: a controlled study.
We examined mortality rates (MR) during 10 years between schizophrenic inpatients with and without tardive dyskinesia (TD). The TD group had a significantly higher MR (41%), as compared with the control group (20%). However, we could not reveal critical factors to explain why the TD patients had the higher MR.


Skipping breakfast: gender effects on resting heart rate measures in preadolescents.
The cardiovascular response in children to morning nutrition has received little attention, and associated gender-related effects are virtually uninvestigated. This study evaluated resting heart-rate (HR) and heart-rate variability (HRV) in preadolescents after overnight fasting and again after eating a standardized breakfast or continuing to fast. HR increased slightly after eating and decreased significantly with continued fasting. These effects were present for both sexes. Relative to children who ate, those who continued fasting showed increases in HRV-particularly for inter-beat-interval and low frequency component (LF: 0.04-0.15 Hz) measures. Analyses revealed significant increases across variability measures for fasting children, but a selective LF decrease in those who were fed-an effect most prominent in females. Otherwise, males and females showed similar treatment-related changes in HRV. While within-gender comparisons showed similar results for HR, i.e., faster HR in fed compared with fasting males and females, respectively, fasting females-but not males-showed significantly greater increases in variability relative to their fed counterparts. Together, these findings suggest that extended overnight fasting initiates an increase in parasympathetic activity that attenuates the expected increase in cardiovascular output following a mid-morning meal. Observed gender differences were related to greater parasympathetic activity in males and to the apparent emphasis on parasympathetic regulation of LF variability. The implications of these findings for health concerns, the nature of responses to physiological and cognitive stressors, and how such differences may influence performance variables-particularly early in development when cardiovascular responses to these stressors may be more sensitive to nutritional factors-are discussed.


Structure-activity relations in promotion of rat urinary bladder carcinogenesis by phenolic antioxidants.
The urinary bladder tumor-promoting potentials of the phenolic antioxidants, 2-tert-butyl-4-methylphenol (TBMP), propylparaben, catechol, resorcinol and hydroquinone, which are structurally related to butylated hydroxyanisole (BHA), were investigated in 170 male F344 rats. The animals were initially given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator in their drinking water for 4 weeks. Three days later, groups of 20 rats received diet containing 1.0% TBMP, 3% propylparaben, 0.8% catechol, 0.8% resorcinol, 0.8% hydroquinone or basal diet alone until the end of week 36. Significant increases in the incidences and average numbers of the putative preneoplastic lesions, papillary or nodular (PN) hyperplasia, and papillomas of the urinary bladder were only observed in the group given TBMP after BBN. Development of these lesions was not enhanced by diet containing the other test compounds and no induction was associated with any of the test chemicals alone. The results thus clearly showed that TBMP, which most closely resembles BHA, promoted urinary bladder carcinogenesis. The similar effects of TBMP and BHA on urinary bladder carcinogenesis suggest a direct link between chemical structure and biological potency.


Deep reinforcement learning in continuous action space for autonomous robotic surgery.
Reinforcement learning methods have shown promising results for the automation of sub-tasks in robotic surgery systems. With the development of these methods, surgical robots have been able to achieve good performances, so that they can be used in complex and high-risk environments such as surgical pattern cutting to reduce stress and pressure on the surgeon and increase surgical accuracy. This study has aimed at providing a deep reinforcement learning-based approach to control the gripper arm when cutting soft tissue in a continuous action space. Surgical soft tissue cutting in this study is performed by controlling the gripper arm in a continuous action space and a grid observation space. In the proposed method using deep reinforcement learning, we find an optimal tensioning policy in the continuous action space that increases the cutting accuracy of the predetermined pattern. The simulation results demonstrated that in the cutting of many complex patterns, the proposed method works better than the methods in which the tensioning was performed in a discrete action space and the observation space was modeled as a partial and random representation. We introduced a deep reinforcement learning-based method for obtaining the optimal tensioning policy in a continuous action space when cutting a predetermined pattern. We showed that the proposed approach outperforms the state-of-the-art method in the soft pattern cutting task with respect to accuracy.


Timing and outcome of right- vs left-sided colonic anastomotic leaks: Is there a difference?
Anastomotic leaks (AL) contribute to postoperative mortality, prolonged hospitalization, and increased health care costs. While left-sided AL (LAL) are well described in the literature, there is a paucity of studies on outcomes and management of right-sided AL (RAL). This study aimed to compare the timing of RAL versus LAL, and the variable diagnosis, management and outcomes of RAL versus LAL. We hypothesized that the timing of RAL may be later compared to LAL and may result in worse overall outcomes. Patients who underwent curative intent surgery for neoplastic disease from January 1995 to December 2015 were included. Patients that underwent an anastomosis below the peritoneal reflection, neoadjuvant treatment, fecal diversion, previous colectomy/anastomosis, multiple anastomoses, and patients with inflammatory bowel disease or hereditary colorectal cancer syndromes were excluded. Patient demographics, neoplastic data, operative data, time to AL, methods utilized for diagnosis of AL, and management of AL were collected. The primary endpoint was timing of AL, and secondary endpoints were management and outcome based on RAL versus LAL. RAL and LAL were analyzed and compared using Chi-squared and categorical variables were expressed as number (percentage) and continuous variables expressed as median (interquartile range). A total of 2223 patients underwent oncologic resection for colonic neoplasia (1457 right sided and 766 left sided anastomoses). 67% of patients were male and median age was 69 years (range, 34-91). There were 48 total AL events (2.16%): 26 RAL (1.78%) and 22 LAL (2.87%). There was no statistical difference in leak rates between RAL and LAL and no difference in time to diagnosis or management (Table 1). RAL had significantly decreased operative time (p = 0.016), decreased intraoperative blood loss (p = 0.002), and increased diagnosis by CT/plain radiograph (p = 0.04). All patients that underwent surgery for leak had some form of fecal diversion performed. Morbidity and mortality were comparable between groups (p = 0.70; p = 1.0). This study found overall very low AL rates with comparable timing of RAL and LAL, and no difference in management or outcome of RAL vs. LAL. These findings are informative for patient and surgeon expectations before and after surgery and when AL is suspected.


Wheat germ cell-free expression system as a pathway to improve protein yield and solubility for the SSGCID pipeline.
Recombinant expression of proteins of interest in Escherichia coli is an important tool in the determination of protein structure. However, lack of expression and insolubility remain significant challenges to the expression and crystallization of these proteins. The SSGCID program uses a wheat germ cell-free expression system as a rescue pathway for proteins that are either not expressed or insoluble when produced in E. coli. Testing indicates that the system is a valuable tool for these protein targets. Further increases in solubility were obtained by the addition of the NVoy polymer reagent to the reaction mixture. These data indicate that this eukaryotic cell-free expression system has a high success rate and that the addition of specific reagents can increase the yield of soluble protein.


[YAP induces chromosomal instability in liver cancer patients].
The Hippo/YAP signaling pathway is a central regulator of organ growth and cell proliferation. Activation of the transcriptional co-activator and oncogene YAP (yes-associated protein) supports the development of liver cancer. The aim of this work was to analyze the molecular mechanisms which are responsible for YAP-induced hepatocarcinogenesis. YAP was silenced using siRNAs in liver cancer cell lines and effects on target gene expression were analyzed via real-time polymerase chain reaction (PCR) and western immunoblotting. Immunoprecipitation and chromatin immunoprecipitation was used to study interacting proteins and binding to target gene promoter regions, respectively. Transgenic mice with liver-specific and inducible YAP expression were used for in vivo analysis. Gene expression data from hepatocellular carcinoma (HCC) patients were used to analyze YAP-dependent gene signatures and to correlate with clinical data. HCC tissue microarrays were analyzed using immunohistochemistry. Together with the transcription factors TEAD4 and FOXM1, YAP induces the expression of genes which are responsible for the development of chromosomal instability (CIN). The overexpression of these CIN genes characterizes liver cancer patients with a poor prognosis. Mechanistically, YAP/TEAD4 and FOXM1 bind to the promoter regions of the CIN genes to directly regulate their expression. The treatment of YAP-transgenic mice with a specific FOXM1 inhibitor reduces the YAP-dependent hepatomegaly, CIN gene expression and CIN. The analysis of human HCC tissue samples confirms the statistical correlation between YAP, FOXM1 and CIN. These results reveal a new oncogenic mechanism of the Hippo/YAP signaling pathway and identify YAP and FOXM1 as potential targets for targeted therapies.


Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis.
Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis.


Psychometric validation of Barkley's Adult Sluggish Cognitive Tempo (SCT) Ratings Scale -Turkish version and distinguishing SCT from attention deficit-hyperactivity disorder (ADHD) among Turkish adults.
SCT is characterized by sluggishness, daydreaming, lethargy/ apathy, slowed behavior/thinking, and mental confusion. For a long time these symptoms were thought to be a part of ADHD but then studies revealed that SCT is a different phenomenon in some cultures. In this study. we aimed to examine the validity and reliability of Barkley's Adult SCT Ratings Scale, and to determine if SCT is an independent factor from ADHD in Turkish adults like in other cultures. 274 Medical School students/trainees enrolled the study (Age: 18-35, 70.4 % female). Data was collected via an online survey including SCT and ADHD rating scales. Exploratory factor analysis demonstrated that the scale consisted of two factors: Daydreaming and Sluggishness.The model demonstrated a good-fit (χ2 = 43.642, p = 0.001; χ2/df = 2.425, GFI = 0.962,RMSEA = 0.072). As expected, there were positive and significant associations between SCT total, Daydreaming, Sluggishness, and ADHD-Inattention scores (r = 0.645, 0.664, 0.382; respectively), but all SCT items loaded within SCT factors and distinquished from ADHD factors. Cronbach's alpha values were: 0.87 for SCT-total, 0.87 for Daydreaming; 0.79 for Sluggishness. Our study provides a valid and reliable SCT screening tool for Turkish adults and increases our confidence in the transcultural generalizability of SCT.


Treatment of purely ligamentous dorsoulnar radiocarpal dislocation with ulnar translation of the carpus: A case report.
Radiocarpal fracture-dislocations are extremely infrequent injuries caused by high-energy trauma and involve significant osseous and ligamentous injuries. If not treated properly, it can lead to serious complications such as ulnar translation of the carpus, multidirectional instability, loss of motion, and post-traumatic arthritis. Purely ligamentous injuries are rarer than fracture-dislocation injuries. Because previous studies have reported small patient cohorts, there has been no standardized treatment strategy for purely ligamentous radiocarpal dislocation. A 24-year-old man suffered a left wrist injury in a motorcycle accident. Plain radiographs revealed dorso-ulnar radiocarpal dislocation without radial fracture and Carpal-ulnar distance ratio (CUDR) was 0.16. MRI scans showed the disruption of the dorsal ligaments and capsules and avulsed from the proximal insertion of the volar radiocarpal ligaments. Dorsoulnar radiocarpal dislocation with purely ligamentous injury. We removed the interposing chondral fragment from the radiocarpal joint and repaired the radioscaphocapitate (RSC) and radiolunate (RL) ligaments with the Jugger Knot Soft Anchor Suture (Biomet, Inc, Warsaw, IN) and applied additional radiocarpal K-wires and an external fixator to maintain reduction and optimal ligament tension. The patient showed good clinical results although ulnar translation of the carpus recurred in radiological follow-up. Aggressive surgical management is needed earlier in the treatment of purely ligamentous radiocarpal dislocation, especially if the ulnar translation of the carpus was observed in the initial radiographs.


The effect of sporting events on emergency department attendance rates in a district general hospital in Northern Ireland.
Previous studies have reported a conflicting relationship between the effect of live and televised sporting events on attendance rates to emergency departments (ED). The objectives of this study were to investigate the relationship of major sporting events on emergency department attendance rates and to determine the potential effects of such events on service provision. A retrospective analysis of ED attendances to a district general hospital (DGH) and subsequent admissions over a 24-h period following live and televised sporting activities was performed over a 5-year period. Data were compiled from the hospital's emergency record books including the number of attendances, patient demographics, clinical complaint and outcome. Review patients were excluded. Analysis of sporting events was compiled for live local, regional and national events as well as world-wide televised sporting broadcasts. A total of 137,668 (80,445 men) patients attended from April 2002 to July 2007. Mean attendance rate per day was 80 patients (men = 47). Mean admission rate was 13.6 patients per day. Major sporting events during the study period included; Soccer: 4 FA Cup and 1 World Cup (WC) finals; Rugby: 47 Six Nations, 25 Six nations games involving Ireland, 1 WC final, 2 WC semi-finals, 2 WC quarter-finals and 4 WC games involving Ireland; and Gaelic Football [Gaelic Athletic Association (GAA)]: 5 All-Ireland finals, 11 semi-finals, 11 quarter-finals and 5 provincial finals. There was a significantly higher patient admission rate during the soccer FA Cup final, Rugby Six Nations and games involving Ireland and for GAA semi- and quarter-final games (p = 0.001-0.01). There was no difference identified in total attendance or non-admission rates for sporting events throughout the study period. Although there was no correlation identified between any of these sporting events and total emergency department attendances (r < 0.15, p > 0.07), multinomial logistic regression demonstrated that FA Cup final (p = 0.001), Rugby Six Nations (p = 0.019), Rugby WC games involving Ireland (p = 0.003), GAA All-Ireland semi- and quarter-finals (p = 0.016; p = 0.016) were predictors of patient admission rates. This study suggests that live or televised sporting events do not significantly affect ED attendances to a DGH. However, some events appeared to be predictors of patient admission rates. Although it may be beneficial to consider the effect of sporting events on service stratification during these periods, the overall effect is probably minimal and should not create a major concern for future service provision despite the implementation of the European Working Time Directive.


Topographical layout of hand, eye, calculation, and language-related areas in the human parietal lobe.
To identify subdivisions of the human parietal cortex, we collected fMRI data while ten subjects performed six tasks: grasping, pointing, saccades, attention, calculation, and phoneme detection. Examination of task intersections revealed a systematic anterior-to-posterior organization of activations associated with grasping only, grasping and pointing, all visuomotor tasks, attention and saccades, and saccades only. Calculation yielded two distinct activations: one unique to calculation in the bilateral anterior IPS mesial to the supramarginal gyrus and the other shared with phoneme detection in the left IPS mesial to the angular gyrus. These results suggest human homologs of the monkey areas AIP, MIP, V6A, and LIP and imply a large cortical expansion of the inferior parietal lobule correlated with the development of human language and calculation abilities.


Regulation of Epstein-Barr virus latency by latent membrane protein 2.
Like other herpesviruses, Epstein-Barr virus persists in its host through its ability to establish a latent infection that periodically reactivates. Latent membrane protein 2A (LMP2A) regulates reactivation from latency by interfering with normal B cell signal transduction processes, and may define a new class of regulators of herpesvirus latency.


Cell membrane permeability coefficients determined by single-step osmotic shift are not applicable for optimization of multi-step addition of cryoprotective agents: As revealed by HepG2 cells.
HepG2 cells have a number of research applications and cryopreservation of these cells would improve supply and thus facilitate the study. Development of effective cryopreservation protocols relies on knowledges of the fundamental mass transport characteristics of HepG2 cell membrane. Currently, the permeability parameters estimated from single-step addition are routinely used to predict the osmotic responses of the cells in multistep protocols, as well as used for prediction of optimal cooling rates. However, the reasonability of this approach has not been rigorously studied. Here we measured the hydraulic conductivity (Lp) and the permeability coefficient (Ps) of HepG2 cells in the absence/presence of dimethyl sulfoxide (Me2SO) at various temperatures with single and multistep addition of Me2SO. We found that the permeability yielded via one-step addition of the Me2SO cannot exactly predict the volume change of the cells when the CPA was added in multiple steps.


The role of van der Waals interaction in the tilted binding of amine molecules to the Au(111) surface.
We present the results of ab initio electronic structure calculations for the adsorption characteristics of three amine molecules on Au(111), which show that the inclusion of van der Waals interactions between the isolated molecule and the surface leads in general to good agreement with experimental data on the binding energies. Each molecule, however, adsorbs with a small tilt angle (between -5 and 9°). For the specific case of 1,4-diaminobenzene (BDA) our calculations reproduce the larger tilt angle (close to 24°) measured by photoemission experiments, when intermolecular (van der Waals) interactions (for about 8% coverage) are included. These results point not only to the important contribution of van der Waals interactions to molecule-surface binding energy, but also that of intermolecular interactions, often considered secondary to that between the molecule and the surface, in determining the adsorption geometry and pattern formation.


Draft Genome Sequences of Six Strains of Vibrio parahaemolyticus Isolated from Early Mortality Syndrome/Acute Hepatopancreatic Necrosis Disease Shrimp in Thailand.
Some strains of Vibrio parahaemolyticus cause acute hepatopancreatic necrosis disease (AHPND) in shrimp. We sequenced 3 AHPND and 3 non-AHPND strains and found that all of them lacked the pathogenicity island relevant to human infection. A unique sequence encoding a type IV pilus/type IV secretion system was found in 3 AHPND strains.


The 13C/12C ratio in black pulmonary pigment: a mass spectrometric study.
Ratios of the two stable isotopes of carbon, 13C and 12C, were measured in black pulmonary pigment and in several endogenous tissues removed during 20 autopsies on Long Island, New York. The mass spectrometer used for carbon isotope ratio analyses has a precision of +/- 1 13C atom per million carbon atoms. The 13C/12C ratio was found to be distinctly lower in black pulmonary pigment than in endogenous tissues, the mean difference amounting to 65 13C atoms per million carbon atoms. The results demonstrate that the elemental carbon fraction of black pulmonary pigment is exogenous and constitutes roughly 30 per cent of the weight of the pigmented material. It was also observed that 13C/12C ratios in endogenous tissues from individual autopsy cases were not quite identical, tending to be slightly greater in corpus callosum than in liver or peripheral lung.


Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.
Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.


Morphological, histochemical, and biochemical studies on the gut of Haemonchus contortus Rud., 1803).
A study has been made on the structure and chemical composition of the gut of Haemonchus contortus (Rud., 1803). The oesophagus has typically a triradiate, cuticle-lined lumen. The intestinal epithelium is provided with a well-developed brush border which contains periodic acid-Schiff-positive mucoproteins. The intestinal epithelium stores glycogen and lipids. It stains diffusely for phospholipids and general proteins and also for terminal-NH2 group. The presence of Fe2+ and Fe3+ containing pigments and activities of acid and alkaline phosphatases, glucose-6-phosphatase, and 5'-nucleotidase have been observed in the intestinal epithelium. Biochemically pH optimum for intestinal acid phosphatase has been found to be 4.8. The brush border shows positive reactions for acid phosphatase and glucose-6-phosphatase, and negative reactions for alkaline phosphatase and 5'-nucleotidase, and negative reactions for alkaline phosphatase and 5'-nucleotidase. The presence of enzymes in the brush border is related to extracellular digestion and absorption of nutrients.


Bovine babesiosis: induction of protective immunity with culture-derived Babesia bovis and Babesia bigemina immunogens.
The comparative protective efficacy of culture-derived Babesia bovis and B. bigemina immunogens against challenge exposure of susceptible crossbred cattle to heterologous strains was examined and correlated with the antigenic threshold requirements for induction of protective immunity. Strong protection was observed in animals vaccinated with 10 ml-equivalent doses of soluble, B. bovis exoantigen-containing supernatant fluids. Similar protective responses to B. bigemina exoantigens were evident even at 1 ml-equivalent dosages. In addition, the efficacy of a combined B. bovis-B. bigemina immunogen was assessed with a dose-response analysis in highly susceptible, purebred cattle. Vaccinated animals were protected against clinical babesiosis, and significant weight gains were recorded after challenge infection with virulent parasites.


Transcranial doppler and near infrared spectroscopy in the perioperative period.
Maintenance of adequate blood flow and oxygen to the brain is one of the principal endpoints of all surgery and anesthesia. During operations in general anesthesia, however, the brain is at particular risk for silent ischemia. Despite this risk, the brain still remains one of the last monitored organs in clincial anesthesiology. Transcranial Doppler (TCD) sonography and near-infrared spectroscopy (NIRS) experience a revival as these noninvasive technologies help to detect silent cerebral ischemia. TCD allows for quantification of blood flow velocities in basal intracranial arteries. TCD-derived variables such as the pulsatility index might hint toward diminished cognitive reserve or raised intracranial pressure. NIRS allows for assessment of regional cerebral oxygenation. Monitoring should be performed during high-risk surgery for silent cerebral ischemia and special circumstances during critical care medicine. Both techniques allow for the assessment of cerebrovascular autoregulation and individualized management of cerebral hemodynamics. TCD and NIRS are noninvasive monitors that anesthesiologists apply to tailor cerebral oxygen delivery, aiming to safeguard brain function in the perioperative period.


Examining the risk of methanol poisoning from methyl acetate-containing products.
This retrospective study aims to review California Poison Control System data to qualitatively describe reported methyl acetate (MA) exposures and determine if a metabolic acidosis develops. We queried the Poison Control System data between January 1997 and December 1, 2010. Inclusion criteria were single MA ingestions. Eighty-three cases were analyzed. Females made up 52% of study subjects. Seventy-five cases (90%) were 5 years or younger. Most (93%) ingestions were unintentional. Sixty-two cases (75%) were referred to a health care facility (HCF). Of these, 75% of cases referred to an HCF had no effect, and 25% of cases had a minor effect. There were no major effects, including deaths reported. One case received single-dose activated charcoal, and 1 case received intravenous fluids as therapy. All other cases were observed only. Of all cases, including home-managed and HCF cases, 63 (76%) had no symptoms. Vomiting was observed in 12 cases (14%), drowsiness in 1 case, ataxia in 1 case, abdominal pain in 1 case, and throat/oral irritation in 5 cases. Fifty-three percent of cases referred to HCF had at least 1 chemistry panel done (27% had >1 chemistry panel done). One patient had a mild metabolic acidosis without symptoms that resolved after a period of observation. There was no renal dysfunction. These data suggest that minor ingestions of MA may be observed at home, but a prospective study is needed to exclude the risk of home observation.


Gender difference in the role of endothelium-derived relaxing factors modulating renal vascular reactivity.
This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in gender differences in the renal vascular reactivity of rats. Renal responses to vasoconstrictors and vasodilators were studied in isolated kidneys from male and female rats under basal conditions, after NO and EDHF blockade or after endothelium removal. Female rat kidneys had reduced responsiveness to vasoconstrictors. The blockade of NO or of EDHF did not completely abolish the differences, but the simultaneous blockade of both factors or endothelium removal abolished gender differences. Male and female kidneys showed a similar responsiveness to endothelium-dependent and -independent vasodilators under basal conditions and after NO or EDHF blockade. (a) the attenuated response to vasoconstrictors in female kidneys is related to an increased production of NO and EDHF; and (b), the contributions of NO and EDHF to endothelium-dependent vasodilation are similar in the male and female renal vasculature.


Protein binding and anticancer activity studies of ruthenium(II) polypyridyl complexes toward BEL-7402 cells.
Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dqtbt)](ClO4)2 (1) (dqtbt=12-(2,3-diphenyl-quinoxalin-6-yl)-4,5,10,13-tetraazabenzo[b]triphenylene, dmb=4,4'-dimethyl-2,2'-bipyridine), [Ru(bpy)2(dqtbt)](ClO4)2 (2) (bpy=2,2'-bipyridine), [Ru(phen)2(dqtbt)](ClO4)2 (3) (phen=1,10-phenanthroline) and [Ru(dmp)2(dqtbt)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. These complexes are sensitive to BEL-7402 cells, the IC50 values are 4.9±0.5, 4.6±0.4, 7.7±1.8 and 1.9±0.3μM toward BEL-7402 cells. The complexes can increase the levels of reactive oxygen species and induce the decrease of mitochondrial membrane potential. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in BEL-7402 cells. Complexes 1-4 inhibit the cell growth at G0/G1 phase in BEL-7402 cell line. The complexes can downregulate the expression of Bcl-2 and Bcl-x proteins and upregulate the levels of Bid protein in BEL-7402 cells. The results show that the complexes induce BEL-7402 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. In addition, the complexes show strong protein-binding affinities.


Comparative simulation study of chemical synthesis of functional DADNE material.
Amorphous molecular simulation to model the reaction species in the synthesis of chemically inert and energetic 1,1-diamino-2,2-dinitroethene (DADNE) explosive material was performed in this work. Nitromethane was selected as the starting reactant to undergo halogenation, nitration, deprotonation, intermolecular condensation, and dehydration to produce the target DADNE product. The Materials Studio (MS) forcite program allowed fast energy calculations and reliable geometric optimization of all aqueous molecular reaction systems (0.1-0.5 M) at 283 K and 298 K. The MS forcite-computed and Gaussian polarizable continuum model (PCM)-computed results were analyzed and compared in order to explore feasible reaction pathways under suitable conditions for the synthesis of DADNE. Through theoretical simulation, the findings revealed that synthesis was possible, and a total energy barrier of 449.6 kJ mol-1 needed to be overcome in order to carry out the reaction according to MS calculation of the energy barriers at each stage at 283 K, as shown by the reaction profiles. Local analysis of intermolecular interaction, together with calculation of the stabilization energy of each reaction system, provided information that can be used as a reference regarding molecular integrated stability. Graphical Abstract Materials Studio software has been suggested for the computation and simulation of DADNE synthesis.


Nonpeptidic quinazolinone derivatives as dual nucleotide-binding oligomerization domain-like receptor 1/2 antagonists for adjuvant cancer chemotherapy.
Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1/2) receptors are potential immune checkpoints. In this article, a quinazolinone derivative (36b) as a NOD1/2 dual antagonist was identified that significantly sensitizes B16 tumor-bearing mice to paclitaxel treatment by inhibiting both nuclear factor κB (NF-κB) and mitogen-activated protein kinase inflammatory signaling that mediated by NOD1/2.


Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule.
Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells. The successful reduction of graphene oxide (GO) to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO). Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells. The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3. Our data demonstrate a single, simple green approach for the synthesis of highly water-dispersible functionalized graphene nanosheets, suggesting a possibility of replacing toxic hydrazine by a natural and safe phenolic compound resveratrol, which has similar efficacy in the reduction of GO to rGO. Resveratrol-based GO reduction would facilitate large-scale production of graphene-based materials for the emerging graphene-based technologies and biomedical applications.


The potential of engineered eukaryotic RNA-binding proteins as molecular tools and therapeutics.
Eukaroytic RNA-binding proteins (RBPs) recognize and process RNAs through recognition of their sequence motifs via RNA-binding domains (RBDs). RBPs usually consist of one or more RBDs and can include additional functional domains that modify or cleave RNA. Engineered RBPs have been used to answer basic biology questions, control gene expression, locate viral RNA in vivo, as well as many other tasks. Given the growing number of diseases associated with RNA and RBPs, engineered RBPs also have the potential to serve as therapeutics. This review provides an in depth description of recent advances in engineered RBPs and discusses opportunities and challenges in the field. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Methods > RNA Nanotechnology RNA in Disease and Development > RNA in Disease.


[Urinary tract infections including pyelonephritis].
Urinary tract infections (UTIs) are among the most common bacterial infections. The clinical phenotypes of UTIs are heterogeneous, ranging from rather benign uncomplicated infections to complicated UTIs and pyelonephritis to severe urosepsis. There has been a sharp increase in the incidence of severe UTIs, whilst the incidence of sepsis in general is declining. The classifications of UTIs partially differ between clinical and regulatory claims. Experience has also been gained over the last few years to define the appropriate endpoints that are used in clinical studies. Above all, patient-centered evaluation strategies of the endpoints were developed, in order to be able to identify the advantages of new antibiotics compared to traditional antibiotics. The development of new antibiotics for UTIs is essential, since multidrug-resistant enterobacteria, which belong to the typical bacterial spectrum of UTIs, are frequently associated with mortality from infections. In recent years, several new antibiotics/combinations that are particularly effective against multi-resistant gram-negative pathogens have been investigated for the treatment of UTIs.


Acute neurologic and psychiatric complications associated with cocaine abuse.
This report reviewed 996 emergency room visits and 279 hospital admissions of patients with complications of cocaine abuse seen at the San Francisco General Hospital between 1979 and 1986. In 143 cases, acute neurologic or psychiatric symptoms were the primary complaint, and case-notes provided sufficient detail for analysis. The major neurologic complications included one or more seizures (n = 29), focal neurologic symptoms or signs (12), headache (10), and transient loss of consciousness (six). Psychiatric disturbances included agitation, anxiety, or depression (33), psychosis and paranoia (24), and suicidal ideation (18). The most serious consequences were found in patients with prolonged seizures or strokes, those who jumped out of buildings, and those who attempted suicide by overdosing with other drugs. There was no correlation between the appearance of complications and the reported route of administration, the amount of cocaine used, or prior experience with cocaine. The number of patients who are seeking hospital attention for these or related complaints appears to be rising substantially. Cocaine abuse, regardless of the use pattern, is associated with a variety of potentially severe neurologic and psychiatric complications.


Minimally invasive field abomasopexy techniques for correction and fixation of left displacement of the abomasum in dairy cows.
To reduce the potential drawbacks associated with laparotomy techniques for correction and fixation of left displaced abomasums (LDA), minimally invasive techniques have been developed. This chapter reviews the toggle pin suture (TPS) and the laparoscopic abomasopexy procedures used in the field for correction and fixation of the abomasum for correction of left-displacement of the abomasum in dairy cows. The importance of case selection cannot be overestimated. By combining laparoscopy with the principle of the TPS procedure, the lack of visual control associated with the TPS procedure is eliminated, while the advantage of the speed of completion and minimal invasiveness provided by both procedures are maintained. Successful LDA treatment includes not only early detection and treatment of the LDA, but also the prevention of secondary ketosis and aggressive treatment of concurrent disease.


Synthesis, structural elucidation and bioevaluation of 4-amino-1,2,4-triazole-3-thione's Schiff base derivatives.
In this study, a series of ten triazole Schiff base derivatives 6a-j were synthesized through microwave assisted imine formation by reacting substituted amino triazole 5 with different substituted aldehydes. All the synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase. Two of the compounds 6a and 6b among the series 6a-j were found to be highly potent tyrosinase inhibitors with IC50 values of 10.09 ± 1.03 and 6.23 ± 0.85 µM, respectively, which were even higher than that of the reference inhibitor kojic acid (IC50 = 16.6 ± 2.8 µM). Compounds 6e and 6f with IC50 values of 20.27 ± 2.78 and 26.02 ± 4.14 µM, respectively, were comparable to the reference inhibitor, and the remaining compounds had a moderate inhibitory activity against mushroom tyrosinase. The most potent compounds (6a, 6b) were used in the kinetic and optical analyses. The inhibition kinetics analyzed with Lineweaver-Burk plots revealed that both compounds 6a and 6b were non-competitive inhibitors of tyrosinase with inhibition constant values of 0.023 and 0.022 mM, respectively.


Mutant rat trypsin selectively cleaves tyrosyl peptide bonds.
A double mutant of rat trypsinogen (Asp189Ser, DeltaAsp223) was constructed by site-directed mutagenesis. The recombinant protein was produced in Escherichia coli under the control of a periplasmic expression vector. The purified and enterokinase-activated enzyme was characterized by synthetic fluorogenic tetrapeptide and natural polypeptide substrates and by a recently developed method. In case of this latter method the specificity profile of the enzyme was examined by simultaneous digestion of a mixture of oligopeptide substrates each differing only at the P(1) site residue, and the results were analyzed by high-performance liquid chromatography. All these assays unanimously demonstrated that the recombinant proteinase lacks trypsin-like activity but acquired a rather unique selectivity: it preferentially hydrolyses peptide bonds C-terminal to tyrosyl residues. This narrow specificity should be useful in peptide-analytical applications such as sequence-specific fragmentation of large proteins prior to sequencing.


Sexual differentiation and environmental endocrine disrupters.
Male sexual differentiation is dependent on normal testicular function, including secretion of testosterone from the Leydig cells, and müllerian-inhibiting substance from the Sertoli cells. External factors, such as anti-androgens and oestrogens, that disturb endocrine balance cause demasculinizing and feminizing effects in the developing male fetus. Oestrogens also causes adverse effects in female fetuses, whereas anti-androgens have little influence. A growing number of chemicals have been found to possess either weak oestrogenic, anti-androgenic or other hormonal activities, and these are often referred to as endocrine disrupters. In animals in the wild, abnormal sexual development has been associated with exposure to mixtures of endocrine disrupters. The emerging adverse trends in human reproductive health, such as increased incidences of cryptorchidism, hypospadias and testicular cancer, and the ubiquitous presence of endocrine disrupters in the environment, support the hypothesis that disturbed sexual differentiation could in some cases be caused by increased exposure to environmental endocrine disrupters.


Isolation and enumeration of Clostridium botulinum by direct inoculation of infant fecal specimens on egg yolk agar and Clostridium botulinum isolation media.
Direct plating of stool specimens on selective (Clostridium botulinum isolation) and nonselective (egg yolk agar) media was evaluated as an aid in confirming infant botulism. C. botulinum was isolated from 13 of 14 culture-positive specimens with C. botulinum isolation and from 8 of 14 egg yolk agar. No lipase reaction was seen on plates of 31 culture-negative specimens.


A 12-year-old Somalian girl presented with chronic kidney disease and died as a result of female genital mutilation- A case report.
The tradition of female genital mutilation (FGM) is practiced in many African countries, including Somalia. FGM is responsible for several short and long-term complications that can negatively influence vital and functional prognosis. We present a case of a 12-year-old girl subjected to FGM who developed urethral meatus stenosis, exacerbated by chronic renal failure and urine infection, leading to her death from a combination of complications. FGM complications, sometimes fatal, remain in developing nations. The fight against these practices must be stepped up, supported by public awareness, education, and communication efforts.


THE FATHER AND THE PATERNAL FUNCTION IN THE PSYCHOANALYTICAL PROCESS: THEORETICAL AND CLINICAL ISSUES.
The author addresses the essential aspects regarding the definition of the paternal function in metapsychological terms: how it forms and develops in the mental world, which functions it serves, or could come to serve, in the dynamic of mental functioning, and lastly, the consequent clinical implications, in particular the formation and development of symbolic capacity. In the second part, using two clinical vignettes and a clinical case, the author attempts to discuss its link to the theme of masculinity, suggesting a brief reflection on the challenges presented to the specificities of the analytical clinic.


Differences in diagnosis and treatment using telemedicine versus in-person evaluation of acute illness.
We designed a telemedicine model for diagnosis of common, acute illness to compare telemedicine and in-person evaluations on reproducibility of diagnosis and treatment. Subjects were seen by usual physicians in ambulatory settings. Subjects were also evaluated separately by experienced general pediatricians (study physicians), either in person or via telemedicine, based on random assignment. The primary measure of reproducibility was study physician agreement with usual physician on primary diagnosis. Analysis compared reproducibility for telemedicine versus in-person evaluations. Relevance of agreement on primary diagnosis was measured by comparing agreement on prescribed medications. Agreement on diagnosis of study physicians with usual physicians for the 492 visits studied was 89%. The difference in the proportion of visits with disagreements between telemedicine study and in-person study evaluations (13.8% vs 8.3%, respectively) bordered on significance (P = .051). Disagreement proportions for prescriptions were similar (32.2% vs 27.4%), however. Telemedicine evaluation for children with upper respiratory tract (URI)-ear symptoms involved unique technical requirements and clinical judgments. For this largest subgroup of 202 visits, disagreement on diagnosis for telemedicine occurred more often than for in-person evaluation (17.6 vs 6.3%, P < .02). For the remaining 290 visits, telemedicine and in-person study physicians disagreed on diagnosis about equally (11.5 vs 9.9%). Excluding the URI-ear group, reproducibility of telemedicine diagnosis did not differ from that of in-person diagnosis. For the URI-ear group, reproducibility of diagnosis by telemedicine and in-person evaluation varied significantly.


The ratio of reactive nitrogen intermediates to tumour necrosis factor and clinical outcome of falciparum malaria disease.
Serum levels of reactive nitrogen intermediates (RNI; nitrate + nitrite), interferon gamma (IFN gamma) and tumour necrosis factor (TNF) were measured in 177 Papua New Guinean children with different clinical manifestations of malaria. The groups investigated were asymptomatic parasitaemic, mild malaria, cerebral malaria survivors and cerebral malaria non-survivors. The levels of TNF were highest among the cases of cerebral malaria who died and lowest among the asymptomatic parasitaemic children (mean log TNF levels 2.183 pg/mL vs. 1.455 pg/mL; P = 0.001). Similarly, the levels of IFN gamma were highest among the cerebral and lowest among the asymptomatic patients (mean log TNF levels 0.338 pg/mL vs 0.054 pg/mL; P < 0.0001). RNI levels were high among both the asymptomatic parasitaemic group and those who died due to cerebral malaria (mean log RNI levels 1.56 microM vs. 1.412 microM; P = 0.18). The ratio of RNI to TNF, however, was significantly higher among the asymptomatic parasitaemic children and lowest among those who died due to cerebral malaria (mean log (RNI:TNF) ratio 0.118 vs. -0.789; P < 0.001). We concluded that the ratio of serum RNI to serum TNF is a more useful indicator of outcome of falciparum malaria in this population than the absolute levels of either alone.


Ultrasound biomicroscopy in the diagnosis and management of intraocular gnathostomiasis.
To describe the use of ultrasound biomicroscopy in the identification of an intraocular nematode in a case of suspected nematode-induced uveitis Observational case report. UBM was performed under topical anesthesia in a patient with acute painful uveitis suspected to result from an intraocular nematode. Clinical examination did not reveal the nematode. Over a 6-minute time span, serial UBM examinations revealed the nematode to move from the iris root into the posterior chamber through the zonules. Subsequently, it was seen adhering to the cornea and could be removed surgically, resulting in symptom relief. UBM is a useful tool in diagnosis and management of parasitic uveitis.


Differences in religiosity among cognitively intact, mildly cognitively impaired, and mildly demented elderly, and its possible relationship with depressive mood.
According to literature, religious attitudes can enhance cognitive functioning in elders, because it gives the sense of purpose in life. Therefore, due to the controversy among studies, it is of great importance to identify whether religiosity levels are greater in cognitively intact elders compared to participants with MCI as well as in patients with mild dementia irrespective etiology. This study aims to examine possible differences with regards to religiosity levels between controls, MCI and patients with mild dementia. Religiosity was measured using the Systems of Belief Inventory (SBI-15R, Holland, et al., 1998), which was standardized in Greek population. According to the ANOVA test, significant main effect was found for group by means of SBI-15R score F(2, 400) = 5.624, p = .004, η2 = .027. Post-hoc comparisons showed that MCI participants had significantly higher total religiosity scores (M = 35.48, SD = 9.67) compared to the healthy controls (M = 31.73, SD = 4.11), p = .002. Additionally, patients with mild dementia had also increased religiosity scores (M = 35.13, SD = 9.09) compared to controls (M = 31.73, SD = 4.11), p = .010. Additionally, Pearson correlation showed significant relationship between GDS with SBI-15R score (r = -.221 p = .023) and Religious beliefs & practices subscale (r = -.260 p = .007) in patients with mild dementia. Results suggested that MCI participants as well as patients with mild dementia demonstrated higher religiosity levels compared to the healthy controls. Moreover, the total religiosity levels were related with depressive symptomatology only in patients with mild dementia unlike to the other two groups.


Plant Biology: To Live, or Not to Live, That Is the Question.
Organisms tread a fine line in balancing the decision to maintain cellular homeostasis or promote cell death to allow for renewal during development or halt the spread of a life-threatening crisis. Recent studies suggest a labyrinth of receptor kinase-cyclic nucleotide-gated ion channel connections mediates life-and-death decisions in plants.


The management of patients with esophageal cancer and coronary artery stenosis undergoing radiotherapy or concurrent chemoradiotherapy: a single-center experience.
The incidence of esophageal cancer (EC) patients with coronary artery stenosis presents particular challenges. The aim of this retrospective study was to evaluate the efficiency of management on patients with both diseases treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Fifty-three patients with both EC and coronary artery stenosis from June 2009 to August 2012 were retrospectively analyzed. The patients received RT or CCRT with coronary artery stenosis management. Cardiac treatments often prescribed included aspirin, β-blockers, statins etc. The adverse effects, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. Most of the patients were 40-70 years old. There were 25 patients in the CCRT group and 28 patients in the RT group. The complete response (CR) rate was higher in the patients in the CCRT group than in those in the RT group (48.0 vs 21.4%; p=0.041). The median PFS was 15.9 months in the CCRT group and 11.6 months in the RT group (p=0.025). OS was 22.4 months in the CCRT group and 15.8 months in the RT group (p=0.013). Though adverse effects were less in the RT group, no significance differences in grade 3-4 toxicity were observed. With the appropriate of coronary artery stenosis management, RT and CCRT were both tolerable and effective in EC patients with coronary artery stenosis.


Structural analyses of the permease like protein SoxT: a member of the sulfur compound metabolizing sox operon.
One of the oldest known gene clusters that are involved in biological oxidation processes is the sox operon. This operon is present in different microbial species. In the present study an attempt has been made to analyze the probable structural role of SoxT protein from Pseudaminobacter salicylatoxidans. This protein has been predicted to be a permease-like protein. A comparative model of the protein has been made and analyzed. The possible membrane spanning region of the protein has been detected by structural bioinformatics approach. The inducer of the sulfur oxidation process has been predicted. And thereby the plausible mechanism of the transport of the sulfur anion inside the bacterial cell has been elucidated. Since this is the first study regarding the structural aspect of the protein this study may shed light on the theory of the yet unknown molecular mechanism of the sulfur oxidation process by sox operon.


An Integrative Review of Mental Health Nurses' and Other Professionals' Experience of Associative Stigma.
Mental health nurses report experiencing stigmatization both from within and outside the profession, and associative stigma provides one way to explore that experience. To better understand the current state of the literature on mental health care professionals' experiences of associative stigma, and particularly on nurses' experience of this phenomenon, an integrative review of the literature on the subject was conducted. The results detail factors associated with associative stigma, the effects of associative stigma on nurses and caregivers of persons with mental illnesses, and the quantification of associative stigma. This article concludes by discussing implications for nursing practice, education, and research.


Follow-up of patients with Hodgkin's disease following curative treatment: the routine CT scan is of little value.
A total of 10-40% of patients with Hodgkin's disease relapse following initial curative therapy. Intensive follow-up is resource intensive and may identify false relapses. We performed a retrospective review of all patients with Hodgkin's disease treated at our centre between 1990 and 1999 to evaluate the utility of the components of follow-up. A total of 107 patients met the inclusion and exclusion criteria. The median age was 33 years and the median duration of follow-up 38 months. The total number of follow-up visits was 1209 and total number of CT scans 283. There were 109 suspected relapses of which 22 proved to be true relapses. Of the latter, 14 were identified clinically, six radiologically and two via lab testing. The routine CT scan detected only two relapses (9%), yet accounted for 29% of the total follow-up costs. Based on data from our centre, the cost per true relapse was $6000 US, 49% incurred by radiological tests. The majority of the cost of follow-up was incurred by routine follow-up (84%) as opposed to the investigation of suspected relapses (16%). We conclude that most true relapses are clinically symptomatic and that the routine CT is an expensive and inefficient mode of routine follow-up.


Effect of an interdisciplinary educational program on antipsychotic prescribing among nursing home residents with dementia.
To assess the effect of an interdisciplinary educational program in reducing the use of antipsychotics in nursing home residents with dementia. We conducted a longitudinal pilot study to test the implementation of a 7-month interdisciplinary educational program in a fixed cohort of residents with dementia receiving antipsychotics. The program included consciousness-raising, educational sessions, and clinical follow-up. Administrators, physicians, pharmacists, nursing staff, and personal care attendants were involved. The effect of the program was assessed over a 6-month period, in terms of the proportion of discontinuations and dose reductions of antipsychotics. Repeated measures for use of other psychotropics and restraints, frequency of disruptive behaviors, and stressful events experienced by nursing staff and personal care attendants were simultaneously assessed. Among the 81 residents still present at the end of the program, there were 40 (49.4%) discontinuations and 11 (13.6%) dose reductions. No significant changes were found in the use of other psychotropics, the use of restraints, or in the number of stressful events experienced by nursing staff and personal care attendants. The frequency of disruptive behaviors decreased significantly over the 6-month period (p<0.001). Our interdisciplinary educational program led to a substantial reduction in the number of residents receiving antipsychotics and to a decrease in the frequency of disruptive behaviors. Our findings suggest that implementation of recognized practice guidelines could be an effective way to target residents who might not benefit from antipsychotics or who may tolerate a dose reduction.


Effect of roasting on ochratoxin A level in green coffee beans inoculated with Aspergillus ochraceus.
The heat stability of ochratoxin A in green coffee beans inoculated with Aspergillus ochraceus was studied. Heat treatment (roasting) at 200 degrees C for 10 or 20 min reduced the levels of ochratoxin A by only 0-12% in the dried whole beans. Almost all of the ochratoxin A was infused into the coffee decoction when the roasted samples were ground and extracted with boiling water. Therefore, the reduction of ochratoxin A concentration of contaminated coffee beans by roasting under these conditions is ineffective.


Rewetting of drought-resistant blue-green algae: Time course of water uptake and reappearance of respiration, photosynthesis, and nitrogen fixation.
The response of the terrestrial blue-green algae Nostoc flagelliforme, Nostoc commune, and Nostoc spec. to water uptake has been investigated after a drought period of approximately 2 years. Rapid half-times of rewetting (0.6, 3.3, and 15.5 min, respectively) are found. The surfaceto-mass ratio of the three species is inversely correlated to the speed of water uptake and loss. The ecological relevance of these different time courses is discussed.Respiration starts immediately after a 30-min rewetting period, whereas photosynthetic oxygen evolution reaches its maximum activity after 6 and 8 h with N. commune and N. flagelliforme, respectively. In the dark, recovery of oxygen uptake by N. commune is somewhat impaired, while slightly stimulated with N. flagelliforme. With both species, recovery of photosynthesis is inhibited by darkness.Using colonies kept dry for two years, nitrogenase activity of N. commune attains its maximum 120 to 150 h after rewetting, while only 50 h were needed with algal mats kept dry for two days.Thus, after a 2-year drought period, the physiological sequence of reactivation is respiration-photosynthesis-nitrogen fixation. Respiration and photosynthesis precede growth and are exhibited by existing vegetative cells, whereas recovery of nitrogen fixation is dependent on newly differentiated heterocysts.


Domestic cat microsphere immunoassays: detection of antibodies during feline immunodeficiency virus infection.
Microsphere immunoassays (MIAs) allow rapid and accurate evaluation of multiple analytes simultaneously within a biological sample. Here we describe the development and validation of domestic cat-specific MIAs for a) the quantification of total IgG and IgA levels in plasma, and b) the detection of IgG and IgA antibodies to feline immunodeficiency virus (FIV) capsid (CA) and surface (SU) proteins, and feline CD134 in plasma. These assays were used to examine the temporal antibody response of domestic cats infected with apathogenic and pathogenic FIVs, and domestic cats infected with parental and chimeric FIVs of varying pathogenicity. The results from these studies demonstrated that a) total IgG antibodies increase over time after infection; b) α-CA and α-SU IgG antibodies are detectable between 9 and 28 days post-infection and increase over time, and these antibodies combined represent a fraction (1.8 to 21.8%) of the total IgG increase due to infection; c) measurable α-CD134 IgG antibody levels vary among individuals and over time, and are not strongly correlated with viral load; d) circulating IgA antibodies, in general, do not increase during the early stage of infection; and e) total IgG, and α-CA and α-SU IgG antibody kinetics and levels vary with FIV viral strain/pathogenicity. The MIAs described here could be used to screen domestic cats for FIV infection, and to evaluate the FIV-specific or total antibody response elicited by various FIV strains/other diseases.


Recent advances of RAF (rapidly accelerated fibrosarcoma) inhibitors as anti-cancer agents.
Frequent oncogenic mutations have been identified in MAPK (mitogen-activated protein kinase) signaling pathway components. As a result, MAPK pathway is associated with human cancer initiation, in particular RAF (rapidly accelerated fibrosarcoma) component. The mutation in RAF component leads to auto-activation of MAPK signaling pathway, stimulating the uncontrolled cell growth and proliferation. In last few years, diverse chemical scaffolds have been identified as RAF inhibitors. Most of these scaffolds show potent anti-cancer activity. The present review highlights the recent investigations of RAF inhibitors during the last five years.


Effect of random interpulse interval modulation on neuromuscular fatigue.
Neuromuscular endurance during electrical stimulation may be enhanced if naturally occurring motor unit firing patterns are used. Variability in the interpulse interval (IPI) distribution may enable brief periods of rest and optimization of force output. Nine individuals participated in three 3-minute fatigue protocols of the thenar muscles elicited by supramaximal stimulation of the median nerve. All protocols consisted of a mean IPI of 33.3 ms and differed only in the type of IPI modulation, which was constant (0%), random (+/-20%), or ramped from 0% to +/-20%. M-wave amplitude declined following all protocols and the reduction was smallest following the ramp protocol. There was no significant difference among the starting or final forces or between the overall force-time integrals for the three protocols. Thus, IPI variability did not improve endurance time during electrical stimulation and the M-wave amplitude was not a reliable indicator of muscle force output.


R&P: the multiple meaning of a research project in general practice.
Rischio e Prevenzione (Risk and Prevention) is a research project that is becoming the paradigm of the Italian research on General Practice. It started from a survey showing that treatment and control of cardiovascular risk is still far from optimal even in very high-risk patients. A group of general practitioners, coordinated by Istituto Mario Negri, wrote the protocol of the study with various proposals: Creating a research network. Building research infrastructure with good research capacity. Building a 'therapeutic alliance' with the patient while presenting the research, not only obtaining their signature for a 'bureaucratic' informed consent. Having the 'Collaborative Group' as the 'sponsor' of a research even if the funds are coming from Pharmaceutical Industry. It is a randomised controlled trial (RCT) carried out in primary care with the normal patient of our daily work, so transferability is very possible. The way to enroll the patients and the request to specify the reason for not joining the project of the outcome study are a kind of participatory research. The outcome study can become a model for implementing new strategy on cardiovascular risk. A specific questionnaire will enquire the different point of view of the patient and of the general practitioner/researcher. The result of this project will help us understand the phenomenon of the poor compliance of the high-risk patients. First results during enrollment allow some optimism.


Evidence for the platelet-derived growth factor-stimulated tyrosine phosphorylation of the platelet-derived growth factor receptor in vivo. Immunopurification using a monoclonal antibody to phosphotyrosine.
The addition of platelet-derived growth factor (PDGF) to intact BALB/c 3T3 cells results in the rapid (less than 1 min), dose-dependent phosphorylation of a number of proteins that could be isolated by a monoclonal antiphosphotyrosine antibody. The predominant tyrosinephosphorylated protein shared many characteristics with the PDGF receptor, including its molecular weight (170,000), isoelectric point (pI of about 4.2), its binding to DEAE-cellulose, and its pattern of binding to lectins. This 170-kDa protein, labeled with [35S] methionine, was substantially purified from PDGF-stimulated cells using the monoclonal anti-phosphotyrosine antibody but was not significantly immunopurified from unstimulated cells. At 37 degrees C, phosphorylation of the 170-kDa protein was maximal by 5-10 min of exposure to PDGF, and thereafter decreased rapidly. However, at 4 degrees C, the phosphorylation continued to increase after 3 h of exposure to PDGF. Subsequently, shifting the cells from 4 to 37 degrees C resulted in an additional rapid burst of tyrosine phosphorylation. Among the other PDGF-stimulated molecules, the most prominent and consistently observed was a cytosolic, acidic (pI of about 4.2), 74-kDa protein. These findings indicate that the action of PDGF in vivo is associated with the rapid and transient tyrosine phosphorylation of several membrane and cytosolic proteins; the most prominent of these proteins, isolated by monoclonal antibody to phosphotyrosine, is likely to be the PDGF receptor. The use of this antibody provides a new approach for purification of the PDGF receptor.


Trace metals in sediment cores from Deception and Penguin Islands (South Shetland Islands, Antarctica).
This paper presents information on the levels of trace elements in sediments collected at Deception and Penguin Islands and tracks the sources of natural and anthropogenic inputs of metals into this sub-Antarctic region. The results suggest that natural processes, such as volcanic activity, hydrothermal processes and sediment transport, are more important than anthropogenic inputs in accounting for the metal concentrations measured in sediments at Deception Island. The higher levels of trace metals recorded in sediments at Penguin Island seem to reflect the composition of the source rocks of the island, which are dominated by the olivine-basalt group. Our findings show that human activities in the study areas may contribute to negligible levels of trace metals associated with anthropogenic inputs (e.g., Cr and Zn) in sediments, and these results can be used in the future as background levels related to low anthropogenic impacts.


Osteochondral Allograft Transplantation for Treatment of Focal Patellar Osteochondral Lesion.
Patellar osteochondral lesions are common and particularly disabling injuries that can affect young and highly active patients. If enough functional impairment, ranging from difficulty climbing stairs to pain with squatting, is present, surgical treatment may be warranted. For the treatment of these lesions, various techniques have been described, including autologous osteochondral transplantation, as well as microfracture surgery. However, these are not without disadvantages. Although morbidity is noted in cases of autologous osteochondral transplantation, uncertain and possibly unsustainable results are associated with the microfracture procedure. Therefore, we present an alternative surgical treatment option for this pathology. The objective of this Technical Note is to describe our preferred approach for an osteochondral allograft transplant procedure to treat a focal patellar osteochondral lesion.


Squamous cell carcinoma arising in mature cystic teratoma of the ovary. Clinicopathologic and topographic analysis.
Clinical and pathologic features of 28 patients with squamous cell carcinoma (SCC) arising in mature cystic teratoma (MCT) of the ovary were analyzed. The overall 5-year survival rate of these patients was 52%. Clinical staging (Stage I versus Stages II or more), histologic differentiation (well versus moderately or poorly differentiated SCC), and the presence of vascular invasion were factors affecting the prognosis of these patients. In 11 tumors, including 2 of the 4 examined in stepwise serial sections, the SCC was considered to have originated from a columnar epithelium (ciliated or nonciliated) or from a metaplastic squamous epithelium. On the other hand, no SCC was a direct transition from the ordinary epidermis of the teratomatous skin tissue. These results strongly support the proposal that SCC arising in MCT derives from the columnar epithelium.


2D projection-based software application for mobile C-arms optimises wire placement in the proximal femur - An experimental study.
A new software application can be used without fixed reference markers or a registration process in wire placement. The aim was to compare placement of Kirschner wires (K-wires) into the proximal femur with the software application versus the conventional method without guiding. As study hypothesis, we assumed less placement attempts, shorter procedure time and shorter fluoroscopy time using the software. The same precision inside a proximal femur bone model using the software application was premised. The software detects a K-wire within the 2D fluoroscopic image. By evaluating its direction and tip location, it superimposes a trajectory on the image, visualizing the intended direction of the K-wire. The K-wire was positioned in 20 artificial bones with the use of software by one surgeon; 20 bones served as conventional controls. A brass thumb tack was placed into the femoral head and its tip targeted with the wire. Number of placement attempts, duration of the procedure, duration of fluoroscopy time and distance to the target in a postoperative 3D scan were recorded. Compared with the conventional method, use of the application showed fewer attempts for optimal wire placement (p=0.026), shorter duration of surgery (p=0.004), shorter fluoroscopy time (p=0.024) and higher precision (p=0.018). Final wire position was achieved in the first attempt in 17 out of 20 cases with the software and in 9 out of 20 cases with the conventional method. The study hypothesis was confirmed. The new application optimised the process of K-wire placement in the proximal femur in an artificial bone model while also improving precision. Benefits lie especially in the reduction of placement attempts and reduction of fluoroscopy time under the aspect of radiation protection. The software runs on a conventional image intensifier and can therefore be easily integrated into the daily surgical routine.


Administrative data algorithms to identify second breast cancer events following early-stage invasive breast cancer.
Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.


Cathepsin D inhibits oxidative stress-induced cell death via activation of autophagy in cancer cells.
Cathepsin D (CatD), a lysosomal aspartic protease, plays an essential role in tumor progression and apoptosis. However, the function of CatD in cell death is not yet fully understood. In this study, we identified CatD as one of up-regulated proteins in human malignant glioblastoma M059J cells that lack the catalytic subunit of DNA-PK compared with its isogenic M059K cells with normal DNA-PK activity. M059J cells were relatively more resistant to genotoxic stress than M059K cells. Overexpression of wild-type CatD but not catalytically inactive mutant CatD (D295N) inhibited H(2)O(2)-induced cell death in HeLa cells. Furthermore, knockdown of CatD expression abolished anti-apoptotic effect by CatD in the presence of H(2)O(2). Interestingly, high expression of CatD in HeLa cells significantly activated autophagy: increase of acidic autophagic vacuoles, LC3-II formation, and GFP-LC3 puncta. These results suggest that CatD can function as an anti-apoptotic mediator by inducing autophagy under cellular stress. In conclusion, inhibition of autophagy could be a novel strategy for the adjuvant chemotherapy of CatD-expressing cancers.