Radical Cyclization of 1,n-Enynes and 1,n-Dienes for the Synthesis of 2-Pyrrolidone.
2-Pyrrolidones have aroused enormous interest as a useful structural moiety in drug discovery; however, not only does their syntheses suffer from low selectivity and yield, but also it requires high catalyst loadings. The radical cyclization of 1,n-enynes and 1,n-dienes has demonstrated to be an attractive method for the synthesis of 2-pyrrolidones due to its mild reaction conditions, fewer steps, higher atom economy, excellent functional group compatibility, and high regioselectivity. Furthermore, radical receptors with unsaturated bonds (i. e. 1,n-enynes and 1,n-dienes) play a crucial role in realizing radical cyclization because of the ability to selectively introduce one or more radical sources. In this review, we discuss representative examples of methods involving the radical cyclization of 1,n-enynes and 1,n-dienes published in the last five years and discuss each prominent reaction design and mechanism, providing favorable tools for the synthesis of valuable 2-pyrrolidone for a variety of applications.


Integration of pain scores, morphine consumption and demand/delivery ratio to evaluate patient-controlled analgesia: the C-SIA score.
Patient-controlled analgesia (PCA) is used to manage postoperative pain. Postoperatively, some patients need to be re-instructed on its correct use. This study explores the efficacy of re-instruction and illustrates a comprehensive version of the Silverman integrated approach (C-SIA), based on the integration of static and dynamic pain scores, morphine consumption, and the ratio between demanded and delivered PCA boluses (the DD ratio). In total, 50 patients operated on for colorectal surgery were studied retrospectively. The change in DD ratio after re-instruction was analyzed as the primary endpoint. Re-instructed and not re-instructed subjects were compared according to DD ratio, pain scores, and morphine consumption. A secondary comparison was performed using the SIA and C-SIA scores, to illustrate the reliability of the latter tool. Agreement between C-SIA and SIA score was assessed using a Bland-Altman analysis. In re-instructed patients, the DD ratio decreased after re-education (P = 0.011). Re-instructed patients had higher DD ratios (P = 0.018) and pain scores at rest (P = 0.024) and movement (P = 0.012) at 24 h after surgery than not re-instructed subjects. These differences disappeared at the 48 h visit. Both the SIA and C-SIA scores reflected these findings. C-SIA scores showed a higher coefficient of correlation with the DD ratio (r = 0.815; P < 0.001) than SIA scores (r = 0.663; P < 0.001). The C-SIA scores, in absolute values, being based on more variables, were, on average, 2.5 times the SIA score. Re-instruction is effective for optimizing PCA therapy. The C-SIA is an alternative to the SIA score that gives an overall measure of PCA therapy efficacy.


Moderate-intensity exercise with blood flow restriction on cardiopulmonary kinetics and efficiency during a subsequent high-intensity exercise in young women: A cross-sectional study.
Blood flow restriction (BFR) training applied prior to a subsequent exercise has been used as a method to induce changes in oxygen uptake pulmonary kinetics (O2P) and exercise performance. However, the effects of a moderate-intensity training associated with BFR on a subsequent high-intensity exercise on O2P and cardiac output (QT) kinetics, exercise tolerance, and efficiency remain unknown.This prospective physiologic study was performed at the Exercise Physiology Lab, University of Brasilia. Ten healthy females (mean ± SD values: age = 21.3 ± 2.2 years; height = 1.6 ± 0.07 m, and weight = 55.6 ± 8.8 kg) underwent moderate-intensity training associated with or without BFR for 6 minutes prior to a maximal high-intensity exercise bout. O2P, heart rate, and QT kinetics and gross efficiency were obtained during the high-intensity constant workload exercise test.No differences were observed in O2P, heart rate, and QT kinetics in the subsequent high-intensity exercise following BFR training. However, exercise tolerance and gross efficiency were significantly greater after BFR (220 ± 45 vs 136 ± 30 seconds; P < .05, and 32.8 ± 6.3 vs 27.1 ± 5.4%; P < .05, respectively), which also resulted in lower oxygen cost (1382 ± 227 vs 1695 ± 305 mL min-1).We concluded that moderate-intensity BFR training implemented prior to a high-intensity protocol did not accelerate subsequent O2P and QT kinetics, but it has the potential to improve both exercise tolerance and work efficiency at high workloads.


Biochemical evidence for presence of dopamine beta-hydroxylase in rat retina.
Previously, we demonstrated immunocytochemically that certain phenylethanolamine N-methyltransferase neurons in the inner nuclear layer of rat retina contain other catecholamine synthesizing enzymes, including tyrosine hydroxylase and aromatic-L-amino acid decarboxylase but not dopamine beta-hydroxylase (DBH), the norepinephrine biosynthetic enzyme. In the present study by using a sensitive radioenzymatic assay for DBH we demonstrated the presence of DBH enzymatic activity in retinal extracts. Immunocytochemical studies, however, failed to demonstrate DBH-immunoreactive perikarya even in animals pretreated with colchicine, an inhibitor of axonal transport. Probably causes for these discrepant findings are discussed.


Effects of haemoglobin levels on the sublingual microcirculation in pregnant women.
Anemia in pregnant women is associated with increased maternal and perinatal mortality and represents an important economic burden in many developing countries. Our goal was to evaluate the impact of anemia on the capillary network during pregnancy. Therefore, we compared microcirculatory parameters of anemic pregnant study participants to that of non-anemic pregnant women employing sublingual microcirculation video imaging technology and novel automated video analysis software.Non-anemic (n = 7) and anemic (n = 44) pregnant women were enrolled in the study at second and third trimesters. Video imaging was applied to the sublingual mucosal surface in five visual fields. The resultant videos were analyzed automatically, avoiding observer bias. Total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPV) were calculated by the software. Both, mean TVD and PVD were significantly increased in the anemic pregnant group, while the PPV was not significantly different. Significant negative correlations were observed between haemoglobin (Hb) levels and both, TVD and PVD. Haemoglobin level seems to play an important determinant role in restructuring the capillary network. An effect that could compensate the impaired tissue oxygen delivery associated with anemia during pregnancy.


The initiation and the maintenance of dieting: structural models for large-scale longitudinal investigations.
Female adolescents who engage in weight loss dieting often experience negative physical and psychological consequences. To reduce the occurrence of dieting, we need information about the factors associated with its initiation and maintenance. This paper outlines two separate structural models developed specifically for that purpose. The theoretical rationale that informed the development of each of the models was derived from careful reviews of the literature on disordered eating, and from relevant psychological theoretical and empirical literature. Separate theoretical models are identified for the initiation of dieting, in which the core component is social influence, and for the maintenance of dieting, which assumes that differences in the persistence of dieting are best understood as motivational. Each model also incorporates individual differences and variables that are hypothesized to mediate the specific effects on dieting or to operate as moderators of the relationship. The operationalization of the components of the models and their application within large-scale longitudinal studies are discussed in relation to the need for systematic investigations of the way dieting begins and how it escalates or is maintained.


Two Finite Binuclear [M2(μ2-OH)(COO)2] (M = Co, Ni) Based Highly Porous Metal-Organic Frameworks with High Performance for Gas Sorption and Separation.
Two highly porous MOFs, [Co2(μ2-OH)(bpdc)(Htpim)2][SiF6]·3.5DMA·2.5CH3OH (JLU-Liu37, H2bpdc = biphenyl-4,4'-dicarboxylate, Htpim = 2,4,5-tri(4-pyridyl)imidazole) and [Ni2(μ2-OH)(bpdc)(Htpim)2][SiF6]·7.5DMA·6CH3OH (JLU-Liu38), have been solvothermally synthesized by using the mixed ligand strategy. Both of the compounds possess finite binuclear [M2(μ2-OH)(COO)2] (M = Co, Ni) secondary building units (SBUs) which formed with a polar functional group, μ2-OH. JLU-Liu37 and JLU-Liu38 exhibit notable adsorption capacities for CO2 and light hydrocarbons (CH4, C2H6, and C3H8). Moreover, both of the materials exhibit arrestive natural gas selective separation ability, especially for C3H8/CH4 (206 for an equimolar mixture under 1 bar and 298 K, for JLU-Liu37). Both of the MOFs may be effectively applied in the separation of industrial light hydrocarbons.


Evidence for a single loss of mineralized teeth in the common avian ancestor.
Edentulism, the absence of teeth, has evolved convergently among vertebrates, including birds, turtles, and several lineages of mammals. Instead of teeth, modern birds (Neornithes) use a horny beak (rhamphotheca) and a muscular gizzard to acquire and process food. We performed comparative genomic analyses representing lineages of nearly all extant bird orders and recovered shared, inactivating mutations within genes expressed in both the enamel and dentin of teeth of other vertebrate species, indicating that the common ancestor of modern birds lacked mineralized teeth. We estimate that tooth loss, or at least the loss of enamel caps that provide the outer layer of mineralized teeth, occurred about 116 million years ago.


Endocardial Changes in Nonvalvular Atrial Fibrillation Without Atrial Thrombus-Thrombomodulin and Tissue Factor Pathway Inhibitor.
Atrial fibrillation (AF) is a well-known cause for thromboembolism. Although blood stasis in the left atrium and hypercoagulable state of the blood have been emphasized as important mechanisms, limited attention has been paid to the endocardial changes in maintaining the balance of local coagulation, which may also contribute to the thrombus formation in AF. In the present study, left atrial appendage samples were obtained at heart surgery from nonvalvular AF and non-AF patients without atrial thrombus. Immunohistochemistry for endocardial markers including thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) was performed and semiquantitatively graded. In immunohistochemistry analysis, decreased expression of TM was found in patients with nonvalvular AF compared with those without AF ( P < .001). There was no difference in TFPI expression between the 2 groups ( P = .213). Patients with TM score of 0 or 1 seemed to have larger left atrial diameter (LAD) than those with TM score of 2 or 3 (44.0 (7.9) vs 40.6 (3.9); P = .009), while no relationship between LAD and TFPI expression was found (43.4 (7.0) vs 42.9 (7.8); P = .485). In conclusion, TM expression in the atrial endocardium is decreased in nonvalvular AF without atrial thrombus, while TFPI expression is not. Downregulated TM expression might be associated with enlarged LAD.


Development of an ionic liquid-based microwave-assisted method for the extraction and determination of taxifolin in different parts of Larix gmelinii.
An ionic liquid-based microwave-assisted extraction method (ILMAE) was successfully applied for the extraction of taxifolin from Larix gmelinii. Different kinds of 1-alkyl-3-methylimidazolium ionic liquids with different kinds of cations and anions were studied and 1-butyl-3-methylimidazolium bromide was chosen as the optimal solvent for taxifolin extraction. The optimal conditions of ILMAE were determined by single factor experiments and Box-Behnken design as follows: [C4mim]Br concentration of 1.00 M, soaking time of 2 h, liquid-solid ratio of 15:1 mL/g, microwave irradiation power of 406 W, microwave irradiation time of 14 min. No degradation of taxifolin had been observed under the optimum conditions as evidenced from the stability studies performed with standard taxifolin. Compared with traditional solvent and methods, ILMAE provided higher extraction yield, lower energy and time consumption. The distribution of taxifolin in different parts of larch and the influences of age, orientation, and season on the accumulation of taxifolin were analyzed for the sufficient utilization of L. gmelinii.


Identification of physician and patient attributes that influence the likelihood of screening for intimate partner violence.
Effective assessment of intimate partner violence (IPV) demands that everyone at risk be screened. To identify potential barriers, paper-and-pencil case scenarios identified possible practitioner and patient attributes that influence IPV screening. First-year residents responded to one of four short written scenarios describing a divorced female patient with nonlocalized abdominal pain; variables were patient's age and abdominal bruising. Residents rated their likelihood of screening for IPV and seven other screening tasks and self-assessed their competence in performing each task. Regression analyses assessed the influence of resident and patient characteristics on screening likelihood. Patient bruising, younger patient age, and resident self-assessed competence best predicted IPV screening. Men were less likely than women to screen for IPV. Although most physicians receive training on IPV in medical school, barriers to IPV screening still exist. Identifying obstacles to IPV risk-assessment is an essential prerequisite for improving educational programs that promote routine IPV screening.


Impacts to water quality and fish habitat associated with maintaining natural channels for flood control.
Field investigation conducted on Boulder Creek in Boulder, Colorado evaluated impacts of flood control maintenance activities on flood conveyance, water quality, and fish habitat. Thirty-nine transects were monitored at one control site and two maintenance sites over a period of eight months. Each site was visited on more than 50 occasions in order to characterize pre- and post-maintenance conditions, and to monitor maintenance activities. Measurements along the transects included substrate composition, flow depth, velocity, and elevation. Reach-average values were assigned to variables such as in-stream vegetation, streambank stability, and woody vegetation before and after maintenance. Water temperature, dissolved oxygen, pH, specific conductance, and turbidity were sampled, and habitat suitability indices were developed pre- and post-maintenance for seven indicator fish species. Water quality impacts during maintenance consisted of high turbidity levels (> 400 NTU), which retumed to background levels (0.1-15 NTU) overnight, as well as changes in mean temperature and pH. Alteration of physical channel characteristics as a result of maintenance had limited effects on habitat quality for four of seven fish species, but caused improvements in habitat quality for three fish species. The main implications of this study for floodplain management are that: (1) Flood control maintenance practices can be in direct conflict with water quality and fish habitat objectives, and should be carefully designed and implemented by an interdisciplinary team. (2) Physical habitat for some fish species can be improved as well as reduced by maintenance activities. Habitat suitability curves may be useful tools for evaluating limiting factors of the habitat and for identifying opportunities for habitat improvements as part of maintenance.


[Effect of lemon essential oil on caries factors of Streptococcus sobrinus].
To investigate the mechanism of lemon peel essential oil (LPE) on the cariogenicity of Streptococcus sobrinus (Ss). LPE was extracted by the authors, and the minimum inhibition concentration (MIC) was measured by disc diffusion method. The LPE was used as the experimental group with concentrations ranging from 2.250 g/L to 0.281 g/L prepared with trypticase peptone yeast (TPY) culture medium, and TPY culture medium was used as the control group. Ss at the concentration of 10(8) CFU/ml was added to each group, and cultured for 6, 18, 24, 48 hours. Neson-Somogyi method was used to measure the content of reducing sugar, and glucosyltransferase (GTF) activity. The activity of lactate dehydrogenase (LDH) was measured by lactic acid and pyruvic acid continuous monitoring method. The content of water insoluble glucan (WIG) was measured by anthrone method, and the pH value of the culture solution was detected. The value of pH before the experiment and the time difference was alculated as ΔpH. At the same time point, the activity of GTF and LDH and the concentration of WIG and the value ΔpH decreased gradually with the increase of concentration of LPE. There were significant differences between each experimental group and control group (P < 0.01). The control group had the maximum value, GTF: (6.71 ± 0.61) mIU, LDH: (135.8 ± 1.7) U/L, WIG: (47.15 ± 5.12) mg/L, ΔpH: (2.67 ± 0.01). The highest drug concentration group had the minimum value: GTF: (0.39 ± 0.07) mIU, LDH: (95.0 ± 5.4) U/L, WIG: (2.44 ± 0.38) mg/L, ΔpH: (0.61 ± 0.01). The LPE below the MIC could still inhibit the GTF, LDH activity and lead to the decrease of WIG and the acid production.


Gender Affects Long-Term Neurological Outcome of Neonates.
We evaluated the possible association between fetal gender and long-term pediatric neurological morbidity. We performed a population-based retrospective cohort analysis comparing the risk of long-term neurological morbidity (up to age 18 years) of children born during the years 1991 to 2013 according to their gender. Neurological morbidity evaluated included hospitalizations in childhood involving pervasive developmental disorder, obstructive sleep apnea, cerebral palsy, epilepsy, and infantile spasms and disorders of eating as recorded in the hospital files. Multiple pregnancies and fetal congenital malformations were excluded. Kaplan-Meier survival curves were constructed to compare the cumulative neurological morbidity over the study period. A Cox proportional hazards model was used to control for obstetrical confounders, including gestational age at birth, birth weight, and maternal factors. During the study period, 240,953 newborns were included in the long-term analysis: 51.0% (n = 122,840) males and 49.0% (n = 118,113) females. Hospitalizations for neurological problems (up to age 18 years) were significantly more common in males compared with females (1.1% vs 0.8%, respectively, odds ratio 1.31, 95% confidence interval 1.2 to 1.4, P < 0.001). Specifically, pervasive developmental disorder and obstructive sleep apnea were found to be significantly more common in males, and cerebral palsy reached borderline significance (0.1% vs 0.04%, odds ratio 1.39, 95% confidence interval 0.9 to 1.9, P = 0.06). The Kaplan-Meier survival curves demonstrated males to have a significantly higher cumulative incidence of total neurological morbidity as well as of pervasive developmental disorder and obstructive sleep apnea (all log-rank test P values <0.001). In the Cox regression model, male gender exhibited an independent association with long-term neurological morbidity, while adjusting for birth weight, gestational age, and other confounding variables (adjusted hazard ratio 1.29, 95% confidence interval 1.2 to 1.4, P < 0.001). Males are at an increased risk for pediatric neurological morbidity independent of gestational age at birth and birth weight.


Oxygen radicals shaping evolution: why fatty acid catabolism leads to peroxisomes while neurons do without it: FADH₂/NADH flux ratios determining mitochondrial radical formation were crucial for the eukaryotic invention of peroxisomes and catabolic tissue differentiation.
Oxygen radical formation in mitochondria is a highly important, but incompletely understood, attribute of eukaryotic cells. I propose a kinetic model in which the ratio between electrons entering the respiratory chain via FADH₂ or NADH is a major determinant in radical formation. During the breakdown of glucose, this ratio is low; during fatty acid breakdown, this ratio is much higher. The longer the fatty acid, the higher the ratio and the higher the level of radical formation. This means that very long chain fatty acids should be broken down without generation of FADH₂ for mitochondria. This is accomplished in peroxisomes, thus explaining their role and evolution. The model explains many recent observations regarding radical formation by the respiratory chain. It also sheds light on the reasons for the lack of neuronal fatty acid (beta-) oxidation and for beneficial aspects of unsaturated fatty acids. Last but not least, it has very important implications for all models describing eukaryotic origins.


Controversies in the medical clearance of recreational scuba divers: updates on asthma, diabetes mellitus, coronary artery disease, and patent foramen ovale.
Primary care and sports medicine physicians are frequently consulted on medical clearance for prospective recreational divers. We discuss four common and controversial medical conditions--asthma, diabetes mellitus, coronary artery disease, and patent foramen ovale--as they relate to fitness to dive. For each condition we review the relevant anatomy and physiology, current recommendations, and the pertinent medical literature. Finally, we offer evidence-based recommendations regarding fitness to dive for potential divers with these conditions.


[A data storage system in computer dialog for dental prosthetics].
It is reported on a data processing system with computer dialogue for the "standardized sheet of findings". The computer-readable form, improved error control, and optimum evaluation possibilities are emphasized as special advantages. Simple handling and optimum data protection permit to have this system operated by trained laymen.


Molecular force field for ionic liquids III: imidazolium, pyridinium, and phosphonium cations; chloride, bromide, and dicyanamide anions.
This is the third set of parameters of a force field for the molecular simulation of ionic liquids, developed within the spirit of the OPLS-AA model and thus oriented toward the calculation of equilibrium thermodynamic and structural properties. The parameter sets reported here concern the cations alkylimidazolium, tetra-alkylphosphonium, and N-alkylpyridinium, and the anions chloride, bromide, and dicyanamide. The force field is built in a stepwise manner that allows the construction of models for an entire family of cations, with alkyl side chains of different length, for example. Due to the transferability of the present force field, the ions studied here can be combined with those reported in our two previous publications to create a large variety of ionic liquids that can be studied by molecular simulation. The parameters reported were obtained through different series of ab initio calculations concerning the geometry, force constants, torsion energy profiles, and electrostatic charge distributions of the ions under study. Validation of the force field consisted of comparison with experimental crystal structure and liquid density data.


The functional method: experience from the Robert Debré Hospital.
In the 1970s a conservative treatment for clubfoot (CF) deformity based on daily physiotherapy combining specific sequences was developed: the French functional method (FFM). Over time, the FFM technique has improved and additional measures have been introduced. The aim of this study was to report mid-term and long-term results of clubfeet treated conservatively by the FFM at birth. All patients consecutively treated for clubfoot by the FFM between 1993 and 2010 were prospectively included. Initial severity was assessed by the Dimeglio classification. All patients were followed up by the same treating surgeon until skeletal maturity. Final assessment was performed using the International Clubfoot Study Group evaluation system (ICFSG). A total of 779 feet were included. Surgery was required in 41% of cases (mean age 2.0±0.1 years). The incidence of surgery significantly decreased after the introduction of percutaneous Achilles tenotomy (PAT) in 2000 (63.4% vs. 29.6%). At latest evaluation (mean follow-up 12±0.2 years), 86% of patients had excellent or good outcomes (mean ICFSG was 1.83±0.1). Mean ankle dorsiflexion was 10° in non-idiopathic CF and 12.1° in idiopathic CF. Eleven percent of the idiopathic clubfeet exhibited decreased ankle function (0-10°). There were no cases of overcorrection into excess ankle dorsiflexion or rocker bottom foot deformities. Current team was the funding institution of the FFM and several modifications were proposed over times to improve outcomes. Eighty-six percent of feet had excellent to good outcomes according to the ICFSG score, with minimal residual deformities (ankle dorsiflexion between 0° and 10°, calcaneal-thigh angle between 10° and 20°) or insufficient radiological correction (defined by talo-calcaneal angle between 10° and 20°) at latest follow-up.


Fermentation of sweet whey by ethanologenic Escherichia coli.
Whey, an abundant byproduct of the dairy industry, contains large amounts of protein and lactose which could be used for fuel ethanol production. We have investigated a new organism as a candidate for such fermentations: recombinant Escherichia coli containing the genes encoding the ethanol pathway from Zymomonas mobilis. The highest level of ethanol achieved, 68 g/L, was produced after 108 hours in Luria broth containing 140 g lactose/L. Fermentations of lower lactose concentrations were completed more rapidly with approximately 88% of theoretical yields. Reconstituted sweet whey (60 g lactose/L)was fermented more slowly than lactose in Luria broth requiring 144 hours to produce 26 g ethanol/L. Supplementing sweet whey with a trace metal mix and ammonium sulfate reduced the required fermentation time to 72 hours and increased final ethanol concentration (28 g ethanol/L). By adding proteinases during fermentation, the requirement for ammonia was completely eliminated, and the rate of fermentation further improved (30 g ethanol/L after 48 hours). This latter increased in rate of ethanol production and ethanol yield are presumed to result from incorporation of amino acids released by hydrolysis of whey proteins. The fermentation of sweet whey by ethanologenic E. coil reduced the nonvolatile residue by approximately 70%. This should reduce biological oxygen demand and reduce the cost of waste treatment. Whey supplemented with trace metals and small amounts of proteinase may represent an economically attractive feedstock for the production of ethanol and other useful chemicals.


GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action.
Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription.


Enzymatic production of trans-4-hydroxy-l-proline by proline 4-hydroxylase.
Trans-4-hydroxy-l-proline (Hyp) is a useful chiral building block for production of many nutritional supplements and pharmaceuticals. However, it is still challenging for industrial production of Hyp due to heavy environmental pollution and low production efficiency. To establish a green and efficient process for Hyp production, the proline 4-hydroxylase (DsP4H) from Dactylosporangium sp. RH1 was overexpressed and functionally characterized in Escherichia coli BL21(DE3). The recombinant DsP4H with l-proline as a substrate exhibited Km , kcat and kcat /Km values up to 0.80 mM, 0.52 s-1 and 0.65 s-1 ·mM-1 respectively. Furthermore, DsP4H showed the highest activity at 35°C and pH 6.5 towards l-proline. The highest enzyme activity of 175.6 U mg-1 was achieved by optimizing culture parameters. Under the optimal transformation conditions in a 5-l fermenter, Hyp titre, conversion rate and productivity were up to 99.9 g l-1 , 99.9% and 2.77 g l-1 h-1 respectively. This strategy described here provides an efficient method for production of Hyp and thus has a great potential in industrial application.


Human leukocyte mobilization and morphology in nickel contact allergy using a skin chamber technique.
An improved skin chamber technique has been devised and used for quantitative evaluation of the leukocyte mobilization rate (LMR). The method was applied in 10 nickel-hypersensitive patients exposed to nickel sulphate. Each patient served as his own control and for additional control purpose, 5 healthy individuals without nickel hypersensitivity were studied. The kinetics of the mobilized leukocytes were followed over a 48-hour period. After an initial lag phase of 2-4 hours, maximum migration was observed from the 24th to the 48th hour, with a wide interindividual variability in the number of mobilized cells at the time of maximum LMR response. The median cumulative leukocyte count was 1.412 x 10(6) leukocytes/cm2/48 h. In the same period a statistically significant increase in the basophils for all the nickel allergic patients was observed. In 8 out of 10 patients a statistically significant effect upon the lymphocytes could be demonstrated. Six of these 8 patients had an increased lymphocyte mobilization. Throughout the period the neutrophil granulocytes were the dominant cell type, although the number decreased as the number of basophils and lymphocytes increased. The chamber technique is a valuable means for quantitative evaluation of leukocyte mobilization and morphology in skin exudates during exposure to an allergen in delayed hypersensitivity reactions.


Translating benefits of exercise on depression for youth with autism spectrum disorder and neurodevelopmental disorders.
Young adults with Autism Spectrum Disorder (ASD) are at increased risk of poor health and depressive symptoms due to difficulty with communication, limited interests, sensory deficits, and sedentary lifestyles. The Piece It Together program was developed to provide socialization and wellness goals for teens and young adults with ASD and other mild neurocognitive deficits. The curriculum includes strength and endurance training, nutrition education, and stress reduction techniques to promote healthy lifestyle choices. Twelve participants, aged 15-27, attended 90-minute classes at the MUSC Wellness Center twice a week for six weeks and were encouraged to increase their activity level every day. The Patient Health Questionnaire (PHQ-9) was administered to each participant at the first and last class. Results showed significantly decreased PHQ-9 depression scores at the end of the program, from mild (7.69) to minimal depression (3.42) (p=0.000063). Overall, the activities completed in the Piece It Together program successfully unified this group to promote healthy lifestyle choices and resulted in improved mood.


The influence of different blood samples treatment methods on pro-gastrin-releasing peptide.
Pro-gastrin-releasing peptide (ProGRP) is the promising molecular tumor marker of small cell lung cancer (SCLC). Here we study the influence of different blood samples treatment methods on ProGRP.Serum with and without separation gel and heparin plasma from 10 SCLC patients and 5 healthy individuals were assayed for ProGRP immediately and 2, 4, 6, 8, 24, and 48 hours after collection.ProGRP of serum with and without separation gel and heparin plasma detected immediately was basically consistent, whereas there was a significant difference in the level of them assayed after 2 hours. No significant variation with time was observed in heparin plasma, but in serum with and without separation gel, ProGRP concentrations gradually declined with time, with statistical significance. When assayed within 2 hours, each time point of ProGRP in heparin plasma had no significant difference and the difference of PrpGRP in serum separating gel existed at 1.5 hours.Heparin plasma is the best option for clinical test of ProGRP. If serum with separation gel is used, optimization methods of turn-around-time which guarantee samples detected within 1 hour after collection can make results more instructive for clinical treatment.


DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation.
NAT10 (N-acetyltransferase 10) is a protein with histone acetylation activity and primarily identified to be involved in regulation of telomerase activity. The presented research shows its transcriptional activation by genotoxic agents and possible role in DNA damage. NAT10 mRNA could be markedly increased by using hydrogen peroxide (H2O2) or cisplatin in a dose- and time-dependent way, and the immunofluorescent staining revealed that the treatment of H2O2 or cisplatin induced focal accumulation of NAT10 protein in cellular nuclei. Both H2O2 and cisplatin could stimulate the transcriptional activity of the NAT10 promoter through the upstream sequences from -615 bp to +110 bp, with which some nuclear proteins interacted. Ectopic expression of NAT10 could enhance the number of survival cells in the presence of H2O2 or cisplatin. The above results suggested that NAT10 could be involved in DNA damage response and increased cellular resistance to genotoxicity.


Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES).
To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES). Clinical data of all patients with ESES (not including patients with Landau-Kleffner syndrome) in four pediatric neurology outpatient clinics were analyzed. Thirty patients with ESES had been treated between 1994 and 2007. Eleven (37%) children had benign partial epilepsies of childhood, five (17%) had cerebral palsy, five (17%) had hydrocephalus, one (3%) had schizencephaly, one (3%) had prenatal parenchymal bleeding, and the etiology was unclear in seven (23%). The duration of ESES ranged between 2 and 60 months. The antiepileptic drugs that were found to be efficacious were: levetiracetam (41%), clobazam (31%), and sulthiame (17%). Valproic acid, lamotrigine, topiramate, and ethosuximide showed no efficacy. Steroids were efficacious in 65%; immunoglobulins were efficacious in 33%. High-dose diazepam was efficacious in 37%, but all the children had temporary response. Seventeen patients (57%) had cognitive deterioration, whereas the rest presented with regression in attention, speech, communication, and behavior. Fourteen children had permanent cognitive deficit. There was a significant correlation (p = 0.029) between the duration of ESES and residual intellectual deficit at follow-up. ESES reflects an evolution of benign partial epilepsy of childhood in more than one-third of the patients, whereas there is an underlying structural brain anomaly in another one-third. The most efficacious antiepileptic drugs (AEDs) are levetiracetam and clobazam. The duration of ESES correlated significantly with residual intellectual deficit at follow-up.


Association between serum uric acid and some cardiovascular risk factors in a Chinese population.
The association between serum uric acid concentration and some cardiovascular risk factors was examined in a working Hong Kong Chinese population (mean age 38 years), consisting of 910 men and 603 women. There was no significant age-related rise in serum uric acid concentration. Positive associations were found between serum uric acid concentration and body mass index, waist hip ratio, systolic and diastolic blood pressure, urea, creatinine, protein, glucose (fasting and 2 hours after 75 g oral glucose load), 2 hour insulin, triglycerides, and apolipoprotein B in men. Similar, but fewer, associations were seen in women, with the addition of a positive association with age. In both sexes, serum uric acid was negatively associated with high-density lipoprotein cholesterol. These findings complement the well-known clinical association between gout and cardiovascular and metabolic diseases, such as hypertension, hyperlipidaemia and diabetes mellitus, and suggest that serum uric acid may be a marker for the presence of an adverse cardiovascular risk factor profile.


Adhesion molecule expression by the FRTL-5 rat thyroid cell line.
We have examined the expression and function of rat CD54, a homologue of human intercellular adhesion molecule-1 (ICAM-1), by the continuously growing rat thyroid cell line FRTL-5. Approximately 10% of FRTL-5 cells express CD54 under basal conditions and this is not influenced by thyrotrophin. Expression of CD54 is increased by cytokines (gamma-interferon, tumour necrosis factor, interleukin-1) and by an activator of C-kinase, phorbol 12-myristate 13-acetate. Blocking ICAM-1 with a monoclonal antibody directed against this molecule significantly (P less than 0.01) reduced the binding of splenic lymphocytes to FRTL-5 cells but inhibition was consistently greater (P less than 0.01) in the presence of antibodies against a rat homologue of lymphocyte function-associated antigen-1, the receptor on T cells for ICAM-1. In no case was complete blocking of cluster formation observed. These results show that a pure line of rat thyroid cells can express an ICAM-1 homologue and this is directly enhanced by cytokines. Expression of this homologue is partially responsible for lymphocyte adhesion to thyroid cells, which is likely to be a major event in T cell recognition of thyroid antigens in autoimmune thyroiditis.


Rapidly destructive arthropathy of the hip joint in patients with rheumatoid arthritis.
This article describes 3 patients with rheumatoid arthritis in which hip joint conditions were similar to rapidly destructive arthropathy of the hip joint. The patients had the following additional characteristics: (1) age at diagnosis was comparatively older; (2) rheumatoid arthritis had an onset after age 40 years; (3) severe rheumatoid arthritis was present in >4 major joints; (4) long-term steroids and disease-modifying antirheumatic drugs were taken due to the high activity of rheumatoid arthritis; and (5) patients were underweight, with body mass indexes <20 kg/m(2).Rapidly destructive arthropathy of the hip joint rarely occurs in osteoarthritis, avascular necrosis of the femoral head, and rheumatoid arthritis. Clinically, rapidly destructive arthropathy of the hip joint occurs in elderly patients who report severe pain but have a relatively preserved range of motion. Typical radiologic changes in rapidly destructive arthropathy of the hip joint are rapid destruction, resorption, or subluxation of the femoral head, destruction of the acetabulum, and minimal spur formation developing 6 to 12 months after symptom onset. Destruction of the hip joint in rheumatoid arthritis occurs in the sequence of depression, flattening, and loss, and commonly progresses gradually. When patients with rheumatoid arthritis report persistent and severe pain in the hip joint with no specific cause, rapidly destructive arthropathy of the hip joint must be identified through repetitive follow-up radiographic observations.


Static and dynamic cervical MRI: two useful exams in cervical myelopathy.
Cervical magnetic resonance imaging (MRI) is the gold standard exam in the assessment of patients affected by cervical myelopathy and is very useful in planning the operation. Herein we present a series of patients affected by long tract symptoms who underwent dynamic MRI in addition to the static exam. In the period between March 2010 and March 2012, three-hundred-ten patients referred to our department since affected by neck/arm pain or symptoms related to cervical myelopathy. Thirty-eight patients complained "long-tract symptoms" related to cervical myelopathy. This series of patients was enrolled in the study. All patients underwent clinical and neurological exam. In all the cases, a static and dynamic cervical MRI was executed using a 3.0-T superconducting MR unit (Intera, Philips, Eindhoven, Netherlands). The dynamic exam was performed with as much neck flexion and extension the patient could achieve alone. On T2-weigthed MRI each level was assessed independently by two neuroradiologists and Muhle scale was applied. According to Muhle's classification of spinal cord compressions, static MRI demonstrated 156 findings: 96 (61.54%) anterior and 60 (38.46%) posterior. Dynamic MRI showed 186 spinal cord compressions: 81 (43.5%) anterior and 105 (56.5%) posterior. The anterior compressions were: grade 1 in 23 cases (28.4%), grade 2 in 52 cases (64.2%), grade 3 in 6 cases (7.4%). The posterior compressions were: 32 (30.48%) of grade 1, 60 (57.14%) of grade 2, 13 (12.38%) of grade 3. The dynamic MRI demonstrated a major number of findings and spinal cord compressions compared to the static exam. Finally, we consider the dynamic exam able to provide useful information in these patients, but we suggest a careful evaluation of the findings in the extension exam since they are probably over-expressed.


HOSPEX in the antipodes.
The Australian Army recently adopted the British concept of hospital exercise (HOSPEX) as a means of evaluating the capabilities of its deployable NATO Role 2E hospital, the 2nd General Health Battalion. The Australian approach to HOSPEX differs from the original UK model. This article describes the reasons why the Australian Army needed to adopt the HOSPEX concept, how it was adapted to suit local circumstances and how the concept may evolve to meet the needs of the wider Australian Defence Force and our allies.


Chinja, a new genus of spider from the Eastern Arc Mountains of Tanzania (Araneae, Zoropsidae).
The new zoropsid spider genus Chinja Polotow Griswold is diagnosed and described and the following two new species are described: C. chinja sp. nov. and C. scharffi sp. nov. The species were collected in the Eastern Arc Mountains of Tanzania and appear to be endemic to this region. The genus belongs to the oval-calamistrum clade (OC Clade), which also includes Dionycha and Lycosoidea. Based on the synapomorphies and diagnostic characters of members of the OC Clade, Chinja is considered a member of Zoropsidae, although without a clear subfamily placement due to insufficient data. Males of Chinja can be distinguished from other Zoropsidae by a straight PER, by lacking a tibial crack, by having a male palpal cymbium with a retrobasal process and the male palpal tibia with an RTA and a retromedian cluster of stout setae. Females have a divided cribellum with cribellar spigots evenly arranged, and the epigynum with the median plate broad and laterally procurved into hooks, and the lateral lobes each with a wide tooth. The following set of characters can be also helpful to identify the genus: presence of a third tarsal claw, absence of claw tufts and presence of a cribellum and calamistrum.


Roundtrip ticket for secretory IgA: role in mucosal homeostasis?
An important activity of mucosal surfaces is the production of Ab referred to as secretory IgA (SIgA). SIgA serves as the first line of defense against microorganisms through a mechanism called immune exclusion. In addition, SIgA adheres selectively to M cells in intestinal Peyer's patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer's patches, SIgA binds and is internalized by dendritic cells in the subepithelial dome region. When used as carrier for Ags in oral immunization, SIgA induces mucosal and systemic responses associated with production of anti-inflammatory cytokines and limits activation of dendritic cells. In terms of humoral immunity at mucosal surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune exclusion) and of a mucosal immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis of the gastrointestinal tract.


Specific depressive symptoms are related with different patterns of alcohol use in community-dwelling older adults.
To explore how individual depressive symptoms might contribute to different patterns of alcohol consumption in Colombian older adults living in the community. A Secondary analysis from a nationally representative cross-sectional study of more than 23,000 older adults, with data from 19,004 participants. Drinking frequency, and level (moderate or heavy drinking) were used to assess alcohol use and depressive symptoms explored with the 15 items-GDS., using bivariate and multivariate adjusted regression models. Lower weekly drinking frequency and a higher number of drinks per serving were associated with total GDS score. For individual symptoms, higher drinking frequency was associated with dropping activities and a preference to stay at home. Lower drinking frequency was associated with low mood, unhappiness, feelings of emptiness, worthlessness, hopelessness, and a lack of vigour. Lower number of drinks per serving was associated with withdrawal/apathy related symptoms; these also related to higher frequency of weekly alcohol consumption. Higher number of drinks per serving was associated with feelings of emptiness, worthlessness, boredom, helplessness, worthlessness. not wanting to be alive, thinking that other people are better off in their mood, being afraid that something bad will happen and subjective memory problems. Moderate drinkers had a higher likelihood of reporting lack of vigour. There were diverse patterns of alcohol use according to individual depressive symptoms. This has implications for interventions to reduce alcohol related harm in older people across a range of depressive symptoms with different patterns of alcohol use.


Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria.
Artemisinin resistance in falciparum malaria is associated with kelch13 propeller mutations, reduced ring stage parasite killing, and, consequently, slow parasite clearance. We assessed how parasite age affects parasite clearance in artemisinin resistance. Developmental stages of Plasmodium falciparum parasites on blood films performed at hospital admission and their kelch13 genotypes were assessed for 816 patients enrolled in a multinational clinical trial of artemisinin combination therapy. Early changes in parasitemia level (ie, 0-6 hours after admission) were determined mainly by modal stage of asexual parasite development, whereas the subsequent log-linear decline was determined mainly by kelch13 propeller mutations. Older circulating parasites on admission were associated with more-rapid parasite clearance, particularly in kelch13 mutant infections. The geometric mean parasite clearance half-life decreased by 11.6% (95% CI 3.4%-19.1%) in kelch13 wild-type infections and by 30% (95% CI 17.8%-40.4%) in kelch13 mutant infections as the mean age of circulating parasites rose from 3 to 21 hours. Following the start of antimalarial treatment, ongoing parasite sequestration and schizogony both affect initial changes in parasitemia. The greater dependency of parasite clearance half-life on parasite age in artemisinin resistant infections is consistent with ring stage resistance and consequent parasite clearance by sequestration. The stage of parasite development should be incorporated in individual assessments of artemisinin resistance.


Clouds of high contrast on Uranus.
Near-infrared images of Uranus taken with the Hubble Space Telescope in July and October 1997 revealed discrete clouds with contrasts exceeding 10 times the highest contrast observed before with other techniques. At visible wavelengths, these 10 clouds had lower contrasts than clouds seen by Voyager 2 in 1986. Uranus' rotational rates for southern latitudes were identical in 1986 and 1997. Clouds in northern latitudes rotate slightly more slowly than clouds in opposite southern latitudes.


Species packing in eco-evolutionary models of seasonally fluctuating environments.
As ecology and evolution become ever more entwined, many areas of ecological theory are being re-examined. Eco-evolutionary analyses of classic coexistence mechanisms are yielding new insights into the structure and stability of communities. We examine fluctuation-dependent coexistence models, identifying communities that are both ecologically and evolutionarily stable. Members of these communities possess distinct environmental preferences, revealing widespread patterns of limiting similarity. This regularity leads to consistent changes in the structure of communities across fluctuation regimes. However, at high amplitudes, subtle differences in the form of fluctuations dramatically affect the collapse of communities. We also show that identical fluctuations can support multiple evolutionarily stable communities - a novel example of alternative stable states within eco-evolutionary systems. Consequently, the configuration of communities will depend on historical contingencies, including details of the adaptive process. Integrating evolution into the study of coexistence offers new insights, while enriching our understanding of ecology.


Radiopacity of household deodorizers, air fresheners, and moth repellents.
Household deodorizers and moth repellents are common agents implicated in many childhood poisonings. Their ingredients usually include either paradichlorobenzene or naphthalene compressed into a solid ball or another shape, sometimes with added essential oils and fragrances. Because medically naphthalene is a more important toxin than paradichlorobenzene, with hematologic and nervous system effects, clinicians often seek to discern which product has been ingested. We discovered fortuitously that a mothball swallowed by a retarded adult was radiopaque, and so designed an in vitro experiment to study the radiopacity of a variety of household deodorizers and products. Of 10 products screened for radiopacity by two radiologists, those containing paradichlorobenzene were consistently strongly radiopaque; those containing naphthalene were radiolucent. A third alternative ingredient which is used in some toilet bowl deodorizers, cetrimonium bromide, was also radiopaque. Radiopacity of paradichlorobenzene or cetrimonium bromide-containing products did not dissipate with time. We speculate that the halogen within the chemical structure of these compounds accounts for their radiopacity. We conclude that paradichlorobenzene-containing commercial products can be distinguished clinically from those containing naphthalene by the performance of an abdominal radiograph.


Behcet disease combined with Sjogren syndrome: A unique case report and literature review.
Behcet disease(BD) and Sjogren syndrome(SS) are separate conditions that rarely concomitantly affect an individual. In theory,mild symptoms of patients with BD or SS are easy to igore and,thus,remain undiagnosed. There,it is reasonable to believe there may be some clinical cases of combined diseases that go undiscovered and which needs to be taken seriously. In addition,it has been suggested that herpes simplex virus(HSV) types 1 and 2 are associated with BD,but have not been shown to be correlated to the direct pathogenesis of BD. The role of HSV in BD needs more research and attention. Here,we report a young woman who had both BD and SS. The first symptom of the disease was fever. However,the HSV type 1 IgG and HSV type 2 IgM antibody results were positive in our case and,which rendered this case unique. BD and SS concomitantly affect the individual,and BD was the acute type. IV methylprednisolone was used for 9 days and then oral glucocorticoids was used to instead,and the treatment works very well. BD and SS can concomitantly affect an individual,and we believe that HSV-2 may be directly related to the pathogenesis of BD. The nature of BD as an auto-inflammatory disorder, autoimmune disorder, or both, is controversial. If we can find more patients who combined affected these two disease, it might helpful for us to understand the nature of BD. For patients with clinical diagnosis of BD or SS,we need to be alert that it may combinded the other disease. Long term follow up and detailed inspection are important means to avoid undiscovered.


Genome-Wide Analysis of Gene Expression Provides New Insights into Cold Responses in Thellungiella salsuginea.
Low temperature is one of the major environmental stresses that affects plant growth and development, and leads to decrease in crop yield and quality. Thellungiella salsuginea (salt cress) exhibits high tolerance to chilling, is an appropriate model to investigate the molecular mechanisms of cold tolerance. Here, we compared transcription changes in the roots and leaves of T. salsuginea under cold stress using RNA-seq. We identified 2,782 and 1,430 differentially expressed genes (DEGs) in leaves and roots upon cold treatment, respectively. The expression levels of some genes were validated by quantitative real-time-PCR (qRT-PCR). Among these DEGs, 159 (11.1%) genes in roots and 232 (8.3%) genes in leaves were annotated as various types of transcription factors. We found that five aquaporin genes (three TIPs, one PIPs, and one NIPs) responded to cold treatment. In addition, the expression of COR47, ICE1, and CBF1 genes of DREB1/CBF-dependent cold signaling pathway genes altered in response to low temperature. KEGG pathway analysis indicated that these cold regulated genes were enriched in metabolism, photosynthesis, circadian rhythm, and transcriptional regulation. Our findings provided a complete picture of the regulatory network of cold stress response in T. salsuginea. These cold-responsive genes could be targeted for detail functional study and utilization in crop cold tolerance improvement.


Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation.
A series of cytotoxic titanocene derivatives have been immobilized onto nanostructured silica-based materials using two different synthetic routes, namely, (i) a simple grafting protocol via protonolysis of the Ti-Cl bond; and (ii) a tethering method by elimination of ethanol using triethoxysilyl moieties of thiolato ligands attached to titanium. The resulting nanostructured systems have been characterized by different techniques such as XRD, XRF, DR-UV, BET, SEM, and TEM, observing the incorporation of the titanocene derivatives onto the nanostructured silica and slight changes in the textural features of the materials after functionalization with the metallodrugs. A complete biological study has been carried out using the synthesized materials exhibiting moderate cytotoxicity in vitro against three human hepatic carcinoma (HepG2, SK-Hep-1, Hep3B) and three human colon carcinomas (DLD-1, HT-29, COLO320) and very low cytotoxicity against normal cell lines. In addition, the cells' metabolic activity was modified by a 24-h exposure in a dose-dependent manner. Despite not having a significant effect on TNFα or the proinflammatory interleukin 1α secretion, the materials strongly modulated tumor necrosis factor (TNF) signaling, even at sub-cytotoxic concentrations. This is achieved mainly by upregulation of the TNFR1 receptor production, something which has not previously been observed for these systems.


Recent Advances in Drug Discovery Toxicology.
Major advances in scientific discovery and insights that stem from the development and use of new techniques and models can bring remarkable progress to conventional toxicology. Although animal testing is still considered as the "gold standard" in traditional toxicity testing, there is a necessity for shift from animal testing to alternative methods regarding the drug safety testing owing to the emerging state-of-art techniques and the proposal of 3Rs (replace, reduce, and refine) towards animal welfare. This review describes some recent research methods in drug discovery toxicology, including in vitro cell and organ-on-a-chip, imaging systems, model organisms (C. elegans, Danio rerio, and Drosophila melanogaster), and toxicogenomics in modern toxicology testing.


[Presence of antigenic determinants in mRNA-containing RNP particles of immune B-lymphocytes].
An iodinated erythrocyte antigen isolated from sheep erythrocytes (125I-EAG) was injected to the BALB/c or CBA mice in a single dose of 20-25 mkg as for protein. The antigen determinants were detected by incorporation of a radioactive label into spleen B-lymphocytes on the 1sh-5th post-immunization days. It was shown that the T-cells contain no label and that 2/3 of the radioactivity of B-lymphocyte suspension of the 125I-EAG-immunized mice are detected in the cell nuclei within mRNP. During electrophoresis of the particles in 2,5% polyacrylamide gel nuclear mRNP isolated from B-lymphocytes of mice immunized with cold EAG are adsorbed by an immunoadsorbent containing antibodies against sheep erythrocytes. Fractionation of 125I-cytoplasmic extract obtained from 125I-EAG-immunized mouse B-lymphocytes in sucrose gradient revealed that the radioactive label was detected in the same two regions of the sucrose gradient, which is occupied by light RNP complexes containing mRNA and polyribosomes. Under experimental conditions allowing to detect the transitions of mRNP complexes into polyribosomes, a shift of the 125I-labelled material (probably together with the RNP particles) towards polyribosomes was observed. Thus, the antigen determinants are detected as part of nuclear and cytoplasmic mRNP of B-lymphocytes during the whole cycle of the primary immune response and are detected within the composition of cytoplasmic mRNP during the immunoglobulin polypeptide chain synthesis.


Implant-safe test in patients with peri-implantitis.
Matrix metalloproteases (MMPs) are a family of zinc-dependent endopeptidases, produced by numerous cell types including fibroblasts, endothelial cells, osteoblasts, macrophages, lymphocytes and neutrophils, and capable of degrading different components of the extracellular matrix (ECM), but also cytokines, receptors and factors that regulate cell motility (1). MMPs represent the main proteolytic enzymes involved in the remodeling and degradation of the components of the extracellular matrix, in the modifications of interactions between cells, and those between cells and the ECM that regulate, for example, the processes of cell migration (2, 3). Due to these characteristics, the MMPs are involved in numerous physiological processes (angiogenesis, apoptosis, bone remodeling, wound repair, morphogenesis, inflammation, immune response) response to incongruous conservative and endodontic treatments (29-37, 46, 47) and pathological (periodontitis, arthritis, cancer, cardiovascular diseases, neurological diseases, osteoporosis etc.) (5). Metalloproteinase-8 (MMP-8) is an important indicator of tissue decomposition and is present in case of periodontitis in the gingiva and in the sulcular fluid. The concentration of MMP-8 in the sulcular fluid of patients with chronic or aggressive periodontitis is higher than that found in healthy patients (4, 6). MMP-8 was also significantly correlated with gingivitis index, plaque index, probing and clinical attack level. For this reason, the concentration of MMP-8 in the sulcular fluid could constitute a useful index to monitor periodontitis activity and be used to predict disease progression, also because of orthodontic treatments (38-45). Patients with periodontitis had elevated concentrations of MMP-8 salivary compared to patients with gingivitis and healthy tissues. Through this experimentation we wanted to demonstrate the real effectiveness of using this test as a means of preventing peri-implant pathology.


Evidence for cooperativity between the four binding sites of dimeric ArsD, an As(III)-responsive transcriptional regulator.
ArsD is a trans-acting repressor of the arsRDABC operon that confers resistance to arsenicals and antimonials in Escherichia coli. It possesses two-pairs of vicinal cysteine residues, Cys(12)-Cys(13) and Cys(112)-Cys(113), that potentially form separate binding sites for the metalloids that trigger dissociation of ArsD from the operon. However, as a homodimer it has four vicinal cysteine pairs. Titration of the steady-state fluorescence of ArsD with metalloids revealed positive cooperativity, with a Hill coefficient of 2, between these sites. Disruption of the Cys(112)-Cys(113) site by mutagenesis of arsD, but not the Cys(12)-Cys(13) site, largely abolished this cooperativity, indicative of interactions between adjacent Cys(112)-Cys(113) sites within the dimer. The kinetics of metalloid binding were determined by stopped flow spectroscopy; the rate increased in a sigmoidal manner, with a Hill coefficient of 4, indicating that the pre-steady-state measurements reported cooperativity between all four sites of the dimer rather than just the intermolecular interactions reported by the steady-state measurements. The kinetics of Sb(III) displacement by As(III) revealed that the metalloid-binding sites behave differentially, with the rapid exchange of As(III) for Sb(III) at one site retarding the release of Sb(III) from the other sites. We propose a model involving the sequential binding and release of metalloids by the four binding sites of dimeric ArsD, with only one site releasing free metalloids.


Urea-Functionalized Fe4 L6 Cages for Supramolecular Gold Catalyst Encapsulation to Control Substrate Activation Modes.
The excellent catalytic performances of enzymes in terms of activity and selectivity are an inspiration for synthetic chemists and this has resulted in the development of synthetic containers for supramolecular catalysis. In such containers the local environment and pre-organization of catalysts and substrates leads to control of the activity and selectivity of the catalyst. Herein we report a supramolecular strategy to encapsulate single catalysts in a urea-functionalized Fe4 L6 cage, which can co-encapsulate a functionalized urea substrate through hydrogen bonding. Distinguished selectivity is obtained, imposed by the cage as site isolation only allows catalysis through π activation of the substrate and as a result the selectivity is independent of catalyst concentration. The encapsulated catalyst is more active than the free analogue, an effect that can be ascribed to transitionstate stabilization rather than substrate pre-organization, as revealed by the MM kinetic data. The simple strategy reported here is expected to be of general use in many reactions, for which the catalyst can be functionalized with a sulfonate group required for encapsulation.


Oral gingival metastasis: A diagnostic dilemma.
Oral cavity is a rare target for metastasis with an incidence of 1% among all oral cancers. In 24% of such cases, oral metastasis is the first indication of an undiagnosed primary. Metastatic oral malignancies have been reported in the mandible, tongue, and gingiva. Although gingival metastasis has been reported from lung, prostate, rectal carcinoma in men and carcinoma of breast, adrenal glands, and genitalia in females, gingival metastasis from carcinoma of the penis has not been reported. Herein, a case of metastatic gingival carcinoma that developed after extraction of teeth from primary carcinoma of the penis is presented. An extensive literature search revealed no such similar case reports.


Development of High-Quality Nuclei Isolation to Study Plant Root-Microbe Interaction for Single-Nuclei Transcriptomic Sequencing in Soybean.
Single-nucleus RNA sequencing (sNucRNA-seq) is an emerging technology that has been rapidly adopted and demonstrated to be a powerful tool for detailed characterization of each cell- and sub cell-types in complex tissues of higher eukaryotes. sNucRNA-seq has also been used to dissect cell-type-specific transcriptional responses to environmental or developmental signals. In plants, this technology is being utilized to identify cell-type-specific trajectories for the study of several tissue types and important traits, including the single-cell dissection of the genetic determinants regulating plant-microbe interactions. The isolation of high-quality nuclei is one of the prerequisite steps to obtain high-quality sNucRNA-seq results. Although nuclei isolation from several plant tissues is well established, this process is highly troublesome when plant tissues are associated with beneficial or pathogenic microbes. For example, root tissues colonized with rhizobium bacteria (nodules), leaf tissue infected with bacterial or fungal pathogens, or roots infected with nematodes pose critical challenges to the isolation of high-quality nuclei and use for downstream application. Therefore, isolation of microbe-free, high-quality nuclei from plant tissues are necessary to avoid clogging or interference with the microfluidic channel (e.g., 10× Genomics) or particle-templated emulsion that are used in sNucRNA-seq platforms. Here, we developed a simple, effective, and efficient method to isolate high-quality nuclei from soybean roots and root nodules, followed by washing out bacterial contamination. This protocol has been designed to be easily implemented into any lab environment, and it can also be scaled up for use with multiple samples and applicable to a variety of samples with the presence of microbes. We validated this protocol by successfully generating a barcoded library using the 10× Genomics microfluidic platform from tissue subjected to this procedure. This workflow was developed to provide an accessible alternative to instrument-based approaches (e.g., fluorescent cell sorting) and will expand the ability of researchers to perform experiments such as sNucRNA-seq and sNucATAC-seq on inherently heterogeneous plant tissue samples.


The Role of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in the Context of Aneurysmal Subarachnoid Hemorrhage (aSAH)-A Prospective Observational Study.
Outcome after aneurysmal subarachnoid hemorrhage (aSAH) is highly variable and largely determined by early brain injury and delayed cerebral ischemia (DCI). Soluble urokinase plasminogen activator receptor (suPAR) represents a promising inflammatory marker which has previously been associated with outcome in traumatic brain injury and stroke patients. However, its relevance in the context of inflammatory changes after aSAH is unclear. Here, we aimed to characterize the role of circulating suPAR in both serum and cerebrospinal fluid (CSF) as a novel biomarker for aSAH patients. A total of 36 aSAH patients, 10 control patients with unruptured abdominal aneurysm and 32 healthy volunteers were included for analysis. suPAR was analyzed on the day of admission in all patients. In aSAH patients, suPAR was also determined on the day of DCI and the respective time frame in asymptomatic patients. One- and two-sample t-tests were used for simple difference comparisons within and between groups. Regression analysis was used to assess the influence of suPAR levels on outcome in terms of modified Rankin score. Significantly elevated suPAR serum levels (suPAR-SL) on admission were found for aSAH patients compared to healthy controls, but not compared to vascular control patients. Disease severity as documented according to Hunt and Hess grade and modified Fisher grade was associated with higher suPAR CSF levels (suPAR-CSFL). In aSAH patients, suPAR-SL increased daily by 4%, while suPAR-CSFL showed a significantly faster daily increase by an average of 22.5% per day. Each increase of the suPAR-SL by 1 ng/ml more than tripled the odds of developing DCI (OR = 3.06). While admission suPAR-CSFL was not predictive of DCI, we observed a significant correlation with modified Rankin's degree of disability at discharge. Elevated suPAR serum level on admission as a biomarker for early inflammation after aSAH is associated with an increased risk of DCI. Elevated suPAR-CSFL levels correlate with a higher degree of disability at discharge. These distinct relations and the observation of a continuous increase over time affirm the role of inflammation in aSAH and require further study.


Cholera in Brazil during 1991-1998: socioeconomic characterization of affected areas.
The paper describes the trends in, and spatial patterns of, the incidence of cholera in Brazil from 1991 to 1998. During this period, 161,432 cases and 1,296 deaths from cholera were reported. The poorest (North and Northeast) regions of the country had the highest morbidity and mortality rates. The remaining regions had self-limited outbreaks. Seventy-eight percent of affected municipalities had populations of fewer than 30,000, and about 65% of them lived in rural areas. The affected municipalities of the North and Northeast regions had consistent indications of deprivation: average Human Development Index was 0.41, infant mortality rate 90.3%, average life expectancy 59.4 years, and adult illiteracy rate 46.5%. The epidemiological profile of the disease in Brazil highlights intra- and inter-regional socioeconomic differentials in the country and indicates the importance of planning and implementing public-health interventions and specific policies aimed at reducing health inequalities.


[Can contact nurses point the way to competence in practice? Nurses as practice mentors in nursing education].
The contact nurse is a central person as a carrier of knowledge and experience in nursing practice, which is important that the student nurse has access to. In order to gain insight into the passage of knowledge between 3 contact nurses and their students, I have carried out a qualitative investigation. The method chosen is that of participation, open observation and semi-structured interviews. While guiding the student, the contact nurse made explicit her way of judging specific nursing situations. She appealed to the use of perceptive insight, and made explicit the complexity in an "everyday situation" in nursing practice. Counselling in patient-situations thus reflects the value of the traditional master-apprentice roles. Professional argumentation delving deeper than more down-to-earth judgements, appears to be absent from the investigation. This shows the importance of a greater degree of reflection in the contact nurse's role as a counsellor.


Double V-Y Island Pedicle Flap for Dorsal Hand Reconstruction Following Mohs Micrographic Surgery.
Medium to large defects on the dorsal hand pose a reconstructive challenge following dermatologic surgery. Repairs in this location can be complicated by a paucity of adjacent tissue reservoirs, competing tension vectors, thin cutaneous tissue, and superficial tendons and vasculature. In such cases, a double V-Y island pedicle flap is an effective reconstructive solution. It preserves hand function, harnesses local tissue with a robust blood supply, facilitates complete closure, and provides skin that closely matches the original's color and texture. Here, we present the repair of a medium to large dorsal hand defect after Mohs micrographic surgery for melanoma in situ, using a double V-Y island pedicle flap.


Unidirectional emission and nanoparticle detection in a deformed circular square resonator.
We propose a novel deformed square resonator which has four asymmetric circular sides. Photons leak out from specific points, depending on the interplay between stable islands and unstable manifolds in phase space. By carefully breaking the mirror reflection symmetry, optical modes with strong chirality approaching 1 and unidirectional emission can be achieved simultaneously. Upon binding of a nanoparticle, the far-field emission pattern of the deformed microcavity changes drastically. Due to the EP point of the degenerate mode pairs in the deformed cavity, chirality-based far-field detection of nanoparticles with ultra-small size can be realized.


Characterization of Candida species isolated from cases of lower respiratory tract infection.
(1) To identify and characterize the Candida species isolates from lower respiratory tract infection. (2) to determine the rate of isolation of Candida species from sputum samples. This study was carried out in the Department of Microbiology, Manipal Teaching Hospital, Pokhara, Nepal from June 2002 to January 2003. A total of 462 sputum samples were collected from patients suspected lower respiratory tract infection. The samples were processed as Gram staining to find out the suitability of the specimen, cultured on Sabouraud's Dextrose Agar (SDA) and also on blood agar and chocolate agar to identify the potential lower respiratory tract pathogens. For the identification of Candida, sputum samples were processed for Gram stain, culture, germ tube test, production of chlamydospore, sugar fermentation and assimilation test. For the identification of bacteria, Gram stain, culture, and biochemical tests were performed by standardized procedure. Out of 462 samples, 246 (53.24%) samples grew potential pathogens of lower respiratory tract. Among them Haemophilus influenzae 61(24.79%) and Streptococcus pneumoniae 57 (23.17%) were the predominant bacterial pathogens. Candida species were isolated from 30 samples (12.2%). The majority of Candida species amongst the Candida isolates were Candida albicans 21(70%) followed by Candida tropicalis 4(13.33%). Candida krusei 3(10%), Candida parapsilosis 1(3.33%) and Candida stellatoidea 1(3.33%). The highest rate of isolation of Candida was between the age of 71 and 80. Candida isolation from sputum samples is important as found in the present study in which Candida species were the third most common pathogen isolated from patients with lower respiratory tract infection.


Double oxidation localizes spin in a Ni bis-phenoxyl radical complex.
The electronic structure of a doubly oxidized Ni salen complex NiSal(tBu) (Sal(tBu) = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-(1R,2R)-diamine) has been investigated by both experimental and theoretical methods. The doubly oxidized product was probed by resonance Raman spectroscopy, UV-vis-NIR, and EPR to determine the locus of oxidation as well as the spectroscopic signature of the complex. It was determined that double oxidation of NiSal(tBu) affords a bis-ligand radical species in solution via the presence of phenoxyl radical bands at ν(7a) (1504 cm(-1)) and ν(8a) (1579 cm(-1)) in the Raman spectrum, and the loss of the intense NIR transition reported for the mono-radical complex (Angew. Chem., Int. Ed., 2007, 46, 5198). Spectroscopic experiments, complemented by DFT calculations, show that the two radical spins are predominantly localized on the phenolate moieties, in opposition to the extensive delocalization over the ligand framework observed for the mono-radical analogue.


Polarization-electric field hysteresis of ferroelectric PVDF films: comparison of different measurement regimes.
Polarization-electric field hysteresis is an important property of ferroelectric materials. Different experimental procedures and measurement regimes are demonstrated and frequently used in order to determine this hysteresis behavior. For the characterization of the poling behavior of ferroelectric polymers it is common to analyze the poling current and separate current contributions, which are based on charging the sample capacitance as well as on conductivity. Experimentally this can be realized with two different measurement regimes, either poling of the sample with bipolar cycles or with a sequence of bipolar and unipolar cycles of the applied electric field. Here, we demonstrate the comparison of both measurement routines by performing poling experiments on the same ferroelectric PVDF sample.


Spontaneous clearance of viral infections by mesoscopic fluctuations.
Spontaneous disease extinction can occur due to a rare stochastic fluctuation. We explore this process, both numerically and theoretically, in two minimal models of stochastic viral infection dynamics. We propose a method that reduces the complexity in models of viral infections so that the remaining dynamics can be studied by previously developed techniques for analyzing epidemiological models. Using this technique, we obtain an expression for the infection clearance time as a function of kinetic parameters. We apply our theoretical results to study stochastic infection clearance for specific stages of HIV and HCV dynamics. Our results show that the typical time for stochastic clearance of a viral infection increases exponentially with the size of the population, but infection still can be cleared spontaneously within a reasonable time interval in a certain population of cells. We also show that the clearance time is exponentially sensitive to the viral decay rate and viral infectivity but only linearly dependent on the lifetime of an infected cell. This suggests that if standard drug therapy fails to clear an infection then intensifying therapy by adding a drug that reduces the rate of cell infection rather than immune modulators that hasten infected cell death may be more useful in ultimately clearing remaining pockets of infection.


Dioscin inhibits colon cancer cells' growth by reactive oxygen species-mediated mitochondrial dysfunction and p38 and JNK pathways.
Dioscin is a natural steroid saponin derived from several plants that shows potent anticancer effects against a variety of cancer cells. Here, we investigated the antitumor effect of dioscin against human colon cancer cells and evaluated the molecular mechanism involved in this process. The cell cytotoxicity was studied by the MTT assay and BrdU incorporation. The proapoptotic mechanism of dioscin was characterized by flow cytometry analysis. A western blot and an immunofluorescence staining were used to investigate how dioscin induces apoptosis in vitro. In our study, dioscin could significantly inhibit the growth of colon cancer cells in a time-dependent and dose-dependent manner. Dioscin induces apoptosis and reactive oxygen species (ROS) generation, promoting the disruption of mitochondrial membrane potential, Bax translocation to the mitochondria, cytochrome C release to cytosol, activations of caspase-9/3, PARP cleavage, and subsequent apoptosis. Dioscin-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38-MAPK. N-acetyl-L-cysteine, a scavenger of ROS, significantly reversed dioscin-induced cell death and activation of JNK and p38. Collectively, the data indicate that the induction of apoptosis by dioscin is mediated through ROS proteins, which are critical upstream signals for JNK/p38-MAPK activation.


Parental Emotion Regulation and Mentalization in Families of Children With ADHD.
Objective: The aim of this study is to examine the role of parental emotion regulation (ER) and parental mentalization as possible contributors to hostile and coercive parenting in families of children with ADHD. Method: Seventy-four Israeli families (64 mothers and 48 fathers) seeking parent training for child ADHD completed measures during the intake session. Measures included parental ER; parental mentalization; hostile, coercive, and submissive parenting; and child symptoms. Results: Findings suggested a relationship between parental ER and coercive parenting independent of child age, symptom level, and parental mentalization. Parental mentalization appeared to buffer against hostility specifically among parents with low ER capacities. Patterns were parallel for mothers and fathers. Conclusion: Study findings highlight the importance of evaluating and addressing parental ER in interventions attempting to reduce coercive parenting. The findings also highlight the potential role of parental mentalization as a protective mechanism against hostile parenting in families of children with ADHD.


[Health service in Zagreb a century ago (1907-1909)].
Throughout a short period of only 3 years (1907-1909) a whole range of medical institutions were founded. They were important not only for Zagreb but for the whole Croatia: the first human bacteriological institute, children's dispensary, first aid station, orthopedic and military hospitals, sanatorium for the affluent and sanatorium for patients with tuberculosis. The state hospital began to be built but was not finished. That was how Zagreb started becoming a real sanitary metropolis a century ago.


Spider toxin (JSTX) on the glutamate synapse.
A new neurotoxin (JSTX) was separated from spider (Nephila clavata, Joro spider) venom. JSTX irreversibly suppressed the excitatory postsynaptic potential (EPSP) and the glutamate potential in the lobster neuromuscular junction with high degree of specificity. The threshold concentration for suppressing EPSPs corresponds to a small fraction of the toxin in a venom gland, roughly estimated as low as 10(-10) M/l. 10(-10) M/l. In the giant synapse of squid stellate ganglion JSTX suppressed EPSPs without affecting the antidromic response. Glutamate-induced membrane depolarization was blocked by JSTX. In mammalian brain slice preparation, JSTX suppressed the orthodromic spike response but failed to affect on the antidromic spike in the hippocampal pyramidal neuron of CA1 and CA3 region. The above results strongly support the view that the squid giant synapse and synapses in the hippocampal pyramidal neuron are mediated by glutamate.


[The role of changes in tissue redox-status in mechanism of paraneoplasia].
To specify mechanisms of paraneoplastic alterations of redox-status of tissues in experimental malignant tumor growth, we investigated electronic paramagnetic centers of blood, skeletal muscle and liver with electronic paramagnetic resonance (EPR) method. We also studied the concentration and activity of antioxidant enzymes. Our experiments on adult white male rats of mixed population with sarcoma C-45 and mice with Ehrlich carcinoma have shown that malignant tumor growth leads to enhanced lipid peroxidation (LPO): production of potent LPO promoters - Fe2+, Mn+2+, NO, ubiquinone; depression of antioxidant defence - reduced production of total ceruloplasmin, elevated blood levels of oxidized ceruloplasmin and enhanced catalase activity. It is suggested that malignant tumor growth is associated with marked paraneoplastic shifts in tissue redox-potential. These alterations are involved in mechanisms of paraneoplastic changes of red cells, microhemocirculation and circulation intensity. All these interrelated processes result in generalized paraneoplastic hypoxia of the organs and tissues. Basing on our and literature data, we propose an original scheme of the mechanisms of paraneoplastic disorders of tissue redox-status, microcirculation and erythrocytes.


Nutrient-dependent enhancement of rectal sensitivity in irritable bowel syndrome (IBS).
Food-related gastrointestinal symptoms are common in irritable bowel syndrome (IBS), but the mechanisms behind this are unclear. Enhanced colorectal sensitivity after duodenal lipid administration in IBS patients has been demonstrated. However, the effects of a regular meal on colorectal sensitivity in these patients and the importance of the composition of the meal are not known. On two separate days, 10 IBS patients and 11 controls randomly received a liquid meal (800 kcal), containing 60% calories from fat (fatty meal) or carbohydrate (carbohydrate meal). Using a barostat rectal sensitivity was assessed during four separate distension sequences before, immediately after and 30 and 60 min after the meal. In the patients, the discomfort (P = 0.04) and the pain thresholds (P = 0.007) were gradually reduced after the fatty meal, whereas only a tendency in the same direction was seen after the carbohydrate meal. In patients VAS ratings for pain increased after the fatty meal (P = 0.03), but not after carbohydrates. In the controls, sensory thresholds were not affected by the meals. In IBS, a liquid meal enhances rectal sensitivity, and this seems to be partly nutrient dependent as a fatty meal has more pronounced effects than a carbohydrate meal. This might be of relevance for their postprandial symptoms.


Predictors of outcome after nonoperative and operative treatment of adhesive capsulitis.
Few studies regarding adhesive capsulitis have concurrently evaluated nonoperative and operative treatment. The objectives were to evaluate the efficacy of operative and nonoperative treatment of adhesive capsulitis and to determine predictors of clinical outcome. Cohort study; Level of evidence, 3. At minimum 24 months' follow-up, 85 patients underwent self-assessment using the Simple Shoulder Test (SST) and American Shoulder and Elbow Surgeons (ASES) score, including 24 patients treated operatively. Mean number of yes responses on the SST improved from 4.0 ± 2.7 at initial presentation to 9.9 ± 2.8 at final follow-up (P < .0001). Patients who received nonoperative treatment and patients who underwent surgery demonstrated similar improvements on the SST. For the entire cohort, forward elevation and external rotation at the side improved from 119° ± 20° to 152° ± 15° and from 29° ± 18° to 46° ± 11° (P < .0001), respectively, between initial presentation and discharge from treatment. Internal rotation to the back improved from the gluteal area to the thoracolumbar junction (P < .0001). Improvements in forward elevation and external rotation were greater for patients undergoing surgery. After nonoperative treatment, patients with diabetes had a lower final SST than patients without diabetes (P < .05). For the entire cohort, initial SST predicted final SST (P < .05), and a shorter duration of symptoms predicted a higher final ASES score (P < .05). Younger patients (P < .001) and those with a lower initial SST (P < .05) were more likely to undergo surgery. A multimodal nonoperative treatment program is effective for most patients with adhesive capsulitis. Patients who do not improve, including those with diabetes, respond well to manipulation and arthroscopic release. Residual motion deficits at discharge from treatment do not appear to affect longer-term clinical outcome.


Multidimensional outcome assessment in cerebral palsy: is it feasible and relevant?
To examine feasibility and relevance of a multidimensional outcome assessment approach using instrumented 3-dimensional gait analysis, via the Gillette Gait Index (GGI), and a set of validated functional and health-related quality of life tools in diplegic cerebral palsy children, before introduction as a nationwide evaluation set. A 3-year prospective government-funded multicenter study was conducted, recruiting patients during a 9-month period classified using the Gross Motor Function Classification System and the Rodda et al sagittal walking patterns. The Gross Motor Classification System Dimensions D and E, the 10-level Gillette Functional Assessment Questionnaire, the Energy Expenditure Index (EEI), the GGI out of 3D gait analysis, and health-related quality of life, assessed by self or proxy with the questionnaire "Vècu et Santè Perçu de l'Adolescent," were selected for the study. Cross-sectional data subset at inclusion of 160 spastic diplegic cerebral palsy patients, the largest series in our country, 6 to 18 years old (mean age, 11.0 years), are reported. The GGI correlated significantly (P < 0.001) with the Gross Motor Classification System, the Functional Assessment Questionnaire, and the EEI for all the patients, and all but one (EEI) correlated if grouped according to Gross Motor Function Classification System or Rodda. No systematic correlation was found between the quality of life scores and the other outcome tools. The outcome evaluation instrument set tested in our study helps to adopt common tools, to be integrated in an evidence-based practice and to compare health status and treatment outcome between countries, specifically in different linguistic environments like in European countries.


Comparison of the Protective Effect of Salvia officinalis and Rosmarinus officinalis Infusions Against Hepatic Damage Induced by Hypotermic-Ischemia in Wistar Rats.
We aimed to evaluate, in this study, the effect of Rosmarinus officinalis L. and Salvia officinalis L. in the amelioration of liver hypothermic conservation in male wistar rats. Livers from each rat were collected and preserved for 24 h at 4 °C in a Krebs solution with or without increasing doses of sage or rosemary infusions (25, 50, and 100 mg/mL). Liver hypothermic conservation induced a decrease in the activity of superoxide dismutase, catalase, and glutathione peroxidase and a significant increase in lipid peroxidation. S. officinalis L. infusion at 25 mg/mL normalized this oxidative disturbance but appears toxic at 50 and 100 mg/mL due to the presence of large amount of pyrogallol which contribute to the cytoplasmic alteration of hepatocytes. The addition of different doses of R. officinalis L. infusion induced an increase in catalase and glutathione peroxidase activities and a decrease in lipid peroxidation with an amelioration of cellular architecture. In conclusion, increasing doses of R. officinalis L. infusion protect against hepatic hypotermic-ischemia while S. officinalis L. infusion could have an hepatoprotective role when administrated at lower dose.


Transforming growth factor-beta1 release from a porous electrostatic spray deposition-derived calcium phosphate coating.
This study evaluated the utilization of a porous coating, derived with electrostatic spray deposition (ESD), as a carrier material for transforming growth factor-beta1 (TGF-beta1). A porous beta-tricalcium phosphate coating was deposited with ESD, and 10 ng of (125) I-labeled TGF-beta1 was loaded on the substrates. A burst release during the first hour of incubation of >90% was observed, in either culture medium or phosphate-buffered saline (PBS). Ninety-nine percent of the growth factor was released after 10 days of incubation. All samples were able to inhibit epithelial cell growth, indicating that the growth factor had remained bioactive after release. Thereafter, osteoblast-like cells were seeded upon substrates with or without 10 ng of TGF-beta1. While proliferation of osteoblast-like cells was increased on TGF-beta1-loaded substrates, differentiation was inhibited or delayed. In conclusion, a porous ESD-derived calcium phosphate coating can be used as a carrier material for TGF-beta1, when a burst release is desired.


[Organ procurement. The Clermont-Ferrand experience].
The authors report the experience of a new kidney collection centre organised at Clermont-Ferrand, which rapidly became involved in the collection of multiple organs. The difficulties encountered during the collection of organs from the first 30 cadavres are presented: 19 kidneys were not grafted, sometimes for anatomical reasons, but especially because of surgical reasons (during the following period, this number fell to 3 for a series of 21 cadavres). 13 hearts and 2 livers were also removed. In conclusion, the authors stress that such organ collection centres can only be created when transplantations are also performed, because of inevitable psychological reasons affecting both the health care team as well as the population of the region.


Shiftworkers in developing countries: health and well-being and supporting measures.
Developing countries currently represent approximately 79% of the world population. Living and working conditions in middle and low income countries are harder and worse than for workers in industrialized countries. In developing countries, workers usually face more dangerous workplaces and unhealthy environmental and occupational conditions than those of industrial countries. Shiftworkers can face even more difficulties, due to constraints caused by their working time and consequences on health. Occupational health actions oriented by health policies were implemented during the 1990s in several Asian countries and in Brazil. these actions are important to promote workers' health. The general aims of this report are: a) to discuss topics related to equity and health; b) to present the main items of international and Brazilian legislation for shiftworkers; and c) to review general and specific measures of occupational health for shiftworkers in developing countries. In order to have equity on health and well-being, supporting measures should encompass micro and macro improvements at local, regional and national levels. Governmental and non-governmental organizations, professional bodies, labor unions, research institutes, universities, technical schools and syndicates, would play important roles to achieve these goals.


Biomechanical response of retrodiscal tissue in the temporomandibular joint under compression.
The present study was conducted to investigate the biomechanical response of bovine retrodiscal tissue of the temporomandibular joint (TMJ) in compression. Using 10 retrodiscal tissues obtained from 10 cattle, the viscoelastic response of the retrodiscal tissue was evaluated by means of stress-strain analyses. These compressive strains were produced at a high strain rate and were kept constant during 5 minutes for stress-relaxation. Although the stress-strain relationship in the retrodiscal tissue was essentially nonlinear represented by a quadratic or power function of strain, a linear model could reasonably represent its elastic property. In this case, the instantaneous and relaxed moduli were 1.54 and 0.21 MPa, respectively. The stress-relaxation curve showed a marked drop in load during the initial 10 seconds, and the stress reached a steady nonzero level. Furthermore, when using Kelvin's model, a satisfactory agreement can be obtained between the experimental and theoretical stress-relaxation curves. It is concluded that bovine retrodiscal tissue has a great capacity for energy dissipation during stress-relaxation, although it has little or no function to pull the articular disc back.


A simple computational method to estimate stance velocity in running.
Running dynamical analyses typically approximate a runner's stance velocity as the average stride cycle velocity (the average running speed). That approximation necessarily overestimates stance velocity and biases subsequent results. Stance velocity is crucial in kinetic spring-mass analyses of running, where approximation of a runner's impact angle and calculation of leg stiffness require that input. Here, a new method is presented to approximate a runner's stance velocity via measurement of contact and flight times with the runner's average speed, leg length or height, and mass. This method accurately estimated the stance velocity of simulated spring-mass systems across typical running speeds of 3.5-5.5 m s-1 (r>0.99) and more accurately estimated the impact angle and leg stiffness. The method also accurately estimated the peak horizontal ground reaction force across speeds (r=0.82), but the bias magnitude increased with speed. Robustness of the new method was further tested for runners at 2.5, 3.5 and 4.5 m s-1, and the new method provided steeper impact angles than those from traditional estimates and correspondingly higher leg stiffnesses, analogous to the observations in the simulation models. Horizontal ground reaction force estimates were weakly correlated in braking and propulsion. They were improved by a corrective algorithm, but the intra- and inter-individual variation persisted. The directionality and magnitude of angle and stiffness estimates in the human runners were similar to simulations, suggesting the new method more accurately modeled runners' spring-mass characteristics by using an accurate approximation of stance velocity. The new method can improve traditional kinetic analyses of running where stance velocity recordings are not captured with kinematic recordings and extend opportunities for accurate field-based analyses with limited measurement sources.


On low-lying excited states of extended nanographenes.
Low-lying excited states of planarly extended nanographenes are investigated using the long-range corrected (LC) density functional theory (DFT) and the spin-flip (SF) time-dependent density functional theory (TDDFT) by exploring the long-range exchange and double-excitation correlation effects on the excitation energies, band gaps, and exciton binding energies. Optimizing the geometries of the nanographenes indicates that the long-range exchange interaction significantly improves the CC bond lengths and amplify their bond length alternations with overall shortening the bond lengths. The calculated TDDFT excitation energies show that long-range exchange interaction is crucial to provide accurate excitation energies of small nanographenes and dominate the exciton binding energies in the excited states of nanographenes. It is, however, also found that the present long-range correction may cause the overestimation of the excitation energy for the infinitely wide graphene due to the discrepancy between the calculated band gaps and vertical ionization potential (IP) minus electron affinity (EA) values. Contrasting to the long-range exchange effects, the SF-TDDFT calculations show that the double-excitation correlation effects are negligible in the low-lying excitations of nanographenes, although this effect is large in the lowest excitation of benzene molecule. It is, therefore, concluded that long-range exchange interactions should be incorporated in TDDFT calculations to quantitatively investigate the excited states of graphenes, although TDDFT using a present LC functional may provide a considerable excitation energy for the infinitely wide graphene mainly due to the discrepancy between the calculated band gaps and IP-EA values. © 2017 Wiley Periodicals, Inc.