Platelet-activating factor stimulates metabolism of phosphoinositides via phospholipase A2 in primary cultured rat hepatocytes.
Addition of platelet-activating factor (PAF) to cells doubly labeled with [14C]glycerol plus [3H]arachidonic acid resulted in a transient decrease of [14C]glycerol-labeled phosphatidylinositol (PI) and a transient increase of [14C]glycerol-labeled lysophosphatidylinositol (LPI). [3H]Arachidonate-labeled PI, on the other hand, decreased in a time-dependent manner. The radioactivity in phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, and phosphatidylserine did not change significantly. The 3H/14C ratio decreased in PI in a time-dependent manner, suggesting the involvement of a phospholipase A2 activity. Although PAF also induced a gradual increase of diacylglycerol (DG), the increase of [14C]glycerol-labeled DG paralleled the loss of triacyl [14C]glycerol and the 3H/14C ratio of DG was 16 times smaller than that of PI. Thus, DG seemed not to be derived from PI. In myo- [3H]inositol-prelabeled cells, PAF induced a transient decrease of [3H]phosphatidylinositol-4,5-bis-phosphate (TPI) and [3H]phosphatidylinositol-4-phosphate (DPI) at 1 min. PAF stimulation of cultured hepatocytes prelabeled with 32Pi induced a transient decrease of [32P]polyphosphoinositides at 20 sec to 1 min. [32P]LPI appeared within 10 sec after stimulation and paralleled the loss of [32P]PI. [3H]Inositol triphosphate, [3H]inositol diphosphate, and [3H]inositol phosphate, which increased in a time-dependent manner upon stimulation with adrenaline, did not accumulate with the stimulation due to PAF. These observations indicate that PAF causes degradation of inositol phospholipids via phospholipase A2 and induces a subsequent resynthesis of these phospholipids.


Investigation of the Manufacturing Orientation Impact on the Mechanical Properties of Composite Fiber-Reinforced Polymer Elements in the Fused Filament Fabrication Process.
This article examines the mechanical properties and compatibility of selected composite materials produced with RP technology and the FFF-fused filament fabrication process. The article scales sophisticated modern materials based on PLA-polylactic acid-plastic and its composite variants. The research is carried out on the 3D FFF printer Felix 3.1 with a dual extruder, which works on the "open-source" principle. In this research, elements of the paradigm and methodology of the processing technology for RP were applied; they were implemented according to EN ISO 527 and ISO 2602 standards. The aim of this study was to investigate the impact of 3D-printing strategy on the mechanical properties of 5 types of PLA composites. The results of this research solve the material compatibility problem, primarily through experimental testing of different combinations of filaments in different printing directions. Analysis of the experimental data showed correlations between the choice of printing strategy and mechanical properties, mainly tensile strength of the selected filaments. The research results show the influence of the printing orientation on mechanical properties of 3D printed samples: parts extruded in length orientation showed higher values of tensile strength compared to parts made in width and height. The CarbonPLA material exhibited 10 times higher tensile strength when printed in length compared to samples.


Screening for temporomandibular disorders in dental practice.
A simple screening procedure to determine evidence of a temporomandibular disorder (TMD) in a patient is presented. The current view is that dentists are responsible for the recognition and management of these disorders. The dentist should therefore perform a TMD screening examination on every patient and document the patient's functional status. If this is not known then it is impossible to discuss with the patient the possible implications of proposed dental treatment which could potentially worsen a pre-existing TMD. Unless functional status is documented and informed consent obtained from the patient prior to proceeding with dental treatment, the dentist may be held liable should TMD problems develop during or after the treatment.


Knowledge and attitudes of primary care nurses and midwives towards health promotion in rural South Africa.
This study was designed to study knowledge, attitudes and views about health promotion among nurse clinicians in rural South Africa. The sample included 90 nurse clinicians (73 primary health care nurses and 17 midwives) in the age range of 24 to 59 years (M age 38.4 yr., SD = 9.3) in the Northern Province. Results indicate that nurses (66.6%) had an inadequate knowledge score on health promotion in this sample. Higher knowledge scores on health promotion were not associated with age and years of experience. However, male nurses had significantly higher knowledge scores on health promotion than female nurses. The majority strongly supported the centrality of their role in health promotion acknowledging the time constraints involved. Better knowledge on health promotion was associated with more positive views on health promotion. More nurses had a satisfactory positive attitude towards health promotion (63.3%) than knowledge about health promotion (33.3%). Finally, the study found that compliance with health promotion was seen as a problem but health counselling was nevertheless seen as cost effective.


Amyloid-β Derived from the Brain of the Alzheimer's Disease Transgenic Mouse Is Resistant to Proteolytic Digestion Due to Its Conformation.
The main pathological feature of Alzheimer's disease (AD) is the formation of abundant amyloid-β (Aβ) plaques in the human brain. Studies have reported that Aβ from the AD brain is resistant to proteolytic digestion, which may explain why Aβ cannot be readily eliminated from this organ. However, there are only a few studies that address this important question. We used the AD transgenic mouse (APP/PS1) model to show that Aβ derived from the brain of the old mouse is resistant to proteolytic digestion. This was in contrast to the proteinase K-sensitive human Aβ peptide, whose amino acid sequence was identical to that of AD mouse-derived Aβ but whose conformation was different (i.e., the native protein, but not the peptide, folded into a three-dimensional conformation). To address this question, we denatured AD mouse-derived Aβ with urea and found that Aβ became proteinase K-sensitive. This phenomenon was concentration-dependent, and these results were confirmed by another protein denaturant, guanidinium hydrochloride. We recovered the conformation of the denatured AD mouse-derived Aβ by eliminating urea and adding the human Aβ peptide, and we found that human Aβ was converted to the proteinase K-resistant form in the presence of partially undenatured AD mouse-derived Aβ. However, upon the addition of the rat Aβ peptide, there were no Aβ proteinase K-resistant fragments. Our results show that the resistance of AD mouse-derived Aβ to proteolytic digestion is dependent on the three-dimensional conformation of Aβ. In summary, this study provides new insights on why Aβ plaques fail to be degraded in the human brain.


A key role for the subunit SUR2B in the preferential activation of vascular KATP channels by isoflurane.
It has been postulated that isoflurane, a volatile anaesthetic, produces vasodilatation through activation of ATP-sensitive K+ (KATP) channels. However, there is no direct evidence for the activation of vascular KATP channels by isoflurane. This study was conducted to examine the effect of isoflurane on vascular KATP channels and compare it with that on cardiac KATP channels. Effects of isoflurane on KATP channels were examined in aortic smooth muscle cells and cardiomyocytes of the mouse using patch clamp techniques. Effects of the anaesthetic on the KATP channels with different combinations of the inward rectifier pore subunits (Kir6.1 and Kir6.2) and sulphonylurea receptor subunits (SUR2A and SUR2B) reconstituted in a heterologous expression system were also examined. Isoflurane increased the coronary flow in Langendorff-perfused mouse hearts in a concentration-dependent manner, which was abolished by 10 microM glibenclamide. In enzymically-dissociated aortic smooth muscle cells, isoflurane evoked a glibenclamide-sensitive current (i.e. KATP current). In isolated mouse ventricular cells, however, isoflurane failed to evoke the KATP current unless the KATP current was preactivated by the K+ channel opener pinacidil. Although isoflurane readily activated the Kir6.1/SUR2B channels (vascular type), the volatile anesthetic could not activate the Kir6.2/SUR2A channels (cardiac type) expressed in HEK293 cells. Isoflurane activated a glibenclamide-sensitive current in HEK293 cells expressing Kir6.2/SUR2B channels. Isoflurane activates KATP channels in vascular smooth muscle cells and produces coronary vasodilation in mouse hearts. SUR2B may be important for the activation of vascular-type KATP channels by isoflurane.


The effect of ractopamine hydrochloride on the carcass cutting yields of finishing swine.
This study was designed to evaluate growth performance, carcass cutting yield, and processing characteristics of boneless hams and bellies from finishing pigs fed diets containing 0, 5, 10, or 20 ppm of the phenethanolamine ractopamine hydrochloride (RAC). Sixty pigs were blocked by starting weight and randomly assigned to pens (four pigs/pen) within each of three blocks. Treatments were then randomly assigned to the pens to total six pens of the 0-ppm level and three pens each at the 5-, 10-, and 20-ppm RAC levels. Weight gain and feed consumption were monitored and animals were slaughtered by weight block after approximately 48 d on trial. Slaughter weight, ADG, and feed/gain were improved (P less than .05) for RAC treatments. Dressing percentage was higher and increased linearly (P less than .05) for RAC treatments. Carcass weight, length, leaf fat weight, backfat thickness, loin eye area, and color, marbling, and firmness of the longissimus were evaluated. The RAC-treated carcasses were heavier (P less than .05) and loin eye area increased linearly (P less than .05). One side of each carcass was fabricated using National Association of Meat Purveyors specifications. Trimmed hams and loins from the RAC treatments were heavier (P less than .05) than those from control animals. No differences (P greater than .05) in carcass cutting yield (percentage of trimmed primal cuts) were observed between treatments. However, trimmed hams and loins from the 20-ppm RAC treatment represented a greater (P less than .05) percentage of carcass weight than did those from control animals. Ractopamine did not affect raw belly or bacon characteristics (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of "personalized oncology".
"Personalized oncology" is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of "radiomics/radiogenomics". Diffusion-weighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that "one size fits all". It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in "personalized oncology".


A difference in larval mosquito size allows a biocontrol agent to target the invasive species.
As the global temperature rises in the coming decades, Aedes albopictus is expected to invade and establish in South East England, where Culex pipiens is currently the most common native mosquito species. Biocontrol measures that use local cyclopoid copepods against Ae. albopictus may be compromised if the copepods prefer alternate Cx. pipiens prey. In this study, I assessed the predation efficiency of Megacyclops viridis copepods against Ae. albopictus larvae from France and larvae that hatched from egg rafts of Cx. pipiens collected in South East England. The experiments were conducted at 15 and 25°C, which are representative of present and future summer temperatures in South East England. Ae. albopictus larvae that survived the course of the experiment in the predator-absent controls were significantly smaller than Cx. pipiens larvae that survived in the absence of predation. The background mortality of Cx. pipiens larvae increased with the 10-degree increase in temperature, and the smaller size of surviving Cx. pipiens larvae at 25°C, relative to survivors at 15°C, suggests that larger Cx. pipiens larvae were more likely to die at the higher temperature setting. Across all experimental treatments, the ratio of copepod body length to mean prey length, based on larval lengths of survivors from the corresponding predator-absent controls, was a significant predictor of the copepod's predation efficiency. Adding temperature setting to the predation efficiency model as a predictor did not improve model fit. Within the mixed prey treatments, the predation efficiency of M. viridis was 34.5 percentage points higher against Ae. albopictus prey than against Cx. pipiens prey. The higher predation efficiency that M. viridis exhibited against invasive Ae. albopictus prey, likely due to the smaller size of these larvae, supports the future use of M. viridis as a biocontrol agent in the United Kingdom.


Comprehensive two-dimensional gas chromatography of polybrominated diphenyl ethers.
Comprehensive two-dimensional gas chromatography with micro electron-capture detection (GCxGC-muECD) was evaluated for the separation of 125 polybrominated diphenyl ethers (PBDEs). From among the six column combinations that were evaluated, DB-1x007-65HT was found to be the most suitable because of: (i) the highest number of BDE congeners separated; (ii) the least decomposition of higher brominated congeners; and (iii) the most suitable maximum operating temperature. The separation of the 125 BDE congeners from five hydroxy- and two methoxy-BDEs and nine other brominated flame retardants (polybrominated biphenyls, tetrabromobisphenol-A, methyl-tetrabromobisphenol-A and hexabromocyclododecane) was also studied. Fluorinated BDEs were found to be valuable internal standards for the determination of BDEs because of their very similar physico-chemical properties and excellent separation from the parent BDEs, mainly in the second dimension. GCxGC-time-of-flight MS and GCxGC-muECD were shown to be useful tools to identify decomposition products of nona- and deca-substituted BDEs, which are formed during the GC run. Three nona-BDEs were shown to be the major decomposition products of BDE 209.


Studies on diarrhea in neonatal calves: the plasma proteins of normal and diarrheic calves during the first ten days of age.
The concentration of serum proteins and plasma fibrinogen were determined in 151 normal and 49 diarrheic calves at intervals from birth to ten days of age. There were significant differences in the concentrations of the various serum proteins in normal calves when the results were analysed at six age intervals. There was no significant relationship between the concentration of the various proteins and the season of the year. Of the diarrheic calves, those that died had significantly lower gamma globulin concentrations than the other calves. Severely diarrheic and dehydrated calves had significantly increased serum albumin and alpha glabulin concentrations and decreased gamma globulin concentrations. No significant variation occurred in total serum protein concentration. Plasma fibrinogen concentrations were similar in normal and diarrheic calves.


Associations of Bone Turnover Markers with Cognitive Function in Patients Undergoing Hemodialysis.
Patients undergoing hemodialysis experience a greater risk of cognitive impairment than the general population, but limited data elucidates the biomarkers on this. We evaluated the association of bone turnover markers on cognitive function among 251 prevalent hemodialysis enrollees in a cross-sectional study. 251 hemodialysis patients (median age = 57.8, 55% men) and 37 control subjects (mean age = 61.2, 56% men) without a prior stroke or dementia diagnosis were enrolled. Serum concentrations of 8 bone markers were analyzed as the association of cognitive function (Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI)) using linear regression analysis. A lower cognitive function was noted in hemodialysis patients compared to control subjects. The receptor activator of nuclear factor kappa-B ligand (RANKL) was the only bone marker found to be associated with cognitive function (MoCA and CASI tests) in hemodialysis patients without a prior stroke or dementia diagnosis. In stepwise multiple linear regression analysis, the association remained significant in MoCA (β = 1.14, 95% CI 0.17 to 2.11) and CASI (β = 3.06, 95% CI 0.24 to 5.88). Short-term memory (β = 0.52, 95% CI 0.01 to 1.02), mental manipulation (β = 0.51, 95% CI 0.05 to 0.96), and abstract thinking (β = 0.57, 95% CI 0.06 to 1.09) were the significant subdomains in the CASI score related to RANKL. Serum RANKL levels were potentially associated with better cognitive function in hemodialysis patients. Further large-scale and prospective studies are needed to confirm our findings.


Hydrolysis, synthesis, and release of acetylcholine in the isolated heart.
The occurrence of unhydrolyzed acetylcholine (ACh) in the cardiac perfusate during vagal stimulation in the absence of cholinesterase inhibition has been demonstrated by several methods. Because some ACh was found unhydrolyzed in the extracellular space for several seconds after vagal stimulation (half-time of decay 2.5 s), it appears that the prolonged time course of the cardiac responses to bursts of vagal activity is determined by a slow rate of transmitter inactivation (diffusion plus hydrolysis) in addition to slowly operating postsynaptic mechanisms mediated by activation of the muscarinic receptor. The neuronal uptake of choline in isolated heart preparations was found to be Na+ dependent, sensitive to hemicholinium 3, and activated by vagal stimulation. Activation occurred after a delay of 1 or 2 min and slowly faded within 5 min after stimulation. Resting release of ACh was insensitive to extracellular Ca2+ and to muscarinic feedback inhibition, in contrast to the evoked transmitter release. Inasmuch as atropine increased ACh release by vagal and field stimulation to the same extent, muscarinic feedback inhibition is likely to occur at postganglionic parasympathetic neurons. Adrenergic agonists and propranolol did not significantly change the release of ACh.


Effects of N-methyl pyrrolidone on the uptake of hypericin in human bladder carcinoma and co-staining with DAPI investigated by confocal microscopy.
Photodynamic diagnosis (PDD) using hypericin (HY), a natural photosensitizer, detects bladder cancer significantly better than white light endoscopy. However, the lipophilicity of HY complicates its administration for clinical applications. Currently, pharmaceutical preparations for HY without plasma protein are being developed. Formulations containing a biocompatible solvent, N-methyl pyrrolidone (NMP) have been shown to enhance the photodynamic therapeutic effects of HY. It was recently reported that, NMP formulations of HY were able to produce significantly higher contrast for fluorescence detection of tumors than albumin-containing HY formulations. This present work hypothesizes that NMP acts both as a solvent and penetration enhancer to improve the delivery of HY into cells by increasing the permeability of cell membranes. This paper reports the use of 3-D confocal microscopy to monitor real-time uptake of HY in human carcinoma. 3-D confocal microscopy was used to investigate the possibility of nuclear localization of HY in MGH cells. The fluorescence of HY was confirmed to be emitted from HY containing cells using spectrometry. The localization of a DNA fluorescent probe 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) was used to confirm the possibility of colocalization of DAPI and HY. The colocalization analysis in the present study suggests that it was very unlikely that HY colocalized in the nucleus that was stained by DAPI. Fluorescein leakage tests showed that 1% NMP changes the permeability of cell membranes, and enhanced the delivery of HY into cells resulting in lower cell survival ratios. Thus, NMP was able to enhance the photodynamic therapeutic effects of HY on cancer cells.


Upregulation of leptin receptor mRNA expression in obese mouse brain.
Leptin receptor gene expression in the brains of lean (+/+) and obese (ob/ob) C57Bl/6 mice was examined using a non-radioactive in situ hybridization detection method. Significant increases in leptin receptor mRNA expression were found in the ventromedial and arcuate hypothalamic nuclei, piriform and olfactory cortices and medial habenular nucleus. There were very minor changes in the amount of leptin receptor mRNA expression in hippocampus proper (CA1-3). Results indicated that leptin receptor is upregulated when there is a lack of functional leptin, as in hereditary obese (ob/ob) mice. It is also suggested that leptin receptor may be an autoreceptor.


Analytic modeling of breast elastography.
The elastic moduli of tumors change during their pathological evolution. Elastographic imaging has potential for detecting and characterizing cancers by mapping the stiffness distribution in tissues. In this paper a micromechanics-based analytical method was developed to detect the location, size, and elastic modulus of a tumor mass embedded in a symmetric two-dimensional breast tissue. A closed-form solution for the strain elastograms (forward problem) was derived. A computational algorithm for the inverse problem was developed for the detection, localization, and characterization of a heterogeneous mass embedded in a breast tissue. Numerical examples were presented to evaluate the proposed method's performance. The detectability of a tumor mass was estimated with respect to lesion location, size, and modulus contrast ratio. It was shown that the micromechanics theory provides a powerful tool for the diagnosis of breast cancer.


Divergent Synthesis of Quinolones and Dihydroepindolidiones via Cu(I)-Catalyzed Cyclization of Anilines with Alkynes.
A unique and efficient method for one-pot synthesis of diverse 4-quinolones from simple and readily available primary anilines and alkynes via Cu(I)-catalyzed direct cyclization has been developed. The (thio)phenols were also found to visible substrates for this reaction. Moreover, an unprecedented synthesis of dihydroepindolidiones has been demonstrated by using secondary anilines as the versatile substrates.


Quantitative charge-tags for sterol and oxysterol analysis.
Global sterol analysis is challenging owing to the extreme diversity of sterol natural products, the tendency of cholesterol to dominate in abundance over all other sterols, and the structural lack of a strong chromophore or readily ionized functional group. We developed a method to overcome these challenges by using different isotope-labeled versions of the Girard P reagent (GP) as quantitative charge-tags for the LC-MS analysis of sterols including oxysterols. Sterols/oxysterols in plasma were extracted in ethanol containing deuterated internal standards, separated by C18 solid-phase extraction, and derivatized with GP, with or without prior oxidation of 3β-hydroxy to 3-oxo groups. By use of different isotope-labeled GPs, it was possible to analyze in a single LC-MS analysis both sterols/oxysterols that naturally possess a 3-oxo group and those with a 3β-hydroxy group. Intra- and interassay CVs were <15%, and recoveries for representative oxysterols and cholestenoic acids were 85%-108%. By adopting a multiplex approach to isotope labeling, we analyzed up to 4 different samples in a single run. Using plasma samples, we could demonstrate the diagnosis of inborn errors of metabolism and also the export of oxysterols from brain via the jugular vein. This method allows the profiling of the widest range of sterols/oxysterols in a single analytical run and can be used to identify inborn errors of cholesterol synthesis and metabolism.


Spatial analysis of histology in 3D: quantification and visualization of organ and tumor level tissue environment.
Histological changes in tissue are of primary importance in pathological research and diagnosis. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue. Conventional histopathological assessments are performed from individual tissue sections, leading to the loss of three-dimensional context of the tissue. Yet, the tissue context and spatial determinants are critical in several pathologies, such as in understanding growth patterns of cancer in its local environment. Here, we develop computational methods for visualization and quantitative assessment of histopathological alterations in three dimensions. First, we reconstruct the 3D representation of the whole organ from serial sectioned tissue. Then, we proceed to analyze the histological characteristics and regions of interest in 3D. As our example cases, we use whole slide images representing hematoxylin-eosin stained whole mouse prostates in a Pten+/- mouse prostate tumor model. We show that quantitative assessment of tumor sizes, shapes, and separation between spatial locations within the organ enable characterizing and grouping tumors. Further, we show that 3D visualization of tissue with computationally quantified features provides an intuitive way to observe tissue pathology. Our results underline the heterogeneity in composition and cellular organization within individual tumors. As an example, we show how prostate tumors have nuclear density gradients indicating areas of tumor growth directions and reflecting varying pressure from the surrounding tissue. The methods presented here are applicable to any tissue and different types of pathologies. This work provides a proof-of-principle for gaining a comprehensive view from histology by studying it quantitatively in 3D.


Results of Harrington instrumentation and fusion in the adult idiopathic scoliosis patient.
Between January 1961 and December 1972, 132 patients over twenty years old with idiopathic scoliosis were surgically treated using Harrington instrumentation and fusion techniques. All patients were seen by us because of curve magnitude or symptoms secondary to scoliosis. The average correction obtained at operation was 48 per cent. Twenty-four patients had early complications. Fifty-two had late complications, the most frequent of which was pseudarthrosis. The majority of patients had significant improvement in symptoms as a result of surgical correction and stabilization.


Gynaecological laparoscopic surgery: eight years experience in the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, Cameroon.
This is a retrospective analysis of eight years of gynaecological laparoscopic surgery in a resource-limited setting. All gynaecological patients managed by laparoscopy at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital from 1 January 2004 to 30 November 2011 were included. Amongst the 9194 gynaecological surgeries performed during the study period, 6.9% (633) were done by laparoscopy. Most of the women underwent an operative laparoscopy (568/592; 95.9%). The most common indication was infertility (415/592; 70.1%). Diagnostic laparoscopies were mostly indicated for chronic pelvic pain (18/24; 75%). The most common surgical finding was tubo-peritoneal adhesions (412/592; 69.6%). A total of 35 patients (35/592; 5.9%) had at least one complication. The mean duration of hospitalization was 3.4 ±1.8 days. The general uptake of gynaecological laparoscopic surgery is low in our setting. The laparoscopic complication rate of 5.9% is encouraging.


Nonlinear elastic response in solid helium: critical velocity or strain?
Torsional oscillator experiments show evidence of mass decoupling in solid 4He. This decoupling is amplitude dependent, suggesting a critical velocity for supersolidity. We observe similar behavior in the elastic shear modulus. By measuring the shear modulus over a wide frequency range, we can distinguish between an amplitude dependence which depends on velocity and one which depends on some other parameter such as displacement. In contrast with the torsional oscillator behavior, the modulus depends on the magnitude of stress, not velocity. We interpret our results in terms of the motion of dislocations which are weakly pinned by 3He impurities but which break away when large stresses are applied.


Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation.
Mycophenolate mofetil (MMF) use may be associated with progressive multifocal leukoencephalopathy (PML). We conducted a retrospective cohort study of 32,757 renal transplant recipients using the United States Renal Data System kidney transplant files for the incidence, prognosis, and clinical features associated with PML occurring after kidney transplant. Subjects were transplanted from January 1, 2000 to July 31, 2004 and followed through December 31, 2004. The incidence density of PML in MMF users was 14.4 cases/100,000 person-years at risk versus 0 for non-MMF users (P=0.11) by log rank test. Factors significantly associated with PML were BK virus infection (22.2% vs. 1.1%), pretransplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%), and use of antirejection medications in the first year (33% vs. 9.2%), all P less than 0.05. PML is rare in the renal transplant population. There was no significant association between PML and MMF, but MMF use in this cohort is too high to accurately assess an association.


Standardization of conditions for the metabolic activation of N-nitrosodiethylamine in mutagenicity tests.
Like all nitrosamines, N-nitrosodiethylamine (NDEA) requires metabolic activation in order to exert its carcinogenic effects. This activation involves cytochrome P450s (CYP), which generates unstable metabolites that react with the DNA of cells in the immediate vicinity of metabolite formation. Although NDEA is carcinogenic, it has been considered a weak mutagen in classic genotoxicity assays. We used optimized Salmonella/mammalian microsome genotoxicity assays to assess the mutagenicity and toxicity of low concentrations of NDEA. Using a fixed concentration of NDEA (36.5 mg/ml), we varied the length of preincubation in the presence of different concentrations of an S9 metabolic activation mixture. Salmonella typhimurium strains TA97 and TA102 were resistant to NDEA-induced mutagenesis, even after a preincubation of up to 120 min and the use of different concentrations of the S9 mix. Strain TA98 was susceptible to mutagenesis by NDEA in the absence of the S9 mix and after preincubation with NDEA for 90 min. When bacteria of this strain were preincubated with NDEA for 60 min, mutagenesis was detected at an S9 mix concentration >9.55 mg/ml. NDEA also induced mutagenesis in strain TA100 after preincubation for 90 or 120 min, and this effect was dependent on the S9 concentration. E. coli strain BH990 also showed a concentration-dependent response, with only 60% of the cells surviving after a 120-min preincubation with NDEA in the presence of 19.1 mg S9 mix/ml.


Variation in the microbiological quality of commercially produced vacuum-packed cooked sliced meat between production and the end of shelf-life.
A study of the microbiological quality of cooked, sliced vacuum-packed meat was undertaken. Three hundred and eighty-one samples were taken (127 sets of three samples) from 55 commercial premises that produced packets of sliced, cooked, vacuum-packed meat for retail sale. The set of three samples consisted of one from the unsliced, cooked meat, one from the sliced product immediately after slicing, and one sliced packet for end of shelf-life testing. Samples were examined for aerobic colony count (ACC), Enterobacteriaceae, Escherichia coli, Listeria, and Salmonella. When compared to current UK guidelines for the quality of ready to eat food, samples were found to be unsatisfactory for ACC, Enterobacteriaceae, and E. coli. Unsatisfactory rates increased at the end of shelf-life compared to the unsliced meat sample results. No samples were positive for Listeria monocytogenes or Salmonella. This data is important for producers setting the shelf-life of their products.


[Chronic kidney disease: contribution to comorbidity in elderly patients with chronic obstructive pulmonary disease].
The aim was to study the prevalence of risk factors for chronic kidney disease (CKD) and frequency of CKD in patients with chronic obstructive pulmonary disease (COPD). 300 patients with a diagnosis of COPD I-IV were examined. A high prevalence of risk factors CKD was revealed, there are close correlations between the risk factors and the age of patients and severity of obstructive disorders and the spectrum of comorbid pathology. The diagnosis of CKD 1-3B stage is set for 47,6 % of the patients. The obtained data determine the necessity of close attention by clinicians to the study of renal function in elderly patients with COPD.


Evaluating traditional and complementary medicines: Where do we go from here?
Traditional and complementary medicines are increasingly considered possible options for prevention and symptomatic treatment of the novel coronavirus, COVID-19. With renewed attention on these therapies from researchers and policy makers alike, the well-documented challenges of evaluating their safety and efficacy are once again of global concern. Between 2005 and 2018, the World Health Organization conducted a series of surveys, in which 88 percent of responding member states confirmed that their biggest challenge in traditional medicine was the need for technical guidance on research and evaluation. As a first step in pursuing this need, our commentary summarizes thirteen international and regional guidance documents by three broad categories on evaluating safety, efficacy, and product quality for market-based approval and distribution of these treatments. We highlight the paucity of updated international recommendations on these subjects and identify gaps that could inform the current evidence base. All available guidance note the need for evidence surrounding the efficacy of these treatments and practices but are also quick to caution against methodological difficulties in the conduct of such evaluations. Evidence suggests that improved evaluation methods on efficacy and effectiveness are crucial toward expanding future research into establishing the cost-effectiveness of these therapies, in the context of shifting acceptance, interest, and integration of traditional medicines into health systems, and as another step toward Universal Health Coverage.


Validation of a semiquantitative food frequency questionnaire for estimation of intakes of energy, fats and cholesterol among Singaporeans.
The aim of this study was to assess the relative validity of a 159-item semiquantitative food frequency questionnaire (FFQ) for use among adult Singaporeans. This FFQ should be able to classify intakes of energy, total fat, saturated fat, polyunsaturated fat, monounsaturated fat and cholesterol into quintiles of intakes for purposes of epidemiological studies. A total of 126 subjects (84 women and 42 men) took part in the study which included an interview using the newly developed FFQ (assess past month's intake) and three 24-h (24 h) recalls (reference method, collected over a period of 1 month). Subjects also collected two 24 h urinary samples for urea from which total nitrogen excretion was assessed to validate protein intake. When compared to the reference method, the FFQ slighty overestimated the intakes of energy, total fat and types of fat as reflected by the difference in means and the ratio of FFQ to 24 h intakes. The overestimation ranged from 1 to 11% of the reference method. Dietary cholesterol was underestimated by 17% by the FFQ. These differences were however, not statistically significant. Pearson's correlation coefficients (95% confidence intervals (CI)) between intakes assessed by FFQ and reference method varied from 0.58 (0.45, 0.69) for total fat to 0.39 (0.23, 0.53) for polyunsaturated fat. Cross-classification into quintiles resulted in correct classification into the same or adjacent quintiles in 70% of subjects, with only one or two subjects being grossly misclassified. Nitrogen (N) intake from the 24 h recalls did not differ significantly from that estimated from the urinary nitrogen excretion. The mean (± SD) difference was 0.0 ± 0.4 g and the Pearson correlation coefficient (95% CI) was 0.55 (0.31, 0.72). It is concluded that the newly developed FFQ is an adequate tool for classifying individuals' intakes into quintiles for epidemiological studies among Singaporean adults.


Is patient safety synonymous with quality nursing care? Should it be? A brief discourse.
Over the course of the past several years, patient safety and the initiatives undertaken to assure it have become highly visible issues in health care delivery. Patient safety is now the focus of national regulatory agencies as well as local health care institutions. At both the national and local levels, significant resources are directed at achieving patient safety goals. As nurses strive to implement and comply with the regulatory directives regarding safe care, has the focus of nursing care shifted from quality nursing care, built on a foundation of caring, of recognizing and attending to a patient's individualized needs, to a base that equates "safe care" with "quality care?" Have safety and quality become synonymous? This shift may indeed be occurring; however, quality nursing care--no matter how safe it is--must include caring as a core value and highlight the integral human relationship between the nurse and the patient.


[Reproduction studies of carboplatin(III)--Intravenous administration to rats during the perinatal and lactation periods].
Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 21 of postpartum at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows: 1. Maternal body weight gains were suppressed during the former part of the lactation period at carboplatin 2 mg/kg and higher. 2. Thymic weights were decreased and lung weights were increased in dams (F0) at carboplatin 2 mg/kg and higher. Further, ovarian weights were reduced in dams (F0) at carboplatin 4 mg/kg. 3. Carboplatin failed to affect the parturition of F0 dams. 4. Carboplatin did not affect the viability of newborns (F1), and postnatal differentiations, early behavioral developments, learning ability, motor activity or emotional development in F1 animals. 5. Carboplatin 4 mg/kg brought a suppression of pituitary weights after mating in F1 male rats and decreases of adrenal and genital organ weights at weaning in F1 female rats, but failed to affect their reproductive ability. 6. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the perinatal and lactation periods. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against dams and 2 mg/kg/day against their offspring.


Survey of nursing research programs in children's hospitals.
Available published literature describing successfully implemented research programs is relatively limited, particularly within children's hospitals. In order to determine the status of research program development within children's hospitals, a mailed survey was sent to 108 free-standing children's hospitals in the United States and Canada. The questionnaire was comprised of questions pertaining to five general sections: (a) institutional demographics; (b) organizational structure for research; (c) research activities; (d) relationship to other agency research; and (e) demographic characteristics of the individual completing the survey. Findings indicated that nursing research within children's hospitals is in an early development state, but that it is recognized as a necessary and credible component of nursing. Differences were noted between the groups of hospitals with the most research activity and those with no research activity. Hospitals were in various stages of research development, a sequential process characterized by a sequential pattern comprised of two phases.


Endoscopic resection of a nasal septal chondrosarcoma: first report of a case.
Advances in endoscopic sinus surgery technique and technology have provided the otolaryngologist with a wide array of surgical options for the management of nasal and paranasal sinus diseases that were once limited to procedures requiring invasive surgery. We describe the case of a patient with a chondrosarcoma of the posterior nasal septum that was resected endoscopically. There have been fewer than 30 reports in the English-language literature of chondrosarcomas arising at this location, and the reported approaches to surgical excision in these case involved craniofacial procedures, facial degloving, facial splitting, and maxillectomy techniques. Until now, no case of endoscopic removal has been reported.


Subacute sclerosing panencephalitis as a cause of chronic dementia and relapsing brain disorder.
Two patients with subacute sclerosing panencephalitis (SSPE) are described because of the course of the disease, which is still thought to be unusual but might prove to be rather common. In both cases there was apparent recovery after about two years of illness. One of the patients had a relapse after eight years of remission and seems to have recovered also from this second period of illness, though with a more severe mental defect than after the first one. Thus, SSPE should be kept in mind as a possible aetiological factor in patients with a persisting slight to severe dementia after a brain disorder. Apparent recovery from SSPE does not exclude the possibility of relapse even many years later.


GAMETE INTERACTIONS AND GENETIC DIFFERENTIATION AMONG THREE SYMPATRIC POLYCHAETES.
The evolution of gamete incompatibility between free-spawning marine invertebrate species has been explained by three hypotheses: (1) independent divergence at gamete recognition loci; (2) selection against hybrids; and (3) a process of sexual selection involving polymorphic gamete recognition loci (Metz and Palumbi 1996). The first two hypotheses predict that gamete incompatibility appears only after gene flow has been halted for other reasons and the third that gamete incompatibility appears simultanously with blocks to gene flow. Here I show that gametes of three sympatric polychaetes in the genus Arctonoe are compatible in all crosses, over a broad range of gamete concentrations and contact times. Although at least some hybrid crosses produce fertile adults, allozyme and mitochondrial DNA sequence data indicate that the three species do not regularly exchange genes. These data are consistent with predictions of the first two hypotheses for the evolution of gamete incompatibility, but allow rejection of the third hypothesis. Gametes of the three species are compatible despite estimated divergence times of 1-3 M.Y.B.P.; in several other marine invertebrates, divergence times of the same magnitude are associated with asymmetric or complete gamete incompatibility. It appears likely that segregation of symbiotic adults on their respective host species restricts mating opportunities, and thus gene flow, among Arctonoe species.


Boron deficiency increases putrescine levels in tobacco plants.
Polyamine concentrations were determined in leaves and roots of tobacco plants (Nicotiana tabacum L.) subjected to a short-term boron deficiency. A decrease in the growth of shoots and, especially, roots was found under this mineral deficiency. Boron deficiency did not lead to a significant decrease in leaf or root ion concentrations when compared to control treatment; however, as expected, leaf boron concentration was lower in boron-deficient plants in comparison to the control. In leaves, the levels of free putrescine and spermidine were similar in both treatments. In roots, a short-term boron deficiency caused an increase in free putrescine. Moreover, boron-deficient plants had higher conjugated polyamine concentration than boron-sufficient plants, which was especially evident for conjugated putrescine in leaves. A possible link between boron and polyamine levels is proposed and discussed.


Aetiologic study on an influenza-like epidemic in horses in China.
About thirty thousands horses were affected and hundreds of them died in an epidemic caused by equine 2 influenza virus (H3N8) in China. The estimated morbidity and mortality accounted for 81% and 2%, respectively. The viral protein and RNA electrophoresis patterns revealed that the new isolates were antigenically different from the prototype strain influenza A/eq/Miami/1/63(H3N8). Therefore, the representative strain of the equine 2 subtype of influenza A virus recommended for producing reference reagents, vaccines, and for serological diagnosis must have been altered by antigenic drift.


Measurement-Based Linear Optics.
A major challenge in optical quantum processing is implementing large, stable interferometers. We offer a novel approach: virtual, measurement-based interferometers that are programed on the fly solely by the choice of homodyne measurement angles. The effects of finite squeezing are captured as uniform amplitude damping. We compare our proposal to existing (physical) interferometers and consider its performance for BosonSampling, which could demonstrate postclassical computational power in the near future. We prove its efficiency in time and squeezing (energy) in this setting.


Histogram parameters derived from T2 weighted images are associated with histopathological findings in rectal cancer - a preliminary study.
Histogram analysis can better reflect tumor heterogeneity than conventional imaging analysis. The present study analyzed possible correlations between histogram parameters derived from T2 weighted images and histopathological features in rectal cancer. Seventeen patients with histopathological proven rectal adenocarcinoma were retrospectively acquired with prebioptic 3 T MRI and available histopathological specimens. Histogram analysis was performed using an in-house matlab tool conducting a whole lesion measurement. Histopathology was investigated using Ki67 specimens with calculation of Ki67-index as well as cellularity and nucleic areas and CD31 specimens, with estimation of microvessel density. Several histogram parameters correlated with average nucleic area. Skewness showed a moderate correlation with microvessel density (P = 0.54, P = 0.02). None of the parameters correlated with Ki67-index. Skewness derived from T2 weighted images might be used as a surrogate parameter for average nucleic area and microvessel density. However, none of the parameters were associated with proliferation index.


Relationship between resting parameters of the mitral valve and exercise capacity in patients with mitral stenosis: can the diastolic filling period predict exercise capacity?
In order to provide patients with better exercise capacity, interventional therapy to the mitral valve is often carried out in mitral stenosis (MS). Hence, it is crucial to determine exercise capacity before deciding on the time of intervention. The study aim was to demonstrate whether resting parameters of the mitral valve, notably left ventricular diastolic filling period (LVDFP) and mitral valve resistance (MVR), relate to restricted exercise capacity. Forty-six patients (30 females, 16 males; mean age 44+/-11 years; range: 33-55 years) with rheumatic MS were enrolled. Exercise capacities of patients were grouped according to NYHA classification and maximal exercise tolerance values obtained using exercise testing. Exercise capacity in male patients was quantified. Relationships between patient variables and exercise capacity were evaluated using simple linear regression analysis. In order to identify determinants of exercise capacity, a discriminate multivariate analysis was performed with variables, which were found to correlate significantly in the univariate analysis. There were no correlations between echo score, MVR, planimetric mitral valve area (MVA), MVA obtained by the pressure half-time method or calculated by the continuity equation, and transmitral mean gradient and exercise capacity classes as defined by both NYHA and exercise testing. The only predictor of exercise capacity class determined by discriminate multivariate analysis using the significant parameters in the linear regression analysis was LVDFP. The quantified exercise capacity in male patients correlated only with LVDFP (r = 0.64, p = 0.008). Exercise capacity cannot be predicted using routine resting parameters of the mitral valve (including MVR) in patients with MS. In this respect, the LVDFP may be of value.


Bee venom acupuncture for adhesive capsulitis: A protocol for systematic review and meta-analysis.
Bee venom acupuncture has been used in treating patients with shoulder adhesive capsulitis, yet the effectiveness and safety remains unclear. Therefore, this systematic review will aim to assess the effectiveness and safety of bee venom acupuncture for shoulder adhesive capsulitis. Electronic databases including EMBASE, PUBMED, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, and Chinese Biomedical Literature Database will be searched for relevant randomized controlled trials from their inception to the search data without language and publication status. Randomized controlled trials involving bee venom acupuncture for treating shoulder adhesive capsulitis will be included. The primary outcome will be pain visual analogue scale, and secondary outcomes include active and passive range of motions, shoulder pain and disability index. Meta-analysis will be conducted using Review Manager software (V.5.3). The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data. The results will be disseminated through a peer-reviewed journal publication. These systematic review findings will provide an evidence of bee venom acupuncture for shoulder adhesive capsulitis, and help to inform clinical practitioners and policy-makers in the decision-making. Ethics approval and patient consent are not required as this study is a systematic review based on published articles.


Intracerebral hemorrhage in blacks. Risk factors, subtypes, and outcome.
Blacks are at a higher risk for intracerebral hemorrhage (ICH) than whites; however, few data are available regarding the demographic and clinical characteristics of ICH among blacks. We determined the frequency of risk factors, etiologic subtypes, and outcome among consecutive black patients admitted with nontraumatic ICH to a university-affiliated public hospital. The most common risk factors in the 403 black patients with ICH were preexisting hypertension (77%), alcohol use (40%), and smoking (30%). Among the 91 nonhypertensive patients, 21 (23%) were diagnosed with hypertension after onset. Compared with women, men had a younger age of onset (54 versus 60 years; P < .001) and higher frequency of alcohol use (54% versus 22%; P < .001) and smoking (39% versus 17%; P < .001). ICH secondary to hypertension (n = 311) and of undetermined etiology (n = 73) were the most common subtypes in blacks. Patients aged 65 years and older (compared with those aged 15 to 44 years; P = .001) and women (compared with men; P = .02) were more likely to be dependent at discharge. Primary preventive strategies are required to reduce the high frequency of modifiable risk factors predisposing to ICH in blacks.


Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral, and anal sphincter function in a dog model. Part 3. nicotinic receptor characterization.
Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response to epibatidine, expressed as percent potassium chloride, was similar (∼35% in controls, 30% in Decentralized, and 24% in ObNT-Reinn). Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). Yet, in all groups, epibatidine-induced strip contractions were similarly inhibited by mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), SR 16584 (α3β4 neuronal nicotinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), and atropine (muscarinic receptor antagonist), indicating that nicotinic receptors (particularly α3β4 subtypes), neuromuscular and muscarinic receptors play roles in bladder contractility. In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function.


Anisotropic Effective Mass, Optical Property, and Enhanced Band Gap in BN/Phosphorene/BN Heterostructures.
Phosphorene is receiving great research interests because of its peculiar physical properties. Nonetheless, the phosphorus has a trouble of degradation due to oxidation. Hereby, we propose that the electrical and optical anisotropic properties can be preserved by encapsulating into hexagonal boron nitride (h-BN). We found that the h-BN contributed to enhancing the band gap of the phosphorene layer. Comparing the band gap of the pristine phosphorene layer, the band gap of the phosphorene/BN(1ML) system was enhanced by 0.15 eV. It was further enhanced by 0.31 eV in the BN(1ML)/phosphorene/BN(1ML) trilayer structure. However, the band gap was not further enhanced when we increased the thickness of the h-BN layers even up to 4 MLs. Interestingly, the anisotropic effective mass and optical property were still preserved in BN/phosphorene/BN heterostructures. Overall, we predict that the capping of phosphorene by the h-BN layers can be an excellent solution to protect the intrinsic properties of the phosphorene.


Isolated lung perfusion for pulmonary metastases, a review and work in progress.
Pulmonary metastasectomy is a widely accepted treatment for many patients with pulmonary metastases from various solid tumors. Nevertheless, 5-year survival is disappointing, with rates of 25-40%, and many patients develop recurrences. Isolated lung perfusion (ILuP) is a promising new technique to deliver high-dose chemotherapy to the lungs, while minimising systemic toxicities. This procedure is technically safe and feasible; however, clinical value and efficacy remain unclear. The aim of this paper is to give a review of literature on ILuP in humans, and to describe the development of the perfusion procedure in our institute.


Predictors of running away from family foster care.
Running away is a frequent but little studied phenomenon among adolescents in foster care. Repeated running from care often leads to premature discharge and homelessness for youth. This article uses cumulative risk theory in the context of normative adolescent development to investigate predicators of running away from foster care. Results indicate risks stemming from individual, foster home, and child welfare system sources, which offer some insight for prevention and intervention.


The effect of witnessing a death. 2: Communication and ethics.
The first part of this unit explored the effect on patients of witnessing a death in hospital or a palliative care environment. It included a literature review and also examined the implications for nursing practice. Part 2 of this unit discusses communication following the death of a patient and ethical issues that should be taken into consideration.


Localization of open-shell molecular orbitals via least change from fragments to molecule.
Both top-down and bottom-up localization schemes are proposed for constructing localized molecular orbitals (LMOs) of open-shell systems, via least change from fragments to molecule. The success of both schemes stems from (1) the primitive fragment LMOs that are local not only in space but also in energy and (2) the "conquer step" that allows arbitrary assignment of the unpaired electrons to fragments. Moreover, integral occupations are retained, so as to facilitate subsequent treatment of electron correlation and excitation.


Nonconvulsive Status Epilepticus Associated with Cerebral Hyperperfusion Syndrome after Carotid Endarterectomy: A Case Report.
We report a case of a 73-year-old man who developed nonconvulsive status epilepticus as a complication of cerebral hyperperfusion syndrome after carotid endarterectomy for carotid artery stenosis. On postoperative day 1, the patient experienced headaches and vomiting. Resting N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow to the entire right hemisphere, and the patient was diagnosed with cerebral hyperperfusion syndrome. He was treated with antihypertensive and antiseizure medications, sedated using propofol, intubated, and placed under mechanical ventilation. On postoperative day 3, computed tomography perfusion imaging showed a reduction in hyperperfusion, and propofol sedation was terminated on postoperative day 4. However, the patient exhibited prolonged impaired awareness and roving eye movements, and long-term video electroencephalographic monitoring revealed electrographic seizures. The patient was diagnosed with nonconvulsive status epilepticus. Propofol sedation was resumed, and the antiseizure medication dose was increased. Subsequently, the state of hyperperfusion in the right hemisphere diminished, and electroencephalographic findings improved, allowing sedation to be terminated on postoperative day 7. The findings from this case suggest that when clinical subtle symptoms, such as impaired awareness and roving eye movements, are observed during treatment of cerebral hyperperfusion syndrome, video electroencephalography should be performed to detect electrographic seizures.


[DNA structure from A to Z--biological implications of structural diversity of DNA].
Deoxyribonucleic acid (DNA) is a biopolymer of nucleotides, usually adopting a double-stranded helical form in cells, with complementary base pairing holding the two strands together. The most stable is B-DNA conformation, although numerous other double helical structures can occur under specific conditions (A-DNA, Z-DNA, P-DNA). The existence of multiple-stranded (triplex, tetraplex) forms in vivo and their biological function in cells are subject of intensive studies.


[Charcot. Dates. Legend and reality].
This introductiion to the session devoted to Charcot reviews the important steps in his career: 1848, the internship, followed by the "chef de clinique" state (1852-53); the central hospital office in 1856; the agregation in 1860; the chair of pathological anatomy in 1872; the clinical chair in diseases of the nervous system in 1882. We review as well the milestones in his scientific work. His arrival in 1862 at the Salpêtrière which he would never leave; there in 1866, he started a "free" course which became the point of departure for his reputation. Taking advantage of histology together with a mastery of the anatomical-clinical method permitted him to achieve considerable progress with a few years (associating locomotor ataxia with lesions of the posterior roots and columns; acute and chronic progressive muscular atrophy with those of the anterior horn: separating multiple sclerosis from Parkinson's disease) which culminated in the masterful description of amyotrophic lateral sclerosis (1874), the pathological anatomy and physiology of the spinal cord (1873) and cerebral localisations of motor areas (1875). Beginning in 1878, he applied the nosological method to the study of hysteria, relying on the notion of "analogous anatomy" in seeking a correspondence between organic lesions and "dynamic lesions". In 1883 and 1884, his approach to aphasia led him to introduce beyond the anatomical-clinical fact a new speculative dimension, that of psycho-physiology. This he applied to interpret hysterical ailments and "psychic paralyses". The personality of Charcot is briefly sketched. In the arts as in politics, he was more of a conservative than an opportunist; authoritarian, shy, and brusque, gloomy and taciturn, he nontheless had a remarkable power to attract.


[Attempt to offer safe and effective epidural analgesia for labor pain at the Hamamatsu University Hospital].
The anesthesiologists began offering epidural analgesia for labor pain at the Hamamatsu University Hospital in cooperation with the obstetricians and the midwives in August, 2005. It is necessary for anesthesiologists to concentrate on caring of the parturients in order to offer safe and effective labor epidural analgesia. We discussed how to begin and continue to offer the labor epidural based on our experience while the number of anesthesiologists is insufficient.


Electromyographic and cinematographic analysis of elbow function in tennis players using single- and double-handed backhand strokes.
It is generally believed that tennis players using a double-handed backhand rarely develop lateral epicondylitis since the helping arm appears to absorb more energy and changes the mechanics of the swing. The purpose of this paper was to compare muscle activity about the elbow in single- and double-handed backhand strokes in competitive tennis players. Muscle activity in 3 elbow extensors, a wrist flexor, and a forearm pronator of the dominant arm was compared during the single-handed (N = 14) and double-handed (N = 13) backhand ground strokes using indwelling electromyography and high-speed cinematography. Significantly higher activity was seen in the double-handed technique in the flexor carpi radialis muscle in the preparation phase and in the pronator teres muscle in the acceleration phase. Higher flexor carpi radialis muscle activity in preparation of the double-handed stroke appeared to be a function of the double-handed grip used on the racquet, and the increased pronator teres muscle activity in acceleration indicated maintenance of greater pronation provided by the grip of the non-dominant hand. The decreased occurrence of lateral epicondylitis in players using a double-handed backhand may not be caused by decreased extensor activity, but rather by factors associated with flawed stroke mechanics more often seen in the single-handed technique.


Formation of Tankyrase Inhibitor-Induced Degradasomes Requires Proteasome Activity.
In canonical Wnt signaling, the protein levels of the key signaling mediator β-catenin are under tight regulation by the multimeric destruction complex that mediates proteasomal degradation of β-catenin. In colorectal cancer, destruction complex activity is often compromised due to mutations in the multifunctional scaffolding protein Adenomatous Polyposis Coli (APC), leading to a stabilization of β-catenin. Recently, tankyrase inhibitors (TNKSi), a novel class of small molecule inhibitors, were shown to re-establish a functional destruction complex in APC-mutant cancer cell lines by stabilizing AXIN1/2, whose protein levels are usually kept low via poly(ADP-ribosyl)ation by the tankyrase enzymes (TNKS1/2). Surprisingly, we found that for the formation of the morphological correlates of destruction complexes, called degradasomes, functional proteasomes are required. In addition we found that AXIN2 is strongly upregulated after 6 h of TNKS inhibition. The proteasome inhibitor MG132 counteracted TNKSi-induced degradasome formation and AXIN2 stabilization, and this was accompanied by reduced transcription of AXIN2. Mechanistically we could implicate the transcription factor FoxM1 in this process, which was recently shown to be a transcriptional activator of AXIN2. We observed a substantial reduction in TNKSi-induced stabilization of AXIN2 after siRNA-mediated depletion of FoxM1 and found that proteasome inhibition reduced the active (phosphorylated) fraction of FoxM1. This can explain the decreased protein levels of AXIN2 after MG132 treatment. Our findings have implications for the design of in vitro studies on the destruction complex and for clinical applications of TNKSi.


Management of rectovaginal fistulas and patient outcome.
Rectovaginal fistulas are a relatively rare, but debilitating condition which pose a significant treatment challenge. Areas covered: In this manuscript we discuss the etiology, classification as well as the manifestations and evaluation of rectovaginal fistulas. We summarize the different surgical techniques and evaluate their success rates and perioperative considerations according to cited sources. Expert commentary: A deep understanding of the disease, treatment options, and familiarity with the different surgical treatment options available is mandatory for choosing the correct treatment. When the surgical treatment is tailored to the specific fistula and patient, many patients can eventually have successful resolution. This review will address the management and patient outcomes after treatment for rectovaginal fistulas.


How Human Is Human Connectional Neuroanatomy?
The structure of the human brain has been studied extensively. Despite all the knowledge accrued, direct information about connections, from origin to termination, in the human brain is extremely limited. Yet there is a widespread misperception that human connectional neuroanatomy is well-established and validated. In this article, we consider what is known directly about human structural and connectional neuroanatomy. Information on neuroanatomical connections in the human brain is derived largely from studies in non-human experimental models in which the entire connectional pathway, including origins, course, and terminations, is directly visualized. Techniques to examine structural connectivity in the human brain are progressing rapidly; nevertheless, our present understanding of such connectivity is limited largely to data derived from homological comparisons, particularly with non-human primates. We take the position that an in-depth and more precise understanding of human connectional neuroanatomy will be obtained by a systematic application of this homological approach.


[Perioperative airway management based on enhanced recovery after surgery for improvement of preoperative pulmonary function in patients with aspirin intolerance triad].
Objective: To explore the effect of perioperative airway management based on the concept of enhanced recovery after surgery (ERAS) on the improvement of preoperative pulmonary function in patients with aspirin intolerance triad (AIT). Methods: Thirty patients with AIT (including 13 males and 17 females, aged from 29 to 75 years old) for sinus surgery from January 2018 to December 2019 were selected, 172 patients (including 105 males and 67 females, aged from 17 to 83 years old) with chronic rhinosinusitis with nasal polyps (CRSwNP) without lower airway disease were selected by random number table at the same period, and their clinical data and preoperative pulmonary function were analyzed and compared retrospectively. FEV1%pred<80% after bronchodilation test was considered as high risk for surgery. Preoperative evaluation and standardized drug intervention were applied in patients with pulmonary function abnormalities at risk for surgery, and improvement of preoperative pulmonary function and tolerability to general anesthesia surgery in the two groups were evaluated. All the statistical analyses were conducted using SPSS 22.0. Results: The main pulmonary function indexes (FEV1%pred, FEV1/FVC%pred, FEF50%pred, FEF75%pred, MMEF%pred) in AIT group decreased significantly than those in CRSwNP group (t values were 10.882, 10.506, 9.141, 10.182, 9.099, respectively, all P<0.001). At admission 86.7% (26/30) patients in the AIT group and 11.6% (20/172) patients in CRSwNP group had high surgical risk for lung function, with significantly difference (χ2 = 81.788, P<0.05); after 3 days with individualized drug intervention, 57.7% (15/26) patients in AIT group reached the standard for surgery, which was significantly less than 90.0% (18/20) patients in CRSwNP group (χ²=4.335,P<0.05); and after 6 days with drug intervention, the patients who reached the standard for surgery in pulmonary function accounted for 92.3% (24/26) in the AIT group and 100% (20/20) in the CRSwNP group. FEV1%pred in the two groups before surgery were significantly improved compared with those at admission respectively ((90.00±6.32)% vs. (64.79±13.60)%,t value was 10.110 in AIT group; (91.65±11.86)% vs. (76.40±9.35)%, t value was 9.346 in CRSwNP group; all P<0.05), and also FEV1/FVC%pred, FEF50%pred, FEF75%pred and MMEF%pred were all significantly improved (all P<0.05). Surgery was completed successfully in the two groups of patients with lung function meeting the surgical standard, and no intraoperative or postoperative airway adverse events occurred. Conclusion: AIT patients have high airway risk for sinus surgery due to poor pulmonary function. Standardized airway management based on the concept of ERAS can improve the pulmonary function of patients, and decrease the incidence of perioperative airway adverse events.


[Oral anticoagulation in the elderly - practical aspects and risk-benefit trade-off in atrial fibrillation].
Use of oral anticoagulants is common in elderly persons. Oral anticoagulation can be used safely in the elderly if careful titration of the loading dose, careful changes in maintenance doses as well as consideration of drug interactions are taken into account. Frequent monitoring of the INR is essential, especially with changes in medical status and in co-medication. Correction of elevated INRs can be done following the recommendations. If vitamin K is used in stable patients, only small doses are required. In patients with atrial fibrillation, ischemic stroke risk and bleeding risk are predicted by overlapping factors. So patients who profit most from stroke risk reduction also show high bleeding risk. Risk stratification for ischemic stroke can be done easily with CHADS2-Score. Fall risk tends to be overestimated as a contraindication, whereas cognitive decline in combination with an unstable social network argues against anticoagulation. In the end, the decision to start or withhold anticoagulation has to be taken individually.


QA-driven guidelines generation for bacteriotherapy.
We propose a question-answering (QA) driven generation approach for automatic acquisition of structured rules that can be used in a knowledge authoring tool for antibiotic prescription guidelines management. The rule generation is seen as a question-answering problem, where the parameters of the questions are known items of the rule (e.g. an infectious disease, caused by a given bacterium) and answers (e.g. some antibiotics) are obtained by a question-answering engine. When looking for a drug given a pathogen and a disease, top-precision of 0.55 is obtained by the combination of the Boolean engine (PubMed) and the relevance-driven engine (easyIR), which means that for more than half of our evaluation benchmark at least one of the recommended antibiotics was automatically acquired by the rule generation method. These results suggest that such an automatic text mining approach could provide a useful tool for guidelines management, by improving knowledge update and discovery.


Congruency of multimodal data-driven personalization with shared decision-making for StayFine: individualized app-based relapse prevention for anxiety and depression in young people.
Tailoring interventions to the individual has been hypothesized to improve treatment efficacy. Personalization of target-specific underlying mechanisms might improve treatment effects as well as adherence. Data-driven personalization of treatment, however, is still in its infancy, especially concerning the integration of multiple sources of data-driven advice with shared decision-making. This study describes an innovative type of data-driven personalization in the context of StayFine, a guided app-based relapse prevention intervention for 13- to 21-year-olds in remission of anxiety or depressive disorders (n = 74). Participants receive six modules, of which three are chosen from five optional modules. Optional modules are Enhancing Positive Affect, Behavioral Activation, Exposure, Sleep, and Wellness. All participants receive Psycho-Education, Cognitive Restructuring, and a Relapse Prevention Plan. The personalization approach is based on four sources: (1) prior diagnoses (diagnostic interview), (2) transdiagnostic psychological factors (online self-report questionnaires), (3) individual symptom networks (ecological momentary assessment, based on a two-week diary with six time points per day), and subsequently, (4) patient preference based on shared decision-making with a trained expert by experience. This study details and evaluates this innovative type of personalization approach, comparing the congruency of advised modules between the data-driven sources (1-3) with one another and with the chosen modules during the shared decision-making process (4). The results show that sources of data-driven personalization provide complementary advice rather than a confirmatory one. The indications of the modules Exposure and Behavioral Activation were mostly based on the diagnostic interview, Sleep on the questionnaires, and Enhancing Positive Affect on the network model. Shared decision-making showed a preference for modules improving positive concepts rather than combating negative ones, as an addition to the data-driven advice. Future studies need to test whether treatment outcomes and dropout rates are improved through personalization.


Human leukocyte antigen typing using a knowledge base coupled with a high-throughput oligonucleotide probe array analysis.
Human leukocyte antigens (HLA) are important biomarkers because multiple diseases, drug toxicity, and vaccine responses reveal strong HLA associations. Current clinical HLA typing is an elimination process requiring serial testing. We present an alternative in situ synthesized DNA-based microarray method that contains hundreds of thousands of probes representing a complete overlapping set covering 1,610 clinically relevant HLA class I alleles accompanied by computational tools for assigning HLA type to 4-digit resolution. Our proof-of-concept experiment included 21 blood samples, 18 cell lines, and multiple controls. The method is accurate, robust, and amenable to automation. Typing errors were restricted to homozygous samples or those with very closely related alleles from the same locus, but readily resolved by targeted DNA sequencing validation of flagged samples. High-throughput HLA typing technologies that are effective, yet inexpensive, can be used to analyze the world's populations, benefiting both global public health and personalized health care.


Sphingosylphosphorylcholine Induces Thrombospondin-1 Secretion in MCF10A Cells via ERK2.
Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and Ca²⁺ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia. TSP-1 promotes aggressive phenotype via epithelial mesenchymal transition (EMT). The relationship between SPC and TSP-1 is unclear. We found SPC induced EMT leading to mesenchymal morphology, decrease of E-cadherin expression and increases of N-cadherin and vimentin. SPC induced secretion of thrombospondin-1 (TSP-1) during SPC-induced EMT of various breast cancer cells. Gene silencing of TSP-1 suppressed SPC-induced EMT as well as migration and invasion of MCF10A cells. An extracellular signal-regulated kinase inhibitor, PD98059, significantly suppressed the secretion of TSP-1, expressions of N-cadherin and vimentin, and decrease of E-cadherin in MCF10A cells. ERK2 siRNA suppressed TSP-1 secretion and EMT. From online PROGgene V2, relapse free survival is low in patients having high TSP-1 expressed breast cancer. Taken together, we found that SPC induced EMT and TSP-1 secretion via ERK2 signaling pathway. These results suggests that SPC-induced TSP-1 might be a new target for suppression of metastasis of breast cancer cells.


PEA3 protects against gentamicin nephrotoxicity: role of mitochondrial dysfunction.
Toxin-induced nephrotoxicity is one of the major causes leading to the acute kidney injury (AKI). Among these nephrotoxic toxins, gentamicin can induce AKI with elusive mechanisms. Emerging evidence demonstrated that PEA3 (polyomavirus enhancer activator 3) contributed to the nephrogenesis, while its role in AKI remains unknown. Thus, this study was to investigate the role of PEA3 in gentamicin nephrotoxicity, as well as the underlying mechanisms. In rats, gentamicin treatment (200 mg/kg twice per day) for two days induced remarkable kidney injury with a peak damage on day 5 evaluated by the tubular injury score, proteinuria, and tubular injury markers of NGAL and KIM-1. In parallel with the tubular injury, PEA3 protein and mRNA expressions were significantly upregulated by gentamicin and peaked on day 5. To define the role of PEA3 in gentamicin nephrotoxicity, proximal tubule cells were transfected with PEA3 plasmid with or without gentamicin treatment (1 mg/ml). Notably, overexpression of PEA3 attenuated gentamicin-induced cell injury shown by the ameliorated cell apoptosis and NGAL and KIM-1 upregulation. Meantime, gentamicin caused severe mitochondrial dysfunction, which was largely normalized by PEA3 overexpression. In contrast, silencing PEA3 by a siRNA strategy further deteriorated gentamicin-induced cell apoptosis and mitochondrial dysfunction. In sum, PEA3 protected against gentamicin nephrotoxicity possibly via a mitochondrial mechanism.


Biotechnological Processes in Microbial Amylase Production.
Amylase is an important and indispensable enzyme that plays a pivotal role in the field of biotechnology. It is produced mainly from microbial sources and is used in many industries. Industrial sectors with top-down and bottom-up approaches are currently focusing on improving microbial amylase production levels by implementing bioengineering technologies. The further support of energy consumption studies, such as those on thermodynamics, pinch technology, and environment-friendly technologies, has hastened the large-scale production of the enzyme. Herein, the importance of microbial (bacteria and fungi) amylase is discussed along with its production methods from the laboratory to industrial scales.


Topical steroid treatment reduces arachidonic acid and leukotriene B4 in lesional skin of psoriasis.
Topical clobetasol propionate or vehicle ointment was applied daily for 3 days to psoriatic plaques on eight patients. Skin chamber exudates from untreated, steroid and vehicle treated lesions were assayed for arachidonic acid (AA), leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) before, and at 24 h and 72 h after treatment. Significant reductions in AA and LTB4 were observed at 72 h in steroid treated lesions. The reduction in 12-HETE levels observed after steroid treatment was not statistically significant. PGE2 levels in lesional psoriatic skin were unaltered. The reduction of AA, and LTB4 was associated with clinical improvement of psoriasis.


Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: prospective case-control study of 136 monochorionic twin pregnancies.
To test the hypothesis that identical twins show no inter-twin differences in cardiovascular structure or physiology in fetal life unless there has been twin-twin transfusion syndrome. Unselected prospective case-control observational study of fetoplacental haemodynamics including echocardiography at a median of 24 (16.7 to 32.3) weeks, with postnatal confirmation of congenital heart disease or normality. Fetal medicine unit. 136 women with monochorionic diamniotic twin pregnancies, of which 47 fetal twin pairs (35%) had twin-twin transfusion syndrome. There were no haemodynamic differences between the bigger fetus (twin 1) and the smaller co-twin (twin 2) in uncomplicated monochorionic diamniotic pairs. In twin-twin transfusion syndrome, recipient fetuses had increased aortic and pulmonary velocities compared with their donor co-twins (mean (SD): 0.73 (0.23) m/s and 0.63 (0.14) m/s), respectively, v 0.53 (0.16) m/s and 0.48 (0.10) m/s in donor twins; p = 0.003 (aortic) and < 0.0001 (pulmonary)), and also in comparison with twin 1 and twin 2. The overall prevalence of congenital heart disease was increased above that in singletons (3.8% v 0.56%; 6.9% in twin-twin transfusion v 2.3% in uncomplicated monochorionic diamniotic twins), with inter-twin discordance for defects. The prevalence in recipient twins was 11.9% (p = 0.014 v uncomplicated control twins). Fetuses with an identical genome but no circulatory imbalance have similar cardiovascular physiology but discordant phenotypic expression of congenital heart disease. The high prevalence of congenital heart disease in monochorionic diamniotic twins merits detailed fetal echocardiography.


Microchannel plate detector detection efficiency to monoenergetic electrons between 3 and 28 keV.
An unshielded microchannel plate (MCP) detector with an ultrafine pore diameter of 2 μm was irradiated by an electron beam to determine the detection efficiency of electrons for creating detector signals, or counts. Tested electron energies spanned a range of 3 kiloelectron volts (keV) to 28 keV. Higher detection efficiencies were measured at the lower end of this energy range, 0.376 counts per incident electron at 3 keV down to 0.155 at 15 keV with an increase to 0.217 at 18 keV and then another decrease down to 0.15 counts per incident electron at 28 keV. The increase at 18 keV is attributed to primary electron interaction with the L shell electrons of lead (Pb), leading to an increase in secondary electron and X-ray generation within the MCP and thus an increase in detection efficiency. For the electron beam directed normal to the MCP surface, the lowest efficiency of 0.15 counts per incident electron was observed at 28 keV. Detection efficiency was also tested as a function of incident angle with angular steps of 5°. Detection efficiency was more sensitive to the angle of incidence as the incident electron energy decreased. The detection efficiency at 3 keV decreased from 0.376 counts per electron at the zero degree angle (normal incidence to MCP surface) to 0.027 counts per electron at an incident angle of 50° (average in both orientations). At 28 keV, the decrease in detection efficiency as a function of increasing angle was less pronounced, ranging from 0.15 counts per electron at zero degrees to 0.08 counts per electron at 50° (average in both orientations). Experimental data showed lower detection efficiencies compared with previously published data.


The role of exact exchange on the structure of water dimer radical cation: Hydrogen bond vs hemibond.
Understanding the structure and chemical bonding in water dimers is central to the study of many (photo-)electrochemical oxidation reactions. Two structures of the water dimer radical cation, namely, proton-transfer and hemi-bonded structures, have been suggested using density functional theory (DFT) and coupled cluster singles, doubles, and perturbative triples [CCSD(T)]. Both structures are identified by us as local minima, and their relative stability strongly depends on the level of theory. The exact exchange correlates linearly to the energy difference between both local minima. DFT functionals with less than 20 percent exact exchange predict the hemi-bonded structure to be more stable, while more than 20 percent of the exact exchange stabilizes the proton-transfer structure. The latter structure is also confirmed by CCSD(T) benchmark computations. These computations, furthermore, indicate that the oxidized water dimer consists of a hydronium cation (H3O+) and an HO· radical. These results are reproduced by DFT functionals with more than 50% of exact exchange (BHandH, M06-2X, and M06-HF). The transition barrier for the interconversion from the proton-transfer to the hemi-bonded structure is 0.6 eV, while the reverse reaction has a barrier of 0.1 eV.


Inhibition of hydroxymethylglutaryl-coenzyme a reductase reduces Th1 development and promotes Th2 development.
Several prospective clinical studies have indicated that hydroxymethylglutaryl-coenzyme A reductase inhibitors, statins, prevent cardiovascular events in part through their antiinflammatory properties. Because inflammation is positively and negatively regulated by T helper (Th) 1 cells and Th2 cells, respectively, we examined the effects of statins on the Th polarization in vitro and in vivo. Here we demonstrated that the statins tested, ie, cerivastatin, simvastatin, lovastatin, and atorvastatin, promoted Th2 polarization through both inhibition of Th1 development and augmentation of Th2 development of CD4+ T cells primed in vitro with anti-CD3 antibody and splenic antigen-presenting cells. Cerivastatin exerted most potent effect on modulation of Th1/Th2 development, and the effect was completely abrogated by an addition of mevalonate. Consistent with in vitro experiments, cerivastatin treatment decreased IFN-gamma production of lymph node cells from mice immunized with ovalbumin emulsified in complete Freund's adjuvant, indicating that Th1 development is also suppressed in an in vivo proinflammatory environment. In this murine model, cerivastatin significantly reduced mesangial matrix expansion of glomeruli in the kidney and attenuated proteinuria. The decrease of glomerular sclerosis by cerivastatin treatment was positively related to the suppression of interferon (IFN)-gamma-producing Th1 response in draining lymph node cells. Hence, these findings strongly suggest that statins' inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase regulates Th1/Th2 polarization in vivo and such a mechanism possibly plays a pathophysiological role in immune-related glomerular injury.


Humanization of the hospital: participatory construction of knowledge and practices on care and ambience.
To identify and implement care and ambience strategies, with a view to hospital humanization. Action-research study, whose investigation process occurred between January and March 2019, with the participation of employees in strategic functions of a medium-sized hospital, through a focus group and strategic focal analysis. The implementation of care and ambience strategies started in May 2019 and remains in progress, with the responsible and multiplying participation of professionals and patients. 18 employees participated in the study. It was found that investigative processes accompanied by practical interventions, especially those related to the promotion of interactive, inclusive, care spaces and the creation of a ludic, attractive and interactive environment favor multi-professional actions, mobilize innovative knowledge and practices, and contribute to the (re)signification of the being and doing of the health professional. Care and ambience, with a view to hospital humanization, include the implementation of strategies designed with the responsible and multiplying participation of all actors (professionals and users) of the hospital. It is important that, in this process, everyone feels they are protagonists of new ways of being, living and doing in health.


Adverse event reporting in clinical trials: room for improvement.
Regulatory and ethical guidelines require clinical trial sponsors to disseminate clinical trial adverse event reports to involved investigators and human research ethics committees. Compliance with these guidelines has resulted in a major administrative burden for ethics committees. This burden does not necessarily contribute to the protection of clinical trial participants. Rationalisation of the adverse event reporting might allow better use of the data and might benefit human research ethics committees.


Contraceptive availability leads to increase in use in conflict-affected Democratic Republic of the Congo: evidence from cross-sectional cluster surveys, facility assessments and service statistics.
Humanitarian assistance standards mandate specific attention to address the sexual and reproductive health (SRH) needs of conflict-affected populations. Despite these internationally recognised standards, access to SRH services is still often compromised in conflict settings. CARE in collaboration with the RAISE Initiative strengthened the Ministry of Health (MOH) to provide contraceptive services in Maniema province, Democratic Republic of the Congo. This study evaluated the effectiveness of this support for MOH health facility provision of contraception. Cross-sectional surveys in 2008 (n = 607) and 2010 (n = 575) of women of reproductive age using a two-stage cluster sampling design were conducted in Kasongo health zone. Facility assessments were conducted to assess the capacity of supported government health facilities to provide contraceptive services in 2007 and 2010. Data on the numbers of clients who started a contraceptive method were also collected monthly from supported facilities for 2008-2014. Current use of any modern contraceptive method doubled from 3.1 to 5.9% (adjusted OR 2.03 [95%CI 1.3-3.2]). Current use of long-acting and permanent methods (LAPM) increased from 0 to 1.7% (p < .001), an increase that was no longer significant after adjustment. All current users except a few condom users reported a health facility as the source of the method. The 2010 facility assessments found that most supported facilities had the capacity to provide short-acting and long-acting methods. Service statistics indicated that the percentage of clients who accepted a long-acting method at supported facilities increased from 8% in 2008 to 83% in 2014 (p < .001). This study demonstrated that contraceptive prevalence doubled between 2008 and 2010; service statistics indicate that utilization of long-acting methods continued to increase to a majority of new clients after 2010. Strengthening the health system to provide contraceptive services enabled individuals to exercise their right to prevent unintended pregnancies. These results suggest that demand for contraception, including long-acting methods, is present even in humanitarian settings, and that women will use them when they are available and of reasonable quality. It is critical that the humanitarian community ensure that such services are available to women affected by crises.


The clinical significance of asymptomatic low molecular weight proteinuria detected on routine screening of children in Japan: a survey of 53 patients.
A nationwide questionnaire survey uncovered 53 patients with asymptomatic low molecular weight (LMW) proteinuria, 52 males and one female, aged 3 to 32 years. There was a slight tendency toward shortening stature with increasing age. Mild proteinuria was present in all of them, and microscopic hematuria was occasionally noted in one-fourth, while glucosuria or aminoaciduria was rare. The share of their urinary LMW proteins was increased as evidenced by an increase in the alpha-globulin fraction on cellulose-acetate membrane electrophoresis (27 patients) and/or by an increase in the LMW proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis (17 patients). Urinary beta 2-microglobulin, one of the LMW proteins, was measured and proved to be increased but electrophoretic analyses were not performed in 25 patients. Urinary N-acetyl-beta-D-glucosaminidase activity, an indicator of renal proximal tubular damage, was elevated in 31 of 38 patients studied: Histological studies of renal biopsies revealed focal changes: focal global sclerosis in seven and tubular atrophy and/or tubular casts in nine out of 32 patients studied.


Stability of Sodium Chlorate Residues in Frozen Tomato and Cantaloupe Homogenates.
The objective of this study was to determine the stability of sodium chlorate in frozen (-24 °C) tomato or cantaloupe homogenates for up to 17 weeks (119 days). Chlorate stability was assessed by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) at two fortification levels (80 or 600 ng/g for tomato and 200 or 3000 ng/g for cantaloupe, n = 3 each) for each fruit after storage for 0, 1, 7, 14, 28, 56, or 119 d. Within matrix type, chlorate recovery was determined by fortifying duplicate blank homogenate samples on the day of analysis with the same concentrations used for the stability samples. Chlorate limits of quantitation for cantaloupe and tomato matrices were 30 and 60 ng/g, respectively. Sodium chlorate residues were stable (P > 0.05) in frozen tomato and cantaloupe homogenates during storage for 119 days at -24 °C.


Burnout and its related factors in Korean dentists.
Dentistry has been identified as one of the most stressful work environments. Knowledge of modifiable work-environment factors related to job stress could lead to a strategy and policy to provide a better work environment for dentists. The aims of this study were to examine the degree and distribution of burnout and to determine the factors associated with burnout subscale of Korean dentists. A cross-sectional survey of Korean dentists was conducted using a custom-designed and validated questionnaire that incorporated the Maslach Burnout Inventory Human Services Survey (MBI-HSS) as well as questions regarding sociodemographic and job-related characteristics. A random sample of 1,000 dentists was selected from 13,207 registered dentists in the Korean Dental Association. The MBI-HSS scores were summarised in the three dimensions of emotional exhaustion, depersonalisation, and personal sense of accomplishment. Bivariate and multivariate analyses were conducted to assess the prevalence of burnout and its related factors. The adjusted response rate was 45.9% (444/967). In the subscales of burnout, 41.2%, 55.9%, and 41.4% of respondents scored highly in emotional exhaustion and depersonalisation and poorly for personal sense of accomplishment, respectively. High burnout seems to be more likely to occur in association with some of the sociodemographic and job-related characteristics, especially younger age, male gender, without occupational calling, and unwilling to reselect a dentistry as a job. This study suggests that burnout is a common problem in Korean dentists and that occupational calling and willing to reselect a dentistry as a job are important factors for managing burnout.


Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome. A prospective, randomised, blinded assessment.
The advantages and disadvantages of endoscopic compared with open carpal tunnel release are controversial. We have performed a prospective, randomised, blinded assessment in a district general hospital in order to determine if there was any demonstrable advantage in undertaking either technique. Twenty-five patients with confirmed bilateral idiopathic carpal tunnel syndrome were randomised to undergo endoscopic release by the single portal Agee technique to one hand and open release to the other. Independent preoperative and postoperative assessment was undertaken by a hand therapist who was blinded to the type of treatment. Follow-up was for 12 months. The operating time was two minutes shorter for the open technique (p < 0.005). At all stages of postoperative assessment, the endoscopic technique had no significant advantages in terms of return of muscle strength and assessment of hand function, grip strength, manual dexterity or sensation. In comparison with open release, single-portal endoscopic carpal tunnel release has a similar incidence of complications and a similar return of hand function, but is a slightly slower technique to undertake.


The reconstructed evolutionary process.
Phylogenies reconstructed from contemporary taxa do not contain information about lineages that have gone extinct. We derive probability models for such phylogenies, allowing real data to be compared with specified null models of evolution, and lineage birth and death rates to be estimated.