Comparison of the safety and efficacy of an oscillating/rotating battery-powered toothbrush and a standard manual toothbrush.
To compare the cleaning efficacy of a battery-powered toothbrush with an oscillating/rotating action (Dr. Best Powerclean) and a standard flat-trimmed manual toothbrush (Elmex super 39) in a single-blind, cross-over clinical study. 78 healthy subjects took part in the study. Subjects were asked to abstain from all oral hygiene procedures for 48 hours, after which hard and soft oral tissues were examined. Plaque was then scored using the Turesky modification of the Quigley-Hein Index, and subjects were instructed to brush their teeth for a total time of 1 minute with either one or the other brush, according to a predetermined randomization schedule. Immediately after brushing, plaque was scored again and hard and soft tissues were re-examined. All plaque scoring was carried out by the same investigator who was blind with respect to the brushes used. Subjects were instructed to continue with their usual oral care routine throughout the study period. They were scheduled to return after 12-14 days, having again abstained from all oral hygiene for 48 hours prior to the visit, in order to repeat the evaluation sequence but brushing with the alternative brush. Prior to analysis of the results, data from the two phases of the study were combined. Both toothbrushes were found to be safe as used in the study. Using the non-parametric Wilcoxon test for paired samples, whole mouth plaque scores were found to be reduced significantly from 2.04 +/- 0.60 to 1.57 +/- 0.51 by the Powerclean toothbrush (P < 0.001), and from 1.99 +/- 0.65 to 1.27 +/- 0.52 by the manual toothbrush (P < 0.001). At approximal surfaces, the plaque scores were also significantly reduced from 2.14 +/- 0.0.59 to 1.69 +/- 0.50 for the Powerclean (P < 0.001), and from 2.08 +/- 0.64 to 1.40 +/- 0.57 for the manual toothbrush (P < 0.001). A comparison of the two brushes revealed that the manual toothbrush removed significantly more plaque than the Powerclean, both for the whole mouth and approximal surfaces (P < 0.001). The Powerclean reduced whole mouth plaque by 23.2 +/- 11.5% compared to 37.8 +/- 14.0% for the manual toothbrush and approximal plaque by 20.9 +/- 10.6% and 34.9 +/- 14.0%, respectively. It is concluded that the Dr. Best Powerclean toothbrush is not as effective as a standard flat-trimmed manual toothbrush.


Occult fractures of the femoral head in children.
Occult fractures of the hip are rare; they are almost absent from published medical literature and the studies that are reported concern fractures in the elderly population. In this paper the cases of two children, nine and 16 years old are presented who suffered occult fractures of the femoral head during high-energy traumatisms. Conventional X-ray did not reveal bone lesions, although it did show a discrete eccentration of the cephalic nucleus and the diagnosis was delayed until more specific image techniques were applied: bone scanning with Tc99, CT and MRI, revealed fracture from compression in Case 1 and osteochondral fracture in Case 2. The treatment consisted of non-weight-bearing of the joint in the first case and removal of the fragment by arthroscopy in the second. The outcome was good in both patients who had no pain in the hip and complete mobility one year later. (Hip International 2004; 14: 34-8).


The adolescent patient: parental responsibility, the right to be informed and the right to be heard.
The increasing emphasis placed on patients' rights, in dentistry as well as in other areas, is also having repercussions on the structure of the relationship between health care staff, the under-age patient and his /her parents. The authors reflect about the decision-making process when the patient is a minor in the field of dentistry and underline the role of the parties involved (dentist, parents, under-age patient) in different circumstances (e.g. ordinary care or non-routine care; urgent situations; conflict between parents; refusal of the parents; disagreement between the parents and the child, refusal of the under-age patient; etc.). The Law must first ensure that the minors' needs for protection are met by awarding their parents the power and duty to care for them and, thus, also to take health care decisions in their interest. At the same time, domestic legislation and international legislation supports the need to give greater weight to minors' opinions as they approach the age of majority and, therefore, as they acquire a certain degree of maturity. The rights of under-age patients are safeguarded by actively involving them in the decision-making process, with particular reference to their right to information and right to be heard, to the extent that their age and understanding allow, with due consideration to the specific situation.


USING DEEP NEURAL NETWORKS FOR RADIOGENOMIC ANALYSIS.
Radiogenomic studies have suggested that biological heterogeneity of tumors is reflected radiographically through visible features on magnetic resonance (MR) images. We apply deep learning techniques to map between tumor gene expression profiles and tumor morphology in pre-operative MR studies of glioblastoma patients. A deep autoencoder was trained on 528 patients, each with 12,042 gene expressions. Then, the autoencoder's weights were used to initialize a supervised deep neural network. The supervised model was trained using a subset of 109 patients with both gene and MR data. For each patient, 20 morphological image features were extracted from contrast-enhancing and peritumoral edema regions. We found that neural network pre-trained with an autoencoder and dropout had lower errors than linear regression in predicting tumor morphology features by an average of 16.98% mean absolute percent error and 0.0114 mean absolute error, where several features were significantly different (adjusted p-value < 0.05). These results indicate neural networks, which can incorporate nonlinear, hierarchical relationships between gene expressions, may have the representational power to find more predictive radiogenomic associations than pairwise or linear methods.


Biochemical characterization and gene expression of two endo-arabinanases from Penicillium chrysogenum 31B.
We previously described five arabinanolytic enzymes secreted by Penicillium chrysogenum 31B into the culture medium. Here, we describe a sixth such enzyme, termed AbnS1. Analysis of the reaction products of debranched arabinan revealed that AbnS1 cleaved the substrate in an endo manner. The optimum temperature of AbnS1 was 60°C, which was much higher than that of a cold-adapted endo-arabinanase (Abnc) produced by this strain. The abns1 cDNA gene encoding AbnS1 was isolated by in vitro cloning. The deduced amino acid sequence of AbnS1 had 70% identity with that of Abnc. Pfam analysis revealed a Glyco_hydro_43 domain at positions 28 to 318 of AbnS1. Semi-quantitative reverse transcription-polymerase chain reaction analysis indicated that the abns1 gene was constitutively expressed in P. chrysogenum 31B at a low level, although the expression was only slightly induced with arabinose and arabinan. In contrast, expression of the abnc gene encoding Abnc was strongly induced by arabinose, arabinitol, and arabinan. Using debranched arabinan as substrate, recombinant AbnS1 (rAbnS1) accumulated arabinobiose and arabinotriose as the major products. Recombinant Abnc (rAbnc) released mainly arabinotriose and lesser amounts of arabinose and arabinobiose than did rAbnS1. Branched arabinan was completely degraded to arabinose by the action of rAbnS1 or rAbnc in combination with α-L: -arabinofuranosidase.


EGFR-mediated cell cycle regulation.
Cancer is a disease of uncontrolled cell proliferation. The cell cycle provides a crucial platform for coordination between proliferation and cell death. Somatic cells undergo replication and division by traversing the tightly regulated cell cycle. Growth factors play a critical role in initiating signaling events stimulating cell cycle progression, which is crucial for their mitogenic and tumorigenic effects. Epidermal growth factor receptor (EGFR) and its ligands are frequently upregulated in human cancers. The oncogenic effects of EGFR include initiation of DNA synthesis, enhanced cell growth, invasion, and metastasis. Specific abrogation of EGFR results in cell cycle arrest, apoptosis, or dedifferentiaton of cancer cells. Downregulation of EGFR signaling has therapeutic benefit in preclinical and clinical studies. Therefore, better understanding of the mechanisms of regulation and coordination between the cell cycle, cell growth, and cell death will lead to the development of novel cancer therapies.


Alteration of cellular RNA splicing and polyadenylation machineries during productive human cytomegalovirus infection.
Alternative processing of human cytomegalovirus (HCMV) UL37 pre-mRNA predominantly produces the unspliced UL37 exon 1 (UL37x1) RNA and multiple, lower abundance, alternatively spliced UL37 RNAs. The relative abundance of UL37x1 unspliced RNA is surprising because it requires the favoured use of a polyadenylation signal within UL37 intron 1, just upstream of the UL37 exon 2 (UL37x2) acceptor. Here, it was shown that a downstream element (DSE) in UL37x2 strongly enhanced processing at the UL37x1 polyadenylation site, but did not influence UL37x1-x2 splicing. There was a potential binding site (UCUU) for polypyrimidine tract-binding protein (PTB) at the UL37x1 polyadenylation/cleavage site and its mutation to UGGG reduced both polyadenylation and splicing of UL37x1-x2 minigene pre-mRNA, suggesting a role in both RNA processing events. To determine whether lytic HCMV infection altered the balance of RNA processing factors, which bind to UL37 pre-mRNA cis elements, these were investigated in permissively infected primary and immortalized human diploid fibroblasts (HFFs) and epithelial cells. Induction of polyadenylation factors in HCMV-infected, serum-starved (G(0)) HFFs was also investigated. Permissive HCMV infection consistently increased, albeit with different kinetics, the abundance of cleavage stimulation factor 64 (CstF-64) and PTB, and altered hypo-phosphorylated SF2 in different cell types. Moreover, the preponderance of UL37x1 RNA increased during infection and correlated with CstF-64 induction, whereas the complexity of the lower abundance UL37 spliced RNAs transiently increased following reduction of hypo-phosphorylated SF2. Collectively, multiple UL37 RNA polyadenylation cis elements and induced cellular factors in HCMV-infected cells strongly favoured the production of UL37x1 unspliced RNA.


Stoichiometric model and flux balance analysis for a mixed culture of Leptospirillum ferriphilum and Ferroplasma acidiphilum.
The oxidation process of sulfide minerals in natural environments is achieved by microbial communities from the Archaea and Bacteria domains. A metabolic reconstruction of two dominant species, Leptospirillum ferriphilum and Ferroplasma acidiphilum, which are always found together as a mixed culture in this natural environments, was made. The metabolic model, composed of 152 internal reactions and 29 transport reactions, describes the main interactions between these species, assuming that both use ferrous iron as energy source, and F. acidiphilum takes advantage of the organic compounds secreted by L. ferriphilum for chemomixotrophic growth. A first metabolic model for a mixed culture used in bacterial leaching is proposed in this article, which pretends to represent the characteristics of the mixed culture in a simplified manner. It was evaluated with experimental data through flux balance analysis (FBA) using as objective function the maximization of biomass. The growth yields on ferrous iron obtained for each microorganism are consistent with experimental data, and the flux distribution obtained allows understanding of the metabolic capabilities of both microorganisms growing together in a bioleaching process. The model was used to simulate the growth of F. acidiphilum on different substrates, to determine in silico which compounds maximize cell growth, and which are essential. Knockout simulations were carried out for L. ferriphilum and F. acidiphilum metabolic models, predicting key enzymes of central metabolism. The results of this analysis are consistent with experimental data from literature, showing a robust behavior of the metabolic model.


[Biological diagnosis of hereditary metabolic diseases. From selective screening to the mutant-cell bank].
The experience of a specialized laboratory for the biological diagnosis of inborn errors of metabolism in selected pediatrics patients is reported. The strategy starts with a wide testing of blood and urine, as many inborn errors of metabolism can be detected through testing of blood and urine for increased concentration of specific metabolites known to be associated with the genetic defect. Then enzymatic or DNA studies are performed to confirm the diagnosis. The mutant cells mostly fibroblasts are stored in a cell bank and available for other research.


Conv-eRVFL: Convolutional Neural Network Based Ensemble RVFL Classifier for Alzheimer's Disease Diagnosis.
As per the latest statistics, Alzheimer's disease (AD) has become a global burden over the following decades. Identifying AD at the intermediate stage became challenging, with mild cognitive impairment (MCI) utilizing credible biomarkers and robust learning approaches. Neuroimaging techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) are practical research approaches that provide structural atrophies and metabolic variations. With the help of MRI and PET scans, metabolic and structural changes in AD patients can be visible even ten years before the disease's onset. This paper proposes a novel wavelet packet transform-based structural and metabolic image fusion approach using MRI and PET scans. An eight-layer trained CNN extracts features from multiple layers and these features are fed to an ensemble of non-iterative random vector functional link (RVFL) models. The RVFL network incorporates the s-membership fuzzy function as an activation function that helps overcome outliers. Lastly, outputs of all the customized RVFL classifiers are averaged and fed to the RVFL classifier to make the final decision. Experiments are performed over Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and classification is made over CN vs. AD vs. MCI. The model performance obtained is decent enough to prove the effectiveness of the fusion-based ensemble approach.


Electrochemical studies of vitamin K1 microdroplets: electrocatalytic hydrogen evolution.
The voltammetry of a basal-plane pyrolytic graphite electrode modified with a random ensemble of unsupported microdroplets of vitamin K, is investigated when the electrode is immersed in aqueous electrolytes. It is shown that in dilute acidic solutions, electroreduction occurs in a single two-electron two-proton process to yield the corresponding hydroquinone at the electrode\vitamin K1 microdroplet\aqueous-electrolyte three-phase boundary. On addition of ionic alkali-metal salts to the aqueous acidic phase, the electrochemical reduction of vitamin K1 to the quinol is accompanied by catalytic hydrogen evolution within and alkali-metal-cation insertion into the organic microdroplets. In strongly alkaline solutions, electrochemical reduction of vitamin K1 at the triple-phase junction is proposed as being a single two-electron process with concomitant uptake of alkali-metal cations in order to maintain electroneutrality within the oil phase. Surprisingly, the relative ease of cation insertion into the oil phase is demonstrated to be governed by the degree of ion-pair formation rather than by the Gibbs transfer energy of the cation across the liquid\liquid interface.


Telomerase activity in candidate stem cells from fetal liver and adult bone marrow.
Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric repeats onto the 3' ends of eukaryotic chromosomes. Activation of telomerase may prevent telomeric shortening and correlates with cell immortality in the germline and certain tumor cells. Candidate hematopoietic stem cells (HSC) from adult bone marrow express low levels of telomerase, which is upregulated with proliferation and/or differentiation. To address this issue, we stimulated purified candidate HSC from human adult bone marrow with stem cell factor (SCF), interleukin-3 (IL-3), and Flt3-ligand (FL). After 5 days in culture, activity was detected in total cell extracts from IL-3-, SCF + FL-, SCF + IL-3-, FL + IL-3-, and SCF + IL-3 + FL-stimulated cultures, but not from cells cultured in SCF or FL alone. Within the CD34(+) fraction of the cultured cells, significant activity was found in the CD34(+)CD71(+) fraction. In addition, PKH26 staining confirmed that detectable telomerase activity was present in dividing PKH26(lo) cells, whereas nondividing PKH26(hi) cells were telomerase negative. Because in these experiments no distinction could be made between cycling "candidate" stem cells that had retained or had lost self-renewal properties, fetal liver cells with a CD34(+)CD38(-) phenotype, highly enriched for cycling stem cells, were also examined and found to express readily detectable levels of telomerase activity. Given the replication-dependent loss of telomeric DNA in hematopoietic cells, these observations suggest that the observed telomerase activity in candidate stem cells is either expressed in a minor subset of stem cells or, more likely, is not sufficient to prevent telomere shortening.


Self-resolution of alcohol problems in young adulthood: a process of securing solid ground.
Quantitative research findings suggest that young adults resolve alcohol problems without participating in support groups or formal treatment programs. However, researchers have failed to fully explain the self-resolution process among this age group. Thus, the authors used grounded theory to better explicate why and how young adults self-resolve alcohol problems. The findings suggest that self-resolving alcohol problems in young adulthood involves a temporal process of seeking and securing solid ground. This process is precipitated by situations in which individuals experience precarious footing and eventually begin to lose their balance. These culminating events lead young adults to pursue personal visions and find safe footing on solid ground, despite some rugged terrain along the way.


Serologic survey for leishmaniasis in free-living red foxes (Vulpes vulpes) in Italy.
Sera from fifty free-ranging red foxes (Vulpes vulpes) from the Imperia province, Liguria, Italy, were examined for antibodies against Leishmania spp. by both immunofluorescence assay (IFA) and enzyme linked immunosorbent assay (ELISA), from January to May 1992. Nine of 50 animals (18%) had antibodies against Leishmania spp. utilizing both IFA and ELISA tests.


Chemical crosslinking of myosin subfragment-1 to F-actin in the presence of nucleotide.
F-Actin and myosin subfragment-1 (S-1) were covalently crosslinked in the absence and presence of nucleotides, adenyl-5'-yl imidodiphosphate (AMPPNP), ATP, and ADP, at various KCl concentrations (0-0.5 M), using a zero-length crosslinker, 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC). The rate of production of the covalent acto-S-1 complex was almost proportional to the amount of the acto-S-1(-nucleotide) complex existing in the reaction medium. However, the Mg-ATPase activity of the covalent acto-S-1 complex thus produced was affected by the presence of nucleotides. When S-1 was crosslinked to F-actin in the absence of nucleotide at 0-0.5 M KCl, the Mg-ATPase activity of S-1 was enhanced from 0.1-0.3 to 12-15 s-1. The Mg-ATPase activity of covalent complex produced in the presence of AMPPNP at 0 M KCl was 13 s-1 which was equal to that produced in the absence of nucleotide. The activity decreased with increasing KCl concentration of the crosslinking medium, reaching 6 s-1 at 0.5 M KCl. Covalent acto-S-1 complex was also produced when acto-S-1-ADP-P was formed during ATP hydrolysis. The Mg-ATPase activity of the covalent acto-S-1 complex crosslinked during ATP hydrolysis at 0 M KCl was about 5 s-1 which was about half of that obtained in the absence of nucleotide, and it decreased to about 2 s-1 at 0.15 M KCl of crosslinking medium. In contrast, the acto-S-1-ADP complex gave a covalent complex which was indistinguishable in its extent and Mg-ATPase activity from that obtained in the absence of nucleotide. These results suggest that the structures of acto-S-1-AMPPNP and acto-S-1-ADP-P complexes are different from those of acto-S-1 and acto-S-1-ADP complexes.


Induced systemic candidiasis in young broiler chickens.
Systemic candidiasis was induced in broiler chickens 14 days old by intravenous injection of a suspension of viable Candida albicans cells. Injection resulted in decreased body weight, moderate mortality, swollen and reddened livers and kidneys, pancreatitis, and disturbances of the nervous system. Three types of neutral disturbances were observed: 1) extreme opisthotonus with spasmodic tremors; 2) extreme torticollis with cranial rotation of 270 degrees: and 3) extreme torticolis which resulted in the head being drawn in a medial-ventral direction. None to 50% of the inoculated birds exhibited these neural disturbances, depending on the isolant of C. albicans used. Microbiological examination of internal organs and blood revealed that C. albicans localized in the meninges of the brain. There was also a significant isolant-related effect of C. albicans on the growth rate of the inoculated birds. These easily quantitated differential effects of various isolants of C. albicans offer the prospect of correlating biochemical characteristics with virulence and obtaining information about the mechanism of pathogenicity of this microorganism.


The control of reactive oxygen species influences porcine oocyte in vitro maturation.
The aim of this study was to examine the effect of varying intracellular reactive oxygen species (ROS) levels during oocyte in vitro maturation with enzymatic ROS production systems (xanthine + xanthine oxidase or xanthine + xanthine oxidase + catalase), scavenger systems (catalase or superoxide dismutase + catalase) or cysteine on porcine oocyte maturation. Oocyte ROS levels showed an increase when H2O2 or O2∙(-) production systems were added to the culture medium (p < 0.05). On the other hand, the presence of ROS scavengers in the maturation medium did not modify oocyte ROS levels compared with the control after 48 h of maturation, but the addition of cysteine induced a decrease in oocyte ROS levels (p < 0.05). The ROS production systems used in this work did not modified the percentage of oocyte nuclear maturation, but increased the decondensation of sperm head (p < 0.05) and decreased the pronuclear formation (p < 0.05). In turn, the addition of O2∙(-) and H2O2 scavenging systems during in vitro maturation did not modify the percentage of oocytes reaching metaphase II nor the oocytes with decondensed sperm head or pronuclei after fertilization. However, both parameters increased in the presence of cysteine (p < 0.05). The exogenous generation of O2∙(-) and H2O2 during oocyte in vitro maturation would not affect nuclear maturation or later sperm penetration, but most of the spermatozoa cannot progress to form the pronuclei after fusion with the oocyte. The decrease in endogenous ROS levels by the addition of cysteine would improve pronuclear formation after sperm penetration.


Responding to pediatric trauma.
Pediatric trauma care can seem daunting even to seasoned critical care nurses, if they have not worked frequently with young patients. Children differ from adults in significant anatomic and physiologic ways and require equipment, supplies, and medication dosages carefully tailored to their body size and weight. This article gives nurses a solid foundation in pediatric care by reviewing the differences between adult and child patients as well as the shared priorities involved in pediatric and adult trauma care.


Flavonoids: a re-run of the carotenoids story?
Flavonoids have powerful antioxidant activities in vitro, but the evidence that they act as antioxidants in vivo in humans is equivocal at best. However, they may be able to help protect the gastro-intestinal tract against reactive oxygen species.


Blood glucose monitoring in type 2 diabetes - Nepalese patients' opinions and experiences.
Blood glucose monitoring forms a vital component of diabetes care. Monitoring conducted at home using glucometers, and in laboratories by professionals, are two common methods of blood glucose monitoring in clinical practice. To investigate Nepalese patients' perceptions and practices of blood glucose monitoring in diabetes. In-depth interviews were conducted with 48 Nepalese participants with type 2 diabetes in Sydney and Kathmandu. The interviews were audio-recorded, transcribed verbatim and thematically analysed. In Australia, most participants perceived home monitoring as useful; and both home and laboratory monitoring were conducted at fairly regular intervals. In Nepal, only a small number conducted home monitoring and the laboratory method formed the primary method of day-to-day monitoring. The laboratory method was preferred due to easy access to laboratories, lack of faith in glucometers and perceptions that home monitoring is costlier. However, overall monitoring was irregular in Nepal. In addition to the healthcare system which enabled cheaper self-monitoring in Australia, Nepalese in Australia also tended to have a better understanding about the purpose of home monitoring. This study has highlighted the disparity in perceptions and practices related to blood glucose monitoring. Understanding the importance of blood glucose monitoring and access to affordable resources are critical facilitators for conducting regular monitoring. Both patient and health-system factors play a key role in ensuring continued diabetes monitoring and management.


[Trematodes (Trematoda) of bats (Chiroptera) from the Middle Volga Region].
The data on species diversity of trematodes from bats collected in the Middle Volga Region are summarized. According to original and literary data, 20 trematode species were recorded in bats of the region examined. Plagiorchis elegans, Lecithodendrium skrjabini, L. rysavyi, Prosthodendrium hurkovaae, and Pycnoporus megacotyle are specified for the bat fauna of Russia for the first time. For 11 species of parasites, new hosts are recorded. The analysis of bat helminthes demonstrated that the fauna of trematodes of the northern bat (12 species of trematodes), of the pond, and of the Brandt's bats is the most diverse, constituting more than 10 parasite species per bat species. The largest number of final hosts in the Middle Volga Region is characteristic of Plagiorchis koreanus and Prosthodendrium chilostomum; the latter species were revealed in 8 and 7 bat species, respectively. Trematodes of bats possess a high degree of host specificity. 17 species parasitize exclusively in bats out of 20 parasite species registered for the order Chiroptera. Only 3 species (Plagiorchis elegans, P. vespertilionis, and Prosthodendrium chilostomum) show wide degree of specificity, being found in other animals. Taxonomic position, the circle of hosts, collecting sites, and brief data in biology and geographical distribution for each helminth species are specified. Morphological descriptions and original figures for all the trematode species revealed in bats of the Middle Volga Region are given.


Entrustment of the on-call senior medical resident role: implications for patient safety and collective care.
The on-call responsibilities of a senior medicine resident (SMR) may include the admission transition of patient care on medical teaching teams (MTT), supervision of junior trainees, and ensuring patient safety. In many institutions, there is no standardised assessment of SMR competency prior to granting these on-call responsibilities in internal medicine. In order to fulfill competency based medical education requirements, training programs need to develop assessment approaches to make and defend such entrustment decisions. The purpose of this study is to understand the clinical activities and outcomes of the on-call SMR role and provide training programs with a rigorous model for entrustment decisions for this role. This four phase study utilizes a constructivist grounded theory approach to collect and analyse the following data sets: case study, focus groups, literature synthesis of supervisory practices and return-of-findings focus groups. The study was conducted in two Academic Health Sciences Centres in Ontario, Canada. The case study included ten attending physicians, 13 SMRs, 19 first year residents and 14 medical students. The focus groups included 19 SMRs. The later, return-of-findings focus groups included ten SMRs. Five core on-call supervisory tasks (overseeing ongoing patient care, briefing, case review, documentation and preparing for handover) were identified, as well as a range of practices associated with these tasks. We also identified challenges that influenced the extent to which SMRs were able to effectively perform the core tasks. At times, these challenges led to omissions of the core tasks and potentially compromised patient safety and the admission transition of care. By identifying the core supervisory tasks and associated practices, we were able to identify the competencies for the on-call SMR role. Our findings can further be used by training programs for assessment and for making entrustment decisions.


Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: a new homology modeling tool.
Modeling by homology is the most accurate computational method for translating an amino acid sequence into a protein structure. Homology modeling can be divided into two sub-problems, placing the polypeptide backbone and adding side-chains. We present a method for rapidly predicting the conformations of protein side-chains, starting from main-chain coordinates alone. The method involves using fewer than ten rotamers per residue from a backbone-dependent rotamer library and a search to remove steric conflicts. The method is initially tested on 299 high resolution crystal structures by rebuilding side-chains onto the experimentally determined backbone structures. A total of 77% of chi1 and 66% of chi(1 + 2) dihedral angles are predicted within 40 degrees of their crystal structure values. We then tested the method on the entire database of known structures in the Protein Data Bank. The predictive accuracy of the algorithm was strongly correlated with the resolution of the structures. In an effort to simulate a realistic homology modeling problem, 9424 homology models were created using three different modeling strategies. For prediction purposes, pairs of structures were identified which shared between 30% and 90% sequence identity. One strategy results in 82% of chi1 and 72% chi(1 + 2) dihedral angles predicted within 40 degrees of the target crystal structure values, suggesting that movements of the backbone associated with this degree of sequence identity are not large enough to disrupt the predictive ability of our method for non-native backbones. These results compared favorably with existing methods over a comprehensive data set.


Two decades of blaVIM-2-producing Pseudomonas aeruginosa dissemination: an interplay between mobile genetic elements and successful clones.
Information on clonal lineages and genetic platforms involved in the mobilization of carbapenemases between Pseudomonas aeruginosa strains in Portugal is scarce. Here, we outline the genetic drivers contributing to the occurrence of blaVIM-2-producing P. aeruginosa over two decades. A collection of carbapenem-resistant P. aeruginosa clinical isolates (n = 263, 1995-2014) was screened for carbapenemase production by Blue-Carba and PCR. Antimicrobial susceptibility testing was performed according to EUCAST and clonal analysis by MLST. Nine isolates representing different integrons and STs were selected for WGS, followed by bioinformatics. Twenty-seven blaVIM-2-producing P. aeruginosa belonging to 10 STs were identified, with ST179 and ST111 being the most prevalent and persistent clones. blaVIM-2 was associated with seven class I integrons frequently co-harbouring aminoglycoside resistance genes. In58 was commonly identified, followed by derivatives and In100. blaVIM-2-harbouring transposons of the Tn3 and Tn402 families were linked to different plasmids or integrative conjugative elements of the clc family. The dissemination of blaVIM-2 carrying integrons is associated with a complex interplay between different mobile genetic elements, including the overlooked integrative conjugative elements, and successful spread of particular clones.


Testicular steroid sulfotransferases: comparison to liver and adrenal steroid sulfotransferases of the mature rat.
Steroid sulfotransferase activity was investigated in cytosol fractions of whole testes, isolated seminiferous tubules, isolated interstitial tissue, livers, and adrenal glands of mature male rats. Enzyme activity was measured by incubating cytosol fractions with 3H-labeled pregnenolone, dehydroepiandrosterone, testosterone, or estradiol and the active sulfate donor 3'-phosphoadenosine-5'-phosphosulfate. Testicular steroid sulfotransferase activity was found in seminiferous tubules. 3 beta-Hydroxysteroid sulfotransferase activity of seminiferous tubules exhibited a pH optimum of 10 in contrast to a pH optimum of 5 reported for cytosol fractions of rat liver. Marked differences in substrate specificity were demonstrated in the three tissues. The preferred substrate for the 3 beta-hydroxysteroid sulfotransferase in seminiferous tubules was pregnenolone, and in liver it was dehydroepiandrosterone, No 3 beta-hydroxysteroid sulfotransferase activity could be detected in cytosol fractions of adrenal glands. Testosterone was sulfated only by hepatic cytosol fractions. All three tissues contained estrogen sulfotransferase activity. These data suggest that the 3 beta-hydroxysteroid sulfotransferase of seminiferous tubules is distinct from the 3 beta-hydroxysteroid sulfotransferase of liver. These differences may relate to different functions of steroid sulfates in liver and testes.


Phase I, Open-Label, Dose-Escalation Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2879552 in Relapsed/Refractory SCLC.
This first-time-in-humans study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of GSK2879552 in patients with relapsed or refractory SCLC. This phase I, multicenter, open-label study (NCT02034123) enrolled patients (≥18 years old) with relapsed or refractory SCLC (after ≥1 platinum-containing chemotherapy or refusal of standard therapy). Part 1 was a dose-escalation study; Part 2 was a dose-expansion study. Dose escalations were based on safety, PK, and PD. The primary end point (Part 1) was to determine the safety, tolerability, and recommended dose and regimen of GSK2879552. Secondary end points were to characterize PK and PD parameters and measure disease control rate at week 16. Part 2 was not conducted. Between February 4, 2014, and April 18, 2017, a total of 29 patients were allocated to one of nine dose cohorts (0.25 mg-3 mg once daily and 3-mg or 4-mg intermittent dosing). In all, 22 patients completed the study; 7 withdrew, primarily owing to adverse events (AEs). Most patients (24 of 29 [83%]) had at least one treatment-related AE, most commonly thrombocytopenia (12 of 29 [41%]). Twelve serious AEs (SAEs) were reported by nine patients; six were considered treatment related, the most common of which was encephalopathy (four SAEs). Three patients died; one death was related to SAEs. PK was characterized by rapid absorption, slow elimination, and a dose-proportional increase in exposure. GSK2879552 is a potent, selective inhibitor of lysine demethylase 1A and has demonstrated favorable PK properties but provided poor disease control and a high AE rate in patients with SCLC. The study was terminated, as the risk-benefit profile did not favor continuation.


Great suffering, great compassion: a transcultural opportunity for school nurses caring for Cambodian refugee children.
The cultural ways of Cambodian refugee families, combined with the physical and psychological health problems inherent in their refugee experience, present opportunities for nurses to engage in transcultural nursing. The purpose of this descriptive study was to understand the nature and meaning of a school district cross-cultural team's experiences of providing health care for children of Cambodian refugee families. Focus group interviews with school nurses and Cambodian liaisons were conducted utilizing S. M. Dobson's conceptual framework of transcultural health visiting as a guiding theoretical perspective. Transcultural and intracultural reciprocity as experienced with Cambodian families are explored and described. Concrete suggestions for fostering transcultural reciprocity with Cambodian refugee families are provided.


Tumor cell membrane as a potential target for methyl-beta-cyclodextrin.
The purpose of this work was to determine the role of methyl-beta-cyclodextrin (MEBCD) in combination with doxorubicin (DOX) on DOX intracellular accumulation and efflux, in comparison to verapamil in a sensitive parental and multidrug-resistant human cancer cell line (HL-60 S and HL-60 R). Moreover, cell membrane and nuclear modifications induced by MEBCD were investigated. At concentration of 10 mumol for 10(6) cells, MEBCD combined with doxorubicin (DOX), was able to significantly enhance the intracellular concentration of DOX in HL-60 S and HL-60 R cell lines during the period of exposure. In the resistant subline, MEBCD activity was higher than that of verapamil. Moreover, treatment of cells with MEBCD resulted in a modification in cell membrane integrity and cell morphology, but had no own activity in the distribution of the cells within cell cycle.


[Echographic markers of fetal chromosomopathies. Diagnostic possibilities with transvaginal ultrasonography and our experience].
Aim of this study was to evaluate, during early pregnancy, the correlation of some anomalies and malformations with fetal chromosomopathies. Morphostructural and biometric anomalies in chromosomopathic fetuses were evaluated. 1331 pregnancies at high risk for genetic disease and malformations referred to our center for prenatal diagnosis. Scans were performed using endovaginal convex probes (5.0 to 7.0 MHz). Urinary, cardiac and cerebral malformations as well as alterations of bone growth were evaluated. With respect to the other malformations, cystic hygroma is more frequently associated with an abnormal fetal karyotype. The majority of morphostructural abnormalities diagnosed during first trimester by transvaginal sonography cannot, in according to personal experience, be used as markers of chromosomopathies.


The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase.
Chromosomal stability is safeguarded by a mitotic checkpoint, of which BUB1 and Mad3/BUBR1 are core components. These paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution, followed by parallel subfunctionalization in which preservation of the ancestral, amino-terminal KEN box or kinase domain was mutually exclusive. In one exception, vertebrate BUBR1-defined by the KEN box-preserved the kinase domain but allowed nonconserved degeneration of catalytic motifs. Although BUBR1 evolved to a typical pseudokinase in some vertebrates, it retained the catalytic triad in humans. However, we show that putative catalysis by human BUBR1 is dispensable for error-free chromosome segregation. Instead, residues that interact with ATP in conventional kinases are essential for conformational stability in BUBR1. We propose that parallel evolution of BUBR1 orthologs rendered its kinase function dispensable in vertebrates, producing an unusual, triad-containing pseudokinase.


[Surgical treatment of bronchial cancer--current status].
It is still difficult to codify the surgical treatment of primary bronchogenic cancer. In spite of improvements of means of diagnosis and of detection of metastases the results at intermediate and long term are frequently modest. The techniques of resection are improved, and this is the method of choice in all cases where function and anatomical situation are permissive. The risk of the operation is minimal if the respiratory function is well, even with very extended resections. This is the greatest progress during the last 30 years. Surgery can cure only tumors which are still localized. Research on complementary treatment of extended forms is still necessary.


Temporal and masking phenomena in persons with sensorineural hearing loss.
Relatively few experimental investigations have studied backward or forward masking, masking level differences, or differential frequency effects in simultaneous masking among persons with hearing impairment. This is regrettable since such efforts may lead to important new understandings of auditory processes. This paper reviews available data, discusses some precautions of experimental procedure, and offers suggestions for future research directions.


Environmental and cultural stimulants in the production of carotenoids from microorganisms.
Commercial production of carotenoids from microorganisms competes mainly with synthetic manufacture by chemical procedures. Efficient stimulation of carotenoid biosynthesis is expected to promote accumulation of carotenoid by microbes. This review describes the variety of environmental and cultural stimulants studied during the last few decades which enhance volumetric production and cellular accumulation of commercially important carotenoids from microalgae, fungi and bacteria. Stimulation of carotenoid production by white-light illumination and temperature fluctuation is discussed along with supplementation of metal ions, salts, organic solvents, preformed precursors and several other chemicals in the culture broth. Reports on the improvements in yield are reviewed and assessed from a biotechnology point of view.