An improved transplantation strategy for mouse mesenchymal stem cells in an acute myocardial infarction model.
To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1(st) BM-MSCs) and 5(th) passage BM-MSCs from β-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6(th) week, animals/tissues from the 1(st) BM-MSCs group, the 5(th) passage BM-MSCs group, control group were examined. Our results revealed that, compared to the 5(th) passage BM-MSCs, the 1(st) BM-MSCs had better therapeutic effects in the mouse MI model. The 1(st) BM-MSCs maintained greater differentiation potentials towards cardiomocytes or vascular endothelial cells in vitro. This is indicated by higher expressions of cardiomyocyte and vascular endothelial cell mature markers in vitro. Furthermore, we identified that 24 proteins were down-regulated and 3 proteins were up-regulated in the 5(th) BM-MSCs in comparison to the 1(st) BM-MSCs, using mass spectrometry following two-dimensional electrophoresis. Our data suggest that transplantation of the 1(st) BM-MSCs may be an effective therapeutic strategy for cardiac tissue regeneration following AMI, and altered protein expression profiles between the 1(st) BM-MSCs and 5(th) passage BM-MSCs may account for the difference in their maintenance of stemness and their therapeutic effects following AMI.


Detection of Puccinia kuehnii Causing Sugarcane Orange Rust with a Loop-Mediated Isothermal Amplification-Based Assay.
Puccinia kuehnii is a fungal pathogen that causes orange rust in sugarcane, which is now prevalent in many countries. At the early stage of disease, it is almost indistinguishable from brown rust, which is caused by Puccinia melanocephala. Although several PCR assays are available to detect these diseases, the loop-mediated isothermal amplification (LAMP)-based assay has been reported to be more economical and easier to perform. Under isothermal conditions, DNA is amplified with high specificity and rapidity. Moreover, visual judgment of color change without further post-amplification processing makes the method convenient. The present study was undertaken to detect P. kuehnii genomic DNA using four primers corresponding to a unique DNA sequence of P. kuehnii. The LAMP assay was found to be optimal when 8 mM MgSO4 was used and the reaction was incubated at 63 °C for 90 min. Positive samples showed a color change from orange to green upon SYBR Green I dye addition. Specificity of the LAMP test was checked with DNA of P. melanocephala, which showed no reaction. Sensitivity of the LAMP method was observed to be the same as real-time PCR at 0.1 ng, thus providing a rapid and more affordable option for early disease detection.


When is a grade 4 pressure ulcer not grade 4?
The adoption of the European Pressure Ulcer Advisory Panel (EPUAP) (2009) pressure ulcer classification system within healthcare trusts in the UK has provided health professionals with a common approach for the description of tissue damage for pressure ulcers. However, the omission of the 'unstageable/unclassified' and 'suspected deep tissue injury under intact skin' has caused difficulties when the visual appearance of pressure ulcers falls outside the four grades listed in the classification system. These difficulties lead health professionals to overestimate the degree of tissue damage, resulting in confusion in regards to determining the true extent of the tissue damage and often misdirection of scarce resources (Moore, 2005). The Berkshire Tissue Viability Nurses Group attempted to bring clarity to the situation by highlighting the issues to raise awareness and stimulate discussion among health professionals. The author, with support of the Berkshire Tissue Viability Nurses Group, first presented the content of this article at a meeting of the No Needless Skin Breakdown Work Stream meeting of the South Central Strategic Health Authority Patient Safety Federation in January 2011.


Caves as a key habitat for rare and endemic species of the west coast of North America: a taxonomic revision of the spider genus Oaphantes (Araneae: Linyphiidae).
The genus Oaphantes is known from the West Coast of North America. Here we revise the genus which now includes three species, two of which are new: O. cryophilus n. sp. and O. prometheus n. sp. All Members of the genus Oaphantes show affinities for cave habitats. Oaphantes pallidulus is known from caves of the Coast Ranges of California and also from epigean records. Oaphantes cryophilus n. sp. is restricted to caves in the southern limit of its distribution in the Sierra Nevada Mountains of California, but in the north it is known from epigean records in Oregon, Washington and British Columbia. Oaphantes prometheus n. sp. is an eyeless troglobite endemic to a single cave in the Sierra Nevada of California. The distribution and relationships of the three species suggest an evolutive scenario likely due to climatic variations and affinities for colder conditions.


Single-cell analysis for drug development using convex lens-induced confinement imaging.
New technologies have powered rapid advances in cellular imaging, genomics and phenotypic analysis in life sciences. However, most of these methods operate at sample population levels and provide statistical averages of aggregated data that fail to capture single-cell heterogeneity, complicating drug discovery and development. Here we demonstrate a new single-cell approach based on convex lens-induced confinement (CLiC) microscopy. We validated CLiC on yeast cells, demonstrating subcellular localization with an enhanced signal-to-noise and fluorescent signal detection sensitivity compared with traditional imaging. In the live-cell CLiC assay, cellular proliferation times were consistent with flask culture. Using methotrexate, we provide drug response data showing a fivefold cell size increase following drug exposure. Taken together, CLiC enables high-quality imaging of single-cell drug response and proliferation for extended observation periods.


Longitudinal Model Predicting Self-Concept in Pediatric Chronic Illness.
Although self-concept has been identified as salient to the psychosocial adjustment of adolescents dealing with a chronic illness (CI), little research has focused on its predictors it. Given that depression and parent-child attachment have been linked to self-concept in the population at large, the goal of this study was to evaluate these relationships longitudinally in a sample of adolescents with CI. Using participant data from the Mastering Each New Direction (MEND) program, a 3-month psychosocial, family based intensive outpatient program for adolescents with CI, we employed multilevel modeling to test longitudinal changes in self-concept, as predicted by depressive symptoms and parent-child attachment, in a sample of 50 youths (Mage = 14.56, SDage = 1.82) participating in MEND. Both "time spent in the program" and decreases in depressive symptoms were associated with increases in self-concept over time. Higher baseline levels of avoidant attachment to both mother and father were also associated with greater initial levels of self-concept. Targeting depressive symptoms and supporting adaptive changes in attachment may be key to promoting a healthy self-concept in pediatric CI populations. The association between avoidant attachment and higher baseline self-concept scores may reflect differences in participants' autonomy, self-confidence, or depression. Limitations of the study include variability in the amount of time spent in the program, attrition in final time point measures, and the inability to fully examine and model all potential covariates due to a small sample size (e.g. power).


A study of new referrals to a menopause clinic and their initial outcomes: how can we improve the service we provide?
This retrospective case-note study was performed to examine the ways in which an already established menopause clinic could improve service to its patients. The management of 151 patients was examined. Most were referred by their general practitioner and the most common reason for referral was to seek an alternative to hormone replacement therapy (HRT). The consultant saw 17% of the patients, and with the trainee was most likely to discharge the patient. Better information on alternatives to HRT, more consultant input and better use of telephone consultation for follow-up would enhance the service provided by the menopause clinic.


Sustainable Feedstocks and Challenges in Biodiesel Production: An Advanced Bibliometric Analysis.
Biodiesel can be produced from vegetable oils, animal fats, frying oils, and from microorganism-synthesized oils. These sources render biodiesel an easily biodegradable fuel. The aim of this work was to perform an advanced bibliometric analysis of primary studies relating to biodiesel production worldwide by identifying the key countries and regions that have shown a strong engagement in this area, and by understanding the dynamics of their collaboration and research outputs. Additionally, an assessment of the main primary feedstocks employed in this research was carried out, along with an analysis of the current and future trends that are expected to define new paths and methodologies to be used in the manufacture of biodegradable and renewable fuels. A total of 4586 academic outputs were selected, including peer-reviewed research articles, conference papers, and literature reviews related to biodiesel production, in the time period spanning from 2010 to 2021. Articles that focused on feedstocks for the production of biodiesel were also included, with a search that returned 330 papers. Lastly, 60 articles relating to biodiesel production via sewage were specifically included to allow for an analysis of this source as a promising feedstock in the future of the biofuel market. Via the geocoding and the document analyses performed, we concluded that China, Malaysia, and India are the largest writers of articles in this area, revealing a great interest in biofuels in Asia. Additionally, it was noted that environmental concerns have caused authors to conduct research on feedstocks that can address the sustainability challenges in the production of biodiesel.


Incompatibility mutants of IncFII plasmid NR1 and their effect on replication control.
DNA from the replication control region of plasmid NR1 or of the Inc- copy mutant pRR12 was cloned into a pBR322 vector plasmid. These pBR322 derivatives were mutagenized in vitro with hydroxylamine and transformed into Escherichia coli cells that harbored either NR1 or pRR12. After selection for the newly introduced pBR322 derivatives only, those cells which retained the unselected resident NR1 or pRR12 plasmids were examined further. By this process, 134 plasmids with Inc- mutations in the cloned NR1 or pRR12 DNA were obtained. These mutants fell into 11 classes. Two of the classes had plasmids with deletions or insertions in the NR1 DNA and were not examined further. Plasmids with apparent point mutations were classified by examining (i) their ability to reconstitute a functional NR1-derived replicon (Rep+ or Rep-), (ii) the copy numbers of the Rep+ reconstituted replicons, (iii) the cross-reactivity of incompatability among the various mutant classes and parental plasmids, and (iv) the trans effects of the mutants on the copy number and stable inheritance of a coresident plasmid.


Increased risk of allergy associated with the use of kerosene fuel in the home.
Allergic diseases are becoming increasingly prevalent in developing countries, consistent with an environmental etiology associated with affluence or urbanization. We have tested the hypothesis that the risk of allergy is increased by the use of non-biomass fuels (kerosene, gas or electricity) in the home, using data from a survey of the urban population of Jimma, Ethiopia. Questionnaire data on allergic symptoms, domestic fuel use and lifestyle factors were collected from 9844 adults and children, and allergen skin sensitization measured in a subsample of 2372. Use of any non-biomass fuel was reported by 959 individuals (10%), usually in combination with biomass fuel, and was significantly associated with an increased risk of allergic sensitization (age, sex and socio-economic status adjusted odds ratio (95% confidence interval) = 1.78 [1.06 to 2.97]) and wheeze (1.56 [1.07 to 2.26]), rhinitis (2.06 [1.46 to 2.91]) and eczema (2.82 [1.61 to 4.96]) relative to use of biomass fuel only. These effects were predominantly due to kerosene, which was significantly related to all outcomes, and gas, which was strongly related to allergic sensitization. Our findings suggest that domestic combustion of refined fossil fuels increases the risk of allergic sensitization and symptoms, and may have contributed to the increasing prevalence of allergic disease.


Francisella tularensis 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase: kinetic characterization and phosphoregulation.
Deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. Isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (MVA) or methylerythritol phosphate (MEP) pathway. While mammals utilize the MVA pathway, many bacteria utilize the MEP pathway, highlighting the latter as an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP cytidylyltransferase, a MEP pathway enzyme and potential target for antibiotic development. Size exclusion chromatography indicates the protein exists as a dimer in solution. Enzyme assays produced an apparentK(MEP)(M) = 178 μM, K(CTP)(M) = 73 μM , k(MEP)(cat) = 1(s-1), k(CTP)(cat) = 0.8( s-1), and a k(MEP)(cat)/ K(MEP)(M) = 3.4 x 10(5) M(-1) min(-1). The enzyme exhibits a strict preference for Mg(+2) as a divalent cation and CTP as the nucleotide. Titanium dioxide chromatography-tandem mass spectrometry identified Thr141 as a site of phosphorylation. T141D and T141E site-directed mutants are catalytically inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP cytidylyltransferase is an excellent target for the development of novel antibiotics against F. tularensis.


Large telangiectatic focal nodular hyperplasia presenting with normal radionuclide studies: case report.
A 9 cm-lesion of telangiectatic focal nodular hyperplasia was incidentally identified in a 31-yr-old female. Despite a typical appearance by X-ray computed tomography and ultrasonography, scintigraphy with technetium-99m-(99mTc) colloid, 99mTc-diethyliminodiacetic acid, and 99mTc-labeled red cells failed to demonstrate any abnormalities. These findings are felt to reflect the relative lack of architectural disruption that histologically characterizes this particular lesion. The present report described the imaging characteristics of the telangiectatic form of focal nodular hyperplasia.


Nucleus: cell volume ratio directs the timing of the increase in blastomere adhesiveness in starfish embryos.
Blastomeres of starfish embryos begin to increase in adhesiveness after the eighth cleavage and form a monolayered hollow blastula. To investigate factors that affect the timing of the adhesiveness increase, we changed the volume of the cytoplasm or the ploidy of embryos and examined the morphologic changes in the descendent blastomeres during early cleavage stages. In parthenogenetic embryos, in which the ploidy is doubled, the timing of the increase in adhesiveness was accelerated by one cell cycle. In contrast, the timing was delayed by approximately one cell cycle in a large-sized embryo formed by the fusion of an egg and a non-nucleate egg fragment. These two sets of observations are in accord with the expectation from the classical concept that the DNA: cytoplasmic ratio may direct the timing of events in early development. However, observations of small-sized embryos with a reduced amount of cytoplasm were contradictory to the expectation based on the DNA: cytoplasmic ratio; the timing of the increase in adhesiveness in half-sized embryos was almost the same as in control embryos and the timing was delayed by only one cell cycle in quarter-sized embryos. Measurement of the diameters of nuclei showed that the size of nuclei was variable, depending on the stage of development, the volume of cytoplasm and ploidy. We calculated a volume ratio of nucleus to cytoplasm (N: C volume ratio) for tetraploid, large-, half- and quarter-sized embryos. We found that the embryonic cells begin to adhere always when their N: C volume ratio reaches 0.06. A plausible model for the cellular timing mechanism of cell contact is proposed.


Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation.
Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 (SAMP8) mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer's disease model mice. Sanjiao acupuncture was used to stimulate Danzhong (CV17), Zhongwan (CV12), Qihai (CV6), bilateral Xuehai (SP10) and bilateral Zusanli (ST36) 15 days before and after implantation of neural stem cells (5 × 105) into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica, was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone, learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.


A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα.
As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells, but the mechanism that controls FcεRIα expression in these cells is poorly understood. In this study, we found that the natural antisense transcript (NAT) of FcεRIα (FCER1A-AS) is co-expressed with the sense transcript (FCER1A-S) in both interleukin (IL)-3-induced FcεRIα-expressing cells and in the high FcεRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by the CRISPR/RfxCas13d (CasRx) approach in MC/9 cells, the expression of both FCER1A-S mRNA and proteins is markedly decreased. Furthermore, FCER1A-AS deficiency was also found to be associated with a lack of FCER1A-S expression in vivo. Correspondingly, homozygous mice deficient in FCER1A-AS demonstrated a similar phenotype to FCER1A knockout mice in Schistosoma japonicum infection and in IgE-FcεRIα-mediated cutaneous anaphylaxis. Thus, we uncovered a novel pathway for the control of FcεRIα expression by its co-expressed natural antisense transcript. IMPORTANCE FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils. Although the expression of FcεRIα is known to be promoted by the IL-3-GATA-2 pathway during its differentiation, the mechanism by which FcεRIα expression is maintained remains unknown. In this study, we discovered that a natural antisense transcript, FCER1A-AS, is co-expressed with the sense transcript. The presence of FCER1A-AS is essential for sense transcript expression in mast cells and basophils, but not for the differentiation of these cells through cis-regulation. Like FcεRIα knockout mice, mice lacking FCER1A-AS also exhibit reduced survival after Schistosoma japonicum infection and a lack of IgE-mediated cutaneous anaphylaxis. Thus, a novel pathway for regulating IgE-mediated allergic diseases through noncoding RNAs has been revealed.


Orally administered CpG oligodeoxynucleotide induces production of CXC and CC chemokines in the gastric mucosa and suppresses bacterial colonization in a mouse model of Helicobacter pylori infection.
Bacterial DNA and unmethylated CpG oligodeoxynucleotides (CpG ODN) are known to be potent stimulators of the innate immune system in vitro and in vivo. We therefore investigated if oral administration of CpG ODN could enhance innate immunity in the gastric mucosa and control the extent of Helicobacter pylori infection in mice. Intragastric administration of a single dose of CpG ODN significantly increased local production of the CC chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES and the CXC chemokine gamma interferon-inducible protein 10 in the stomach and/or the small intestine. Importantly, intragastric administration of CpG ODN to mice with an already established H. pylori infection, in the absence of any coadministered antigen, was found to reduce the bacterial load in the stomach compared to the load in H. pylori-infected control mice, while similar administration of non-CpG ODN had no effect on the bacterial load. The reduction in the bacterial numbers in the stomachs of mice treated with CpG ODN was associated with enhanced infiltration of immune cells and increased RANTES production in the gastric mucosa compared to the infiltration of immune cells and RANTES production in H. pylori-infected control animals. These findings suggest that intragastric administration of CpG ODN without antigen codelivery may represent a valuable strategy for induction of innate immunity against H. pylori infection.


Temporomandibular disorders, trismus and malignancy: development of a checklist to improve patient safety.
Trismus is a restriction in the ability to open the mouth. Trismus can occur following trauma, surgery, radiation therapy, infection, inflammatory diseases, temporomandibular disorders (TMD) or less commonly as a result of malignancy. Following two cases of delayed diagnosis of carcinoma presenting with features of TMD to a specialist clinic, a checklist was developed for completion in cases of trismus, to alert the clinician to suspicious features suggesting a possible non-TMD cause. The use of this checklist, together with an increased awareness, has improved early recognition of atypical features in patients presenting with trismus and has contributed to the early diagnosis of a further case of malignancy presenting to this clinic. This article discusses the presentation of malignancy with trismus, the relevance of imaging in these cases, and the implementation of a checklist to reduce the risk of future misdiagnosis.


Titrating a modified ketogenic diet for patients with McArdle disease: A pilot study.
Glycogen storage disease type V (GSDV) is a rare inborn error of carbohydrate metabolism. Patients present with exercise intolerance due to blocked glycogen breakdown in skeletal muscle. Introducing alternative fuel substrates, such as ketone bodies (KBs), could potentially alleviate muscle symptoms. This pilot study investigates which of three different modified ketogenic diet regimes is optimal for GSDV-patients to follow in a future large-scale study. Participants were randomised to follow one of three diet regimes for 3 weeks (#1: 65%/15%/20%; #2: 75%/15%/10%, or #3: 80%/15%/5%, fat/protein/carbohydrate). The primary outcome was exercise tolerance assessed by heart rate (HR) changes during constant load cycling. Secondary outcomes included levels of ketosis, and changes in perceived exertion and indirect calorimetry measures during exercise. Ten GSDV-patients were included. Eight completed the study. The other two were excluded. Diet #3 showed the highest average KB level (1.1 mmol/L) vs #2 (0.5 mmol/L) and #1 (0.3 mmol/L). Five patients reported subjective symptom relief, all of whom were on diets #2 and #3. All diet regimes seemed to improve fatty acid oxidation rates and exercise capacity as indicated by a small decrease in HR and perceived exertion. The results of this open-label pilot study show that diets #2 and #3 induce ketosis and improve symptoms and exercise capacity in GSDV-patients. Diet #2 had the highest acceptability score and was superior or equal to diet #3 in all other parameters, except level of ketosis. Based on this, we suggest testing diet #2 in a large-scale, placebo-controlled study in GSDV.


Study on legibility of characters for the elderly--effects of character display modes on legibility.
It is more crucial than ever to consider the elderly when designing products. One of the important things to remember is the legibility of characters, since this influences the accessibility and usability of products. We studied the effects of character attributes on legibility using 70 subjects (60 aged 46-79 with no apparent ocular problems except presbyopia, and 10 aged 68-80 with cataracts). Thirty 10-key television remote control models were made. The characters on each were different, and were based on combinations of three attributes-height (5 levels), thickness (3 levels), and display mode (2 levels; positive: black characters on a white background, negative: white characters on a black background). Participants subjectively evaluated the legibility of the characters for each 10-key sample under two ambient illuminance conditions: 500 lx and 50 lx. They also performed paired comparisons on samples with the same height and thickness but different display modes. Subjective data were analyzed using a three-way factorial ANOVA for character height, thickness, and display mode. Legibility was significantly affected by all factors for those without cataracts under both illuminance conditions, and the interaction between thickness and display mode was significant. A two-way factorial ANOVA was performed for height and display mode for each thickness. Legibility was, in general, better for thinner characters in negative mode and was better in negative mode under dark illuminance for those with and without cataracts. This tendency was more pronounced in the elderly (over 65 years old). Paired comparisons showed that legibility was better in negative mode under both illuminance conditions, especially with medium and thin characters, for those with and without cataracts. Although there are few accounts of the effects of positive and negative modes in various existing guidelines, this finding would suggest that legibility can be enhanced by using the negative mode.


Bilateral axillary apocrine nevi--a case report.
Apocrine glands are tubular glands, which function as scent glands. These are found at only a few sites like the axillae and anogenital region. They are present as modified glands in the external ear canal (ceruminous glands), in the eyelid (Moll's glands) and in the breast (mammary glands). Occasionally, apocrine glands are found on the face, in the scalp and on the abdomen where they are usually small and non-functional. Apocrine glands develop their secretory portion and become functional only at puberty. Tumours of these glands involving only apocrine tissue are very rare. We present an uncommon case of benign apocrine nevi of the axilla, which occurred bilaterally. These nevi are uncommon and only occasional reports are available in literature.


Three-Dimensional Calibration for Routine Analyses of Bromide and Nitrate Ions as Indicators of Groundwater Quality in Coastal Territories.
Nitrate and bromide ions are generally considered indicators of anthropogenic pollution and seawater intrusion, respectively, in the groundwater of coastal territories. The analysis of these species is generally carried out with routine chromatographic analyses which generally afford partially merged or poorly resolved peaks. In the present paper a simple method for the correct evaluation of their concentration in water is reported. This method does not imply utilization of other instruments or technologies, only the mathematical elaboration of the data obtained from routine analysis of standard solutions containing the two species. Standard binary solutions of nitrate and bromide ions at different concentrations, ranging between 0.1 and 2 mM, were analyzed by means of ion chromatography. Splitting two partially merged chromatographic peaks and considering each resulting area as originating from a single species produces "measured" concentration values which differ from the nominal ones. Such a procedure generates errors (one per species) which can be written as a function of the above mentioned "measured" concentrations and which can be graphically represented by means of a surface in a three-dimensional (3D) space. In this way, "measured" concentrations of bromide and nitrate ions can be corrected by calculating the errors generated under the experimental conditions at which the chromatographic separation is performed. Notably, this is analogous with the two-dimensional (2D) calibration normally carried out for analytical purposes. Indeed, both methods allow estimation of the unknown concentration of species in solution by correlating the instrumental response with the concentration of standard solutions.


Which types of televised anti-tobacco campaigns prompt more quitline calls from disadvantaged groups?
To examine the efficacy of different types of mass media ads in driving lower socio-economic smokers (SES) to utilize quitlines. This study collected all 33 719 calls to the Victorian quitline in Australia over a 2-year period. Negative binomial regressions examined the relationship between weekly levels of exposure to different types of anti-smoking ads and quitline calls, after adjusting for covariates. Interaction terms were added to determine whether relationships differed by SES. In total, smokers were exposed 88.39 times to anti-smoking ads over the 2-year period, as estimated by target audience ratings points. Higher emotion narrative ad exposure had the strongest association with quitline calls, increasing call rates by 13% for every additional ad exposure per week (per 100 points, rate ratio = 1.132, P = 0.001). Substantially, greater increases in calls to quitline from lower SES groups were observed when higher emotion narrative ads were on air compared with when other ad types were on air, and this advantage was not as strong among higher SES groups. Airing higher emotion narrative anti-smoking ads may contribute to reducing, but not eliminating, socio-economic disparities in calls to the quitline through maximizing the responses of the lower SES smokers.


Interaction of clindamycin and cefpimizole (U63196E) in vitro against aerobic gram-negative rods and aerobic gram-positive cocci.
The combination of clindamycin plus a new semisynthetic cephalosporin, U63196E for which the United States approved name is cefpimizole, was tested against 47 aerobic Gram-negative rods and 30 aerobic Gram-positive cocci. Synergy was seen with Klebsiella pneumoniae (3 of 19 isolates) and Escherichia coli (2 of 21 isolates). All isolates of Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staph. aureus, and enterococci demonstrated either indifference or antagonistic reactions to the drug combination.


[Outcomes of open endovascular operations on the internal carotid artery in acute stage of ischaemic stroke].
The authors share their experience in diagnosis and treatment of patients with acute ischaemic stroke. The study included a total of 33 patients. Of these, 20 patients (Study Group) were operated on at terms ranging from 2 to 7 days after onset of acute cerebral circulatory impairment. The Control Group was composed of 13 patients with ischaemic stroke, having refused surgical prevention of recurrent stroke. Both groups were matched by age, gender, level of neurological deficiency and size of cerebral ischaemic foci. Surgical management in the Study Group consisted in either carotid endarterectomy (n=15) or stenting of the internal carotid artery (n=5). Depending on the severity of coronary artery lesion and the presence of accompanying therapeutic pathology, options of operative treatment with various anaesthesiological support were offered. At discharge, neurological deficit in the Study Group patients was lower - 1.2 points by the NIH Stroke Scale versus 2.7 points in the Control Group, however, this difference was not statistically significant (p=0.45). In the Study Group there were two complications: haematoma of the postoperative injury requiring its revision and a transient ischaemic attack during stenting of the internal carotid artery, having disappeared on the operation table after the distal cerebral protection device was removed. Significantly better results were obtained by the following parameters: in the Study Group the number of patients discharged with no neurological deficit (scoring 0 by the NIHSS scale) was significantly higher compared with the Control Group; 50% vs 7.7% (p<0.001). There were no lethal outcomes in either group. One patient (7.7%) from the Study Group developed recurrent ischaemic stroke, whereas neither intra- nor postoperative stroke was registered in the Control Group patients (p<0.001). In carefully selected patients with ischaemic stroke (neurological deficit not exceeding 3 points by the Rankin scale and not more than 11 points by the NIHSS, with the size of the ischaemic focus not exceeding 4 cm), surgical prevention of recurrent stroke within 7 days after the onset of an ischaemic event may be performed effectively and safely. Early operation effectively prevents relapsing ischaemic events at the in-hospital stage. Besides, reconstruction of brachiocephalic arteries during an acute stage of stroke in operated patients improves the neurological status in the postoperative period, decreases the degree of motor and sensory disorders and makes it possible in half of patients to completely eliminate neurological deficit present at admission.


Fourier-transform infrared spectroscopy study of dioleoylphosphatidylcholine and monooleoylglycerol in lamellar and cubic liquid crystals.
The liquid-crystalline phases of the systems monooleoylglycerol (MO)/water, dioleoylphosphatidylcholine (DOPC)/water, and MO/DOPC/water have been studied by Fourier-transform infrared (FTIR) spectroscopy. In the latter ternary system, the sn-3 OH group of MO competes with water to interact with the polar head group of DOPC, and an intramolecular hydrogen bonding of MO is broken up. The hydration of the ester carbonyl groups in the lamellar phases of both the MO/water and DOPC/water systems increases with increasing water content. Similarly, the addition of small amounts either of MO to a DOPC/water system or of DOPC to an MO/water system also results in an increase in the hydration of the ester carbonyl groups. This leads to an unfavorable hydrocarbon-water contact which is counteracted by the formation of a cubic phase, except for the DOPC/water system, where the lamellar phase is stable also at the highest water concentrations. The phase behavior of the different systems can be described in terms of lipid monolayer curvature and molecular packing in the lipid aggregates. Finally, it is shown by the water association band in the FTIR spectrum that the water hydrogen bonding is considerably different in the liquid-crystalline phases than in bulk water.


A New Cell Topology for 4H-SiC Planar Power MOSFETs for High-Frequency Switching.
A new cell topology named the dodecagonal (a polygon with twelve sides, short for Dod) cell is proposed to optimize the gate-to-drain capacitance (Cgd) and reduce the specific ON-resistance (Ron,sp) of 4H-SiC planar power MOSFETs. The Dod and the octagonal (Oct) cells are used in the layout design of the 650 V SiC MOSFETs in this work. The experimental results confirm that the Dod-cell MOSFET achieves a 2.2× lower Ron,sp, 2.1× smaller high-frequency figure of merit (HF-FOM), higher turn on/off dv/dt, and 29% less switching loss than the fabricated Oct-cell MOSFET. The results demonstrate that the Dod cell is an attractive candidate for high-frequency power applications.


Dietary Supplement Use during Pregnancy: Perceptions versus Reality.
This study aimed to examine the prevalence, associated factors and perceptions of dietary supplement use among pregnant Chinese women. A cross-sectional study was conducted to collect data about prevalence, purchase channels, perceptions, and related factors of dietary supplement use from 572 pregnant women, through a face-to-face survey, using a self-designed questionnaire. Of the respondents, 94.8% used at least one dietary supplement, whereas 29.8% used more than four supplements in the previous month. The majority of the pregnant women were highly educated (81.2% had a bachelor's degree or above) and had the perception that dietary supplements could prevent and improve (89.2%), or treat, nutrition-related diseases (78.7%). Multivariate analysis showed that pregnant women who had used multiple (more than four) supplements were more likely to have a larger gestational age, received fertility treatment, more prenatal visits, and hypothyroidism during pregnancy. Furthermore, pregnant women not only purchased dietary supplements through hospitals (72.6%) and pharmacies (45.1%), but overseas Daigou or online purchases (31.8%) were also a major channel of purchase. A high prevalence of dietary supplement use during pregnancy was observed, with extensive and repeated consumption of nutrients. Pregnant women's craze for dietary supplements calls for more comprehensive guidelines in China.


What do proton motive force driven multidrug resistance transporters have in common?
The extensive progress of genome sequencing projects in recent years has demonstrated that multidrug resistance (MDR) transporters are widely spread among all domains of life. This indicates that they play crucial roles in the survival of organisms. Moreover, antibiotic and chemotherapeutic treatments have revealed that microorganisms and cancer cells may use MDR transporters to fight the cytotoxic action of drugs. Currently, several MDR extrusion systems are being investigated in detail. It is expected that understanding of the molecular basis of multidrug recognition and the transport mechanisms will allow a more rational design of new drugs which either will not be recognized and expelled by or will efficiently inhibit the activity of the MDR transporters. MDR transporters either utilize ATP hydrolysis or an ion motive force as an energy source to drive drugs out of the cell. This review summarizes the recent progress in the field of bacterial proton motive force driven MDR transporters.


Modern total hip arthroplasty in patients younger than 21 years.
Total hip arthroplasty (THA) is not commonly performed in adolescents. However, it may be the only option for pain control with continued mobility for advanced disease. We report our experience with modern alternative-bearing THA in patients younger than 21 years. Twenty-one THAs (18 patients) were followed. Preoperative and postoperative Harris hip scores were recorded, and radiographs were reviewed. Average follow-up was 49 months (range, 25-89). Underlying etiology was chemotherapy-induced osteonecrosis (33%), steroid-induced osteonecrosis (29%), sickle cell disease (24%), and chronic dislocation (14%). Articulation bearings were ceramic/ceramic (67%), metal/highly cross-linked polyethylene (29%), and metal resurfacing (5%). Mean age was 18 years (range, 13-20). Harris hip scores improved from 43.6 to 83.6 (P < .001). At final follow-up, there was no radiographic loosening; 1 THA was revised for a cracked ceramic liner. At intermediate-term follow-up, clinical and radiographic results are favorable after alternative-bearing THA in patients younger than 21 years.


Disorders of phosphorus homeostasis.
The study of phosphorus physiology and investigations into clinical disorders of phosphorus metabolism has blossomed over the past decade. Recent work has confirmed and further extended our knowledge of basic mechanisms of phosphorus metabolism. This review will focus on FGF-23 and Klotho, and on the recent further dissection of their roles in phosphorus and skeletal metabolism. Additionally, this review will detail recent studies that implicate a role for these phosphaturic and vitamin D regulating factors in extraskeletal calcification, including that occurring in soft tissue and vascular beds. These findings in total provide fertile ground for investigations into the cause and treatment of abnormal skeletal and extraskeletal calcification in patients with inherited hypophosphatemic disorders. More importantly, and certainly with wider potential clinical application, these studies likewise imply a role for these factors in the pathogenesis of accelerated cardiovascular disease that occurs in patients with the most common hyperphosphatemic disorder, chronic kidney disease. Future studies are needed to confirm a harmful or possibly even beneficial role for FGF-23 and other factors in these disease states, and to determine whether therapeutic manipulation of these factors does truly affect clinical outcomes in patients with hypophosphatemia and hyperphosphatemia.


The Impact of the Doctorate of Nursing Practice Nurse in a Hospital Setting.
This article describes the initiatives of doctorate of nursing practice (DNP)-prepared nurses in a large healthcare system supporting the DNP competencies as outlined by the American Association of Colleges of Nursing. The goal of this group was to demonstrate the impact of DNP education on the roles for nurse administrators, advanced practice nurses, and educators in a large health system. Exemplars profile nurse administrators, clinical nurse specialists, and a nurse educator.


Does an Antibiotic Stewardship Applied in a Pig Farm Lead to Low ESBL Prevalence?
Background. The aim of the present study was to prospectively evaluate the prevalence of intestinal carriage of colistin-resistant and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales among pigs from a Swiss farm attending an animal health and antibiotic stewardship program and to determine the associated mechanisms of resistance. Materials/Methods. Eighty-one fecal samples were recovered and screened for either β-lactam-resistant, colistin-resistant, or aminoglycoside-resistant Enterobacterales, using respective screening media. All recovered isolates were tested for antimicrobial susceptibility and their clonal relationship (PFGE and MLST). Plasmid typing was performed by plasmid-based replicon typing (PBRT). Resistance genes were searched by PCR and sequencing. Results. A total of 38 ESBL-producing Escherichia coli and a single ESBL-producing Enterobacter cloacae were recovered from 81 pigs, corresponding to a prevalence of 50%, no other β-lactamase producer being identified. Among the 38 ESBL-producing E. coli, all belonged to sequence type (ST) ST10, except two ST34 and ST744 isolates. Among the ST10-blaCTX-M-1 isolates, three subclones (n = 22, n = 13, and n = 1, respectively) were identified according to the PFGE analysis. The most commonly identified IncI1 plasmid harboring the blaCTX-M-1 gene was 143 kb in size and coharbored other resistance genes. Only three colistin-resistant Enterobacterales isolates were recovered, namely two Klebsiella pneumoniae isolates and a single E. cloacae isolate. Screening for the plasmid-borne mcr-1 to mcr-9 genes in these three isolates gave negative results. The two K. pneumoniae isolates were clonally related, belonged to ST76, and harbored a truncated mgrB chromosomal gene being the source of colistin resistance. Conclusion. A high prevalence of fecal carriage of ESBL-producing E. coli was found, being mainly caused by the spread of a clonal lineage within the farm. By contrast, a low prevalence of colistin-resistant Enterobacterales was found.


GATA factors induce mouse embryonic stem cell differentiation toward extraembryonic endoderm.
The GATA family of transcription factors are implicated in early embryonic development. There are six factors in this family in vertebrates. GATA4 and GATA6 have been demonstrated to induce mouse embryonic stem (mES) cells differentiation toward extraembryonic endoderm (ExE). We investigated the effect of GATA3 on the differentiation of mES cells both in the ES cell and in the embryoid body (EB) states. The results demonstrate that GATA3 overexpression can initiate the ES cell differentiation program toward ExE. Furthermore, overexpression of GATA1 and GATA2 in ES cells and EBs resulted in similar effects. We believe this finding can augment our understanding of mouse ES cell differentiation.


Severe telomere shortening in patients with paroxysmal nocturnal hemoglobinuria affects both GPI- and GPI+ hematopoiesis.
A most distinctive feature of paroxysmal nocturnal hemoglobinuria (PNH) is that in each patient glycosylphosphatidylinositol-negative (GPI-) and GPI+ hematopoietic stem cells (HSCs) coexist, and both contribute to hematopoiesis. Telomere size correlates inversely with the cell division history of HSCs. In 10 patients with hemolytic PNH the telomeres in sorted GPI- granulocytes were shorter than in sorted GPI+ granulocytes in 4 cases, comparable in 2 cases, and longer in the remaining 4 cases. Furthermore, the telomeres of both GPI- and GPI+ hematopoietic cells were markedly shortened compared with age-matched controls. The short telomeres in the GPI- cells probably reflect the large number of cell divisions required for the progeny of a single cell to contribute a large proportion of hematopoiesis. The short telomeres of the GPI+ cells indicate that the residual hematopoiesis contributed by these cells is not normal. This epigenetic change is an additional feature shared by PNH and aplastic anemia.


Identification of Photocatalytic Alkaloids from Coptidis Rhizome by an Offline HPLC/CC/SCD Approach.
Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.


Arrested development of secondary sexual adornments in subordinate adult male mandrills (Mandrillus sphinx).
Previous studies of semifree-ranging mandrills identified two morphological and social variants of the adult male, based on behavioral and secondary sexual characteristics. "Fatted" males are social, with highly developed sex skin coloration, large testes, high plasma testosterone levels, and fat rumps; while "nonfatted" males are peripheral or solitary, with paler sex skin, smaller testes, lower plasma testosterone, and slimmer rumps. We present a detailed study of morphology and group association for 10 adult male mandrills, living in two semifree-ranging groups in Gabon, in order to relate differences between males to dominance rank. The results show that rather than existing as two distinct morphotypes, male mandrills represent a continuous spectrum of possibilities between social males with fully developed secondary sexual characteristics, and solitary males with muted secondary sexual characteristics. Alpha males (N = 2) had the highest testosterone levels, the most colorful sex skin, and the most active sternal glands, and were the only males to spend 100% of their time with the social group. Rank relationships between nonalpha males (N = 8) were not always clear, but all subordinate males had lower testosterone levels and less development of the secondary sexual adornments, and were less group-associated than alpha males. These findings suggest that only alpha males have sufficient testosterone to develop full secondary sexual characteristics, and we propose possible socioendocrine mechanisms underlying the suppression of testosterone and secondary sexual development in subordinate adults. We discuss differences in secondary sexual development in relation to reproductive strategies, and discuss the evolution of alternative reproductive morphs in primates.


Adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist in patients with substance use disorders.
Diagnosing attention deficit/hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) is a complicated process in which a screening tool may be useful. We analyzed the ASRS-v1.1 validity in patients with SUD, considering the addiction severity and co-morbidity with depressive disorders, antisocial and borderline personality. Eighty outpatients with SUD were evaluated with the following instruments: ASRS-v1.1, CAAD-II, EuropASI, SCID-I, SCID-II. A factor analysis was performed with Varimax rotation to determine the structure of the intercorrelations among the items. Accuracy of ASRS-v1.1 was also analyzed. The diagnostic interview CAADID used as a gold standard indicated that 20% (95% confidence interval [CI]: 11-29) meet the criteria for ADHD. The ASRSv1.1 factor structure is marked by two factors related to inattention and hyperactivity / impulsivity that account for 67.7% of the variance. ASRS-v1.1, with a 4 cut-off, showed an 87.5% sensitivity and 68.6% specificity. ASRS-v1.1 is a simple screening tool that is useful and has acceptable validity for the identification of ADHD among addicted patients.


Association between the PAI-1 4G/5G Gene Polymorphism and the Risk of Systemic Lupus Erythematosus/Lupus Nephritis.
Plasminogen activator inhibitor type 1 (PAI-1) correlates with the risk and progression of systemic lupus erythematosus (SLE). We aimed to assess the relationship between the PAI-1 4G/5G gene polymorphism and SLE/lupus nephritis risk. We identified the eligible studies regarding the association between the PAI-1 4G/5G gene polymorphism and the risk of SLE/lupus nephritis. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effects model or, in the presence of heterogeneity, a random-effects model. A total of six studies were enrolled in our pooled analysis. The PAI-1 4G/5G gene polymorphism had no significant association with the risk of SLE among overall populations, Asians and Caucasians. Nor was it associated with susceptibility to lupus nephritis among overall populations, Asians and Caucasians. Sensitivity analysis yielded similar results. No marked publication bias was noted. In conclusion, the PAI-1 4G/5G gene polymorphism is not associated with susceptibility to SLE/lupus nephritis among overall populations, Asians and Caucasians. However, more studies should be conducted in the future.


Prospective Outcomes of Injury Study 10 Years on (POIS-10): An Observational Cohort Study.
Injury is a leading cause of disability and is costly. This prospective cohort study extension aims to improve disability, health, and wellbeing outcomes for injured New Zealanders, including for Māori. We will identify predictors and modifiable risk factors of long-term outcomes (positive and negative), and develop an Injury Early Care Tool (INJECT) to inform the implementation of effective interventions to improve outcomes. In the Prospective Outcomes of Injury Study (POIS), 2856 people participated following an injury (occurring between 2007 and 2009) registered with New Zealand's no-fault accident compensation scheme (ACC). POIS-10 will invite 2121 people (including 358 Māori) who completed a 24-month POIS interview and agreed to follow-up, anticipating 75% participation (n = 1591). Interviews will collect sociodemographic characteristics, life events, comorbidities, and new injuries since participants' 24-month interview, as well as key disability, health, and wellbeing outcomes 12 years post-injury. Injury-related data will be collected from ACC and hospitalisation records 12 years post-injury. Regression models for the main outcomes will examine the direct effects of predictor variables after adjustment for a wide range of confounders. POIS-10 is enhanced by our partnership with ACC, and expert advisors and will benefit injured people, including Māori, through increased understanding of mechanisms and interventions to improve long-term post-injury outcomes.


[Aging in Québec : from one generation to another.].
Throughout the upcoming century, retirement will be different from what it is today on several points. It will be comprised of a proportionately larger population, of more autonomous women, of elderly people more educated and more sensitive to the issues of growing old. This, along with the fact that government will be in a weaker position tomorrow than it is today to manage the needs of the elderly (social and medical services), brings the author to suggest a new approach to the golden age. Instead of trying to adjust themselves to becoming old, the author emphasizes that individuals should take charge of their future as an elderly person. As well, the author recommends a theoretical approach based on a dynamic perspective of retirement ; focussing attention on a person's life experience rather than a point in time (passage from middle age to golden age) and, therefore, respecting their personal growth.


The role of gaze and road edge information during high-speed locomotion.
Robust control of skilled actions requires the flexible combination of multiple sources of information. Here we examined the role of gaze during high-speed locomotor steering and in particular the role of feedback from the visible road edges. Participants were required to maintain one of three lateral positions on the road when one or both edges were degraded (either by fading or removing them). Steering became increasingly impaired as road edge information was degraded, with gaze being predominantly directed toward the required road position. When either of the road edges were removed, we observed systematic shifts in steering and gaze direction dependent upon both the required road position and the visible edge. A second experiment required fixation on the road center or beyond the road edges. The results showed that the direction of gaze led to predictable steering biases, which increased as road edge information became degraded. A new steering model demonstrates that the direction of gaze and both road edges influence steering in a manner consistent with the flexible weighted combination of near road feedback information and prospective gaze information.


[Distribution of a diffusible tracer in the subcapsular sinus and the cortex of lymph nodes in the rat].
The observations of a previous work on the architecture of the rat node suggested that the organ is divided into "physiological compartments". Each compartment corresponds to a node portion stimulated by the immunogenic content poured by an opening of an afferent lymphatic or a branch of it. The same study also investigated the lymph flow in the organ sinuses by analysing the distribution, in draining nodes, of a locally injected small dose of China ink. It was found that the ink, pouring into a node from a lymphatic opening, had spread in a restricted portion of its subcapsular sinus corresponding to that of a compartment. The finding thus supported the proposal on the physiological compartmentation of the organ. However, the question arose as to whether such restricted ink distribution in the sinus did not result from the non-diffusible and unphysiological nature of the ink. We, therefore, repeated the latter analysis with a diffusible and physiological tracer: uridine-3H. The similarity of the results of the latter analysis, with those of the preceeding one, indicate that the observations witness the physiological modalities of the pattern of lymph flow in the organ sinuses. It, therefore, confirms that the node is divided into physiological compartments. Additional observations of present work, further demonstrate that small sized lymph substances diffuse from the subcapsular sinus into the cortex. The process is maximal under a lymphatic opening and decreases along the sinus with distance from the opening.


Bacteria as trigger for chronic gastrointestinal disorders.
Apart from acute infections, microorganisms may also induce or perpetuate chronic inflammatory diseases and reversible or irreversible proliferation of various cells in the gastrointestinal tract (the extreme being adenocarcinoma and lymphoma). Helicobacter pylori is not only involved in the pathogenesis of lymphoma and gastric adenocarcinoma. The steps and mechanisms of the carcinogenic process involve host predisposition, environmental factors, and strain virulence. The steps of lymphoma genesis include chronic inflammation, acquisition of mucosa-associated lymphoid tissue in the stomach, proliferation of the B lymphocytes in an inflammatory context, acquisition of genetic anomalies and dysregulation of the NF-κB pathway. The role of Campylobacter jejuni in immunoproliferative small bowel disease has also been shown and eradication of this bacterium can cure the lymphoma at its early stage. The evidence for the role of some bacteria in colon cancer development is discussed. Opportunistic pathogens are detected in the stools or mucosa of a proportion of subjects with Crohn's disease. They include Mycobacterium avium paratuberculosis, adherent invasive Escherichia coli, and Clostridium difficile. A dysbiosis has been repeatedly observed in patients with inflammatory bowel disease. Instability of the dominant microbiota and decreased biodiversity (especially in the firmicutes phylum) are major characteristics. The decrease of Faecalibacterium prausnitzii seems to have a prognostic value to predict relapse of Crohn's disease after surgery. Finally, important perspectives are opened by new tools such as metagenomics and metabolomics of the gastrointestinal ecosystems. Major tracks concern irritable bowel syndrome, colon cancer and obesity.


Enhanced formation of a confined nano-water meniscus using a 780 nm laser with a quartz tuning fork-atomic force microscope.
Demonstrated herein is the optical-field-induced enhancement of the formation of a confined nanowater meniscus using a distance-regulated quartz tuning fork-atomic force microscope (QTF-AFM) with a 780 nm laser. While a pulled optical fiber tip approaches the surface, the laser is suddenly turned on and focuses on the front spot of the tip by the shape of the pulled optical fiber, which plays the role of an objective lens and induces the gathering effect of the water molecules directed to the electromagnetic-field gradient in air. This phenomenon facilitates a new boundary condition to form a long-range confined nano-scale liquid bridge between the tip and the surface. After the pulling of the optical fiber, 20-nm-thick gold was sputtered on the apex (diameter: approximately 100 nm) of the tip to guide and focus the beam on the spot. The critical power of the laser to overcome the barrier for the formation of a new boundary is 100 microW at the distance of 22 nm from the substrate.


Factor 390 chromophores: phosphodiester between AMP or GMP and methanogen factor 420.
Two chromophores with absorbance maxima at 390 nm (factors 390) have been isolated from oxidized cells of Methanobacterium thermoautotrophicum delta H. The isolation procedure included anion-exchange chromatography of the soluble cofactor pool followed by reverse-phase chromatography. The factor 390 species are novel derivatives of methanogen coenzyme factor 420 in which the 5-deazaflavin 8-hydroxy group is in a phosphodiester linkage to adenosine 5'-phosphate or guanosine 5'-phosphate. The structural assignments were based, in part, on the UV-visible and 1H NMR spectra. In addition, the results from amino acid analysis, phosphate determination, 31P NMR spectroscopy, and fast atom bombardment mass spectrometry were consistent with the proposed structures. Confirmation of the factor 390 structures was made following phosphodiesterase release of the nucleotide monophosphates from factor 420. The nucleotide monophosphates were identified as AMP and GMP by UV-visible spectra and based on elution position by using reverse-phase and anion-exchange high-performance liquid chromatography. The presence of AMP was further demonstrated by using adenylate-5'-phosphate kinase which induced a spectral shift during conversion of the sample to IMP. In addition, the presence of GMP was established by a specific enzymatic assay.


Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice.
Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity against Helicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice. H. pylori was completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be beneficial in the treatment of H. pylori-infected individuals.


Preparation and observation of fresh-frozen sections of the green fluorescent protein transgenic mouse head.
Hard tissue decalcification can cause variation in the constituent protein characteristics. This paper describes a method of preparating of frozen mouse head sections so as to clearly observe the nature of the constituent proteins. Frozen sections of various green fluorescent protein (GFP) transgenic mouse heads were prepared using the film method developed by Kawamoto and Shimizu. This method made specimen dissection without decalcification possible, wherein GFP was clearly observed in an undamaged state. Conversely, using the same method with decalcification made GFP observation in the transgenic mouse head difficult. This new method is suitable for observing GFP marked cells, enabling us to follow the transplanted GFP marked cells within frozen head sections.


Phases and Transitions of Serious Illness: A Structure for Teaching Palliative Care.
Palliative care (PC) focuses on listening to patient preferences, goals, and values to help health care providers educate, support, and collaborate during challenging disease processes, demanding treatments, and difficult decision-making. A recently developed Phases and Transitions Model for Serious Illness helps guide nursing students in initiating therapeutic conversations about PC. Each phase and transition shows unique characteristics of illness and treatment to clarify the importance of introducing PC for that phase. Interventions in education, support, and treatment help students guide patients and families through the trajectory of serious illness. The Phases and Transitions Model for Serious Illness and PC interventions provide a clear and practical structure to educate and empower nursing students to engage in PC conversations. Nursing educators can integrate this new model to broaden the perspective of PC as an everyday nursing practice for patients who have a serious illness. [J Nurs Educ. 2023;62(5):279-284.].


Salutary effect of reduced glutathione on renal function in coronary artery bypass operation.
Renal dysfunction and acute renal failure are serious complications of open heart operations. Previous reports have suggested beneficial effects of exogenous glutathione for preservation of renal function after ischemic renal injury. We prospectively studied the effect of perioperative administration of glutathione on renal function in patients who underwent coronary artery bypass operation. Two hundred mg per kg of glutathione was administered to the treated group (n = 10) before cardiopulmonary bypass, and on the first and second postoperative days. The control group was administered placebo in the same volume. Hemodynamics, renal function, and plasma hormone levels were measured consecutively. In the glutathione group, the mean arterial pressure and systemic vascular resistance index were lower than in the control group. Urine volume, creatinine clearance, and renal excretory index were well preserved in the group treated with glutathione. Moreover, the fractional excretion of sodium was lower and urine and plasma osmolarity was higher in the group treated with glutathione. No differences in plasma renin activity, angiotensin II, or aldosterone concentrations between the two groups were observed. Perioperative glutathione treatment has a salutary effect on perioperative renal function through effects on both renal hemodynamics and tubular mechanism.


Comparability of outcome frameworks in medical education: Implications for framework development.
Given the increasing mobility of medical students and practitioners, there is a growing need for harmonization of medical education and qualifications. Although several initiatives have sought to compare national outcome frameworks, this task has proven a challenge. Drawing on an analysis of existing outcome frameworks, we identify factors that hinder comparability and suggest ways of facilitating comparability during framework development and revisions. We searched MedLine, EmBase and the Internet for outcome frameworks in medical education published by national or governmental organizations. We analyzed these frameworks for differences and similarities that influence comparability. Of 1816 search results, 13 outcome frameworks met our inclusion criteria. These frameworks differ in five core features: history and origins, formal structure, medical education system, target audience and key terms. Many frameworks reference other frameworks without acknowledging these differences. Importantly, the level of detail of the outcomes specified differs both within and between frameworks. The differences identified explain some of the challenges involved in comparing outcome frameworks and medical qualifications. We propose a two-level model distinguishing between "core" competencies and culture-specific "secondary" competencies. This approach could strike a balance between local specifics and cross-national comparability of outcome frameworks and medical education.


We can do that! Collaborative assessment of school environments to promote healthy adolescent nutrition and physical activity behaviors.
Evidence for effectiveness of school-based studies for prevention of adolescent obesity is equivocal. Tailoring interventions to specific settings is considered necessary for effectiveness and sustainability. The PRECEDE framework provides a formative research approach for comprehensive understanding of school environments and identification of key issues/areas to focus resources and energies. No reported studies have tested applicability of the PRECEDE framework in schools in relation to obesity. Adolescents (n = 362), parents (n = 349) and teachers (n = 146) from six secondary schools participated in two quantitative studies and two qualitative studies. Data collected from these studies permitted confirmation of adolescent overweight/obesity a health issue for schools; the need for secondary schools to focus health promotion efforts on healthy nutrition, with inclusion of parents/homes and appreciation for gender differences in developing interventions. Community buy-in and commitment to school-based obesity prevention programs may be dependent on initially addressing what may be perceived as minor issues, and developing policies to guide practices within schools in relation to supply and access to healthy foods, use of sporting equipment and participation in physical activities. The PRECEDE framework allows systematic assessment of school environments and provided opportunity to identify realistic and relevant interventions for promoting healthy adolescent physical activity and nutrition behaviors.


Seminal vesicle invasion in radical prostatectomies: which is the most common route of invasion?
Very few studies have been published on seminal vesicle invasion (SVI), and these have obtained conflicting results. The aim of the present investigation was to determine the most frequent of three possible routes of seminal vesicle invasion: (1) extraprostatic extension (EPE) into soft tissue adjacent to the seminal vesicle and then into the wall of the seminal vesicle, (2) invasion via the sheath of the ejaculatory duct, penetrating the muscular wall of the ejaculatory duct or extending up the ejaculatory duct into the seminal vesicle muscle wall, or (3) discontinuous metastases. The surgical specimens of 230 consecutive patients submitted to radical prostatectomy were histologically evaluated by complete embedding and whole-mount processing. Of the surgical specimens obtained from 230 patients, 28 (12.17%) showed the presence of either unilateral or bilateral SVI. The routes of SVI in these 28 specimens were: (1) only via the sheath of the ejaculatory duct (0/28; 0%); (2) discontinuous metastases (3/28; 11%), (3) both EPE and via the sheath of the ejaculatory duct (6/28; 21%), and (4) only EPE (19/28; 68%). One-half (14/28; 50%) of the 28 seminal vesicles involved had unilateral invasion and, in most of these cases (42.85%), EPE was unilateral and ipsilateral. Our results suggest that the most important and most frequent route of SVI is extraprostatic extension of prostate carcinoma into the soft tissue adjacent to the ipsilateral seminal vesicle and then into the wall of the seminal vesicle.


Histomorphometric analysis on bone dynamics in denture supporting tissue under masticatory pressure in rat.
The bone dynamics under denture base has not been clarified sufficiently. The purpose of this study was to evaluate histomorphometrically the bone dynamics in denture supporting tissue with relation to the intensity of the masticatory pressure. The removable denture bases, which exerted four different regulated masticatory pressures (0.0, 1.0, 20.0 or 40.0 kPa), were inserted to the hard palate of the molar region of 22-week-old rats. The palatal tissues were excised from 1 to 12 weeks after denture insertion at intervals of 1 week and embedded in methyl-methacrylate. No bone resorption was observed throughout the experimental period in the 0.0 and 1.0 kPa groups. In the 1.0 kPa group compared with the 0.0 kPa group, bone formation parameters except for bone formation rate significantly increased at 4 weeks, but there was no significant difference between these groups in the other experimental periods. In the 20.0 and 40.0 kPa groups, bone resorption was observed until 3 and 5 weeks, respectively, and the amounts of bone resorption (AoBR) were 45 +/- 25 and 104 +/- 21 microm, respectively. After bone resorption, bone formation parameters in these two groups showed transiently significant decrease compared with the 0.0 kPa group, but were the same time course as the 0.0 kPa group following this decrease. In conclusion, masticatory pressure caused different time courses of the bone dynamics in denture supporting tissue depending on the initial intensity of the pressure. The AoBR responded to the initial intensity of masticatory pressure. Bone formation following bone resorption did not cause equivalent recovery of the bone surface level to the level observed in the case without bone resorption in the present study.


Surgical management of AN inverted AND impacted maxillary central incisor - case report.
Impacted maxillary permanent central incisor is not a frequently reported case in our dental practice. Dilaceration is one of the causes of failure of eruption of permanent maxillary incisor. It is a developmental anomaly of the form of a tooth that commonly occurs in permanent incisors .We report a case of a 14-year-old boy with an impacted central incisor in the maxillary region managed at Dr.H.Gordon Roberts's hospital, Meghalaya, India. The tooth was completely upside down with the crown facing towards the nasal floor and the root towards the alveolar process with severe dilaceration. Surgical removal of the impacted central incisor was performed under local anesthesia without disturbing the floor of the nose.


Combined effect of traditional Chinese and Western medicine on inflammatory factors in patients with diabetes-induced xerophthalmia.
Diabetes-induced xerophthalmia is a general metabolic disorder with high incidence and increased treatment difficulty. Our study aimed to explore the combined effect of traditional Chinese and Western medicines on diabetes-associated xerophthalmia. We recruited 60 diabetic xerophthalmia patients, and randomly assigned them to either the control (Western medicine treatment) or the experimental (combined treatment of traditional Chinese medicine and Western medicine) groups. Pre-treatment and post-treatment analyses were performed to assess the combined therapeutic effect of traditional Chinese and Western medicine on xerophthalmia-associated indicators. We found that the experimental group expressed reduced levels of IL-1, IL-8, and TNF-α (P < 0.05) as compared to the control group. Furthermore, the experimental group showed higher treatment efficacy as compared to the control group (85.00 vs 51.67% Z = 22.244, P < 0.05). In addition, break-up time (t = 20.582, P < 0.05) and tear section (t = 23.082, P < 0.05) was increased in the experimental group as compared to the controls. Lastly, it was found that the combined treatment of traditional Chinese and Western medicine effectively reduced corneal injuries, as indicated by reduced fluorescein staining. This study suggested that a combination treatment consisting of both traditional Chinese and Western medicines may be effective against xerophthalmia in diabetes, and that inflammatory factors are potential biomarkers to examine the treatment efficacy.


[Septal displacements during intraventricular conduction disorders. Echocardiographical study].
We have analysed the echocardiograms of ten healthy subjects, sixty patients with disorders of intra-ventricular conduction, and ten who were treated by a temporary intracavitary pacemaker. There was found to be a pre-ejection displacement of the septum towards the posterior wall, beginning just after electrical depolarisation of the ventricle followed, in most cases, by 'paradoxical' displacement towards the anterior wall during systole. Such a displacement, producing a 'beaked' image on the echocardiogram, is only found when the ventricular complexes have the characteristics of complete left bundle branch block (LBBB), whether this is spontaneous LBBB or a functional LBBB produced by an intracavitary pacemaker. The results support the hypothesis that the posterior displacement of the septum in cases of LBBB is related to abnormal spread of excitation. Under these conditions, during the pre-ejection period the septal forces predominante over those of the free wall of the left ventricle. In a patient with LBBB who had failed to show this typical septal displacement in several investigations, the 'beak' of the septum could be observed only when the electrical axis deviated to the left, and when the QRS complex exceeded 0.14/s to 0.16/s, this condition being fulfilled because the LBBB was really complete at the time of the last investigation.


[Phosphorescent analysis of the intramolecular dynamics of the muscle glycogen phosphorylase b].
Large-scale functionally significant changes in the intramolecular dynamics of muscle glycogen phosphorylase b (EC 18.104.22.168) in solution upon ligand binding, transition from dimeric to tetrameric form, temperature denaturation and aggregation were registered at room temperature using the tryptophan phosphorescence technique. It was shown that binding of glucose-1-phosphate (substrate, 0.25-4 mM) and glucose (competitive inhibitor, 0.5-8 mM) to the active site and temperature-induced protein aggregation decrease large-scale structural fluctuations of the protein matrix at the level of domains and subunits; whereas the transition of glycogen phosphorylase b to tetrameric form (R-conformation) leads to a dramatic increase in the structural flexibility of the peripheral parts of the protein globule.


The Effect of Perceived Stress, Family Companionship, and Mental Health on the Subjective Happiness of Chinese Healthcare Workers: A Mixed Research Method.
Aim: This study aimed to understand the impact of perceived stress on the subjective happiness of Chinese healthcare workers (HCWs) and to further explore the chain-mediating role of family companionship and mental health. Background: In the face of tense doctor-patient relationships; a heavy workload; long working hours; seemingly endless shifts; potential professional title promotions; work performance assessments; and the difficult balance between family, work, and other aspects of life, HCWs are often under great pressure, which can endanger mental health and reduce subjective happiness. However, the role of healthcare workers' active participation in family companionship in mental health and subjective happiness is not clear. Method: We used a mixed research design to collect data in two locations (Hospital A and Hospital B) in Wuhan, China. A self-distributed questionnaire was assigned to HCWs through the Research Electronic Data Capture survey. A total of 368 valid surveys were obtained. Results: Hospital A's perceived stress level and mental health problems were more severe, while Hospital B had a higher subjective happiness score and more time to spend with their families. Subjective happiness was affected by children, education, occupation, health status, commuting time, and the scores of perceived stress and depression. The scores of perceived stress and mental health were significantly negatively associated with subjective happiness and family companionship, and there was a significant positive correlation between subjective happiness and family companionship. The results also showed that family companionship and mental health acted as serial mediators between perceived stress and subjective happiness. However, family companionship did not play a mediating role between perceived stress and subjective happiness. Most HCWs had work-family conflicts, and a high amount of work pressure and feelings of powerlessness and not having sufficient time were common when they accompanied their families. Conclusions: HCWs had a high level of perceived stress and psychological distress, and their subjective happiness score was lower than that of the general population. Many HCWs experienced negative emotions when taking care of their families. Only a small number of people had enough time to spend time with their families and perform more prominently in busier hospitals. More importantly, perceived stress can indirectly have an impact on subjective happiness through a chain-mediating effect of family companionship and mental health, and family companionship may not always promote subjective happiness unless mental health is maintained. Therefore, in the future, we can consider carrying out interventions based on family companionship and mental health among HCWs to promote the healthy and harmonious development of individuals, families, and hospitals.


Peripheral Blood Mononuclear Cells Oxidative Stress and Plasma Inflammatory Biomarkers in Adults with Normal Weight, Overweight and Obesity.
Background: Obesity is an important pathology in public health worldwide. Obese patients are characterized by higher cardiovascular risk and a pro-inflammatory profile. Objective: To assess the oxidative stress in peripheral blood mononuclear cells (PBMCs) and inflammatory biomarkers in plasma in adults with normal weight, overweight and obesity. Methods: One hundred and fifty adults (55-80-years-old; 60% women) from the Balearic Islands, Spain, were recruited and classified according to body mass index (BMI). Anthropometric measurements were carried out, fasting blood samples were collected and plasma and PBMCs were obtained. Biochemical parameters, hemogram, antioxidant enzyme activities and protein levels, reactive oxygen species production (ROS), malondialdehyde (MDA), and cytokine (tumour necrosis factor, TNFα, and interleukin 6, IL-6) levels were measured. Results: Glycaemia, triglyceridemia, abdominal obesity, and waist-to-height ratio (WHtR) were higher, and HDL-cholesterol was lower in obese patients. MDA and TNFα plasma levels were higher in the obese compared to normal-weight group, while the levels of IL-6 were higher in both obese and overweight subjects with respect to normal-weight peers. The activities of all antioxidant enzymes in PBMCs as well as the production ROS progressively increased with BMI. The protein levels of catalase in PBMCs were higher in obese and glutathione reductase in obese and overweight subjects compared to normal-weight peers. No other differences were observed. Conclusion: The current results show that overweight and obesity are related to an increase in pro-oxidant and proinflammatory status in plasma and PBMCs. The studied biomarkers may be useful for monitoring the progression/reversal of obesity.


Pricing Policies of Green Dual-Channel Supply Chain with Fairness Concerns and Altruistic Preferences Based on Consumers' Environmental Awareness and Channel Preference.
Taking into consideration fairness concerns and altruistic preferences of manufacturers, this paper aims to propose a green dual-channel supply chain that incorporates consumers' environmental awareness (CEA) and channel preference. The purpose of this work is to explore and further compare the optimal outcomes in a green dual-channel supply chain in three scenarios, which are the fairness-neutrality scenario (Model N), the manufacturer is concerned with fairness scenario (Model F), and the manufacturer has altruistic preference (Model A), respectively. The game-theoretical models with different fairness preferences, comparative, and numerical analyses are used to put forward the impacts of consumers' channel preference and CEA on pricing, profits, and utilities, and to identify the differences in decisional outcomes between the three models. The results indicate that CEA always contributes to developing the green market while adversely affecting common products. Moreover, consumers' channel preferences might enable the manufacturer and retailer to enhance profitability under certain conditions. The findings also reveal that manufacturer's fairness concerns can possibly increase the demand for green products but impair the overall performance of the supply chain in general. Moreover, while the manufacturer's altruistic preference benefits the retailer's profits, it has a detrimental effect on the performance of the green supply chain. The practical implications of this research come to promote green consumption and increasing consumer awareness of environmental protection are effective ways to develop a green supply chain. It is also important to note that in order to maintain the durability and stability of the sup-ply chain, the manufacturer must maintain a moderate level of fairness preference behaviors so that downstream retailers will remain enthusiastic about establishing long-term relationships.


Tips of the trade #32. Gradual closure of fasciotomy wounds.
A technique of gradual closure of fasciotomy wounds is presented. At the time of fasciotomy, staples are placed at the edge of the fasciotomy wound. A large nylon suture is threaded through the staples in a pattern similar to the lacing of a shoe. Postoperatively, this suture is tightened daily; this results in gradual closure of the wounds without further surgery.


Pharmacokinetics and pharmacodynamics of linezolid in plasma/cerebrospinal fluid in patients with cerebral hemorrhage after lateral ventricular drainage by Monte Carlo simulation.
We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. Ten patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs). The maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC0-24 h)/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 μg/mL, whereas it could be achieved in CSF with a MIC of ≤1 μg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 μg/mL. For patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect.


[Fusarium and fusariosis].
The submitted review deals with the problem of hyalohyphomycoses caused by the genus Fusarium. Attention is drawn to the fact that members of this genus cannot be considered any longer in medical microbiology as mere saprophytes but that they are able to cause superficial, organ and disseminated infections. The number of patients infected with these fungi is increasing.


Using the MMPI to assess reported cognitive disturbances and somatization as a core feature of complex PTSD.
Minnesota Multiphasic Personality Inventory (MMPI) clinical scales as well as 4 sets of MMPI items known to be sensitive to neurological dysfunction (closed head injury, cerebrovascular disorder) were administered to survivors of childhood physical and/or sexual abuse and to non-abused adults. As predicted, relative to the comparison group of psychiatric patients, the abused participants scored significantly higher on Scale 8 (Schizophrenia) and on all 4 sets of items associated with neurological dysfunction. The results suggest that early abuse/trauma is associated with cognitive disturbances and somatization. Findings appear to support the conceptualization of these psychophysical experiences as a central part of what is often called "complex posttraumatic stress disorder." Limitations and suggestions for further study are discussed.


Obtaining greater value from health care: the roles of the U.S. government.
The problems of quality and cost in the U.S. health care system are unlikely to be solved without strong leadership from the federal government, which can mobilize action to set national priorities for quality; develop and promulgate standards for care; and stimulate implementation of performance measures and standards for providers. All of these functions would best be carried out by a new federal agency. Furthermore, the federal government should design payment policies based on the performance standards, invest in needed information technology, and invest in research related to improving care and in training professionals to support nationwide quality improvement.


Polymeric and Lipid Nanoparticles: Which Applications in Pediatrics?
This review aims to provide the state of the art on polymeric and lipid nanoparticles, used or suggested to approach pediatric diseases' problems and needs, and to inspire new researches in this field. Several drugs are currently not available in formulations suitable for pediatric patients. The United States Pediatric Formulation Initiative suggested applying new technologies to pediatric drug formulations, for instance, nanotechnology. The literature analysis showed that polymeric and lipid nanoparticles have been widely studied to treat pediatric diseases, and albumin nanoparticles and liposomes are already used in clinical practice. Nevertheless, these studies are focused almost exclusively on pediatric cancer treatment. Although nanomedicine may solve many needs of pediatric diseases and medicines, the unavailability of data on pharmacokinetics, safety and efficacy of both drugs and nanoparticles in pediatric patients limits the development of new pediatric medicines based on nanoparticles. Therefore, nanomedicine applied in pediatrics remains a significant challenge in the near future.


An evolutionary hybrid cellular automaton model of solid tumour growth.
We propose a cellular automaton model of solid tumour growth, in which each cell is equipped with a micro-environment response network. This network is modelled using a feed-forward artificial neural network, that takes environmental variables as an input and from these determines the cellular behaviour as the output. The response of the network is determined by connection weights and thresholds in the network, which are subject to mutations when the cells divide. As both available space and nutrients are limited resources for the tumour, this gives rise to clonal evolution where only the fittest cells survive. Using this approach we have investigated the impact of the tissue oxygen concentration on the growth and evolutionary dynamics of the tumour. The results show that the oxygen concentration affects the selection pressure, cell population diversity and morphology of the tumour. A low oxygen concentration in the tissue gives rise to a tumour with a fingered morphology that contains aggressive phenotypes with a small apoptotic potential, while a high oxygen concentration in the tissue gives rise to a tumour with a round morphology containing less evolved phenotypes. The tissue oxygen concentration thus affects the tumour at both the morphological level and on the phenotype level.


A study on the effect of the duration of subcutaneous heparin injection on bruising and pain.
This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. This study was designed as within-subject, quasi-experimental research. The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. When administering subcutaneous heparin injections, it is important to extend the duration of the injection.


B-type natriuretic peptide levels: a potential novel "white count" for congestive heart failure.
Finding a simple blood test to aid in the diagnosis and treatment of patients with congestive heart failure could have a favorable impact on the costs associated with the disease. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles, and its level correlates with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation, thus making peptide the first potential "white count" for heart failure. Data indicate that serial point-of-care testing of BNP should be helpful in patients presenting to urgent care clinics with dyspnea. BNP may also serve as a screen for patients referred for echocardiography. A low BNP level makes left ventricular dysfunction (both systolic and diastolic) highly unlikely. BNP may also provide an effective means of improving in-hospital management of patients admitted with decompensated congestive heart failure. In some cases, BNP level observations may obviate the need for invasive hemodynamic monitoring and, when such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as in assessing the state of neurohormonal compensation of the patient.


Influence of fluoro-substitution on the planarity of 4-chlorobiphenyl (PCB 3).
Accurate structure determinations by X-ray crystal analysis and computation using semi-empirical self-consistent field molecular orbital calculations are described and compared for five monofluorinated analogues of 4-chlorobiphenyl, i.e. 2-fluoro-4-chlorobiphenyl, 2'-fluoro-4-chlorobiphenyl, 3-fluoro-4-chlorobiphenyl, 3'-fluoro-4-chlorobiphenyl and 4'-fluoro-4-chlorobiphenyl. Intermolecular interactions for all monofluorinated isomers are dominated by phenyl-phenyl stacking and C-H-phenyl interactions. C-F bond lengths varied between 1.341 and 1.374 A, C-Cl between 1.733 and 1.765 A, and both correlate with electron-density differences as determined by (13)C NMR shifts. The interior ring angles at ipso-fluoro substitution increase up to 122.2-124.2 degrees due to hyperconjugation by 2p-pi-orbital overlapping, a phenomenon that was also reflected in the computer calculation. The angles of C-F and C-Cl relative to the aromatic ring for vicinal fluoro- and chloro substituents show an attraction, not a repulsion, between the adjacent F and Cl substituents. This finding is explained on the basis of electron donor and acceptor properties. The dihedral angles of ortho-substituted biphenyls show that monofluoro substitution results in slightly smaller increases compared with chlorine, while additional ortho-fluorination results in little further change in the dihedral angle. In contrast, ortho-chlorination strongly decreases the co-planarity. This is likely to be due to interior ring-angle distortion and the size of the halogen substituent. Fluoro substitution does indeed affect the planarity of the PCB3 analogues, but these effects are minor compared with chloro substitution. Fluorine tagging offers promise for use in in vitro and in vivo studies. Differences in computational versus measured data emphasize the need to use a variety of methods to ascertain the true nature of the physical properties of a compound.