Non-identifiability of the Rayleigh damping material model in magnetic resonance elastography.
Magnetic Resonance Elastography (MRE) is an emerging imaging modality for quantifying soft tissue elasticity deduced from displacement measurements within the tissue obtained by phase sensitive Magnetic Resonance Imaging (MRI) techniques. MRE has potential to detect a range of pathologies, diseases and cancer formations, especially tumors. The mechanical model commonly used in MRE is linear viscoelasticity (VE). An alternative Rayleigh damping (RD) model for soft tissue attenuation is used with a subspace-based nonlinear inversion (SNLI) algorithm to reconstruct viscoelastic properties, energy attenuation mechanisms and concomitant damping behavior of the tissue-simulating phantoms. This research performs a thorough evaluation of the RD model in MRE focusing on unique identification of RD parameters, μI and ρI. Results show the non-identifiability of the RD model at a single input frequency based on a structural analysis with a series of supporting experimental phantom results. The estimated real shear modulus values (μR) were substantially correct in characterising various material types and correlated well with the expected stiffness contrast of the physical phantoms. However, estimated RD parameters displayed consistent poor reconstruction accuracy leading to unpredictable trends in parameter behaviour. To overcome this issue, two alternative approaches were developed: (1) simultaneous multi-frequency inversion; and (2) parametric-based reconstruction. Overall, the RD model estimates the real shear shear modulus (μR) well, but identifying damping parameters (μI and ρI) is not possible without an alternative approach.


Demethylation of G-Protein-Coupled Receptor 151 Promoter Facilitates the Binding of Krüppel-Like Factor 5 and Enhances Neuropathic Pain after Nerve Injury in Mice.
G-protein-coupled receptors are considered to be cell-surface sensors of extracellular signals, thereby having a crucial role in signal transduction and being the most fruitful targets for drug discovery. G-protein-coupled receptor 151 (GPR151) was reported to be expressed specifically in the habenular area. Here we report the expression and the epigenetic regulation of GRP151 in the spinal cord after spinal nerve ligation (SNL) and the contribution of GPR151 to neuropathic pain in male mice. SNL dramatically increased GPR151 expression in spinal neurons. GPR151 mutation or spinal inhibition by shRNA alleviated SNL-induced mechanical allodynia and heat hyperalgesia. Interestingly, the CpG island in the GPR151 gene promoter region was demethylated, the expression of DNA methyltransferase 3b (DNMT3b) was decreased, and the binding of DNMT3b with GPR151 promoter was reduced after SNL. Overexpression of DNMT3b in the spinal cord decreased GPR151 expression and attenuated SNL-induced neuropathic pain. Furthermore, Krüppel-like factor 5 (KLF5), a transcriptional factor of the KLF family, was upregulated in spinal neurons, and the binding affinity of KLF5 with GPR151 promoter was increased after SNL. Inhibition of KLF5 reduced GPR151 expression and attenuated SNL-induced pain hypersensitivity. Further mRNA microarray analysis revealed that mutation of GPR151 reduced the expression of a variety of pain-related genes in response to SNL, especially mitogen-activated protein kinase (MAPK) signaling pathway-associated genes. This study reveals that GPR151, increased by DNA demethylation and the enhanced interaction with KLF5, contributes to the maintenance of neuropathic pain via increasing MAPK pathway-related gene expression.SIGNIFICANCE STATEMENT G-protein-coupled receptors (GPCRs) are targets of various clinically approved drugs. Here we report that SNL increased GPR151 expression in the spinal cord, and mutation or inhibition of GPR151 alleviated SNL-induced neuropathic pain. In addition, SNL downregulated the expression of DNMT3b, which caused demethylation of GPR151 gene promoter, facilitated the binding of transcriptional factor KLF5 with the GPR151 promoter, and further increased GPR151 expression in spinal neurons. The increased GPR151 may contribute to the pathogenesis of neuropathic pain via activating MAPK signaling and increasing pain-related gene expression. Our study reveals an epigenetic mechanism underlying GPR151 expression and suggests that targeting GPR151 may offer a new strategy for the treatment of neuropathic pain.


Service user satisfaction with cognitive behavioural therapy for psychosis: Associations with therapy outcomes and perceptions of the therapist.
Few studies have investigated service user satisfaction with cognitive behavioural therapy for psychosis (CBTp). This study explored its associations with clinical presentation and outcomes, retrospective expectations of progress, perceptions of the therapist, and demographic variables. One hundred and sixty-five service users completed self-report questionnaires pre- and post-CBTp in relation to the constructs of interest. Regression analyses explored associations with (1) overall satisfaction with therapy and (2) perceived progress, skills, and knowledge gained. Ninety-six per cent of service users reported satisfaction with therapy. Higher levels of overall satisfaction with, and perceived benefit from, therapy were associated with positive therapy expectations, positive ratings of therapist's personal qualities, competence and trustworthiness, lower pre-therapy depression, and improvements in quality of life. Symptom improvements were not related to overall satisfaction with therapy; however, with the exception of voices, better clinical outcomes were associated with subjective ratings of having made more progress and gained more CBT skills and knowledge. Demographic factors were not associated with satisfaction or perceived progress. In multiple regression analyses, expectations of progress showed the strongest associations with both satisfaction and perceived benefits. Other remaining significant associations consisted of perceptions of the therapist for satisfaction, and both pre-therapy levels of, and changes in, depression for perceived benefits. Qualitative feedback emphasized the importance of the therapeutic relationship and developing new coping strategies. The findings provide preliminary evidence that high levels of satisfaction with therapy are not contingent on good clinical outcomes and are instead associated with positive therapy expectations and perceptions of the therapist. Therapy expectations represent a neglected area of research and may have implications for levels of satisfaction with therapy and perceived benefit. The findings reinforce the importance of cognitive behavioural therapy for psychosis (CBTp) therapists demonstrating that they are supportive, competent, and trustworthy. The findings suggest that positive experiences of therapy do not require changes in psychosis symptoms and are instead related to changes in quality of life. Depressive symptoms at the start of therapy may adversely influence the extent to which CBT skills and knowledge are gained and levels of perceived progress at the end of therapy. The present sample was restricted to service users who completed therapy. Satisfaction levels were high. Further research is needed to explore factors associated with dissatisfaction with therapy.


Pericentric H3K9me3 Formation by HP1 Interaction-defective Histone Methyltransferase Suv39h1.
Pericentric regions form epigenetically organized, silent heterochromatin structures that accumulate histone H3 lysine 9 tri-methylation (H3K9me3) and heterochromatin protein 1 (HP1), a methylated H3K9-binding protein. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1. However, the importance of HP1 interaction for Suv39h-mediated H3K9me3 formation at the pericentromere is not well characterized. To address this question, we introduced HP1 binding-defective, N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient cells. Pericentric H3K9me3-positive cells were not detected by endogenous-level expression of ΔN. Notably, ΔN could induce pericentric accumulation of H3K9me3 as wild type Suv39h1 did if it was overexpressed. These findings demonstrate that the N-terminal region of Suv39h1, presumably via HP1-Suv39h1 interaction, is required for Suv39h1-mediated pericentric H3K9me3 formation, but can be overridden if Suv39h1 is overproduced, indicating that Suv39h1-mediated heterochromatin formation is controlled by multiple modules, including HP1.


Xath5 regulates neurogenesis in the Xenopus olfactory placode.
Helix-loop-helix (HLH) genes function as important regulators of neurogenesis in both the peripheral and central nervous systems. The olfactory system is an ideal tissue in which to study the role of these genes in regulating the acquisition of neuronal cell fate, particularly that of the olfactory receptor neuron (ORN). Here we describe the expression of several basic HLH (bHLH) and repeat HLH (rHLH) factors during olfactory placode development in Xenopus laevis. Our work reveals that a combination of both bHLH and rHLH genes are sequentially expressed within the nascent olfactory placode during normal development. Moreover, overexpression of the bHLH factor, Xenopus atonal homologue 5 (Xath5), promotes olfactory neural fate independent of cellular proliferation within a restricted domain at the anterior of the embryo. Collectively, our data argue that HLH genes are expressed in a cascade during olfactory placode development and that the activity of an atonal homologue, Xath5, can promote ORN fate but only in the appropriate developmental context.


Biochemical and biophysical CO2 concentrating mechanisms in two species of freshwater macrophyte within the genus Ottelia (Hydrocharitaceae).
Two freshwater macrophytes, Ottelia alismoides and O. acuminata, were grown at low (mean 5 μmol L(-1)) and high (mean 400 μmol L(-1)) CO2 concentrations under natural conditions. The ratio of PEPC to RuBisCO activity was 1.8 in O. acuminata in both treatments. In O. alismoides, this ratio was 2.8 and 5.9 when grown at high and low CO2, respectively, as a result of a twofold increase in PEPC activity. The activity of PPDK was similar to, and changed with, PEPC (1.9-fold change). The activity of the decarboxylating NADP-malic enzyme (ME) was very low in both species, while NAD-ME activity was high and increased with PEPC activity in O. alismoides. These results suggest that O. alismoides might perform a type of C4 metabolism with NAD-ME decarboxylation, despite lacking Kranz anatomy. The C4-activity was still present at high CO2 suggesting that it could be constitutive. O. alismoides at low CO2 showed diel acidity variation of up to 34 μequiv g(-1) FW indicating that it may also operate a form of crassulacean acid metabolism (CAM). pH-drift experiments showed that both species were able to use bicarbonate. In O. acuminata, the kinetics of carbon uptake were altered by CO2 growth conditions, unlike in O. alismoides. Thus, the two species appear to regulate their carbon concentrating mechanisms differently in response to changing CO2. O. alismoides is potentially using three different concentrating mechanisms. The Hydrocharitaceae have many species with evidence for C4, CAM or some other metabolism involving organic acids, and are worthy of further study.


Artificial Selection Finds New Hypotheses for the Mechanism of Wolbachia-Mediated Dengue Blocking in Mosquitoes.
Wolbachia is an intracellular bacterium that blocks virus replication in insects and has been introduced into the mosquito, Aedes aegypti for the biocontrol of arboviruses including dengue, Zika, and chikungunya. Despite ongoing research, the mechanism of Wolbachia-mediated virus blocking remains unclear. We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia-mediated dengue blocking. From our results, we hypothesize that Wolbachia may block virus replication by increasing the regeneration rate of mosquito cells via the Notch signaling pathway. We also propose that Wolbachia modulates the host's transcriptional pausing pathway either to prime the host's anti-viral response or to directly inhibit viral replication.


Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigen-specific regulatory T cells.
The outcome of T-cell-mediated responses, immunity or tolerance, critically depends on the balance of cytopathic versus regulatory T (T(reg)) cells. In the creation of stable tolerance to MHC incompatible allografts, reducing the unusually large mass of donor-reactive cytopathic T effector (T(eff)) cells via apoptosis is often required. Cyclosporine (CsA) blocks activation-induced cell death (AICD) of T(eff) cells, and is detrimental to tolerance induction by costimulation blockade, whereas Rapamycin (RPM) preserves AICD, and augments the potential of costimulation blockade to create tolerance. While differences between CsA and RPM in influencing apoptosis of activated graft-destructive T(eff) cells are apparent, their effects on graft-protective T(reg) cells remain enigmatic. Moreover, it is unclear whether tolerizing regimens foster conversion of naïve peripheral T cells into alloantigen-specific T(reg) cells for graft protection. Here we show, using reporter mice for T(reg) marker Foxp3, that RPM promotes de novo conversion of alloantigen-specific T(reg) cells, whereas CsA completely inhibits this process. Upon transfer, in vivo converted T(reg) cells potently suppress the rejection of donor but not third party skin grafts. Thus, the differential effects of RPM and CsA on T(eff) and T(reg) cells favor the use of RPM in shifting the balance of aggressive to protective type alloimmunity.


Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD.
Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.


Pharmacokinetic alteration of baclofen by multiple oral administration of herbal medicines in rats.
The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42-4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a ) of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.


[Reflections on the authorship of the scientific studies].
This document aims to comment on the currently used concepts of authorship of scientific articles. Parallelly, the question of the order of the authors is discussed. The concept of authorship according to contribution and of the special case of the group publications is approached. Special emphasis has been made in the bibliographic search on obtaining publications from groups of Spanish authors to illustrate how the group signing of the publications in our setting is done. Finally, the Clinical Research Group in Primary Care (G-ICAP) makes a series of recommendations in order to facilitate decision-making on these subjects, both for the studies of the G-ICAP itself as well as for other scientific studies developed in the health sciences setting. (c) 2009 Elsevier España, S.L. All rights reserved.


Oxidative Metabolism Drives Immortalization of Neural Stem Cells during Tumorigenesis.
Metabolic reprogramming is a key feature of many cancers, but how and when it contributes to tumorigenesis remains unclear. Here we demonstrate that metabolic reprogramming induced by mitochondrial fusion can be rate-limiting for immortalization of tumor-initiating cells (TICs) and trigger their irreversible dedication to tumorigenesis. Using single-cell transcriptomics, we find that Drosophila brain tumors contain a rapidly dividing stem cell population defined by upregulation of oxidative phosphorylation (OxPhos). We combine targeted metabolomics and in vivo genetic screening to demonstrate that OxPhos is required for tumor cell immortalization but dispensable in neural stem cells (NSCs) giving rise to tumors. Employing an in vivo NADH/NAD+ sensor, we show that NSCs precisely increase OxPhos during immortalization. Blocking OxPhos or mitochondrial fusion stalls TICs in quiescence and prevents tumorigenesis through impaired NAD+ regeneration. Our work establishes a unique connection between cellular metabolism and immortalization of tumor-initiating cells.


The Women's Study for the Alleviation of Vasomotor Symptoms (WAVS): a randomized, controlled trial of a plant-based diet and whole soybeans for postmenopausal women.
This study aimed to assess the effects of the combination of a low-fat plant-based diet and soybeans on the frequency and severity of menopausal hot flashes. Postmenopausal women (n = 38) reporting two or more hot flashes/day were randomly assigned to a low-fat, vegan diet, including ½ cup (86 g) of cooked soybeans daily, or to no diet changes for 12 weeks. Frequency and severity of hot flashes were recorded using a mobile application, and vasomotor, psychosocial, physical, and sexual symptoms were assessed using the Menopause-Specific Quality of Life Questionnaire. Significance was assessed using t-tests (continuous outcomes) and chi-squared/McNemar tests (binary outcomes). Total hot flashes decreased 79% in the intervention group (P < 0.001) and 49% in the control group (P = 0.002; between-group P = 0.01). Moderate-to-severe hot flashes decreased 84% in the intervention group (P < 0.001) and 42% in the control group P = 0.009; between-group P = 0.01). From 0 to 12 weeks, 59% (10/17) of intervention-group participants reported becoming free of moderate and severe hot flashes (P = 0.002). There was no change in this variable in the control group (between-group P < 0.001). The Menopause-Specific Quality of Life Questionnaire revealed significantly greater reductions in the intervention group in vasomotor (P < 0.0001), psychosocial (P = 0.04), physical (P < 0.002), and sexual (P = 0.01) domains. The combination of a low-fat, vegan diet and whole soybeans was associated with reduced frequency and severity of hot flashes and improved quality of life in vasomotor, psychosocial, physical, and sexual domains in postmenopausal women. During the 12-week study period, the majority of intervention-group participants became free of moderate-to-severe hot flashes.


Analytical report of the 2016 dengue outbreak in Córdoba city, Argentina.
After elimination of the Aedes aegypti vector in South America in the 1960s, dengue outbreaks started to reoccur during the 1990s; strongly in Argentina since 1998. In 2016, Córdoba City had the largest dengue outbreak in its history. In this article we report this outbreak including spatio-temporal analysis of cases and vectors in the city. A total of 653 dengue cases were recorded by the laboratory-based dengue surveillance system and georeferenced by their residential addresses. Case maps were generated from the epidemiological week 1 (beginning of January) to week 19 (mid-May). Dengue outbreak temporal evolution was analysed globally and three specific, high-incidence zones were detected using Knox analysis to characterising its spatio-temporal attributes. Field and remotely sensed data were collected and analysed in real time and a vector presence map based on the MaxEnt approach was generated to define hotspots, towards which the pesticide- based strategy was then targeted. The recorded pattern of cases evolution within the community suggests that dengue control measures should be improved.


Survivin as a novel target protein for reducing the proliferation of cancer cells.
Survivin, also known as baculoviral inhibitor of apoptosis repeat-containing 5, is a novel member of the inhibitor of apoptosis protein family. Survivin is highly expressed in tumors and embryonic tissues and is associated with tumor cell differentiation, proliferation, invasion and metastasis; however, survivin is expressed at low levels in normal terminally differentiated adult tissues. Meanwhile, the expression level of survivin is also a negative prognostic factor for patients with cancer. These unique characteristics of survivin make it an exciting potential therapeutic target for cancer treatment. This review will discuss the biological characteristics of survivin and its potential use as a treatment target to reduce cancer cell proliferation.


Empagliflozin Treatment Attenuates Hepatic Steatosis by Promoting White Adipose Expansion in Obese TallyHo Mice.
Sodium-glucose co-transporters (SGLTs) serve to reabsorb glucose in the kidney. Recently, these transporters, mainly SGLT2, have emerged as new therapeutic targets for patients with diabetes and kidney disease; by inhibiting glucose reabsorption, they promote glycosuria, weight loss, and improve glucose tolerance. They have also been linked to cardiac protection and mitigation of liver injury. However, to date, the mechanism(s) by which SGLT2 inhibition promotes systemic improvements is not fully appreciated. Using an obese TallyHo mouse model which recapitulates the human condition of diabetes and nonalcoholic fatty liver disease (NAFLD), we sought to determine how modulation of renal glucose handling impacts liver structure and function. Apart from an attenuation of hyperglycemia, Empagliflozin was found to decrease circulating triglycerides and lipid accumulation in the liver in male TallyHo mice. This correlated with lowered hepatic cholesterol esters. Using in vivo MRI analysis, we further determined that the reduction in hepatic steatosis in male TallyHo mice was associated with an increase in nuchal white fat indicative of "healthy adipose expansion". Notably, this whitening of the adipose came at the expense of brown adipose tissue. Collectively, these data indicate that the modulation of renal glucose handling has systemic effects and may be useful as a treatment option for NAFLD and steatohepatitis.


[Isoenzyme characteristics of glucose-6-phosphage dehydrogenase and lactate dehydrogenase of continuous cells from the collection of the Sverdlovsk Research Institute of Virus Infections].
An analysis of isoenzymes of glucose-6-phosphage dehydrogenase (G-6-P-DH) and lactage dehydrogenase (LDH) of continuous cells from the collection of Sverdlovsk Research Institute of Virus Infections was carried out. Seventeen continous human and animal cell lines were examined by electrophoresis in a vertical block of 7% polyacrylamide gel followed by histochemical detection of the enzymes. The HEp-2, HEp-2 clone No. 23, KB, RH, and FL cells were shown to have the electrophoretic motility of G-6-PDG characteristic of HeLa cell line. LEP and SOC cell lines were contaminated with mouse cells. A culture of rat fibroblasts had isoenzymes of G-6-PDG and LDG characteristic of HeLa cell line. The remaining cell lines had the isoenzymatic characteristics corresponding to their species appurtenance.


Evaluation of densitometric bone-muscle relationships in Crohn's disease.
Patients with Crohn's disease (CD) are 1.4 to 2.5 times more likely than the normal population to sustain a fracture but the factors involved in the pathogenesis are not clearly understood. Bone mass is affected both by nutrition and by muscular activity. Trauma excepted, the largest voluntary loads on bones come from muscle contraction, not body weight. To assess the relationship between bone mass (bone mineral content) and muscle mass (lean mass) in CD patients. Adult CD patients who had had a whole body, lumbar and hip densitometric evaluation were selected. Information regarding age, gender, weight, duration of CD, age at diagnosis, use of glucocorticoids and disease activity during the year before densitometric evaluation and laboratory parameters were collected. Data from 65 patients (28.8+/-10.6 years, F=44, M=21) were analyzed. Lumbar bone mineral content (BMC), BMC in both hips, total and regional BMC significantly correlated with body weight and total and regional lean mass (LM). In multiple regression analysis, only total LM was shown to be independently associated with lumbar BMC, BMC in both hips and total BMC. LM in upper and lower limbs was shown to be independently associated with BMC in upper and lower limbs, respectively. These results suggest that muscular mass and activity, rather than overall body weight, are important determinants of bone mass and, hence of bone strength in Crohn's disease. Thus, the management of bone loss in inflammatory bowel disease should address the effects of both nutrition and exercise on muscle mass.


Glaucomatocyclitic crisis.
Ten patients with glaucomatocyclitic crisis were examined for glaucoma during the interval. The follow-up period was over ten years. One patient had primary open angle glaucoma and two had suspicion of glaucoma. These findings confirmed our previous concept of an association between glaucomatocyclitic crises and open angle glaucoma. Six patients were examined during acute attacks. Focal segmental ischaemia of the iris of different degree was typical during the attack, later in the immediate postattack phase congestion, leakage and even extreme hypotony were found. Iris angiography during the interval showed generally a rich vascular pattern, and in some cases, tortuous vascular tufts. Stromal atrophy and atrophy of the sphincter were considered secondary to pressure attacks. The role of the abnormal reactivity of the vessels of the ciliary vascular system on the development of acute attacks is discussed.


Effective geometry for light traveling in material media.
Working with electrodynamics in the geometrical optics approximation, we derive the expression representing the "effective geometry" seen by electromagnetic waves propagating in media whose physical properties depend on an external electric field. Some previous results are generalized and some special cases are recovered.


Percutaneous Intervention in ST-Elevation Myocardial Infarction: Culprit-only or Complete Revascularization?
The best approach of multivessel coronary artery disease in the context of acute myocardial infarction with ST segment elevation and primary percutaneous coronary intervention is one of the main reasons for controversy in cardiology. Although the main global guidelines do not recommend routine complete revascularization in these patients, recent randomized clinical trials have demonstrated benefit of this approach in reducing cardiovascular outcomes. For this reason, an adequate review of this evidence is essential in order to establish scientifically based strategy and achieve better outcomes for these patients who present with acute myocardial infarction. This review aims to present objectively the most recent evidence available on this topic.


Long noncoding RNA-mediated maintenance of DNA methylation and transcriptional gene silencing.
Establishment of silencing by noncoding RNAs (ncRNAs) via targeting of chromatin remodelers is relatively well investigated; however, their role in the maintenance of silencing is poorly understood. Here, we explored the functional role of the long ncRNA Kcnq1ot1 in the maintenance of transcriptional gene silencing in the one mega-base Kcnq1 imprinted domain in a transgenic mouse model. By conditionally deleting the Kcnq1ot1 ncRNA at different stages of mouse development, we suggest that Kcnq1ot1 ncRNA is required for the maintenance of the silencing of ubiquitously imprinted genes (UIGs) at all developmental stages. In addition, Kcnq1ot1 ncRNA is also involved in guiding and maintaining the CpG methylation at somatic differentially methylated regions flanking the UIGs, which is a hitherto unknown role for a long ncRNA. On the other hand, silencing of some of the placental-specific imprinted genes (PIGs) is maintained independently of Kcnq1ot1 ncRNA. Interestingly, the non-imprinted genes (NIGs) that escape RNA-mediated silencing are enriched with enhancer-specific modifications. Taken together, this study illustrates the gene-specific maintenance mechanisms operational at the Kcnq1 locus for tissue-specific transcriptional gene silencing and activation.


The association of C-reactive protein levels with carotid intima-media complex thickness and plaque formation in the general population.
An inflammatory response has been associated with the development of atherosclerosis. Our aim was to clarify which atherosclerotic changes (intima-media complex thickness [IMT] increase, plaque formation, and arterial dilatation) are associated with C-reactive protein (CRP) levels and to determine whether there are any gender differences. Carotid ultrasound and measurement of high-sensitivity CRP (hs-CRP) levels were performed in 2056 subjects selected from a general population (mean age 58.3 years; 1290 men). In both genders, IMT significantly increased with increasing hs-CRP quartile (P<0.001), but this relationship disappeared after adjustment for age and other traditional cardiovascular risk factors. In men, but not women, carotid luminal diameter significantly increased with increasing hs-CRP levels (P<0.05), but again, this relationship disappeared with adjustment for age and other risk factors. However, in men, but not women, plaque score increased significantly with increasing hs-CRP quartile (P<0.01), even after adjustment for age and other traditional risk factors. CRP level was closely associated with early atherosclerotic changes represented by carotid plaque formation. However, the IMT increase was strongly associated with aging and other traditional cardiovascular risk factors rather than CRP level. In the general population, CRP may serve as a complementary and quantitative marker for atherosclerotic plaque formation in men but not women.


Dissemination of VanA-Type Enterococcus faecium Isolates in Hungary.
Although vanA carrying Enterococcus faecium human clinical isolates have been rarely found in Hungary before 2012, they have been detected in continuously increasing numbers since then. To identify factors associated with their dissemination, we investigated the clonal relatedness and plasmids of 30 vanA carrying E. faecium isolates originating from different Hungarian healthcare institutions from 2012 to 2014. Molecular typing of the isolates (n = 30) was performed with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, Tn1546 polymerase chain reaction mapping, plasmid restriction fragment length polymorphism analysis, and sequencing. A single Tn1546 variant was detected in all of the isolates. It harbored IS1251 in the vanS-vanH intergenic region, had an entire deletion of the transposase gene and a partial deletion of the resolvase gene, and was located on a pRUM-like plasmid. Based on PFGE, the isolates could be grouped into 13 pulsotypes. Representative strains of these pulsotypes belonged to ST17, ST18, ST80, ST117, and ST203, which are known to be part of the hospital-adapted clades. The increase in the number of vanA carrying E. faecium clinical isolates in Hungary could be explained by the dissemination of pRUM-like vancomycin resistance plasmids in hospital-adapted clonal lineages.


Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide.
Mixtures of Cu2+ and H2O2 at pH 7.4 caused damage to the bases in DNA greater than that caused by mixtures of Fe3+ and H2O2. Addition of ascorbic acid to the Cu2+/H2O2 system caused a very large increase in base damage, much greater than that produced by the Fe3+/H2O2/ascorbic acid system. The products of base damage in the presence of Cu2+ were typical products that have been shown to result from attack of hydroxyl radicals upon the DNA bases. Cytosine glycol, thymine glycol, 8-hydroxyadenine and especially 8-hydroxyguanine were the major products in both the Cu2+/H2O2 and the Cu2+/H2O2/ascorbic acid systems. Base damage in DNA by these systems was inhibited by the chelating agents EDTA and nitrilotriacetic acid and by catalase, but not by superoxide dismutase, nor by the hydroxyl-radical scavenger mannitol. It is proposed that Cu2+ ions bound to the DNA react with H2O2 and ascorbic acid to generate hydroxyl radicals, which then immediately attack the DNA bases in a site-specific manner. A hypoxanthine/xanthine oxidase system also caused damage to the DNA bases in the presence of Cu2+ ions. This was inhibited by superoxide dismutase and catalase. The high activity of Cu2+ ions, when compared with Fe3- ions, in causing hydroxyl-radical-dependent damage to DNA and to other biomolecules, means that the availability of Cu2+ ions in vivo must be carefully controlled.


A randomised comparative study on customised versus fixed sized pillow for tracheal intubation in the sniffing position by Macintosh laryngoscopy.
The sniffing position has been most commonly used for positioning of the head and neck to facilitate tracheal intubation. However, the optimum degree of head elevation for the optimal laryngeal view is not well studied, especially in non-Western countries. The present study was aimed to compare the use of a fixed height pillow versus a customised pillow (CP) height for head elevation, in terms of glottis visualisation and time required for tracheal intubation. With research and ethics committee approval from the institute, this randomised study was conducted among patients of both sexes aged 16 years or more and American Society of Anesthesiologists physical Status I to IV. A total of 134 patients were randomly allocated into routinely used fixed-sized pillow (FP) and CP group (to achieve horizontal alignment of external auditory meatus [EAM] and sternal notch). Primary and secondary outcomes were Cormack-Lehane (C-L) grade of glottic visualisation and time required for tracheal intubation, respectively. They were compared using unpaired t-test and Fisher's exact test as applicable; P < 0.05 was considered statistically significant. One hundred and nineteen patients completed the study. Both groups were similar in terms of demographic and external airway measurements. The mean ± standard deviation height of pillow required in Group CP was 6.26 ± 0.97 cm. Group FP had C-L Grade 3 view more often than Group CP (28.33% vs. 13.56%). In patients with modified Mallampati (MMP) Grade ≥3, the C-L grades and time required for intubation were both significantly lower in group CP. The time required for tracheal intubation was significantly lower in group CP (P = 0.04), even though the C-L grades were similar. Customising pillow for head elevation to horizontally align the EAM and the sternal notch gives better glottic visualisation and intubating conditions in patients with higher MMP grades.


An unusual presentation: trichomycosis (trichobacteriosis) capitis in an infant.
Trichomycosis (trichobacteriosis) is an asymptomatic superficial bacterial colonization of the hair shaft that is clinically characterized by pale yellowish, reddish or blackish sticky, cylindrical concretions surrounding the hair shaft in the axillary or pubic region. As far as we know, the first and only case of trichomycosis capitis was reported in a 8-year-old boy in 2011. We encountered no cases of trichomycosis in infancy in the literature. The current case displays an atypical presentation of trichobacteriosis involving head hair in a 10-month-old male infant.


Gait analysis using a shoe-integrated wireless sensor system.
We describe a wireless wearable system that was developed to provide quantitative gait analysis outside the confines of the traditional motion laboratory. The sensor suite includes three orthogonal accelerometers, three orthogonal gyroscopes, four force sensors, two bidirectional bend sensors, two dynamic pressure sensors, as well as electric field height sensors. The "GaitShoe" was built to be worn in any shoe, without interfering with gait and was designed to collect data unobtrusively, in any environment, and over long periods. The calibrated sensor outputs were analyzed and validated with results obtained simultaneously from the Massachusetts General Hospital, Biomotion Laboratory. The GaitShoe proved highly capable of detecting heel-strike and toe-off, as well as estimating foot orientation and position, inter alia.


Determining rubella immunity in pregnant Alberta women 2009-2012.
Rubella IgG levels for 157,763 pregnant women residing in Alberta between 2009 and 2012 were analyzed. As there have been no reported cases of indigenous rubella infection in Canada since 2005, there has been a lack of naturally acquired immunity, and the current prenatal population depends almost entirely on vaccine induced immunity for protection. Rubella antibody levels are significantly lower in younger maternal cohorts with 16.8% of those born prior to universal vaccination programs (1971-1980), and 33.8% of those born after (1981-1990) having IgG levels that are not considered protective (<15 IU/mL). Analysis across pregnancies showed only 35.0% of women responded with a 4-fold increase in antibody levels following post-natal vaccination. Additionally, 41.2% of women with antibody levels <15 IU/mL had previously received 2 doses of rubella containing vaccine. These discordant interpretations generate a great deal of confusion for laboratorians and physicians alike, and result in significant patient follow-up by Public Health teams. To assess the current antibody levels in the prenatal population, latent class modeling was employed to generate a two class fit model representing women with an antibody response to rubella, and women without an antibody response. The declining level of vaccine-induced antibodies in our population is disconcerting, and a combined approach from the laboratory and Public Health may be required to provide appropriate follow up for women who are truly susceptible to rubella infection.


A pilot study of the long-term effects of acipimox in polycystic ovarian syndrome.
To evaluate the effects of long-term acipimox administration on glucose-induced insulin secretion and peripheral insulin sensitivity in polycystic ovarian syndrome (PCOS), 20 PCOS subjects (eight lean and 12 obese) and 14 body mass index-matched controls (seven lean and seven obese) were investigated. Fasting blood samples were collected for basal hormone and lipoprotein assays, after which patients underwent an oral glucose tolerance test (OGTT). The following day a euglycaemic-hyperinsulinaemic clamp was performed. After 4-6 weeks of treatment with acipimox at a dose of 250 mg given orally three times a day, the patients repeated the study protocol. No significant differences were found in the glucose, insulin or C-peptide responses to OGTT before and after anti-lipolytic drug administration in any group, nor was there any effect on insulin sensitivity. Concerning the lipid profile, acipimox administration led to a significant decrease of cholesterol and low-density lipoprotein levels in obese PCOS patients as well as in obese and lean controls. Lower triglycerides were found after the drug administration in both obese groups. Post-treatment free fatty acid levels were not significantly different when compared with basal values. Acipimox does not appear to be an effective insulin-lowering drug in PCOS, even if it can be used in obese women with PCOS as an additional therapeutic agent to ameliorate the atherogenic lipid profile of the syndrome.


Symmetry and Correlation Effects on Band Structure Explain the Anomalous Transport Properties of (111) LaAlO_{3}/SrTiO_{3}.
The interface between the two insulating oxides SrTiO_{3} and LaAlO_{3} gives rise to a two-dimensional electron system with intriguing transport phenomena, including superconductivity, which are controllable by a gate. Previous measurements on the (001) interface have shown that the superconducting critical temperature, the Hall density, and the frequency of quantum oscillations, vary nonmonotonically and in a correlated fashion with the gate voltage. In this Letter we experimentally demonstrate that the (111) interface features a qualitatively distinct behavior, in which the frequency of Shubnikov-de Haas oscillations changes monotonically, while the variation of other properties is nonmonotonic albeit uncorrelated. We develop a theoretical model, incorporating the different symmetries of these interfaces as well as electronic-correlation-induced band competition. We show that the latter dominates at (001), leading to similar nonmonotonicity in all observables, while the former is more important at (111), giving rise to highly curved Fermi contours, and accounting for all its anomalous transport measurements.


TMD pain is partly heritable. A systematic review of family studies and genetic association studies.
The aim of this study was to describe the current knowledge on the role of heritability in TMD pain through a systematic review of the literature, including familiar aggregation studies and genetic association studies. For the systematic search of the literature, the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines were followed. In total, 21 studies were included in the review, including five familiar aggregation studies and 16 genetic association studies. From both familiar aggregation studies and genetic association studies, modest evidence for the role of heritability in TMD pain was found. The literature mainly suggests genetic contributions from candidate genes that encode proteins involved in the processing of painful stimuli from the serotonergic and catecholaminergic system. This systematic review shows that the evidence for the role of heritability in the development of TMD pain is cumulating.


[Intra-arterial chemotherapy and chemoembolization in the combined treatment for locally advanced carcinoma of the head and neck].
We evaluated the role of intra-arterial chemotherapy and/or chemoembolization, intravenous systemic chemotherapy and radiotherapy in combined treatment for locally advanced unresectable carcinoma of the head and neck. Transfemoral approach for catheterization with chemoinfusion/chemoembolization of the external carotid artery branches with carboplatin (300 mg/m2), 5-fluorouracil (1000 mg/m2) and gelatin sponge was attempted in 25 patients. Out of that number, 18 received additional radiotherapy. Bleeding episodes and relevant high risk in the future were indications for embolization treatment. There was complete (2) and partial (8) tumor regression or stabilization (5) (83%), progression (3) (17%). Arterial and systemic chemotherapy without irradiation resulted in one partial response, 3 cases of stabilization (57%), and 3 cases of progression (out of 7) (43%). There were no episodes of chronic tumor-related bleeding (7). Hence, combined treatment for locally advanced carcinoma of the head and neck including intra-arterial chemotherapy, chemoembolization, intravenous systemic chemotherapy and radiotherapy can be safely delivered with high response rates and low systemic toxicity. Since all these measures are accompanied by relatively low risks of chronic bleeding a choice of palliative or radical dosage of radiation is possible.


Prognostic value of SUVmax and metabolic tumor volume on 18F-FDG PET/CT in early stage non-small cell lung cancer patients without LN metastasis.
This paper aimed to evaluate the prognostic value of maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the primary tumor on (18)F-FDG PET/CT scan in early stage non-small cell cancer (NSCLC) patients without lymph node (LN) metastasis. In the experiment, eighty NSCLC patients pathologically staged as T1N0 or T2N0 were included (M:F=50:30; mean age, 64.8 years). All patients had preoperative (18)F-FDG PET/CT scan and curative surgery. FDG uptake in the primary tumor was measured by SUVmax and MTV with various SUV threshold values. SUVmax, MTV of the primary tumor, age, tumor size, histology and differentiation grade were analyzed for association with disease-free survival (DFS). The experimental results showed that the histology types included adenocarcinoma (n=58), squamous cell carcinoma (n=20), and others (n=2); Twenty-two (27.5%) of the 80 patients had a recurrence during follow-up at a median time of 29.1 months; The median SUVmax was 5.26, and the median MTV2.5 was 2.2 cm(3). Univariate analysis showed higher SUVmax (>4), greater MTV (MTV2.5 >4 cm(3)), and non-squamous histology were significantly associated with shorter period DFS (p=0.001, p=0.030 and p<0.001). In multivariate analysis, higher SUVmax (p=0.004) and adenocarcinoma histology (p=0.005) were associated with shorter DFS. Therefore, high SUVmax (>4) of the primary tumor on preoperative (18)F-FDG PET/CT scan is an independent prognostic factor of shorter DFS in early stage of NSCLC.


Hyperspectral and multispectral bioluminescence optical tomography for small animal imaging.
For bioluminescence imaging studies in small animals, it is important to be able to accurately localize the three-dimensional (3D) distribution of the underlying bioluminescent source. The spectrum of light produced by the source that escapes the subject varies with the depth of the emission source because of the wavelength-dependence of the optical properties of tissue. Consequently, multispectral or hyperspectral data acquisition should help in the 3D localization of deep sources. In this paper, we describe a framework for fully 3D bioluminescence tomographic image acquisition and reconstruction that exploits spectral information. We describe regularized tomographic reconstruction techniques that use semi-infinite slab or FEM-based diffusion approximations of photon transport through turbid media. Singular value decomposition analysis was used for data dimensionality reduction and to illustrate the advantage of using hyperspectral rather than achromatic data. Simulation studies in an atlas-mouse geometry indicated that sub-millimeter resolution may be attainable given accurate knowledge of the optical properties of the animal. A fixed arrangement of mirrors and a single CCD camera were used for simultaneous acquisition of multispectral imaging data over most of the surface of the animal. Phantom studies conducted using this system demonstrated our ability to accurately localize deep point-like sources and show that a resolution of 1.5 to 2.2 mm for depths up to 6 mm can be achieved. We also include an in vivo study of a mouse with a brain tumour expressing firefly luciferase. Co-registration of the reconstructed 3D bioluminescent image with magnetic resonance images indicated good anatomical localization of the tumour.


[Recent Knowledge of Smoking and Peripheral Arterial Disease in Lower Extremities].
Peripheral arterial disease (PAD) is an atherosclerotic obstructive disease of the arteries in lower extremities. Patients with PAD show high rates of mortality from coronary artery disease (CAD) and stroke. Smoking as well as diabetes is an important risk factor for PAD. A lesion of PAD in the lower extremities tends to be more proximal in smokers than in nonsmokers and to be more distal in patients with diabetes than in nondiabetics. By a systematic review, the odds ratio for PAD of smokers vs nonsmokers has been reported to be in the range of 1.7-7.4. Previous epidemiological studies suggest a stronger association of smoking with PAD than that with CAD. Nitric oxide (NO) is an important molecule suppressing the progression of atherosclerosis, but this function is compromised by smoking. Smoking decreases the bioactivity of NO and the expression level of NO synthase. In addition, smoking results in deteriorations of risk factors for atherosclerosis such as decreases in blood HDL (high-density lipoprotein) cholesterol and tissue plasminogen activator levels and increases in the levels of blood triglycerides, LDL (low-density lipoprotein) cholesterol, fibrinogen and the von Willebrand factor. Thus, smoking increases blood coagulability and deteriorates the blood lipid profile, resulting in thrombogenetic proneness and dyslipidemia. Smoking also increases the generation of atherogenic oxidized LDL in blood and decreases antiatherogenic prostacyclin production in the vascular endothelium. Smoking cessation is important for the prevention and therapy of PAD, and to this end, counseling by physicians and nicotine replacement therapy are useful and strongly recommended for patients with PAD.


Random walk with chaotically driven bias.
We investigate two types of random walks with a fluctuating probability (bias) in which the random walker jumps to the right. One is a 'time-quenched framework' using bias time series such as periodic, quasi-periodic, and chaotic time series (chaotically driven bias). The other is a 'time-annealed framework' using the fluctuating bias generated by a stochastic process, which is not quenched in time. We show that the diffusive properties in the time-quenched framework can be characterised by the ensemble average of the time-averaged variance (ETVAR), whereas the ensemble average of the time-averaged mean square displacement (ETMSD) fails to capture the diffusion, even when the total bias is zero. We demonstrate that the ETVAR increases linearly with time, and the diffusion coefficient can be estimated by the time average of the local diffusion coefficient. In the time-annealed framework, we analytically and numerically show normal diffusion and superdiffusion, similar to the Lévy walk. Our findings will lead to new developments in information and communication technologies, such as efficient energy transfer for information propagation and quick solution searching.


Divergence of the Floral A-Function between an Asterid and a Rosid Species.
The ABC model is widely used as a genetic framework for understanding floral development and evolution. In this model, the A-function is required for the development of sepals and petals and to antagonize the C-function in the outer floral whorls. In the rosid species Arabidopsis thaliana, the AP2-type AP2 transcription factor represents a major A-function protein, but how the A-function is encoded in other species is not well understood. Here, we show that in the asterid species petunia (Petunia hybrida), AP2B/BLIND ENHANCER (BEN) confines the C-function to the inner petunia floral whorls, in parallel with the microRNA BLINDBEN belongs to the TOE-type AP2 gene family, members of which control flowering time in Arabidopsis. In turn, we demonstrate that the petunia AP2-type REPRESSOR OF B-FUNCTION (ROB) genes repress the B-function (but not the C-function) in the first floral whorl, together with BEN We propose a combinatorial model for patterning the B- and C-functions, leading to the homeotic conversion of sepals into petals, carpels, or stamens, depending on the genetic context. Combined with earlier results, our findings suggest that the molecular mechanisms controlling the spatial restriction of the floral organ identity genes are more diverse than the well-conserved B and C floral organ identity functions.


Teaching advanced practice nursing students how to use the Internet to support an evidence-based clinical practice.
In the past decade, clinicians have dramatically increased their use of the Internet as an information resource to guide clinical practice. The amount of evidence-based information on the World Wide Web (WWW) is growing at an explosive rate. Although the term "Internet" actually refers to the wires that link computers, and the term "World Wide Web" refers to the linked information, these terms will be used interchangeably in this article. Advanced practice nurses (APNs) need to learn how to locate evidence-based information efficiently on the Internet, how to evaluate the validity and relevance of the information, and how to use the information to support their practice decisions. This article describes a research course that the author teaches to APN students at the University of San Francisco School of Nursing. The course was designed to improve students' skills in using the Internet to support an evidence-based clinical practice (EBCP). The information in this article can assist nurse educators in teaching their APN students how to locate and evaluate evidence-based information on the Internet. It also can assist practicing APNs in using the Internet to facilitate an EBCP.


Capturing genomic relationships that matter.
There is a strong interrelationship within the cell nucleus between form and function of the genome. This connection is exhibited across multiple hierarchies, ranging from grand-scale positioning of chromosomes and their intersection with specific nuclear functional activities, the segregation of chromosome structure into distinct domains and long-range regulatory contacts that drive spatial and temporal expression patterns of genes. Fifteen years ago, the development of the chromosome conformation capture method placed the nature of specific, long-range regulatory interactions under scrutiny. However, its development and integration with next-generation sequencing technologies has greatly expanded the breadth and scope of what is detected. The sheer scale of data offered by these important advances has come with new and challenging bottlenecks that are both experimental and bioinformatical. Here, we discuss the recent and prospective development and implementation of new methodologies and analytical tools that are allowing an in-depth, yet focussed characterisation of genomic contacts that are associated with functional activities in the nucleus.


Roles of the three transcriptional attenuators of the Bacillus subtilis pyrimidine biosynthetic operon in the regulation of its expression.
Expression of the Bacillus subtilis pyr operon is regulated by exogenous pyrimidines and the protein product of the first gene of the operon, PyrR. It has been proposed that PyrR mediates transcriptional attenuation at three untranslated segments of the operon (R.J. Turner, Y. Lu, and R.L. Switzer, J. Bacteriol., 176:3708-3722, 1994). In this study, transcriptional fusions of the pyr promoter followed by the pyr attenuation sequences, either individually or in tandem to a lacZ reporter gene, were used to examine the physiological functions of all three attenuators through their ability to affect beta-galactosidase expression. These fusions were studied as chromosomal integrants in various B. subtilis strains to examine the entire range of control by pyrimidines, PyrR dependence, amd developmental control of pyr gene expression. The nutritional regulation of each attenuator separately was roughly equivalent to that of the other two and was totally dependent upon PyrR, and that of tandem attenuators was cumulative. The regulation of a fusion of the spac promoter followed by the pyrP:pyrB intercistronic region to lacZ produced results similar to those obtained with the corresponding fusion containing the pyr promoter, demonstrating that attenuator-dependent regulation is independent of the promoter. Extreme pyrimidine starvation gave rise to two- to threefold-higher levels of expression of a pyr-lacZ fusion that lacked attenuators, independent of PyrR, than were obtained with cells that were not starved. Increased expression of a similar spac-lacZ fusion during pyrimidine starvation was also observed, however, indicating that attenuator-independent regulation is not a specific property of the pyr operon. Conversion of the initiator AUG codon in a small open reading frame in the pyrP:pyrB intercistronic region to UAG reduced expression by about half but did not alter regulation by pyrimidines, which excludes the possibility of a coupled transcription-translation attenuation mechanism. Developmental regulation of pyr expression during early stationary phase was found to be dependent upon the attenuators and PyrR, and the participation of SpoOA was excluded.


Multiprofessional team simulation training, based on an obstetric model, can improve teamwork in other areas of health care.
This interrupted time-series study evaluated the impact of multiprofessional scenario-based training on the safety culture and teamwork climate of 3 surgical wards during a time of reduced financial resources. The authors ran 22 team training sessions for teams of 4 to 5 medical and nursing staff over a 4-month period on 3 surgical wards, using 2 scenarios based on a previously successful obstetric training program. Safety culture was measured before and after training using a validated psychometric questionnaire. After training there was a statistically significant improvement in safety culture (P = .036) on the wards. Teamwork climate improved, but the evidence was not as strong (P = .052). Perceptions of hospital management and adequacy of staffing levels showed significant deterioration. Simple, low-resource interventions can have a significant positive impact on safety culture and possibly teamwork climate on surgical wards. This could be of great value in maintaining patient safety at times of financial constraint.


Effect of treadmill exercise on transmural distribution of blood flow in hypertrophied left ventricle.
Pressure-overload left ventricular (LV) hypertrophy (LVH) is associated with increased vulnerability to subendocardial hypoperfusion during exercise. Abnormal perfusion could be the result of failure of the coronary vessels to grow in proportion to the degree of myocyte hypertrophy or could be due to increased extravascular forces acting on the intramural coronary vasculature. This study assessed the contribution of extravascular forces by examining the effect of exercise on the distribution of myocardial blood flow when coronary vasomotor tone was abolished with a maximal vasodilating dose of intracoronary adenosine. One year after ascending aortic banding in six dogs, the LV-to-body weight ratio was 7.80 +/- 0.38 g/kg compared with 4.57 +/- 0.20 g/kg in nine normal dogs (P < 0.01). Under awake resting conditions blood flow in LVH hearts increased from 1.17 +/- 0.27 ml . min-1 . g-1 during basal conditions to 5.78 +/- 1.06 ml . min-1 . g-1 during adenosine (at a coronary pressure of 100 +/- 6 mmHg), whereas in normal dogs blood flow increased from 1.22 +/- 0.17 to 5.26 +/- 0.71 ml . min-1 . g-1 (at a coronary pressure of 62 +/- 4 mmHg). At rest the transmural distribution of blood flow during adenosine was not different between hypertrophied and normal hearts, with subendocardial-to-subepicardial (Endo-to-Epi) blood flow ratios of 1. 01 +/- 0.09 and 1.14 +/- 0.13, respectively (P = not significant). During adenosine infusion, treadmill exercise to produce heart rates of 200-220 beats/min caused redistribution of blood flow away from the subendocardium that was much more marked in LVH (Endo-to-Epi blood flow ratio = 0.35 +/- 0.04) than in normal hearts (Endo-to-Epi blood flow ratio = 0.76 +/- 0.09, P < 0.05 vs. LVH). In comparison with normal, the exaggerated decrease in subendocardial blood flow produced by exercise in LVH hearts resulted from abnormally increased extravascular compressive forces, including a greater decrease in diastolic duration and an increase in LV end-diastolic pressure.


[The abbreviated mental test in a German version for detection of postoperative delirium].
Delirium is the most common acute organic psychosis postoperatively, and occurs more frequently in the elderly than anticipated. The abbreviated mental test (AMT) is a widely used cognitive test in Great Britain. The present study assessed the AMT in a German version for diagnosis of postoperative delirium. 40 patients (older than 65 years), scheduled for total knee or hip replacement, were tested repeatedly for delirium according to the ICD-10. These patients were investigated with the AMT simultaneously by a second investigator. Delirium was present in four orthopaedic patients (10 %) and was diagnosed correctly in these patients by the AMT. All but one patient without delirium showed no deterioriation in AMT score. As in Great Britain, the AMT in its German version is useful in diagnosing delirium. We recommend the use of the AMT preoperatively in elderly patients at risk for delirium.


Healthy decisions in the cued-attribute food choice paradigm have high test-retest reliability.
Food choice paradigms are commonly used to study decision mechanisms, individual differences, and intervention efficacy. Here, we measured behavior from twenty-three healthy young adults who completed five repetitions of a cued-attribute food choice paradigm over two weeks. This task includes cues prompting participants to explicitly consider the healthiness of the food items before making a selection, or to choose naturally based on whatever freely comes to mind. We found that the average patterns of food choices following both cue types and ratings about the palatability (i.e. taste) and healthiness of the food items were similar across all five repetitions. At the individual level, the test-retest reliability for choices in both conditions and healthiness ratings was excellent. However, test-retest reliability for taste ratings was only fair, suggesting that estimates about palatability may vary more from day to day for the same individual.


Oncolytic viruses: do they have a role in anti-cancer therapy?
Oncolytic viruses are replication competent, tumor selective and lyse cancer cells. Their potential for anti-cancer therapy is based upon the concept that selective intratumoral replication will produce a potent anti-tumor effect and possibly bystander or remote cell killing, whilst minimizing normal tissue toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic activity, and possess a host of different mechanisms to provide tumor selectivity. Clinical use of live replicating viruses is associated with a unique set of safety issues. Clinical experience has so far provided evidence of limited efficacy and a favourable toxicity profile. The interaction with the host immune system is complex. An anti-viral immune response may limit efficacy by rapidly clearing the virus. However, virally-induced cell lysis releases tumor associated antigens in a 'dangerous' context, and limited evidence suggests that this can lead to the generation of a specific anti-tumor immune response. Combination therapy with chemotherapy or radiotherapy represents a promising avenue for ongoing translation of oncolytic viruses into clinical practice. Obstacles to therapy include highly effective non-specific host mechanisms to clear virus following systemic delivery, immune-mediated clearance, and intratumoral barriers limiting virus spread. A number of novel strategies are now under investigation to overcome these barriers. This review provides an overview of the potential role of oncolytic viruses, highlighting recent progress towards developing effective therapy and asks if they are a realistic therapeutic option at this stage.


Occurrence of bullous pemphigoid after furosemide therapy.
A 78-year-old woman with Parkinson disease developed tense bullous lesions on the chest, arms, and in the groin that were diagnosed as bullous pemphigoid. Histologic examination, as well as immunofluorescence tests, confirmed this diagnosis. The possibility of a drug-induced disease was considered because she was taking seven different medications. Furosemide (Lasix) was suspected primarily. Complete clearing occurred with prednisone therapy, but readministration of furosemide resulted in bulla formation.


Herpesvirus saimiri open reading frame 14, a protein encoded by T lymphotropic herpesvirus, binds to MHC class II molecules and stimulates T cell proliferation.
Herpesvirus saimiri (HVS) is an oncogenic, lymphotropic, gamma-herpesvirus that transforms human and simian T cells in vitro and causes lymphomas and leukemias in various species of New World primates. Nucleotide sequence analysis of the HVS genome revealed an open reading frame with 22% amino acid identity to the mouse mammary tumor virus 7 superantigen. In this study, we demonstrate that this open reading frame, HVS14, encodes a heavily glycosylated protein that is secreted. Both the HVS14 present in the supernatant of transfected cells and a chimeric HVS14.Fc fusion protein were found to bind to heterodimeric MHC class II HLA-DR molecules. The supernatant from HVS14-transfected cells induced the proliferation of human PBMC, which could be specifically inhibited by HVS14-specific mAbs. Purified peripheral blood T cells were induced to proliferate in the presence of accessory cells and HVS14-containing supernatant. Whereas the HVS14 protein stimulated T cell proliferation, the HVS14.Fc fusion protein blocked proliferative responses to soluble Ags in vitro. Collectively, these data indicate that HVS14 can function as an immunomodulator that may contribute to the immunopathology of HVS infection.


No Loss of Strength After Insertional Achilles Tendon Reconstruction With Single-Anchor or Double-Row Repair.
Many different types of surgical repair for insertional Achilles tendinosis have been described. Strength after surgery is an essential factor for patient function and satisfaction. A retrospective series of patients that underwent surgery for insertional Achilles tendon surgery were contacted to come in for prospective strength testing, with the tester blinded to the type of surgery performed. Thirty-seven patients came in for testing, 24 with a single-anchor repair and 13 with a double-row repair. Strength of plantarflexion was tested at 60°/s and 120°/s and was compared. First each operative leg was compared to the nonoperative leg as a control. Then the percentage change, or symmetry, from the control leg to the operative leg was compared between those with a single-anchor and double-row repair. Satisfaction was also assessed with a simple questionnaire and compared the types of repair. The results demonstrated there was no statistically significant change in strength after surgery compared to the nonoperative leg, and there was no difference in limb symmetry between types of repair. Similarly, there was no difference between the groups in satisfaction. Our study showed that there is, on average, no loss of strength after insertional Achilles tendon surgery at an average follow-up of nearly 2 years, regardless of type of repair.


Dietary protein does not alter intrinsic reactivity of renal microcirculation to angiotensin II in rodents.
The effect of dietary protein on renal function and on renal microvascular reactivity to angiotensin II was determined in rats fed a high-protein diet (40% protein), a low-protein diet (6% protein), or a normal diet (23% protein). Inulin clearance was higher in high-protein-fed rats (n = 7) than in rats fed a low-protein diet (n = 7), 0.88 +/- 0.14 (means +/- SE) vs. 0.54 +/- 0.07 ml.min-1.g kidney wt-1 (P < 0.05). We also used videomicroscopy to assess the effect of angiotensin II on the renal microcirculation in a hydronephrotic kidney preparation. The afferent and efferent arterioles constricted to angiotensin II and norepinephrine in both high- and low-protein-fed rats; this constriction was diminished to angiotensin II but not to norepinephrine, in rats fed a high-protein diet (-24.3 +/- 4.5, -20.2 +/- 4.2%) compared with rats fed a low-protein diet (-39 +/- 5.1, -39.1 +/- 5.7%). The vasoconstrictor responses to angiotensin II in rats fed a high-protein diet and a normal diet were significantly greater following inhibition of angiotensin II formation with captopril but not in low-protein-fed rats. The apparent high-endogenous level of angiotensin II among rats fed a high-protein diet may account for the diminished reactivity to exogenous angiotensin II. Thus alterations in intrinsic vascular reactivity to angiotensin II are not responsible for the altered hemodynamics associated with dietary protein.


Extreme repeated mating as a counter-adaptation to sexual conflict?
The Australian scaly cricket, Ornebius aperta, can copulate over 50 times with the same partner; the benefits of such extreme repeated copulation are unclear. We support the hypothesis that repeated copulation increases insemination success, as the number of sperm transferred increases with each spermatophore. This probably increases paternity for males, as on average a female mates with over 40 males. Despite intense sperm competition each ejaculate has only a few hundred sperm, orders of magnitude less than in related crickets. We show that all sperm are transferred from each spermatophore in the few seconds before a female removes and eats it. Repeated copulation increases effective copulation duration while a small ejaculate ensures that this strategy is not excessively costly. Thus repeated copulation in these crickets may have arisen as a counter-adaptation to female-imposed limits on copulation.


An international qualitative study of functioning in autism spectrum disorder using the World Health Organization international classification of functioning, disability and health framework.
This is the third in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Autism Spectrum Disorder (ASD). The present study aimed to describe functioning in ASD (as operationalized by the ICF) derived from the perspectives of diagnosed individuals, family members, and professionals. A qualitative study using focus groups and semi-structured interviews were conducted with 19 stakeholder groups (N = 90) from Canada, India, Saudi Arabia, South Africa, and Sweden. Meaningful concepts from the focus groups and individual interviews were linked to ICF categories using a deductive qualitative approach with standardized linking procedures. The deductive qualitative content analysis yielded meaningful functioning concepts that were linked to 110 ICF categories across all four ICF components. Broad variation of environmental factors and activities and participation categories were identified in this study, while body functions consisted mainly of mental functions. Body structures were sparsely mentioned by the participants. Positive aspects of ASD included honesty, attention to detail, and memory. The experiences provided by international stakeholders support the need to understand individuals with ASD in a broader perspective, extending beyond diagnostic criteria into many areas of functioning and environmental domains. This study is part of a larger systematic effort that will provide the basis to define ICF Core Sets for ASD, from which assessment tools can be generated for use in clinical practice, research, and health care policy making. Autism Res 2018, 11: 463-475. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. The study findings support the need to understand the living experiences of individuals with Autism Spectrum Disorder (ASD) from a broader perspective, taking into account many areas of an individual's functioning and environment. The ICF can serve as foundation for exploring these living experiences more extensively by offering tools that enable wide variety of individual difficulties and strengths to be captured along with important environmental influences. As such, these tools can facilitate interventions that meet the needs and goals of the individual.


Drug-induced hypomethylation of a posttranscriptionally silenced transgene locus of tobacco leads to partial release of silencing.
The effect of DNA methylation upon posttranscriptional gene silencing (PTGS) has been investigated in transgenic tobacco lines showing PTGS and methylation of the neomycin phosphotransferase II (nptII) reporter genes. Application of the hypomethylation drugs dihydroxypropyladenine or 5-azacytidine resulted in approximately 30% reduced methylation of cytosines located in a non-symmetrical context in the 3' untranslated region of the nptII transgenes. The hypomethylation was accompanied by up to 12-fold increase in NPTII protein levels, suggesting that methylation of non-symmetrical motifs may account for an increased degree of PTGS. Models for the possible role of DNA methylation in PTGS are discussed.


Caulobacter crescentus Adapts to Phosphate Starvation by Synthesizing Anionic Glycoglycerolipids and a Novel Glycosphingolipid.
Caulobacter crescentus adapts to phosphate starvation by elongating its cell body and a polar stalk structure. The stalk is an extension of the Gram-negative envelope containing inner and outer membranes as well as a peptidoglycan cell wall. Cellular elongation requires a 6- to 7-fold increase in membrane synthesis, yet phosphate limitation would preclude the incorporation of additional phospholipids. In the place of phospholipids, C. crescentus can synthesize several glycolipid species, including a novel glycosphingolipid (GSL-2). While glycosphingolipids are ubiquitous in eukaryotes, the presence of GSL-2 in C. crescentus is surprising since GSLs had previously been found only in Sphingomonas species, in which they play a role in outer membrane integrity. In this paper, we identify three proteins required for GSL-2 synthesis: CcbF catalyzes the first step in ceramide synthesis, while Sgt1 and Sgt2 sequentially glycosylate ceramides to produce GSL-2. Unlike in Sphingomonas, GSLs are nonessential in C. crescentus; however, the presence of ceramides does contribute to phage resistance and susceptibility to the cationic antimicrobial peptide polymyxin B. The identification of a novel lipid species specifically produced upon phosphate starvation suggests that bacteria may be able to synthesize a wider variety of lipids in response to stresses than previously observed. Uncovering these lipids and their functional relevance will provide greater insight into microbial physiology and environmental adaptation.IMPORTANCE Bacteria adapt to environmental changes in a variety of ways, including altering their cell shape. Caulobacter crescentus adapts to phosphate starvation by elongating its cell body and a polar stalk structure containing both inner and outer membranes. While we generally think of cellular membranes being composed largely of phospholipids, cellular elongation occurs when environmental phosphate, and therefore phospholipid synthesis, is limited. In order to adapt to these environmental constraints, C. crescentus synthesizes several glycolipid species, including a novel glycosphingolipid. This finding is significant because glycosphingolipids, while ubiquitous in eukaryotes, are extremely rare in bacteria. In this paper, we identify three proteins required for GSL-2 synthesis and demonstrate that they contribute to phage resistance. These findings suggest that bacteria may synthesize a wider variety of lipids in response to stresses than previously observed.


Racial and ethnic disparities in common inpatient safety outcomes in a children's hospital cohort.
Emerging evidence has shown racial and ethnic disparities in rates of harm for hospitalised children. Previous work has also demonstrated how highly heterogeneous approaches to collection of race and ethnicity data pose challenges to population-level analyses. This work aims to both create an approach to aggregating safety data from multiple hospitals by race and ethnicity and apply the approach to the examination of potential disparities in high-frequency harm conditions. In this cross-sectional, multicentre study, a cohort of hospitals from the Solutions for Patient Safety network with varying race and ethnicity data collection systems submitted validated central line-associated bloodstream infection (CLABSI) and unplanned extubation (UE) data stratified by patient race and ethnicity categories. Data were submitted using a crosswalk created by the study team that reconciled varying approaches to race and ethnicity data collection by participating hospitals. Harm rates for race and ethnicity categories were compared with reference values reflective of the cohort and broader children's hospital population. Racial and ethnic disparities were identified in both harm types. Multiracial Hispanic, Combined Hispanic and Native Hawaiian or other Pacific Islander patients had CLABSI rates of 2.6-3.6 SD above reference values. For Black or African American patients, UE rates were 3.2-4.4 SD higher. Rates of both events in White patients were significantly lower than reference values. The combination of harm data across hospitals with varying race and ethnicity collection systems was accomplished through iterative development of a race and ethnicity category framework. We identified racial and ethnic disparities in CLABSI and UE that can be addressed in future improvement work by identifying and modifying care delivery factors that contribute to safety disparities.


Combined Surgical, Radiation, and Medical Therapies for Osteochondrodysplasia in a Scottish Fold Cat.
Osteochondrodysplasia affects both homozygous and heterozygous Scottish Fold cats, and various treatments have been attempted to control chronic pain and improve mobility in these animals. However, to date, there is no single effective treatment that can be used to treat all cats with Scottish Fold osteochondrodysplasia (SFOCD). A 4 yr old castrated Scottish Fold cat presented with plantar exostoses in the right hindlimb, the largest of which was caudal to the tarsometatarsal joint and had stretched the overlying skin, causing ulceration and bleeding. There was right hindlimb lameness. The cat was diagnosed with SFOCD, and the skin lesions were treated by excision of the exostoses, removal of the damaged skin, and wound closure. All extremities were treated with radiotherapy and subcutaneous pentosan polysulfate for chronic pain. The cat's gait improved after surgery, and increased activity was noted after radiotherapy. There were no signs of excessive bone proliferation or adverse effects at 80 wk postoperatively. In conclusion, a combination of surgical, radiation, and medical therapies could be an effective treatment strategy for SFOCD with skin ulceration.


Preterm birth, intrauterine infection, and fetal inflammation.
Preterm birth (PTB) (delivery before 37 weeks' gestation) is a leading cause of neonatal death and disease in industrialized and developing countries alike. Infection (most notably in high-risk deliveries occurring before 28 weeks' gestation) is hypothesized to initiate an intrauterine inflammatory response that plays a key role in the premature initiation of labor as well as a host of the pathologies associated with prematurity. As such, a better understanding of intrauterine inflammation in pregnancy is critical to our understanding of preterm labor and fetal injury, as well as on-going efforts to prevent PTB. Focusing on the fetal innate immune system responses to intrauterine infection, the present paper will review clinical and experimental studies to discuss the capacity for a fetal contribution to the intrauterine inflammation associated with PTB. Evidence from experimental studies to suggest that the fetus has the capacity to elicit a pro-inflammatory response to intrauterine infection is highlighted, with reference to the contribution of the lung, skin, and gastrointestinal tract. The paper will conclude that pathological intrauterine inflammation is a complex process that is modified by multiple factors including time, type of agonist, host genetics, and tissue.


Immunotherapy for Infarcts: In Vivo Postinfarction Macrophage Modulation Using Intramyocardial Microparticle Delivery of Map4k4 Small Interfering RNA.
The myeloid cells infiltrating the heart early after acute myocardial infarction elaborate a secretome that largely orchestrates subsequent ventricular wall repair. Regulating this innate immune response could be a means to improve infarct healing. To pilot this concept, we utilized (β1,3-d-) glucan-encapsulated small interfering RNA (siRNA)-containing particles (GeRPs), targeting mononuclear phagocytes, delivered to mice as a one-time intramyocardial injection immediately after acute infarction. Findings demonstrated that cardiac macrophages phagocytosed GeRPs in vivo and had little systemic dissemination, thus providing a means to deliver local therapeutics. Acute infarcts were then injected in vivo with phosphate-buffered saline (PBS; vehicle) or GeRPs loaded with siRNA to Map4k4, and excised hearts were examined at 3 and 7 days by quantitative polymerase chain reaction, flow cytometry, and histology. Compared with infarcted PBS-treated hearts, hearts with intrainfarct injections of siRNA-loaded GeRPs exhibited 69-89% reductions in transcripts for Map4k4 (mitogen-activated protein kinase kinase kinase kinase 4), interleukin (IL)-1β, and tumor necrosis factor α at 3 days. Expression of other factors relevant to matrix remodeling-monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases, hyaluronan synthases, matricellular proteins, and profibrotic factors transforming growth factor beta (TGF-β), and connective tissue growth factor (CTGF)-were also decreased. Most effects peaked at 3 days, but, in some instances (Map4k4, IL-1β, TGF-β, CTGF, versican, and periostin), suppression persisted to 7 days. Thus, direct intramyocardial GeRP injection could serve as a novel and clinically translatable platform for in vivo RNA delivery to intracardiac macrophages for local and selective immunomodulation of the infarct microenvironment.


The Correlated Appearance of Prolamellar Bodies, Protochlorophyll(ide) Species, and the Shibata Shift during Development of Bean Etioplasts in the Dark.
The structure and physiology of the etioplast was investigated in developing primary leaves of 3- to 9-day-old dark-grown bean (Phaseolus vulgaris L. var. Red Kidney) seedlings. Increase in total protochlorophyll(ide) content followed that of leaf fresh weight. In 3- to 4-day-old bean leaves more than 50% of the protochlorophyll(ide) is in the form of protochlorophyll(ide) 628, which is nontransformable by light. Most of the transformable pigment is protochlorophyll(ide) 635, with smaller amounts of protochlorophyll(ide) 650. During leaf development from the 3rd to the 7th day phototransformable protochlorophyll(ide) with an absorbance maximum at 650 nm accumulates faster than nontransformable protochlorophyll(ide) or protochlorophyll(ide) 635. This increase in protochlorophyll(ide) 650 is correlated with the formation and enlargement of prolamellar bodies.The transformable protochlorophyll(ide) is converted by light directly to chlorophyll(ide) 672 in young leaves which do not yet have prolamellar bodies, and chlorophyll(ide) 672 may arise largely from the protochlorophyll(ide) 635. In older leaves the protochlorophyll(ide), largely protochlorophyll(ide) 650, is converted to chlorophyll(ide) 683, and a Shibata shift results in a change in the wavelength of absorption to 672 nm. The increase in protochlorophyll(ide) 650, the formation of prolamellar bodies, and the presence of the Shibata shift appear to be closely correlated. A model is briefly presented to provide a unified interpretation of these findings, including certain similarities between dark-grown Euglena cells and 3- to 4-day-old etiolated bean leaves.


Targeting CAND1 promotes caspase-8/RIP1-dependent apoptosis in liver cancer cells.
Cullin-associated NEDD8-dissociated 1 (CAND1) plays a vital role in regulating the activity of Cullin-RING ubiquitin ligases (CRLs), which are frequently dysregulated in cancer. However, the role of CAND1 in hepatocellular carcinoma (HCC) remains unknown. Here, we found that CAND1 was overexpressed in HCC tissues compared to corresponding adjacent liver tissues (71.7% vs 16.7%); high expression of CAND1 was associated with poor overall survival (40.7 vs 57.3 months, P=0.0013); and CAND1 was an independent risk factor for the prognosis of HCC patients (N=138, P=0.018). Functional studies revealed that CAND1 knockdown efficiently suppressed the proliferation of liver cancer cells by activating caspase-8-dependent mitochondrial apoptosis. We also observed a mutual activation loop between caspase-8 and Receptor Interacting Protein 1 (RIP1), which amplified CAND1 knockdown-induced apoptotic signals in the cells. Furthermore, RIP1 inhibitor Necrostatin-1 eliminated the activation of caspase-8. In conclusion, our study pioneered in reporting high CAND1 expression as a predictor of poor prognosis for HCC patients. CAND1 silencing suppressed HCC cell proliferation by inducing caspase-8/RIP1-dependent apoptosis. These findings supported that CAND1 could be a new therapeutic target for liver cancer.


Phosphoserine phosphatase is expressed in the neural stem cell niche and regulates neural stem and progenitor cell proliferation.
Phosphoserine phosphatase (PSP) metabolizes the conversion of l-phosphoserine to l-serine, classically known as an amino acid necessary for protein and nucleotide synthesis and more recently suggested to be involved in cell-to-cell signaling. Previously, we identified PSP as being enriched in proliferating neural progenitors and highly expressed by embryonic and hematopoietic stem cells, suggesting a general role in stem cells. Here we demonstrate that PSP is highly expressed in periventricular neural progenitors in the embryonic brain. In the adult brain, PSP expression was observed in slowly dividing or quiescent glial fibrillary acidic protein (GFAP)-positive cells and CD24-positive ependymal cells in the forebrain germinal zone adjacent to the lateral ventricle and within GFAP-positive cells of the hippocampal subgranular zone, consistent with expression in adult neural stem cells. In vitro, PSP overexpression promoted proliferation, whereas small interfering RNA-induced knockdown inhibited proliferation of neural stem cells derived from embryonic cortex and adult striatal subventricular zone. The effects of PSP knockdown were partially rescued by exogenous l-serine. These data support a role for PSP in neural stem cell proliferation and suggest that in the adult periventricular germinal zones, PSP may regulate signaling between neural stem cells and other cells within the stem cell niche. Disclosure of potential conflicts of interest is found at the end of this article.


[THE ORGANIZATION OF CONTROLLING QUALITY OF ORTHODONTIC CARE OF POPULATION].
The article presents originally developed model of quality of orthodontic care of population on the level of subject of the Russian Federation. The model includes the following elements: demand of population in orthodontic care, mission of orthodontic service, regulations of orthodontic service, table of facilities, staff list, standards of evaluation of effectiveness and audit of effectiveness of orthodontic care of population, and standards of quality control. The developed standards of quality control exemplified by typical stomatological polyclinic, demonstrated reserves of further development of quality and accessibility of orthodontic service to population in functioning of medical organization.


The validation of a quality of life scale to assess the impact of arm morbidity in breast cancer patients post-operatively.
This paper documents the validation of a quality of life scale (QOL) designed to assess the impact of arm morbidity on patients following breast cancer surgery. A four item arm subscale was developed to supplement a multi-dimensional, validated breast cancer QOL tool, the functional assessment of cancer therapy (FACT-B.) The new questionnaire, the FACT-B + 4, was validated on 279 women participating in a trial of sentinel node guided axillary therapy and 29 women attending a lymphoedema clinic. The subscale demonstrated good internal consistency (alpha co-efficient = 0.62 to 0.88) and stability (test-retest reliability = 0.97). Lymphoedema patients reported significantly greater arm problems than a matched sample of pre-operative trial participants. The lymphoedema group also scored lower than trial patients on the FACT-B + 4 indicating a poorer quality of life (p < 0.05). A subset of 66 trial patients who had completed three consecutive assessments was used to evaluate the sensitivity of the questionnaire to change over time. Scores on the FACT-B + 4 were found to decline significantly between the pre-operative assessment and post-operative assessment at 1 month. Arm problems significantly increased during this period. FACT-B + 4 score increased again from 1 month to 12 weeks post-surgery and symptoms reduced, as the extent of arm morbidity resolved. The FACT-B + 4 appears to be psychometrically robust and sensitive to patient rehabilitation, making it suitable for use in longitudinal surgical trials. Given the dearth of existing scales available to measure arm morbidity, we hope this new tool will prove useful to researchers.


Prevalence and Relationships among Physical Activity Policy, Environment, and Practices in Licensed Childcare Centers from a Manager and Staff Perspective.
Physical activity (PA) is critical to early childhood health and development, and childcare is a key setting for establishing physically active play. In British Columbia (BC), a provincial standard for active play in childcare was enacted, identified here as the Active Play (AP) standard. Pragmatic constraints limit real-world data collection for evaluating policy impact. We explored whether information about policies, practices, and the environment varied when it was collected from managers or staff. Surveys were distributed to BC childcare centers before AP standard enactment to ascertain current PA and fundamental movement skill policies and practices. The full sample (n = 1037 from 625 facilities) and a subsample of paired managers and staff (n = 261 centers) were used to explore agreement across managers and staff in reported prevalence and relationships among indicators. The policy prevalence and relationships for active play and outdoor play variables were relatively similar for manager and staff data, although the matched data had modest agreement and less than optimal intraclass correlations. The prevalence of manager-reported PA policies ranged from 47% for screen-time limits to 77% for fundamental movement skill activities. The manager and staff data highlighted indoor and outdoor space as a primary factor in AP standard adherence. With reliance on sampling staff unfeasible, it appears that the manager data may adequately describe the policies and practices of childcare providers with some notable issues.


Ultrasonic Electroporation for Cells Grown on Piezoelectric Film Composed of Hydroxyapatite Nanowire and PVDF.
The delivery of cell impermeable exogenous material into live cells by external stimuli is critical for both biological research and therapeutic applications. Although electroporation-based delivery of foreign materials inside the cell is a powerful approach, cell viability is often compromised due to the requirement of high voltage. Here, we report a piezoelectric hydroxyapatite nanowire-embedded poly(vinylidene fluoride) (PVDF) film for ultrasonic electroporation-based delivery of foreign materials to adherent cells. We found that 9 wt % loading of hydroxyapatite nanowires into PVDF can enhance the piezoelectric property by 2-3 times (with a piezoelectric constant value of 58 pm/V) than pure PVDF/nanowire, which is comparable to commonly known piezoelectric ceramics. These films can harvest mechanical as well as ultrasound-based energy to produce electrical potential up to 2 V. This biocompatible film can be used to grow cells on top of it and for subsequent application of ultrasound to exert electric voltage on cell membrane. We found that ultrasonic exposure to adhered cells leads to reversible pore formation on cell membrane that offers intracellular delivery of FITC-dextran with 75% efficiency. The developed piezoelectric film-based ultrasonic electroporation can be used for wireless electroporation in remote areas.


The anhydride route to Group 15/16 ligands in oligomeric and polymeric environments: from metal complexes to supraionic chemistry.
The aim of this paper is to introduce a synthetic concept suitable for the preparation of a broad variety of compounds. The so-called anhydride route (in this article the term anhydride is used for compounds derived from corresponding acids by formal loss of H2O, H2S and H2Se) has so far led to a range of unusual Group 15/16 ligands in oligomeric and polymeric environments. Commonly, reactions of neutral precursor molecules, for example, [{RP(S)(mu-S)}2] (R=4-anisyl) Lawesson's reagent or [{PhP(Se)(mu-Se)}2] Woollins's reagent and metal salts are performed to result in novel coordination compounds in which ligands and metal atoms form coordination oligomers and polymers. An attempt is made to relate the outcome of the investigations to the type of metal used. By relating the strength of ionic interactions, which correspond to metal-donor distances, to phenomena observed in the solid-state structures, an aspect of supraionic chemistry is described. Chemistry of and beyond novel Group 15/16 anions is further discussed using a novel approach in coordination chemistry where the chemical nature of ligands is unknown prior to the experiment despite the use of a range of similar starting materials.


Micro-morphological properties of osteons reveal changes in cortical bone stability during aging, osteoporosis, and bisphosphonate treatment in women.
We analyzed morphological characteristics of osteons along with the geometrical indices of individual osteonal mechanical stability in young, healthy aged, untreated osteoporotic, and bisphosphonate-treated osteoporotic women. Our study revealed significant intergroup differences in osteonal morphology and osteocyte lacunae indicating different remodeling patterns with implications for fracture susceptibility. Bone remodeling is the key process in bone structural reorganization, and its alterations lead to changes in bone mechanical strength. Since osteons reflect different bone remodeling patterns, we hypothesize that the femoral cortices of females under miscellaneous age, disease and treatment conditions will display distinct osteonal morphology and osteocyte lacunar numbers along with different mechanical properties. The specimens used in this study were collected at autopsy from 35 female donors (young group, n = 6, age 32 ± 8 years; aged group, n = 10, age 79 ± 9 years; osteoporosis group, n = 10, age 81 ± 9 years; and bisphosphonate group, n = 9, age 81 ± 7 years). Von Kossa-modified stained femoral proximal diaphyseal sections were evaluated for osteonal morphometric parameters and osteocyte lacunar data. Geometrical indices of osteonal cross-sections were calculated to assess the mechanical stability of individual osteons, in terms of their resistance to compression, bending, and buckling. The morphological assessment of osteons and quantification of their osteocyte lacunae revealed significant differences between the young, aged, osteoporosis and bisphosphonate-treated groups. Calculated osteonal geometric indices provided estimates of the individual osteons' resistance to compression, bending and buckling based on their size. In particular, the osteons in the bisphosphonate-treated group presented improved osteonal geometry along with increased numbers of osteocyte lacunae that had been formerly impaired due to aging and osteoporosis. The data derived from osteons (as the basic structural units of the cortical bone) in different skeletal conditions can be employed to highlight structural factors contributing to the fracture susceptibility of various groups of individuals.