Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer.
Ovarian cancer is the fifth leading cause of cancer death and the most deadly gynecological malignancy in women. Epigenetic modifications play an important role in regulating gene transcription. Specifically, aberrant promoter hypermethylation has been implicated as a hallmark of cancer. In order to identify genes that are differentially methylated in ovarian cancer, we performed meDIP-chip in various ovarian cancer cell lines using Agilent 244K CpG island microarray. One of the targets, ARNTL which is a core component of the circadian clock is methylated in a sub-set of ovarian cancer cell lines. Combined bisulfite restriction analysis (COBRA) confirmed the results of the microarray. Additional analysis using ChIP-PCR revealed that promoter of ARNTL is enriched with the repressive histone mark H3K27me3 in CP70 and MCP2 ovarian cancer cells. Treatment with the EZH2 inhibitor (GSK126) significantly restored ARNTL expression in these cells (CP70 and MCP2). Further functional analysis demonstrated that overexpression of ARNTL inhibited cell growth and enhanced chemosensitivity of cisplatin in ovarian cancer cells. Finally, overexpression of ARNTL restored the rhythmic activity of c-MYC in ovarian cancer cells. These results suggested that ARNTL may be a tumor suppressor and is epigenetically silenced in ovarian cancer.


Severe hypercalcaemia and respiratory insufficiency associated with infantile hypophosphatasia caused by two novel mutations of the tissue-nonspecific alkaline phosphatase gene.
We report the case of a male patient with infantile hypophosphatasia associated with severe hypercalcaemia and mild respiratory insufficiency. At the age of 2 months, severe hypercalcaemia, low levels of serum alkaline phosphatase activity, and elevated urinary excretion of calcium and phosphoethanolamine were noted. Radiological findings showed generalized osteopenia and disturbed and irregular ossification of the metaphyses. Their involvement had spontaneously improved at the age of 6 months. A genetic study revealed that the tissue-nonspecific alkaline phosphatase gene of the patient had two novel mutations, K207E and G409C, derived from the mother and father, respectively. A reconsitution experiment revealed that both mutant gene products had low but significant enzymatic activity. The detection of tissue-nonspecific alkaline phosphatase gene mutations and expression studies to determine the enzymatic activity of mutant gene products was useful for assessing the clinical course of this patient with hypophosphatasia.


Feasibility of FAIR imaging for evaluating tumor perfusion.
To evaluate the feasibility of flow-sensitive alternating inversion recovery (FAIR) for measuring blood flow in tumor models. In eight mice tumor models, FAIR and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed. The reliability for measuring blood flow on FAIR was evaluated using the coefficient of variation of blood flow on psoas muscle. Three regions of interest (ROIs) were drawn in the peripheral, intermediate, and central portions within each tumor. The location of ROI was the same on FAIR and DCE-MR images. The correlation between the blood flow on FAIR and perfusion-related parameters on DCE-MRI was evaluated using the Pearson correlation coefficient. The coefficient of variation for measuring blood flow was 9.8%. Blood flow on FAIR showed a strong correlation with Kep (r = 0.77), percent relative enhancement (r = 0.73), and percent enhancement ratio (r = 0.81). The mean values of blood flow (mL/100 g/min) (358 vs. 207), Kep (sec(-) (1)) (7.46 vs. 1.31), percent relative enhancement (179% vs. 134%), and percent enhancement ratio (42% vs. 26%) were greater in the peripheral portion than in the central portion (P < 0.01). As blood flow measurement on FAIR is reliable and closely related with that on DCE-MR, FAIR is feasible for measuring tumor blood flow.


Evidence that dicot-infecting mastreviruses are particularly prone to inter-species recombination and have likely been circulating in Australia for longer than in Africa and the Middle East.
Viruses of the genus Mastrevirus (family Geminiviridae) are transmitted by leafhoppers and infect either mono- or dicotyledonous plants. Here we have determined the full length sequences of 49 dicot-infecting mastrevirus isolates sampled in Australia, Eritrea, India, Iran, Pakistan, Syria, Turkey and Yemen. Comprehensive analysis of all available dicot-infecting mastrevirus sequences showed the diversity of these viruses in Australia to be greater than in the rest of their known range, consistent with earlier studies, and that, in contrast with the situation in monocot-infecting mastreviruses, detected inter-species recombination events outnumbered intra-species recombination events. Consistent with Australia having the greatest diversity of known dicot-infecting mastreviruses phylogeographic analyses indicating the most plausible scheme for the spread of these viruses to their present locations, suggest that most recent common ancestor of these viruses is likely nearer Australia than it is to the other regions investigated.


Patterns of performance and improvement in US Medicare's Hospital Star Ratings, 2016-2017.
Publicly reported quality data can help consumers make informed choices about where to seek medical care. The Centers for Medicare and Medicaid Services developed a composite Hospital Compare Overall Star Rating for US acute-care hospitals in 2016. However, patterns of performance and improvement have not been previously described. To characterise high-quality and low-quality hospitals as assessed by Star Ratings. We performed a retrospective cross-sectional study of 3429 US acute-care hospitals assigned Overall Star Ratings in both 2016 and 2017. We used multivariable logistic regression models to identify characteristics associated with receiving 4 or 5 stars. Small hospitals were more likely to receive 4 or 5 stars in 2016 (33% of small hospitals, 26% of medium hospitals and 21% of large hospitals, OR for medium 0.78, p=0.02, and for large, 0.61, p=0.003). Non-profit status (OR 1.37, p=0.01), midwest region (OR=2.30, p<0.001), west region (OR 1.30 in 2016, p=0.06) and system membership (OR 1.33, p=0.003) were associated with higher odds of achieving a higher Star Rating. Hospitals with the most Medicaid patients were markedly less likely to receive 4 or 5 stars (OR for highest quartile=0.32, p<0.001), and hospitals with the highest proportion of Medicare patients were somewhat less likely to do so (OR for highest quartile=0.68, p=0.01). These associations remained largely consistent over the first two years of reporting and were also associated with the highest likelihood of improvement. Small hospitals with fewer Medicaid patients had the highest odds of performing well on Star Ratings. Further monitoring of these trends is needed as patients, clinicians and policymakers strive to use this information to promote high-quality care.


Synthesis of truncated analogues of preptin-(1–16), and investigation of their ability to stimulate osteoblast proliferation.
Preptin, a 34-amino acid residue peptide hormone is co-secreted with insulin from the β-pancreatic cells and is active in fuel metabolism. We have previously established that a shorter fragment of preptin, namely preptin-(1–16), stimulates bone growth by proliferation and increasing the survival rate of osteoblasts. This was demonstrated in both in vitro and in vivo models. These findings suggest that preptin-(1–16) could play an important role in the anabolic therapy of osteoporosis. However, due to the large size of the peptide it is not an ideal therapeutic agent. The aim of this study was to identify the shortest preptin analogue that retains or even increases the bone anabolic activity as compared to the parent preptin-(1–16) peptide. Truncations were made in a methodical manner from both the N-terminus and the C-terminus of the peptide, and the effect of these deletions on the resulting biological activity was assessed. In order to improve the enzymatic stability of the shortest yet active analogue identified, ruthenium-catalysed ring closing metathesis was used to generate a macrocyclic peptide using allylglycine residues as handles for ring formation. We have successfully identified a short 8-amino acid preptin (1–8) fragment that retains an anabolic effect on the proliferation of primary rat osteoblasts and enhances bone nodule formation. Preptin (1–8) is a useful lead compound for the development of orally active therapeutics for the treatment of osteoporosis.


Long-term effectiveness of irreversible electroporation in a murine model of colorectal liver metastasis.
Irreversible electroporation (IRE) has recently gained in popularity as an ablative technique, however little is known about its oncological long-term outcomes. To determine the long-time survival of animals treated with a high dose of IRE and which histological changes it induces in tumoral tissue, IRE ablation was performed in forty-six athymic-nude mice with KM12C tumors implanted in the liver by applying electric current with different voltages (2000 V/cm, 1000 V/cm). The tumors were allowed to continue to grow until the animals reached the end-point criteria. Histology was harvested and the extent of tumor necrosis was semi-quantitatively assessed. IRE treatment with the 2000 V/cm protocol significantly prolonged median mouse survival from 74.3 ± 6.9 days in the sham group to 112.5 ± 15.2 days in the 2000 V/cm group. No differences were observed between the mean survival of the 1000 V/cm and the sham group (83.2 ± 16.4 days, p = 0.62). Histology revealed 63.05% ± 23.12 of tumor necrosis in animals of the 2000 V/cm group as compared to 17.50% ± 2.50 in the 1000 V/cm group and 25.6% ± 22.1 in the Sham group (p = 0.001). IRE prolonged the survival of animals treated with the highest electric field (2000 V/cm). The animals in this group showed significantly higher rate of tumoral necrosis.


[Surgical overview on kidney and pancreas transplantation].
The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed.


Can bisphosphonates play a role in the treatment of children with chronic kidney disease?
In patients with chronic kidney disease (CKD) renal osteodystrophy, in the form of either low- or high-turnover bone disease, is quite common. While renal transplantation is expected to reverse renal osteodystrophy, long-term treatment with glucocorticoids before and/or after transplantation may lead to osteoporosis instead. Osteoporosis is defined as a skeletal disease with low bone mineral density, microarchitectural deterioration, and concomitant fragility. In adults, bisphosphonates are widely used to treat osteoporosis and other diseases associated with excessive bone resorption. In pediatric CKD patients the efficacy and safety of these drugs have not yet been addressed adequately and thus no evidence-based recommendations regarding the optimal type of bisphosphonate, dosage, or duration of therapy are available. Furthermore, while in adults the determination of areal bone mineral density is sufficient to diagnose osteoporosis, this is not the case in children. Instead, in pediatric patients, careful morphological assessment of bone structure and formation is required. Indeed, data from studies with uremic rats indicated that bisphosphonates, via a deceleration of bone turnover, have the potential not only to aggravate pre-existing adynamic bone disease, but also to impair longitudinal growth. Thus, the widespread use of bisphosphonates in children with CKD should be discouraged until the risks and benefits have been carefully elucidated in clinical trials.


Loss of dendritic inhibition in the hippocampus after repeated early-life hyperthermic seizures in rats.
Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but not heated. At PND 65-75, paired-pulse inhibition in area CA1 was evaluated under urethane anesthesia, using CA3 and medial perforant path (MPP) stimulation to excite the proximal and distal apical-dendrites, respectively, and the evoked field potentials were analyzed by current source density. There was no difference in the CA1 response to single-pulse stimulation of CA3 or MPP. In control rats, a high-intensity CA3 stimulus inhibited a subsequent MPP-evoked CA1 distal dendritic excitatory sink, and the inhibition at 150-200 ms was blocked by a GABA(B) receptor antagonist. Seizure as compared to control rats showed a decrease in a CA3-evoked inhibition of the CA1 distal dendritic excitation, 30-400 ms after the CA3 stimulus. In addition, seizure as compared to control rats showed a reduced early (20-80 ms) inhibition of a CA1 mid-apical dendritic sink following paired-pulse CA3 stimulation. In conclusion, long-term alterations in dendritic inhibition in CA1 were found following early-life seizures.


Epithelial cell adhesion to extracellular matrix proteins induces tyrosine phosphorylation of the Epstein-Barr virus latent membrane protein 2: a role for C-terminal Src kinase.
The Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2) is expressed in latently EBV-infected B cells, where it forms patches in the plasma membrane and interferes with B-cell receptor signal transduction through dominant-negative effects on protein kinases. LMP2 transcripts are detected in nasopharyngeal carcinoma, an epithelial-cell malignancy. In this study the function of LMP2A in epithelial cells was investigated. LMP2A was found to coprecipitate with protein kinase activities and to become phosphorylated in in vitro kinase assays. Analysis of LMP2A deletion mutants demonstrated that tyrosines implicated in interacting with Src family kinase SH2 domains and the SH2 domain of Csk, as well as the LMP2A immunoreceptor tyrosine-based activation motif, are important for its phosphorylation in epithelial cells. LMP2A tyrosine phosphorylation was triggered by cell adhesion to extracellular-matrix (ECM) proteins. Src family kinases, whose involvement in cell-ECM signaling and LMP2A phosphorylation in B lymphocytes has been well established, were found not to be responsible for LMP2A phosphorylation in epithelial cells. Instead, coexpression of Csk, a negative Src regulator, and LMP2A led to an increase in LMP2A phosphorylation both in nonadherent cells and upon cell adhesion. Csk also phosphorylated LMP2A in vitro. These results suggest that LMP2A has a different role in epithelial cells, where it interacts with cell adhesion-initiated signaling pathways. Although tyrosine phosphorylation of LMP2A occurs in both cell types, different protein kinases seem to be used: Src family kinases in B lymphocytes and Csk in epithelial cells.


Ratio of Maximal Inspiratory to Expiratory Flow Aids in the Separation of COPD from Asthma.
Patients who have chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) share symptoms such as, dyspnoea, cough and wheeze. Differentiating these diseases in the ambulatory setting can be challenging especially in older adult smokers who are being treated with a variety of medications. The objective of this study was to test the value of adding a maximal inspiratory manoeuvre to basic spirometry to differentiate COPD and BA. One hundred forty-three COPD patients and 142 BA patients had measurements of maximal inspiratory and expiratory flow during routine spirometry. Parameters from these tests were used to assess diagnostic accuracy using receiver-operating characteristic (ROC) analyses followed by logistic regression. The association of two independent parameters were analyzed using linear regression analyses. Results show that forced expiratory volume in one second/forced vital capacity (FEV1/FVC%) <62.4 was the best independent predictor to diagnose COPD. The combination of FEV1/FVC% <62.4 and the ratio of peak inspiratory flow/maximal expiratory flow at 50% FVC (PIF/MEF50) >3.06 significantly predicted COPD. Post-test probability for prediction of COPD was 82.0% when patients had both parameters. When asthmatic patients with a smoking history were compared with COPD patients, FEV1/FVC% <63.4 and PIF/MEF50 >3.29 were both independent predictors of COPD. The post-test probability for COPD was 94.4% when patients had both parameters. The association between FEV1/FVC% and PIF/MEF50 was significantly different between COPD and BA. In conclusion, the addition of the maximal inspiratory effort to routine pulmonary function measurements provides a simple test to help differentiate COPD and BA.


New data on the world distribution of paraoxonase (PON1 Gln 192 --> Arg) gene frequencies.
The physiological role of human paraoxonase (PON), a serum enzyme that hydrolyzes organophosphate insecticides and nerve agents, is not clear. Of the three genes in the paraoxonase gene family, PON1 shows a polymorphism, Gln 192 --> Arg, governed by two common alleles named *Q and *R. These determine two different isoforms associated, respectively, with lower and higher activity towards paraoxon, a toxic metabolic product of the insecticide parathion. The *R allele has often been found associated with an increased risk of coronary heart disease. As human populations tend towards greater exposure to environmental changes, including changes in dietary habits and contact with insecticides or other toxic substances, health risks will change as well. In studying the prevention of these newly emerging risks, it could be important to know the distribution of the two alleles in the various world populations. In this paper we report on the genotype and allele frequencies of this polymorphism in different populations, most of which have never been examined for this polymorphism. Samples were taken from mainland Italy, Sardinia, Ethiopia, Benin, and Ecuador. The *R allele frequencies for the samples were: 0.313, 0.248, 0.408, 0.612, and 0.789, respectively. The data show a large variability in allele frequencies, and, in particular, that PON1 allele distribution depends on membership to different geographic populations.


TH-17 cells in rheumatoid arthritis.
The aim of this study was to quantify the number of T-helper (TH)-17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and to determine the level of interleukin (IL)-17 cytokine in RA, osteoarthritis (OA) and normal synovial tissue, as well as to examine SF macrophages for the presence of IL-23, IL-27 and interferon (IFN)-gamma. Peripheral blood (PB) mononuclear cells from normal and RA donors and mononuclear cells from RA SF were examined either without stimulation or after pretreatment with IL-23 followed by stimulation with phorbol myristate acetate (PMA) plus ionomycin (P/I). The abundance of TH-17 cells in RA SF was determined by flow cytometry. IL-17 levels were quantified in synovial tissue from RA, OA and normal individuals by ELISA and IL-23 was identified in SFs by ELISA. RA SF and control in vitro differentiated macrophages were either untreated or treated with the toll-like receptor (TLR) 2 ligand peptidoglycan, and then IL-23, IL-27 and IFN-gamma mRNA levels were quantified by real-time polymerase chain reaction (RT-PCR). Treatment with P/I alone or combined with IL-23 significantly increased the number of TH-17 cells in normal, RA PB and RA SF. With or without P/I plus IL-23, the percentage of TH-17 cells was higher in RA SF compared with normal and RA PB. IL-17 levels were comparable in OA and normal synovial tissues, and these values were significantly increased in RA synovial tissue. Although IL-17 was readily detected in RA SFs, IL-23 was rarely identified in RA SF. However, IL-23 mRNA was significantly increased in RA SF macrophages compared with control macrophages, with or without TLR2 ligation. IL-27 mRNA was also significantly higher in RA SF compared with control macrophages, but there was no difference in IL-27 levels between RA and control macrophages after TLR2 ligation. IFN-gamma mRNA was also detectable in RA SF macrophages but not control macrophages and the increase of IFN-gamma mRNA following TLR2 ligation was greater in RA SF macrophages compared with control macrophages. These observations support a role for TH-17 cells in RA. Our observations do not strongly support a role for IL-23 in the generation of TH-17 cells in the RA joint, however, they suggest strategies that enhance IL-27 or IFN-gamma might modulate the presence of TH-17 cells in RA.


Clinical and radiological outcomes of kinesiotaping in patients with chronic neck pain: A double-blinded, randomized, placebo-controlled study.
In this study, we aimed to evaluate the efficacy of kinesiotaping (KT) in patients with chronic non-specific neck pain (NSNP) in terms of pain, disability, cervical range of motion (ROM), and cervical lordosis. Between October 2013 and March 2014, a total of 50 patients (10 males, 40 females; mean age 35.1±9.9 years; range, 17 to 62 years) with chronic NSNP were randomized into the KT (n=25) or the sham KT intervention (n=25) groups. Both groups were additionally given a therapeutic exercise (TE) program. The Visual Analog Scale (VAS) and Neck Disability Index (NDI) scores and ROM measurements were recorded at baseline, at the end of treatment, and at one month. Lateral cervical digital radiographs were analyzed by the Cobb, posterior tangent and effective lordosis methods at baseline and at one month after the treatment. There was a statistically significant decrease in the VAS scores compared to baseline in the KT group. The NDI scores significantly decreased in both groups. The patients in the KT group experienced a significant increase in all planes of cervical ROM after the treatment. Cervical radiographs revealed a significant increase in the Cobb and posterior tangent angles only in the KT group. Our study results suggest that KT significantly improves VAS, NDI scores, ROM and cervical lordosis angles. The combination of TE and KT is useful in reducing pain and disability and improving ROM and cervical lordosis loss in patients with chronic NSNP.


Shift and deviate: Saccades reveal that shifts of covert attention evoked by trained spatial stimuli are obligatory.
The premotor theory of attention predicts that motor movements, including manual movements and eye movements, are preceded by an obligatory shift of attention to the location of the planned response. We investigated whether the shifts of attention evoked by trained spatial cues (e.g., Dodd & Wilson, 2009) are obligatory by using an extreme prediction of the premotor theory: If individuals are trained to associate a color cue with a manual movement to the left or right, the shift of attention evoked by the color cue should also influence eye movements in an unrelated task. Participants were trained to associate an irrelevant color cue with left/right space via a training session in which directional responses were made. Experiment 1 showed that, posttraining, vertical saccades deviated in the direction of the trained response, despite the fact that the color cue was irrelevant. Experiment 2 showed that latencies of horizontal saccades were shorter when an eye movement had to be made in the direction of the trained response. These results demonstrate that the shifts of attention evoked by trained stimuli are obligatory, in addition to providing support for the premotor theory and for a connection between the attentional, motor, and oculomotor systems.


Widespread complex flow in the interior of the antarctic ice sheet
It has been suggested that as much as 90% of the discharge from the Antarctic Ice Sheet is drained through a small number of fast-moving ice streams and outlet glaciers fed by relatively stable and inactive catchment areas. Here, evidence obtained from balance velocity estimates suggests that each major drainage basin is fed by complex systems of tributaries that penetrate up to 1000 kilometers from the grounding line into the interior of the ice sheet. This finding has important consequences for the modeled or estimated dynamic response time of past and present ice sheets to climate forcing.


Development of visual motion processing: phase and peak latencies of direction-specific visual evoked potential.
The direction-reversal visual evoked potential (DR-VEP) latency is a key measure of the development of motion processing in infancy. However, the latency of this response has not been previously investigated. For other stimuli, both the latency of an initial peak and a latency measure calculated from steady-state phase as a function of frequency have been shown to be important and distinctive indicators of development. The latter measure is hypothesized to reflect the time course of cortical processing beyond the initial response that generates the first positive peak. DR-VEP was tested in 61 adults at 1-16 reversals per second (r/s) and 76 infants (age 7.7-79.0 weeks) at 2-8 r/s. In addition to measuring the transient peak latency at 1-3 r/s, latencies from the gradient of phase against reversal rates were also calculated from steady-state recordings at 1-16 r/s. For both adults and infants, peak latencies were similar for 1-3 r/s, while the calculated latency was substantially longer. Thirty-nine percent of adults and 17% of infants showed additional early transient peaks. We suggest that this early peak may reflect activation of extrastriate areas by motion, by a route that bypasses V1. While both transient latencies were similar to adult values around the onset of DR responses at 10 weeks of age, the latency calculated from phase values did not asymptote to the adult value of 207 ms until around 30 weeks. The overall time course of the response to direction reversal is prolonged compared with the transmission delay that generates the initial transient peak, presumably reflecting feed-forward, lateral, and recurrent connections that refine and elaborate the directional response of cortical neurons. While the peak latencies stay relatively unchanged throughout development, the dynamics of further motion processing are not mature until after 8 months of age. These measures may prove important indicators of motion development in future clinical evaluations.


Is the SenseWear Armband accurate enough to quantify and estimate energy expenditure in healthy adults?
The SenseWear Armband (SWA) is a monitor that can be used to estimate energy expenditure (EE); however, it has not been validated in healthy adults. The objective of this paper was to study the validity of the SWA for quantifying EE levels. Twenty-three healthy adults (age 40-55 years, mean: 48±3.42 years) performed different types of standardized physical activity (PA) for 10 minutes (rest, walking at 3 and 5 km·h-1, running at 7 and 9 km·h-1, and sitting/standing at a rate of 30 cycle·min-1). Participants wore the SWA on their right arm, and their EE was measured by indirect calorimetry (IC) the gold standard. There were significant differences between the SWA and IC, except in the group that ran at 9 km·h-1 (>9 METs). Bland-Altman analysis showed a BIAS of 1.56 METs (±1.83 METs) and limits of agreement (LOA) at 95% of -2.03 to 5.16 METs. There were indications of heteroscedasticity (R2 =0.03; P<0.05). Analysis of the receiver operating characteristic (ROC) curves showed that the SWA seems to be not sensitive enough to estimate the level of EE at highest intensities. The SWA is not as precise in estimating EE as IC, but it could be a useful tool to determine levels of EE at low intensities.


Discriminative ability of the generic and condition-specific Child-Oral Impacts on Daily Performances (Child-OIDP) by the Limpopo-Arusha School Health (LASH) project: a cross-sectional study.
Generic and condition-specific (CS) oral-health-related quality-of-life (OHRQoL) instruments assess the impacts of general oral conditions and specific oral diseases. Focusing schoolchildren from Arusha and Dar es Salaam, in Tanzania, this study compared the discriminative ability of the generic Child OIDP with respect to dental caries and periodontal problems across the study sites. Secondly, the discriminative ability of the generic-and the CS Child OIDP attributed to dental caries, periodontal problems and malocclusion was compared with respect to various oral conditions as part of a construct validation. In Arusha, 1077 school children (mean age 14.9 years, range 12-17 years) and 1601 school children in Dar es Salaam (mean age 13.0 years, range 12-14 years) underwent oral clinical examinations and completed the Kiswahili version of the generic and CS Child-OIDP inventories. The discriminative ability was assessed as differences in overall mean and prevalence scores between groups, corresponding effect sizes and odd ratios, OR. The differences in the prevalence scores and the overall mean generic Child-OIDP scores were significant between the groups with (DMFT > 0) and without (DMFT = 0) caries experience and with (simplified oral hygiene index [OHI-S] > 1) and without periodontal problems (OHI-S ≤ 1) in Arusha and Dar es Salaam. In Dar es Salaam, differences in the generic and CS Child-OIDP scores were observed between the groups with and without dental caries, differences in the generic Child-OIDP scores were observed between the groups with and without periodontal problems, and differences in the CS Child-OIDP scores were observed between malocclusion groups. The adjusted OR for the association between dental caries and the CS Child-OIDP score attributed to dental caries was 5.4. The adjusted OR for the association between malocclusion and CS Child-OIDP attributed to malocclusion varied from 8.8 to 2.5. The generic Child-OIDP discriminated equally well between children with and without dental caries and periodontal problems across socio-culturally different study sites. Compared with its generic form, the CS Child-OIDP discriminated most strongly between children with and without dental caries and malocclusion. The CS Child OIDP attributed to dental caries and malocclusion seems to be better suited to support clinical indicators when estimating oral health needs among school children in Tanzania.


Hepatitis C virus infection suppresses GLUT2 gene expression via downregulation of hepatocyte nuclear factor 1α.
Hepatitis C virus (HCV) infection causes not only intrahepatic diseases but also extrahepatic manifestations, including type 2 diabetes. We previously reported that HCV replication suppresses cellular glucose uptake by downregulation of cell surface expression of glucose transporter 2 (GLUT2) (D. Kasai et al., J. Hepatol. 50:883-894, 2009). GLUT2 mRNA levels were decreased in both HCV RNA replicon cells and HCV J6/JFH1-infected cells. To elucidate molecular mechanisms of HCV-induced suppression of GLUT2 gene expression, we analyzed transcriptional regulation of the GLUT2 promoter using a series of GLUT2 promoter-luciferase reporter plasmids. HCV-induced suppression of GLUT2 promoter activity was abrogated when the hepatocyte nuclear factor 1α (HNF-1α)-binding motif was deleted from the GLUT2 promoter. HNF-1α mRNA levels were significantly reduced in HCV J6/JFH1-infected cells. Furthermore, HCV infection remarkably decreased HNF-1α protein levels. We assessed the effects of proteasome inhibitor or lysosomal protease inhibitors on the HCV-induced reduction of HNF-1α protein levels. Treatment of HCV-infected cells with a lysosomal protease inhibitor, but not with a proteasome inhibitor, restored HNF-1α protein levels, suggesting that HCV infection promotes lysosomal degradation of HNF-1α protein. Overexpression of NS5A protein enhanced lysosomal degradation of HNF-1α protein and suppressed GLUT2 promoter activity. Immunoprecipitation analyses revealed that the region from amino acids 1 to 126 of the NS5A domain I physically interacts with HNF-1α protein. Taken together, our results suggest that HCV infection suppresses GLUT2 gene expression via downregulation of HNF-1α expression at transcriptional and posttranslational levels. HCV-induced downregulation of HNF-1α expression may play a crucial role in glucose metabolic disorders caused by HCV.


Ocean wave patterns under hurricane gloria: observation with an airborne synthetic-aperture radar.
Surface imagery of ocean waves under Hurricane Gloria (September 1976) has been obtained with an airborne synthetic-aperture imaging radar. Observations were obtained over most of the area within a radius of 150 kilometers around the center of the eye. These direct observations made it possible to derive the wave patterns in the region around a hurricane eye.


Asymmetric pathways in the electrochemical conversion reaction of NiO as battery electrode with high storage capacity.
Electrochemical conversion reactions of transition metal compounds create opportunities for large energy storage capabilities exceeding modern Li-ion batteries. However, for practical electrodes to be envisaged, a detailed understanding of their mechanisms is needed, especially vis-à-vis the voltage hysteresis observed between reduction and oxidation. Here, we present such insight at scales from local atomic arrangements to whole electrodes. NiO was chosen as a simple model system. The most important finding is that the voltage hysteresis has its origin in the differing chemical pathways during reduction and oxidation. This asymmetry is enabled by the presence of small metallic clusters and, thus, is likely to apply to other transition metal oxide systems. The presence of nanoparticles also influences the electrochemical activity of the electrolyte and its degradation products and can create differences in transport properties within an electrode, resulting in localized reactions around converted domains that lead to compositional inhomogeneities at the microscale.


Prevalence of Positive Troponin and Echocardiogram Findings and Association With Mortality in Acute Ischemic Stroke.
Acute ischemic stroke (AIS) patients may have raised serum cardiac troponin levels on admission, although it is unclear what prognostic implications this has, and whether elevated levels are associated with cardiac causes of stroke or structural cardiac disease as seen on echocardiogram. We investigated the positivity of cardiac troponin and echocardiogram testing within a large biracial AIS population and any association with poststroke mortality. Within a catchment area of 1.3 million, we screened emergency department admissions from 2010 using International Classification of Diseases, Ninth Edition, discharge codes 430 to 436 and ascertained all physician-confirmed AIS cases by retrospective chart review. Hypertroponinemia was defined as elevation in cardiac troponin above the standard 99th percentile. Multiple logistic regression was performed, controlling for stroke severity, history of cardiac disease, and all other stroke risk factors. Of 1999 AIS cases, 1706 (85.3%) had a cardiac troponin drawn and 1590 (79.5%) had echocardiograms. Hypertroponinemia occurred in 353 of 1706 (20.7%) and 160 of 1590 (10.1%) had echocardiogram findings of interest. Among 1377 who had both tests performed, hypertroponinemia was independently associated with echocardiogram findings (odds ratio, 2.9; 95% confidence interval, 2-4.2). When concurrent myocardial infarctions (3.5%) were excluded, hypertroponinemia was also associated with increased mortality at 1 year (35%; odds ratio, 3.45; 95% confidence interval, 2.1-5.6) and 3 years (60%; odds ratio, 2.91; 95% confidence interval, 2.06-4.11). Hypertroponinemia in the context of AIS without concurrent myocardial infarction was associated with structural cardiac disease and long-term mortality. Prospective studies are needed to determine whether further cardiac evaluation might improve the long-term mortality rates seen in this group.


A haploid HSV-1 genome platform for vector development: testing of the tetracycline-responsive switch shows interference by infected cell protein 0.
Although herpes simplex virus type 1 (HSV-1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of approximately 15.4 kb of DNA sequences that are duplicated in the HSV-1 genome, complicating vector construction and stability. As a useful platform for building HSV-1 vectors, we have constructed a fully haploid HSV-1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired. We used this ΔIR mutant to subsequently investigate whether the insertion of tetracycline-responsive tetO elements into the ICP34.5-ICP0 gene region can be used to control HSV-1 lytic replication. The results of the present study show that ΔIR mutants deleted for ICP34.5 are viable for replication but not when the ICP0 promoter is also disrupted, thus indicating that regulation of infected cell protein 0 (ICP0) levels in the absence of ICP34.5 could be a viable means for controlling growth of HSV-1 vectors. Surprisingly, however, the tetO elements inserted into the ICP0 promoter did not confer ligand responsiveness to growth or ICP0 expression. Further analysis by transfection experiments revealed that ICP0 itself interferes with the tetracycline switch and reduces the the inducibility of this system. Our new haploid HSV-1 BAC is a useful platform for building multiply deleted HSV-1 vectors. Deletion of the gene for ICP34.5 in this backbone renders viral growth dependent on ICP0, although ICP0 expression could not be regulated by tet-responsive transcriptional regulators.


Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells.
Aminoglycosides (AGs) are broad-spectrum antibiotics that are associated with kidney damage, balance disorders, and permanent hearing loss. This damage occurs primarily by killing of proximal tubule kidney cells and mechanosensory hair cells, though the mechanisms underlying cell death are not clear. Imaging molecules of interest in living cells can elucidate how molecules enter cells, traverse intracellular compartments, and interact with sites of activity. Here, we have imaged fluorescently labeled AGs in live zebrafish mechanosensory hair cells. We determined that AGs enter hair cells via both nonendocytic and endocytic pathways. Both routes deliver AGs from the extracellular space to lysosomes, and structural differences between AGs alter the efficiency of this delivery. AGs with slower delivery to lysosomes were immediately toxic to hair cells, and impeding lysosome delivery increased AG-induced death. Therefore, pro-death cascades induced at early time points of AG exposure do not appear to derive from the lysosome. Our findings help clarify how AGs induce hair cell death and reveal properties that predict toxicity. Establishing signatures for AG toxicity may enable more efficient evaluation of AG treatment paradigms and structural modifications to reduce hair cell damage. Further, this work demonstrates how following fluorescently labeled drugs at high resolution in living cells can reveal important details about how drugs of interest behave.


Network Approaches to Understand Individual Differences in Brain Connectivity: Opportunities for Personality Neuroscience.
Over the past decade, advances in the interdisciplinary field of network science have provided a framework for understanding the intrinsic structure and function of human brain networks. A particularly fruitful area of this work has focused on patterns of functional connectivity derived from non-invasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI). An important subset of these efforts has bridged the computational approaches of network science with the rich empirical data and biological hypotheses of neuroscience, and this research has begun to identify features of brain networks that explain individual differences in social, emotional, and cognitive functioning. The most common approach estimates connections assuming a single configuration of edges that is stable across the experimental session. In the literature, this is referred to as a static network approach, and researchers measure static brain networks while a subject is either at rest or performing a cognitively demanding task. Research on social and emotional functioning has primarily focused on linking static brain networks with individual differences, but recent advances have extended this work to examine temporal fluctuations in dynamic brain networks. Mounting evidence suggests that both the strength and flexibility of time-evolving brain networks influence individual differences in executive function, attention, working memory, and learning. In this review, we first examine the current evidence for brain networks involved in cognitive functioning. Then we review some preliminary evidence linking static network properties to individual differences in social and emotional functioning. We then discuss the applicability of emerging dynamic network methods for examining individual differences in social and emotional functioning. We close with an outline of important frontiers at the intersection between network science and neuroscience that will enhance our understanding of the neurobiological underpinnings of social behavior.


Social Reactions After Disclosing Suicide Loss Among Women.
Background: Suicide loss is often concealed. While initial evidence suggests that disclosure is important for healthy grieving, observed beneficial effects may depend on social reactions. Aim: The current study aimed to identify social reactions and associated consequences experienced by persons who lost a loved one to suicide (i.e., suicide loss survivors). Method: We conducted qualitative interviews with 22 female adult suicide loss survivors focusing on social reactions after suicide loss. Interviews were transcribed and analyzed using qualitative content analysis. Results: When talking about their loss with others, suicide loss survivors experienced a broad range of social reactions including compassionate and supportive responses, speechlessness and insecurity, curiosity and gossip, stigmatization, and grieving expectations. Depending on these social reactions, disclosing suicide loss was associated with both negative and positive long-term effects. Limitations: The findings are limited to the current female sample. Conclusion: Interventions that help suicide loss survivors in finding supportive confidants, combined with public interventions to decrease public suicide stigma and improve the public's readiness to provide helpful support to suicide loss survivors, could improve grieving outcomes among this group.


Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma.
For recipients of liver transplantations (LTs) for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus (SRL), an immunosuppressant with anticarcinogenic properties, may reduce HCC recurrence and improve survival. In our study, the US Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early SRL use with recurrence, cancer-specific mortality, and all-cause mortality, adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of interleukin 2 induction therapy, and allocated and calculated Model for End-Stage Liver Disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Among the 3936 included HCC LTs, 234 (6%) were SRL users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in SRL users and nonusers (adjusted hazard ratio [aHR], 1.01; 95% CI, 0.73-1.39). HCC recurrence and cancer-specific mortality rates appeared lower in SRL users, but associations were not statistically significant (recurrence aHR, 0.86; 95% CI, 0.45-1.65; cancer-specific mortality aHR, 0.80; 95% CI, 0.43-1.50). Among recipients >55 years old, associations were suggestive of better outcomes for SRL users (all-cause mortality aHR, 0.62; 95% CI, 0.38-1.01; recurrence aHR, 0.52; 95% CI, 0.19-1.44; cancer-specific mortality aHR, 0.34; 95% CI, 0.11-1.09), whereas among recipients ≤55 years old, SRL users had worse outcomes (all-cause mortality aHR, 1.76; 95% CI, 1.12-2.75; recurrence aHR, 1.49; 95% CI, 0.62-3.61; cancer-specific mortality aHR, 1.54; 95% CI, 0.71-3.32). In conclusion, among HCC liver recipients overall, SRL did not appear beneficial in reducing all-cause mortality. However, there were suggestions of reductions in recurrence and cancer-specific mortality, and effects appeared to be modified by age at transplantation. Liver Transplantation 22 627-634 2016 AASLD.


Toward a redefinition of implicit memory: process dissociations following elaborative processing and self-generation.
Does conceptual processing affect unconscious uses of memory? We used a process-dissociation procedure to separate automatic (unconscious) and consciously controlled uses of memory in a stem-completion task. Contrary to results from indirect test conditions, estimates derived from our procedure showed no effect of self-generation and no differential effect of semantic and nonsemantic study conditions on automatic uses of memory. These results provide evidence that (a) indirect tests are often contaminated by conscious uses of memory and (b) stem completion is highly dependent on prior perceptual (and perhaps lexical) processing. The experiments demonstrate the advantages of using process-dissociation procedures over comparisons between direct and indirect tests.


The effect of chronic peripheral nesfatin-1 application on blood pressure in normal and chronic restraint stressed rats: related with circulating level of blood pressure regulators.
Nesfatin is a peptide secreted by peripheral tissues, central and peripheral nervous system. It is involved in the regulation of homeostasis. Although the effects of nesfatin-1 on nutrition have been studied widely in the literature, the mechanisms of nesfatin-1 action and also relations with other physiological parameters are still not clarified well. We aimed to investigate the effect of peripheral chronic nesfatin-1 application on blood pressure regulation in normal and in rats exposed to restraint immobilization stress. In our study, three month-old male Wistar rats were used. Rats were divided into 4 groups as Control, Stress, Control+Nesfatin-1, Nesfatin-1+Stress. Angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone, cortisol, nesfatin-1 levels were determined in plasma samples by ELISA. Our results have shown that chronic peripheral nesfatin-1 administration increases blood pressure in normal and in rats exposed to chronic restraint stress. Effect of nesfatin-1 on circulating level of angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone and cortisol has been identified. We can conclude that elevated high blood pressure after chronic peripheral nesfatin-1 administration in rats exposed to chronic restraint stress may be related to decreased plasma level of endothelial nitric oxide synthase concentration.


Management of heart failure: evidence versus practice. Does current prescribing provide optimal treatment for heart failure patients?
Heart failure is an increasingly common and costly chronic disorder, with a rising prevalence of at least 2% in populations over the age of 45 years, mortality rates that are as poor as common solid cancers, and very high health care utilisation costs. Despite increased evidence supporting a range of effective interventions, predominantly therapeutic, there remain significant degrees of physician underperformance in terms of heart failure diagnosis and management. Until the early 1990s, the management of heart failure was largely confined to the symptomatic relief of patients with well established heart failure in fluid overload. The introduction of angiotensin-converting enzyme (ACE) inhibitors provided the first treatments that beneficially altered the prognosis of patients with the most common expression of heart failure, namely established systolic dysfunction, whether symptomatic or asymptomatic. Evidence has now extended these benefits to delaying progression of heart failure and reducing hospitalisation. Much of our understanding of the pathophysiology of heart failure stems from these studies. More recent data has clarified the limited role of digoxin, the important benefits of beta-blockade and aldosterone blockers as adjuvants to ACE inhibition, and the emerging evidence on angiotensin II antagonists. There are, in contrast to these positive findings, reliable data from Europe and North America revealing significant underperformance of primary care and hospital physicians in heart failure diagnosis and management, with evidence of underuse and underdosing of evidence-based therapies. Limited qualitative data suggest the reasons for this underperformance are complex and relate to lack of access to objective testing of ventricular function and exaggerated concerns over treatment risks and side-effects. Heart failure represents a complex cluster of aetiologies and risks that are not easy to correctly identify, even in specialist settings. Since there is now powerful evidence on how heart failure can be modified and improved, explicit guidance is needed for which suspected patients should be referred, for confirmation of diagnosis and advice on appropriate treatment regimes, and for which patients can be handled mainly within primary care but with enhanced access to objective non-invasive tests to improve diagnostic reliability and to stratify patients to evidence-based therapies. Current evidence suggests that in North America and Europe today primary care physicians do underperform in their management of patients with heart failure, often owing to factors outside of their immediate control.


Health Self-Efficacy Among Populations with Multiple Chronic Conditions: the Value of Patient-Centered Communication.
Using cross-sectional survey data, we assessed the association between chronic illness burden and health-related self-efficacy, evaluating whether patient-centered communication is associated with self-efficacy and if that relationship varies by chronic illness burden. Data were from the Health Information National Trends Survey, a cross-sectional survey of the US adult population collected in 2012-2013 (n = 3630). Health-related self-efficacy was measured with the item: "Overall, how confident are you about your ability to take good care of your health?" and the prevalence of six chronic conditions and depression/anxiety was assessed. Patient-centered communication was measured as the frequency with which respondents perceived their healthcare providers allowed them to ask questions, gave attention to their emotions, involved them in decisions, made sure they understood how to take care of their health, helped them to deal with uncertainty, and if they felt they could rely on their healthcare providers to take care of their healthcare needs. Health-related self-efficacy was significantly lower among individuals with greater illness burden. In adjusted analysis, individuals who experienced more positive patient-centered communication reported higher levels of self-efficacy (β = 0.26, P < 0.0001); this association was strongest among those with greater illness burden. Higher levels of self-efficacy were observed among patients reporting more positive patient-centered communication; the observed association was stronger among those with greater chronic illness burden.


Serum lipid effects of a monounsaturated (palmitoleic) fatty acid-rich diet based on macadamia nuts in healthy, young Japanese women.
1. Recent studies have identified potential beneficial effects of eating nuts, most of which have substantial amounts of monounsaturated fatty acids (MUFA). Macadamia nuts consist of 75% fat by weight, 80% of which is MUFA (palmitoleic acid). 2. To examine variations in serum lipid levels in response to a high-MUFA diet based on macadamia nuts, 3 week interventions of macadamia nuts, coconuts and butter were determined in young, healthy Japanese female students. 3. After 3 weeks intervention, serum concentrations of total cholesterol and low-density lipoprotein-cholesterol were significantly decreased in the macadamia nut and coconut diets and bodyweight and body mass index were decreased in the group fed macadamia nuts, although there were no statistically significant changes in the group fed butter.


Post-anthesis moisture increased Fusarium head blight and deoxynivalenol levels in North Carolina winter wheat.
ABSTRACT Current models for forecasting Fusarium head blight (FHB) and deoxynivalenol (DON) levels in wheat are based on weather near anthesis, and breeding for resistance to FHB pathogens often relies on irrigation before and shortly after anthesis to encourage disease development. The effects of post-anthesis environmental conditions on FHB are poorly understood. We performed a field experiment at Kinston, NC, to explore the effects of increasing duration of post-anthesis moisture on disease incidence, disease severity, Fusarium-damaged kernels (FDK), percent infected kernels, and DON. The experiment had a split-plot design, and one trial was conducted in each of two successive years. Main plots consisted of post-anthesis mist durations of 0, 10, 20, or 30 days. Subplots were of eight cultivars in the first year and seven in the second year, two being susceptible to FHB and the remainder each with varying degrees of apparent type I and type II resistance. Plots were inoculated by spraying Fusarium graminearum macroconidia at mid-anthesis. Averaging across years and cultivars, 10 or 20 days of post-anthesis mist had the same effect (P > or = 0.198) and were associated with an approximately fourfold increase in mean disease incidence and eightfold increase in disease severity compared with 0 days of mist (P < or = 0.0002). In both years, mean FDK percentages at 0 and 10 days post-anthesis mist were the same and significantly lower than FDK percentages under 20 or 30 days of post-anthesis mist. Mist duration had a significant effect on percent kernels infected with Fusarium spp. as detected by a selective medium assay of 2007 samples. Averaging across all cultivars, in both years, DON levels increased significantly for 10 days compared with 0 days of mist, and increased again with 20 days of mist (P < or = 0.04). This is the first investigation to show that extended post-flowering moisture can have a significant enhancing effect on FHB, FDK, DON, and percent infected kernels of wheat. For all disease and toxin assays, cultivar rankings were significantly noncorrelated among mist durations in at least 1 year, suggesting that FHB screening programs might rank genotypes differently under extended post-anthesis moisture than without it. Our findings also imply that accurate forecasts of DON in small grains must take account of post-anthesis weather conditions.


Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome.
Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced activity levels associated with heightened feelings of fatigue. Previous research has demonstrated that exercise training has beneficial effects on fatigue-related symptoms in individuals with CFS. PURPOSE: The aim of this study was to sustain an increase in daily physical activity in CFS patients for 4 weeks and assess the effects on fatigue, muscle pain and overall mood. METHODS: Six CFS and seven sedentary controls were studied. Daily activity was assessed by a CSA accelerometer. Following a two week baseline period, CFS subjects were asked to increase their daily physical activity by 30% over baseline by walking a prescribed amount each day for a period of four weeks. Fatigue, muscle pain and overall mood were reported daily using a 0 to 100 visual analog scale and weekly using the Profile of Mood States (Bipolar) questionnaire. RESULTS: CFS patients had significantly lower daily activity counts than controls (162.5 +/- 51.7 x 103 counts/day vs. 267.2 +/- 79.5 x 103 counts/day) during a 2-week baseline period. At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue and muscle pain intensity compared to controls but the groups did not differ in overall mood. CFS subjects increased their daily activity by 28 +/- 19.7% over a 4 week period. Overall mood and muscle pain worsened in the CFS patients with increased activity. CONCLUSION: CFS patients were able to increase their daily physical activity for a period of four weeks. In contrast to previous studies fatigue, muscle pain, and overall mood did not improve with increased activity. Increased activity was not presented as a treatment which may account for the differential findings between this and previous studies. The results suggest that a daily "activity limit" may exist in this population. Future studies on the impact of physical activity on the symptoms of CFS patients are needed.


Flat metasurfaces to focus electromagnetic waves in reflection geometry.
We show that a flat metasurface with a parabolic reflection-phase distribution can focus an impinging plane wave to a point image in reflection geometry. Our system is much thinner than conventional geometric-optics devices and does not suffer the energy-loss issues encountered by many metamaterial devices working in transmission geometry. We designed realistic microwave samples and performed near-field scanning experiments to verify the focusing effect. Experimental results are in good agreement with full wave simulations, model calculations, and theoretical analyses.


Antiretroviral program associated with reduction in untreated prevalent tuberculosis in a South African township.
In 2005, we reported high prevalence of untreated pulmonary tuberculosis (TB) in a South African community. Prevalent untreated TB is the main source of transmission. In settings with large burdens of human immunodeficiency virus (HIV) and TB, highly active antiretroviral therapy (HAART) may contribute to TB control. To assess the community-level impact of HAART on TB prevalence, we repeated a community-based TB prevalence cross-sectional survey in 2008 following HAART roll-out. A random 10% adult population sample was identified from the community. Participants provided two sputum specimens for acid-fast bacilli microscopy and TB culture. Oral transudate specimen was collected for anonymous HIV testing, linked to TB diagnosis. An interviewer-administered, structured questionnaire identified TB and HIV history and risk factors. In the 2008 survey, 1,250 adults participated (90% response rate); 306 (25%) tested HIV positive, of which 60 (20%) were receiving HAART. A total of 20 TB cases were identified (12 receiving TB treatment), representing a significant decline in prevalence from 3.2 to 1.6% (P = 0.02) between the surveys. TB prevalence in participants not infected with HIV was unchanged (P = 0.90). The decline occurred among participants not infected with HIV, decreasing from 9.2 to 3.6% in 2005 to 2008, respectively (P = 0.003). In participants infected with HIV, prevalence of treated TB declined from 4 to 2.3% (P = 0.06), and untreated TB prevalence from 5.2 to 1.3% (P = 0.02). The proportion of untreated TB in patients receiving HAART decreased significantly, from 22 to 0% (P < 0.001). Prevalence of undiagnosed TB declined significantly over a period of increasing HAART availability. The decline was predominantly in individuals infected with HIV receiving HAART.


The Combination of piR-823 and Eukaryotic Initiation Factor 3 B (EIF3B) Activates Hepatic Stellate Cells via Upregulating TGF-β1 in Liver Fibrogenesis.
BACKGROUND Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA, which has also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. piR-823 is increased in liver cirrhosis and hepatocellular carcinoma (HCC). However, there is no report on the function of piR-823 in hepatic stellate cells (HSCs) activation during hepatic fibrosis. The present study investigated the role of piR-823 in HSC activation. MATERIAL AND METHODS Liver fibrosis was induced in mice by carbon tetrachloride (CCL4) injection and bile duct ligation (BDL). The primary HSCs were isolated from mice and cultured. The expression of piR-823 was measured by real-time PCR. The effect of piR-823 on HSCs was evaluated by either sense sequence or antisense sequence of piR-823 carried by liposome. Proteins binding to piR-823 were assayed by RNA pull-down technique and liquid chromatography-mass spectrometry (LC-MS). RESULTS Our data for the first time show that piR-823 is significantly upregulated in activated HSCs. Overexpression of piR-823 promoted HSC proliferation, α-SMA and COL1a1 production, whereas inhibition of piR-823 suppressed the activity of HSCs. Interestingly, the combination of piR-823 and EIF3B promoted TGF-β1 expression. CONCLUSIONS Our data illustrate a novel mechanism of piR-823 in HSC activities. The combination of piR-823 and EIF3B increased TGF-β1 expression, which activates HSCs in liver fibrosis. piR-823 may be a new target in the treatment of liver fibrosis.


3D deformation field in growing plant roots reveals both mechanical and biological responses to axial mechanical forces.
Strong regions and physical barriers in soils may slow root elongation, leading to reduced water and nutrient uptake and decreased yield. In this study, the biomechanical responses of roots to axial mechanical forces were assessed by combining 3D live imaging, kinematics and a novel mechanical sensor. This system quantified Young's elastic modulus of intact poplar roots (32MPa), a rapid <0.2 mN touch-elongation sensitivity, and the critical elongation force applied by growing roots that resulted in bending. Kinematic analysis revealed a multiphase bio-mechanical response of elongation rate and curvature in 3D. Measured critical elongation force was accurately predicted from an Euler buckling model, indicating that no biologically mediated accommodation to mechanical forces influenced bending during this short period of time. Force applied by growing roots increased more than 15-fold when buckling was prevented by lateral bracing of the root. The junction between the growing and the mature zones was identified as a zone of mechanical weakness that seemed critical to the bending process. This work identified key limiting factors for root growth and buckling under mechanical constraints. The findings are relevant to crop and soil sciences, and advance our understanding of root growth in heterogeneous structured soils.


White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.
Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment.


Radiotherapy-induced anti-tumor immune response and immune-related adverse events in a case of recurrent nasopharyngeal carcinoma undergoing anti-PD-1 immunotherapy.
Treatment of recurrent nasopharyngeal carcinoma is a challenging clinical problem. We report the case of a 46 year old male showing excellent response and signs of immunostimulation following re-re-irradiation for recurrent nasopharyngeal carcinoma under systemic treatment with pembrolizumab. Patient was first diagnosed with locoregionally advanced, non-keratinizing nasopharyngeal carcinoma in 2010. After achieving complete remission following induction chemotherapy and concurrent curative chemoradiation, the patient subsequently developed distant and locoregionally recurrent disease. He received various treatments (neck dissection, radiotherapy to a bony metastasis, palliative chemotherapy, stereotactic re-irradiation of local recurrence) before initiation of anti- PD-1 immunotherapy with pembrolizumab in January of 2016. Following marked local progression 6 months thereafter, we performed re-re-irradiation of the recurrent tumor after careful evaluation and treatment planning. While treatment was well tolerated, the patient subsequently developed marked clinical and radiological signs of immunostimulation with mucosal irritation and swelling of lacrimal and salivary glands as described in the report. Immunotherapy with pembrolizumab was reinitiated, with re- staging showing excellent response with regression of all tumorous lesions. At the time of this report, following near complete recovery of inflammatory symptoms, the patient remains in excellent condition and free from recurrence under treatment with pembrolizumab. To our knowledge, we report the first observation of a combined effect of immunotherapy and radiotherapy in a patient with recurrent nasopharyngeal carcinoma. Demonstrating distinct signs of immunostimulation as well as excellent tumor response in a heavily pretreated patient progressing under anti-PD-1 immunotherapy, the case adds to the rising paradigm of an immunostimulatory effect of radiotherapy in patients undergoing treatment with immune checkpoint inhibitors.


Herbal tea induced hepatic veno-occlusive disease: quantification of toxic alkaloid exposure in adults.
Four young Chinese women took daily doses of an unidentified 'Indian' herbal tea as treatment for psoriasis. Three (one of whom died), developed ascites, hepatomegaly and biochemical abnormalities within 19-45 days. The fourth patient discontinued herbal tea after 21 days when she developed a skin rash. Two patients had portal hypertension, while all had liver histology showing features of veno-occlusive disease. Pyrrolizidine alkaloids were identified spectrophotometrically in the brewed tea, and in the chopped leaves of the herbal mixture; the mean dose in the tea prepared for consumption being 12 mg/day of alkaloid base and 18 mg/day of N-oxide. The mean cumulative dose of alkaloids (base + N-oxide) before onset of symptoms (three patients), was estimated to be 18 mg/kg. In the asymptomatic patient with histological liver disease only, the corresponding dose was 15 mg/kg. These cases thus provide some measure of pyrrolizidine alkaloid toxicity in adults.


Mitochondrial regulation of intracellular Ca2+ signaling: more than just simple Ca2+ buffers.
Mitochondrial Ca(2+) uptake shapes the profile of intracellular Ca(2+) signals, both spatially and temporally. In addition, such uptake controls the gating of Ca(2+) release and store-operated Ca(2+) entry channels, partitions cells into subcellular Ca(2+) hotspots, and can result in the release of diffusible signals into the cytosol that subsequently regulate protein function.


Visibility of gingiva - An important determinant for an esthetic smile.
Need for having better esthetics is the new emerging trend seen in patients' demands and expectations. Various periodontal procedures including the mucogingival procedures have been designed to enhance the esthetics. The amount of gingival display of the patient is also an important parameter while considering the esthetics of the patient. Till date, very few studies have been done in which the amount of gingival visibility have been determined. So, the aim of this study was to evaluate the amount of visibility of gingiva during natural smile and forced smile in the patients visiting Himachal Dental College and Hospital. A total of 400 patients (242 females and 158 males), aged between 18 to 49 years, attending the outpatient department of Himachal Dental College, were included in this study. Patients were divided into two groups according to age and gender. Clinical photographs of the patients were taken and analyzed according to the following classification: (1) Very high smile line that is more than 2 mm of marginal gingiva visible or more than 2 mm apical to the cementoenamel junction visible for the reduced but healthy periodontium, (2) high smile line that is between 0 and 2 mm of marginal gingiva visible or between 0 and 2 mm apical to the cementoenamel junction visible for the reduced but healthy periodontium, (3) average smile line in which only gingival embrasures are visible, (4) low smile line in which gingival embrasures and cementoenamel junction not visible. Examination of the gingiva was done for both natural smile and forced smile. During smile analysis, the following results were revealed for Natural smile and forced smile. Natural smile analysis revealed following: C1: 1%, C2: 6%, C3: 43.50% and C4 was 49.50%. Forced smile analysis revealed the following: C1: 1%, C2: 15.50%, C3: 59% and C4: 24.50%. Excessive gingival display is an esthetic concern both to the patient and clinician. Therefore, understanding the etiology and treatment options is crucial for the treatment of such patients. So, it becomes utmost duty of the dentist to see that visual attractiveness of the smile is associated strongly with the health of the periodontium.


Occupation-Based Life Expectancy: Actuarial Fairness in Determining Statutory Retirement Age.
This study examines occupation-based differences in life expectancy and the extent to which health accounts for these differences. Twentyseven-year survival follow-up data were used from the Dutch population-based Longitudinal Aging Study Amsterdam (n = 2,531), initial ages 55-85 years. Occupation was based on longest-held job. Results show that the non-skilled general, technical and transport domains had an up to 3.5-year shorter life expectancy than the academic professions, accounting for the compositional characteristics age and gender. Statutory retirement age could be made to vary accordingly, by allowing a proportionally greater pension build-up in the shorter-lived domains. Health accounted for a substantial portion of the longevity difference, ranging from 20 to 66%, depending on the health indicator. Thus, health differences between occupational domains today can be used as a means to tailor retirement ages to individuals' risks of longevity. These data provide a proof of principle for the development of an actuarially fair method to determine statutory retirement ages.


Intimate partner violence and help-seeking--a cross-sectional study of women in Sweden.
Intimate partner violence (IPV) is a global public health concern with possible detrimental consequences for its victims. Studies have found prevalence rates of 15 to 71% for IPV. There is evidence that IPV exposed women perceive barriers to help-seeking and many remain undetected by care givers and authorities. This cross-sectional study aimed to examine IPV exposed women in relation to help-seeking versus non help-seeking from the social services or women's shelters with regard to social and psychological characteristics as well as relationship with the perpetrator and type of violence exposure. Two groups of Swedish IPV exposed women were included: non help-seekers (n = 128) were recruited through ads in newspapers, while help-seekers (n = 347) were recruited from four social service sites and twenty women's shelters around Sweden. Participants were assessed with questionnaires regarding age, education, occupation and relation to the perpetrator as well as validated instruments measuring psychological distress, psychosocial functioning alcohol use and violence. Analyses were made using Chi2 and multivariate logistic regression. Help-seekers had significantly more often children together with the perpetrator than non help-seekers (64% and 29% respectively) and a high association was found in the fully adjusted model (Adj. OR = 5.46 95% CI 2.99-9.97). Many women in both groups reported a poor social situation and high levels of psychological distress, although more psychological distress was associated with elevated odds for help-seeking (Adj. OR = 2.83 95% CI 1.84-4.34). No differences were found between the groups regarding violence exposure and most women in both groups had experienced severe violence from an intimate partner (95% to 98%). Results indicate a high problem load among women who had not contacted the social services or women's shelters due to IPV, and that non help-seekers had similar experiences of severe IPV as help-seekers. This stresses a need to identify IPV exposed women outside specialized settings within the social services and women's shelters. Asking about partner violence in various health and social care settings could be a feasible strategy to identify battered women and provide them with alternatives for help that ultimately could lead to a life without violence.


European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.
Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.


Psychological interventions for non-ulcer dyspepsia.
Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain. This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores patients with NUD. Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using very broad subject headings and text words. Bibliographies of retrieved articles were also searched and experts in the field were contacted. All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified. Data collected included individual, global dyspepsia symptom scores and quality of life (QoL) scores. We identified only four trials, each using different psychological interventions and three presenting results in a manner, that did not allow synthesis of the data to form a meta-analysis. All trials suggest that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials use statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size of these papers was too small. Unadjusted data was not statistically significant. The other problem of psychological intervention include low recruitment and high drop out rate which has been shown to be greater in patients receiving group therapy. There is currently insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD. There is also no evidence on the combined effects of pharmacological and psychological therapy. Nevertheless, if there are any benefits of psychological therapies, they are likely to persist long-term and NUD is a chronic relapsing and remitting disorder. Psychological therapies may therefore be offered to patients with severe symptoms that have not responded to pharmacological therapies.


Effects of potential confounding variables on accuracy of a commercially available veterinary point-of-care hematocrit meter in the evaluation of blood samples from dogs and cats.
To assess the agreement in measurements of Hct values and hemoglobin (Hgb) concentrations in blood samples from dogs and cats between a commercially available veterinary point-of-care (POC) Hct meter and a laboratory-based (LAB) analyzer and to determine the effects of various conditions (ie, lipemia, hyperbilirubinemia, hemolysis, autoagglutination, and reticulocytosis) on the accuracy of the POC meter. Blood samples from 86 dogs and 18 cats. Blood samples were run in duplicate on the POC meter, which reported Hgb concentration, measured via optical reflectance, and a calculated Hct value. The POC meter results were compared with results from a LAB analyzer. Blood samples with grossly visible lipemia, icterus, hemolysis, and autoagglutination were noted. Mean ± SD values for LAB Hct were 33.9 ± 15.73% (range, 3.9% to 75.8%), and for LAB Hgb were 11.2 ± 5.4 g/dL (range, 1 to 24.6 g/dL). Mean bias between POC Hct and LAB Hct values was -1.8% with 95% limits of agreement (LOAs) of -11.1% to 7.5% and between POC Hgb and LAB Hgb concentrations was -0.5 g/dL with 95% LOAs of -3.8 to 2.8 g/dL. There was no influence of lipemia (14 samples), icterus (23), autoagglutination (14), hemolysis (12), or high reticulocyte count (15) on the accuracy of the POC meter. The POC meter was unable to read 13 blood samples; 9 had a LAB Hct ≤ 12%, and 4 had a LAB Hct concentration between 13% and 17%. Overall, measurements from the POC meter had good agreement with those from the LAB analyzer. However, LOAs were fairly wide, indicating that there may be clinically important differences between measurements from the POC meter and LAB analyzer.


A mathematical model for the determination of total area under glucose tolerance and other metabolic curves.
To develop a mathematical model for the determination of total areas under curves from various metabolic studies. In Tai's Model, the total area under a curve is computed by dividing the area under the curve between two designated values on the X-axis (abscissas) into small segments (rectangles and triangles) whose areas can be accurately calculated from their respective geometrical formulas. The total sum of these individual areas thus represents the total area under the curve. Validity of the model is established by comparing total areas obtained from this model to these same areas obtained from graphic method (less than +/- 0.4%). Other formulas widely applied by researchers under- or overestimated total area under a metabolic curve by a great margin. Tai's model proves to be able to 1) determine total area under a curve with precision; 2) calculate area with varied shapes that may or may not intercept on one or both X/Y axes; 3) estimate total area under a curve plotted against varied time intervals (abscissas), whereas other formulas only allow the same time interval; and 4) compare total areas of metabolic curves produced by different studies. The Tai model allows flexibility in experimental conditions, which means, in the case of the glucose-response curve, samples can be taken with differing time intervals and total area under the curve can still be determined with precision.


Self-Powered Chemical Sensing Driven by Graphene-Based Photovoltaic Heterojunctions with Chemically Tunable Built-In Potentials.
Ultralow power chemical sensing is essential toward realizing the Internet of Things. However, electrically driven sensors must consume power to generate an electrical readout. Here, a different class of self-powered chemical sensing platform based on unconventional photovoltaic heterojunctions consisting of a top graphene (Gr) layer in contact with underlying photoactive semiconductors including bulk silicon and layered transition metal dichalcogenides is proposed. Owing to the chemically tunable electrochemical potential of Gr, the built-in potential at the junction is effectively modulated by absorbed gas molecules in a predictable manner depending on their redox characteristics. Such ability distinctive from bulk photovoltaic counterparts enables photovoltaic-driven chemical sensing without electric power consumption. Furthermore, it is demonstrated that the hydrogen (H2 ) sensing properties are independent of the light intensity, but sensitive to the gas concentration down to the 1 ppm level at room temperature. These results present an innovative strategy to realize extremely energy-efficient sensors, providing an important advancement for future ubiquitous sensing.


Effect of dietary intake and lifestyle factors on in vivo mutant frequency at the HPRT gene locus in healthy human subjects.
This paper describes the results of a study designed to assess the effects of a variety of dietary and lifestyle factors on background levels of mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene locus in humans. Eighty-three healthy and free-living subjects (aged 20-80 yr; 61 males and 22 females; mean age of 63.07 +/- 14.71 yr) were recruited. Background levels of MF were determined for each subject using a cloning assay. The mean MF/10(6) clonable cells (MF) for the study subjects was 4.63 +/- 2.20. An interview-administered questionnaire was completed by each study subject in order to assess details of dietary history, physical activity, health and potential genotoxin exposure history. A 7-day estimated dietary record method with a food frequency questionnaire was used to determine average intakes of energy and macronutrients (including alcohol), and a range of micronutrients (including vitamin and mineral supplement usage). The relationships between individual dietary and lifestyle factors and HPRT MF were investigated by univariate and multivariate analysis (data was adjusted for age, lymphocyte plating efficiency [PE] and energy intake [EI]). Univariate analysis revealed a significant positive correlation between EI and MF and multivariate analysis revealed significant positive correlations between, body mass index (BMI), % energy intake from total carbohydrate, starch, fat and MF. These findings suggest that a reduction in EI may be a useful preventative measure against the onset of carcinogenesis in humans. No correlations were found between alcohol intake and MF or between estimated antioxidant intake and MF. Thus, estimated intakes of antioxidants may not reflect their bioavailability and functional capacity in vivo and it may be more useful to examine actual plasma/cell levels vs. MF to establish if any significant relationship exists.


Dynamic designing of microstructures by chemical gradient-mediated growth.
Shape is one of the most important determinants of the properties of microstructures. Despite of a recent progress on microfabrication techniques, production of three-dimensional micro-objects are yet to be fully achieved. Nature uses reaction-diffusion process during bottom-up self-assembly to create functional shapes and patterns with high complexity. Here we report a method to produce polymeric microstructures by using a dynamic reaction-diffusion process during top-down photolithography, providing unprecedented control over shape and composition. In radical polymerization, oxygen inhibits reaction, and therefore diffusion of oxygen significantly alters spatial distribution of growth rate. Therefore, growth pathways of the microstructures can be controlled by engineering a concentration gradient of oxygen. Moreover, stepwise control of chemical gradients enables the creation of highly complex microstructures. The ease of use and high controllability of this technology provide new opportunities for microfabrication and for fundamental studies on the relationships between shape and function for the materials.


Effectiveness and experience of arts-based pedagogy among undergraduate nursing students: a mixed methods systematic review.
To develop well rounded professional nurses, educators need diverse pedagogical approaches. There is growing interest in arts-based pedagogy (ABP) as the arts can facilitate reflection, create meaning and engage healthcare students. However, the emerging body of research about ABP needs to be systematically examined. To synthesize the best available evidence on the effectiveness of ABP in enhancing competencies and learning behaviors in undergraduate nursing education and to explore nursing students' experiences with art-based pedagogy. The review considered studies that included participants who are undergraduate nursing students. The qualitative (QL) component considered studies investigating nursing students' experiences of ABP, and the quantitative (QN) component considered studies evaluating the effectiveness of ABP in undergraduate nursing education. The QL component considered QL studies including designs such as phenomenology, grounded theory, ethnography, action research and feminist research. The QN component considered studies that examined the effectiveness of ABP including designs such as randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case-control studies, analytical cross-sectional studies, case series, individual case reports and descriptive cross-sectional studies. The following QN outcomes of ABP were assessed: knowledge acquisition, level of empathy, attitudes toward others, emotional states, reflective practice, self-transcendence, cognitive/ethical maturity, learning behaviors and students' perspectives of ABP. An extensive three-step search strategy was conducted for primary research studies published between January 1, 1994 and April 7, 2015. The strategy included searching CINAHL, MEDLINE, ERIC, PsycINFO, Academic Search Complete, Arts and Humanities Citation Index, Art Full Text, Scopus, ProQuest Dissertations and Theses, A&I, and gray literature. Only studies published in English were included. Two reviewers assessed all studies for methodological quality using appropriate critical appraisal checklists from the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) or the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Data were extracted from included articles using the standardized data extraction tool from JBI-QARI or JBI-MAStARI. Qualitative studies were pooled through a meta-synthesis. Data from the QN studies were combined using a narrative synthesis as a meta-analysis was not possible. The researchers used a segregated mixed methods approach to integrate the QL and QN components. Twenty-one QL studies of high methodological quality were included. The two synthesized findings revealed that art forms could create meaning and inspire learning in undergraduate nursing education and that ABP can develop important learner outcomes/competencies for professional nursing. These synthesized findings received a moderate ConQual rating. Fifteen experimental/quasi-experimental studies of moderate methodological quality were included. The narrative synthesis suggested that ABP improved nursing students' knowledge acquisition, level of empathy, attitude toward others, emotional states, level of reflective practice, learning behaviors and aspects of cognitive/ethical maturity. In five cross-sectional studies, the majority of students had a positive perspective of ABP. When the QL and QN findings were interpreted as a whole, ABP appeared to facilitate learning in the cognitive and affective domains and may be especially useful in addressing the affective domain. Nurse educators should consider using ABP as students found that this approach offered a meaningful way of learning and resulted in the development of important competencies for professional nursing. The QN studies provide a very low level of evidence that ABP improved students' knowledge acquisition, level of empathy, attitude toward others, emotional states, level of reflective practice, learning behaviors and aspects of cognitive/ethical maturity. Although the QN findings can inform future research, the evidence is not robust enough to demonstrate improved outcomes.


Evaluation of remedial options for a benzene-contaminated site through a simulation-based fuzzy-MCDA approach.
A simulation-based fuzzy multi-criteria decision analysis (SFMCDA) method is developed for supporting the selection of remediation strategies for petroleum contaminated sites. SFMCDA integrates process modeling (using BIOPLUME III) and fuzzy ranking (based on fuzzy TOPSIS) into a general management framework, and can compare various remediation alternatives, in light of both cost-risk tradeoffs and uncertainty impacts. The proposed method is applied to a hypothetical contaminated site suffering from a benzene leakage problem. Six remediation alternatives are taken into consideration, including natural attenuation (NA), pump-and-treat (PAT), enhanced natural attenuation (ENA), and a number of their combinations. Six fuzzy criteria, including both cost and risk information, are used to compare different alternatives through fuzzy TOPSIS. The results demonstrates that the proposed method can help systematically analyze fuzzy inputs from contaminant transport modeling, cost implications and stakeholders' preferences, and provide useful ranking information covering a variety of decision-relevant remediation options for decision makers.


Evaluation of the Effect of Glow Discharge Plasma Surface Treatment on Bonding Cements to Zirconia.
The major difference in the chemical composition of Y-TZP ceramics, as compared with conventional porcelain, led researchers to develop alternative solutions for achieving durable and long term bonding with the zirconia surface. The study aims to evaluate the effects of glow discharge treatment on the bonding between cement and zirconia. The zirconia rings and rods were prepared with the Zirconia Y-TZP powder and TZ-3YSB-E (Tosoh-Zirconia) through auto-mix to investigate the glow discharge and thermo-cycling. An orientation Teflon mold was used to centralize each rod into the zirconia ring, and aided as a cementation jig during the cementation procedure. Cohesive failure (2/3 or more of luting agent remained on the zirconia surface) has been majorly observed with RelyX Ultimate, while adhesion failure (less than 1/3 of the luting agent remained on the zirconia surface) has been primarily observed in Ketac-Cem. Mixed failure was observed among the three specimen including Rely X Unicem 2, Multilink Auto-mix and Ceramir. The glow discharge surface treatment procedure had a major impact on bond strength to zirconia.


Scedosporium apiospermum (Pseudallescheria boydii) infection in a heart transplant recipient: a case of mistaken identity.
We report a case of fatal central nervous system infection with Scedosporium apiospermum (Pseudallescheria boydii) in a heart transplant recipient. This ubiquitous fungus is known to cause mycetoma and localized infections in patients with otherwise normal conditions. Disseminated infections occur rarely and are seen primarily in patients who are receiving immunosuppressive medications or who have neutropenia. Often life-threatening when infection is disseminated and involves the central nervous system, this diagnosis is difficult to make rapidly because S. apiospermum (P. boydii) mimics Aspergillus spp. and Fusarium spp., both clinically and histopathologically. Imidazoles such as miconazole, but not amphotericin B, are considered the therapeutic compounds of choice. Improved diagnostic and treatment options are needed to optimize management of infections with S. apiospermum (P. boydii).


The symmetry rule: a seven-year study of symptoms and explanatory labels among Gulf War veterans.
Noticing medical symptoms can cause one to search for explanatory labels such as "ate bad food" or even "exposed to anthrax," and perhaps these labels may cause new symptom reports. The present study examined whether there is empirical support for this symptom-label "symmetry rule." We interviewed veterans (N= 362) from the Gulf War Registry in 1995 and 2002 about their medical symptoms and about their exposure to war-related hazards and stressors. Health symptom reports were strongly correlated between the two time periods and showed relatively stable mean levels, whereas recall of war-related exposures was notably unstable. Veterans starting with fewer medical symptoms recalled fewer war-related exposures seven years later. Initial recollection of chemical and biological warfare exposure (but not other exposures) longitudinally predicted novel medical symptoms. The findings generally support the symmetry rule hypotheses, although the evidence for the label to symptom link was less strong. The findings account for some variability in symptoms and exposure recall over time, but they do not, on their own, account for the Gulf War veterans' elevated number of unexplained medical symptoms.


A Review of the Essential Components of Quality Palliative Care in the Home.
The home is an important and often preferable setting of palliative care. While much research has demonstrated the benefits of specialized palliative homecare on patient and system outcomes, there has been little delineation of the underlying components of these efficacious programs. We synthesized the essential elements of palliative homecare from a combined review of successful programs, perspectives of patients and caregivers, and views of healthcare providers in palliative care. Five unique palliative homecare studies were included in the rapid review and synthesis-(1) systematic review of the components of efficacious programs; (2) in-depth analysis of 11 effective community-based teams; (3) survey of bereaved caregivers; (4) survey of the general public; and (5) interviews of providers and administrators. A qualitative approach was used to identify transcending themes across the studies. Six essential elements of quality palliative homecare were common across the studies: (1) Integrated teamwork; (2) Management of pain and physical symptoms; (3) Holistic care; (4) Caring, compassionate, and skilled providers; (5) Timely and responsive care; and (6) Patient and family preparedness. Our metasynthesis of effective palliative homecare models, as well as, the values of those who use and provide these services, illuminates the underpinning elements of quality home-based care for patients with a life-limiting illness. However, the application of these elements must be relevant to the local community context. To create impactful, sustainable homecare programs, it is critical to capitalize on existing processes, partnerships, and assets.