title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Incidence of remission in adults with type 2 diabetes: the diabetes & aging study. | To estimate the incidence of remission in adults with type 2 diabetes not treated with bariatric surgery and to identify variables associated with remission. We quantified the incidence of diabetes remission and examined its correlates among 122,781 adults with type 2 diabetes in an integrated healthcare delivery system. Remission required the absence of ongoing drug therapy and was defined as follows: 1) partial: at least 1 year of subdiabetic hyperglycemia (hemoglobin A1c [HbA₁c] level 5.7-6.4% [39-46 mmol/mol]); 2) complete: at least 1 year of normoglycemia (HbA₁c level <5.7% [<39 mmol/mol]); and 3) prolonged: complete remission for at least 5 years. The incidence density (remissions per 1,000 person-years; 95% CI) of partial, complete, or prolonged remission was 2.8 (2.6-2.9), 0.24 (0.20-0.28), and 0.04 (0.01-0.06), respectively. The 7-year cumulative incidence of partial, complete, or prolonged remission was 1.47% (1.40-1.54%), 0.14% (0.12-0.16%), and 0.007% (0.003-0.020%), respectively. The 7-year cumulative incidence of achieving any remission was 1.60% in the whole cohort (1.53-1.68%) and 4.6% in the subgroup with new-onset diabetes (<2 years since diagnosis) (4.3-4.9%). After adjusting for demographic and clinical characteristics, correlates of remission included age >65 years, African American race, <2 years since diagnosis, baseline HbA₁c level <5.7% (<39 mmol/mol), and no diabetes medication at baseline. In community settings, remission of type 2 diabetes does occur without bariatric surgery, but it is very rare. | 25,231,895 | [
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Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes. | Sulfonylureas (SUs) are effective at controlling glycemia in permanent neonatal diabetes mellitus (PNDM) caused by KCNJ11 (Kir6.2) mutations. We report the case of a woman with PNDM who continued high doses of glibenclamide (85 mg/day) during her pregnancy. The baby was born preterm, and presented with macrosomia and severe hyperinsulinemic hypoglycemia requiring high-rate intravenous glucose infusion. Postnatal genetic testing excluded a KCNJ11 mutation in the baby. Glibenclamide was detected in both the baby's blood and the maternal milk. We hypothesize that high doses of glibenclamide in the mother led to transplacental passage of the drug and overstimulation of fetal β-cells, which resulted in severe hyperinsulinemic hypoglycemia in the neonate (who did not carry the mutation) and contributed to fetal macrosomia. We suggest that glibenclamide (and other SUs) should be avoided in mothers with PNDM if the baby does not carry the mutation or if prenatal screening has not been performed, while glibenclamide may be beneficial when the fetus is a PNDM carrier. | 25,231,897 | [
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Each degree of glucose intolerance in pregnancy predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum. | Glucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes mellitus (T2DM) that is proportional to the severity of antepartum dysglycemia (i.e., highest in women with gestational diabetes mellitus [GDM], followed by those with milder dysglycemia). However, the pathophysiologic changes driving this risk are not known. Thus, we evaluated the longitudinal changes in β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum after gestational dysglycemia. A total of 337 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at 3 months, 1 year, and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (GIGT; n = 60); abnormal GCT, followed by normal glucose tolerance (NGT) on the OGTT (abnormal GCT NGT; n = 96); and normal GCT with NGT (n = 76). At each of 3 months, 1 year, and 3 years postpartum, the prevalence of glucose intolerance increased from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P < 0.001), whereas β-cell function, assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2), and insulin sensitivity (Matsuda index), progressively decreased across the groups (all P < 0.002). Each group predicted distinct trajectories of ISSI-2, Matsuda index, and fasting and 2-h glucose (all P < 0.001). Notably, GDM, GIGT, and abnormal GCT NGT predicted varying rates of declining β-cell function and insulin sensitivity, as well as rising glycemia, compared with normal GCT NGT. Each degree of gestational glucose intolerance predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum that drive their differential risk of future T2DM. | 25,231,898 | [
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Comprehensive phosphoproteome analysis unravels the core signaling network that initiates the earliest synapse pathology in preclinical Alzheimer's disease brain. | Using a high-end mass spectrometry, we screened phosphoproteins and phosphopeptides in four types of Alzheimer's disease (AD) mouse models and human AD postmortem brains. We identified commonly changed phosphoproteins in multiple models and also determined phosphoproteins related to initiation of amyloid beta (Aβ) deposition in the mouse brain. After confirming these proteins were also changed in and human AD brains, we put the proteins on experimentally verified protein-protein interaction databases. Surprisingly, most of the core phosphoproteins were directly connected, and they formed a functional network linked to synaptic spine formation. The change of the core network started at a preclinical stage even before histological Aβ deposition. Systems biology analyses suggested that phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS) by overactivated kinases including protein kinases C and calmodulin-dependent kinases initiates synapse pathology. Two-photon microscopic observation revealed recovery of abnormal spine formation in the AD model mice by targeting a core protein MARCKS or by inhibiting candidate kinases, supporting our hypothesis formulated based on phosphoproteome analysis. | 25,231,903 | [
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Childhood consequences of maternal obesity and excessive weight gain during pregnancy. | Obesity is a major public health concern. In western countries, the prevalence of obesity in pregnant women has strongly increased, with reported prevalence rates reaching 30%. Also, up to 40% of women gain an excessive amount of weight during pregnancy. Recent observational studies and meta-analyses strongly suggest long-term impact of maternal obesity and excessive weight gain during pregnancy on adiposity, cardiovascular and respiratory related health outcomes in their children. These observations suggest that maternal adiposity during pregnancy may program common health problems in the offspring. Currently, it remains unclear whether the observed associations are causal, or just reflect confounding by family-based sociodemographic or lifestyle-related factors. Parent-offspring studies, sibling comparison studies, Mendelian randomization studies and randomized trials can help to explore the causality and underlying mechanisms. Also, the potential for prevention of common diseases in future generations by reducing maternal obesity and excessive weight gain during pregnancy needs to be explored. | 25,231,923 | [
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Bimodal oscillations of cyclic nucleotide concentrations in the circadian system of the Madeira cockroach Rhyparobia maderae. | Pigment-dispersing factor (PDF) is the most important coupling factor of the circadian system in insects, comparable to its functional ortholog vasoactive intestinal polypeptide of the mammalian circadian clock. In Drosophila melanogaster, PDF signals via activation of adenylyl cyclases, controlling circadian locomotor activity rhythms at dusk and dawn. In addition, PDF mediates circadian rhythms of the visual system and is involved in entrainment to different photoperiods. We examined whether PDF daytime-dependently elevates cAMP levels in the Madeira cockroach Rhyparobia maderae and whether cAMP mimics PDF effects on locomotor activity rhythms. To determine time windows of PDF release, we searched for circadian rhythms in concentrations of cAMP and its functional opponent cGMP in the accessory medulla (AMe), the insect circadian pacemaker controlling locomotor activity rhythms, and in the optic lobes, as the major input and output area of the circadian clock. Enzyme-linked immunosorbent assays detected PDF-dependent increases of cAMP in optic lobes and daytime-dependent oscillations of cAMP and cGMP baseline levels in the AMe, both with maxima at dusk and dawn. Although these rhythms disappeared at the first day in constant conditions (DD1), cAMP but not cGMP oscillations returned at the second day in constant conditions (DD2). Whereas in light-dark cycles the cAMP baseline level remained constant in other optic lobe neuropils, it oscillated in phase with the AMe at DD2. To determine whether cAMP and cGMP mimic PDF-dependent control of locomotor activity rhythms, both cyclic nucleotides were injected at different times of the circadian day using running-wheel assays. Whereas cAMP injections generated delays at dusk and advances at dawn, cGMP only delayed locomotor activity at dusk. For the first time we found PDF-dependent phase advances at dawn in addition to previously described phase delays at dusk. Thus, we hypothesize that PDF release at dusk and dawn controls locomotor activity rhythms and visual system processing cAMP-dependently. | 25,231,947 | [
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Comparative analysis of MAMP-induced calcium influx in Arabidopsis seedlings and protoplasts. | Rapid transient elevation of cytoplasmic calcium (Ca(2+)) levels in plant cells is an early signaling event triggered by many environmental cues including abiotic and biotic stresses. Cellular Ca(2+) levels and their alterations can be monitored by genetically encoded reporter systems such as the bioluminescent protein, aequorin. Employment of proteinaceous Ca(2+) sensors is usually performed in transgenic lines that constitutively express the reporter construct. Such settings limit the usage of these Ca(2+) biosensors to particular reporter variants and plant genetic backgrounds, which can be a severe constraint in genetic pathway analysis. Here we systematically explored the potential of Arabidopsis thaliana leaf mesophyll protoplasts, either derived from a transgenic apoaequorin-expressing line or transfected with apoaequorin reporter constructs, as a complementary biological resource to monitor cytoplasmic changes of Ca(2+) levels in response to various biotic stress elicitors. We tested a range of endogenous and pathogen-derived elicitors in seedlings and protoplasts of the corresponding apoaequorin-expressing reporter line. We found that the protoplast system largely reflects the Ca(2+) signatures seen in intact transgenic seedlings. Results of inhibitor experiments including the calculation of IC50 values indicated that the protoplast system is also suitable for pharmacological studies. Moreover, analyses of Ca(2+)signatures in mutant backgrounds, genetic complementation of the mutant phenotypes and expression of sensor variants targeted to different subcellular localizations can be readily performed. Thus, in addition to the prevalent use of seedlings, the leaf mesophyll protoplast setup represents a versatile and convenient tool for the analysis of Ca(2+) signaling pathways in plant cells. | 25,231,962 | [
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Whole-plant growth and N utilization in transgenic rice plants with increased or decreased Rubisco content under different CO2 partial pressures. | Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) strongly limits photosynthesis at lower CO2 concentration [CO2] whereas [corrected] Rubisco limitation is cancelled by elevated [CO2]. Therefore, increase or reduction in Rubisco content by transformation with a sense or an antisense RBCS construct are expected to alter the biomass production under different CO2 levels. RBCS-sense (125% Rubisco of wild-type) and -antisense (35% Rubisco of wild-type) rice (Oryza sativa L.) plants were grown for 63 days at three different CO2 levels: low [CO2] (28 Pa), normal [CO2] (40 Pa) and elevated [CO2] (120 Pa). The biomass of RBCS-sense plants was 32% and 15% greater at low [CO2] and normal [CO2] than that of the wild-type plants, respectively, but did not differ at elevated [CO2]. Conversely, the biomass of RBCS-antisense plants was the smallest at low [CO2]. Thus, overproduction of Rubisco was effective for biomass production at low [CO2]. Greater biomass production at low [CO2] in RBCS-sense plants was caused by an increase in the net assimilation rate, and associated with an increase in the amount of N uptake. Furthermore, Rubisco overproduction in RBCS-sense plants was also promoted at low [CO2]. Although it seems that low [CO2]-growth additionally stimulates the effect of RBCS overexpression, such a phenomenon observed at low [CO2] was mediated through an increase in total leaf N content. Thus, the dependence of the growth improvement in RBCS-sense rice on growth [CO2] was closely related to the degree of Rubisco overproduction which was accompanied not only by leaf N content but also by whole plant N content. | 25,231,963 | [
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Ultraviolet-B radiation and water deficit interact to alter flavonol and anthocyanin profiles in grapevine berries through transcriptomic regulation. | UV-B radiation and water deficit may trigger flavonol and anthocyanin biosynthesis in plant tissues. In addition, previous research has showed strong qualitative effects on grape berry skin flavonol and anthocyanin profiles in response to UV-B and water deficit. The aim of this study is to identify the mechanisms leading to quantitative and qualitative changes in flavonol and anthocyanin profiles, in response to separate and combined UV-B and water deficit. Grapevines (Vitis vinifera L. cv. Tempranillo) were exposed to three levels of UV-B radiation (0, 5.98 and 9.66 kJ m(-2) day(-1)) and subjected to two water regimes. A strong effect of UV-B on flavonol and anthocyanin biosynthesis was found, resulting in an increased anthocyanin concentration and a change in their profile. Concomitantly, two key biosynthetic genes (FLS1 and UFGT) were up-regulated by UV-B, leading to increased flavonol and anthocyanin skin concentration. Changes in flavonol and anthocyanin composition were explained to a large extend by transcript levels of F3'H, F3'5'H and OMT2. A significant interaction between UV-B and water deficit was found in the relative abundance of 3'4' and 3'4'5' substituted flavonols, but not in their anthocyanin homologues. The ratio between 3'4'5' and 3'4' substituted flavonols was linearly related to the ratios of F3'5'H and FLS1 transcription, two steps up-regulated independently by water deficit and UV-B radiation, respectively. Our results indicate that changes in flavonol profiles in response to environmental conditions are not only a consequence of changes in the expression of flavonoid hydroxylases; but also the result of the competition of FLS, F3'5'H and F3'H enzymes for the same flavonol substrates. | 25,231,967 | [
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Structure and function of REP34 implicates carboxypeptidase activity in Francisella tularensis host cell invasion. | Francisella tularensis is the etiological agent of tularemia, or rabbit fever. Although F. tularensis is a recognized biothreat agent with broad and expanding geographical range, its mechanism of infection and environmental persistence remain poorly understood. Previously, we identified seven F. tularensis proteins that induce a rapid encystment phenotype (REP) in the free-living amoeba, Acanthamoeba castellanii. Encystment is essential to the pathogen's long term intracellular survival in the amoeba. Here, we characterize the cellular and molecular function of REP34, a REP protein with a mass of 34 kDa. A REP34 knock-out strain of F. tularensis has a reduced ability to both induce encystment in A. castellanii and invade human macrophages. We determined the crystal structure of REP34 to 2.05-Å resolution and demonstrate robust carboxypeptidase B-like activity for the enzyme. REP34 is a zinc-containing monomeric protein with close structural homology to the metallocarboxypeptidase family of peptidases. REP34 possesses a novel topology and substrate binding pocket that deviates from the canonical funnelin structure of carboxypeptidases, putatively resulting in a catalytic role for a conserved tyrosine and distinct S1' recognition site. Taken together, these results identify REP34 as an active carboxypeptidase, implicate the enzyme as a potential key F. tularensis effector protein, and may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. | 25,231,992 | [
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NRF2/long noncoding RNA ROR signaling regulates mammary stem cell expansion and protects against estrogen genotoxicity. | Long noncoding RNAs (lncRNAs) have emerged as key regulators of gene expression in embryonic stem cell (ESC) self-renewal and differentiation. In ESCs, lncRNAs are regulated at the genetic level via transcription factor binding to lncRNA gene promoters. Here we demonstrate that the key cytoprotective transcription factor NRF2 controls lncRNA expression in mammary stem cells. By profiling lncRNAs in wild-type and NRF2 knockdown mammary stem cells, we demonstrate that the lncRNA ROR, a regulator of embryonic stem cell pluripotency, is overexpressed upon NRF2 knockdown. We performed promoter analyses and examined predicted NRF2 binding elements in the ROR promoter using luciferase reporter constructs of a ROR promoter deletion series. Our studies revealed that NRF2 binds to two specific NRF2 response elements flanking the ROR promoter and that these two NRF2 response elements are equally important to suppress ROR transcription. In addition, we identified associated H3K27me3 chromatin modification and EZH2 binding at the ROR promoter that was dependent on NRF2 binding. We observed that NRF2 knockdown or ROR overexpression leads to increased stem cell self-renewal in mammary stem cells. Furthermore, we demonstrate Nrf2 regulation of the mammary stem cell population in vivo. These observations provide further evidence for the critical role of NRF2 in maintaining normal stem cell subpopulations in mammary epithelium. | 25,231,996 | [
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Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data. | Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare the efficacy of six versus fewer planned cycles of platinum-based chemotherapy. All randomised trials comparing six versus fewer planned cycles of first-line platinum-based chemotherapy for patients with advanced non-small-cell lung cancer were eligible for inclusion in this systematic review and meta-analysis. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients with an objective response, and toxicity. Statistical analyses were by intention-to-treat, stratified by trial. Overall survival and progression-free survival were compared by log-rank test. The proportion of patients with an objective response was compared with a Mantel-Haenszel test. Prespecified analyses explored effect variations by trial and patient characteristics. Five eligible trials were identified; individual patient data could be collected from four of these trials, which included 1139 patients-568 of whom were assigned to six cycles, and 571 to three cycles (two trials) or four cycles (two trials). Patients received cisplatin (two trials) or carboplatin (two trials). No evidence indicated a benefit of six cycles of chemotherapy on overall survival (median 9·54 months [95% CI 8·98-10·69] in patients assigned to six cycles vs 8·68 months [8·03-9·54] in those assigned to fewer cycles; hazard ratio [HR] 0·94 [95% CI 0·83-1·07], p=0·33) with slight heterogeneity between trials (p=0·076; I(2)=56%). We recorded no evidence of a treatment interaction with histology, sex, performance status, or age. Median progression-free survival was 6·09 months (95% CI 5·82-6·87) in patients assigned to six cycles and 5·33 months (4·90-5·62) in those assigned to fewer cycles (HR 0·79, 95% CI 0·68-0·90; p=0·0007), and 173 (41·3%) of 419 patients assigned to six cycles and 152 (36·5%) of 416 patients assigned to three or four cycles had an objective response (p=0·16), without heterogeneity between the four trials. Anaemia at grade 3 or higher was slightly more frequent with a longer duration of treatment: 12 (2·9%) of 416 patients assigned to three-to-four cycles and 32 (7·8%) of 411 patients assigned to six cycles had severe anaemia. Six cycles of first-line platinum-based chemotherapy did not improve overall survival compared with three or four courses in patients with advanced non-small-cell lung cancer. Our findings suggest that fewer than six planned cycles of chemotherapy is a valid treatment option for these patients. None. | 25,232,001 | [
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TBC1D9B functions as a GTPase-activating protein for Rab11a in polarized MDCK cells. | Rab11a is a key modulator of vesicular trafficking processes, but there is limited information about the guanine nucleotide-exchange factors and GTPase-activating proteins (GAPs) that regulate its GTP-GDP cycle. We observed that in the presence of Mg(2+) (2.5 mM), TBC1D9B interacted via its Tre2-Bub2-Cdc16 (TBC) domain with Rab11a, Rab11b, and Rab4a in a nucleotide-dependent manner. However, only Rab11a was a substrate for TBC1D9B-stimulated GTP hydrolysis. At limiting Mg(2+) concentrations (<0.5 mM), Rab8a was an additional substrate for this GAP. In polarized Madin-Darby canine kidney cells, endogenous TBC1D9B colocalized with Rab11a-positive recycling endosomes but less so with EEA1-positive early endosomes, transferrin-positive recycling endosomes, or late endosomes. Overexpression of TBC1D9B, but not an inactive mutant, decreased the rate of basolateral-to-apical IgA transcytosis--a Rab11a-dependent pathway--and shRNA-mediated depletion of TBC1D9B increased the rate of this process. In contrast, TBC1D9B had no effect on two Rab11a-independent pathways--basolateral recycling of the transferrin receptor or degradation of the epidermal growth factor receptor. Finally, expression of TBC1D9B decreased the amount of active Rab11a in the cell and concomitantly disrupted the interaction between Rab11a and its effector, Sec15A. We conclude that TBC1D9B is a Rab11a GAP that regulates basolateral-to-apical transcytosis in polarized MDCK cells. | 25,232,007 | [
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A1 adenosine receptor-stimulated exocytosis in bladder umbrella cells requires phosphorylation of ADAM17 Ser-811 and EGF receptor transactivation. | Despite the importance of ADAM17-dependent cleavage in normal biology and disease, the physiological cues that trigger its activity, the effector pathways that promote its function, and the mechanisms that control its activity, particularly the role of phosphorylation, remain unresolved. Using native bladder epithelium, in some cases transduced with adenoviruses encoding small interfering RNA, we observe that stimulation of apically localized A1 adenosine receptors (A1ARs) triggers a Gi-Gβγ-phospholipase C-protein kinase C (PKC) cascade that promotes ADAM17-dependent HB-EGF cleavage, EGFR transactivation, and apical exocytosis. We further show that the cytoplasmic tail of rat ADAM17 contains a conserved serine residue at position 811, which resides in a canonical PKC phosphorylation site, and is phosphorylated in response to A1AR activation. Preventing this phosphorylation event by expression of a nonphosphorylatable ADAM17(S811A) mutant or expression of a tail-minus construct inhibits A1AR-stimulated, ADAM17-dependent HB-EGF cleavage. Furthermore, expression of ADAM17(S811A) in bladder tissues impairs A1AR-induced apical exocytosis. We conclude that adenosine-stimulated exocytosis requires PKC- and ADAM17-dependent EGFR transactivation and that the function of ADAM17 in this pathway depends on the phosphorylation state of Ser-811 in its cytoplasmic domain. | 25,232,008 | [
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Polycystic kidneys and GM2 gangliosidosis-like disease in neonatal springboks (Antidorcas marsupialis). | Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks (Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008-2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 μm in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 μm in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies. | 25,232,033 | [
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Micronuclei and nuclear abnormalities in buccal mucosa cells in patients with anorexia and bulimia nervosa. | The aim of this study is to assess the frequency of micronucleated cell (MNC) and nuclear abnormalities (NA) in the buccal mucosa cells of females with anorexia nervosa (AN) or bulimia nervosa (BN), compared with healthy women. Individuals with AN and BN have inadequate feeding and compensatory behaviour to avoid weight gain. These behaviours can cause extreme body stress, thereby inducing DNA damage. In a cross-sectional study, we assessed the frequency of MNC and NA in the buccal mucosa cells of female participants with AN or BN. All of these patients had been admitted to a private clinic for the treatment of eating disorders after diagnosis with AN (n = 10) or BN (n = 7) according to the DSM-IV. Age-matched healthy female participants (n = 17) composed the control group. Oral mucosa samples were collected, fixed, stained by aceto-orcein/fast green and microscopically examined. Normal cells, MNC and NAs were counted within a 2000 cell sample. The results were analyzed with the Kruskal-Wallis and Mann-Whitney tests. Differences were observed in the frequency of MNC in healthy females (1.2±0.9) versus that of patients with AN (3.4±1.5) (P < 0.0001) and BN (4.1±2.2) (P < 0.001). No differences were found among these groups in terms of NA. AN and BN are related to the loss of genetic material through chromosomal fractures and/or damage to the mitotic spindle (i.e. possibly a result of a deficiency in DNA precursors). Self-imposed compensatory behaviours in AN and BN, such as severe food restriction, potential malnutrition, vomiting, use of diuretics and laxatives and acute exhaustive exercise, are possible inducers of MNC and genotoxic damage. Of these compensatory behaviours, only vomiting has not been linked to genotoxic damage. This is the first report in women with BN, which should be studied in the future. | 25,232,046 | [
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Magnetic field-driven induction of ZENK in the trigeminal system of pigeons (Columba livia). | Magnetoreception remains one of the few unsolved mysteries in sensory biology. The upper beak, which is innervated by the ophthalmic branch of the trigeminal nerve (V1), has been suggested to contain magnetic sensors based on ferromagnetic structures. Recently, its existence in pigeons has been seriously challenged by studies suggesting that the previously described iron-accumulations are macrophages, not magnetosensitive nerve endings. This raised the fundamental question of whether V1 is involved in magnetoreception in pigeons at all. We exposed pigeons to either a constantly changing magnetic field (CMF), to a zero magnetic field providing no magnetic information, or to CMF conditions after V1 was cut bilaterally. Using immediate early genes as a marker of neuronal responsiveness, we report that the trigeminal brainstem nuclei of pigeons, which receive V1 input, are activated under CMF conditions and that this neuronal activation disappears if the magnetic stimuli are removed or if V1 is cut. Our data suggest that the trigeminal system in pigeons is involved in processing magnetic field information and that V1 transmits this information from currently unknown, V1-associated magnetosensors to the brain. | 25,232,052 | [
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Recurrence of hip instability after reconstructive surgery in patients with cerebral palsy. | Hip instability can cause major problems in children with cerebral palsy, although good outcomes of hip reconstructive surgery for hip instability have been reported. In the present study, we investigated the recurrence of hip instability after reconstructive surgery and the factors influencing this recurrence in patients with cerebral palsy. We examined consecutive patients with hip instability related to cerebral palsy who had undergone hip reconstructive surgery including femoral varus derotational osteotomy. The neck-shaft angle, head-shaft angle, and migration percentage were measured at each postoperative follow-up evaluation. For each Gross Motor Function Classification System (GMFCS) level, annual changes in radiographic indices were adjusted for multiple factors with use of a linear mixed model, with sex as the fixed effect and laterality and each subject as the random effects. A total of 144 hips (seventy-six patients) were included in this study, and 845 radiographs were evaluated. The GMFCS level was II or III for twelve patients, IV for thirty, and V for thirty-four. The neck-shaft angle showed no significant change in the patients with GMFCS level II or III (p = 0.425), IV (p = 0.106), or V (p = 0.972). The head-shaft angle showed a significant change in those with GMFCS level IV (p = 0.008) but not in those with level II or III (p = 0.201) or V (p = 0.591). The migration percentage did not change significantly in patients with GMFCS level II or III (p = 0.742), but it increased significantly by 2.0% per year (p < 0.001) in patients with GMFCS level IV and by 3.5% per year (p = 0.003) in those with level V. Periodic monitoring and follow-up for the recurrence of hip instability is important in patients with cerebral palsy and a GMFCS level of IV or V. | 25,232,076 | [
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Emerging multidrug resistance of methicillin-resistant Staphylococcus aureus in hand infections. | Methicillin-resistant Staphylococcus aureus has been the most commonly identified pathogen in hand infections at urban centers, but the evolving antibiotic sensitivity profiles of methicillin-resistant Staphylococcus aureus are not known. The purposes of this study are to determine if multidrug resistance in methicillin-resistant Staphylococcus aureus is emerging and to provide current recommendations for empiric antibiotic selection for hand infections in endemic regions. An eight-year longitudinal, retrospective chart review was performed on all culture-positive hand infections encountered by an urban hospital from 2005 to 2012. The proportions of all major organisms were calculated for each year. Methicillin-resistant Staphylococcus aureus infections were additionally analyzed for antibiotic sensitivity. A total of 683 culture-positive hand infections were identified. Overall, methicillin-resistant Staphylococcus aureus grew on culture in 49% of cases; the annual incidence peaked at 65% in 2007. Over the study period, methicillin-resistant Staphylococcus aureus was universally resistant to penicillin, oxacillin, and ampicillin. Clindamycin resistance significantly increased, approaching 20% by 2012 (p = 0.02). Levofloxacin resistance linearly increased from 12% to 50% (p < 0.01). Resistance to trimethoprim-sulfamethoxazole, tetracycline, gentamicin, and moxifloxacin was only sporadically observed. Resistance to vancomycin, daptomycin, linezolid, and rifampin was not observed. Significant increases in resistance to clindamycin and levofloxacin were observed in recent years, and empiric therapy with these drugs may have limited efficacy, especially in urban centers. Hand infections caused by methicillin-resistant Staphylococcus aureus may be developing increasing resistance to clindamycin and levofloxacin in recent years. This longitudinal study examines the effectiveness of a variety of antibiotics to methicillin-resistant Staphylococcus aureus. | 25,232,077 | [
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Factors predicting complication and reoperation rates following surgical fixation of proximal humeral fractures. | The purpose of this study was to report complication and reoperation rates following non-arthroplasty fixation of shoulder fractures determined on the basis of observational, population-based data from all inpatient admissions in California over an eleven-year period. Records from all inpatient hospital discharges and subsequent readmissions related to operative non-arthroplasty treatment of proximal humeral fractures were obtained for patients in California from December 1994 through December 2005. These admissions were evaluated to identify patient and hospital characteristics associated with short and intermediate-term complications (within and after ninety days, respectively) as well as reoperation rates. Procedures performed included open reduction and internal fixation in 9254 patients, closed reduction and internal fixation in 1903 patients, and internal fixation without reduction in 302 patients. The short-term complications included mortality in 401 patients (3.5%), which was associated with a higher Charlson comorbidity index (odds ratio [OR] = 1.5, p < 0.001) and male sex (OR = 1.7, p < 0.001); and pulmonary embolism in sixty patients (0.5%), which was associated with male sex (OR = 2.2, p = 0.007) and patient age of seventy-five years or older (OR = 3.6, p = 0.001). Intermediate-term reoperations included conversion to hemiarthroplasty in 174 patients (1.5%); and conversion to total shoulder arthroplasty in eight patients (0.07%), which was associated with an age of fifty to sixty-four years (hazard ratio = 2.8, p = 0.007). Overall, an age of sixty-five years or older, male sex, residence in an area with an income in the lowest two quintiles, and the presence of preexisting comorbidities were associated with elevated risks of short-term complications but not of intermediate-term conversion to arthroplasty. The ninety-day revision rate was 5.3%. Surgical fixation of proximal humeral fractures has a low complication and mortality profile. The data provided in this study can serve in counseling patients about risks associated with operative fixation of displaced proximal humeral fractures. | 25,232,078 | [
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Regulation of synaptic extracellular matrix composition is critical for proper synapse morphology. | Synapses are surrounded by a layer of extracellular matrix (ECM), which is instrumental for their development and maintenance. ECM composition is dynamically controlled by proteases, but how the precise composition of the ECM affects synaptic morphology is largely unknown. Through an unbiased forward genetic screen, we found that Caenorhabditis elegans gon-1, a conserved extracellular ADAMTS protease, is required for maintaining proper synaptic morphology at the neuromuscular junction. In gon-1 mutants, once synapse formation is complete, motor neuron presynaptic varicosities develop into large bulbous protrusions that contain synaptic vesicles and active zone proteins. A concomitant overgrowth of postsynaptic muscle membrane is found in close apposition to presynaptic axonal protrusions. Mutations in the muscle-specific, actin-severing protein cofilin (unc-60) suppress the axon phenotype, suggesting that muscle outgrowth is necessary for presynaptic protrusions. gon-1 mutants can also be suppressed by loss of the ECM components collagen IV (EMB-9) and fibulin (FBL-1). We propose that GON-1 regulates a developmental switch out of an initial "pro-growth" phase during which muscle arms grow out and form synapses with motor neuron axons. We postulate that this switch involves degradation or reorganization of collagen IV (EMB-9), whereas FBL-1 opposes GON-1 by stabilizing EMB-9. Our results describe a mechanism for regulating synaptic ECM composition and reveal the importance of precise ECM composition for neuronal morphology and synapse integrity. | 25,232,106 | [
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The recurrent case for the Renshaw cell. | Although Renshaw cells (RCs) were discovered over half a century ago, their precise role in recurrent inhibition and ability to modulate motoneuron excitability have yet to be established. Indirect measurements of recurrent inhibition have suggested only a weak modulatory effect but are limited by the lack of observed motoneuron responses to inputs from single RCs. Here we present dual recordings between connected RC-motoneuron pairs, performed on mouse spinal cord. Motoneuron responses demonstrated that Renshaw synapses elicit large inhibitory conductances and show short-term potentiation. Anatomical reconstruction, combined with a novel method of quantal analysis, showed that the strong inhibitory input from RCs results from the large number of synaptic contacts that they make onto individual motoneurons. We used the NEURON simulation environment to construct realistic electrotonic models, which showed that inhibitory conductances from Renshaw inputs exert considerable shunting effects in motoneurons and reduce the frequency of spikes generated by excitatory inputs. This was confirmed experimentally by showing that excitation of a single RC or selective activation of the recurrent inhibitory pathway to generate equivalent inhibitory conductances both suppress motoneuron firing. We conclude that recurrent inhibition is remarkably effective, in that a single action potential from one RC is sufficient to silence a motoneuron. Although our results may differ from previous indirect observations, they underline a need for a reevaluation of the role that RCs perform in one of the first neuronal circuits to be discovered. | 25,232,126 | [
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Invalid controls undermine conclusions of FDA studies. | This issue of Toxicological Sciences features several exciting changes: a redesigned cover, revised category subheadings, and this "Look Inside ToxSci" feature. Together with my esteemed colleagues in the field of green chemistry, we have outlined some exciting opportunities for the field of toxicology in the editorial on green chemistry and toxicology. There are insightful articles on the regulatory challenges regarding mixtures that are being addressed by the European Union and on risk assessment of carbon nanotubes. In the past, we have highlighted a single article from each issue. It has become increasingly difficult to select just one article from the volume of high quality work, so beginning this month we will highlight multiple articles in each issue here in "Look Inside ToxSci." From solvents, pesticides, and nanoparticles to the microbiome, the highlighted articles span the breadth of our field. Of course, this issue contains something that will never change; our raison d'etre …the best original research in the field of toxicology. -Gary W. Miller. | 25,232,149 | [
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Multilocus sequence typing (MLST) and whole-genome MLST of Campylobacter jejuni isolates from human infections in three districts during a seasonal peak in Finland. | A total of 95 human Campylobacter jejuni isolates acquired from domestic infections and collected from three districts in Finland during the seasonal peak (June to September) in 2012 were analyzed by PCR-based multilocus sequence typing (MLST) and by whole-genome sequencing (WGS). Four predominant sequence types (STs) were detected among the isolates: ST-45 (21%) and ST-230 (14%, ST-45 clonal complex [CC]), ST-267 (21%, ST-283 CC), and ST-677 (19%, ST-677 CC). In districts 1 and 3, most of the infections occurred from early July to the middle of August, with a peak at weeks 29 to 31, but in district 2, the infections were dispersed more evenly throughout 3 months (June to August). WGS data were used for further whole-genome MLST (wgMLST) analyses of the isolates representing the four common STs. Shared loci of the isolates within each ST were analyzed as distance matrices of allelic profiles by the neighbor-net algorithm. The highest allelic variations (>400 different alleles) were detected between different clusters of ST-45 isolates (1,121 shared loci), while ST-230 (1,264 shared loci), ST-677 (1,169 shared loci), and ST-267 isolates (1,217 shared loci) were less diverse with the clusters differing by <40 alleles. Closely related isolates showing no allelic variation (subclusters) were detected among all four major STs. In some cases, they originated from different districts, suggesting that isolates can be epidemiologically connected and may have the same infection source despite being originally identified as sporadic infections. | 25,232,158 | [
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The fringe benefits of cloning cancer. | A new approach to monitoring tumor clone dynamics (Carreira et al., this issue) uses sequential biopsies and circulating DNA to help optimize treatment in metastatic prostate cancer. | 25,232,174 | [
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EbpA vaccine antibodies block binding of Enterococcus faecalis to fibrinogen to prevent catheter-associated bladder infection in mice. | Enterococci bacteria are a frequent cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infection. Treatment has become increasingly challenging because of the emergence of multiantibiotic-resistant enterococcal strains and their ability to form biofilms on catheters. We identified and targeted a critical step in biofilm formation and developed a vaccine that prevents catheter-associated urinary tract infections in mice. In the murine model, formation of catheter-associated biofilms by Enterococcus faecalis depends on EbpA, which is the minor subunit at the tip of a heteropolymeric surface fiber known as the endocarditis- and biofilm-associated pilus (Ebp). We show that EbpA is an adhesin that mediates bacterial attachment to host fibrinogen, which is released and deposited on catheters after introduction of the catheter into the mouse bladder. Fibrinogen-binding activity resides in the amino-terminal domain of EbpA (EbpA(NTD)), and vaccination with EbpA and EbpA(NTD), but not its carboxyl-terminal domain or other Ebp subunits, inhibited biofilm formation in vivo and protected against catheter-associated urinary tract infection. Analyses in vitro demonstrated that protection was associated with a serum antibody response that blocked EbpA binding to fibrinogen and the formation of a fibrinogen-dependent biofilm on catheters. This approach may provide a new strategy for the prevention of catheter-associated urinary tract infections. | 25,232,179 | [
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Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. | Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whether treatment amplifies previously induced T cell responses or whether it induces new tumor-specific T cell reactivities. Using a combination ultraviolet (UV)-induced peptide exchange and peptide-major histocompatibility complex (pMHC) combinatorial coding, we monitored immune reactivity against a panel of 145 melanoma-associated epitopes in a cohort of patients receiving anti-CTLA-4 treatment. Comparison of pre- and posttreatment T cell reactivities in peripheral blood mononuclear cell samples of 40 melanoma patients demonstrated that anti-CTLA-4 treatment induces a significant increase in the number of detectable melanoma-specific CD8 T cell responses (P = 0.0009). In striking contrast, the magnitude of both virus-specific and melanoma-specific T cell responses that were already detected before start of therapy remained unaltered by treatment (P = 0.74). The observation that anti-CTLA-4 treatment induces a significant number of newly detected T cell responses-but only infrequently boosts preexisting immune responses-provides strong evidence for anti-CTLA-4 therapy-enhanced T cell priming as a component of the clinical mode of action. | 25,232,180 | [
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Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases. | A 64-year-old man was admitted to the Sun Yat-Sen University Cancer Center with chief complaints of recurrent abdominal pain and diarrhea for about 3 years and with a history of surgical repair for intestinal perforation owing to stress ulcer. Positron emission tomography (PET)/computed tomography (CT) demonstrated a primary tumor on the pancreatic tail with multifocal liver metastases. Pathological and immunohistochemistry staining revealed the lesion to be a pancreatic neuroendocrine tumor (pNET). According to the latest World Health Organization (WHO, 2013) classification, the tumor was classified as stage IV functional G1 pNET. After referral to the multidisciplinary treatment board (MDT), the patient was started on periodic dose of omeprazole, somatostatin analogues and Interferon α (IFNα) and had scanning follow-ups. Based upon the imaging results, CT-guided radioactive iodine-125 ((125)I) seeds implantation therapy, radiofrequency ablation therapy (RFA) or microwave ablation technique were chosen for the treatment of the primary tumor. Transarterial chemoembolization (TACE), RFA and microwave ablation techniques were decided upon for liver metastases. The patient showed beneficial response to the treatment with clinically manageable low-grade side effects and attained partial remission (RECIST criteria) with a good quality of life. | 25,232,226 | [
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Cell-type specificity of β-actin expression and its clinicopathological correlation in gastric adenocarcinoma. | To investigate cell type specific distribution of β-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters. β-actin is a housekeeping gene, frequently used as loading control, but, differentially expresses in cancer. In gastric cancer, an overall increased expression of β-actin has been reported using tissue disruptive techniques. At present, no histological data is available to indicate its cell type-specific expression and distribution pattern. In the present study, we analyzed β-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry (IHC), a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Correlation of β-actin level with clinicopathological parameters was done using univariate analysis. The results of this study showed significant overexpression, at both mRNA and protein level in tumor tissues as confirmed by RT-PCR (1.47 ± 0.13 vs 2.36 ± 0.16; P < 0.001) and western blotting (1.92 ± 0.26 vs 2.88 ± 0.32; P < 0.01). IHC revealed that β-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues. Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal (2.46 ± 0.13 vs 5.92 ± 0.23, P < 0.001), as well as, in tumor tissues (2.79 ± 0.24 vs 6.71 ± 0.14, P < 0.001). Further, comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpress β-actin in tumor tissues, however, significant difference was observed only in inflammatory cells (5.92 ± 0.23 vs 6.71 ± 0.14, P < 0.01). Moreover, combined expression in epithelial and inflammatory cells also showed significant increase (4.19 ± 0.15 vs 4.75 ± 0.14, P < 0.05) in tumor tissues. In addition, univariate analysis showed a positive correlation of β-actin level of inflammatory cells with tumor grade (P < 0.05) while epithelial cells exhibited negative correlation (P > 0.05). In gastric cancer, β-actin showed an overall higher expression predominantly contributed by inflammatory or tumor infiltrating immune cells of the tissue microenvironment and correlates with tumor grade. | 25,232,253 | [
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Helicobacter pylori infection in Mongolian gerbils does not initiate hematological diseases. | To investigate whether Helicobacter pylori (H. pylori) infection contributes to idiopathic thrombocytopenic purpura (ITP) or iron-deficiency anemia (IDA) onset in gerbils. A total of 135 Mongolian gerbils were randomly divided into two groups: an H. pylori infection group and a control group. Both groups were fed the same diet and the same amount of food. Each group was then divided into three subgroups, which were sacrificed at 6, 12, or 18 mo for analysis. At each time point, arterial blood was collected from the abdominal aorta and a complete blood cell count was analyzed in the clinical laboratory in the First Affiliated Hospital of Nanchang University. There were no significant differences in platelet counts (938.00 ± 270.27/L vs 962.95 ± 162.56 × 10(9)/L), red blood cell counts (8.11 ± 1.25/L vs 8.44 ± 1.48 × 10(12)/L), or hemoglobin levels (136.9 ± 8.76 g/L vs 123.21 ± 18.42 g/L) between the control and the H. pylori groups, respectively, at 18 mo. With the exception of the mean corpuscular volume (MCV), all other indicators, including white blood cell counts, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, mean platelet volume, platelet distribution width, lymphocyte count, and lymphocyte count percentage, showed no significant differences between the control and H. pylori infection groups at each time point. The MCV in the H. pylori infection group (52.32 f/L ± 2.86 f/L) was significantly lower than the control group (55.63 ± 1.89 f/L) at 18 mo (P = 0.005), though no significant differences were observed at 6 (54.40 ± 2.44 f/L vs 53.30 ± 1.86 f/L) or 12 mo (53.73 ± 2.31 f/L vs 54.80 ± 3.34 f/L). A single H. pylori infection is insufficient to cause onset of ITP or IDA and other factors may be required for disease onset. | 25,232,266 | [
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Osteonecrosis of the femoral head with collapsed medial lesion. | A 60-year-old female experienced the gradual onset of left hip pain without any triggering event. Radiographs showed vertical sclerosis in the center of the femoral head and the lesion inside the boundary demonstrated diffuse bony sclerosis. No collapse was observed at the weight-bearing portion on radiograph. However, computed tomography showed a subchondral collapse at the medial lesion. On T2-weighted magnetic resonance imaging, the necrotic lesion showed diffuse high-intensity signals that indicated a prominent repair process. Bone biopsy diagnosed osteonecrosis with associated prominent appositional bone and vascular granulation tissue. | 25,232,284 | [
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Stereochemistry and Mechanism of Enzymatic and Non-Enzymatic Hydrolysis of Benzylic <i>sec</i>-Sulfate Esters. | The substrate scope of inverting alkylsulfatase Pisa1 was extended towards benzylic <isec</i-sulfate esters by suppression of competing non-enzymatic autohydrolysis by addition of dimethyl sulfoxide as co-solvent. Detailed investigation of the mechanism of autohydrolysis in <sup18</supO-labeled buffer by using an enantiopure <isec</i-benzylic sulfate ester as substrate revealed that from the three possible pathways (i) inverting S<subN</sub2-type nucleophilic attack of [OH<sup-</sup] at the benzylic carbon represents the major pathway, whereas (ii) S<subN</sub1-type formation of a planar benzylic carbenium ion leading to racemization was a minor event, and (iii) Retaining S<subN</sub2-type nucleophilic attack at sulfur took place at the limits of detection. The data obtained are interpreted by analysis of Hammett constants of <imeta</i substituents. | 25,232,289 | [
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MEFV gene mutations in Egyptian children with Henoch-Schonlein purpura. | Due to an increased frequency of vasculitis in FMF patients, many investigators have studied MEFV mutations in patients with HSP. The aim of the study is to investigate the frequency and clinical significance of MEFV mutations in Egyptian children with Henoch-Schonlein purpura (HSP). Investigating MEFV mutations in controls may help in estimating the prevalence of MEFV mutation carrier rate in Egyptian children. The study enrolled 90 individuals, sixty children with Henoch-Schonlein purpura (HSP), together with 30 sex-and age-matched apparently healthy controls. The entire study group was screened for 12 common MEFV mutations using a reverse hybridization assay of biotinylated PCR products. Patients with HSP had a significantly higher frequency of MEFV mutations (61.7%), when compared to the apparently healthy control population (36.7%). V726A was the most frequent mutation with an allelic frequency of 10.8%. Ninety- one percent of patients with MEFV mutations were heterozygous for one mutation, while 8.1% had a compound heterozygous MEFV gene mutations. The mutation V726A, followed by E148Q, were the leading mutations, present in 16.6% and in 13.3% of controls. MEFV mutations may be related to HSP susceptibility in children. The mutations were not associated with any clinical and laboratory manifestations. Screening for MEFV mutations in larger number of HSP children may be beneficial to evaluate any possible relationship between certain types of MEFV mutations and HSP, and compare the HSP MEFV mutations to the types of MEFV mutations associated with FMF. | 25,232,290 | [
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A case of metastatic bladder cancer in both lungs treated with korean medicine therapy alone. | This case report is aimed to investigate the effects of Korean medicine therapy (KMT) including oral herbal medicine and herb nebulizer therapy in treating metastatic bladder cancer in the lungs. A 74-year-old man was diagnosed with metastatic bladder cancer in both lungs in August 2013. He refused any chemotherapy and was admitted to our hospital in a much progressed state on January 11, 2014. Since then, he was treated with KMT until May 17, 2014. The main oral herbal medicines were Hyunamdan made of heat-processed ginseng, Hangamdan S made of Cordyceps militaris, Panax ginseng radix, Commiphora myrrha, calculus bovis, margarita, Boswellia carteri, Panax notoginseng radix and Cremastra appendiculata tuber, and nebulizer therapy with Soram nebulizer solution made of wild ginseng and Cordyceps sinensis distillate. Their effect was evaluated considering the change of the main symptoms and using serial chest X-ray. The size and number of multiple metastatic nodules in both lungs were markedly decreased and the symptoms had disappeared. These results suggest that KMT can be an effective method to treat metastatic bladder cancer in the lungs. | 25,232,323 | [
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Cynophobic fear adaptively extends peri-personal space. | Peri-personal space (PPS) is defined as the space immediately surrounding our bodies, which is critical in the adaptation of our social behavior. As a space of interaction with the external world, PPS is involved in the control of motor action as well as in the protection of the body. The boundaries of this PPS are known to be flexible but so far, little is known about how PPS boundaries are influenced by unreasonable fear. We hypothesized that unreasonable fear extends the neural representation of the multisensory space immediately surrounding the body in the presence of a feared object, with the aim of expanding the space of protection around the body. To test this hypothesis, we explored the impact of unreasonable fear on the size of PPS in two groups of non-clinical participants: dog-fearful and non-fearful participants. The sensitivity to cynophobia was assessed with a questionnaire. We measured participants' PPS extent in the presence of threatening (dog growling) and non-threatening (sheep bleating) auditory stimuli. The sound stimuli were processed through binaural rendering so that the virtual sound sources were looming toward participants from their rear hemi-field. We found that, when in the presence of the auditory dog stimulus, the PPS of dog-fearful participants is larger than that of non-fearful participants. Our results demonstrate that PPS size is adaptively modulated by cynophobia and suggest that anxiety tailors PPS boundaries when exposed to fear-relevant features. Anxiety, with the exception of social phobia, has rarely been studied as a disorder of social interaction. These findings could help develop new treatment strategies for anxious disorders by involving the link between space and interpersonal interaction in the approach of the disorder. | 25,232,342 | [
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Age-related impairment of pancreatic Beta-cell function: pathophysiological and cellular mechanisms. | The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions. | 25,232,350 | [
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TCPs, WUSs, and WINDs: families of transcription factors that regulate shoot meristem formation, stem cell maintenance, and somatic cell differentiation. | In contrast to somatic mammalian cells, which cannot alter their fate, plant cells can dedifferentiate to form totipotent callus cells and regenerate a whole plant, following treatment with specific phytohormones. However, the regulatory mechanisms and key factors that control differentiation-dedifferentiation and cell totipotency have not been completely clarified in plants. Recently, several plant transcription factors that regulate meristem formation and dedifferentiation have been identified and include members of the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP), WUSCHEL (WUS), and WOUND INDUCED DEDIFFERENTIATION (WIND1) families. WUS and WIND positively control plant cell totipotency, while TCP negatively controls it. Interestingly, TCP is a transcriptional activator that acts as a negative regulator of shoot meristem formation, and WUS is a transcriptional repressor that positively maintains totipotency of the stem cells of the shoot meristem. We describe here the functions of TCP, WUS, and WIND transcription factors in the regulation of differentiation-dedifferentiation by positive and negative transcriptional regulators. | 25,232,356 | [
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The role of photosynthesis and amino acid metabolism in the energy status during seed development. | Seeds are the major organs responsible for the evolutionary upkeep of angiosperm plants. Seeds accumulate significant amounts of storage compounds used as nutrients and energy reserves during the initial stages of seed germination. The accumulation of storage compounds requires significant amounts of energy, the generation of which can be limited due to reduced penetration of oxygen and light particularly into the inner parts of seeds. In this review, we discuss the adjustment of seed metabolism to limited energy production resulting from the suboptimal penetration of oxygen into the seed tissues. We also discuss the role of photosynthesis during seed development and its contribution to the energy status of developing seeds. Finally, we describe the contribution of amino acid metabolism to the seed energy status, focusing on the Asp-family pathway that leads to the synthesis and catabolism of Lys, Thr, Met, and Ile. | 25,232,362 | [
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The Perceived Needs and Availability of Eye Care Services for Older Adults in Long-term Care Facilities. | The objective was to evaluate the eye care services offered to older residents living in long-term care facilities (LTCFs). A questionnaire targeting residents aged ≥65 years was sent to all LTCFs in Quebec. Questions related to the institution's characteristics, demographic data related to residents, oculovisual health of residents and barriers to eye care, eye care services offered within and outside the institution, and degree of satisfaction regarding the eye care services offered to residents. 196/428 (45.8%) LTCFs completed the questionnaire. Participating LTCFs had an average of 97.0 ± 5.1 residents with a mean age of 82.8 ± 3.0 yrs and 69% women. Eye care services were mostly offered outside the institution, on a "per request" basis. The main barriers to eye care were the perception that residents could not cooperate and the lack of eye care professionals. Most LTCFs were satisfied with the eye care services offered to residents. The fact that the LTCFs were satisfied with the eye care services offered to their residents, although it was neither provided on a regular basis nor to all residents, suggests that eye care professionals should take a proactive educational role for improving services to older institutionalized adults. | 25,232,370 | [
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Detection of common carotid artery calcifications on panoramic radiographs: prevalence and reliability. | The aim of this study was to determine the prevalence of common carotid artery calcifications (CCAC) detected by panoramic radiographs (PR) in the population and main risk factors with review of the literature. Furthermore, the reliability of PR was verified to detect these calcifications. CCAC detected on PR was powerful markers for future cardiovascular or cerebrovascular events. We found that the prevalence of CCAC identified by PR may range from 0.43% to 9.4%, depending on the age and lifestyle of the population studied. In individuals with systemic diseases the prevalence was higher than in the general population, reaching up to 38.8%. The radiopaque masses compatible with CCAC identified by PR were more common in women and occurred unilaterally or both sides, without preference for one or the other. According to the literature reviewed PR had low sensitivity and acceptable accuracy for detecting CCAC. We conclude that calcified atheroma in the common carotid artery can be demonstrated in PR, and this is an important tool for early detection of CCAC. However, it is always necessary to refer the patient to a cardiology service to confirm the findings, determine the real extent of the disease and establish its corresponding treatment. | 25,232,373 | [
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Effect of trichostatin a on SGC-7901 gastric cancer cells. | To explore Trichostatin A (TSA) effect on SGC-7901 gastric cancer cells. MTT, fluorescence microscopy, and flow cytometry were used to assess TSA effect on cell growth and apoptosis in SGC-7901. Immunocytochemistry was used to evaluate the expression of acetylated histone H4 in SGC-7901 cells.Gene expression profile was determined by microarray assays. Glycoprotein hormones alpha subunit (CGA) gene and protein expressions in SGC-7901 cells were evaluated by Real-time PCR and Western blot, respectively. In addition, CGA protein levels in gastric adenocarcinoma and normal adjacent tissues were assessed by immunohistochemistry. TSA inhibited SGC-7901 cell growth. In addition, cell proliferation was significantly decreased (P = 0.02) in TSA treatment groups (0.93 ± 0.07) compared with controls (1.15 ± 0.07). Apoptosis related morphological changes, including nuclear chromatin condensation and fluorescence strength, were observed by fluorescence microscopy. These findings corroborated the increased expression of acetylated histone H4 observed in TSA treated cells compared to controls, as determined by immunocytochemistry. Interestingly, treatment of SGC-7901 cells with TSA (75 ng/ml) resulted in CGA gene down-regulation (P = 0.0381). Accordingly, CGA protein levels were decreased in TSA treated SGC-7901 cells. Finally, immunohistochemistry analysis showed that CGA expression was significantly higher in gastric adenocarcinoma tissues than normal adjacent tissues (P = 0.001). TSA induces cell apoptosis and increases the levels of acetylated histone H4 in SGC-7901 cells. In addition, TSA treatment decreases the expression in gastric cancer cells of the CGA gene, which is upregulated in gastric adenocarcinoma tissues. | 25,232,376 | [
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Effects and mechanisms of indol-2,3-dione on atherosclerosis. | Indol-2,3-dione (ISA), a natural substance with clear structure, has been shown to process anti-inflammatory, antioxidant and anti-atherosclerosis activity in vivo. The purpose of this study was to investigate the effect and mechanism of ISA on AS by primary rat cardiac microvascular endothelial cells (rCMEC). rCMEC cells were primary cultured, appraised by cell morphology and immune cell chemical dyeing, and passaged to the 3(rd) generation. The effect of ISA on the activity of rCMEC induced by oxidized low-density lipoprotein (ox-LDL) was detected by MTT method. Then we studied the effect of ISA on the adhesion of monocyte with rCMEC induced by ox-LDL. The secretion of interleutin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by rCMEC were measured by enzyme-linked immunosorbent assay (ELISA) method. Finally the mRNA level of IL-6 and TNF-α of rCMEC were analyzed by real time RT-PCR. Results MTT result indicated that ISA (10(-8)-10(-6) g/L) could inhibit rCMEC injury induced by ox-LDL in a dose-dependent manner (P < 0.05). The adhesion of monocyte with rCMEC induced by ox-LDL was inhibited by ISA in a dose-dependent manner (P < 0.05). The levels of IL-6 and TNF-α of ISA groups were significantly decreased in a dose-dependent manner compared with model group (P < 0.05). The mRNA expressions of IL-6 and TNF-α of ISA groups were also downregulated significantly compared with model group (P < 0.05). Conclusions ISA can prevent atherosclerotic lesion. Its mechanism may be that it can defend against the oxidation damage to rCMEC, inhibit the adhesion of monocyte to rCMEC, and reduce inflammatory secretions of IL-6 and TNF-α. | 25,232,391 | [
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Assessment of ventricular repolarization inhomogeneity in patients with mitral valve prolapse: value of T wave peak to end interval. | Mitral valve prolapse (MVP) has been long known for causing susceptibility for ventricular arrhythmogenesis, and this risk was evaluated by various methods, mostly by using QT interval related measurements on surface electrocardiogram. T wave peak to end (Tp-e) interval is a relatively new marker for ventricular arrhythmogenesis and repolarization heterogeneity. Prolongation of this interval represents a period of potential vulnerability to re-entrant ventricular arrhythmias. However, there is no information available assessing the Tp-e interval and related calculations in patients with MVP. The aim of this study was to assess ventricular repolarization in patients with MVP by using QT, corrected QT (QTc) and Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Electrocardiogram of consecutive 72 patients, who were followed by outpatient clinic because of mitral valve prolapse, were obtained and scanned. Electrocardiograms of age and sex matched 60 healthy control individuals were also gained for comparison. QT, QTc, Tp-e/QT and Tp-e/QTc were calculated. Baseline characteristics were similar in both groups. QT (405.1±64.3 vs. 362.1±39.1; p<0.001), QTc (457.6±44.4 vs. 428.3±44.7; p<0.001), Tp-e (100.2±22.1 vs. 74.6±10.2; p<0.001) and Tp-e/QT (0.24 vs. 0.20; p<0.001) and Tp-e/QTc (0.21 vs. 0.17; p<0.001) were significantly worse in MVP group. Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in MVP patients. Tp-e interval and Tp-e/QT ratio might be a useful marker of cardiovascular morbidity and mortality due to ventricular arrhythmias in patients with MVP. | 25,232,403 | [
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Polymeric immunoglobulin receptor expression is predictive of poor prognosis in glioma patients. | Although there have been recent advances in surgery, radiotherapy, and chemotherapy, the survival of patient with glioma remains poor. Increased expression of polymeric immunoglobulin receptor (pIgR) in tumor tissue has been detected in various cancer forms. However, the clinical relevance of pIgR in glioma remains unclear. The aim of this study was to assess the prognostic value of pIgR in patients with glioma after surgical resection. pIgR expression was evaluated by immunohistochemistry in paraffin-embedded glioma tissues from 146 patients. The relation between pIgR expression and clinicopathologic factors and long-term prognosis in these 146 patients was retrospectively examined. The prognostic significance of negative or positive pIgR exspression in glioma was assessed using Kaplan-Meier survival analysis and log-rank tests. Positive expression of pIgR was statistically significantly associated with poor prognosis of patients with glioma. Our results indicated that pIgR could be a novel predictor for poor prognosis of patients with glioma after surgical resection. | 25,232,405 | [
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Effects of hypertonic saline - hydroxyethyl starch and mannitol on serum osmolality, dural tension and hemodynamics in patients undergoing elective neurosurgical procedures. | To investigate effect of equal volumes (250 ml) of 7.2% hypertonic saline - 6% hydroxyethyl starch (HS-HES) and 20% mannitol (M) on dural tension, serum osmolality and hemodynamics in patients during elective neurosurgical procedures. Forty ASA I-II patients scheduled for elective neurosurgical supratentorial procedures were randomly assigned to two groups. About 30 min before skull opening, patients received either HS-HES or M at infusion rate 750 ml/h. Dural tension score was used to evaluate the dural tension by neurosurgeons. Serum osmolality was tested at following time points: before, 125 ml infused, 250 ml infused, 30 min and 60 min after infusion. Hemodynamic variables were measured by FloTrac. Patients who received HS-HES had a significant decrease in dural tension scores (P < 0.05) and obtained more satisfactory brain relaxation for neurosurgeon (95% vs. 75%). In HS-HES group, the peak of serum osmolality occurred earlier and hyperosmolality lasted for longer time. Transient decrease in mean arterial pressure was observed in M group at 10 min after the start infusion (P < 0.01). Heart rate significantly decreased after HS-HES infusion, whereas no significant changes were observed in M group. In HS-HES group, stroke volume variation significantly decreased from 9.7 ± 3.5 at the initiation of infusion to 6.7 ± 2.4 at 30 min after the infusion and remained decreased more than 60 min while it decreased from 6.8 ± 3.1 to 5.3 ± 1.5 in M group. Moreover, urine output in HS-HES group from initiation to 60 min after the infusion was significantly less than those in M group. HS-HES might be an alternative to mannitol in treatment of intracranial hypertension. | 25,232,419 | [
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Effect of hepatitis C virus infection on the right ventricular functions, pulmonary arterypressure and pulmonary vascular resistance. | Hepatitis secondary to infection with the hepatitis C virus (HCV) is one of themost common causes of viral hepatitis worldwide. Multiple extrahepatic manifestations of HCV infection have been recognized. In this study we aimed to examine right ventricular systolic functions and pulmonary artery pressure in HCV patients. The study included 50 HCV patients (mean age; 34 ± 12 years) and 50 other persons (mean age; 28 ± 11 years) as control group. Transthorasic echocardiography was performed in all the participants. Right ventricle systolic parameters, pulmonary artery pressure, pulmonary vascular resistance (PVR) were compared between these two groups. In the group of the patients with HCV, the right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE) and RV myocardial systolic velocity (St) values were lower than control group (31 ± 10 vs 48 ± 12%; 13.5 ± 1.5 vs 19.2 ± 3.4 mm and 8.3 ± 1.1 vs 17.7 ± 3.3 cm/s all P < 0.001, respectively); the right atrium (RA) and RV diameters were higher than controls (4.8 ± 1.3 vs 3.6 ± 0.6 cm, P < 0.001; 4.4 ± 0.8 vs 3.3 ± 0.5 cm P < 0.001, respectively); additionally systolic pulmonary artery pressure and PVR were higher than control (36.3 ± 9.9 vs 23 ± 7.8 mmHg, 3.5 ± 1.1 vs 2.1 ± 0.8; P < 0.001, respectively). The findings showed that HCV infection may be associated with right ventricular systolic dysfunction and pulmonary hypertension. | 25,232,427 | [
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Role of endoscopic ultrasound in the diagnosis of pancreatic cancer. | Endoscopic ultrasonography (EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography, computed tomography (CT) and transabdominal ultrasound for recognising early pancreatic tumors. As a diagnostic modality for pancreatic cancer, EUS has proved rates higher than 90%, especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT. Besides, EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer. The complication rate of EUS is as low as 1.1%-3.0%. New technical developments such as elastography and the use of contrast agents have recently been applied to EUS, improving its diagnostic capability. EUS has been found to be superior to the recent multidetector CT for T staging with less risk of overstaying in comparison to both CT and magnetic resonance imaging, so that patients are not being ruled out of a potentially beneficial resection. The accuracy for N staging with EUS is 64%-82%. In unresectable cancers, EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block, biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy. | 25,232,461 | [
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Activation of the Wnt pathway through Wnt2 promotes metastasis in pancreatic cancer. | Wnt signaling pathway plays an important role in physiological and pathological process, including in the occurrence and development of tumor. The purpose of this study is to determine whether Wnt2 and sFRP4, key molecules of signaling pathway, are of prognostic value for survival in patients with pancreatic cancer. We performed immunohistochemistry on tissue microarrays containing 90 pancreatic cancer specimens to evaluate the protein expression of Wnt2 and sFRP4. Our results showed that the cytoplasmic expression level of Wnt2 in pancreatic cancer tissues was significantly associated with LNM (P=0.029) and AJCC stage (P=0.008). Additionally, Kaplan-Meier analysis indicated that high Wnt2 expression was significantly correlated with poor clinical outcomes of patients with pancreatic cancer. In conclusion, Wnt2 may play an important role in the development of pancreatic cancer through activation of the Wnt pathways and serve as a potential candidate for treatment target of pancreatic cancer. | 25,232,495 | [
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Anticancer properties of novel aminoacetonitrile derivative monepantel (ADD 1566) in pre-clinical models of human ovarian cancer. | Monepantel (MPL) is a new anthelmintic agent approved for the treatment of nematode infections in farm animals. As a nematicide, it acts through a nematode-specific nicotinic receptor subtype which explains its exceptional safety in rodents and mammals. In the present study, we evaluated its potential as an anticancer agent. In vitro treatment of epithelial ovarian cancer cells with MPL resulted in reduced cell viability, inhibition of cell proliferation and suppression of colony formation. Proliferation of human ovarian surface epithelial cells and other non-malignant cells were however minimally affected. MPL-induced inhibition was found to be independent of the acetylcholine nicotinic receptor (nAChR) indicating that, its target in cancer cells is probably different from that in nematodes. Analysis of MPL treated cells by flow cytometry revealed G1 phase cell cycle arrest. Accordingly, MPL treated cells expressed reduced levels of cyclins D1 and A whereas cyclin E2 expression was enhanced. Consistent with a G1 phase arrest, cellular levels of cyclin dependent kinases (CDKs) 2 and 4 were lower, whereas expression of CDK inhibitor p27(kip) was increased. In cells expressing the wild-type p53, MPL treatment led to increased p53 expression. In line with these results, MPL suppressed cellular thymidine incorporation thus impairing DNA synthesis and inducing cleavage of poly (ADP-ribose) polymerase (PARP-1). Combined these pre-clinical findings reveal for the first time the anticancer potential of monepantel. | 25,232,496 | [
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The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis. | Myc-interacting zinc finger protein 1 (Miz-1) is a BTB/POZ domain transcription factor that regulates complex processes such as proliferation and apoptosis. Constitutively Miz-1-deficient animals arrest embryonic development at E14.5 due to severe anemia and fetal liver cells lacking Miz-1 show a high cell death rate and a significant reduction of mature Ter119(+)ckit(-) or Ter119(+)CD71(-/low) cells. Consistently, the numbers of BFU-Es and CFU-Es were severely reduced in colony forming assays. Mice with conditional Miz-1 alleles deleted around E14.5 were born at expected ratios, but had reduced numbers of erythrocytes, and showed an increase in reticulocytes and Macro-RBCs in the peripheral blood. When challenged with the hemolytic agent phenylhydrazine (PHZ), Miz-1 deficient mice responded with a severe anemia after 4 days of treatment, but showed a delay in the recovery from this anemia with regard to RBC counts, hematocrit and hemoglobin levels compared to controls. In addition, an accumulation of immature CD71(+)Ter119(+) cells occurred in the bone marrow and spleen of mice lacking a functional Miz-1. We conclude from our studies that Miz-1 is important for erythroid differentiation and development. Moreover, Miz-1 is necessary to maintain a peripheral red blood cell homeostasis in particular in response to hemolysis after oxidative stress. | 25,232,500 | [
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Somatic complaints in frontotemporal dementia. | Frontotemporal dementia (FTD) is associated with a broad spectrum of clinical characteristics. The objective of this study was to analyze the prevalence of unexplained somatic complaints in neuropathologically verified FTD. We also examined whether the somatic presentations correlated with protein pathology or regional brain pathology and if the patients with these somatic features showed more depressive traits. Ninety-seven consecutively neuropathologically verified FTLD patients were selected. All 97 patients were part of a longitudinal study of FTD and all medical records were systematically reviewed. The somatic complaints focused on were headache, musculoskeletal, gastro/urogenital and abnormal pain response. Symptoms of somatic character (either somatic complaints and/or abnormal pain response) were found in 40.2%. These patients did not differ from the total group with regard to gender, age at onset or duration. Six patients showed exaggerated reactions to sensory stimuli, whereas three patients showed reduced response to pain. Depressive traits were present in 38% and did not correlate with somatic complaints. Suicidal behavior was present in 17 patients, in 10 of these suicidal behavior was concurrent with somatic complaints. No clear correlation between somatic complaints and brain protein pathology, regional pathology or asymmetric hemispherical atrophy was found. Our results show that many FTD patients suffer from unexplained somatic complaints before and/or during dementia where no clear correlation can be found with protein pathology or regional degeneration. Somatic complaints are not covered by current diagnostic criteria for FTD, but need to be considered in diagnostics and care. The need for prospective studies with neuropathological follow up must be stressed as these phenomena remain unexplained, misinterpreted, bizarre and, in many cases, excruciating. | 25,232,513 | [
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Epicardium Formation as a Sensor in Toxicology. | Zebrafish (<iDanio</i rerio) are an excellent vertebrate model for studying heart development, regeneration and cardiotoxicity. Zebrafish embryos exposed during the temporal window of epicardium development to the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-<ip</i-dioxin (TCDD) exhibit severe heart malformations. TCDD exposure prevents both proepicardial organ (PE) and epicardium development. Exposure later in development, after the epicardium has formed, does not produce cardiac toxicity. It is not until the adult zebrafish heart is stimulated to regenerate does TCDD again cause detrimental effects. TCDD exposure prior to ventricular resection prevents cardiac regeneration. It is likely that TCDD-induced inhibition of epicardium development and cardiac regeneration occur via a common mechanism. Here, we describe experiments that focus on the epicardium as a target and sensor of zebrafish heart toxicity. | 25,232,532 | [
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Interspinous posterior devices: What is the real surgical indication? | Interspinous posterior device (IPD) is a term used to identify a relatively recent group of implants used to treat lumbar spinal degenerative disease. This kind of device is classified as part of the group of the dynamic stabilization systems of the spine. The concept of dynamic stabilization has been replaced by that of dynamic neutralization of hypermobility, with the intention of clarifying that the primary aim of this kind of system is not the preservation of the movement, but the dynamic neutralization of the segmental hypermobility which is at the root of the pathological condition. The indications for the implantation of an IPD are spinal stenosis and neurogenic claudication, assuming that its function is the enlargement of the neural foramen and the decompression of the roots forming the cauda equina in the central part of the vertebral canal. In the last 10 years, use of these implants has been very common but to date, no long-term clinical follow-up regarding clinical and radiological aspects are available. The high rate of reoperation, recurrence of symptoms and progression of degenerative changes is evident in the literature. If these devices are effectively a miracle cure for lumbar spinal stenosis, why do the utilization and implantation of IPD remain extremely controversial and should they be investigated further? Excluding the problems related to the high cost of the device, the main problem remains the pathological substrate on which the device is explicit in its action: the degenerative pathology of the spine. | 25,232,541 | [
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A comparison of the different animal models of fetal alcohol spectrum disorders and their use in studying complex behaviors. | Prenatal ethanol exposure (PNEE) has been linked to widespread impairments in brain structure and function. There are a number of animal models that are used to study the structural and functional deficits caused by PNEE, including, but not limited to invertebrates, fish, rodents, and non-human primates. Animal models enable a researcher to control important variables such as the route of ethanol administration, as well as the timing, frequency and amount of ethanol exposure. Each animal model and system of exposure has its place, depending on the research question being undertaken. In this review, we will examine the different routes of ethanol administration and the various animal models of fetal alcohol spectrum disorders (FASD) that are commonly used in research, emphasizing their strengths and limitations. We will also present an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on behavior across the lifespan, focusing on learning and memory, olfaction, social, executive, and motor functions. Special emphasis will be placed where the various animal models best represent deficits observed in the human condition and offer a viable test bed to examine potential therapeutics for human beings with FASD. | 25,232,537 | [
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Upper esophageal sphincter abnormalities are strongly predictive of treatment response in patients with achalasia. | To investigate the relationship between upper esophageal sphincter abnormalities achalasia treatment We performed a retrospective study of 41 consecutive patients referred for high resolution esophageal manometry with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of Upper esophageal sphincter (UES) abnormality, and clinical and manometric profiles were compared. Correlation between UES abnormality and sub-type (i.e., hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness, psychiatric illness, surgical history, dominant presenting symptom, treatment type, age and gender were also evaluated. Among all 41 patients, 24 (58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profiles. Among those with UES abnormalities, the majority were either hypertensive (41.67%) or had impaired relaxation (37.5%) as compared to hypotensive (20.83%), although this did not reach statistical significance (P = 0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority (78.57%) had good treatment response, as compared to 21.43% with poor treatment response (P = 0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality (P = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response compared to those with no UES abnormality (P = 0.017). The presence of UES abnormalities in patients with achalasia significantly predicted poorer treatment response as compared to those with normal UES function. | 25,232,548 | [
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Pneumatosis cystoides intestinalis associated with toxic epidermal necrolysis: A case report. | Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction, which is characterized by erythema, blisters, and/or erosions of the mucous membranes and skin, but intestinal involvement is rare. In contrast, pneumatosis cystoides intestinalis (PCI) is a rare condition associated with a wide variety of underlying diseases, but to date no patient has presented with PCI associated with TEN. A 55-year-old man was admitted to intensive care unit for treatment of TEN caused by phenobarbital. On day 8 after admission, he presented with progressive abdominal distention and hypotension. Computed tomography (CT) showed gas in the superior mesenteric vein and air filled cysts in the walls of the small intestine. He was suspected of having septic shock due to PCI. As there were no indications of bowel ischemia or necrosis, the patient was managed conservatively with antibiotics and oxygen therapy. On day 10 after admission, he was weaned off catecholamines, with CT on day 11 showing complete resolution of gas in the superior mesenteric vein and air filled cysts. To our knowledge, this article describes the first patient presenting with PCI associated with TEN. | 25,232,553 | [
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Champagne bottle neck sign in a patient with Moyamoya syndrome. | The champagne bottle neck (CBN) sign refers to a reduction in the diameter of the proximal portion of the internal carotid artery that resembles a CBN, and is a characteristic feature of Moyamoya disease. A 43-year-old woman with an infarction of the posterior limb of the left internal capsule was diagnosed with Moyamoya syndrome associated with Graves' disease. The CBN sign was observed bilaterally. Cerebral revascularization surgery was performed, including left-sided superficial temporal artery to middle cerebral artery anastomosis. During four years of follow-up, she maintained a euthyroid state and did not have any further cerebral ischemic events. The CBN signs remained unchanged on both sides during this time. This is the first report of the CBN sign in a patient with Moyamoya syndrome associated with Graves' disease. | 25,232,554 | [
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Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study. | Chromosome 9p21 single nucleotide polymorphism (SNP) is a susceptibility variant for acute myocardial infarction (AMI) in the primary prevention setting. However, it is controversial whether this SNP is also associated with recurrent myocardial infarction (ReMI) in the secondary prevention setting. The purpose of this study is to evaluate the impact of chromosome 9p21 SNP on ReMI in patients receiving secondary prevention programmes after AMI. A prospective observational study. Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. 2022 patients from the OACIS database. Genotyping of the 9p21 rs1333049 variant. ReMI event after survival discharge for 1 year. A total of 43 ReMI occurred during the 1 year follow-up period. Although the rs1333049 C allele had an increased susceptibility to their first AMI in an additive model when compared with 1373 healthy controls (OR 1.20, 95% CI 1.09 to 1.33, p=2.3*10(−4)), patients with the CC genotype had a lower incidence of ReMI at 1 year after discharge of AMI (log-rank p=0.005). The adjusted HR of the CC genotype as compared with the CG/GG genotypes was 0.20 (0.06 to 0.65, p=0.007). Subgroup analysis demonstrated that the association between the rs1333049 CC genotype and a lower incidence of 1 year ReMI was common to all subgroups. Homozygous carriers of the rs1333049 C allele on chromosome 9p21 showed a reduced risk of 1 year ReMI in the contemporary percutaneous coronary intervention era, although the C allele had conferred susceptibility to their first AMI. | 25,232,560 | [
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Early detection of left ventricular contractility abnormalities by two-dimensional speckle tracking strain in Chagas’ disease. | Chagas' disease is an important cause of heart failure, and early identification of cardiac involvement may help to identify patients at risk for disease progression. Two-dimensional (2D) speckle tracking (ST) strain seems to be a useful tool to detect incipient ventricular dysfunction. This study aims to analyze if 2D strain can detect contractility abnormalities in asymptomatic patients with Chagas' disease. Seventy-eight asymptomatic Chagas' disease patients (46% male; age 44.7 ± 8.6 years) with normal cardiovascular exams and a control group of 38 healthy subjects (58% male; age 44.1 ± 9.2 years) were included in the study. Using 2D strain software, left ventricular (LV) end-systolic longitudinal, radial, and circumferential strain were measured. Global right ventricular (RV) longitudinal strain was also assessed. Echocardiographic parameters of LV systolic and diastolic function were similar between patients and controls. 2D longitudinal strain in the basal inferior, and inferoseptal walls, as well as apical segment of the inferolateral wall were lower in patients compared with controls. 2D radial strain was reduced in several segments of the LV walls as well as the global radial strain. 2D circumferential strain at the basal segment of the anterior wall showed a lower value in patients compared with controls, whereas global circumferential strain was similar between patients and controls. 2D RV strain did not differ between groups. In a subgroup of asymptomatic patients with Chagas' disease without evident cardiac involvement, 2D strain was reduced compared with healthy individuals, suggesting incipient LV dysfunction in these patients. 2D ST strain has the potential for detecting early myocardial impairment in the setting of Chagas' disease. | 25,232,573 | [
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The taxonomic status of badgers (Mammalia, Mustelidae) from Southwest Asia based on cranial morphometrics, with the redescription of Meles canescens. | The Eurasian badgers (Meles spp.) are widespread in the Palaearctic Region, occurring from the British Islands in the west to the Japanese Islands in the east, including the Scandinavia, Southwest Asia and southern China. The morphometric variation in 30 cranial characters of 692 skulls of Meles from across the Palaearctic was here analyzed. This craniometric analysis revealed a significant difference between the European and Asian badger phylogenetic lineages, which can be further split in two pairs of taxa: meles - canescens and leucurus - anakuma. Overall, European badger populations are very similar morphologically, particularly with regards to the skull shape, but differ notably from those from Asia Minor, the Middle East and Transcaucasia. Based on the current survey of badger specimens available in main world museums, we have recognized four distinctive, parapatric species: Meles meles, found in most of Europe; Meles leucurus from continental Asia; M. anakuma from Japan; and M. canescens from Southwest Asia and the mountains of Middle Asia. These results are in agreement with those based on recent molecular data analyses. The morphological peculiarities and distribution range of M. canescens are discussed. The origin and evolution of Meles species, which is yet poorly understood, is also briefly discussed. | 25,232,583 | [
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New records of gonodactylids (Crustacea: Stomatopoda: Gonodactylidae) from the Pacific Coast of Mexico with remarks on the morphology of Neogonodactylus lalibertadensis (Schmitt, 1940). | Eight species of the genus Neogonodactylus have been reported from the eastern Pacific. Up to now, only three of these species have been collected in Mexican waters: Neogonodactylus stanschi (Schmitt, 1940), N. lalibertadensis (Schmitt, 1940), and N. zacae (Manning, 1972). Recent sampling of stomatopods in several localities of the Pacific coast of Mexico, from Mazatlán, in the southwestern Gulf of California, to Oaxaca, allowed us to collect fresh material of these three species and five specimens that agree with the general description of N. lalibertadensis, but with differences in the telson ornamentation and the length of the ophthalmic somite. A close examination of this material and examination of photographs of the holotype led us to establish that it shows slight variation from the typical form. A revised key to the species of Neogonodactylus occurring in the eastern Pacific is provided. | 25,232,595 | [
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A new genus of highly specialized ants in Cretaceous Burmese amber (Hymenoptera: Formicidae). | A new genus of ants, Zigrasimecia Barden and Grimaldi, is described for a new and uniquely specialized species, Z. tonsora Barden and Grimaldi n.sp., preserved in Cretaceous amber from Myanmar. The amber is radiometrically dated at 99 myo. Zigrasimecia is closely related to another basal genus of ants known only in Burmese and French Cretaceous amber, Sphecomyrmodes Engel and Grimaldi, based in part on the shared possession of a comb of pegs on the clypeal margin, as well as mandible structure. Highly specialized features of Zigrasimecia include extensive development of the clypeal comb, a thick brush of setae on the oral surface of the mandibles and on the labrum, and a head that is broad, flattened, and which bears a crown of blackened, rugose cuticle. Mouthparts are hypothesized to have functioned in a unique manner, showing no clear signs of dentition representative of "chewing" or otherwise processing solid food. Although all ants in Burmese amber are basal, stem-group taxa, there is an unexpected diversity of mouthpart morphologies and probable feeding modes. | 25,232,618 | [
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Glyptothorax igniculus, a new species of sisorid catfish (Teleostei: Siluriformes) from Myanmar. | Glyptothorax igniculus, new species, is described from the Chindwin River system (part of the Irrawaddy River drainage) in northwestern Myanmar. It differs from other species of Glyptothorax in the Irrawaddy drainage except G. burmanicus in having a thoracic adhesive apparatus with a lanceolate central depression that is nearly enclosed posteriorly by skin ridges, vs. having an adhestive apparatus that is open caudally. In G. burmanicus the adhesive apparatus is oval in outline and completely closed. Glyptothorax chindwinicus Vishwanath & Linthoingambi, 2007 is shown to be a junior synonym of G. burmanicus Prashad & Mukerji, 1929. Glyptothorax rugimentum is reported for the first time from the Chindwin drainage. | 25,232,627 | [
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Description of the nymph of Massartella alegrettae Ulmer, 1943 (Ephemeroptera: Leptophlebiidae: Atalophlebiinae) with a key to Massartella Lestage, 1930 nymphs. | The South American genus Massartella Lestage, 1930 is composed of five species. Massartella alegrettae Ulmer, 1943 is the only species with the nymph unknown. In this paper, we describe the nymph of M. alegrettae based on specimens from the state of São Paulo, Brazil. This is the first record of the species from southeastern Brazil. The nymph can be easily recognized by the gills present on segments I-V, with dark gray membrane and without apical processes. | 25,232,630 | [
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Bacterially synthesized ferrite nanoparticles for magnetic hyperthermia applications. | Magnetic hyperthermia uses AC stimulation of magnetic nanoparticles to generate heat for cancer cell destruction. Whilst nanoparticles produced inside magnetotactic bacteria have shown amongst the highest reported heating to date, these particles are magnetically blocked so that strong heating occurs only for mobile particles, unless magnetic field parameters are far outside clinical limits. Here, nanoparticles extracellularly produced by the bacteria Geobacter sulfurreducens are investigated that contain Co or Zn dopants to tune the magnetic anisotropy, saturation magnetization and nanoparticle sizes, enabling heating within clinical field constraints. The heating mechanisms specific to either Co or Zn doping are determined from frequency dependent specific absorption rate (SAR) measurements and innovative AC susceptometry simulations that use a realistic model concerning clusters of polydisperse nanoparticles in suspension. Whilst both particle types undergo magnetization relaxation and show heating effects in water under low AC frequency and field, only Zn doped particles maintain relaxation combined with hysteresis losses even when immobilized. This magnetic heating process could prove important in the biological environment where nanoparticle mobility may not be possible. Obtained SARs are discussed regarding clinical conditions which, together with their enhanced MRI contrast, indicate that biogenic Zn doped particles are promising for combined diagnostics and cancer therapy. | 25,232,657 | [
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Site-specific growth of AgPd nanodendrites on highly purified Au bipyramids with remarkable catalytic performance. | Au nanorods have been extensively explored in various applications as the template for heterogeneous metallic nanostructures. However, Au bipyramids (AuBPs) have been paid much less attention although they possess an intriguing crystalline structure and extremely superior plasmonic properties which are absent in AuNRs. The state-of-the-art synthesis cannot produce pure AuBPs, which has become a major barrier to their various applications like catalysis since purity is often critical for achieving the desired performance. Herein, we have shown a facile approach to obtain large-scale high-purity AuBPs. The purity of AuBPs can be improved from 30 to 50% for the as-synthesized AuBP solution to over 95% for the purified solution. Site-specific growth of AgPd nanodendrites on multiply twinned AuBPs from core-shell to tipped nanostructures was achieved for the first time by coupling a galvanic replacement with a co-reduction process, which show remarkable catalytic activity in the reduction reaction of 4-nitrophenol (4-NP) by NaBH4. The use of ascorbic acid (AA) as a reductant in the co-reduction process and the intriguing crystalline structure of AuBPs play a critical role in forming these unique structures. We believe that this work would provide a general strategy to prepare high-purity AuBP based trimetallic nanostructures, which offers the opportunity for AuBPs to be widely used in catalysis or other plasmonic-effect related applications in the near future. | 25,232,660 | [
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Antimicrobial activity of Antarctic bryozoans: an ecological perspective with potential for clinical applications. | The antimicrobial activity of Antarctic bryozoans and the ecological functions of the chemical compounds involved remain largely unknown. To determine the significant ecological and applied antimicrobial effects, 16 ether and 16 butanol extracts obtained from 13 different bryozoan species were tested against six Antarctic (including Psychrobacter luti, Shewanella livingstonensis and 4 new isolated strains) and two bacterial strains from culture collections (Escherichia coli and Bacillus cereus). Results from the bioassays reveal that all ether extracts exhibited antimicrobial activity against some bacteria. Only one butanol extract produced inhibition, indicating that antimicrobial compounds are mainly lipophilic. Ether extracts of the genus Camptoplites inhibited the majority of bacterial strains, thus indicating a broad-spectrum of antimicrobial activity. Moreover, most ether extracts presented activities against bacterial strains from culture collections, suggesting the potential use of these extracts as antimicrobial drugs against pathogenic bacteria. | 25,232,675 | [
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A novel index of hypoxemia for assessment of risk during procedural sedation. | Procedural sedation is essential for many procedures. Sedation has an excellent safety profile; however, it is not without risks. Assessment of risk using clinical outcomes in clinical studies is difficult due to their rare occurrence. Therefore, surrogate end points are frequently used in a clinical study in lieu of clinical outcomes. As a clinician integrates multiple aspects of a physiological variable to determine potential risk, a surrogate end point should consider a similar approach. In this study, we identified and tested the appropriateness of a new surrogate end point that may be used in clinical studies, area under the curve of oxygen desaturation (AUCDesat). A review of patient sedation records by anesthesiologists was conducted to assess its relationship to the anesthesia professional perception of risk. This study was a post hoc analysis and assessment of perceived risk by anesthesiologists. It consisted of 13 U.S.-trained board-certified anesthesiologists ranking physiological variables as indicators of risk and then reviewing 204 records from 3 completed sedation studies involving the SEDASYS System. After review, each anesthesiologist assigned a Likert score based on his or her perception of risk for oversedation-related sequelae in each record. These scores were analyzed to determine their relationship to desaturation presence/absence, duration, depth, number of events, and AUCDesat that incorporates each component. Anesthesiologists ranked arterial oxygenation to be the most important factor in assessing risk post hoc (mean rank of 4.69 of 5, P = 0.0007 compared with next highest ranked factor-respiratory rate, N = 13). AUCDesat was better correlated to the Likert scores (rs = 0.85) when compared with the individual elements of AUCDesat, binary assessment of desaturation (rs = 0.73), desaturation depth (rs = -0.70), desaturation duration (rs = 0.70), and incidence of desaturations (rs = 0.55) (all 4 comparisons versus rs = 0.85, P < 0.0001). Anesthesiologists determined arterial oxygenation to be the most important physiological variable in assessing sedation risk and the potential for adverse clinical outcomes. AUCDesat, a composite index that incorporates duration, incidence, and depth of oxygen desaturation, was better correlated to the Likert scores. AUCDesat, given that it is a single numerical variable, is an ideal end point for assessment of risk of adverse clinical outcomes in clinical sedation studies. Future studies using AUCDesat and actual physiological outcomes may be useful in further defining this end point. | 25,232,693 | [
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Challenges and opportunities of microRNAs in lymphomas. | MicroRNAs (miRNAs) are small non-coding RNAs that control the expression of many target messenger RNAs (mRNAs) involved in normal cell functions (differentiation, proliferation and apoptosis). Consequently their aberrant expression and/or functions are related to pathogenesis of many human diseases including cancers. Haematopoiesis is a highly regulated process controlled by a complex network of molecular mechanisms that simultaneously regulate commitment, differentiation, proliferation, and apoptosis of hematopoietic stem cells (HSC). Alterations on this network could affect the normal haematopoiesis, leading to the development of haematological malignancies such as lymphomas. The incidence of lymphomas is rising and a significant proportion of patients are refractory to standard therapies. Accurate diagnosis, prognosis and therapy still require additional markers to be used for diagnostic and prognostic purpose and evaluation of clinical outcome. The dysregulated expression or function of miRNAs in various types of lymphomas has been associated with lymphoma pathogenesis. Indeed, many recent findings suggest that almost all lymphomas seem to have a distinct and specific miRNA profile and some miRNAs are related to therapy resistance or have a distinct kinetics during therapy. MiRNAs are easily detectable in fresh or paraffin-embedded diagnostic tissue and serum where they are highly stable and quantifiable within the diagnostic laboratory at each consultation. Accordingly they could be specific biomarkers for lymphoma diagnosis, as well as useful for evaluating prognosis or disease response to the therapy, especially for evaluation of early relapse detection and for greatly assisting clinical decisions making. Here we summarize the current knowledge on the role of miRNAs in normal and aberrant lymphopoiesis in order to highlight their clinical value as specific diagnosis and prognosis markers of lymphoid malignancies or for prediction of therapy response. Finally, we discuss their controversial therapeutic role and future applications in therapy by modulating miRNA. | 25,232,701 | [
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Cerebral tissue oxygenation during the initiation of venovenous ECMO. | In an acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (vvECMO) can rapidly normalize arterial hypoxemia and carbon dioxide tension (PaCO2). Considering the positive relationship between PaCO2 and cerebral blood flow, the aim of the current study was to evaluate cerebral regional tissue oxygen saturation (rSO2) during the implementation of vvECMO. Fifteen acute respiratory distress syndrome patients with recordings of cerebral rSO2 by near-infrared spectroscopy before vvECMO implementation until the optimization of the ECMO/ventilator settings were retrospectively studied. median (interquartile range). The cerebral rSO2 increased significantly (p < 0.05) from 69(61-74) to 75(60-80)% after ECMO was started, concomitant to the arterial oxygenation. Until the end of the observation period after 83(44-132) minutes, cerebral rSO2 decreased significantly to 61(52-71)%. PaCO2 decreased from 70(61-87) to 43(38-54) mm Hg and the pH increased from 7.23(7.14-7.29) to 7.39(7.34-7.43). The baseline arterial oxygen saturation and tension as well as the actual bicarbonate concentration were negatively correlated with the absolute change in cerebral rSO2 (ΔrSO2). In the 11 nonhypoxemic patients (arterial oxygen saturation ≥90%) ΔPaCO2 was significantly correlated with ΔrSO2. Patients receiving vvECMO treatment are at risk for a decrease in cerebral rSO2. This decrease is more distinct in patients with normal baseline arterial oxygenation and high actual bicarbonate. | 25,232,765 | [
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Conservative management of type II and III odontoid fractures in the elderly at a regional spine centre: A prospective and retrospective cohort study. | The optimal management of odontoid fractures in the elderly population is unclear and management of this group of patients is complicated by multiple co-morbidities. This study aimed to determine the outcomes after conservative management strategies were applied in this patient group. We carried out retrospective and prospective analyses of all patients with axial cervical spine injuries, at a single centre. We included patients aged over 60 years with type II and III odontoid fractures. Information was gathered on demographics, ASA grading-associated injuries and complications. The outcome measures were rates and type of union, pain and neurological functions, specifically ambulation. Fifty-seven adult patients with a median age of 78 years (range 60-92 years) were included. There were 42 type II and 15 type III odontoid fractures. Three patients required surgical fixation due to displaced fractures, which could not be reduced with manual traction. Twenty-four (41%) patients were managed with a rigid pinned halo orthosis to obtain adequate reduction and immobilisation. The remaining 30 (53%) were managed in a hard cervical collar. Patients managed with a halo were significantly younger and had more associated injuries than patients managed in a collar (age: t-test=4.05, p<0.01, associated injuries: Chi-square=4.38, p<0.05). At a mean follow-up of 25 weeks, 87% of type II and 100% of type III fractures had achieved bony union or stable, fibrous non-union. There were no statistical differences in fracture type, follow-up or neurological outcomes between the halo and collar groups. However, overall more patients managed in a collar developed stable fibrous non-union than bony fusion (Fisher's exact test, p<0.05), although this was not significant when analysed by each fracture type individually. A regression model was constructed and identified fracture type as the only independent predictor of time to union, with type III fractures healing faster than type II. High rates of bony union and stable fibrous non-union with a good functional outcome can be achieved in the elderly population sustaining type II or III odontoid fractures, when managed non-surgically. Halo orthosis may not offer any clear advantage over hard collar in this group. Close follow-up is needed for late complications and there must be a willingness to perform surgery if conservative measures fail. | 25,232,807 | [
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A new approach for monitoring ebolavirus in wild great apes. | Central Africa is a "hotspot" for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%. | 25,232,832 | [
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Novel copy-number variants in a population-based investigation of classic heterotaxy. | Heterotaxy is a clinically and genetically heterogeneous disorder. We investigated whether screening cases restricted to a classic phenotype would result in the discovery of novel, potentially causal copy-number variants. We identified 77 cases of classic heterotaxy from all live births in New York State during 1998-2005. DNA extracted from each infant's newborn dried blood spot was genotyped with a microarray containing 2.5 million single-nucleotide polymorphisms. Copy-number variants were identified with PennCNV and cnvPartition software. Candidates were selected for follow-up if they were absent in unaffected controls, contained 10 or more consecutive probes, and had minimal overlap with variants published in the Database of Genomic Variants. We identified 20 rare copy-number variants including a deletion of BMP2, which has been linked to laterality disorders in mice but not previously reported in humans. We also identified a large, terminal deletion of 10q and a microdeletion at 1q23.1 involving the MNDA gene; both are rare variants suspected to be associated with heterotaxy. Our findings implicate rare copy-number variants in classic heterotaxy and highlight several candidate gene regions for further investigation. We also demonstrate the efficacy of copy-number variant genotyping in blood spots using microarrays. | 25,232,849 | [
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Naked bodies, naked genomes: the special (but not exceptional) nature of genomic information. | Genetic exceptionalism, the view that genomic information is different from other types of sensitive information and deserves exceptional types of protections, has been roundly criticized. However, the public still expresses special fears about the access others might have to their genomic information. In this article, it is argued that there may be a basis for the public perception that genomic information is special, even if it cannot be said that policies could or should be enacted to protect the privacy and confidentiality of genomic information that would be exceptional relative to the protections one would enact to protect other types of sensitive information. The special nature of genomic information lies in understanding that it is neither personal property nor mere information. A genome is, at one and the same time, a physical aspect of a person and information about that person. Genomic data are embodied information that partially constitutes as well as describes individuals and that connects them in physical ways to their ancestors and their relatives. All forms of privacy need to be protected, but some intimate aspects of our lives command special respect. To see a genome is more analogous to seeing a naked body than to seeing a social security number. This metaphor suggests that clinicians and investigators ought to respect the special concerns of patients regarding genomic information while not claiming that there are any exceptional measures one could take to protect genomic privacy. Suggestions are given for how this view might affect patient interactions, consent discussions, public policy, and public trust in genomic research and clinical genetics. | 25,232,853 | [
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The effect of leaf litter cover on surface runoff and soil erosion in Northern China. | The role of leaf litter in hydrological processes and soil erosion of forest ecosystems is poorly understood. A field experiment was conducted under simulated rainfall in runoff plots with a slope of 10%. Two common types of litter in North China (from Quercus variabilis, representing broadleaf litter, and Pinus tabulaeformis, representing needle leaf litter), four amounts of litter, and five rainfall intensities were tested. Results revealed that the litter reduced runoff and delayed the beginning of runoff, but significantly reduced soil loss (p<0.05). Average runoff yield was 29.5% and 31.3% less than bare-soil plot, and for Q. variabilis and P. tabulaeformis, respectively, and average sediment yield was 85.1% and 79.9% lower. Rainfall intensity significantly affected runoff (R = 0.99, p<0.05), and the efficiency in runoff reduction by litter decreased considerably. Runoff yield and the runoff coefficient increased dramatically by 72.9 and 5.4 times, respectively. The period of time before runoff appeared decreased approximately 96.7% when rainfall intensity increased from 5.7 to 75.6 mm h-1. Broadleaf and needle leaf litter showed similarly relevant effects on runoff and soil erosion control, since no significant differences (p≤0.05) were observed in runoff and sediment variables between two litter-covered plots. In contrast, litter mass was probably not a main factor in determining runoff and sediment because a significant correlation was found only with sediment in Q. variabilis litter plot. Finally, runoff yield was significantly correlated (p<0.05) with sediment yield. These results suggest that the protective role of leaf litter in runoff and erosion processes was crucial, and both rainfall intensity and litter characteristics had an impact on these processes. | 25,232,858 | [
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Effects of experimental tooth clenching on pain and intramuscular release of 5-HT and glutamate in patients with myofascial TMD. | It has been suggested that tooth clenching may be associated with local metabolic changes, and is a risk factor for myofascial temporomandibular disorders (M-TMD). This study investigated the effects of experimental tooth clenching on the levels of 5-HT, glutamate, pyruvate, and lactate, as well as on blood flow and pain intensity, in the masseter muscles of M-TMD patients. Fifteen patients with M-TMD and 15 pain-free controls participated. Intramuscular microdialysis was performed to collect 5-HT, glutamate, pyruvate, and lactate and to assess blood flow. Two hours after the insertion of a microdialysis catheter, participants performed a 20-minute repetitive tooth clenching task (50% of maximal voluntary contraction). Pain intensity was measured throughout. A significant effect of group (P<0.01), but not of time, was observed on 5-HT levels and blood flow. No significant effects of time or group occurred on glutamate, pyruvate, or lactate levels. Time and group had significant main effects on pain intensity (P<0.05 and <0.001). No significant correlations were identified between: (1) 5-HT, glutamate, and pain intensity; or between (2) pyruvate, lactate, and blood flow. This experimental tooth clenching model increased jaw muscle pain levels in M-TMD patients and evoked low levels of jaw muscle pain in controls. M-TMD patients had significantly higher levels of 5-HT than controls and significantly lower blood flow. These 2 factors may facilitate the release of other algesic substances that may cause pain. | 25,232,860 | [
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Parents' Analgesic Trade-Off Dilemmas: How Analgesic Knowledge Influences Their Decisions to Give Opioids. | Ineffective analgesic decisions in the home may jeopardize the safety and comfort of children, yet little is known about factors influencing parental decisions. This study explored how parents' analgesic understanding influenced their hypothetical decisions to give opioids when faced with important trade-off dilemmas where pain and adverse drug event (ADE) symptoms were both present. A total of 514 parents whose children required opioids after discharge completed surveys assessing their Gist ADE Understanding (ie, knowledge of opioid-related ADEs and their seriousness) and other comparative analgesic perceptions. Parents then made hypothetical decisions to give or withhold prescribed opioids to a postoperative child with varying pain levels and serious (oversedation) and nonserious (nausea) ADE symptoms. Gist ADE Understanding influenced decisions to withhold opioids for a child with nausea/vomiting (β=0.85 [95% confidence interval (CI), 0.74-0.98]) or oversedation (β=0.86 [95% CI, 0.77-0.97]), but not for one with no ADE (β=1.00 [95% CI, 0.98-1.02]). However, while perceived higher seriousness of oversedation influenced withholding opioids when this ADE was present (mean difference=0.36 [95% CI, 0.11-0.61], P=0.005), knowledge that oversedation was possible did not by itself affect behavior (odds ratio=0.80 [95% CI, 0.50-1.29], P=0.362). These data suggest that gist understanding of ADE seriousness, not just its possible presence, is needed to facilitate safe analgesic decisions. Importantly, higher overall ADE understanding did not influence parents' opioid decisions in the presence of high pain and absence of ADEs. Thus, risk information about specific ADEs is unlikely to dissuade parents from efforts to manage pain but may improve their decisions if ADEs should occur. | 25,232,863 | [
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Implanting a Nonpulsatile Axial Flow Left Ventricular Assist Device as a Bridge to Transplant for Systemic Ventricular Failure After A Mustard Procedure. | Right (systemic) ventricular failure is well described after a Mustard procedure for transposition of the great arteries. Sixty-one percent of patients have been reported to show moderate-to-severe dysfunction of the systemic ventricle, 25 years after repair of transposition of the great arteries by a Mustard procedure. In such cases, heart transplant often seems to be the only option. When severe heart failure with hemodynamic instability develops, the only way to bridge these patients to a transplant is implantation of a mechanical circulatory support system. Because of the special anatomic features of the right ventricle, the implantation procedure can be challenging. Here, we report the case of a patient who underwent a left ventricular assist device implant owing to severe heart failure, 36 years after undergoing a Mustard procedure. | 25,232,871 | [
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Concussion: key stakeholders and multidisciplinary participation in making sports safe. | As unstructured play declines, organized sports leagues have become a highly popular form of physical activity in young people. As concussive injuries are garnering increased media attention and public awareness, there is a growing concern for athlete safety. Although athletic trainers and physicians play a large role in keeping athletes healthy and safe, this article investigates nontraditional, multidisciplinary teams that are involved in promoting athlete safety, including the role of equipment makers, coaches, referees, governing bodies of sport, lawmakers, and fans. As opposed to a focus on diagnosing or managing concussive injuries, this article seeks to promote injury prevention strategies. | 25,232,875 | [
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Establishing a clinical service for the management of sports-related concussions. | The clinical management of sports-related concussions is a specialized area of interest with a lack of empirical findings regarding best practice approaches. The University of Pittsburgh Medical Center Sports Concussion Program was the first of its kind; 13 years after its inception, it remains a leader in the clinical management and research of sports-related concussions. This article outlines the essential components of a successful clinical service for the management of sports-related concussions, using the University of Pittsburgh Medical Center Sports Concussion Program as a case example. Drawing on both empirical evidence and anecdotal conclusions from this high-volume clinical practice, this article provides a detailed account of the inner workings of a multidisciplinary concussion clinic with a comprehensive approach to the management of sports-related concussions. A detailed description of the evaluation process and an in-depth analysis of targeted clinical pathways and subtypes of sports-related concussions effectively set the stage for a comprehensive understanding of the assessment, treatment, and rehabilitation model used in Pittsburgh today. | 25,232,886 | [
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Sideline assessment tools for the evaluation of concussion in athletes: a review. | Sports-related concussions, which have become more prevalent in the past decade, are an extremely common phenomenon in organized athletics and create a substantial economic burden on the health care system. Furthermore, they can have devastating impacts on the athletic careers and long-term health of athletes. However, concussion evaluation remains a controversy with respect to diagnosis, management, and return-to-play guidelines for sports-related concussions. This is especially true of the immediate evaluation of sports-related concussion on the sidelines, where decisions must be made quickly and effectively with limited diagnostic resources. Considerable effort has been directed toward developing reliable and valid sidelines assessment modalities for concussion evaluation with a goal of accurately determining whether an athlete requires rapid removal from or is able to return to competition. This paper discusses the role of the concussion specialist on the sidelines during athletic competition and examines the current tools and resources available for the sidelines assessment of concussion. Additionally, new technologies, including electronic applications for Smartphones and tablets, as well as future directions in sidelines assessment of concussion are examined. | 25,232,887 | [
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Boron-doped manganese dioxide for supercapacitors. | The addition of boron as a dopant during the reaction between carbon fiber and permanganate led to significant enhancement of the growth-rate and formation of the porous framework. The doped MnO2 was superior to the pristine sample as electrode materials for supercapacitors in terms of the specific capacitance and rate capability. | 25,232,909 | [
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Enhanced synergism of thermo-chemotherapy by combining highly efficient magnetic hyperthermia with magnetothermally-facilitated drug release. | A magnetothermally-responsive nanocarrier was developed for efficient thermo-chemotherapy by combining efficient magnetic hyperthermia (MH) and magnetothermally-facilitated drug release. The effective magnetothermal-response contributed to high enhancement of tumor cell killing by an operating mechanism involving MH-facilitated cellular uptake and Heat Shock Protein over-expression. | 25,232,926 | [
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Sortase A induces Th17-mediated and antibody-independent immunity to heterologous serotypes of group A streptococci. | Group A streptococci (GAS) are associated with a variety of mucosal and invasive human infections. Recurrent infections by highly heterologous serotypes indicate that cross-serotype immunity is critical for prevention of GAS infections; however, mechanisms underlying serotype-independent protection are poorly understood. Here we report that intranasal vaccination of mice with Sortase A (SrtA), a conserved cell wall bound protein, reduced colonization of nasal-associated lymphoid tissue (NALT) by heterologous serotypes of GAS. Vaccination significantly increased CD4+ IL-17A+ cells in NALT and depletion of IL-17A by neutralizing antibody prevented GAS clearance from NALT which was dependent on immunization with SrtA. Vaccination also induced high levels of SrtA-specific antibodies; however, immunized, B cell-deficient mice cleared streptococcal challenges as efficiently as wild type mice, indicating that the cross-serotype protection is Th17-biased and antibody-independent. Furthermore, efficient GAS clearance from NALT was associated with a rapid neutrophil influx into NALT of immunized mice. These results suggest that serotype independent immune protection against GAS mucosal infection can be achieved by intranasal vaccination with SrtA and enhanced neutrophil function is critical for anti-GAS defense and might be a target for prevention of GAS infections. | 25,232,948 | [
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Effects of multidisciplinary rehabilitation on chronic fatigue in multiple sclerosis: a randomized controlled trial. | Several rehabilitation programmes aim at reducing the impact of fatigue in MS patients. Acute and chronic fatigue should require different management. To assess the effects of individually tailored, multidisciplinary outpatient rehabilitation (MDR) on chronic fatigue. Forty-eight ambulatory MS patients with chronic fatigue were randomized to MDR or to MS-nurse consultation. Fatigue was assessed by the Checklist Individual Strength (CIS-20R). Secondary outcomes included the Modified Fatigue Impact Scale, Fatigue Severity Scale, Functional Independence Measure, Disability and Impact Profile (DIP), Multiple Sclerosis Impact Scale and the Impact on Participation and Autonomy (IPA). The primary outcome measure CIS-20R overall score showed no significant differences between groups at 12 weeks (P = 0.39) and 24 weeks follow-up (P = 0.14), nor for subscales (t = 12 and t = 24, 0.19≤P≤0.88). No significant within-group effects were found for both groups with respect to the primary (0.57≤p≤0.97) and secondary (0.11≤p≤0.92) outcome measures from baseline to 12 or 24 weeks. Multidisciplinary rehabilitation was not more effective in terms of reducing self-reported fatigue in MS patients compared to MS-nurse consultation. Our results suggest that chronic fatigue in patients with MS may be highly invariant over time, irrespective of interventions. controlled-trials.com ISRCTN05017507. | 25,232,955 | [
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Association between polycystic ovary syndrome, oral microbiota and systemic antibody responses. | Polycystic ovary syndrome (PCOS) is a hormonal disorder of women that not only is the leading cause of infertility but also shows a reciprocal link with oral health. This study aimed to investigate the hypothesis that the levels of putative periodontal pathogens in saliva and their antibody response in serum are elevated in PCOS, compared to systemic health. A total of 125 women were included in four groups; 45 women with PCOS and healthy periodontium, 35 women with PCOS and gingivitis, 25 systemically and periodontally healthy women, 20 systemically healthy women with gingivitis. Salivary levels of seven putative periodontal pathogens were analyzed by quantitative real-time polymerase chain reaction and serum antibody levels were analyzed by ELISA. In women with PCOS, salivary Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus oralis and Tannerella forsythia levels were higher than matched systemically healthy women, particularly in the case of gingivitis. Aggregatibacter actinomycetemcomitans and Treponema denticola levels were similar among study groups. The presence of PCOS also enhanced P. gingivalis, Prevotella intermedia and S. oralis serum antibody levels, when gingivitis was also present. Gingival inflammation correlated positively with levels of the studied taxa in saliva, particularly in PCOS. The presence of P. gingivalis and F. nucleatum in saliva also exhibited a strong positive correlation with the corresponding serum antibody levels. In conclusion, as an underlying systemic endocrine condition, PCOS may quantitatively affect the composition of oral microbiota and the raised systemic response to selective members of this microbial community, exerting a confounding role in resultant gingival inflammation and periodontal health. The most consistent effect appeared to be exerted on P. gingivalis. | 25,232,962 | [
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Personality effects on romantic relationship quality through friendship quality: a ten-year longitudinal study in youths. | This study examined whether individuals with different personality types (i.e., overcontrollers, undercontrollers, resilients) had different friendship quality development throughout adolescence. It also investigated whether personality types were indirectly related to romantic relationship quality in young adulthood, via friendship quality development in adolescence. The study employed six waves of longitudinal questionnaire data from Dutch youths who had a romantic relationship when they were young adults. Two age cohorts were followed, from 12 to 21 years and from 16 to 25 years, respectively. Findings showed that resilients reported higher mean levels of friendship quality during adolescence (i.e., more support from, less negative interaction with and less dominance from their best friend) than both overcontrollers and undercontrollers. Through the mean levels of friendship quality throughout adolescence, resilients indirectly experienced higher romantic relationship quality during young adulthood than both overcontrollers and undercontrollers. Thus, results provide support for a developmental model in which adolescent friendship quality is a mechanism linking personality types with young adulthood romantic relationship quality. | 25,232,964 | [
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Scarless gene deletion in methylotrophic Hansenula polymorpha by using mazF as counter-selectable marker. | With increasing application of Hansenula polymorpha in fundamental research and biotechnology, many more genetic manipulations are required. However, these have been restricted for the finiteness of selectable markers. Here, MazF, a toxin protein from Escherichia coli, was investigated as a counter-selectable marker in H. polymorpha. The lethal effect of MazF on yeast cells suggested that it is a candidate for counter-selection in H. polymorpha. Markerless or scarless gene deletion in H. polymorpha was conducted based on selectable markers cassette mazF-zeoR, in which the zeocin resistance cassette and mazF expression cassette were used as positive and counter-selectable markers, respectively. For markerless deletion, the target region can be replaced by CYC1TT via two-step homologous recombination. For scarless deletion, the innate upstream region (5'UP) of target genes rather than CYC1TT mediates homologous recombination to excise both selectable markers and 5' sequence of target genes. Moreover, scarless deletion can be accomplished by using short homologous arms for the effectiveness of mazF as a counter-selectable marker. The applicability of the strategies in markerless or scarless deletion of PEP4, LEU2, and TRP1 indicates that this study provides easy, time-efficient, and host-independent protocols for single or multiple genetic manipulations in H. polymorpha. | 25,233,001 | [
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PCN pincer palladium(II) complex catalyzed enantioselective hydrophosphination of enones: synthesis of pyridine-functionalized chiral phosphine oxides as NC(sp(3))O pincer preligands. | A series of chiral PCN pincer Pd(II) complexes VI-XIII with aryl-based aminophosphine-imidazoline or phosphinite-imidazoline ligands were synthesized and characterized. They were examined as enantioselective catalysts for the hydrophosphination of enones. Among them, complex IX, which features a Ph2PO donor as well as an imidazoline donor with (4S)-phenyl and N-Tol-p groups, was found to be the optimal catalyst. Thus, in the presence of 2-5 mol % of complex IX a wide variety of enones reacted smoothly with diarylphosphines to give the corresponding chiral phosphine derivatives in high yields with enantioselectivities of up to 98% ee. In particular, heteroaryl species such as 2-thienyl-, 2-furyl-, and 2-pyridinyl-containing enones that have a strong coordination ability to the Pd center were also appropriate substrates for the current catalytic system. For example, hydrophosphination of 2-alkenoylpyridines with diphenylphosphine followed by oxidation with H2O2 afforded the corresponding pyridine-functionalized chiral phosphine oxides in good yields with good to excellent enantioselectivities (10 examples, up to 95% ee). Furthermore, it had been demonstrated that the obtained pyridine-containing phosphine oxide acted as a tridentate ligand in the reaction with PdCl2 to form an intriguing NCsp(3)O pincer Pd(II) complex via Csp(3)-H bond activation, which to our knowledge is the first example of a chiral DCsp(3)D' Pd pincer (D ≠ D'; D and D' denote donor atoms such as P, N, etc.). | 25,233,005 | [
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Benefit and adherence of the disease management program "diabetes 2": a comparison of Turkish immigrants and German natives with diabetes. | There is an ongoing debate about equity and equality in health care, and whether immigrants benefit equally from services as the non-immigrant population. The study focuses on benefits from and adherence to the diabetes mellitus type 2 (DM 2) disease management program (DMP) among Turkish immigrants in Germany. So far, it has not been researched whether this group benefits from enrollment in the DMP as well as diabetics from the non-immigrant population. Data on the non-immigrant sample (N = 702) stem from a survey among members of a German health insurance, the Turkish immigrant sample (N = 102) was recruited in the area of Hamburg. Identical questions in both surveys enable comparing major components. Regarding process quality, Turkish diabetics do not differ from the non-immigrant sample; moreover, they have significantly more often received documentation and diabetes training. In terms of outcome quality however, results display a greater benefit on behalf of the non-immigrant sample (e.g., blood parameters and body mass index), and they also met more of the DMP criteria. This underlines the need of diabetics with Turkish background for further education and information in order to become the empowered patient as is intended by the DMP as well as to prevent comorbidities. | 25,233,016 | [
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Enhancement in photocatalytic activity of NiO by supporting onto an Iranian clinoptilolite nano-particles of aqueous solution of cefuroxime pharmaceutical capsule. | NiO/nano-clinoptilolite (NiO-NCP) was prepared by ion exchanging process of the prepared ball-mill nano-clinoptilolite particles with nickel(II) chloride aqueous solution. The prepared composite was characterized by XRD, UV-Vis DRS, TEM and FT-IR and then used as a catalyst in the photodegradation of cefuroxime (CF) using Hg lamp. The best experimental parameters were obtained as: 0.025 g L(-1) of the photocatalyst containing 13.3% NiO, 50 times diluted cefuroxime solution at pH 5. The degradation extent was monitored by UV-Vis spectroscopy and the results were confirmed by HPLC and COD. The kinetics of the photodegradation process obeyed the Langmuir-Hinshelwood model. | 25,233,023 | [
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0.1011522,
-0.009511328,
0.3901894,
0.2990847,
-0.1067769,
0.06003501,
... |
Impact of sediment characteristics on the heavy metal concentration and their ecological risk level of surface sediments of Vaigai river, Tamilnadu, India. | The distributions of the metals (Al, Fe, Mg, Cd, Cr, Cu, Ni, Pb and Zn) were measured for the surface sediments of the Vaigai river, Tamilnadu, India. These values are compared with different standard values to assess the level of toxicity of the heavy metals in the sediments. Risk indices (CF, PLI and PER) are also calculated to understand the level of toxicity of the metals. Multivariate statistical analyses (Pearson's correlation analysis, cluster analysis and factor analysis) are carried out to know the inter-relationship between sediment characteristics and the heavy metals. From this analysis, it is confirmed that the contents of clay and organic matter play an important role to raise the level of heavy metal contents as well as PLI and PER (level of toxicity). Heavy metal concentrations of the samples (after removing silt and clay fractions from bulk samples) show decrease in their concentrations and risk indices compared to the level of bulk samples. | 25,233,032 | [
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Triggering protein adsorption on tailored cationic cellulose surfaces. | The equipment of cellulose ultrathin films with BSA (bovine serum albumin) via cationization of the surface by tailor-made cationic celluloses is described. In this way, matrices for controlled protein deposition are created, whereas the extent of protein affinity to these surfaces is controlled by the charge density and solubility of the tailored cationic cellulose derivative. In order to understand the impact of the cationic cellulose derivatives on the protein affinity, their interaction capacity with fluorescently labeled BSA is investigated at different concentrations and pH values. The amount of deposited material is quantified using QCM-D (quartz crystal microbalance with dissipation monitoring, wet mass) and MP-SPR (multi-parameter surface plasmon resonance, dry mass), and the mass of coupled water is evaluated by combination of QCM-D and SPR data. It turns out that adsorption can be tuned over a wide range (0.6-3.9 mg dry mass m(-2)) depending on the used conditions for adsorption and the type of employed cationic cellulose. After evaluation of protein adsorption, patterned cellulose thin films have been prepared and the cationic celluloses were adsorbed in a similar fashion as in the QCM-D and SPR experiments. Onto these cationic surfaces, fluorescently labeled BSA in different concentrations is deposited by an automatized spotting apparatus and a correlation between the amount of the deposited protein and the fluorescence intensity is established. | 25,233,035 | [
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0.03911164... |
Validation of a questionnaire against clinical assessment in the diagnosis of asthma in school children. | A questionnaire has been used repeatedly in cross-sectional studies to determine the prevalence of asthma, allergic rhinoconjunctivitis (AR) and eczema among schoolchildren in Nordland County, Norway. The current study was designed to validate the questionnaire against clinical assessment as the diagnostic gold standard and to investigate the extent of possible misclassification. A subsample of 801 schoolchildren of 4150, whose parents had answered a questionnaire covering asthma and atopic diseases, underwent a detailed clinical evaluation including a standardized interview, a clinical examination, skin prick tests (SPT), blood samples, spirometry an exercise treadmill test (EIB test) and measurement of exhaled nitrogen oxide (FeNO). The questionnaire had a sensitivity of 0.96 and a specificity of 0.87 for the diagnosis of asthma ever compared to clinical assessment. The overall agreement (kappa) was 0.80. After clinical assessment the prevalence of asthma ever was adjusted from 17.6 % to 16.9 % (95% CI: 15.8-18.0). The most sensitive and specific questions in identifying asthmatic children by the questionnaire were questions asking about diagnosis ('Has the child ever had asthma?') rather than those covering asthma symptoms such as wheeze, shortness of breath and/or cough. A positive exercise test increased the post-test probability for the asthma diagnosis only to a minimal degree. Based on the good agreement between the questionnaire responses and the clinical assessments, it is concluded that the questionnaire had good validity and served as a useful epidemiological tool. Detailed clinical testing added little additional information. | 25,233,047 | [
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Switching and redox isomerism in first-row transition metal complexes containing redox active Schiff base ligands. | The reversible redox isomerisms in first row transition metal complexes of the type ML2 were studied. The six ML2 complexes (M = Mn(III) (), Fe(II) (), Co(III) (), Ni(II) (), Cu(II) () and Zn(II) ()) were synthesized with a redox active Schiff base ligand [2-(3,5-di-tert-butyl-2-hydroxyphenylamino)-4-chlorophenol] (H3L) presenting different oxidation states from -2 to 0 (L(2-), L(-) and L(0)). EPR spectra and magnetic susceptibility measurements indicate the presence of complexes of the type [Mn(III)(L(2-))(L(-))] () with S = 1/2, [Fe(II)(L(-))2] () with S = 2, [Co(III)(L(2-))(L(-))] () with S = 1/2, [Ni(II)(L(-))2] () with S = 1, [Cu(II)(L(-))2] () with S = 1/2 and [Zn(II)(L(-))2] () with S = 0 at high temperatures. Temperature and solvents influence the electronic structures of the species and give several valence tautomers. At low temperatures these complexes present thermally induced metal-to-ligand (, , ) or ligand-to-ligand (in , ) electron transfer (partial or total), resulting in compounds of the type [Mn(IV)(L(2-))2] () with S = 1/2, [Fe(III)(L(-))(L(2-))] () with S = 1, [Ni(III)(L(2-))(L(-))] () with S = 0, [Cu(II)(L(2-))(L(0))] () with S = 1/2 and [Zn(II)(L(2-))(L(0))] () with S = 1. This electron transfer is in agreement with the general trend in the redox potentials of the first row transition metal ions from Mn(ii) to Zn(ii), and it allows us to prepare and stabilize reversibly switchable tautomeric forms in transition metal complexes with redox-active ligands. | 25,233,051 | [
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... |
General slowing of lexical and nonlexical information processing in dementia of the Alzheimer type. | Individuals with very mild and mild dementia of the Alzheimer type (DAT) and age-matched controls performed three lexical and three nonlexical speeded information-processing tasks. The DAT group was slower than the control group on all six tasks. As predicted by general slowing (Nebes & Brady, 1992), most main effects of task condition were accompanied by Group × Condition interactions. That is, as task complexity increased, the response times (RTs) of the DAT group increased more than the RTs of the control group. Multitask regression analyses confirmed the existence of general slowing in DAT, such that the DAT group took approximately 1.8 times as long to process information as the controls on all six tasks. Importantly, lexical and nonlexical processing speed were equivalently affected by DAT. This pattern was observed both in very mild and mild DAT, although the degree of general slowing increased with the severity of the dementia. | 25,233,058 | [
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... |
Undertreatment of dyslipidemia: from the Arabian Gulf to the USA. Time to solve this problem! | Undertreatment of dyslipideamia is a universal problem and reduces the efficasy of hypolipidaemic drugs to reduce cardiovascular event rates. The means to face this problem are available and should be utilized to optimize dyslipidaemia control and clinical outcomes. | 25,233,064 | [
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0.01896865,
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0.1166785,
-0.10250... |
Central nervous system germ cell tumors: an update. | Malignant germ cell tumors in the central nervous system are rare and not well known because they occur mainly in adolescents, an age in which patients are dispersed in adult and pediatric wards. Their biology starts to be unraveled by high-throughput genomics and their treatment is now well defined thanks to international studies, including patients from childhood through adulthood. Chemotherapy gained definitively a role apart from radiotherapy in order to improve tumor control in secreting neoplasms, but also to decrease the volume or dose of radiation therapy in germinomas. Neurocognitive outcome remains good with some disparities because of tumor location, patients with pineal tumors being less impaired than those with supratentorial malignant germ cell tumors. Alterations in the KIT/RAS as well as in the mTOR/AKT pathways have been frequently reported and could represent interesting opportunities to introduce targeted therapies in these neoplasms. Diagnosis and treatment of malignant germ cell tumor of the brain are now well established within experienced multidisciplinary teams taking care of adolescents and young adults. The prognosis of secreting tumors has not yet reached the excellent results obtained for germinomas but aggressive chemotherapy including high-dose chemotherapy with stem-cell support may contribute to improve their outcome. The role of targeted therapies has yet to be determined in view of the recently described molecular findings. | 25,233,069 | [
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Development and validation of the inventory of perceptions of medication administration errors for nurses in Taiwan. | Medication administration errors (MAEs) account for most medication errors, which not only threaten the safety of patients and increase hospital medical costs but also damage the personal and professional development of affected nurses. A feasible instrument measures the perceptions of committing an MAE that may provide support for nurses. The purpose of this study was to conduct psychometric testing of the Inventory of Perceptions for Medication Administration Errors (IPMAE). Psychometric testing of the IPMAE used snowball sampling to collect data from nurse volunteers. Six hundred eighteen nurses completed the IPMAE and a personal profile. The construct validity and the Cronbach's alpha of the inventory were tested. The results indicated that the 12-item IPMAE consisted of four factors, including coping strategy, emotional reaction, fear of blame, and segregation behavior. These four factors accounted for 78.8% of the total variance. The IPMAE showed that both fit indices and Cronbach's alpha coefficients (overall = .90 and subscales = .83-.88) were acceptable. The IPMAE is a valid and reliable instrument for measuring perceptions of MAE occurring among nurses. Nursing directors may use the results generated by the IPMAE to help reduce the negative consequences of MAE events among nurses. | 25,233,070 | [
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-... |
Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells. | Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAHs) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LCs) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LCs rapidly internalize and accumulate DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1 independent. Thus, LCs make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation. | 25,233,073 | [
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0.1265255,
0.3556633,
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-0.... |
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