title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Porphyromonas gingivalis gingipains selectively reduce CD14 expression, leading to macrophage hyporesponsiveness to bacterial infection. | Cysteine proteases (gingipains) from Porphyromonas gingivalis are key virulence factors in chronic periodontitis. Innate immune receptors CD14, Toll-like receptor (TLR) 2 and TLR4 are important in P. gingivalis recognition. We examined the ability of gingipains to cleave CD14, TLR2 and TLR4, and the consequences for the cellular response to bacterial challenge. Macrophages were exposed to Arg (RgpA and RgpB)- and Lys (Kgp)-gingipains, and residual expression of TLR2, TLR4 and CD14 was determined by flow cytometry. The cellular response to live bacteria following exposure to purified gingipains was evaluated by TNFα production and bacterial phagocytosis. RgpA and Kgp decreased CD14 detection in a concentration (p = 0.0000002)- and time (p = 0.03)-dependent manner, whereas RgpB had no significant effect. TLR2 and TLR4 expression were unaffected. Reduction in CD14 expression was more efficient with Lys-gingipain than with Arg-gingipain. A reduced CD14 surface level correlated with decreased TNFα secretion and bacterial phagocytosis following challenge with live P. gingivalis, but the response to heat-killed bacteria was unaffected. Therefore, gingipains reduce CD14 expression without affecting expression of the bacterial-sensing TLRs. Reduced CD14 expression depends on the gingipain hemagglutinin/adhesion site and results in macrophage hyporesponsiveness to bacterial challenge. Further studies are needed to determine if reduced CD14 expression is linked to periodontitis induced by P. gingivalis. | 25,228,314 | [
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Quantitative analysis of resistance to natural killer attacks reveals stepwise killing kinetics. | Molecular mechanisms can protect cancer cells from immune attacks. At the level of bulk tissue, these survival mechanisms are often indistinguishable and simply appear as reduced cell death. However, by tracking individual cell survival and death times, we found broad variation in the kinetics of immune evasion. In response to attacks by natural killer cells, we observed that some cancer lines exhibited exponential survival time distributions. Slowly killed cancer lines had reduced exponential rate constants. In contrast, a line engineered to express the serpin protein PI-9, which is known to promote resistance to immune killing, exhibited a markedly nonexponential survival time distribution. By following the histories of individual cancer cells with multiplexed reporters, we obtained evidence that two or more immune attacks are likely required to kill serpin-expressing cells. Thus, resistance is a finite and measurable quantity, with a distinct kinetic signature. A quantitative model based on independently measured parameters is consistent with our conclusions. | 25,228,316 | [
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An experimental study investigating the effect of pain relief from oral analgesia on lumbar range of motion, velocity, acceleration and movement irregularity. | Movement alterations are often reported in individuals with back pain. However the mechanisms behind these movement alterations are not well understood. A commonly cited mechanism is pain. The aim of this study was to investigate the effect of pain reduction, from oral analgesia, on lumbar kinematics in individuals with acute and chronic low back pain. A prospective, cross-sectional, experimental repeated-measures design was used. Twenty acute and 20 chronic individuals with low back pain were recruited from General Practitioner and self-referrals to therapy departments for low back pain. Participants complained of movement evoked low back pain. Inertial sensors were attached to the sacrum and lumbar spine and used to measure kinematics. Kinematic variables measured were range of motion, angular velocity and angular acceleration as well as a determining movement irregularity (a measure of deviation from smooth motion). Kinematics were investigated before and after administration of oral analgesia to instigate pain reduction. Pain was significantly reduced following oral analgesia. There were no significant effects on the kinematic variables before and after pain reduction from oral analgesia. There was no interaction between the variables group (acute and chronic) and time (pre and post pain reduction). The results demonstrate that pain reduction did not alter lumbar range of motion, angular velocity, angular acceleration or movement irregularity questioning the role of pain in lumbar kinematics. | 25,228,332 | [
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What drove reversions to quadrupedality in ornithischian dinosaurs? Testing hypotheses using centre of mass modelling. | The exceptionally rare transition to quadrupedalism from bipedal ancestors occurred on three independent occasions in ornithischian dinosaurs. The possible driving forces behind these transitions remain elusive, but several hypotheses-including the development of dermal armour and the expansion of head size and cranial ornamentation-have been proposed to account for this major shift in stance. We modelled the position of the centre of mass (CoM) in several exemplar ornithischian taxa and demonstrate that the anterior shifts in CoM position associated with the development of an enlarged skull ornamented with horns and frills for display/defence may have been one of the drivers promoting ceratopsian quadrupedality. A posterior shift in CoM position coincident with the development of extensive dermal armour in thyreophorans demonstrates this cannot have been a primary causative mechanism for quadrupedality in this clade. Quadrupedalism developed in response to different selective pressures in each ornithischian lineage, indicating different evolutionary pathways to convergent quadrupedal morphology. | 25,228,349 | [
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Informed consent form challenges for genetic research in a developing Arab country with high risk for genetic disease. | The prevalence of genetic disease is high in the Middle East, particularly in the United Arab Emirates. Our study assesses the information provided in, and the readability ease of, informed consent forms (ICF) for genetic research studies. A multicenter retrospective cross-sectional review of 54 ICFs was conducted to assess compliance by comparing them with standard good clinical practice guidelines for developing consent forms. Readability of the forms was determined using the Flesch-Kincaid scale. Overall Good Clinical Practice compliance for the ICFs averaged at 63 %. Information regarding privacy, confidentiality, specimen collection and storage were absent from the majority of the ICFs. Readability ease score was low (36.7 ± 4.6) and required college-level (11.8 ± 1.4) reading skills to understand the information. Our study highlights the need to improve the readability and information contained in the ICFs for genetic research studies in our setting. Our findings may be generalized to similar cultures in the Middle East and Asia. | 25,228,356 | [
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Risk factors of open converted cholecystectomy for cholelithiasis after endoscopic removal of choledocholithiasis. | Open converted cholecystectomy could occur in patients who planned for laparoscopic cholecystectomy after endoscopic removal of choledocholithiasis. To evaluate the risk factors associated with open converted cholecystectomy. The data for all patients who underwent cholecystectomy after endoscopic removal of choledocholithiasis were retrospectively reviewed. Factors predictive for conversion to open cholecystectomy were analyzed. The rate of open converted cholecystectomy was 15.7 %. In multivariate analysis, cholecystitis (OR 1.908, 95 % CI 1.390-6.388, p = 0.005), mechanical lithotripsy (OR 6.129, 95 % CI 1.867-20.123, p < 0.005), and two or more choledocholithiases (OR 2.202, 95 % CI 1.097-4.420, p = 0.026) revealed significant risk factors for conversion to open cholecystectomy. Analyzing the risk factors for open converted cholecystectomy according to duration from endoscopic stone removal to cholecystectomy (within 2 weeks, between 2 and 6 weeks, and beyond 6 weeks), acute cholangitis (OR 3.374, 95 % CI 1.267-8.988, p = 0.015), cholecystitis (OR 3.127, 95 % CI 1.100-8.894, p = 0.033), and mechanical lithotripsy (OR 17.504, 95 % CI 3.548-86.355, p < 0.005) were related to open converted cholecystectomy in ≤2 weeks group. For patients who need cholecystectomy after endoscopic removal of choledocholithiasis, endoscopic retrograde cholangiography-related factors predictive for open converted cholecystectomy are helpful in planning the appropriate timing of surgery. | 25,228,363 | [
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ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate antiviral responses. | Upon binding to RNA structures from invading viruses, RIG-I and MDA5 are recruited to mitochondria to interact with VISA and initiate antiviral type I interferon (IFN) responses. How this process is mediated is less understood. In this report, we demonstrate that ECSIT is an essential scaffolding protein that mediates the association of VISA and RIG-I or MDA5. Overexpression of ECSIT potentiated virus-triggered activation of IFN-regulatory factor 3 (IRF3) and expression of IFNB1, whereas knockdown of ECSIT impaired viral infection-induced activation of IRF3 and expression of IFNB1 as well as cellular antiviral responses. Mechanistically, ECSIT was associated with VISA on mitochondria and important for bridging RIG-I and MDA5 to VISA. Our findings suggest that ECSIT mediates virus-triggered type I IFN induction by bridging RIG-I and MDA5 to the VISA complex, and provide new insights into the molecular events of innate antiviral immune responses. | 25,228,397 | [
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Central emboli rather than saddle emboli predict adverse outcomes in patients with acute pulmonary embolism. | In patients with acute pulmonary embolism (PE), the prognostic implications of saddle or central emboli, as observed on computed tomography (CT), remain to be established. The aim of the present study was to assess whether the presence of saddle and central emboli could be used to predict clinical outcomes in patients with PE. The authors retrospectively reviewed 743 consecutive patients hospitalized at a tertiary referral center with a diagnosis of PE based on multi-detector row CT scan. All the clinical variables did not differ between saddle emboli (5.8% [n = 43]) and right or left pulmonary artery emboli (29.7% [n = 221]), and the frequency of an adverse outcome was not significantly different between the two groups. Saddle emboli and right or left pulmonary artery emboli were grouped into central emboli (35.5% [n = 264]). Patients were allocated to an adverse outcome group (10.5% [n = 78]) or a control group (89.5% [n = 665]). Multivariate analysis demonstrated that PE severity index (PESI) score (class IV-V), N-terminal-pro-B-type natriuretic peptide level (≥ 1,406 pg/mL), right ventricular dilation on CT (right ventricle/left ventricle diameter ratio ≥ 1), and central emboli significantly predicted an adverse outcome. The addition of central emboli to other established prognostic factors such as PESI enhanced the positive predictive values and positive likelihood ratios of an adverse outcome for acute PE. Rather than saddle emboli, central emboli could be an independent prognostic factor of adverse outcomes in patients with acute PE and provide additional prognostic value when combined with other prognostic factors. | 25,228,399 | [
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Hyperpolarized and inert gas MRI: the future. | Magnetic resonance imaging (MRI) is a potentially ideal imaging modality for noninvasive, nonionizing, and longitudinal assessment of disease. Hyperpolarized (HP) agents have been developed in the past 20 years for MR imaging, and they have the potential to vastly improve MRI sensitivity for the diagnosis and management of various diseases. The polarization of nuclear magnetic resonance (NMR)-sensitive nuclei other than (1)H (e.g., (3)He, (129)Xe) can be enhanced by a factor of up to 100,000 times above thermal equilibrium levels, which enables direct detection of the HP agent with no background signal. In this review, a number of HP media applications in MR imaging are discussed, including HP (3)He and (129)Xe lung imaging, HP (129)Xe brain imaging, and HP (129)Xe biosensors. Inert fluorinated gas MRI, which is a new lung imaging technique that does not require hyperpolarization, is also briefly discussed. This technique will likely be an important future direction for the HP gas lung imaging community. | 25,228,404 | [
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Maternal and perinatal predictors of newborn iron status. | To describe iron status at birth in a population sample of children. Cord blood samples were obtained at birth from 131 infants enrolled in the cohort study Growing Up in New Zealand. Cord blood serum ferritin (SF) and haemoglobin (Hb) concentrations were measured and associations of SF and Hb with maternal and birth characteristics were determined. Demographics were comparable to the larger cohort, except for having a higher pre-pregnancy body mass index (26.9 vs. 25.4 kg/m2, P=0.005), lower frequency of cigarette smoking during pregnancy (2% vs. 11%, P=0.0004), and smaller proportion with birth-weight <2500 g (0% vs. 5%, P=0.03). Median (interquartile range) SF was 135 (88-180) mcg/L and mean (plus or minus SD) Hb was 160 plus or minus 17 g/L. Eight newborns (7%) had cord SF levels indicative of iron deficiency (SF <35 mcg/L), two newborns were anaemic (Hb <130 g/L) and none had iron deficiency anaemia. Median SF was lower in newborns whose mothers consumed greater than or equal to 3 servings of milk/day during the pregnancy (131 vs. 151 mcg/L, P=0.04). No other associations with SF or Hb were observed. Iron deficiency is present in 7% of newborns in New Zealand. Newborns whose mothers consumed more milk during pregnancy had a lower median SF concentration. | 25,228,422 | [
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Prognostic value and long-term variation of high sensitivity troponin T in clinically stable haemodialysis patients. | To provide data on the long-term prognostic relevance and variation of high sensitivity troponin T (hsTnT) in haemodialysis patients. In 238 stable, asymptomatic haemodialysis patients from a single-centre hsTnT was measured at baseline, 18 and 22 months and outcomes assessed for 24 months. Baseline hsTnT was a significant predictor of all cause (+10 ng/l, HR 1.017, 95%CI 1.011-1.023, p<0.0001) and cardiovascular death (HR 1.02, 95%CI 1.013-1.0026, p<0.0001). HsTnT>140 ng/L was a strong predictor of cardiovascular mortality (HR 8.51, 95%CI 1.907-38.032; p<0.0001). HsTnT increased by >50% in less than one-third of patients, and doubled in only 10% of patients, during 18 and 22 months follow up. In clinically stable hemodialysis patients, higher hsTnT was associated with both total and CV mortality. In most patients variation in levels of hsTnT between 18 and 22 months was <50%, and on average the increase in hsTnT was small. | 25,228,425 | [
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Incidence of abnormal retropharyngeal lymph nodes in sinonasal malignancies among adults. | The aim of this study is to investigate the relationship between abnormal retropharyngeal lymph nodes (RPLNs) and sinonasal malignancies among adults. Magnetic resonance and computed tomography images from 89 patients over 20 years old who were all histopathologically confirmed to have sinonasal malignancies from September 2001 to April 2014 were assessed retrospectively. Abnormal RPLNs were determined as those >5 mm in shortest axis or showing heterogeneous enhancement on axial images. Locations of sinonasal malignancies were categorized using the anterior border of the pterygopalatine fossa as a boundary: (a) anterior lesions, only present anterior to the boundary, or (b) posterior lesions, present or extending posterior to the boundary. Fisher's exact test was used for the analysis of the relationship between frequency of abnormal RPLNs and lesion location. Abnormal RPLNs were present in 13 of 89 patients (15%), including 6 of 41 squamous cell carcinomas (15%), 4 of 24 malignant lymphomas (17%), 3 of 5 olfactory neuroblastomas (60%), and 0 of 19 others (0%). Four of the 39 patients (10%) with anterior lesions showed abnormal RPLNs, compared to 9 of 50 patients (18%) with posterior lesions. No significant difference in frequency of abnormal RPLNs was apparent between anterior and posterior lesions (P = 0.37). In primary sinonasal malignancies among adults, the highest incidence of abnormal RPLNs was seen with olfactory neuroblastoma. The frequency of abnormal RPLNs was unaffected by the location of sinonasal malignancies among adults. | 25,228,450 | [
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Drug fever due to a single dose of pantoprazole. | Although proton pump inhibitors (PPI) are generally well tolerated, with most adverse effects being minor and self-limiting, there are singular reports on hypersensitivity immune reactions triggered by a PPI or its metabolites. Here we report a case of acute drug-induced fever with leukocytosis and a transient increase in CRP due to pantoprazole. This was apparently an idiosyncratic reaction (inflammatory fever), showing no cross-sensitivity towards esomeprazole. | 25,228,460 | [
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On-chip sample preparation and analyte quantification using a microfluidic aqueous two-phase extraction coupled with an immunoassay. | Immunoassays are fast and sensitive techniques for analyte quantification, and their use in point-of-care devices for medical, environmental, and food safety applications has potential benefits of cost, portability, and multiplexing. However, immunoassays are often affected by matrix interference effects, requiring the use of complex laboratory extraction and concentration procedures in order to achieve the required sensitivity. In this paper we propose an integrated microfluidic device for the simultaneous matrix clean-up, concentration and detection. This device consists of two modules in series, the first performing an aqueous two-phase extraction (ATPE) for matrix extraction and analyte pre-concentration, and the second an immunoassay for quantification. The model analyte was the mycotoxin ochratoxin A (OTA) in a wine matrix. Using this strategy, a limit of detection (LoD) of 0.26 ng mL(-1) was obtained for red wine spiked with OTA, well below the regulatory limit for OTA in wines of 2 ng mL(-1) set by the European Union. Furthermore, the linear response on the logarithmic concentration scale was observed to span 3 orders of magnitude (0.1-100 ng mL(-1)). These results are comparable to those obtained for the quantification of OTA in plain buffer without an integrated ATPE (LoD = 0.15 ng mL(-1)). The proposed method was also found to provide similar results for markedly different matrices, such as red and white wines. This novel approach based on aqueous two-phase systems can help the development of point-of-care devices that can directly deal with real samples in complex matrices without the need for extra extraction processes and equipment. | 25,228,473 | [
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Genome segment 4 of Antheraea mylitta cytoplasmic polyhedrosis virus encodes RNA triphosphatase and methyltransferases. | Cloning and sequencing of Antheraea mylitta cytoplasmic polyhedrosis virus (AmCPV) genome segment S4 showed that it consists of 3410 nt with a single ORF of 1110 aa which could encode a protein of ~127 kDa (p127). Bioinformatics analysis showed the presence of a 5' RNA triphosphatase (RTPase) domain (LRDR), a S-adenosyl-l-methionine (SAM)-binding (GxGxG) motif and the KDKE tetrad of 2'-O-methyltransferase (MTase), which suggested that S4 may encode RTPase and MTase. The ORF of S4 was expressed in Escherichia coli as a His-tagged fusion protein and purified by nickel-nitrilotriacetic acid affinity chromatography. Biochemical analysis of recombinant p127 showed its RTPase as well as SAM-dependent guanine N(7)-and ribose 2'-O-MTase activities. A MTase assay using in vitro transcribed AmCPV S2 RNA having a 5' G*pppG end showed that guanine N(7) methylation occurred prior to the ribose 2'-O methylation to yield a m(7)GpppG/m(7)GpppGm RNA cap. Mutagenesis of the SAM-binding (GxGxG) motif (G831A) completely abolished N(7)- and 2'-O-MTase activities, indicating the importance of these residues for capping. From the kinetic analysis, the Km values of N(7)-MTase for SAM and RNA were calculated as 4.41 and 0.39 µM, respectively. These results suggested that AmCPV S4-encoded p127 catalyses RTPase and two cap methylation reactions for capping the 5' end of viral RNA. | 25,228,490 | [
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Rationale and Applications of Survival Tree and Survival Ensemble Methods. | Classification and Regression Trees (CART), and their successors-bagging and random forests, are statistical learning tools that are receiving increasing attention. However, due to characteristics of censored data collection, standard CART algorithms are not immediately transferable to the context of survival analysis. Questions about the occurrence and timing of events arise throughout psychological and behavioral sciences, especially in longitudinal studies. The prediction power and other key features of tree-based methods are promising in studies where an event occurrence is the outcome of interest. This article reviews existing tree algorithms designed specifically for censored responses as well as recently developed survival ensemble methods, and introduces available computer software. Through simulations and a practical example, merits and limitations of these methods are discussed. Suggestions are provided for practical use. | 25,228,495 | [
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Impaired degradation and aberrant phagocytosis of necrotic cell debris in the peripheral blood of patients with primary Sjögren's syndrome. | Aberrant removal of necrotic debris is considered a feature with inflammatory consequences in SLE. Herein, primary Sjögren's syndrome (SS) patients were investigated for the first time for the capacity of their sera to degrade secondary necrotic cell remnants (SNEC) and DNA (endonuclease DNase1 activity), as well as for uptake of SNEC by blood-borne phagocytes. For comparison, specimens from unselected SLE and RA patients and from healthy blood donors (HBD) were also studied. Compared to HBD, the sera from SS and SLE patients studied (but not RA) were found to exhibit significantly impaired capacity for degradation of SNEC (both for p = 0.007) and deficient DNase1 activity (both for p < 0.0001). The deficient DNase1 activity in SS and SLE sera did not owe to decreased DNase1 protein levels. It correlated inversely with increased serum levels of circulating nucleosomes and cell-free DNA (p < 0.0001), as well as with the disease activity indices of SS (r = -0.445, p = 0.0001) and SLE (r = -0.500, p = 0.013). In ex-vivo whole blood analyses, SS and SLE patients (but not RA) also manifested significantly increased SNEC-phagocytosis by monocytes and granulocytes (all for p < 0.0001) that also correlated with disease severity indices of SS (p = 0.001) and SLE (p = 0.01). In various cross-admixture experiments, such aberration was found to reside in the hyperfunctional activity of phagocytes, the impaired degrading activity of serum DNase1 and the SNEC-binding capacity of serum IgG of SS and SLE patients. The sera of SS and SLE patients (but not of RA) induced significant SNEC-phagocytosis by healthy monocytes that correlated inversely with the DNase1 activity (r = -0.634, p < 0.0001) of these sera. In line with this, the inhibition of DNase1 in HBD sera by G-actin was found to lead to significantly diminished SNEC degradation and increased SNEC uptake by healthy phagocytes (p = 0.0009), supporting the important physiologic role of serum DNase1 in the prevention of SNEC-phagocytosis. Purified serum IgG preparations from SS and SLE patients manifested increased binding to SNEC and were able to enhance significantly the engulfment of SNEC by healthy phagocytes both directly (under serum-free conditions, p ≤ 0.009) and via the prevention of physiologic degradation of SNEC by serum, most likely due to their "shielding" against endonuclease digestion (p = 0.0005). These data indicate that upon cell necrosis, the immune system of SS and SLE patients may be overly exposed to the necrotic debris, a fact that probably holds a key role in the pathogenesis of inflammatory and autoimmune reactions observed in these disorders. | 25,228,497 | [
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Rho-kinase inhibitor reduces hypersensitivity to ANG II in human mesenteric arteries retrieved and conserved under the same conditions as transplanted organs. | Rho-kinase and GTP-ase Rho are important regulators of vascular tone and blood pressure. The aim of this study was to investigate the role of Rho-kinase in artery reactions induced by angiotensin II (ANG II) and the effects of ischemia-reperfusion injury as well as the function of intra- and extracellular calcium in these reactions. Experiments were performed on mesenteric superior arteries procured from cadaveric organ donors and conserved under the same conditions as transplanted kidneys. The vascular contraction in reaction to ANG II was measured in the presence of Rho-kinase inhibitor Y-27632, after ischemia and reperfusion, in Ca2+ and Ca2+-free solution. The maximal response to ANG II was reduced after ischemia, while an increase was observed after reperfusion. Vascular contraction induced by ANG II was decreased by Y-27632. Y-27632 reduced vascular contraction after reperfusion, both in Ca2+ and Ca2+-free solution. Reperfusion augments vascular contraction in reaction to ANG II. The Rho-kinase inhibitor Y-27632 reduces the hypersensitivity to ANG II after reperfusion mediated by both intra- and extracellular calcium. These results confirm the role of Rho-kinase in receptor-independent function of ANG II and in reperfusion-induced hypersensitivity. | 25,228,510 | [
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[Possible involvement of 5-HT₇ receptor in pathophysiology of affective disorders and action of antidepressant drugs]. | The 5-HT7 receptor has recently received considerable attention since its involvement has been implicated in cognitive disturbances, sleep and circadian rhythmicity disorders, anxiety and depression. At the cellular level, 5-HT7 receptors increase the excitability of excitatory cells and appear to modulate both glutamatergic and GABAergic transmission in the hippocampus. It has been proposed that 5-HT7 receptors also modulate glutamatergic and GABAergic transmission in the raphe nuclei and these effects may play a role in the regulation of circadian rhythms. Repeated administration of the selective 5-HT7 receptor antagonist induced functional desensitization of the 5-HT7 receptor system at the level of its reactivity and effector proteins. These effects resemble the outcome of treatment of rats with antidepressant drugs. Chronic stress and elevated level of corticosterone increase the reactivity of 5-HT7 receptors in the hippocampus. Treatment of rats with a selective 5-HT7 receptor antagonist also results in attenuation of glutamatergic transmission in the frontal cortex and it prevents the occurrence of stress-induced modifications of glutamatergic transmission and long-term synaptic plasticity. These results are consistent with the hypothesis that 5-HT7 receptor antagonism might, potentially, be used for the treatment of cognitive deficits and mood disorders. | 25,228,519 | [
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[The importance of selenium in Hashimoto's disease]. | The aim of this study was to present the current state of knowledge on the role of selenium in the treatment of Hashimoto's disease. In recent years, the number of cases of autoimmune Hashimoto's thyroiditis - a chronic disease that usually leads to hypothyroidism - has increased. Most patients have elevated levels of anti-TPO antibodies. The presence of these antibodies has an effect on subsequent thyroid damage. So far we have not developed an effective, standard therapy of this disease. However, more attention is being paid to the relationship between supplementation of selenium deficiency and inhibition of production of anti-TPO antibodies in patients with Hashimoto's thyroiditis. Therefore, selenium supplementation may be an effective option in the treatment of this disease. | 25,228,521 | [
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Acute lymphoblastic leukemia in adolescents and young adults. | The cure rate of acute lymphoblastic leukemia (ALL) in children is 80%, compared to less than half in adults. A major proportion of this cure rate drop occurs in adolescents and young adults (AYAs). The age range defining this population varies between studies, biological characteristics are different from both younger children and older adults, and AYAs are treated either by pediatric or adult oncologists, who often apply different treatment approaches to the same ALL patient population. The outcome of AYAs aged 15-21 years treated by more contemporary pediatric protocols is similar to that of younger children but is inferior when using adult regimens. This motivated studying AYA patients, including those above the age of 21 years, with pediatric or 'pediatrics-inspired' regimens that intensified nonmyelosuppressive drugs such as vincristine, steroids and asparaginase, with very promising preliminary results. Discovering new mutations in AYA ALL will help stratify patients into risk subgroups and identify targets for novel agents. This, together with fine-tuning pediatric chemotherapy principles will hopefully finally decrease the cure rate gap between children and AYAs - and even older adults. | 25,228,551 | [
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The challenging aspects of managing adolescents and young adults with Hodgkin's lymphoma. | Cancer in the adolescent and young adult (AYA) is the second leading cause of nonaccidental death with hematological malignancies spiking during this period. Treatment of AYAs with hematological malignancies usually follows either pediatric or adult protocols with sufficient information lacking on subgroup analyses regarding course and outcome. In this review we will outline up-to-date treatment possibilities for AYAs diagnosed with Hodgkin's lymphoma. Early and late toxicities will be addressed and future directions of research suggested. | 25,228,552 | [
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Adolescents and young adults with non-Hodgkin's lymphoma: slipping between the cracks. | Adolescents and young adults (AYAs) with cancer have inferior survival as compared to children. The reasons for this survival gap are multifactorial and related to psychosocial aspects, patient- and disease-related biological characteristics as well as to therapeutic approaches within this age span. Non-Hodgkin's lymphoma (NHL) comprises approximately 7% of cancer among AYAs, and patient allocation and therapy vary between health systems. In this systematic review we focus on the current biological and clinical knowledge relevant to AYAs with NHL applying these data to the clinical approach and practice. Data are insufficient to recommend a pediatric or an adult approach for AYAs with diffuse large B-cell lymphoma and anaplastic large cell lymphoma. Dose-adjusted EPOCH-R seems to be a promising, radiation-free approach for AYAs with primary mediastinal B-cell lymphoma. Limitations in data interpretation include the lack of interventional trials tailored specifically for the AYA population and the lack of uniform criteria for staging and response assessment in pediatric and adult trials. | 25,228,553 | [
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Aplastic anemia in adolescents and young adults. | Adolescent and young adult patient presentations of aplastic anemia require a particular perspective on both diagnosis and treatment. This unique age group necessitates a thorough diagnostic evaluation to ensure the etiology, acquired or inherited, is sufficiently determined. The treatment options include human leukocyte antigen-identical sibling hematopoietic cell transplantation or immunosuppressive therapy, and both require attention to the specific medical and social needs of these adolescents and young adults. Longitudinal surveillance throughout life for the development of late complications of the disease and treatment is mandatory. | 25,228,559 | [
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[Treatment of hepatitis C - an imminent revolution]. | Treatment of hepatitis C is approaching a revolution. During the last years, many agents have been developed that directly interfere with the viral replication cycle. Therapy of hepatitis C will no longer need Interferon in the future. The new therapies will be shorter, more efficient and with fewer side effects. For patients, the burden of treatment will drop substantially. Even patients are traditionally classified who as "difficult to treat", such as cirrhotic patients, HIV/hepatitis C coinfected patients and patients after liver transplantation will have better chances of cure. For more patients to benefit from the new therapies, identification of infected individuals and diagnostic investigations have to be improved. | 25,228,574 | [
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[Progressive cutaneous and pulmonary lesions without infectious etiology: two cases reports of sweet syndrome with pulmonary involvement]. | Sweet syndrome is a non infectious febrile disease with a neutrophilic infiltrate of dermis. Extracutaneous involvement can occur. We report two cases of Sweet syndrome with cutaneous and pulmonary involvement and give a short review of the literature of pulmonary involvement in Sweet syndrome. | 25,228,576 | [
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Explicating the role of sexual coercion and vulnerability alcohol expectancies in rape attributions. | Despite evidence suggesting that alcohol expectancies may influence people's rape perceptions, no study to date has measured context-specific expectancies comprehensively. This study represents an initial investigation of the role of sexual coercion and vulnerability alcohol expectancies in young Australian adults' rape blame attributions. Using a vignette method, it was hypothesized that participants' stronger expectancy endorsement would predict lesser perpetrator blame and greater victim blame. Participants (n = 210; 34.9% males; 18-25 years) read a hypothetical rape scenario and rated dimensions of blameworthiness attributed to the intoxicated sexual perpetrator and victim. Participants completed the Sexual Coercion and Sexual Vulnerability subscales of the Drinking Expectancy Sexual Vulnerabilities Questionnaire for the targets self, men, and women in addition to measures of traditional gender role attitudes and rape myth acceptance. Hierarchical multiple regressions revealed that, as expected, stronger sexual coercion expectancy predicted lower perpetrator blame and greater victim blame. Self-oriented expectancy predicted evaluations of the perpetrator whereas other-oriented expectancy predicted victim evaluations. These effects were robust after controlling for gender role attitudes and rape myth acceptance. Alcohol expectancies appear to be part of a network of beliefs and attitudes which perpetuate biased rape attributions and may be useful to challenge in altering rape perceptions. | 25,228,594 | [
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Establishing National Neonatal Perinatal Database and birth defects registry network - need of the hour! | Early detection and prevention of birth defects is necessary to further reduce neonatal morbidity and mortality. A birth defect registry or surveillance system is necessary to assess the exact magnitude, profile and modifiable risk factors for birth defects. We review the existing efforts and suggest possible options for addressing this important issue. Connecting birth defects registry with the pre-existing programs such as National Neonatal Perinatal Database could be one of the option. | 25,228,597 | [
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Molecular copro-prevalence of Cryptosporidium in Egyptian children and evaluation of three diagnostic methods. | To determine molecular prevalence of Cryptosporidium in a cohort of Egyptian children and compare three diagnostic tests. Stool samples from children with diarrhea (n=150) and from apparently healthy children (n=100) were examined for Cryptosporidium using microscopy, enzyme linked immuosorbant assay (ELISA) and nested polymerase chain reaction (nPCR). nPCR detected Cryptosporidium in 22.4% of children. Acid-fast stain and ELISA showed false negativity but 100% specificity with nPCR as gold standard. Cryptosporidium is a common cause of diarrhea in children in Egypt. | 25,228,606 | [
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ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes. | ZNF750 controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes, a role underscored by pathogenic ZNF750 mutations in cancer and psoriasis. How ZNF750 accomplishes these dual gene regulatory impacts is unknown. Here, we characterized ZNF750 as a transcription factor that binds both the progenitor and differentiation genes that it controls at a CCNNAGGC DNA motif. ZNF750 interacts with the pluripotency transcription factor KLF4 and chromatin regulators RCOR1, KDM1A, and CTBP1/2 through conserved PLNLS sequences. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) and gene depletion revealed that KLF4 colocalizes ∼ 10 base pairs from ZNF750 at differentiation target genes to facilitate their activation but is unnecessary for ZNF750-mediated progenitor gene repression. In contrast, KDM1A colocalizes with ZNF750 at progenitor genes and facilitates their repression but is unnecessary for ZNF750-driven differentiation. ZNF750 thus controls differentiation in concert with RCOR1 and CTBP1/2 by acting with either KDM1A to repress progenitor genes or KLF4 to induce differentiation genes. | 25,228,645 | [
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Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells. | Transcription of endogenous retroviruses (ERVs) is inhibited by de novo DNA methylation during gametogenesis, a process initiated after birth in oocytes and at approximately embryonic day 15.5 (E15.5) in prospermatogonia. Earlier in germline development, the genome, including most retrotransposons, is progressively demethylated. Young ERVK and ERV1 elements, however, retain intermediate methylation levels. As DNA methylation reaches a low point in E13.5 primordial germ cells (PGCs) of both sexes, we determined whether retrotransposons are marked by H3K9me3 and H3K27me3 using a recently developed low-input ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing) method. Although these repressive histone modifications are found predominantly on distinct genomic regions in E13.5 PGCs, they concurrently mark partially methylated long terminal repeats (LTRs) and LINE1 elements. Germline-specific conditional knockout of the H3K9 methyltransferase SETDB1 yields a decrease of both marks and DNA methylation at H3K9me3-enriched retrotransposon families. Strikingly, Setdb1 knockout E13.5 PGCs show concomitant derepression of many marked ERVs, including intracisternal A particle (IAP), ETn, and ERVK10C elements, and ERV-proximal genes, a subset in a sex-dependent manner. Furthermore, Setdb1 deficiency is associated with a reduced number of male E13.5 PGCs and postnatal hypogonadism in both sexes. Taken together, these observations reveal that SETDB1 is an essential guardian against proviral expression prior to the onset of de novo DNA methylation in the germline. | 25,228,647 | [
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Effect of Cilostazol Following Endovascular Intervention for Peripheral Artery Disease. | Efficacy of endovascular therapy (EVT) with nitinol stents for femoropopliteal (FP) lesions is limited by restenosis. Oral cilostazol reduces angiographic restenosis rate; however, treatment duration remains unclear. In a retrospective analysis of a multicenter database of 3471 consecutive limbs in 2737 patients (mean age: 72 ± 9 years; 61% diabetic; and 26% on regular dialysis) undergoing EVT for FP lesions between January 2004 and December 2011, we compared Kaplan-Meier estimated primary patency after EVT followed or not by cilostazol treatment. We used Cox hazard regression analysis to assess temporal association between cilostazol treatment and post-EVT restenosis. Five-year primary patency was higher in the cilostazol group than in the noncilostazol group (57% vs 47%, P < .0001). Cilostazol treatment was inversely associated with restenosis for the first 2 years following EVT (P < .05); however, no significant association was observed thereafter. Cilostazol use therefore appears efficacious in preventing restenosis up to 2 years after EVT for FP lesions. | 25,228,649 | [
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Handling an Isolated Malleus Handle Fracture: Current Diagnostic Work-up and Treatment Options. | An isolated malleus handle fracture is rare and presents with vague otological symptoms. Diagnosis depends on careful history taking and otoscopic examination. Different treatment options are available. Reconstruction with hydroxyapatite bone cement is a relatively new technique. The aim of this article is to review the current diagnostic work-up and treatment options and to demonstrate our method of treatment with hydroxyapatite bone cement. Three cases, repaired with hydroxyapatite bone cement in a tertiary referral otologic center, were retrospectively analyzed. A review of the literature on diagnosis and treatment procedures was performed. One fracture occurred by withdrawing a finger from the external auditory canal and 2 occurred without clear prior trauma. Our 3 cases were successfully repaired with hydroxyapatite bone cement. Diagnosis of an isolated malleus handle fracture still depends on careful clinical examination. In addition to pure tone audiometry, both low and higher frequency tympanometry may be useful. High resolution computed tomography with reformatting through the malleus handle is the most accurate imaging modality. Reconstruction with hydroxyapatite bone cement is reliable by restoring the original situation with only minimal manipulation and without additional ossicular interruption. | 25,228,668 | [
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Fluoroquinolone use in a child associated with development of osteochondritis dissecans. | Several aetiological theories have been proposed for the development of osteochondritis dissecans. Cartilage toxicity after fluoroquinolone use has been well documented in vitro. We present a case report of a 10-year-old child who underwent a prolonged 18-month course of ciprofloxacin therapy for chronic urinary tract infections. This patient later developed an osteochondritis dissecans lesion of the medial femoral condyle. We hypothesise that the fluoroquinolone therapy disrupted normal endochondral ossification, resulting in development of osteochondritis dissecans. The aetiology of osteochondritis dissecans is still unclear, and this case describes an association between fluoroquinolone use and osteochondritis dissecans development. | 25,228,675 | [
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Idiopathic intracranial hypertension: Clinical nosography and field-testing of the ICHD diagnostic criteria. A case-control study. | The aims of this article are to characterize the headache in idiopathic intracranial hypertension (IIH) and to field-test the ICHD diagnostic criteria for headache attributed to IIH. We included 44 patients with new-onset IIH. Thirty-four patients with suspected but unconfirmed IIH served as controls. Headache and other IIH-related symptoms were assessed by a detailed standardized interview. In participants referred before diagnostic lumbar puncture (n = 67), we recorded headache intensity before and after cerebrospinal fluid (CSF) withdrawal. Headache in patients with IIH was daily occurring in 86%, focal in 84% and pulsating in 52%. Aggravation of headache by coughing or straining and relief after CSF withdrawal were significantly more frequent in patients than in controls (p ≤ 0.002). From the ICHD-2 to the ICHD-3 beta classification the sensitivity increased from 60% to 86% whereas the specificity decreased from 86% to 53%. Based on our data the headache criteria can be revised to increase sensitivity to 95% and specificity to 65%. Aggravation of headache by coughing or straining, relief after CSF withdrawal, retrobulbar pain and pulsatile tinnitus may suggest intracranial hypertension. Based on data from a well-defined IIH cohort, we propose a revision of the ICDH-3 beta diagnostic criteria with improved clinical applicability and increased sensitivity and specificity. | 25,228,684 | [
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Unique functional and structural properties of the LRRK2 protein ATP-binding pocket. | Pathogenic mutations in the LRRK2 gene can cause late-onset Parkinson disease. The most common mutation, G2019S, resides in the kinase domain and enhances activity. LRRK2 possesses the unique property of cis-autophosphorylation of its own GTPase domain. Because high-resolution structures of the human LRRK2 kinase domain are not available, we used novel high-throughput assays that measured both cis-autophosphorylation and trans-peptide phosphorylation to probe the ATP-binding pocket. We disclose hundreds of commercially available activity-selective LRRK2 kinase inhibitors. Some compounds inhibit cis-autophosphorylation more strongly than trans-peptide phosphorylation, and other compounds inhibit G2019S-LRRK2 more strongly than WT-LRRK2. Through exploitation of structure-activity relationships revealed through high-throughput analyses, we identified a useful probe inhibitor, SRI-29132 (11). SRI-29132 is exquisitely selective for LRRK2 kinase activity and is effective in attenuating proinflammatory responses in macrophages and rescuing neurite retraction phenotypes in neurons. Furthermore, the compound demonstrates excellent potency, is highly blood-brain barrier-permeant, but suffers from rapid first-pass metabolism. Despite the observed selectivity of SRI-29132, docking models highlighted critical interactions with residues conserved in many protein kinases, implying a unique structural configuration for the LRRK2 ATP-binding pocket. Although the human LRRK2 kinase domain is unstable and insoluble, we demonstrate that the LRRK2 homolog from ameba can be mutated to approximate some aspects of the human LRRK2 ATP-binding pocket. Our results provide a rich resource for LRRK2 small molecule inhibitor development. More broadly, our results provide a precedent for the functional interrogation of ATP-binding pockets when traditional approaches to ascertain structure prove difficult. | 25,228,699 | [
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High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria. | Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes. A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09-2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors. High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM. | 25,228,706 | [
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Assisted reproductive technology in SLE and APS. | Assisted reproductive technology (ART) procedures, which include in vitro fertilization (IVF), are performed frequently and may be considered for patients with systemic lupus erythematosus and antiphospholipid syndrome. These procedures do not appear to increase the risk of disease flare or thrombosis in these patients. In addition, the presence of antiphospholipid antibodies (aPL) does not independently predict the outcome of IVF pregnancies. As with pregnancies that are achieved naturally, candidates for ART should have quiescent disease for at least 6 months prior to attempting pregnancy for the best possible outcome for mother and child. | 25,228,714 | [
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Antiphospholipid scoring: significance in diagnosis and prognosis. | Recently our group introduced the "antiphospholipid score" (aPL-S), a quantitative marker that represents aPL profile. We have validated its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis. The study comprised two independent sets of patients with autoimmune diseases. In the first set of patients (n=233), the aPL-S was established by analyzing aPL profiles. In the second set of patients (n=411), the predictive value of the aPL-S for thrombosis was evaluated. To define aPL-S, we calculated the relative risks (approximated by odds ratios (ORs)) of having APS manifestations (thrombosis and/or pregnancy morbidity) for each of the aPL tests and devised an original formula in which aPL-S was determined by OR: aPL-S=5 × exp ([OR] -5)/4. The receiver operating characteristic (ROC) curve showed a hyperbolic pattern and the area under the ROC curve value was 0.752 (0.686 for revised Sapporo criteria), implying that aPL-S is a potential quantitative marker for APS diagnosis. The OR for thrombosis in patients with a high aPL-S (≥ 30) was 5.27 (95% confidence interval (95% CI) 2.32-11.95, p<0.0001). By multivariate analysis, an aPL-S of ≥ 30 appeared to be an independent risk factor for thrombosis (hazard ratio 3.144 (95% CI 1.383-7.150), p=0.006). The aPL-S is a useful quantitative index for diagnosing APS and may be a predictive marker for thrombosis in autoimmune diseases. | 25,228,723 | [
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Thrombotic risk assessment in APS: the Global APS Score (GAPSS). | Recently, we developed a risk score for antiphospholipid syndrome (APS) (Global APS Score or GAPSS). This score derived from the combination of independent risk factors for thrombosis and pregnancy loss, taking into account the antiphospholipid antibodies (aPL) profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors, and the autoimmune antibodies profile. We demonstrate that risk profile in APS can be successfully assessed, suggesting that GAPSS can be a potential quantitative marker of APS-related clinical manifestations. | 25,228,728 | [
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Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients†. | Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. The purpose of this study was to compare the preoperative condition and outcome of LDLLT patients with those of conventional cadaveric lung transplantation (CLT) patients. A new lung transplant programme was established in 2008 at Kyoto University. Between June 2008 and January 2014, we performed 79 lung transplants, including 42 LDLLTs (10 single, 32 bilateral) and 37 CLTs (22 single, 15 bilateral). Data collected included pre- and perioperative variables and mid-term survival. All data were analysed retrospectively as of January 2014. The majority of patients were female (57.1%) in the LDLLT group and male (64.9%) in the CLT group. The average age was similar (36.6 ± 20.7 vs 39.7 ± 12.6 years, P = 0.42) between the two groups. Preoperatively, interstitial lung disease was more common in LDLLT patients than in CLT patients (47.6 vs 24.3%, P = 0.048); prior haematopoietic stem cell transplantation was performed more often in LDLLT patients than in CLT patients (33.3 vs 13.5%, P = 0.040) and there were more steroid-dependent LDLLT patients than CLT patients (64.3 vs 29.7%, P = 0.0022). Based on preoperative criteria of lower body mass index (17.2 ± 4.0 vs 19.3 ± 3.3 kg/m(2), P = 0.013), less ambulatory ability (42.9 vs 86.5%, P = 0.0001) and more ventilator dependence (11.9 vs 2.7%, P = 0.12), LDLLT patients were more debilitated than CLT patients. LDLLT patients required longer postoperative mechanical ventilation than CLT patients (15.6 ± 16.2 vs 8.5 ± 8.1 days, P = 0.025). However, 1- and 3-year survival rates were similar between the two groups (89.7 and 86.1% vs 88.3 and 83.1%, P = 0.55). All living donors returned to their previous lifestyles without restriction. Although LDLLT patients were in a worse preoperative condition than CLT patients, LDLLT patients demonstrated survival rates similar to CLT patients. LDLLT is a viable option for patients too ill to survive a long waiting time for cadaveric donors. | 25,228,745 | [
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Application of caspofungin in China compared with amphotericin B and fluconazole. | Fungal infection has increased in the past 2 decades in China. There are three classes of antifungal drugs, polyenes, azoles, and echinocandins, that are applied frequently in China. Caspofungin, which disrupts the fungal cell wall glucan formation through inhibiting the enzyme 1,3-β-glucan synthase, is one of the echinocandins. According to the results of clinical practices applied in China, caspofungin has shown to be superior to the other two classes of antifungal drugs, due to its efficacy in treating fungal infection (15% superior to fluconazole); fewer adverse events such as infusion-related reaction, hepatic dysfunction, and vomiting (25%-50% lower incidence rate); rapid resolution of symptoms (about 3 days quicker than amphotericin B); and absence of antagonism in combination with other antifungal drugs. However, caspofungin will remain as a second-line antifungal drug in the near future because of its high price and the policy of health insurance reimbursement in China. | 25,228,811 | [
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Sex differences in long-term outcomes of coronary patients treated with drug-eluting stents at a tertiary medical center. | Limited data exist on contemporary sex-related differences in long-term outcomes of coronary patients receiving drug-eluting stents. In this study we evaluate differences for males (M) and females (F) in 2-year target lesion failure (TLF) in an unselected consecutive series of patients treated with everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) at a tertiary medical center. Data on 348 consecutive patients (M 221, F 127) stented with EES and PES were retrospectively analyzed. The primary end point of the study was to compare sex-related outcomes in TLF, defined as the combined end point of cardiac death, nonfatal myocardial infarction, and target lesion revascularization (TLR). Secondary end points included TLR, target vessel failure, target vessel revascularization, acute stent thrombosis as defined by the Academic Research Consortium, and cardiac death. The cineangiograms of the first consecutive 162 patients (M 105, F 57) were independently reviewed by a cardiologist blinded to clinical outcome, and SYNTAX scoring was performed. Follow-up was achieved using medical records and/or phone calls and was censored at 2 years. Descriptive analysis was performed on all variables. Univariate analysis compared the M and F cohorts. Multivariate analysis using Cox regression was performed to determine independent predictors of TLF with time, including sex as an independent variable in the model. M had more prior percutaneous coronary interventions and restenotic lesions and a higher prevalence of smoking. They also had longer length of disease and received more stents than F. F were older and had a higher prevalence of prior stroke. Angiographic complexity was not statistically different between the two groups, as judged by SYNTAX scoring (M 20.8±13.8, F 19.7±13.9, P=0.650). At 2-year follow-up, TLF was 27.4% and 24.8% (P=0.614) with no statistical difference between TLR (23.3% versus [vs] 21.6%), cardiac death (2.8% vs 3.2%), and definite and probable stent thrombosis (2.3% vs 0.0%) in M and F, respectively. Cox regression analysis using backward elimination showed that the number of stents per patient was the only independent predictor of TLF with time (hazard ratio 1.201, 95% confidence interval 1.126-1.280, P=0.001). In this cohort of patients receiving EES and PES, M and F did not have statistically different outcomes at 2-year follow-up, consistent with recent reports in the current era of percutaneous coronary interventions. | 25,228,813 | [
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Bevacizumab in Japanese patients with malignant glioma: from basic research to clinical trial. | An antiangiogenic approach is especially suitable for the treatment of malignant gliomas. Recently, two large clinical trials in newly diagnosed glioblastoma (the Avastin in Glioblastoma study and Radiation Therapy Oncology Group 0825 study) showed a 3- to 4-month prolongation of progression-free survival (PFS) with bevacizumab, but no significant effect on overall survival (OS). Japan is the first, and so far only, country to approve the use of bevacizumab in newly diagnosed glioblastoma in combination with radiotherapy and temozolomide chemotherapy. The drug is also approved for use as monotherapy for recurrent glioblastoma and certain other types of high-grade glioma after previous therapy. The effectiveness of bevacizumab on Japanese malignant glioma patients was reviewed. The Phase II clinical trial demonstrated that the PFS with bevacizumab alone was 34% at 6 months and 3.3 months at median for 32 patients with recurrent malignant gliomas. In the Avastin in Glioblastoma study, 44 Japanese patients were registered from Japan. PFS and OS for bevacizumab combined with standard temozolomide and radiotherapy were 12.2 months and 29.2 months at median, respectively, for the patients with newly diagnosed glioblastoma. PFS and OS tended to be longer for those treated with bevacizumab than for those not treated with the drug. In addition, biomarkers of bevacizumab effectiveness were investigated in Japanese patients. Vascular endothelial growth factor concentration, matrix metalloproteinase 9 activities in urine, and apparent diffusion coefficient values on magnetic resonance imaging may be biomarkers that predict patient prognosis. Finally, novel experiments for vascular endothelial growth factor antibody action were described; these include the induction of glioma cell apoptosis, an antibody treatment failure model, and a study of the synergistic effect with chemotherapeutic agents. | 25,228,814 | [
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Antiangiogenic cancer drug sunitinib exhibits unexpected proangiogenic effects on endothelial cells. | Angiogenesis, the formation of new blood vessels, is an essential step for cancer progression, but antiangiogenic therapies have shown limited success. Therefore, a better understanding of the effects of antiangiogenic treatments on endothelial cells is necessary. In this study, we evaluate the changes in cell surface vascular endothelial growth factor receptor (VEGFR) expression on endothelial cells in culture treated with the antiangiogenic tyrosine kinase inhibitor drug sunitinib, using quantitative flow cytometry. We find that proangiogenic VEGFR2 cell surface receptor numbers are increased with sunitinib treatment. This proangiogenic effect might account for the limited effects of sunitinib as a cancer therapy. We also find that this increase is inhibited by brefeldin A, an inhibitor of protein transport from the endoplasmic reticulum to the Golgi apparatus. The complex dynamics of cell surface VEGFRs may be important for successful treatment of cancer with antiangiogenic therapeutics. | 25,228,815 | [
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Lung Parenchymal Signal Intensity in MRI: A Technical Review with Educational Aspirations Regarding Reversible Versus Irreversible Transverse Relaxation Effects in Common Pulse Sequences. | Lung parenchyma is challenging to image with proton MRI. The large air space results in ~l/5th as many signal-generating protons compared to other organs. Air/tissue magnetic susceptibility differences lead to strong magnetic field gradients throughout the lungs and to broad frequency distributions, much broader than within other organs. Such distributions have been the subject of experimental and theoretical analyses which may reveal aspects of lung microarchitecture useful for diagnosis. Their most immediate relevance to current imaging practice is to cause rapid signal decays, commonly discussed in terms of short T<sub2</sub<sup*</sup values of 1 ms or lower at typical imaging field strengths. Herein we provide a brief review of previous studies describing and interpreting proton lung spectra. We then link these broad frequency distributions to rapid signal decays, though not necessarily the exponential decays generally used to define T<sub2</sub<sup*</sup values. We examine how these decays influence observed signal intensities and spatial mapping features associated with the most prominent torso imaging sequences, including spoiled gradient and spin echo sequences. Effects of imperfect refocusing pulses on the multiple echo signal decays in single shot fast spin echo (SSFSE) sequences and effects of broad frequency distributions on balanced steady state free precession (bSSFP) sequence signal intensities are also provided. The theoretical analyses are based on the concept of explicitly separating the effects of reversible and irreversible transverse relaxation processes, thus providing a somewhat novel and more general framework from which to estimate lung signal intensity behavior in modern imaging practice. | 25,228,852 | [
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Facilitated detection of social cues conveyed by familiar faces. | Recognition of the identity of familiar faces in conditions with poor visibility or over large changes in head angle, lighting and partial occlusion is far more accurate than recognition of unfamiliar faces in similar conditions. Here we used a visual search paradigm to test if one class of social cues transmitted by faces-direction of another's attention as conveyed by gaze direction and head orientation-is perceived more rapidly in personally familiar faces than in unfamiliar faces. We found a strong effect of familiarity on the detection of these social cues, suggesting that the times to process these signals in familiar faces are markedly faster than the corresponding processing times for unfamiliar faces. In the light of these new data, hypotheses on the organization of the visual system for processing faces are formulated and discussed. | 25,228,873 | [
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Enactivism and neonatal imitation: conceptual and empirical considerations and clarifications. | Recently within social cognition it has been argued that understanding others is primarily characterized by dynamic and second person interactive processes, rather than by taking a third person observational stance. Within this enactivist view of intersubjective understanding, researchers differ in their claims regarding the innateness of such processes. Here we proposed to distinguish nativist enactivists-who argue that studies on neonatal imitation support the view that infants already have a non-mentalistic embodied form of intersubjective understanding present at birth-from empiricist enactivists, who claim that those intersubjective processes are learned through social interaction. In this article, we critically examine the empirical studies on neonate imitation and conclude that the available evidence is at least mixed for most types of specific gesture imitations. In the end, only the tongue protrusion imitation appears to be consistent across different studies. If neonates imitate only one single gesture, then a more parsimonious explanation for the tongue protrusion effect could be put forward. Consequently, the nativist enactivist claim that understanding others depends on second person interactive processes already present at birth seems no longer plausible. Although other strands of evidence provide converging evidence for the importance of intersubjective processes in adult social cognition, the available evidence on neonatal imitation calls for a more careful view on the innateness of such processes and suggests that this way of interacting needs to be learned over time. Therefore the available empirical evidence on neonate imitation is in our view compatible with the empiricist enactivist position, but not with the nativist enactivist position. | 25,228,895 | [
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PeptideManager: a peptide selection tool for targeted proteomic studies involving mixed samples from different species. | The search for clinically useful protein biomarkers using advanced mass spectrometry approaches represents a major focus in cancer research. However, the direct analysis of human samples may be challenging due to limited availability, the absence of appropriate control samples, or the large background variability observed in patient material. As an alternative approach, human tumors orthotopically implanted into a different species (xenografts) are clinically relevant models that have proven their utility in pre-clinical research. Patient derived xenografts for glioblastoma have been extensively characterized in our laboratory and have been shown to retain the characteristics of the parental tumor at the phenotypic and genetic level. Such models were also found to adequately mimic the behavior and treatment response of human tumors. The reproducibility of such xenograft models, the possibility to identify their host background and perform tumor-host interaction studies, are major advantages over the direct analysis of human samples. At the proteome level, the analysis of xenograft samples is challenged by the presence of proteins from two different species which, depending on tumor size, type or location, often appear at variable ratios. Any proteomics approach aimed at quantifying proteins within such samples must consider the identification of species specific peptides in order to avoid biases introduced by the host proteome. Here, we present an in-house methodology and tool developed to select peptides used as surrogates for protein candidates from a defined proteome (e.g., human) in a host proteome background (e.g., mouse, rat) suited for a mass spectrometry analysis. The tools presented here are applicable to any species specific proteome, provided a protein database is available. By linking the information from both proteomes, PeptideManager significantly facilitates and expedites the selection of peptides used as surrogates to analyze proteins of interest. | 25,228,907 | [
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From bench to bedside: the realities of reducing global prostate cancer disparity in black men. | Prostate cancer in black men of African descent has a different tumour biology compared to those of other races. Its clinical manifestations depict a more aggressive disease with higher morbidity and mortality. This study proposes, through a literature search, identifying applied laboratory and clinical research in prostate cancer directed to improve outcomes and decrease global disparities of prostate cancer in black men of African descent. This review identified five categories pertinent for research: prostate-specific antigen (PSA) testing for early detection and screening, the potential of epigenetics, cultural determinants and health-seeking behaviours, other biomarkers for prostate cancers, and the economics of treating advanced prostate cancer. The analysis revealed that in developed countries, men of African descent are underrepresented in the sampling pools in both laboratory and clinical research, and thus the applicability and relevance of these results to men of African descent are circumspect. However, developing countries with high populations of black males have limited laboratory and clinical research publications. This is due to limited funding to support research programmes and basic clinical services for early detection and treatment. The study concludes that for the involvement of developing countries in bench research, they should do it in collaboration, like fostering partnerships with credible academic-based institutions and organisations. This requires a realm of transparency, respect, protection of the rights and dignity of the patients, and an equity in participation and sharing of the benefits to be accrued. The current transatlantic and Caribbean collaborations in research, education, and health service delivery in prostate cancer care for men of African descent exemplify the successes of such partnerships. | 25,228,914 | [
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Polyisoprenylated methylated protein methyl esterase as a putative drug target for androgen-insensitive prostate cancer. | Prostate cancer (CaP) is the most frequently diagnosed cancer in US men, with an estimated 236,590 new cases and 29,720 deaths in 2013. There exists the need to identify biomarkers/therapeutic targets for the early/companion diagnosis and development of novel therapies against the recalcitrant disease. Mutation and overexpression-induced abnormal activities of polyisoprenylated proteins have been implicated in CaP. Polyisoprenylated methylated protein methyl esterase (PMPMEase) catalyses the only reversible and terminal reaction of the polyisoprenylation pathway and may promote the effects of G proteins on cell viability. In this review, the potential role of PMPMEase to serve as a new drug target for androgen-insensitive CaP was determined. Specific PMPMEase activities were found to be 3.5- and 4.5-fold higher in androgen-sensitive 22Rv1 and androgen-dependent LNCaP and 1.5- and 9.8-fold higher in castration-resistant DU 145 and PC-3 CaP cells compared to normal WPE1-NA22 prostate cells. The PMPMEase inhibitor, L-28, induced apoptosis with EC50 values ranging from 1.8 to 4.6 μM. The PMPMEase activity in the cells following treatment with L-28 followed a similar profile, with IC50 ranging from 2.3 to 130 μM. L-28 disrupted F-actin filament organisation at 5 μM and inhibited cell migration 4-fold at 2 μM. Analysis of a CaP tissue microarray for PMPMEase expression revealed intermediate, strong, and very strong staining in 94.5% of the 92 adenocarcinoma cases compared to trace and weak staining in the normal and normal-adjacent tissue controls. The data are an indication that effective targeting of PMPMEase through the development of more potent agents may lead to the successful treatment of metastatic CaP. | 25,228,915 | [
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A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD. | A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. We conclude that CXCL10 and CXCL9 are promising candidate inflammatory signals linked to the regulation of central metabolism genes in skeletal muscles. On a methodological level, our work also shows that a system level analysis of animal models of diseases can be very effective to generate clinically relevant hypothesis. | 25,228,925 | [
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O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. | Hemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. However, it has proven to be insensitive at pre-diabetic threshold values. O-linked-β-N-acetylglucosamine (O-GlcNAc) modification has emerged as a sensitive biomarker. The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. Healthy, young males (18-35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts. The relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. Moreover, a positive association between HOMA-IR and O-GlcNAc emerged, while no relationship was found between HbA1c and HOMA-IR. This effect was not related to OGT expression. Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies. | 25,228,926 | [
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International electives in the final year of German medical school education--a student's perspective. | The final year of medical school has a unique role for introducing students to their future responsibilities and challenges. At many medical schools, electives at an accredited institution abroad are a common part of the student's final year experience. International electives provide an opportunity for a personal and academic experience that will often create new perspectives on clinical medicine and research, medical education and healthcare policy. In this article the authors reflect on their experience as elective students abroad and discuss the contribution of international electives to the constant development and progress of local final year rotations. They identify key areas for improving final year electives and outline essential features for a valuable and successful final year elective. | 25,228,928 | [
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Hands-on - general medicine - circuit-training in the auditorium--a practical equivalent to a lecture. | Traditional university teaching formats are of limited use when it comes to conveying the inner workings and specific remit of general medicine in a practical way. Small supervised groups present themselves as a plausible and effective alternative for learning to interact with patients in low prevalence areas. A frontal lecture was transformed into an interactive seminar-like lecture for 280 students. Short kick-off presentations served as an introduction to rotating circuit stations. Knowledge, skills and professional attitude specific to general and family medicine were intensively trained by 28 small groups in and around the auditorium by means of activating didactic methods. The small groups were supervised by experienced GP's trained as tutors. During six days, consisting of 3.5 hour sessions per day, working methods, a large variety of common medical conditions, preventive primary care and care for the elderly were amongst the topics addressed. This new format was successfully implemented and developed with regards to content as well as organisation. Well over 90% of the 274 participating students evaluated tutors' commitment, coherent delivery of content, learner-oriented atmosphere and practical focus positively. Given the advantages of a small-group learning situation, the somewhat cramped conditions were accepted by 92%. The innovative concept was able to work successfully within the specific framework of patient care in a general and family medicine setting. A creative approach to the lack of space managed to mobilise resources for practical small-group work. Being able to work on specific general practice problems in a small-group setting and immediately reflect upon them was rated positively overall. Responsibilities and specific working methods in general practice / family medicine can be trained successfully even with large groups of students when limited space is used creatively. In a supervised circuit-training setting, students are able to apply their existing knowledge and skills in a practical way. Further research is needed to assess individual learning success and gains in competence under this novel learning situation. | 25,228,929 | [
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Laparoscopy for ventriculoperitoneal shunt implantation and revision surgery. | Ventriculoperitoneal shunting (VPS) is a widely accepted technique for the treatment of hydrocephalus. The probability of shunt dysfunction is pretty high throughout life. Laparoscopy has become a valuable tool to perform VPS and treat abdominal complications. An electronic literature search was performed to reveal the published data relating laparoscopy and ventriculoperitoneal shunt in Medline, Embase, Scielo and Lilacs databases. The keywords employed were "laparoscopy" OR "laparoscopic surgery" AND "ventriculoperitoneal shunt" OR "shunt" AND "surgery" OR "implantation" OR "revision" OR "complication". No high quality trials were developed comparing conventional laparotomic incision vs laparoscopic approach. Both approaches have evolved and currently there are less invasive options for laparotomy, like periumbilical small incisions; and for laparoscopy, like smaller and less incisions. Operating room time, blood loss and hospital stay may be potentially smaller in laparoscopic surgery and complications are probably the same as laparotomy. In revision surgery for abdominal complications after VPS, visualization of whole abdominal cavity is fundamental to address properly the problem and laparoscopic approach is valuable once it is safe, fast and much less invasive than laparotomy. Ventriculoperitoneal shunting is a widely accepted technique for the treatment of hydrocephalus. Laparoscopy assisted shunt surgery in selected cases might be a less invasive and more effective option for intrabdominal manipulation. The laparoscopic approach allows a better catheter positioning, lysis of fibrotic bundles and peritoneal inspection as well, without any additional complication. | 25,228,943 | [
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Innate immune receptors in heart failure: Side effect or potential therapeutic target? | Heart failure (HF) is a leading cause of mortality and morbidity in western countries and occasions major expenses for public health systems. Although optimal medical treatment is widely available according to current guidelines, the prognosis of patients with HF is still poor. Despite the etiology of the disease, increased systemic or cardiac activation of the innate immune system is well documented in several types of HF. In some cases there is evidence of an association between innate immune activation and clinical outcome of patients with this disease. However, the few large trials conducted with the use of anti-inflammatory medication in HF have not revealed its benefits. Thus, greater understanding of the relationship between alteration in the immune system and development and progression of HF is urgently necessary: prior to designing therapeutic interventions that target pathological inflammatory processes in preventing harmful cardiac effects of immune modulatory therapy. In this regard, relatively recently discovered receptors of the innate immune system, i.e., namely toll-like receptors (TLRs) and nod-like receptors (NLRs)-are the focus of intense cardiovascular research. These receptors are main up-stream regulators of cytokine activation. This review will focus on current knowledge of the role of TLRs and NLRs, as well as on downstream cytokine activation, and will discuss potential therapeutic implications. | 25,228,958 | [
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Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention. | Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction (NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention (PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed. | 25,228,966 | [
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Late intervention in an asymptomatic pediatric patient with anomalous left coronary artery. | Anomalous left coronary artery from the pulmonary artery (ALCAPA) is most commonly diagnosed within the first year of life with congestive heart failure symptomatology reflecting left ventricle (LV) dysfunction. The late diagnosis of ALCAPA is presented in a 5-year-old without significant LV dysfunction, mild LV dilatation and only mild mitral regurgitation that did not change significantly after surgery. The timing of surgical intervention in the late diagnosis of ALCAPA remains unclear despite risks of significant ongoing myocardial injury secondary to coronary artery hypoperfusion and progressive mitral valve dysfunction. Intervention in this case allows for revascularization which may reverse ventricular and valvular dysfunction. | 25,228,967 | [
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Long-term efficacy of endoscopic submucosal dissection compared with surgery for early gastric cancer: a retrospective cohort study. | This study aimed to compare the outcomes of endoscopic submucosal dissection (ESD) and gastrectomy based on the two sets of indications for ESD, namely guideline criteria (GC) and expanded criteria (EC). Between January 2004 and July 2007, 213 early gastric cancer (EGC) patients were enrolled in this study. Of these patients, 142 underwent ESD, and 71 underwent gastrectomy. We evaluated the clinical outcomes of these patients according to the criteria. The complication rates in the ESD and gastrectomy groups were 8.5% and 28.2%, respectively. The duration of hospital stay was significantly shorter in the ESD group than the gastrectomy group according to the GC and EC (p<0.001 and p<0.001, respectively). There was no recurrence in the ESD and gastrectomy groups according to the GC, and the recurrence rates in the ESD and gastrectomy groups were 4.7% and 0.0% according to the EC, respectively (p=0.279). The occurrence rates of metachronous cancer in the ESD and gastrectomy groups were 5.7% and 5.0% according to the GC (p=1.000) and 7.5% and 0.0% according to the EC (p=0.055), respectively. Based on safety, duration of hospital stay, and long-term outcomes, ESD may be an effective and safe first-line treatment for EGC according to the EC and GC. | 25,228,976 | [
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Is endoscopic retrograde cholangiopancreatography safe in patients 90 years of age and older? | This case-control study evaluated the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in patients 90 years of age and older. From January 2005 to August 2011, 5,070 cases of ERCP were performed at our institution. Of these, 43 cases involved patients 90 years of age and older (mean age, 91.7±1.9 years). A control group of 129 cases (mean age, 65.7±14.8 years) was matched by the patient sex, sphincterotomy, and presence of choledocholithiasis using a propensity score. The patients' medical records were retrospectively reviewed for comorbidity, periampullary diverticulum, urgent procedure, conscious sedation, technical success, procedure duration, ERCP-related complication, and death. Between the case and control groups, there was no significant difference with regard to comorbidity, periampullary diverticulum, and urgent procedure. Conscious sedation was performed significantly less in the patient group versus the control group (28 [65%] vs 119 [92%], respectively; p=0.000). There was no significant difference in the technical success, procedure duration, or ERCP-related complications. In both groups, there was no major bleeding or perforation related to ERCP. Post-ERCP pancreatitis occurred significantly less in the patient group compared to the control group (0 vs 13 [10%], respectively; p=0.004). One death occurred from respiratory arrest in the case group. ERCP can be performed safely and successfully in patients aged 90 years and older without any significant increase in complications. | 25,228,977 | [
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Allergic diseases and multiple chemical sensitivity in korean adults. | Multiple chemical sensitivity (MCS) is a clinical syndrome representing multi-organ and psychological symptoms caused by chronic exposure to various chemicals in low concentrations. We evaluated the prevalence and related factors of MCS targeting Korean adults using the Quick Environmental Exposure and Sensitivity Inventory (QEESI©). A total of 446 participants were recruited from Severance Hospital. Participants underwent a questionnaire interview including questions on sociodemographic factors, occupational and environmental factors, allergic diseases, and the QEESI©. Among them, 379 participants completed the questionnaire and the QEESI©. According to the QEESI© interpretation results, participants were divided into very suggestive (VS) group and less suggestive (LS) group. The estimated prevalence of MCS was higher in allergic patients than non-allergic participants (19.7% and 11.3%, respectively, P=0.04). In the multivariate logistic regression analysis, ages of 30-39 (OR, 2.94; 95% CI, 1.25-6.95) and those of 40-49 (OR, 2.51; 95% CI, 1.02-6.21) were significantly related to MCS compared to those aged less than 30 years. Female sex (OR, 2.16; 95% CI, 1.11-4.18), experience of dwelling in a new house (OR, 2.05; 95% CI, 1.04-4.03), and atopic dermatitis (OR, 1.95; 95% CI, 1.04-3.69) were also significantly related to MCS. However, only age of 30-39 in the allergic group was significant in the stratified analysis. The estimated prevalence of MCS was higher among allergic patients than non-allergic participants. People with experience of dwelling in a new house and atopic dermatitis were more at risk of being intolerant to chemicals. Further studies to provide the nationally representative prevalence data and clarify risk factors and mechanisms of MCS are required. | 25,228,997 | [
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Exploring Household-level Risk Factors for Self-reported Prevalence of Allergic Diseases Among Low-income Households in Seoul, Korea. | Indoor risk factors for allergic diseases in low-income households in Korea have been characterized only partially. We evaluated the prevalences of atopic dermatitis, asthma, and allergic rhinitis in Seoul, Korea, to identify key housing and behavioral risk factors of low-income households. Statistical analysis of the prevalence of these diseases and various risk factors was conducted using data from a 2010 Ministry of Environment household survey. Logistic regression models were generated using data from 511 low-income household apartments in districts of Seoul. In general, housing factors such as renovation history (P<0.1) and crowding status (P<0.01) were associated with allergic rhinitis, whereas behavioral factors such as frequency of indoor ventilation (P<0.05) and cleaning (P<0.1) were inversely correlated with atopic dermatitis. Indoor smoking was a major trigger of asthma and atopic dermatitis in low-income households (P<0.05). The presence of mold and water leakage in houses were the most important risk factors for all three diseases (P<0.05). Various risk factors play a role in triggering allergic diseases among low-income households in Seoul, and health or environmental programs mitigating allergic diseases should be tailored to address appropriate housing or behavioral factors in target populations. | 25,228,999 | [
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The impact of asthma control on salivary cortisol level in adult asthmatics. | Asthma is a chronic disease causing psychological stress which leads to the activation of hypothalamus-pituitary-adrenal axis. The purpose of this study is to compare morning salivary cortisol levels in persistent asthma patients according to their disease severities and control status. Total 206 adult asthma patients were recruited from four university hospitals. Spirometry, questionnaire of Asthma Quality of Life (AQOL) and Asthma Control Test (ACT) were completed, and saliva samples were collected prospectively to measure morning cortisol level. The mean patient age was 56.5±15.3 years with mean asthma duration of 9.1±11.1 years. Sixty five patents (31.6%) were classified as mild persistent asthma, and 141 patients (68.4%) were classified as moderate persistent asthma according to the Expert Panel Report 3. The mean predicted FEV1 was 88.8%±18.4%, and the methacholine PC20 was 9.6±8.5 mg/mL in all study population. The mean ACT score for all patients was 19.9±3.6, and there were 71 (34.5%) patients in poorly controlled and 135 (65.5%) in well controlled asthma. The poorly controlled asthma patients were characterized by significantly lower FEV1 (84.6%±17.6% vs 91.1%±18.5%, P=0.018), lower AQOL scores (46.0±13.9 vs 73.8±26.3, P<0.001), and lower salivary cortisol levels (0.14±0.08 vs 0.18±0.11 µg/dL, P=0.04) compared to well controlled asthma. The ACT score was significantly related to salivary cortisol levels (P=0.034) after adjusting for age. There was no significant difference in salivary cortisol levels (0.17±0.12 vs 0.16±0.08, P=0.725) when analyzed according to the dose of used corticosteroid and lung function. Asthma control status affects morning salivary cortisol level. Measuring the morning salivary cortisol level might be a simple and new way to assess asthma control status. | 25,229,005 | [
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Effect of constraint-induced movement therapy and mirror therapy for patients with subacute stroke. | To evaluate the effectiveness of constraint-induced movement therapy (CIMT) and combined mirror therapy for inpatient rehabilitation of the patients with subacute stroke. Twenty-six patients with subacute stroke were enrolled and randomly divided into three groups: CIMT combined with mirror therapy group, CIMT only group, and control group. Two weeks of CIMT for 6 hours a day with or without mirror therapy for 30 minutes a day were performed under supervision. All groups received conventional occupational therapy for 40 minutes a day for the same period. The CIMT only group and control group also received additional self-exercise to substitute for mirror therapy. The box and block test, 9-hole Pegboard test, grip strength, Brunnstrom stage, Wolf motor function test, Fugl-Meyer assessment, and the Korean version of Modified Barthel Index were performed prior to and two weeks after the treatment. After two weeks of treatment, the CIMT groups with and without mirror therapy showed higher improvement (p<0.05) than the control group, in most of functional assessments for hemiplegic upper extremity. The CIMT combined with mirror therapy group showed higher improvement than CIMT only group in box and block test, 9-hole Pegboard test, and grip strength, which represent fine motor functions of the upper extremity. The short-term CIMT combined with mirror therapy group showed more improvement compared to CIMT only group and control group, in the fine motor functions of hemiplegic upper extremity for the patients with subacute stroke. | 25,229,024 | [
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Activations of deep lumbar stabilizing muscles by transcutaneous neuromuscular electrical stimulation of lumbar paraspinal regions. | To investigate changes in lumbar multifidus (LM) and deep lumbar stabilizing abdominal muscles (transverse abdominis [TrA] and obliquus internus [OI]) during transcutaneous neuromuscular electrical stimulation (NMES) of lumbar paraspinal L4-L5 regions using real-time ultrasound imaging (RUSI). Lumbar paraspinal regions of 20 healthy physically active male volunteers were stimulated at 20, 50, and 80 Hz. Ultrasound images of the LM, TrA, OI, and obliquus externus (OE) were captured during stimulation at each frequency. The thicknesses of superficial LM and deep LM as measured by RUSI were greater during NMES than at rest for all three frequencies (p<0.05). The thicknesses in TrA, OI, and OE were also significantly greater during NMES of lumbar paraspinal regions than at rest (p<0.05). The studied transcutaneous NMES of the lumbar paraspinal region significantly activated deep spinal stabilizing muscle (LM) and the abdominal lumbar stabilizing muscles TrA and OI as evidenced by RUSI. The findings of this study suggested that transcutaneous NMES might be useful for improving spinal stability and strength in patients having difficulty initiating contraction of these muscles. | 25,229,029 | [
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Medical management for intractable pain arising from primary sjögren syndrome involving both brain and spinal cord: a case report. | Primary Sjögren syndrome, which involves lesions in both the brain and spinal cord, is rarely reported. Related symptoms, such as intractable pain due to central nervous system involvement, are very rare. A 73-year-old woman diagnosed with primary Sjögren syndrome manifested with subacute encephalopathy and extensive transverse myelitis. She complained of severe whole body neuropathic pain. Magnetic resonance imaging demonstrated a non-enhancing ill-defined high intensity signal involving the posterior limb of the both internal capsule and right thalamus on a T2 fluid-attenuated inversion recovery image. Additionally, multifocal intramedullary ill-defined contrast-enhancing lesion with cord swelling from the C-spine to L-spine was also visible on the T2-weighted image. Her intractable pain remarkably improved after administration of concomitant oral doses of gabapentin, venlafaxine, and carbamazepine. | 25,229,038 | [
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Total knee arthroplasty in a patient with an ankylosing knee after previous patellectomy. | Patellectomized patients may have less satisfactory clinical outcomes following total knee arthroplasty (TKA) due to a decreased extensor mechanism efficiency and potential instability. Furthermore, the existing literature does not provide concrete guidance on the expected results of TKA or the type of implant that should be used in patellectomized patients. We present a case of a patient with an ankylosing knee who had undergone patellectomy due to gunshot injury 45 years ago and was treated with primary TKA using a posterior stabilized prosthesis at our institution. TKA using this prosthesis in the ankylosed knee with a previous history of patellectomy yielded good results in terms of postoperative clinical scores, range of motion and joint stability. | 25,229,049 | [
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Lean mass is the strongest predictor of bone mineral content in type-2 diabetes and normal individuals: an eastern India perspective. | Impact of body fat distribution on bone mineral content (BMC) and density (BMD) at different sites has not been studied in type-2 diabetes (T2DM). This study aimed to compare BMC and BMD in normal (BMI < 25 kg/m(2)) and increased BMI (BMI ≥ 25 kg/m(2)) T2DM patients with age and BMI matched normal controls, and evaluate the impact of lean mass and body fat distribution parameters on them. Seventy-six T2DM patients and 56 normal controls underwent anthropometric assessment, blood sampling and estimation of BMC, BMD, body fat and lean mass distribution by dual energy X-ray absorptiometry (DXA). Increased BMI individuals (n = 63) had significantly higher BMD, BMC, fat mass and significantly lower 25-hydroxy-vitamin-D (25OHD), as compared to normal BMI individuals (n = 69). Lean mass had stronger positive correlation with BMC and BMD, compared to fat mass. BMI, sagittal abdominal diameter (SAD) and Android/Gynoid (A/G) ratio had positive correlation with BMC and BMD. Percent body fat had negative correlation with BMC and BMD. T2DM patients had higher central obesity (A/G ratio). WC was the best predictor of A/G ratio. Regression analysis revealed lean mass to be the strongest predictor of BMC after adjusting for age, sex, BMI and 25OHD, in normal individuals and patients with diabetes, followed by fat mass. BMD right femur, BMC, lean mass and A/G ratios were significantly higher in males (n = 74). Fat mass and percent body fat were significantly higher in females (n = 58). Fat mass was the best predictor of BMC in males where as lean mass was the best predictor of BMC in females. Increased BMI and T2DM are associated with increased BMC and BMD at different sites, with lean mass having the strongest impact on BMC in normal individuals and patients with diabetes. Males have higher BMC and BMD as compared to females, likely due to a greater lean mass, A/G ratio, along with lesser fat mass and percent body fat. | 25,229,052 | [
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Molecular level computational studies of polyethylene and polyacrylonitrile composites containing single walled carbon nanotubes: effect of carboxylic acid functionalization on nanotube-polymer interfacial properties. | Molecular dynamics (MD) and molecular mechanics (MM) methods have been used to investigate additive-polymer interfacial properties in single walled carbon nanotube (SWNT)-polyethylene and SWNT-polyacrylonitrile composites. Properties such as the interfacial shear stress and bonding energy are similar for the two composites. In contrast, functionalizing the SWNT with carboxylic acid groups leads to an increase in these properties, with a larger increase for the polar polyacrylonitrile composite. Increasing the percentage of carbon atoms that were functionalized from 1 to 5% also leads to an increase in the interfacial properties. In addition, the interfacial properties depend on the location of the functional groups on the SWNT wall. | 25,229,056 | [
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How to follow the NEWS. | it is not known how best to respond to changes in the National Early Warning Score (NEWS) after hospital admission. This report manipulates and extrapolates previously published data on the trajectories of the abbreviated early warning score (AbEWS i.e. NEWS that does not include mental status). trajectories of averaged AbEWS for patients for their first 5 days in hospital and their last 5 days in hospital were combined to obtain an approximation of what happens to the average patient while in hospital. the trajectories of patients admitted with a low score are different from those admitted with a high score. Patients should be observed for 12 to 24 hours before their outcome can be predicted. The score of most patients who die in hospital trends upward on the second or third day after admission. Patients admitted with a score of 0-2 who raise their score to >=3 have a ten-fold increase in-hospital mortality. the trajectories of early warning scores after admission are of prognostic importance, and escalation protocols should relate changes in the score to its initial value on admission. | 25,229,059 | [
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Problem based review: the pregnant woman presenting to the AMU with palpitations. | Pregnant patients commonly present to the acute medical team with symptoms requiring further investigation. Palpitations are a common reason for presentation on the acute medical take, and most acute physicians will be familiar with the process of investigation. The combination of pregnancy and palpitations raises a broad differential diagnosis and can complicate the management pathway. This problem based review is designed to summarise the key issues which may arise during the management of a typical patient presenting in this way. | 25,229,066 | [
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Quantum cutting in nanoparticles producing two green photons. | A synthetic route to nanoscale NaGdF4:Ln is presented which allows for quantum cutting based on the Gd-Er-Tb system. This shows, that cross-relaxation and other energy transfer processes necessary for multiphoton emission can be achieved in nanoparticles even if the large surface and the potentially huge amount of killer traps would suggest a lack of subsequent emission. | 25,229,069 | [
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A cellulose based hydrophilic, oleophobic hydrated filter for water/oil separation. | A hydrated regular cellulose paper filter modified with nanofibrillated cellulose (NFC) hydrogel was successfully fabricated for water/oil separation. The fabricated filter's hydrophilic and oleophobic properties resulted in increased filter life and decreased environmental impact, while displaying water flux of 89.6 L h(-1) m(-2) with efficiency ≥99% under gravitational force. | 25,229,071 | [
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From a historic review to horizons beyond: lithium-sulphur batteries run on the wheels. | In terms of sustainable development and environmental issues, the design and fabrication of efficient energy storage devices will be more critical in the future than at any time in the past. Li-S batteries are promising candidates for such a purpose due to their high specific capacity and low environmental impact. This review has systematically retraced the advances in the field of Li-S batteries over the past half century and highlighted the main breakthroughs in a number of areas, covering the mechanism determination, cathode engineering, theoretical simulation, and electrolyte tailoring and anode protection. Furthermore, we discuss the remaining challenges towards their practical application. It is expected that Li-S batteries with 3D inter-connected or conformal assemblies will surpass new horizons in the coming years. | 25,229,072 | [
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Redescription of Paragaleus tengi (Chen, 1963) (Carcharhiniformes: Hemigaleidae) and first record of Paragaleus randalli Compagno, Krupp & Carpenter, 1996 from the western North Pacific. | Paragaleus tengi was previously considered to be the only member of this genus occurring in the Western Pacific, with Paragaleus randalli occurring in the Indian Ocean and allopatric in distribution. Recent molecular and morphological studies showed that P. randalli also occurs in the Western Pacific with records from Thailand, Malaysia and Indonesia previously mostly incorrectly attributed to P. tengi. This paper provides a redescription of P. tengi and confirms the presence of P. randalli from off Taiwan in the western North Pacific. These two species are morphologically very similar in appearance but differ in meristics, dentition, some coloration attributes and minor morphological characters. The conservation status of these two species needs to be reassessed based on this new information. | 25,229,113 | [
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The transmembrane domain peptide of vesicular stomatitis virus promotes both intermediate and pore formation during PEG-mediated vesicle fusion. | We propose mechanisms by which the transmembrane domain of vesicular stomatitis virus (VSV-TMD) promotes both initiation of fusion and formation of a fusion pore. Time courses of polyethyleneglycol (PEG)-mediated fusion of 25 nm small unilamellar vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine (DOPE), bovine brain sphingomyelin, and cholesterol (35:30:15:20 molar ratio) were recorded at pH 7.4 at five different temperatures (from 17°C to 37°C) and compared with time courses obtained with the same vesicles containing the fusion-active TMD of the G protein of VSV. Multiple time courses were fitted globally to a one-intermediate ensemble kinetic model to estimate the rate constants for conversion of the aggregated state to an intermediate hemifused state (k1, stalk, or I1) that rapidly transits to an unstable intermediate (I2 state) that converts to a final fusion pore state with a combined rate k3. The probabilities of lipid mixing, contents mixing, and contents leakage in the three states were also obtained from this analysis. The activation thermodynamics for each step were consistent with previously published models of lipid rearrangements during intermediate and pore formation. The influences of VSV-TMD, hexadecane, and VSV-TMD + hexadecane on the kinetics, activation thermodynamics, and membrane structure support the hypothesis that these two agents do not catalyze fusion by a common mechanism, except possibly at the lowest temperatures examined. VSV-TMD primarily catalyzed initial intermediate formation, although it substantially increased the probability of contents mixing in the intermediate state. Our results support the hypothesis that the catalytic influence of VSV-TMD on the initial-intermediate- and pore-forming steps of PEG-mediated fusion derives from its ability to impose a positive intrinsic curvature and thereby stress small unilamellar vesicle outer leaflets as well as the periphery of intermediate microstructures. | 25,229,140 | [
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Water penetration profile at the protein-lipid interface in Na,K-ATPase membranes. | The affinity of ionized fatty acids for the Na,K-ATPase is used to determine the transmembrane profile of water penetration at the protein-lipid interface. The standardized intensity of the electron spin echo envelope modulation (ESEEM) from (2)H-hyperfine interaction with D2O is determined for stearic acid, n-SASL, spin-labeled systematically at the C-n atoms throughout the chain. In both native Na,K-ATPase membranes from shark salt gland and bilayers of the extracted membrane lipids, the D2O-ESEEM intensities of fully charged n-SASL decrease progressively with position down the fatty acid chain toward the terminal methyl group. Whereas the D2O intensities decrease sharply at the n = 9 position in the lipid bilayers, a much broader transition region in the range n = 6 to 10 is found with Na,K-ATPase membranes. Correction for the bilayer population in the membranes yields the intrinsic D2O-intensity profile at the protein-lipid interface. For positions at either end of the chains, the D2O concentrations at the protein interface are greater than in the lipid bilayer, and the positional profile is much broader. This reveals the higher polarity, and consequently higher intramembrane water concentration, at the protein-lipid interface. In particular, there is a significant water concentration adjacent to the protein at the membrane midplane, unlike the situation in the bilayer regions of this cholesterol-rich membrane. Experiments with protonated fatty acid and phosphatidylcholine spin labels, both of which have a considerably lower affinity for the Na,K-ATPase, confirm these results. | 25,229,145 | [
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Sensor-based electromagnetic navigation to facilitate implantation of left ventricular leads in cardiac resynchronization therapy. | Implantation of cardiac resynchronization therapy (CRT) devices can be challenging, time consuming, and fluoroscopy intense. To facilitate placement of left ventricular (LV) leads, a novel electromagnetic navigation system (MediGuide™, St. Jude Medical, St. Paul, MN, USA) has been developed, displaying real-time 3-D location of sensor-embedded delivery tools superimposed on prerecorded X-ray cine-loops of coronary sinus venograms. We report our experience and advanced progress in the use of this new electromagnetic tracking system to guide LV lead implantation. Between January 2012 and December 2013, 71 consecutive patients (69 ± 9 years, 76% male) were implanted with a CRT device using the new electromagnetic tracking system. Demographics, procedural data, and periprocedural adverse events were gathered. The impact of the operator's experience, optimized workflow, and improved software technology on procedural data were analyzed. LV lead implantation was successfully achieved in all patients without severe adverse events. Total procedure time measured 87 ± 37 minutes and the median total fluoroscopy time (skin-to-skin) was 4.9 (2.5-7.8) minutes with a median dose-area-product of 476 (260-1056) cGy*cm(2) . An additional comparison with conventional CRT device implantations showed a significant reduction in fluoroscopy time from 8.0 (5.8; 11.5) to 4.5 (2.8; 7.3) minutes (P = 0.016) and radiation dose from 603 (330; 969) to 338 (176; 680) cGy*cm(2) , respectively (P = 0.044 ). Use of the new navigation system enables safe and successful LV lead placement with improved orientation and significantly reduced radiation exposure during CRT implantation. | 25,229,158 | [
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Exposure to peer deviance during childhood and risk for drug abuse: a Swedish national co-relative control study. | Peer deviance (PD) is associated with risk for drug abuse (DA). Is this association causal? DA was recorded in official records. PD was defined as the percentage of peers residing in small communities with future DA registrations. We examined offspring in families whose community PD changed when the offspring was 0-15 years of age and then examined families where cousins or siblings differed in their years of exposure to low or high PD communities. The duration of exposure to PD was strongly associated with future DA. Co-relative analyses for families whose exposure to PD declined suggested that the PD-DA association was largely non-causal. Within full-sibling pairs in such families, the length of exposure to low PD environments was unrelated to risk for DA. By contrast, co-relative analyses in families where exposure to PD increased over time indicated that the PD-DA association was largely causal. In such families, siblings who differed in the duration of their exposure to high PD differed in their risk for subsequent DA. These results were replicated in families whose PD changed because they moved or because of changes in the community in which they resided. Within families whose social environment is improving over time, the association between PD exposure and offspring DA outcomes is not causal but is due to familial confounding. Within families whose social environment is deteriorating, the PD-DA association seems to be largely causal. Our measure of PD may also reflect broader aspects of the community environment beyond peers. | 25,229,163 | [
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Impact of lifestyle factors on caries experience in three different age groups: 9, 15, and 21-year-olds. | To study the impact of lifestyle factors on dental caries experiences in addition to the effect of demographic characteristics at the ages of 9, 15, and 21 years. The data were obtained from the study 'Oral health in children and adolescents in the Netherlands'. Data were collected through questionnaires and a clinical oral examination. Because the DMFS count data were highly skewed with a peak at zero, the negative binomial hurdle model was used for the analyses. The first part of the hurdle predicted the probability of having caries experience or not, and the second part predicted the degree of caries experience. For the 9- and 15-year-old age groups, the breakfast frequency per week was related with having caries experience, while the frequency of brushing teeth per day was related with the degree of caries experience. In addition, the number of food and drinks consumed per day was important for the younger age group. These relations were not found in the 21-year-olds age group. Findings of this study suggest that components to promote structure and regularity, including having breakfast and the number of food and drink moments, may be important to include in programs to prevent dental caries in children. | 25,229,181 | [
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The effect of the section thickness used for 2- and 3-dimensional quantification of dual-energy perfusion computed tomography. | To retrospectively investigate the effect of the section thickness used for quantifying dual-energy perfusion computed tomography (DEpCT) during 2- and 3-dimensional evaluation. Sixty-six patients (22 males and 44 females; mean age, 59.3 years) suspected of having an acute pulmonary embolism underwent DEpCT, and 15patients were diagnosed to have intrapulmonary clots (IPCs). Two-dimensional DEpCT images were reconstructed into various section thicknesses from 1 to 10 mm at the main pulmonary artery, and the ratios of the low attenuation area (LAA) ranging from 1 to 5 HU (%LAA5) and 10 HU (%LAA10) on DEpCT were compared with the relative areas of the lung with attenuation coefficients lower than -950 HU (RA-950) using the lung CT images of each section thickness. Three-dimensional values of DEpCT were reconstructed with 3 different section thicknesses (1, 3, and 10 mm) and were analyzed for the presence of IPC burden using the factors suggesting IPC burden, including the right/left ventricular diameter ratio and CT obstruction index. The mean attenuation and image noise were decreased as the section thickness increased. In the 2-dimensional analysis, the %LAA5 and %LAA10 had the smallest value at 1-mm section, and DEpCT with thinner sections had a correlation with the RA-950 (r = 0.22-0.23, P < 0.05). The 3-dimensional values of DEpCT reconstructed with a 1- or 3-mm section thickness had a correlation with the CT obstruction index (r = 0.52-0.59, P < 0.05) and right/left ventricular diameter ratio (r = 0.60-0.68, P < 0.01). The thinner images should be used for 2- and 3-dimensional quantification of DEpCT. | 25,229,200 | [
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Laboratory evaluation of the development of Aedes aegypti in two seasons: influence of different places and different densities. | Aedes aegypti is an important vector in Brazil being the main vector of the dengue-fever. This paper employs survival curves to describe the time in days from larvae to adult forms of Aedes aegypti raised, individually and collectively, and compares it during winter and spring when positioned inside and outside a laboratory. The study was conducted in São Vicente, a coastal city in Southeastern Brazil. The lowest water temperature in winter and in spring was 20 °C and the highest was 26 °C in spring. Higher and more stable temperatures were measured in the intra compared to the peri in both seasons. Consequently, larvae positioned in the intra resulted in the lowest median time to develop in the individual and collective experiment (nine and ten days, respectively). At least 25% of the larvae positioned in the intra in the individual experiment in the spring took only seven days to reach adulthood. Sex ratios and the median time development by sex did not show significant differences. These results indicate that efforts to control Aedes aegypti must be continuous and directed mainly to prevent the intra-domiciliary sites that can be infested in a week in order to reduce the human-vector contact. | 25,229,215 | [
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Detection of Leishmania (Viannia) IN Nyssomyia neivai and Nyssomyia whitmani by multiplex polymerase chain reaction, in Southern Brazil. | Sandflies transmit pathogens of leishmaniasis. The natural infection of sandflies by Leishmania (Viannia) was assessed in municipalities, in the state of Paraná, in Southern Brazil. Sandflies were collected with Falcão and Shannon traps. After dissection in search of flagellates in digestive tubes and identification of the species, female sandflies were submitted to the Multiplex Polymerase Chain Reaction (multiplex PCR) for detection of the fragment of the kDNA of Leishmania (Viannia) and the fragment from the IVS6 cacophony gene region of the phlebotomine insects. The analysis was performed in pools containing seven to 12 guts from females of the same species. A total of 510 female sandflies were analyzed, including nine Migonemyia migonei, 17 Pintomyia fischeri, 216 Nyssomyia neivai, and 268 Nyssomyia whitmani. Although none of the females was found naturally infected by flagellates through dissection, the fragment of DNA from Leishmania (Viannia) was shown by multiplex PCR in one sample of Ny. neivai (0.46%) and three samples of Ny. whitmani (1.12%). It was concluded that Ny. neivai and Ny. whitmani are susceptible to Leishmania infection, and that multiplex PCR can be used in epidemiological studies to detect the natural infection of the sandfly vector, because of its sensitivity, specificity and feasibility. | 25,229,218 | [
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Do girls have a nutritional disadvantage compared with boys? Statistical models of breastfeeding and food consumption inequalities among Indian siblings. | India is the only nation where girls have greater risks of under-5 mortality than boys. We test whether female disadvantage in breastfeeding and food allocation accounts for gender disparities in mortality. Secondary, publicly available anonymized and de-identified data were used; no ethics committee review was required. Multivariate regression and Cox models were performed using Round 3 of India's National Family and Health Survey (2005-2006; response rate = 93.5%). Models were disaggregated by birth order and sibling gender, and adjusted for maternal age, education, and fixed effects, urban residence, household deprivation, and other sociodemographics. Mothers' reported practices of WHO/UNICEF recommendations for breastfeeding initiation, exclusivity, and total duration (ages 0-59 months), children's consumption of 24 food items (6-59 months), and child survival (0-59 months) were examined for first- and secondborns (n = 20,395). Girls were breastfed on average for 0.45 months less than boys (95% CI: = 0.15 months to 0.75 months, p = 0.004). There were no gender differences in breastfeeding initiation (OR = 1.04, 95% CI: 0.97 to 1.12) or exclusivity (OR = 1.06, 95% CI: 0.99 to 1.14). Differences in breastfeeding cessation emerged between 12 and 36 months in secondborn females. Compared with boys, girls had lower consumption of fresh milk by 14% (95% CI: 79% to 94%, p = 0.001) and breast milk by 21% (95% CI: 70% to 90%, p<0.000). Each additional month of breastfeeding was associated with a 24% lower risk of mortality (OR = 0.76, 95% CI: 0.73 to 0.79, p<0.000). Girls' shorter breastfeeding duration accounted for an 11% increased probability of dying before age 5, accounting for about 50% of their survival disadvantage compared with other low-income countries. Indian girls are breastfed for shorter periods than boys and consume less milk. Future research should investigate the role of additional factors driving India's female survival disadvantage. | 25,229,235 | [
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High visceral leishmaniasis mortality rate in Barra Mansa, a new area of visceral leishmaniasis transmission in the State of Rio de Janeiro, Brazil. | Nine cases of visceral leishmaniasis occurred recently in Barra Mansa, State of Rio de Janeiro, with a high mortality rate. We reviewed the medical records of the patients. Eight were male; 7 were adults. Patients who died progressed to death quickly and presented with aggravating factors: systemic steroid therapy before diagnosis, bleeding, severe liver involvement, infection, and/or refusal to receive transfusion. We warn clinicians to be aware of the emergence of visceral leishmaniasis in new areas and to keep in mind the possibility of atypical clinical pictures and aggravating factors, so timely diagnosis can be made and prompt and adequate treatment can be initiated. | 25,229,297 | [
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Use of density functional theory orbitals in the GVVPT2 variant of second-order multistate multireference perturbation theory. | A new variation of the second-order generalized van Vleck perturbation theory (GVVPT2) for molecular electronic structure is suggested. In contrast to the established procedure, in which CASSCF or MCSCF orbitals are first obtained and subsequently used to define a many-electron model (or reference) space, the use of an orbital space obtained from the local density approximation (LDA) variant of density functional theory is considered. Through a final, noniterative diagonalization of an average Fock matrix within orbital subspaces, quasicanonical orbitals that are otherwise indistinguishable from quasicanonical orbitals obtained from a CASSCF or MCSCF calculation are obtained. Consequently, all advantages of the GVVPT2 method are retained, including use of macroconfigurations to define incomplete active spaces and rigorous avoidance of intruder states. The suggested variant is vetted on three well-known model problems: the symmetric stretching of the O-H bonds in water, the dissociation of N2, and the stretching of ground and excited states C2 to more than twice the equilibrium bond length of the ground state. It is observed that the LDA-based GVVPT2 calculations yield good results, of comparable quality to conventional CASSCF-based calculations. This is true even for the C2 model problem, in which the orbital space for each state was defined by the LDA orbitals. These results suggest that GVVPT2 can be applied to much larger problems than previously accessible. | 25,229,307 | [
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Three-component bicyclization providing an expedient access to pyrano[2',3':5,6]pyrano[2,3-b]pyridines and its derivatives. | A new three-component bicyclization for the efficient synthesis of a fused pyrano[2,3-b]pyridine library has been developed. The syntheses were achieved by reacting diverse C,O-containing nucleophiles, aldehydes, and 2-aminoprop-1-ene-1,1,3-tricarbonitrile under microwave irradiation, providing 50 examples of chemically and biomedically significant pyrano[2,3-b]pyridine analogues with the concomitant formation of two new rings and four σ bonds. This procedure features short reaction times, low-cost, and easily available starting materials, reliable scalability and mild reaction conditions, as well as operational simplicity. | 25,229,308 | [
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Wollamides: antimycobacterial cyclic hexapeptides from an Australian soil Streptomyces. | A soil Streptomyces nov. sp. (MST-115088) isolated from semiarid terrain near Wollogorang Station, Queensland, returned two known and two new examples of a rare class of cyclic hexapeptide, desotamides A and B (1 and 2) and E and F (3 and 4), respectively, together with two new d-Orn homologues, wollamides A and B (5 and 6). Structures were assigned by detailed spectroscopic and C3 Marfey's analysis. The desotamides/wollamides exhibit growth inhibitory activity against Gram-positive bacteria (IC50 0.6-7 μM) and are noncytotoxic to mammalian cells (IC50 >30 μM). The wollamides exhibit antimycobacterial activity (IC50 2.8 and 3.1 μM), including reduction in the intracellular mycobacterial survival in murine bone marrow-derived macrophages. | 25,229,313 | [
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[Inhalation therapy, patient's perspective]. | The cornerstone of drug application in obstructive pulmonary diseases is by inhalation as advocated by all treatment guidelines. Today, there exists an extensive choice of inhalers and new models. Numerous inhaler types are constantly being developed and introduced into the market making the "correct" selection a wearying task for the physician as well as for the patient. Improvement in the management of this aspect, which is often neglected in its importance in daily practice as well as in guidelines, is therefore reliant not only on the medications themselves but also on their effective delivery. Complicated inhaler mechanics and poor inhaler technique which do not meet the patient requirements and desires contribute to poor compliance eventually leading to poor disease control. In this review, the importance of inhaler acceptance and the degree of satisfaction with different inhaler types are discussed. This paper focuses on the behavioral and attitudinal evidence that the acceptance of the inhaler is linked to patient compliance, and its linkage on health and patient-reported outcomes. | 25,229,316 | [
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Seasonal plasticity in telencephalon mass of a benthic fish. | To gain a deeper understanding of how environmental conditions affect brain plasticity, brain size was explored across different seasons using the invasive round goby Neogobius melanostomus. The results show that N. melanostomus had heavier telencephalon in the spring compared to the autumn across the two years of study. Furthermore, fish in reproductive condition had heavier telencephala, indicating that tissue investment and brain plasticity may be related to reproductive needs in N. melanostomus. | 25,229,327 | [
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Involvement of IQGAP family proteins in the regulation of mammalian cell cytokinesis. | IQGAP family proteins, comprising IQGAP1, -2, and -3 in mammals, are involved in diverse ranges of cellular processes such as adhesion and migration. IQGAP proteins in yeast also play important roles in cytokinesis. However, the involvement of IQGAP proteins in cytokinesis in mammals remains unaddressed. In this study, we showed that IQGAP3 specifically localized to the equatorial cortex at anaphase, whereas IQGAP1 localized to the cell cortex uniformly and IQGAP2 was unexpressed in HeLa cells. IQGAP3, but neither IQGAP1 nor -2, was able to interact with anillin, which was required for the localization of IQGAP3 to the contractile ring. The suppressed expression of IQGAP3 inhibited the completion of cleavage furrow ingression and led to the multinucleation of cells. The suppression of IQGAP1 also had similar inhibitory effects on cytokinesis, and the simultaneous suppression of IQGAP1 and -3 induced more severe effects. The localization of anillin and RhoA to the contractile ring was impaired by the suppression of IQGAP1 and -3, whereas their upstream regulators, the centralspindlin complex and Ect2, remained unaffected. These results suggested that mammalian IQGAP proteins may play a role in cytokinesis by regulating the localization of key cytokinesis regulatory proteins to the contractile apparatus during mitosis. | 25,229,330 | [
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Binding of a Smad4/Ets-1 complex to a novel intragenic regulatory element in exon12 of FPGS underlies decreased gene expression and antifolate resistance in leukemia. | Polyglutamylation of antifolates catalyzed by folylpoly-γ-glutamate synthetase (FPGS) is essential for their intracellular retention and cytotoxic activity. Hence, loss of FPGS expression and/or function results in lack of antifolate polyglutamylation and drug resistance. Members of the TGF-β/Smad signaling pathway are negative regulators of hematopoiesis and deregulation of this pathway is considered a major contributor to leukemogenesis. Here we show that FPGS gene expression is inversely correlated with the binding of a Smad4/Ets-1 complex to exon12 of FPGS in both acute lymphoblastic leukemia cells and acute myeloid leukemia blast specimens. We demonstrate that antifolate resistant leukemia cells harbor a heterozygous point mutation in exon12 of FPGS which disrupts FPGS activity by abolishing ATP binding, and alters the binding pattern of transcription factors to the genomic region of exon12. This in turn results in the near complete silencing of the wild type allele leading to a 97% loss of FPGS activity. We show that exon12 is a novel intragenic transcriptional regulator, endowed with the ability to drive transcription in vitro, and is occupied by transcription factors and chromatin remodeling agents (e.g. Smad4/Ets-1, HP-1 and Brg1) in vivo. These findings bear important implications for the rational overcoming of antifolate resistance in leukemia. | 25,229,333 | [
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Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury. | Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors. | 25,229,339 | [
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[Pharmaceutical intervention in duration of antimicrobial treatment at hospital ambit]. | To estimate the acceptance of the pharmaceutical intervention in controlling duration of antimicrobial therapy and to evaluate their impact on optimizing the treatment. Prospective observational study for two years in a General University Hospital. For the patients record, we followed non critical adult patients with antibiotic treatment. When the duration of antimicrobial treatment not complied with established criteria for each antibiotic and pathology, there was a communication with the physician, at which is recommended to assess the need for continue treatment. The acceptance of pharmaceutical intervention was collected and afterwards we analyzed the impact of this work by antimicrobial consumption and incidence of Clostridium difficile. . In 122 patients the pharmacist made a pharmaceutical intervention due to prolonged antibiotic treatment. The most prevalent antibiotics were β-lactams, specifically meropenem. The intravenous administration was more frequent. In 77 cases it was decided to recommend the suspension of treatment, we conducted an orally prospective intervention at 70.15 % and the rest of interventions were written. Acceptance was 65.95 % and 65.00%, respectively. During the study period, the DDD of the antimicrobials decreased by 8.89% and expenditure on antimicrobials one 40.12%. The incidence of C. difficile was stable. . In a hospital, a pharmaceutical counselling program on the duration of antimicrobial therapy is well accepted by the prescriber physician, but it must be improved. The route of information does not affect the degree of acceptance. These actions could involve a reduction of antimicrobial consumption. | 25,229,371 | [
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Emergency contraception in Senegal: challenges and opportunities. | This paper highlights lessons from introductory efforts and presents new data on community, provider and key opinion leader perspectives to support expanded use of emergency contraception (EC) in Senegal. The paper draws on four data sources: (i) a literature review; (ii) a secondary analysis of a household survey conducted by the Urban Reproductive Health Initiative; (iii) in-depth interviews with key opinion leaders; and (iv) a quantitative survey of healthcare providers from a range of service delivery points. ANALYSIS OF DATA: Knowledge of EC among women is low in urban areas, with only 20% of women having heard of the method and 4% having ever used it. There were serious gaps in providers' technical knowledge about EC; only 57% knew its mode of action and 34% were aware of the need for timely use (within 120 h). Moreover, nearly half reported reluctance to provide EC to married women and even fewer were willing to provide it to youths, particularly to adolescent girls. Responses from key opinion leaders were mixed, demonstrating ambivalence about EC and how it could be offered. In Senegal, the current positive political climate for family planning provides a good opportunity for strengthening EC programming to address knowledge and attitudinal barriers among providers, key opinion leaders and communities. | 25,229,389 | [
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Are Re(i) phenanthroline complexes suitable candidates for OLEDs? Answers from DFT and TD-DFT investigations. | The electronic structure and spectroscopic properties of seven recently reported rhenium(i) phenanthroline complexes were investigated theoretically by density functional theory (DFT) and time dependent density functional theory (TD-DFT) methods. All the seven complexes are shown here to be better electron transport materials with high quantum efficiency in OLED devices due to their high electron transport mobility and low λ(electron) values. Particularly, among these seven chosen complexes the difference between λhole and λ(electron) for tricarbonyl Re(i) complexes is smaller, suggesting that these complexes have a better hole- and electron-transport balance in OLED devices. The absorption is associated with (1)MLCT/(1)LLCT transitions while the emission transition has (3)MLCT/(3)LLCT/(3)ILCT character as revealed by natural transition orbital (NTO) analysis. The calculated results show that the absorption and emission transitions and device efficiency can be changed by varying the nature and position of the axial ligands as revealed by the structural and bonding features of the complexes through natural bond orbital (NBO) and quantum theory of atoms in molecule (QTAIM) analysis. | 25,229,400 | [
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Effects of dietary pyrroloquinoline quinone disodium on growth performance, carcass yield and antioxidant status of broiler chicks. | Pyrroloquinoline quinone (PQQ), a putative essential nutrient and redox modulator in microorganisms, cell and animal models, has been recognized as a growth promoter in rodents. Growth performance, carcass yield and antioxidant status were evaluated on broiler chickens fed different levels of PQQ disodium (PQQ.Na2). A total of 784 day-old male Arbor Acres (AA) broilers were randomly allotted into seven dietary groups: negative control group (NC) fed a basal diet without virginiamycin (VIR) or PQQ.Na2; a positive control group (PC) fed a diet with 15 mg of VIR/kg diet; and PQQ.Na2 groups fed with 0.05, 0.10, 0.20, 0.40 or 0.80 mg PQQ.Na2/kg diet. Each treatment contained eight replicates with 14 birds each. The feeding trial lasted for 6 weeks. The results showed that chicks fed 0.2 mg PQQ.Na2/kg diet significantly improved growth performance comparable to those in PC group, and the feed efficiency enhancement effects of dietary PQQ.Na2 was more apparent in grower phase. Dietary addition of PQQ.Na2 had the potential to stimulate immune organs development, and low level dietary addition (<0.1 mg/kg) increased plasma lysozyme level. Broilers fed 0.2 mg PQQ.Na2/kg diet gained more carcasses at day 42, and had lower lipid peroxide malondialdehyde content and higher total antioxidant power in plasma. The results indicated that dietary PQQ.Na2 (0.2 mg/kg diet) had the potential to act as a growth promoter comparable to antibiotic in broiler chicks. | 25,229,409 | [
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Comparison of four methods to assess erosive substance loss of dentin. | Erosion of dentin results in a complex multi-layered lesion. Several methods have been used to measure erosive substance loss of dentin, but were found to have only limited agreement, in parts because they assess different structural parameters. The present study compared the agreement of four different methods (transversal microradiography [TMR], Confocal Laser Scanning Microscopy [CLSM], Laser Profilometry [LPM] and modified Knoop Hardness measurement [KHM]) to measure erosive substance loss in vitro. Ninety-six dentin specimens were prepared from bovine roots, embedded, ground, polished and covered with nail-varnish except for an experimental window. Erosion was performed for 1 h using citric acid concentrations of 0.00% (control), 0.07%, 0.25% and 1.00% (n=24/group). Adjacent surfaces served as sound reference. Two examiners independently determined the substance loss. After 1 h erosion with 1% citric acid solution, substance losses (mean ± SD) of 12.0 ± 1.3 µm (TMR), 2.9 ± 1.3 µm (LPM), 3.9 ± 1.3 µm (KHM) and 17.0 ± 2.6 µm (CLSM) were detected. ROC curve analysis found all methods to have high accuracy for discriminating different degrees of erosive substance loss (AUC 0.83-1.00). Stepwise discriminatory analysis found TMR and CLSM to have the highest discriminatory power. All methods showed significant relative and proportional bias (p<0.001). The smallest albeit significant disagreement was found between LPM and KHM. No significant inter-rater bias was detected except for KHM. LPM is prone to underestimate erosive loss, possibly due to detection of the organic surface layer. KHM was not found suitable to measure erosive loss in dentin. TMR and CLSM detected the loss of mineralised tissue, showed high reliability, and had the highest discriminatory power. Different methods might be suitable to measure different structural parameters. | 25,229,410 | [
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The emerging role of the peptidome in biomarker discovery and degradome profiling. | The peptidome represents the array of endogenous peptides that are present in both the intracellular and extracellular space of the body. Peptides are constantly generated in vivo by active synthesis, and by proteolytic processing of larger precursor proteins, often yielding protein fragments that mediate a variety of physiological functions. Given that aberrant proteolysis is a hallmark of various pathological diseases, many studies have now turned to the peptidome. Differential regulation of endogenous peptides may play a role in many pathological conditions. Mass spectrometry (MS) -based investigation of peptides in a system-wide manner is currently facilitating the identification of potential biomarkers. Furthermore, peptidomic approaches have provided major contributions to the identification of protease-substrate relationships; representing one of the major challenges in understanding and therapeutically exploiting protease function in health and disease. As such, degradomic studies looking for cleavage products via peptidomics in particular, have warranted a significant research interest in recent years. Given that substantial studies are accumulating in the field of peptidomics, this review highlights recent advances of MS-based peptidomic strategies in facilitating the identification of potential peptides as novel clinical markers and protease-substrate profiling. | 25,229,414 | [
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... |
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