title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Placental ischemia in pregnant rats impairs cerebral blood flow autoregulation and increases blood-brain barrier permeability. | Cerebrovascular events contribute to ~40% of preeclampsia/eclampsia-related deaths, and neurological symptoms are common among preeclamptic patients. We previously reported that placental ischemia, induced by reducing utero-placental perfusion pressure, leads to impaired myogenic reactivity and cerebral edema in the pregnant rat. Whether the impaired myogenic reactivity is associated with altered cerebral blood flow (CBF) autoregulation and the edema is due to altered blood-brain barrier (BBB) permeability remains unclear. Therefore, we tested the hypothesis that placental ischemia leads to impaired CBF autoregulation and a disruption of the BBB. CBF autoregulation, measured in vivo by laser Doppler flowmetry, was significantly impaired in placental ischemic rats. Brain water content was increased in the anterior cerebrum of placental ischemic rats and BBB permeability, assayed using the Evans blue extravasation method, was increased in the anterior cerebrum. The expression of the tight junction proteins: claudin-1 was increased in the posterior cerebrum, while zonula occludens-1, and occludin, were not significantly altered in either the anterior or posterior cerebrum. These results are consistent with the hypothesis that placental ischemia mediates anterior cerebral edema through impaired CBF autoregulation and associated increased transmission of pressure to small vessels that increases BBB permeability leading to cerebral edema. | 25,168,877 | [
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Expression and vitamin D-mediated regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy skin and in diabetic foot ulcers. | Diabetic foot ulcers (DFUs) are chronic wounds with high matrix metalloproteinase (MMP) activity, and are a frequent complication on diabetics. This work studied the expression of selected MMP and tissue inhibitor of metalloproteinases (TIMP) gene family members in DFU and normal skin biopsies, and in vitamin D-treated keratinocytes cultured from those biopsies. We report for the first time the expression of some of these genes in healthy skin. Our results suggest that vitamin D may modulate the expression of some MMP gene family members in keratinocytes. Gene expression in DFU and in non-diabetic healthy skin (control) biopsies was evaluated by RT-qPCR for MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-19, TIMP-1 and TIMP-2, and also by immunohistochemistry for MMP-1 and MMP-9. Primary keratinocytes cultured from DFU and healthy skin biopsies were used for gene expression analyses of selected MMPs and TIMPs by RT-qPCR, both in the presence and absence of calcitriol. The expression of MMP-1, MMP-8, MMP-9, MMP-10, and TIMP-2 in healthy skin is reported here for the first time. DFUs showed increased MMP-1, MMP-9 and TIMP-1 expression, compared to healthy skin. Calcitriol down-regulated MMP-1 and MMP-10 expression in DFU-derived keratinocytes but not in those derived from healthy skin. Our data demonstrate the expression of certain MMPs that had not been previously described in healthy skin, and further support previous reports of MMP and TIMP up-regulation in DFUs. Our results point to calcitriol as a potential modulator for the expression of certain MMP members in DFUs. | 25,168,880 | [
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Determinants of height and biological inequality in Mediterranean Spain, 1859-1967. | This article analyses not only the determinants of the height of Spain's male populations between 1859 and 1960 but also the influence that social inequality had upon biological well-being. The height data of 82,039 conscripts constitute the principal source for this analysis. The study area comprises the current Valencian region, located in central Mediterranean Spain. During the period under study, the average height of conscripts increased by 7.5cm, while the coefficient of variation decreased by 0.6 between the 1870s and 1930 indicating that height inequality declined, although it increased by 0.2 among the cohorts born during the period of Francoist regime. Our results show that, in the long run, the height and biological well-being of the populations conscripted in Mediterranean Spain were determined by socioeconomic status and environmental contexts: that there was a close correlation among education, occupation, income, and stature. Literate conscripts were always taller than illiterate ones (by nearly 1cm), and agricultural workers, with fewer economic resources, were significantly shorter (by 3.6cm) than highly qualified non-manual workers. | 25,168,885 | [
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SLURP-1 modulates corneal homeostasis by serving as a soluble scavenger of urokinase-type plasminogen activator. | Our previous study revealed the immunomodulatory property of the secreted lymphocyte antigen (Ly6)/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP1), abundantly expressed in the cornea and associated with the hyperkeratotic disorder Mal de Meleda. Here, we test the hypothesis that SLURP1 modulates the functions of membrane-tethered uPAR by acting as a soluble scavenger of its ligand urokinase-type plasminogen activator (uPA). Human corneal limbal epithelial (HCLE) and mouse corneal stromal fibroblast MK/T-1 cells were employed to examine the effect of SLURP1 on cell proliferation and migration. Human corneal limbal epithelial cell clones stably expressing SLURP1 under the control of cytomegalovirus (CMV) promoter were generated using lentiviral vectors. Recombinant 6× His-mouse Slurp1 and maltose-binding protein (MBP)-mouse uPA were expressed in Escherichia coli and partially purified using nickel-ion and amylose columns, respectively. Slurp1 interaction with uPA was detected using ligand blots, ELISA, pull-down assays, and immunofluorescent staining. Stable expression of SLURP1 in HCLE cells was confirmed by immunoblots and immunofluorescent staining. Human corneal limbal epithelial and MK/T-1 cell proliferation and migration rates were suppressed by exogenous SLURP1. Ligand blots, ELISA, and pull-down assays indicated that Slurp1 efficiently interacts with uPA. Immunofluorescent staining demonstrated that exogenous SLURP1 decreased the amount of cell surface-bound uPA in the leading edges of migrating cells. In gap-filling assays, wild-type HCLE cells responded to uPA by increasing their velocity and closing larger area, while the SLURP1-expressing HCLE cells failed to do so. SLURP1 modulates corneal homeostasis by serving as a soluble scavenger of uPA and regulating the uPA-dependent functions of uPAR. | 25,168,896 | [
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Expression of granzyme B sensitizes ALK+ ALCL tumour cells to apoptosis-inducing drugs. | The serine protease Granzyme B (GzB) is primarily expressed by cytotoxic T lymphocytes and natural killer cells, and functions in allowing these cells to induce apoptosis in virally-infected or transformed cells. Cancers of both lymphoid and non-lymphoid origin also express GzB, and in some cases this expression has been linked to pathogenesis or sensitizing tumour cells to cell death. For example, GzB expression in urothelial carcinoma was implicated in promoting tumour cell invasion, whereas its expression in nasal-type NK/T lymphomas was found to correlate with increased apoptosis. GzB expression is also a hallmark of the non-Hodgkin lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL). Given the fact that ALK+ ALCL exhibits high levels of apoptosis and is typically responsive to conventional chemotherapy, we examined whether GzB expression might play a role in sensitizing ALK+ ALCL tumour cells to apoptosis. ALK+ ALCL cell lines stably expressing GzB or non-targeting (control) shRNA were generated and apoptosis was examined by anti-PARP western blotting and terminal deoxynucleotidyl transferase dUTP nick end labelling. Both spontaneous apoptosis and apoptosis in response to treatment with staurosporine or doxorubicin were investigated. In order to assess whether additional granzymes might be important in promoting cell death in ALK+ ALCL, we examined whether other human granzymes were expressed in ALK+ ALCL cell lines using reverse-transcriptase PCR and western blotting. Expression of several GzB shRNAs in multiple ALK+ ALCL cell lines resulted in a significant decrease in GzB levels and activity. While spontaneous apoptosis was similar in ALK+ ALCL cell lines expressing either GzB or control shRNA, GzB shRNA-expressing cells were less sensitive to staurosporine or doxorubicin-induced apoptosis as evidenced by reduced PARP cleavage and decreased DNA fragmentation. Furthermore, we found that GzB is the only granzyme that is expressed at significant levels in ALK+ ALCL cell lines. Our findings are the first to demonstrate that GzB expression sensitizes ALK+ ALCL cell lines to drug-induced apoptosis. This suggests that GzB expression may be a factor contributing to the favourable response of this lymphoma to treatment. | 25,168,906 | [
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Imaging of site specific bone turnover in osteoporosis using positron emission tomography. | The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer. | 25,168,931 | [
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Treatment of intracerebral hemorrhage associated with new oral anticoagulant use: the neurologist's view. | Intracerebral hemorrhage (ICH) associated with the use of oral anticoagulants (OAC-ICH) results in particularly severe strokes. A key target for the treatment of OAC-ICH is rapid restoration of effective coagulation. In patients receiving vitamin K antagonists, hemostatic factors such as prothrombin complex concentrate (PCC), fresh frozen plasma, and recombinant activated factor VII, in addition to vitamin K, can be used for anticoagulation reversal. However, emergency management of ICH during treatment with the new direct OACs (NOACs) is a major challenge. In the absence of specific antidotes, PCCs are recommended for NOAC reversal, mainly based on preclinical data. | 25,168,944 | [
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Serum Endocan Level and the Severity of Coronary Artery Disease: A Pilot Study. | Endothelial-specific molecule 1 (endocan) is expressed in endothelial cells. We investigated the relationship between acute coronary syndrome (ACS) and serum endocan levels. We included 30 individuals as a control group and 53 patients diagnosed with ACS. The severity of coronary artery disease was assessed by a modified Gensini stenosis and SYNTAX scoring system. There was a significant difference in serum endocan levels between the control group and the ACS group (0.75 ± 0.13 vs 0.86 ± 0.25 ng/mL, P = .014). There was also a significant difference in serum endocan levels between diabetic patients with ACS and nondiabetic patients with ACS (1.02 ± 0.33 vs 0.81 ± 0.21 ng/mL, P = .016). There was no significant correlation between serum endocan level, Gensini, and SYNTAX score (r = .11, P = .53 and r = .16, P = .37). Endocan, a new biomarker of endothelial pathology, is significantly increased in patients with ACS. | 25,168,956 | [
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In vitro antifungal susceptibility of Malassezia furfur from bloodstream infections. | Fungaemia caused by Malassezia spp. in hospitalized patients requires prompt and appropriate therapy, but standard methods for the definition of the in vitro antifungal susceptibility have not been established yet. In this study, the in vitro susceptibility of Malassezia furfur from bloodstream infections (BSIs) to amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), posaconazole (POS) and voriconazole (VRC) was assessed using the broth microdilution (BMD) method of the Clinical and Laboratory Standards Institute (CLSI) with different media such as modified Sabouraud dextrose broth (SDB), RPMI and Christensen's urea broth (CUB). Optimal broth media that allow sufficient growth of M. furfur, and produce reliable and reproducible MICs using the CLSI BMD protocol were assessed. Thirty-six M. furfur isolates collected from BSIs of patients before and during AMB therapy, and receiving FLC prophylaxis, were tested. A good growth of M. furfur was observed in RPMI, CUB and SDB at 32 °C for 48 and 72 h. No statistically significant differences were detected between the MIC values registered after 48 and 72 h incubation. ITC, POS and VRC displayed lower MICs than FLC and AMB. These last two antifungal drugs showed higher and lower MICs, respectively, when the isolates were tested in SDB. SDB is the only medium in which it is possible to detect isolates with high FLC MICs in patients receiving FLC prophylaxis. A large number of isolates showed high AMB MIC values regardless of the media used. In conclusion, SDB might be suitable to determine triazole susceptibility. However, the media, the drug formulation or the breakpoints herein applied might not be useful for assessing the AMB susceptibility of M. furfur from BSIs. | 25,168,965 | [
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Across-shift changes of exhaled nitric oxide and spirometric indices among cotton textile workers. | For the purpose of evaluation of exhaled NO as an index of airway inflammation, we assessed changes in fractional exhaled NO (FeNO) across a work shift and its relationship with respiratory complaints. Chronic and work-aggravated respiratory complaints were assessed using a questionnaire in 89 male textile workers. FeNO and spirometry were performed before and after a work shift and all the changes were registered. A significant increase in FeNO after a work shift was observed. Post-shift FeNO was significantly higher among the subjects with chronic respiratory complaints. There was an obvious decrease in FVC, and FEV1 after a work shift; however, we couldn't find a significant relationship between changes in respiratory parameters and concentration of inhalable dusts. FeNO increase after a work shift along with pulmonary function decrement and higher post-shift FeNO among subjects with respiratory complaints makes across-shift FeNO a non-invasive test for assessment of airway hyper-responsiveness in textile workers. | 25,168,972 | [
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Investigation of the relationship between illogical thoughts and dependence on others and marriage compatibility in the Iranian Veterans exposed to chemicals in Iran-Iraq War. | Marital satisfaction is one of the main determinants of a family's correct function. A large number of veterans have been reported to suffer from depression, anxiety, mood disorders, post-traumatic stress disorder, and physical disorders. The objective of this study is to examine association between Illogical thoughts and Dependence on Others and Marriage Compatibility in the Iranian Veterans Exposed to Chemicals in Iran-Iraq War. The present cross-sectional, analytical study was conducted on 200 veterans exposed to chemicals who were covered by the Foundation of Martyrs and Veterans Affairs, Gilangharb, Kermanshah, Iran. The study sample size was determined according to Krejcie and Morgan formula and the subjects were selected through random sampling. The study data were collected using marriage compatibility questionnaire, illogical thoughts questionnaire, and dependence on others questionnaire. The study data were analyzed using the SPSS statistical software (version18). Pearson correlation coefficient, multiple regression, and t-test were used in order to determine the relationships among the variables and compare the means. The findings of the current study revealed no significant relationship between dependence on others, anxious attention, helplessness, avoiding problems, perfectionism, and autonomy and marriage compatibility. However, a significant relationship was found between failure and marriage compatibility. Overall, the findings of the present study showed that the veterans of Gilangharb did not have disorders, but depended on others, particularly their spouses, due to their abnormal physical status. Sometimes, they cannot even do their personal tasks which results in their dependence on others eventually putting the veterans under pressure and stress. | 25,168,982 | [
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Design and evaluation of electronic briefs of neonatal intensive care unit in Taleghani hospital, Tabriz, Iran. | More than 9 million neonatal deaths are reported through out the world each year happening in the early weeks of life most of which relate to developing countries. Thus it is very important to present a better way to keep the infants healthy which could be possible by accessing accurate information at any time required during hospitalization of infants. Therefore the required data should be collected, stored and analyzed before which is best possible by using computer. The main objective of this research is enabling researchers and clinicians quick access to the data of the babies admitted in NICU. This study involves the stage of developing a system design and its implementation following the evaluation of the electronic records which is done in a query form. By defining the neccessary terminology and designing a data model, the database and user interface are developed by using a programing language and data base tools. Finally, the system has been evaluated by user satisfaction showing to be about 85% As a result we suggest the hospitals take serious in buying the suitable technology for the NICU ward along with teaching the staffs how to work with it. | 25,168,989 | [
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Assessment of patient satisfaction of the quality of health care provided by outpatient services of an oncology hospital. | The purpose of this research is to investigate the patient's satisfaction (patient's satisfaction) with medical services provided in Outpatients' Departments of a Greek Anti-Cancer Hospital in morning and afternoon clinics. The assessment of patients and identification of factors that contribute to their satisfaction will highlight the organizational and operational problems of outpatient department and assist in finding solutions to upgrade the quality of services provided. For the collection of data, a questionnaire with closed answers in a five-point scale 'Likert' scale was used. The questions were related to demographics, social data users, and the overall service process in the outpatient Hospital. The sample consisted of 100 patients (RR: 76%) who visited the outpatient clinic in the morning or afternoon over a month long period of time. The results of our research showed that cancer patients reported a high satisfaction rate with the health services provided in outpatient department of Anti-Cancer Hospital. The highest reported levels of satisfaction were related to working with medical staff because of the special relationship of trust that patients develop with their physician. Some problems were noted during the morning shift by patients. Patients reported frustration over long waiting times to get an appointment, last minute appointments, lack of flexibility when making appointments and long waiting times before being examined by a doctor. No statistically significant relationship was found between overall satisfaction with demographics' and other factors, although the grading services seem to be affected by the health status of patients, education and sex. | 25,169,006 | [
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Triptolide-induced oxidative stress involved with Nrf2 contribute to cardiomyocyte apoptosis through mitochondrial dependent pathways. | Triptolide (TP), a major active ingredient extracted from the widely used Chinese herb Tripterygium wilfordii Hook f. (TWHF), has been demonstrated to possess various biological activities. However, the clinical applications of TP are limited by its narrow therapeutic window and severe toxicity. The current study aimed to investigate the roles of reactive oxygen species (ROS) and mitochondria in TP-induced cardiac injury. Male BALB/C mice were intravenously (i.v.) treated with a single dose of TP (1.2 mg/kg). After 24h, TP induced the oxidative stress, mitochondrial dysfunction, apoptotic damage, and pathological changes of heart tissue. In vitro studies also indicated that the cytotoxic effects of TP involved the ROS-mediated mitochondria-dependent pathway in H9c2 cells. TP treatment increased the accumulation of ROS and subsequently triggered cell apoptosis by depolarizing the mitochondrial membrane potential (ΔΨm), reduced the ratio of Bax/Bcl-2, released cytochrome c and, ultimately, activated caspase-3. Nrf2, as well as its downstream antioxidants, were also suppressed by TP. Taken together, these results suggest that TP induces cardiotoxicity in vivo and in vitro via oxidative stress, which was associated with down regulated Nrf2 activation, and the mitochondria-mediated apoptotic signaling pathway. | 25,169,008 | [
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Intrinsic religiousness and well-being among cancer patients: the mediating role of control-related religious coping and self-efficacy for coping with cancer. | We examined the relationship between intrinsic religiousness and well-being, with control-related religious coping and self-efficacy for coping with cancer as potential mediators of this relationship among cancer patients. In a cross-sectional design, 179 ambulatory cancer patients completed measures of intrinsic religiousness, religious coping, self-efficacy for coping with cancer, well-being, and demographic variables. Type of cancer, stage of cancer, and time since diagnosis were collected from electronic medical charts. In a path model, the positive association between intrinsic religiousness and three types of well-being--physical, functional, and social-was fully mediated by active religious surrender and self-efficacy for coping with cancer. In addition, the negative association between passive religious deferral and all four types of well-being--physical, functional, social, and emotional--was fully mediated by self-efficacy for coping with cancer. Finally, there was a negative direct association between pleading for God's direct intercession and emotional well-being. These findings suggest pathways by which intrinsic religiousness and control-related religious coping are linked to various dimensions of well-being among cancer patients. | 25,169,026 | [
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Modified cranialization and secondary cranioplasty for frontal sinus infection after craniotomy: technical note. | Frontal sinus infection after incorrect treatment of an opened frontal sinus may require extended approaches. This article aims to introduce modified cranialization technique and secondary cranioplasty for frontal sinus infection involving the frontal sinus outflow tract after craniotomy. Eight patients with delayed onset frontal sinus infection involving frontal outflow tract after craniotomy were treated from 2008 to 2012. Debridement and cranialization involving the elimination of the frontal outflow tract was performed. Unilateral sinus cranialization combined with reduction of the non-affected contralateral sinus was carried out for the patients with unilateral sinusitis. A pericranial-frontalis muscle flap was used to separate the intracranial and extracranial spaces. Secondary cranioplasty with hydroxyapatite was performed approximately 3 months after the cranialization. The patients' original conditions included brain tumors (n = 3), frontal sinus fractures (n = 2), and subarachnoid hemorrhage (n = 3). The mean interval between the initial treatment and the onset of sinus infection was 23 years. The frontal sinus infection was bilateral in six cases and unilateral in two cases. Frontal sinus outflow tract was involved in sinus infection in every case. None of the patients suffered recurrent rhinogenic infections within the follow-up period (mean = 35 months) after the secondary cranioplasty. Aesthetic results were satisfactory in every case. Modified cranialization involving elimination of the frontal outflow tract is an alternative method for the patients with pathology in the frontal outflow tract after frontal craniotomy. Secondary cranioplasty provides an esthetically pleasing appearance in such cases. | 25,169,030 | [
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Plasma lipidomics discloses metabolic syndrome with a specific HDL phenotype. | Lipidomics reveals a remarkable diversity of lipids in human plasma. In this study, we have performed an in-depth lipidomic analysis of human plasma from healthy individuals and subjects with metabolic syndrome (MetS) in order to determine the lipidomic profile that allows prognosis of a pathological subpopulation with altered high-density lipoprotein (HDL) metabolism. The MetS population was categorized as having pathological or nonpathological HDL. Anthropometric parameters, cardiovascular risk markers, and lipoprotein subclasses of HDL and low-density lipoproteins were also evaluated. Lipidomic analysis revealed 357 differential molecules that were clustered (k means) in the two groups. The molecules identified in the whole lipidome showed that MetS subjects presented lower levels of glycerolipids and higher levels of glycerophospholipids with respect to control subjects. In contrast, when only statistically differential lipids were taken into account, differences were found between the two groups in almost cases. Furthermore, levels of saturated fatty acids were higher in patients with pathological HDL levels than in controls, whereas levels of unsaturated fatty acids were lower. These results highlight the potential of lipidomics as a clinical tool for risk assessment and monitoring of disease. | 25,169,057 | [
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WIP is necessary for matrix invasion by breast cancer cells. | Actin filament assembly and reorganisation during cell migration and invasion into extracellular matrices is a well-documented phenomenon. Among actin-binding proteins regulating its polymerisation, the members of the WASP (Wiskott Aldrich Syndrome Protein) family are generally thought to play the most significant role in supporting cell invasiveness. In situ, cytosolic N-WASP (neural WASP) is associated with a partner protein termed WIP (WASP Interacting Protein) that is bound to the N-terminal domain of N-WASP. Despite much effort, rather little is known about the role of WIP in regulating N-WASP and consequent actin-filament assembly. Even less is known about the function of WIP within the specialised cell adhesion and attachment structures known as podosomes and invadopodia. In particular, whilst the interaction of WIP with known participants in the development and maturation of invadopodia such as N-WASP, the Arp2/3 complex and cortactin has been described, little is known concerning the direct contribution of WIP to invadopodia and its potential role as a regulator of cancer cell invasion. In this report, we use 2D and 3D culture systems to describe the role played by WIP in modulating the morphology and invasiveness of metastatic breast cancer cells in vitro, as well as its effect on the process of mesenchymal-epithelial transition (MET) seen in these cells. We demonstrate that WIP is necessary for invadopodium formation and matrix degradation by basal breast cancer cells, but not sufficient to induce invasiveness in luminal cells. | 25,169,059 | [
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Changes in the perfusion waveform of the internal cerebral vein and intraventricular hemorrhage in the acute management of extremely low-birth-weight infants. | This prospective observational study aimed to investigate the association between changes in the Doppler perfusion waveform of the internal cerebral vein and risk of intraventricular hemorrhage (IVH) in extremely low-birth-weight (ELBW) infants. We evaluated the perfusion waveform of the internal cerebral vein every 8 h from immediately after birth to 144 h post-birth in 80 ELBW infants (<1,000 g) in our hospital. Fluctuations in the measured perfusion waveform were categorized into four patterns according to their increasing magnitude, from grade 0 (steady flow waveform) to grade 3; the IVH rate was investigated. Infants with grades 0-1 fluctuations of the perfusion waveform were classified as low grade (n = 55), and those with grades 2-3 fluctuations were classified as high grade (n = 25). The IVH rate was significantly higher in the high-grade group than the low-grade group (28 vs. 1%, p < 0.001). The IVH group (n = 8) showed a significantly greater rate of high-grade perfusion waveform than the non-IVH group (n = 72) (87 vs. 25%, p < 0.001). Changes in the perfusion waveform of the internal cerebral vein during the acute management of ELBW infants may be associated with IVH. | 25,169,064 | [
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[Levels of complement components C3a and C5a in renal injury among trichloroethylene-sensitized BALB/c mice]. | To determine the levels of complement components C3a and C5a in the kidneys of trichloroethylene (TCE)-sensitized BALB/c mice, and to investigate the role of complement components in TCE-induced renal injury among BALB/c mice. Sixty-two female BALB/c mice were randomly divided into blank control group, vehicle control group, and TCE sensitization group. The mice in TCE sensitization group were sensitized by one intracutaneous injection and one abdominal smear of TCE. At 24 h, 48 h, 72 h, and 7 d after the second sensitization, mice were sacrificed, and the blood and kidneys were collected. An automatic biochemical analyzer was used in the determination of serum blood urea nitrogen (BUN) and creatinine (Cr). The levels of C3a and C5a in the kidneys were determined by immunohistochemistry. The sensitization rate of TCE sensitization group was 42.0%. Kidney coefficient and serum levels of BUN and Cr were significantly increased in the TCE sensitization group as compared with the vehicle control group at 48 h and 72 h after sensitization (P < 0.05). The kidney coefficients of the TCE sensitization group at 48 h and 72 h were significantly higher than those of the control groups (P < 0.05). In comparison with the vehicle control group, however, no significant change was found in kidney coefficient, serum BUN, or serum Cr at 7 d after TCE sensitization (P > 0.05). Levels of C3a and C5a at 48 h (3.80±0.84 and 4.00±1.00, respectively) and 72 h (4.40 ± 1.14 and 4.40 ± 1.14, respectively) after sensitization were all significantly higher than those of the vehicle control group (P < 0.05), but no significant difference was found in level of C3a (1.80±0.45) or C5a (2.00 ± 0.71) at 7 d (P > 0.05). TCE sensitization can induce renal injury in mice. Levels of complement components C3a and C5a are elevated in the kidneys of sensitized mice, indicating that C3a and C5a may be involved in the renal injury induced by TCE sensitization. | 25,169,086 | [
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[Preventive effects of garlic oil against the benzene-induced hematotoxicity in mice]. | To investigate the preventive effects of garlic oil (GO) on benzene-induced hematotoxicity in mice. Specific pathogen-free male Kunming mice were randomly divided into 5 groups, i.e., control group, model group, and low-, middle-, and high-dose GO groups (n = 20 in each group). Mice in GO groups were orally given GO at 20, 40, or 80 mg/kg BW, while mice in the other two groups received an equal volume of corn oil. Two hours later, mice in model group and GO groups were orally given benzene (20%, v/v, dissolved in corn oil, 10 ml/kg BW) for 21 days consecutively. On the 22nd day, blood was collected from the orbital sinus, to determine the counts of red blood cells (RBC), white blood cells (WBC), and platelets (PLT) and hemoglobin level using an automatic blood cell counter. The mice were sacrificed thereafter. The spleen was excised and weighed for calculation of the spleen index (spleen weight/body weight×100%). The counts of WBC, RBC, and PLT and Hb level in the model group were reduced by 40%, 18%, 28%, and 23.6%, respectively, as compared with those in the control group (P < 0.01). Compared with those in the model group, WBC and PLT counts in the high-dose GO group increased by 95% and 66%, respectively (P < 0.01), wherein lymphocytes and monocytes increased by 142% and 100%, respectively (P < 0.01); the RBC count and Hb level in the low-dose GO group increased by 15% and 16%, respectively (P < 0.05). GO significantly suppressed benzene-induced decreases in spleen weight and spleen index. GO is capable of suppressing benzene-induced hematotoxicity in mice. One possible mechanism may be promotion of hematopoiesis in the spleen. | 25,169,096 | [
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Aggregatibacter actinomycetemcomitans leukotoxin (LtxA; Leukothera) induces cofilin dephosphorylation and actin depolymerization during killing of malignant monocytes. | Leukotoxin (LtxA; Leukothera), a protein toxin secreted by the oral bacterium Aggregatibacter actinomycetemcomitans, specifically kills white blood cells (WBCs). LtxA binds to the receptor known as lymphocyte function associated antigen-1 (LFA-1), a β2 integrin expressed only on the surface of WBCs. LtxA is being studied as a virulence factor that helps A. actinomycetemcomitans evade host defences and as a potential therapeutic agent for the treatment of WBC diseases. LtxA-mediated cell death in monocytes involves both caspases and lysosomes; however, the signalling proteins that regulate and mediate cell death remain largely unknown. We used a 2D-gel proteomics approach to analyse the global protein expression changes that occur in response to LtxA. This approach identified the protein cofilin, which underwent dephosphorylation upon LtxA treatment. Cofilin is a ubiquitous actin-binding protein known to regulate actin dynamics and is regulated by LIM kinase (LIMK)-mediated phosphorylation. LtxA-mediated cofilin dephosphorylation was dependent on LFA-1 and cofilin dephosphorylation did not occur when LFA-1 bound to its natural ligand, ICAM-1. Treatment of cells with an inhibitor of LIMK (LIMKi) also led to cofilin dephosphorylation and enhanced killing by LtxA. This enhanced sensitivity to LtxA coincided with an increase in lysosomal disruption, and an increase in LFA-1 surface expression and clustering. Both LIMKi and LtxA treatment also induced actin depolymerization, which could play a role in trafficking and surface distribution of LFA-1. We propose a model in which LtxA-mediated cofilin dephosphorylation leads to actin depolymerization, LFA-1 overexpression/clustering, and enhanced lysosomal-mediated cell death. | 25,169,107 | [
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Physiologic comparison of neurally adjusted ventilator assist, proportional assist and pressure support ventilation in critically ill patients. | To compare, in a group of difficult to wean critically ill patients, the short-term effects of neurally adjusted ventilator assist (NAVA), proportional assist (PAV+) and pressure support (PSV) ventilation on patient-ventilator interaction. Seventeen patients were studied during NAVA, PAV+ and PSV with and without artificial increase in ventilator demands (dead space in 10 and chest load in 7 patients). Prior to challenge addition the level of assist in each of the three modes tested was adjusted to get the same level of patient's effort. Compared to PSV, proportional modes favored tidal volume variability. Patient effort increase after dead space was comparable among the three modes. After chest load, patient effort increased significantly more with NAVA and PSV compared to PAV+. Triggering delay was significantly higher with PAV+. The linear correlation between tidal volume and inspiratory integral of transdiaphragmatic pressure (PTPdi) was weaker with NAVA than with PAV+ and PSV on account of a weaker inspiratory integral of the electrical activity of the diaphragm (∫EAdi)-PTPdi linear correlation during NAVA [median (interquartile range) of r(2), determination of coefficient, 16.2% (1.4-30.9%)]. Compared to PSV, proportional modes favored tidal volume variability. The weak ∫EAdi-PTPdi linear relationship during NAVA and poor triggering function during PAV+ may limit the effectiveness of these modes to proportionally assist the inspiratory effort. | 25,169,117 | [
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A low level of GPR37 is associated with human hepatocellular carcinoma progression and poor patient survival. | GPR37, also known as parkin-associated endothelin-like receptor (Pael-R), is an orphan G protein-coupled receptor (GPCR). It has been reported that GPCRs play vital roles in the development and progression of cancer. To investigate the potential roles of GPR37 in hepatocellular carcinoma (HCC), expression of GPR37 was examined in human HCC samples. Immunohistochemistry and Western blot analyses were performed for GPR37 in 57 hepatocellular carcinoma samples. GPR37 expression was low in hepatocellular carcinoma as compared with the adjacent non-tumorous tissues. Clinicopathological analysis showed that GPR37 expression was significantly correlated with histological grade and the level of alpha fetal protein (AFP) (P = 0.000 and 0.002, respectively). The Kaplan-Meier survival curves revealed that decreasing GPR37 expression was associated with poor prognosis in HCC patients, while in vitro, following the release from serum starvation of HuH7 HCC cell, the expression of GPR37 was downregulated. In addition, the transient GPR37 knockdown by siRNA in HuH7 cells significantly decreased the apoptosis of hepatoma cells with activation of the phosphatidylinositol 3-kinase-Akt signaling pathway. Our data suggest that GPR37 may play an important role in the pathogenesis of hepatocellular carcinoma by affecting the proliferation of H CC cells, and it could be a novel potential molecular therapy target for HCC. | 25,169,131 | [
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Nuclear model analysis of excitation functions of proton and deuteron induced reactions on (64)Zn and (3)He- and α-particle induced reactions on (59)Co leading to the formation of copper-61: Comparison of major production routes. | Cross section data for formation of the medically important radionuclide (61)Cu (T½=3.33h) in proton and deuteron induced reactions on enriched (64)Zn and in (3)He- and α-particle induced reactions on (59)Co were analyzed by using the nuclear model calculational codes, EMPIRE and TALYS. A well-defined statistical procedure was then employed to derive the recommended excitation functions, and therefrom to obtain integral yields. A comparison of major production routes of (61)Cu was done. | 25,169,133 | [
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Disparate plasma cortisol concentrations in sexually abused female children from Johannesburg, South Africa. | A growing body of research indicates that a bidirectional response to a stressor may occur in maltreated children and may be associated with later life psychopathology. However, few studies have investigated stress reactivity in children when they first present to a sexual abuse clinic. Thus, in order to evaluate whether HPA axis dysregulation would be evident at first presentation to a sexual abuse clinic in young girls (n = 26), between the ages of 6-12 years old, blood samples were obtained immediately following examination at a forensic sexual abuse clinic and from the matched control group of children (n = 14; 10.1 ± 0.8) immediately following a bone density scan. Stratification of the sexually abused group into those children who were reportedly abused by a stranger and had no other family stressors (n = 15, 10.4 ± 1.8) and those children whose parents reported abuse of the child by a stranger and other family stressors (n = 11; 9.5 ± 1.8) revealed differences in stress reactivity. Plasma concentrations, of the children from the forensic clinic, were significantly increased in children who reported abuse by a stranger only (322.3 ± 117.4 nmol/l) and significantly decreased in children whose histories indicated sexual abuse by a stranger and other family stressors (149.6 ± 39.7 nmol/l) when compared to the control group (225.5 ± 47.5 nmol/l). In conclusion, following sexual abuse and a secondary stressor, the forensic examination, there is evidence of divergent cortisol responses in the stratified clinical group of children. | 25,169,148 | [
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SWI/SNF chromatin remodeling complexes and cancer. | The identification of mutations and deletions in the SMARCB1 locus in chromosome band 22q11.2 in pediatric rhabdoid tumors provided the first evidence for the involvement of the SWI/SNF chromatin remodeling complex in cancer. Over the last 15 years, alterations in more than 20 members of the complex have been reported in a variety of human tumors. These include germline mutations and copy number alterations in SMARCB1, SMARCA4, SMARCE1, and PBRM1 that predispose carriers to both benign and malignant neoplasms. Somatic mutations, structural abnormalities, or epigenetic modifications that lead to reduced or aberrant expression of complex members have now been reported in more than 20% of malignancies, including both solid tumors and hematologic disorders in both children and adults. In this review, we will highlight the role of SMARCB1 in cancer as a paradigm for other tumors with alterations in SWI/SNF complex members and demonstrate the broad spectrum of mutations observed in complex members in different tumor types. | 25,169,151 | [
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Middle school student attitudes about school drinking fountains and water intake. | To describe middle school student attitudes about school drinking fountains, investigate whether such attitudes are associated with intentions to drink water at school, and determine how intentions relate to overall water intake. Students (n = 3211) in 9 California middle schools completed surveys between 2009 and 2011. We used multivariate linear regression, adjusting for school sociodemographic characteristics, to examine how attitudes about fountains (5-point scale; higher scores indicating more positive attitudes) were associated with intentions to drink water at school and how intentions to drink water at school were related to overall water intake. Mean age of students was 12.3 (SD = 0.7) years; 75% were Latino, 89% low income, and 39% foreign born. Fifty-two percent reported lower than recommended overall water intake (<3 glasses/day), and 30% reported that they were unlikely or extremely unlikely to drink water at school. Fifty-nine percent reported that school fountains were unclean, 48% that fountain water does not taste good, 33% that fountains could make them sick, 31% that it was not okay to drink from fountains, and 24% that fountain water is contaminated. In adjusted analyses, attitudes about school drinking fountains were related to intentions to drink water at school (β = 0.41; P < .001); intentions to drink water at school were also associated with overall water intake (β = 0.20; P < .001). Students have negative attitudes about school fountains. To increase overall water intake, it may be important to promote and improve drinking water sources not only at school but also at home and in other community environments. | 25,169,158 | [
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Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. | Recent studies showed that lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease (CVD). However, whether Lp(a) modifies clinical risk assessment was not established. This study was conducted to determine whether Lp(a) improves CVD risk prediction. In 1995, Lp(a) was measured in 826 men and women (age range, 45 to 84 years) from the general community. Incidence of CVD was recorded over 15 years of follow-up. In models adjusted for Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) variables, the hazard ratio (HR) for incident CVD was 1.37 per 1-SD higher Lp(a) level (SD = 32 mg/dl) and 2.37 when comparing the top fifth quintile with other quintiles. The addition of Lp(a) to the RRS increased the C-index by 0.016. Of the 502 subjects who remained free of CVD, 82 were correctly reclassified to a lower risk category and 49 were reclassified to a higher risk category (predicted 15-year categories: <7.5%, 7.5% to <15%, 15% to <30%, ≥30%) (p < 0.001). Of the 148 subjects who developed CVD, 18 were correctly reclassified to a higher risk category and 17 were reclassified to a lower risk category. In subjects at intermediate risk (15% to <30%), the net reclassification improvement afforded by Lp(a) was 22.5% for noncases, 17.1% for cases, and 39.6% overall. Allele-specific Lp(a) levels did not add to the predictive ability of the FRS or RRS or to Lp(a). Elevated Lp(a) predicts 15-year CVD outcomes and improves CVD risk prediction. These findings suggest that Lp(a) levels may be used in risk assessment of subjects in the general community, particularly in intermediate-risk groups. | 25,169,167 | [
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Programmed cell death of retinal cone bipolar cells is independent of afferent or target control. | Programmed cell death contributes to the histogenesis of the nervous system, and is believed to be modulated through the sustaining effects of afferents and targets during the period of synaptogenesis. Cone bipolar cells undergo programmed cell death during development, and we confirm that the numbers of three different types are increased when the pro-apoptotic Bax gene is knocked out. When their cone afferents are selectively eliminated, or when the population of retinal ganglion cells is increased, however, cone bipolar cell number remains unchanged. Programmed cell death of the cone bipolar cell populations, therefore, may be modulated cell-intrinsically rather than via interactions with these synaptic partners. | 25,169,191 | [
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Transient substrate-induced catalyst formation in a dynamic molecular network. | In biology enzyme concentrations are continuously regulated, yet for synthetic catalytic systems such regulatory mechanisms are underdeveloped. We now report how a substrate of a chemical reaction induces the formation of its own catalyst from a dynamic molecular network. After complete conversion of the substrate, the network disassembles the catalyst. These results open up new opportunities for controlling catalysis in synthetic chemical systems. | 25,169,198 | [
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Effectiveness of the population-based Check your health preventive programme conducted in primary care with 4 years follow-up [the CORE trial]: study protocol for a randomised controlled trial. | The periodic health check-up has been a fundamental part of routine medical practice for decades, despite a lack of consensus regarding its value in health promotion and disease prevention. A large-scale Danish population-based preventive programme 'Check your health' was developed based on available evidence of screening and successive accepted treatment, prevention for diseases and health promotion, and is closely aligned with the current health care system.The objective of the 'Check your health' [CORE] trial is to investigate effectiveness on health outcomes of a preventive health check offered at a population-level to all individuals aged 30-49 years, and to establish the cost-effectiveness. The trial will be conducted as a pragmatic household-cluster randomised controlled trial involving 10,505 individuals. All individuals within a well-defined geographical area in the Central Denmark Region, Denmark (DK) were randomised to be offered a preventive health check (Intervention group, n = 5250) or to maintain routine access to healthcare until a delayed intervention (Comparison group, n = 5255). The programme consists of a health examination which yields an individual risk profile, and according to this participants are assigned to one of the following interventions: (a) referral to a health promoting consultation in general practice, (b) behavioural programmes at the local Health Centre, or (c) no need for follow-up.The primary outcomes at 4 years follow-up are: ten-year-risk of fatal cardiovascular event (Heart-SCORE model), physical activity level (self-report and cardiorespiratory fitness), quality of life (SF12), sick leave and labour market attachment. Cost-effectiveness will be evaluated according to life years gained, direct costs and total health costs. Intention to treat analysis will be performed. Results from the largest Danish health check programme conducted within the current healthcare system, spanning the sectors which share responsibility for the individual, will provide a scientific basis to be used in the development of systems to optimise population health in the 21st century. The trial has registered at ClinicalTrials.gov with an ID: NCT02028195 (7. March 2014). | 25,169,211 | [
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[Health status analysis of Guangzhou traffic police officers in 2013]. | To analyze the health examination results of Guangzhou traffic police officers in 2013, and to investigate their health status and provide a scientific basis for the health management of traffic police officers. The physical examination data of the Guangzhou traffic police officers in 2013 were analyzed. The data were sorted in Excel and analyzed using SPSS software. The results showed that 82.95%of the Guangzhou traffic police officers who underwent physical examination in our hospital in 2013 had diseases or abnormal examination indices. The diseases or abnormal examination indices that ranked among the top three were hyperlipidemia (53.70%), hyperuricemia (46.51%), and overweight/obesity (43.43%). All diseases or abnormal examination indices except thyroid diseases were significantly higher in males than in females (P < 0.05). The proportion of diseases or abnormal examination indices varied significantly between different age groups (P < 0.05). Among the 345 female traffic police officers, the prevalence of mammary gland hyperplasia or mammary nodules was the highest, and the prevalence of mammary gland hyperplasia or mammary nodules, cervicitis, and uterine fibroids varied significantly between different age groups (P < 0.05). The health problems in Guangzhou traffic police officers are serious, especially chronic noninfectious diseases. Therefore, both society and individuals should take effective measures in order to deal with this problem. Regular health check-ups are necessary to promote good health for Guangzhou traffic police officers. | 25,169,223 | [
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[Risk assessment and risk control for occupational exposure to chemical toxicants from an isophorone nitrile device]. | Risk assessment and risk control for occupational exposure to chemical toxicants were performed on an isophorone nitrile device with an annual production of 5,000 tons, based on improved Singaporean semi-quantitative risk assessment method, with consideration of actual situation in China and in the present project. With the use of engineering analysis and identification of occupational hazards in the improved Singaporean semi-quantitative risk assessment method, hazard rating (HR) and risk assessment were performed on chemical toxicants from an isophorone nitrile device with an annual production of 5,000 tons. The chemical toxicants in the isophorone nitrile device were mainly isophorone, hydrocyanic acid, methanol, phosphoric acid, sodium hydroxide, and sodium cyanide; the HR values were mild hazard (2), extreme hazard (5), mild hazard (2), mild hazard (2), moderate hazard (3), and extreme hazard (5), respectively, and the corresponding exposure rating (ER) values were 2.09, 2.72, 2.76, 1.68, 2.0, and 1.59, respectively. The risk of chemical toxicants in this project was assessed according to the formula Risk = [HR×ER](1/2). Hydrocyanic acid was determined as high risk, sodium hydroxide and sodium cyanide as medium risk, and isophorone, methanol, and phosphoric acid as low risk. Priority in handling of risks was determined by risk rating. The table of risk control measure was established for pre-assessment of occupational hazards. With risk assessment in this study, we concluded that the isophorone nitrile device with 5,000 ton annual production was a high-occupational hazard device. This device is a project of extreme occupational hazard. The improved Singaporean semi-quantitative risk assessment method is a scientific and applicable method, and is especially suitable for pre-evaluation of on-site project with no analogy. | 25,169,239 | [
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Dexmedetomidine in the treatment of serotonin syndrome. | Patients suffering from moderate to severe serotonin syndrome frequently present with autonomic instability and altered mental status. Management of serotonin syndrome can be complex and may be refractory to treatment with benzodiazepines alone. The objective of this series is to present 3 cases of serotonin syndrome that demonstrated clinical improvement with initiation of dexmedetomidine. We present 3 cases of severe serotonin syndrome in adolescents requiring intubation that were refractory to midazolam and/or propofol. Dexmedetomidine, an α-2 receptor agonist, was used in all 3 cases with temporal stabilization of the autonomic nervous system and improvement of agitation, and aided in successful extubation. Although no human studies exist, rat and mouse models offer evidence that dexmedetomidine can reduce serotonin excess and stabilize signs of serotonin neurotoxicity. Accordingly, health care providers may consider using dexmedetomidine as adjunctive therapy for cases of severe serotonin syndrome that are refractory to standard treatment. | 25,169,248 | [
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Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs. | Layer-by-layer (LbL)-engineered nanoparticles (NPs) are a promising group of therapeutic carriers used in an increasing number of biomedical applications. The present study uses a controlled LbL process to create a multidrug-loaded nanoplatform capable of promoting blood circulation time, biodistribution profile and controlling drug release in the dynamic systemic environment. LbL assembly is achieved by sequential deposition of poly-l-lysine (PLL) and poly(ethylene glycol)-block-poly(l-aspartic acid) (PEG-b-PLD) on liposomal nanoparticles (LbL-LNPs). This generates spherical and stable multilayered NPs ∼240nm in size, enabling effective systemic administration. The numerous functional groups and compartments in the polyelectrolyte shell and core facilitate loading with doxorubicin and mitoxantrone. The nanoarchitecture effectively controls burst release, providing different release kinetics for each drug. LbL-LNPs are pH-sensitive, indicating that intracellular drug release can be increased by the acidic milieu of cancer cells. We further demonstrate that the LbL nanoarchitecture significantly reduces the elimination rates of both drugs tested and markedly extends their systemic circulation times, paving the way for efficacious tumor drug delivery. Because this delivery system accommodates multiple drugs, improves drug half-life and diminishes burst release, it provides an exciting platform with remarkable potential for combination therapeutics in cancer therapy. | 25,169,256 | [
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Hydrothermal synthesis of Pt-Ag alloy nano-octahedra and their enhanced electrocatalytic activity for the methanol oxidation reaction. | The high-quality Pt48Ag52 alloy nano-octahedra are synthesized via one-pot hydrothermal method. The catalytic growth of Ag(0) atoms on Pt nuclei and selective oxidative etching on the Ag(0) atoms contribute to the formation of alloy nano-octahedra. Pt48Ag52 alloy nano-octahedra show excellent electrocatalytic activity and durability for the methanol oxidation reaction (MOR). | 25,169,420 | [
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Cephalometric analysis of craniofacial morphology and growth in unrepaired isolated cleft palate patients. | The aim of this study is to analyze the craniofacial morphology in patients with unrepaired isolated cleft palate (UICP) at childhood, adolescence and adulthood, in order to assess the influence of nonsurgical factors on the craniofacial growth in these patients. Lateral and posteroanterior cephalograms of 106 non-syndromic UICP patients and 102 normal matched controls were obtained and analyzed. Patients and controls were divided into three subgroups: children (5-7 years), adolescents (12-14 years), and adults (>18 years). UICP patients in childhood showed a shortened cranial basal length; reduced bony nasopharyngeal height; short maxillary depth and height with a posterior positioned maxilla and an increased width of the nasal cavity, maxilla and orbit; and a shortened mandibular length and height. UICP patients in adulthood showed a normal nasopharyngeal and mandibular morphology. However, the patients in this subgroup still showed a shortened cranial basal length, and short maxillary depth and anterior height with increased width of the nasal cavity, maxilla and orbit. Craniofacial morphology and growth in patients with UICP were significantly affected by nonsurgical factors. Growth of the cranial base and upper face were absolutely reduced, while growth of the bony nasopharynx and mandible were only postponed. | 25,169,446 | [
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Considerations and evidence for an ADHD outcome measure. | The 2011 American Academy of Pediatrics attention-deficit/hyperactivity disorder (ADHD) guideline emphasizes monitoring and measuring outcomes of children diagnosed with ADHD; however, recommendations for how to measure improvement are less clear. A long-term goal was to develop an outcome measure that assesses the quality of care for children with ADHD. As a first step in that process, we conducted a literature synthesis on the efficacy and effectiveness of guideline-recommended ADHD treatments on patient outcomes. A literature search was conducted in PubMed according to PRISMA protocol and using MeSH terms. US Preventive Services Task Force (USPSTF) criteria were used to assess the level of evidence. Studies of interest were published after 2002 and assessed prospective ADHD improvement using recommended ADHD treatments. The systematic review resulted in 35 studies. According to USPSTF criteria, included studies were level I (n = 24), level II-1 (n = 1), and level II-2 (n = 10) and were rated as good (n = 20) or fair (n = 15). DSM-criteria-based rating scales were used most frequently to measure ADHD treatment outcomes. All included treatments resulted in ADHD improvement. Regardless of outcome measure, tool, or treatment type, symptom reduction and improvement were relatively large, with mean percentage reductions ranging from 20% to 86% on ADHD-Behavior Rating Scales scales, with only 1 study with <25% reduction. Effect sizes ranged from 0.15 to 4.57. On the basis of this literature review, a consistent pattern of improvement in pediatric ADHD patients' core symptoms emerged across studies, study designs, and recommended treatment approaches. This evidence supports the notion that an improvement of core symptoms within 1 year could satisfy the requirements of an effective outcome measure, which should be further investigated. | 25,169,459 | [
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Population-based cervical cancer screening using high-risk HPV DNA test and liquid-based cytology in northern Thailand. | Northern Thailand is a region with a high cervical cancer incidence. Combined high-risk HPV (hrHPV) DNA testing and cytology (co-testing) has increasingly gained acceptance for cervical cancer screening. However, to our knowledge, data from a population-based screening using co-testing have not been available in this region. This study therefore aimed to evaluate the performance of cytology and hrHPV test in women in northern Thailand. Cervical samples were collected for hybrid capture 2 (HC2) testing and liquid-based cytology from women aged 30 to 60 years who were residents in 3 prefectures of Chiang Mai in northern Thailand between May and September 2011. Women with positive cytology were referred to colposcopy, while women with positive for HC2 only were followed for 2 years. Of 2,752 women included in this study, 3.0% were positive in both tests, 4.1% for HC2 only, and 1.3% had positive cytology only. At baseline screening, positive HC2 was observed in 70.6% among cytology-positive women compared with 4.3% among cytology-negative women. The prevalence of positive HC2 or cytology peaked in the age group 35-39 years and was lowest in the age group 55-60 years. High-grade squamous intraepithelial lesion or worse lesions (HSIL+) were histologically detected in 23.5% of women with positive baseline cytology and in 9.8% of women with positive baseline HC2 only on follow-up. All women with histologic HSIL+ had positive baseline HC2. The hrHPV test is superior to cytology in the early detection of high-grade cervical epithelial lesions. In this study, the prevalence of histologic HSIL+ on follow-up of women with positive hrHPV test was rather high, and these women should be kept under careful surveillance. In northern Thailand, hrHPV testing has a potential to be used as a primary screening test for cervical cancer with cytology applied as a triage test. | 25,169,534 | [
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Association between the HSPA1B ±1267A/G polymorphism and cancer risk: a meta-analysis of 14 case-control studies. | Previous epidemiological studies have suggested a potential role of the HSPA1B±1267A/G polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ±1267A/G was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p< 0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs OR=0.39, 95%CI 0.20-0.70, p=0.007). This meta-analysis suggests associations between the HSPA1B ±1267A/G polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings. | 25,169,537 | [
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Activity and expression pattern of NF-κB /P65 in peripheral blood from hepatocellular carcinoma patients - link to hypoxia inducible factor -1α. | Hepatocellular carcinoma is a complex and heterogeneous tumor with poor prognosis due to frequent intrahepatic spread and extrahepatic metastasis. The molecular mechanisms underlying HCC pathogenesis still remain obscure. We aimed to investigate the abundance and the DNA binding activity of nuclear factor kappa B/p65 subunit in peripheral blood mononuclear cells from patients with HCC and to assess its prognostic significance and association with hypoxia inducible factor one alpha (HIF-1α) in blood. This study was carried out on 40 patients classified equally into liver cirrhosis (group I) and HCC (group II), in addition to 20 healthy volunteers (group III). All groups were subjected to measurement of NF-κB /P65 subunit expression levels by real time-PCR, and DNA binding activity was evaluated by transcription factor binding immunoassay. Serum HIF-1α levels were estimated by enzyme-linked immunosorbent assay (ELISA). Significant increase of both the expression level and DNA binding activity of NF-κB /P65 subunit together with serum HIF-1 alpha levels was noted in HCC patients compared to liver cirrhosis and control subjects, with significant positive correlation with parameters for bad prognosis of HCC. In conclusion, NF-κB signaling is activated in HCC and associated with disease prognosis and with high circulating levels of HIF-1 alpha. | 25,169,545 | [
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MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-γ. | Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-γ (SNCG). The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC. | 25,169,552 | [
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Combined effects of six cytokine gene polymorphisms and SNP-SNP interactions on hepatocellular carcinoma risk in Southern Guangxi, China. | Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-γ, IL-1β, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-γ-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk. | 25,169,554 | [
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Hypogonadism in the HIV-infected man. | Androgen deficiency occurs frequently in men with human immunodeficiency virus (HIV) infection. Antiretroviral treatments had reduced the prevalence of male hypogonadism. The pathogenesis of testosterone (T) deficiency in HIV is multifactorial. Several mechanisms have been proposed; among them, drugs, fat redistribution, and a poor health status could explain the mechanism leading to gonadotropins inhibition and hypogonadotropic hypogonadism. The diagnosis of hypogonadism in HIV-infected men should be made based on clinical symptoms and a specific workup including T measurement. The interpretation of the results of biochemical testing is more difficult in men with HIV due to several confounding factors. T treatment should be offered to HIV-infected men with documented clinical hypogonadism and symptoms, especially if they are losing lean mass. | 25,169,563 | [
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Dynamic contrast-enhanced (DCE) MRI assessment of microvascular characteristics in the murine orthotopic pancreatic cancer model. | The aim of this study was to assess the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters between two contrast agents in a murine orthotopic pancreatic cancer model and to evaluate the tumor heterogeneity and the potential association between kinetic parameters and angiogenic markers such as the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression by immunohistochemistry. Human pancreatic adenocarcinoma cell line MIAPaCa-2 was injected into the pancreas of BALB/C nu/nu mice. DCE-MRI was performed using Gd-DTPA and Gd-EOB-DTPA. Quantitative and semi-quantitative vascular parameters (K(trans), Kep, Ve and AUC) were calculated by using a dedicated postprocessing software program. Values were compared with tumor rim, tumor core and the entire tumor. The MVD and VEGF expressions between tumor rim and tumor core were also compared. There were no significant differences in K(trans), Kep, Ve, and AUC values of the three groups when using Gd-DTPA. However there were significant differences in K(trans), Kep, and AUC values of the three groups when using Gd-EOB-DTPA (P=0.014, 0.022, 0.007, respectively), in addition, the K(trans) and Kep values of tumor core were significantly lower than those of the entire tumor (adjusted P=0.014 and 0.027, respectively), the AUC values of core were significantly lower than those of the entire tumor and rim (adjusted P=0.039 and 0.009, respectively). Immunohistology results revealed that MVD and VEGF expression in the tumor rim was significantly higher than that in the core. There was positive correlation between AUC and MVD, VEGF. The murine orthotopic pancreatic cancer model provides an ideal animal model to study human pancreatic cancer. It can more sensitively semi-quantitatively and quantitatively analyze tumor angiogenesis through selecting the albumin-binding contrast agent. | 25,169,584 | [
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Reverse genetics systems as tools for the development of novel therapies against filoviruses. | Filoviruses cause severe hemorrhagic fevers with case fatality rates of up to 90%, for which no antivirals are currently available. Their categorization as biosafety level 4 agents restricts work with infectious viruses to a few maximum containment laboratories worldwide, which constitutes a significant obstacle for the development of countermeasures. Reverse genetics facilitates the generation of recombinant filoviruses, including reporter-expressing viruses, which have been increasingly used for drug screening and development in recent years. Further, reverse-genetics based lifecycle modeling systems allow modeling of the filovirus lifecycle without the need for a maximum containment laboratory and have recently been optimized for use in high-throughput assays. The availability of these reverse genetics-based tools will significantly improve our ability to find novel antivirals against filoviruses. | 25,169,588 | [
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Talking about cancer with confidence: evaluation of cancer awareness training for community-based health workers. | To examine the impact of cancer awareness training for community-based health workers on confidence to talk about cancer, and knowledge of cancer risk factors and signs and symptoms. Community-based health workers from Sandwell, Birmingham and Solihull were invited to take part in one of 14 one-day training workshops. Trainees completed questionnaires at the beginning of the workshop and were followed up one month later. Confidence in talking about cancer was examined. Knowledge of cancer risk factors and signs and symptoms was assessed. Trainees were asked to rate the usefulness of the workshop, whether they would recommend it to others and whether they had put what they had learnt into practice. A total of 187 community-based health workers took part in the workshops, and 167 (89%) completed the one-month follow-up. Considerable improvements were observed in confidence to discuss cancer. For example, the proportion of participants reporting feeling 'very confident'/'fairly confident' in discussing signs and symptoms of cancer increased from 32% to 96% (p < .001). Substantial improvements in trainees' knowledge were also observed, with 79% of participants correctly identifying 10 out of 11 known risk factors for cancer at one month compared with 21% before training (p < .001). Average (unprompted) recall of cancer signs and symptoms also increased from 2.3 (± 1.6) to 2.7 (± 1.5), (p = .02). Most trainees (83%) rated the workshop as 'very useful', and 89% said they would 'definitely' recommend the workshop. The cancer awareness training was reviewed positively by community-based health workers and led to improvements in confidence to talk about cancer, and knowledge of risk factors and warning signs of cancer. It is hoped that raising awareness among this group will help them to communicate and drive behaviour change in the at-risk populations with whom they work. | 25,169,613 | [
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[Mutation analysis of mucopolysaccharidosis type II and prenatal diagnosis]. | To analyze the mutations of IDS gene in a mucopolysaccharidosis type II (MPSII) family and to make prenatal diagnosis on the high-risk fetus which has been pregnant for eleven weeks. IDS gene was analyzed by bidirectional DNA sequencing in 2 patients and their mother, and 5 unaffected individuals. Prenatal diagnosis for the high-risk fetus was performed by chorionic villus sampling after the genotypes was identified. The mutation c.344delA (N115fsX15) was detected in the two patients, and the mother of patients carried the heterozygous c.344delA (N115fsX15) mutation. None of the mutant was detected in the 5 unaffected subjects. The fetus carried c.344delA (N115fsX15) heterozygous mutation and was a carrier. The deletion mutation c.344delA (N115fsX15) is causative to the pedigree of MPSII, and prenatal diagnosis is the efficient method to avoid defect birth. | 25,169,630 | [
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Biooxidation of n-butane to 1-butanol by engineered P450 monooxygenase under increased pressure. | In addition to the traditional 1-butanol production by hydroformylation of gaseous propene and by fermentation of biomass, the cytochrome P450-catalyzed direct terminal oxidation of n-butane into the primary alcohol 1-butanol constitutes an alternative route to provide the high demand of this basic chemical. Moreover the use of n-butane offers an unexploited ubiquitous feed stock available in large quantities. Based on protein engineering of CYP153A from Polaromonas sp. JS666 and the improvement of the native redox system, a highly ω-regioselective (>96%) fusion protein variant (CYP153AP.sp.(G254A)-CPRBM3) for the conversion of n-butane into 1-butanol was developed. Maximum yield of 3.12g/L butanol, of which 2.99g/L comprise for 1-butanol, has been obtained after 20h reaction time. Due to the poor solubility of n-butane in an aqueous system, a high pressure reaction assembly was applied to increase the conversion. After optimization a maximum product content of 4.35g/L 1-butanol from a total amount of 4.53g/L butanol catalyzed by the self-sufficient fusion monooxygenase has been obtained at 15bar pressure. In comparison to the CYP153A wild type the 1-butanol concentration was enhanced fivefold using the engineered monooxygenase whole cell system by using the high-pressure reaction assembly. | 25,169,664 | [
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Hyperglycemia in the intensive care unit: is insulin the only option? | Current guidelines advocate the use of insulin for the management of hyperglycemia in the hospital setting. However, insulin is limited by a narrow therapeutic window, frequent errors, a need for expertise and systems-based monitoring, and lack of specificity for metabolic abnormalities that occur during critical illness. As a result, non-insulin alternatives have garnered increasing interest for managing hyperglycemia in the hospital. However, non-insulin therapies have had safety and tolerability concerns, patients may still need insulin for glycemic control, and there have been limited outcomes data supporting their use. In the study by Christiansen and colleagues in the previous issue of Critical Care, pre-admission metformin therapy was associated with reduced mortality in critically ill patients with type 2 diabetes. The mortality benefit persisted after controlling for other variables, and was particularly prominent when metformin was continued during admission. Furthermore, the reduction in mortality was observed despite a slightly increased prevalence of lactic acidosis in metformin users. The protective effects of metformin are purported to be related to pleiotropic, possibly anti-inflammatory mechanisms, raising the question of benefit in patients without diabetes. Thus, the findings warrant a re-appraisal of the risks and benefits of metformin use during critical illness. However, in order to justify the revision of multiple guidelines and changes in product labeling, clinical trials in carefully selected patient populations are indicated. | 25,169,675 | [
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Age-specific incidence of all neoplasms after colorectal cancer. | Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. | 25,169,681 | [
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Ethnicity and alcohol consumption among US adults with diabetes. | The drinking practices of a nationally representative sample of white, black, Mexican American, and other Hispanic adult diabetics are described and compared. Combined years (2005/2006-2011/2012) of the National Health and Nutrition Examination Survey provided home interview data from 2220 adults with self-reported diabetes of white (n = 875), black (n = 720), Mexican American (n = 402), and other Hispanic (n = 223) ethnicity. Current drinking status, the number of drinks consumed per week, and binge drinking were compared across ethnicity. The multivariate findings for both diabetic men and women showed no statistically significant ethnic differences in current drinking status, and among women, there were no statistically significant ethnic differences in binge drinking. Among male diabetics, Mexican Americans consumed more drinks per week than whites (b = 0.35; 95% confidence interval, 0.13-0.58; P = .002) and were at increased risk for binge drinking (odds ratio, 2.04; 95% confidence interval, 1.30-3.21; P = .002). Binge drinking is prevalent among Mexican American male diabetics. This pattern of drinking may put them at risk for poor diabetes management and control. It is important that health care providers routinely assess their patients' drinking practices and address the health risks associated with alcohol consumption. | 25,169,682 | [
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The experience of family members of ICU patients who require extensive monitoring: a qualitative study. | A mixed methods study using family research with a phenomenological approach (n = 5 families) was conducted to explore family members' perceptions about the extensive monitoring technology used on their critically ill family member after cardiac surgery, as experienced when family members initially visited the patient in the cardiovascular intensive care unit. Five relevant themes emerged: overwhelmed by all of the machines; feelings of uncertainty; methods of coping; meaning of the numbers on the machines; and need for education. | 25,169,690 | [
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Epilepsy transition: challenges of caring for adults with childhood-onset seizures. | Children with severe chronic epilepsy are living longer, and they eventually transition to the adult health care system. Additional research is required to better define the population that is being transferred and the qualifications of those who are assuming their care. We aimed to evaluate the complexity of epilepsy patients transitioning between tertiary centers, and to evaluate neurologists' confidence in dealing with childhood-onset epilepsies. Patients aged from 18 to 25 years were divided into two groups: Group 1 comprised patients referred from the pediatric tertiary center; and Group 2 comprised patients referred from the community. Clinical data were retrospectively studied and groups were compared using appropriate statistics. We also created a survey to evaluate neurologists' levels of confidence in diagnosing and treating childhood-onset epilepsies. Differences among responders were compared. Group 1 comprised 170 patients, whereas group 2 had 132. Patients in group 1 had earlier seizure onset, longer epilepsy duration (p < 0.001), and more patients with symptomatic etiologies, epileptic encephalopathy, and cognitive delay (p < 0.001). Group 1 patients required more referrals to other specialties (p = 0.001). Treatment with polytherapy (p = 0.003), epilepsy surgery (p < 0.001), ketogenic diet (p < 0.001), and vagus nerve stimulator were more common in group 1 (p < 0.001). In addition, our survey applied to adult (n = 86) and pediatric (n = 29) neurologists indicated that adult neurologists have lower levels of confidence in diagnosing and treating severe forms of childhood-onset epilepsies (p < 0.001), as well as epilepsy associated with cognitive delay (p < 0.001). These findings suggest that patients from tertiary centers present more complex health care needs and require more resources than age-matched patients from the community; and that adult neurologists may not feel prepared to diagnose and treat adult patients with some childhood-onset epilepsies. | 25,169,716 | [
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Photocatalytic degradation of selected anticancer drugs and identification of their transformation products in water by liquid chromatography-high resolution mass spectrometry. | A study on the fate of two antineoplastic drugs, methotrexate and doxorubicin, in the aquatic environment is presented. The investigation involved a study of their decomposition under dark experiments, homogeneous photolysis and heterogeneous photocatalysis using titanium dioxide, the identification of intermediate compounds, as well as the assessment of acute toxicity over time. The analysis were carried out using LC (ESI positive mode) coupled with LTQ-Orbitrap analyser; accurate mass-to-charge ratios of parent ions were reported with inaccuracy below 10mmu, which guarantee the correct assignment of their molecular formula in all cases, while their MS(2) and MS(3) spectra showed several structural-diagnostic ions that allowed to characterize the different transformation products and to discriminate the isobaric species. Fourteen and eight main species were identified subsequently to doxorubicin or methotrexate transformation. The major transformation processes for doxorubicin involved (poli)hydroxylation and/or oxidation of the molecule, or the detachment of the sugar moiety. Methotrexate transformation involved decarboxylation or the molecule cleavage. Acute toxicity measurements showed that not only the two drugs exhibit high toxicity, but also their initial transformation products are highly toxic. | 25,169,721 | [
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Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling. | Progranulin (PGRN) was previously isolated as an osteoarthritis (OA)-associated growth factor. Additionally, PGRN was found to play a therapeutic role in inflammatory arthritis mice models through antagonising tumour necrosis factor α (TNF-α). This study was aimed at investigating the role of PGRN in degradation of cartilage and progression of OA. Progression of OA was analysed in both spontaneous and surgically induced OA models in wild type and PGRN-deficient mice. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry and ELISA. Additionally, mRNA expression of degenerative factors and catabolic markers known to be involved in cartilage degeneration in OA were analysed. Furthermore, the anabolic effects and underlying mechanisms of PGRN were investigated by in vitro experiments with primary chondrocytes. Here, we found that deficiency of PGRN led to spontaneous OA-like phenotype in 'aged' mice. Additionally, PGRN-deficient mice exhibited exaggerated breakdown of cartilage structure and OA progression, while local delivery of recombinant PGRN protein attenuated degradation of cartilage matrix and protected against OA development in surgically induced OA models. Furthermore, PGRN activated extracellular signal-regulated kinases (ERK) 1/2 signalling and elevated the levels of anabolic biomarkers in human chondrocyte, and the protective function of PGRN was mediated mainly through TNF receptor 2. Additionally, PGRN suppressed inflammatory action of TNF-α and inhibited the activation of β-Catenin signalling in cartilage and chondrocytes. Collectively, this study provides new insight into the pathogenesis of OA, and also presents PGRN as a potential target for the treatment of joint degenerative diseases, including OA. | 25,169,730 | [
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Validating screening tools for depression in epilepsy. | Depression is a common comorbidity of epilepsy, and its timely identification in persons with epilepsy is essential. The use of screening tools to detect depression is common in epilepsy, but some scales in current use have not been validated using a gold standard in this population. The present study aims to validate three commonly used depression-screening scales and assess new cut points for scoring in those with epilepsy. Persons with epilepsy (n = 300) from the only epilepsy clinic in a large urban health region completed questionnaires (e.g., sociodemographics, adverse event profile) and three depression-screening tools (Hospital Anxiety and Depression Scale [HADS]; Patient Health Questionnaire [PHQ]-9 and PHQ-2). One hundred eighty-five patients participated in a gold-standard structured clinical interview to assess depression. The diagnostic accuracy of the depression scales was assessed comparing a variety of scoring cut points to the gold-standard diagnosis of depression. The prevalence of current depression in this population, according to the gold-standard, was 14.6%. The scale with the highest sensitivity (84.6%) was the HADS with a cut point of 6 and the scale with the highest specificity (96.2%) was the PHQ-9 algorithm scoring method. Overall, the PHQ-9 at a cut point of 9 and the HADS at a cut point of 7 resulted in the greatest balance of sensitivity and specificity (area under the curve: 88% and 90%, respectively). The PHQ-9 at a cut point of 9 and the HADS at a cut point of 7 had the best overall balance of sensitivity and specificity. However, for screening purposes the PHQ-9 algorithm method is ideal (optimizing specificity), whereas for case finding the HADS at a cut point of 6 performed best (optimizing sensitivity). Appropriate scale cut points should be chosen based on the study's goals and available resources. Disease-specific scale cut points are recommended for future studies assessing depression in persons with epilepsy. | 25,169,800 | [
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Programmable co-assembly of oppositely charged microgels. | Here we report the development of an aqueous, self-assembling system of oppositely charged colloids leading towards particle arrangements with controlled order. The colloidal system consists of two types of particles, each consisting of refractive index matched colloidal core-shell microgel particles, which are either negatively charged or amphoteric. By slowly decreasing the pH of our system below the isoelectric point of the amphoteric particles, changing their net charge from negative to positive, the co-assembly of the colloids is induced. By using different buffer concentrations, we gain temporal and kinetic control over the acidification process and thus the ability to program the co-assembly of the two particles species. | 25,169,820 | [
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Early life stress shapes female reproductive strategy through eggshell pigmentation in Japanese quail. | Physiological constraints on colouration have been widely reported; especially in birds, which trade-off antioxidant responses against colourful costly signals. One female extended phenotypic trait, which might also highlight important physiological trade-offs, is the pigmentation of their eggshells. In ground-nesting species, producing eggs that are visually undetectable by predators is the best camouflage strategy. However, the condition-dependence of eggshell pigmentation, and the pigments role in oxidative stress, may constrain females to trade-off between their antioxidant capacity and maximising the camouflage of their eggs when they deposit eggshell pigments. Developmental stress is one factor that influences female antioxidant capacity, and could lead to variations in eggshell pigmentation that might have crucial consequences on individual fitness if egg crypsis is compromised especially under stressful conditions. We investigated the interaction between developmental and breeding conditions with respect to eggshell pigmentation in Japanese quail. We studied 30 females that bred under both control and stressful conditions, and were exposed to pre- and/or post-natal stress, or neither. Pre- and post-natal stress independently influenced eggshell pigmentation strategies under stressful breeding conditions. Under stressful reproduction, eggshell protoporphyrin concentration and maculation were affected by pre-natal stress, whereas eggshell reflectance and biliverdin concentration were influenced by post-natal stress. These changes may reflect potential adaptive strategies shaped by developmental stress, but additional data on the benefit of egg crypsis in quail, combined with studies on the role of both pigments on chick survival, will help to clarify whether early life stress can enhance fitness through eggshell pigmentation when developmental and reproductive environments match. | 25,169,834 | [
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Burden of chronic obstructive pulmonary disease in the elderly population. | Chronic obstructive pulmonary disease (COPD) is a common disease and an important health care problem in older adults. The impact of age and specific geriatric issues on COPD in elderly patients has not been well established. A cross-sectional study of elderly COPD patients was conducted in Japan by using a regional COPD registry database. We compared indices of disease severity (pulmonary function, exercise tolerance, quality of life, and frequency of exacerbations), presence of comorbidities, geriatric conditions (cognitive function, mental status, and activities of daily living [ADL]), and adherence to prescribed drug regimens between elderly and younger patients with COPD. In total, 279 patients with stable COPD (median age, 74 years) were identified; 86% of these patients were elderly (65 years of age or older). Elderly COPD patients, especially those who were 75 years of age or older, had significantly more cases of dyspnea, lower exercise tolerance, and poorer ADL and a higher incidence of severe exacerbations than younger patients (all P<0.05). In addition, the prevalence of comorbidities, including cardiovascular disease and cancer, was significantly higher in elderly COPD patients. Elderly COPD patients had specific geriatric conditions, including cognitive impairment. Adherence to inhaled drug regimens in elderly patients was as favorable as that in younger patients. Age and specific geriatric conditions have a great negative impact on COPD in elderly patients. Geriatric conditions should be addressed in the management of elderly COPD patients. | 25,169,845 | [
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Genome Sequence of Paenibacillus polymyxa Strain CICC 10580, Isolated from the Fruit of Noni (Morinda citrifolia L.) Grown in the Paracel Islands. | Noni is a plant reported to have nutritional and therapeutic properties. Paenibacillus polymyxa CICC 10580 is a strain that was isolated from the fruit of noni and showed comprehensive antagonistic activity against many pathogens. Its genome was sequenced and assembled (6.10 Mb). The coding sequences (CDSs) correlated with antagonistic activity were annotated. | 25,169,860 | [
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Draft Genome Sequence of the Fish Pathogen Yersinia ruckeri Strain 37551, Serotype O1b, Isolated from Diseased, Vaccinated Atlantic Salmon (Salmo salar) in Chile. | We sequenced the genome of a motile O1b Yersinia ruckeri field isolate from Chile, which is causing enteric redmouth disease (ERM) in vaccinated Atlantic salmon (Salmo salar). The draft genome has 3,775,486 bp, a G+C content of 47.1%, and is predicted to contain 3,406 coding sequences. | 25,169,862 | [
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Clinical, EEG, MRI, MEG, and surgical outcomes of pediatric epilepsy with astrocytic inclusions versus focal cortical dysplasia. | Astrocytic inclusions (AIs) have been identified on histologic specimens of patients with early onset seizures, and the proteomic contents have been described. The aim of this study was to compare the clinical, electroencephalography (EEG), magnetoencephalography (MEG), magnetic resonance imaging (MRI), and surgical outcomes of AIs relative to focal cortical dysplasia (FCD). We assessed the clinical manifestations, semiology, ictal and interictal features on video-EEG, MEG, MRI features, and surgical outcomes of children with histologically proven AIs compared to FCD. Six children had AIs and 27 had FCD. Children with AIs had an earlier age at seizure onset, periodic spasms (all children), and interictal epileptiform discharges consisting of a mixture of generalized or diffuse hemispheric slow waves, sharp waves, spikes and polyspikes. Children with FCD were less likely to have spasms (4/27 [15%]), and the morphology of the diffuse hemispheric or generalized discharges were different from those of AI, consisting of spike-and-waves, polyspike-and-waves, sharp-and-slow waves, and paroxysmal fast activity. Patients with AIs were less likely to have tightly clustered MEG spike sources (3/6 [50%] vs. 23/27 [85%]), and more likely to demonstrate abnormal sulcation and gyration pattern (4/6 [67%] vs. 2/27 [7%]) and gray matter heterotopia (2/6 [33%] vs. 0/27 [0%]) than patients with FCD. Four children with AIs had resection and two had biopsy but did not undergo resection. Children with AIs had lower rates of seizure freedom after surgery compared to FCD (1/4 [25%] vs. 15/27 [56%], respectively). Although there were some similarities between AIs and FCD, patients with AIs were more likely to present with early onset periodic spasms, have unusual interictal epileptiform discharges, abnormal sulcation, gyration pattern, and gray matter heterotopia, and were less likely to be seizure free following surgical resection relative to FCD. Further study with a larger sample size is needed to validate our findings. | 25,169,867 | [
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Computational design of patterned interfaces using reduced order models. | Patterning is a familiar approach for imparting novel functionalities to free surfaces. We extend the patterning paradigm to interfaces between crystalline solids. Many interfaces have non-uniform internal structures comprised of misfit dislocations, which in turn govern interface properties. We develop and validate a computational strategy for designing interfaces with controlled misfit dislocation patterns by tailoring interface crystallography and composition. Our approach relies on a novel method for predicting the internal structure of interfaces: rather than obtaining it from resource-intensive atomistic simulations, we compute it using an efficient reduced order model based on anisotropic elasticity theory. Moreover, our strategy incorporates interface synthesis as a constraint on the design process. As an illustration, we apply our approach to the design of interfaces with rapid, 1-D point defect diffusion. Patterned interfaces may be integrated into the microstructure of composite materials, markedly improving performance. | 25,169,868 | [
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Assessing uncertainty in pollutant wash-off modelling via model validation. | Stormwater pollution is linked to stream ecosystem degradation. In predicting stormwater pollution, various types of modelling techniques are adopted. The accuracy of predictions provided by these models depends on the data quality, appropriate estimation of model parameters, and the validation undertaken. It is well understood that available water quality datasets in urban areas span only relatively short time scales unlike water quantity data, which limits the applicability of the developed models in engineering and ecological assessment of urban waterways. This paper presents the application of leave-one-out (LOO) and Monte Carlo cross validation (MCCV) procedures in a Monte Carlo framework for the validation and estimation of uncertainty associated with pollutant wash-off when models are developed using a limited dataset. It was found that the application of MCCV is likely to result in a more realistic measure of model coefficients than LOO. Most importantly, MCCV and LOO were found to be effective in model validation when dealing with a small sample size which hinders detailed model validation and can undermine the effectiveness of stormwater quality management strategies. | 25,169,872 | [
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Prevalence, incidence, and comorbidity of clinically diagnosed obsessive-compulsive disorder in Taiwan: a national population-based study. | Obsessive-compulsive disorder (OCD) is a chronic debilitating anxiety disorder significant in intrusive thoughts and compensation repetitive behaviors. Few studies have reported on this condition Asia. This study estimated the prevalence, incidence and psychiatric comorbidities of OCD in Taiwan. We identified study subjects for 2000-2008 with a principal diagnosis of OCD according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic criteria by using National Health Research Institute database. These patients received either outpatient or inpatient care for their condition. Rates were directly age- and sex-adjusted to the 2004 Taiwan population distribution. The estimated mean annual incidence was 27.57 per 10(5) inhabitants and the one year prevalence was 65.05 per 10(5) inhabitants. Incidence and prevalence increased with age, peaking at age 18-24 years in males and at 35-44 years in females. About 53% of adults (≥18 years) and 48% of child and adolescent patients (6-17 years) had one or more comorbid psychiatric conditions. The most common comorbid diagnosis was depressive disorders for both adult and child-adolescent patients. We found a lower prevalence and incidence of clinically diagnosed OCD than that of community studies. Many Asian patients with OCD also had various psychiatric comorbidities, a clinically relevant finding. | 25,169,892 | [
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Socio-demographic vulnerability to heatwave impacts in Brisbane, Australia: a time series analysis. | Examining the association between socioeconomic disadvantage and heat-related emergency department (ED) visits during heatwave periods in Brisbane, 2000-2008. Data from 10 public EDs were analysed using a generalised additive model for disease categories, age groups and gender. Cumulative relative risks (RR) for non-external causes other than cardiovascular and respiratory diseases were 1.11 and 1.05 in most and least disadvantaged areas, respectively. The pattern persisted on lags 0-2. Elevated risks were observed for all age groups above 15 years in all areas. However, with RRs of 1.19-1.28, the 65-74 years age group in more disadvantaged areas stood out, compared with RR=1.08 in less disadvantaged areas. This pattern was observed on lag 0 but did not persist. The RRs for male presentations were 1.10 and 1.04 in most and less disadvantaged areas; for females, RR was 1.04 in less disadvantaged areas. This pattern persisted across lags 0-2. Heat-related ED visits increased during heatwaves. However, due to overlapping confidence intervals, variations across socioeconomic areas should be interpreted cautiously. ED data may be utilised for monitoring heat-related health impacts, particularly on the first day of heatwaves, to facilitate prompt interventions and targeted resource allocation. | 25,169,903 | [
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Saikosaponin-D attenuates heat stress-induced oxidative damage in LLC-PK1 cells by increasing the expression of anti-oxidant enzymes and HSP72. | Heat stress stimulates the production of reactive oxygen species (ROS), which cause oxidative damage in the kidney. This study clarifies the mechanism by which saikosaponin-d (SSd), which is extracted from the roots of Bupleurum falcatum L, protects heat-stressed pig kidney proximal tubular (LLC-PK1) cells against oxidative damage. SSd alone is not cytotoxic at concentrations of 1 or 3 μg/mL as demonstrated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To assess the effects of SSd on heat stress-induced cellular damage, LLC-PK1 cells were pretreated with various concentrations of SSd, heat stressed at 42°C for 1 h, and then returned to 37°C for 9 h. DNA ladder and MTT assays demonstrated that SSd helped to prevent heat stress-induced cellular damage when compared to untreated cells. Additionally, pretreatment with SSd increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) but decreased the concentration of malondialdehyde (MDA) in a dose-dependent manner when compared to controls. Furthermore, real-time PCR and Western blot analysis demonstrated that SSd significantly increased the expression of copper and zinc superoxide dismutase (SOD-1), CAT, GPx-1 and heat shock protein 72 (HSP72) at both the mRNA and protein levels. In conclusion, these results are the first to demonstrate that SSd ameliorates heat stress-induced oxidative damage by modulating the activity of anti-oxidant enzymes and HSP72 in LLC-PK1 cells. | 25,169,909 | [
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Electrodermal screening of biologically active points for upper gastrointestinal bleeding. | The purpose of this case-control study was to investigate the relationship between the electrical resistance of the skin at biologically active points (BAPs) on the main meridians and upper gastrointestinal bleeding (UGIB). Electrical resistance to direct current at 20 BAPs on the fingers and toes of 100 patients with (38 men, 12 women; mean age [range], 58.20 ± 19.62 [18-83] years) and without (27 men, 23 women; 49.54 ± 12.12 [22-74] years) UGIB was measured through electrodermal screening (EDS), based on the theory of electroacupuncture according to Voll (EAV). Data were compared through analysis of variance (ANOVA), receiver operating characteristic (ROC) curve analysis, and logistic regression. The initial readings were lower in the UGIB group, indicating blood and energy deficiency due to UGIB. Significant differences in indicator drop values were observed at nine BAPs (p < 0.05) on the bilateral small intestine, bilateral stomach, bilateral circulation, bilateral fibroid degeneration, and right lymph meridians. The area under the ROC curve values of the BAPs on the bilateral small intestine and stomach meridians were larger than 0.5, suggesting the diagnostic accuracy of EDS for UGIB on the basis of the indicator drop of these BAPs. Logistic regression revealed that when the indicator drop of the BAP on the left stomach meridian increased by one score, the risk of UGIB increased by about 1.545-3.523 times. In conclusion, the change in the electrical resistance of the skin measured by EDS at the BAPs on the bilateral small intestine and stomach meridians provides specific information on UGIB. | 25,169,911 | [
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Vitamin D receptor gene polymorphisms and the risk of Parkinson's disease. | The effect of vitamin D receptor (VDR) gene polymorphisms on Parkinson's disease (PD) has recently gained interest. However, evidence on this relationship is controversial. We searched PubMed, EMBASE and the Cochrane Library database targeted all studies that evaluated VDR gene polymorphisms and PD up to April 2,014. A meta-analysis was conducted on the association between VDR ApaI, BsmI, TaqI and FokI polymorphisms and PD using (1) allelic contrast, (2) dominant, (3) recessive, and (4) additive models. A total of five relevant studies involving PD patients (n = 1,266) and controls (n = 1,649) were included in the analysis. There was a significant association between FokI polymorphism and PD. In the pooled allelic analysis, the F allele was associated with increased risk of PD (OR 1.41, 95% CI 1.14-1.75). In the genotype analysis, FF + Ff versus ff showed a significant association with PD in the dominant model (OR 2.32, 95% CI 1.49-3.61, P = 0.0002). FF versus ff showed a significant association with PD in the additive model (OR 2.45, 95% CI 1.52-3.93, P = 0.0002). There was also a statistically significant association between VDR BsmI polymorphisms in the recessive model, BB versus Bb + bb showed a significant increased risk of PD (OR 1.37, 95% CI 1.01-1.87, P = 0.04). No significant associations were observed between VDR ApaI and TaqI polymorphisms and PD. To sum up, VDR BsmI and FokI polymorphisms were associated with increased risk of PD. | 25,169,913 | [
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Thoracoscopic repair of esophageal atresia and tracheo-esophageal fistula in neonates: the current state of the art. | The first thoracoscopic esophageal atresia with tracheo-esophageal fistula (EATEF) repair was performed in March of 2000. This report evaluates the results and evolution of the technique over the last decade. Thoracoscopic esophageal atresia repair has proven to be an effective and safe technique. Initial experience resulted in a higher stricture rate but this improved with experience and changes in technique over the last decade. The outcomes are similar to or superior to that of an open thoracotomy and avoid the musculoskeletal morbidity associated with that technique. | 25,169,923 | [
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Apparent diffusion coefficient scalars correlate with near-infrared spectroscopy markers of cerebrovascular autoregulation in neonates cooled for perinatal hypoxic-ischemic injury. | Neurologic morbidity remains high in neonates with perinatal hypoxic-ischemic injury despite therapeutic hypothermia. DTI provides qualitative and quantitative information about the microstructure of the brain, and a near-infrared spectroscopy index can assess cerebrovascular autoregulation. We hypothesized that lower ADC values would correlate with worse autoregulatory function. Thirty-one neonates with hypoxic-ischemic injury were enrolled. ADC scalars were measured in 27 neonates (age range, 4-15 days) in the anterior and posterior centrum semiovale, basal ganglia, thalamus, posterior limb of the internal capsule, pons, and middle cerebellar peduncle on MRI obtained after completion of therapeutic hypothermia. The blood pressure range of each neonate with the most robust autoregulation was identified by using a near-infrared spectroscopy index. Autoregulatory function was measured by blood pressure deviation below the range with optimal autoregulation. In neonates who had MRI on day of life ≥10, lower ADC scalars in the posterior centrum semiovale (r = -0.87, P = .003, n = 9) and the posterior limb of the internal capsule (r = -0.68, P = .04, n = 9) correlated with blood pressure deviation below the range with optimal autoregulation during hypothermia. Lower ADC scalars in the basal ganglia correlated with worse autoregulation during rewarming (r = -0.71, P = .05, n = 8). Blood pressure deviation from the optimal autoregulatory range may be an early biomarker of injury in the posterior centrum semiovale, posterior limb of the internal capsule, and basal ganglia. Optimizing blood pressure to support autoregulation may decrease the risk of brain injury in cooled neonates with hypoxic-ischemic injury. | 25,169,927 | [
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A transcriptomic approach to ribbon worm systematics (nemertea): resolving the pilidiophora problem. | Resolving the deep relationships of ancient animal lineages has proven difficult using standard Sanger-sequencing approaches with a handful of markers. We thus reassess the relatively well-studied phylogeny of the phylum Nemertea (ribbon worms)-for which the targeted gene approaches had resolved many clades but had left key phylogenetic gaps-by using a phylogenomic approach using Illumina-based de novo assembled transcriptomes and automatic orthology prediction methods. The analysis of a concatenated data set of 2,779 genes (411,138 amino acids) with about 78% gene occupancy and a reduced version with 95% gene occupancy, under evolutionary models accounting or not for site-specific amino acid replacement patterns results in a well-supported phylogeny that recovers all major accepted nemertean clades with the monophyly of Heteronemertea, Hoplonemertea, Monostilifera, being well supported. Significantly, all the ambiguous patterns inferred from Sanger-based approaches were resolved, namely the monophyly of Palaeonemertea and Pilidiophora. By testing for possible conflict in the analyzed supermatrix, we observed that concatenation was the best solution, and the results of the analyses should settle prior debates on nemertean phylogeny. The study highlights the importance, feasibility, and completeness of Illumina-based phylogenomic data matrices. | 25,169,929 | [
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The impact of bacteremia on the outcome of bone infections. | We have used a medical database to analyze our activity since 2005. We observed a frequent association between bone and joint infection (BI) and bacteremia. Our aim was to characterize patients with BI and bacteremia, and focus on the outcome. Our database includes the prospective recording of 28 characteristics of all hospitalized patients, including diagnosis, comorbid conditions, microbiological data, therapy, and outcome. We selected patients presenting with BI in this database, from July 2005 to December 2012. Fever before blood culture was retrospectively documented from the patient's chart. Chronic BI was defined as a disease lasting more than 1 month. An unfavorable outcome was defined by the need for intensive care or death. Six hundred and thirty-two patients presented with BI and 125 with bacteremia (19.8%). We used a stepwise logistic regression analysis and determined that bacteremia was associated with vertebral osteomyelitis, OR, 3.97, P<0.001; alcohol abuse, OR, 2.51, P=0.010; fever, OR, 2.43, P<0.001; neurological and/or psychiatric diseases, OR, 2.41, P ≤ 0.001; and Staphylococcus aureus infection, OR, 2.32, P<0.001. The outcome was unfavorable in 23 cases (3.6%), associated with bacteremia, OR, 8.00, P<0.001, age> 60 years, OR, 4.78, P=0.018, and S. aureus infection, OR, 3.96, P=0.010. No single comorbid condition was significantly associated with an unfavorable outcome. Bacteremia occurred in nearly 20% of the patients presenting with BI, and was associated with identifiable comorbid conditions; it was the main risk factor for an unfavorable outcome. | 25,169,941 | [
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Awake extracorporeal membrane oxygenation bridging for pulmonary retransplantation provides comparable results to elective retransplantation. | Lung retransplantation became an accepted treatment for bronchiolitis obliterans syndrome (BOS). However, the value of different bridging modalities for these patients is controversial. We analyzed outcomes of 39 patients listed for retransplantation between 2008 and 2012. Patients were divided in 3 groups: 23 patients without any bridge modality (elective, Group 1), 11 patients on ventilation and full sedation with or without extracorporeal membrane oxygenation (ECMO) support (sedated bridging, Group 2), and 5 patients awake on ECMO support (awake bridging, Group 3). Waiting list mortality was 13% in Group 1, 39% in Group 2, and 0% in Group 3. Perioperative mortality was 20% in Group 1, 29% in Group 2, and 0% in Group 3. Significant differences between Groups 1 and 2 were calculated for time on post-operative ventilation (17.4 vs 27.3 days, p = 0.022), intensive care unit stay (22.0 vs 32.9 days, p = 0.026), and hospital stay (34.7 vs 54.1 days, p = 0.013). However, there were no significant differences between Groups 1 and 3 for post-operative ventilation time (17.4 vs 13.4 days, p = 0.192), for intensive care unit stay (22.0 vs 26.4 days, p = 0.169), or for hospital stay (34.7 vs 34.8 days, p = 0.367). Survival rates at 90 days, 1 year, and 2 years were 80%, 70%, and 53% in Group 1; 71%, 43%, and 29% in Group 2; and 100%, 60%, and 60% in Group 3, respectively. Awake ECMO bridging for retransplantation provides comparable results to elective retransplantation. | 25,169,957 | [
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Attenuated development of cardiac fibrosis in left ventricular pressure overload by SM16, an orally active inhibitor of ALK5. | Pressure overload-induced TGF-β signaling activates cardiac fibroblasts (CFB) and leads to increased extracellular matrix (ECM) protein synthesis including fibrosis. Excessive ECM accumulation may in turn affect cardiac function contributing to development of heart failure. The aim of this study was to examine the effects of SM16, an orally active small molecular inhibitor of ALK5, on pressure overload-induced cardiac fibrosis. One week after aortic banding (AB), C57Bl/6J mice were randomized to standard chow or chow with SM16. Sham operated animals served as controls. Following 4 weeks AB, mice were characterized by echocardiography and cardiovascular magnetic resonance before sacrifice. SM16 abolished phosphorylation of SMAD2 induced by AB in vivo and by TGF-β in CFB in vitro. Interestingly, Masson Trichrome and Picrosirius Red stained myocardial left ventricular tissue revealed reduced development of fibrosis and collagen cross-linking following AB in the SM16 treated group, which was confirmed by reduced hydroxyproline incorporation. Furthermore, treatment with SM16 attenuated mRNA expression following induction of AB in vivo and stimulation with TGF-β in CFB in vitro of Col1a2, the cross-linking enzyme LOX, and the pro-fibrotic glycoproteins SPARC and osteopontin. Reduced ECM synthesis by CFB and a reduction in myocardial stiffness due to attenuated development of fibrosis and collagen cross-linking might have contributed to the improved diastolic function and cardiac output seen in vivo, in combination with reduced lung weight and ANP expression by treatment with SM16. Despite these beneficial effects on cardiac function and development of heart failure, mice treated with SM16 exhibited increased mortality, increased LV dilatation and inflammatory heart valve lesions that may limit the use of SM16 and possibly also other small molecular inhibitors of ALK5, as future therapeutic drugs. | 25,169,971 | [
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Reducing Deviance Through Youths' Mutual Aid Group Dynamics. | The mutual aid group, as supported by the social worker, emerges to play a vital role in helping group members reduce their deviance or behavioral problem. However, how the collaboration of the group and social worker accomplishes the reduction has remained uncharted. Based on social capital theory, mutual aid and cohesion within the group and social workers' specific aid for the group are likely responsible for the reduction. The test of such hypotheses relies on a two-wave panel survey of the members of 60 mutual aid groups who had deviant behavioral problems, located in Hong Kong, China. These groups had 241 youths completing both initial and 1-year follow-up surveys. Results manifested the direct or unconditional contributions of mutual aid, group cohesion, and social workers' specific aid to reducing deviance. Hence, social workers can enhance the effectiveness of the mutual aid group in reducing youths' deviance. | 25,169,973 | [
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Gene transfers shaped the evolution of de novo NAD+ biosynthesis in eukaryotes. | NAD(+) is an essential molecule for life, present in each living cell. It can function as an electron carrier or cofactor in redox biochemistry and energetics, and serves as substrate to generate the secondary messenger cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate. Although de novo NAD(+) biosynthesis is essential, different metabolic pathways exist in different eukaryotic clades. The kynurenine pathway starting with tryptophan was most likely present in the last common ancestor of all eukaryotes, and is active in fungi and animals. The aspartate pathway, detected in most photosynthetic eukaryotes, was probably acquired from the cyanobacterial endosymbiont that gave rise to chloroplasts. An evolutionary analysis of enzymes catalyzing de novo NAD(+) biosynthesis resulted in evolutionary trees incongruent with established organismal phylogeny, indicating numerous gene transfers. Endosymbiotic gene transfers probably introduced the aspartate pathway into eukaryotes and may have distributed it among different photosynthetic clades. In addition, several horizontal gene transfers substituted eukaryotic genes with bacterial orthologs. Although horizontal gene transfer is accepted as a key mechanism in prokaryotic evolution, it is supposed to be rare in eukaryotic evolution. The essential metabolic pathway of de novo NAD(+) biosynthesis in eukaryotes was shaped by numerous gene transfers. | 25,169,983 | [
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Prevalence of glucose-6-phosphate dehydrogenase deficiency and the role of the A- variant in a Saudi population. | To estimate the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among Saudi men, and to establish the frequency of the two mutations/polymorphisms associated with the G6PD A- mutation--G to A at nucleotide 202 (G202A) and A to G at nucleotide 376 (A376G)--in those found to have G6PD deficiency. Blood samples were obtained from healthy male Saudi donors and screened for G6PD deficiency using a fluorescent spot test. Samples from subjects shown to be G6PD deficient and controls were then analysed for the presence of the G202A and A376G mutations on exons 4 and 5, respectively, of the G6PD gene using polymerase chain reaction followed by restriction fragment length polymorphism. A total of 2100 male subjects were screened; of these, 100 (4.76%) were shown to be G6PD deficient. The G6PD A- mutation (presence of both G202A and A376G) was observed in two (2%) of the 100 subjects with G6PD deficiency. There was no significant difference in the frequency of this mutation between those with G6PD deficiency and controls. The G6PD A- mutation (G202A and A376G) does not appear to have a role in G6PD deficiency in a Saudi population. | 25,169,987 | [
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Activation of the retinoid X receptor modulates angiotensin II-induced smooth muscle gene expression and inflammation in vascular smooth muscle cells. | The retinoid X receptor (RXR) partners with numerous nuclear receptors, such as the peroxisome proliferator activated receptor (PPAR) family, liver X receptors (LXRs), and farnesoid X receptor (FXR). Although each heterodimer can be activated by specific ligands, a subset of these receptors, defined as permissive nuclear receptors, can also be activated by RXR agonists known as rexinoids. Many individual RXR heterodimers have beneficial effects in vascular smooth muscle cells (SMCs). Because rexinoids can potently activate multiple RXR pathways, we hypothesized that treating SMCs with rexinoids would more effectively reverse the pathophysiologic effects of angiotensin II than an individual heterodimer agonist. Cultured rat aortic SMCs were pretreated with either an RXR agonist (bexarotene or 9-cis retinoic acid) or vehicle (dimethylsulfoxide) for 24 hours before stimulation with angiotensin II. Compared with dimethylsulfoxide, bexarotene blocked angiotensin II-induced SM contractile gene induction (calponin and smooth muscle-α-actin) and protein synthesis ([(3)H]leucine incorporation). Bexarotene also decreased angiotensin II-mediated inflammation, as measured by decreased expression of monocyte chemoattractant protein-1 (MCP-1). Activation of p38 mitogen-activated protein (MAP) kinase but not extracellular signal-related kinase (ERK) or protein kinase B (Akt) was also blunted by bexarotene. We compared bexarotene to five agonists of nuclear receptors (PPARα, PPARγ, PPARδ, LXR, and FXR). Bexarotene had a greater effect on calponin reduction, MCP-1 inhibition, and p38 MAP kinase inhibition than any individual agonist. PPARγ knockout cells demonstrated blunted responses to bexarotene, indicating that PPARγ is necessary for the effects of bexarotene. These data demonstrate that RXR is a potent modulator of angiotensin II-mediated responses in the vasculature, partially through inhibition of p38. | 25,169,989 | [
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Noxious family environments in relation to adult and childhood caries. | The authors tested hypotheses that more noxious family environments are associated with poorer adult and child oral health. A community sample of married or cohabiting couples (N = 135) and their elementary school-aged children participated. Dental hygienists determined the number of decayed, missing and filled surfaces via oral examination. Subjective oral health impacts were measured by means of questionnaires completed by the parents and children. The parents completed questionnaires about interparental and parent-to-child physical aggression (for example, pushing) and emotional aggression (for example, derision), as well as harsh discipline. Observers rated the couples' hostile behavior in laboratory interactions. The extent of women's and men's caries experience was associated positively with their partners' levels of overall noxious behavior toward them. The extent of children's caries experience was associated positively with the level of their mothers' emotional aggression toward their partners. Noxious family environments may be implicated in compromised oral health. Future research that replicates and extends these findings can provide the foundation to translate them into preventive interventions. Noxious family environments may help explain the limitations of routine oral health preventive strategies. Interprofessional strategies that also address the family environment ultimately may prove to be more effective than are single modality approaches. | 25,169,999 | [
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The relationship between various parameters of complete denture quality and patients' satisfaction. | Patients' appreciation of their conventional complete dentures might be affected by the quality of the dentures. A random sample of 33 edentulous patients who were rehabilitated by means of conventional complete dentures participated in the study. Three independent investigators who underwent technique calibration evaluated the dentures on the basis of seven clinical criteria by using a validated examination form. The patients filled out a validated denture satisfaction scale. The author used Pearson product-moment correlation and analysis of covariance to identify possible correlations. The study results showed that most patients were between "reasonably satisfied" and "very satisfied" with their dentures. The author found nominally higher satisfaction among those receiving both mandibular and maxillary dentures and significant positive correlations between the overall denture satisfaction score and the stability of the mandibular denture (P = .039) and retention of the mandibular denture (P = .005). In contrast, esthetic lip support and lower lip line, occlusion, and maxillary stability and retention were not correlated with participants' overall satisfaction level (P > .064). The results of this study show that a clinically stable mandibular denture was the most important determinant of patients' satisfaction. The study findings highlight the most important denture quality parameters that can aid clinicians in meeting their patients' expectations. | 25,170,001 | [
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Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry. | Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. | 25,170,014 | [
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An exploratory fMRI study into inferences of self-agency. | Building on the recent findings that the experience of self-agency over actions and corresponding outcomes can also rely on cognitive inferential processes, rather than motor prediction processes, this study aims to investigate the brain areas involved in agency inference processing in a setting where action and outcome are independent. Twenty-three right-handed subjects were scanned using functional MRI while performing an agency inference task, in which action outcomes matched or mismatched goals. The experience of self-agency was associated with increased activation in the inferior parietal lobule as well as the bilateral (medial) superior frontal cortex and medial prefrontal cortex. These findings provide new and exciting insights in the processing of inferential self-agency, providing a first look at the neural correlates of self-agency processing independent of motor-prediction processes. | 25,170,021 | [
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Standardised clients as assessors in a veterinary communication OSCE: a reliability and validity study. | In human medicine, standardised patients (SP) have been shown to reliably and accurately assess learners' communication performance in high-stakes certification Objective Structured Clinical Examinations (OSCE), offering a feasible way to reduce the need for recruitment, time commitment and coordination of faculty assessors. In this study, we evaluated the use of standardised clients (SC) as a viable option for assessing veterinary students' communication performance. We designed a four-station, two-track communication skills OSCE. SC assessors used an adapted nine-item Liverpool Undergraduate Communication Assessment Scale (LUCAS). Faculty used a 21-item checklist derived from the Calgary-Cambridge Guide (CCG) and a five-point global rating scale. Participants were second year veterinary students (n=96). For the four stations, intrastation reliability (α) ranged from 0.63 to 0.82 for the LUCAS, and 0.73 to 0.87 for the CCG. The interstation reliability coefficients were 0.85 for the LUCAS and 0.89 for the CGG. The calculated Generalisability (G) coefficients were 0.62 for the LUCAS and 0.60 for the CGG. Supporting construct validity, SC and faculty assessors showed a significant correlation between the LUCAS and CCG total percent scores (r=0.45, P<0.001), and likewise between the LUCAS and global rating scores (r=0.49, P<0.001).Study results support that SC assessors offer a reliable and valid approach for assessing veterinary communication OSCE. | 25,170,035 | [
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T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. | The pathogen recognition theory dictates that, upon viral infection, the innate immune system first detects microbial products and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that tissue resident memory CD8 T cells (T(RM) cells), non-recirculating cells located at common sites of infection, can achieve near-sterilizing immunity against viral infections by reversing this flow of information. Upon antigen resensitization within the mouse female reproductive mucosae, CD8(+) T(RM) cells secrete cytokines that trigger rapid adaptive and innate immune responses, including local humoral responses, maturation of local dendritic cells, and activation of natural killer cells. This provided near-sterilizing immunity against an antigenically unrelated viral infection. Thus, CD8(+) T(RM) cells rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens. | 25,170,049 | [
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Infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses. | Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines. | 25,170,051 | [
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A deregulated intestinal cell cycle program disrupts tissue homeostasis without affecting longevity in Drosophila. | Recent studies illuminate a complex relationship between the control of stem cell division and intestinal tissue organization in the model system Drosophila melanogaster. Host and microbial signals drive intestinal proliferation to maintain an effective epithelial barrier. Although it is widely assumed that proliferation induces dysplasia and shortens the life span of the host, the phenotypic consequences of deregulated intestinal proliferation for an otherwise healthy host remain unexplored. To address this question, we genetically isolated and manipulated the cell cycle programs of adult stem cells and enterocytes. Our studies revealed that cell cycle alterations led to extensive cell death and morphological disruptions. Despite the extensive tissue damage, we did not observe an impact on longevity, suggesting a remarkable degree of plasticity in intestinal function. | 25,170,078 | [
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Allosteric modulation of β-arrestin-biased angiotensin II type 1 receptor signaling by membrane stretch. | It has recently been appreciated that the angiotensin II type 1 receptor (AT1R), a prototypic member of the G protein-coupled receptor superfamily, also functions as a mechanosensor. Specifically, mechanical stretch activates the AT1R to promote downstream signaling mediated exclusively by the multifunctional scaffold protein, β-arrestin, in a manner consistent with previously identified β-arrestin-biased ligands. However, the ligand-independent mechanism by which mechanical stretch promotes β-arrestin-biased signaling remains unknown. Implicit in the concept of biased agonism (i.e. the ability of an agonist to activate a subset of receptor-mediated signaling pathways) is the notion that distinct active conformations of the receptor mediate differential activation of signaling pathways. Here we determined whether mechanical stretch stabilizes distinct β-arrestin-activating conformations of the AT1R by using β-arrestin2-biased agonists as conformational probes in pharmacological and biophysical assays. When tested at cells expressing the AT1R fused to β-arrestin (AT1R-β-arrestin2), we found that osmotic stretch increased the binding affinity and potency of the β-arrestin-biased agonist TRV120023, with no effect on the balanced agonist AngII. In addition, the effect of osmotic stretch on ERK activation was markedly augmented in cells expressing the AT1R-β-arrestin2 fusion compared with the wild type AT1R and completely blocked in cells expressing the AT1R-Gq fusion. Biophysical experiments with an intramolecular BRET β-arrestin2 biosensor revealed that osmotic stretch and TRV120023 activate AT1Rs to stabilize β-arrestin2 active conformations that differ from those stabilized by the AT1R activated by angiotensin II. Together, these data support a novel ligand-independent mechanism whereby mechanical stretch allosterically stabilizes specific β-arrestin-biased active conformations of the AT1R and has important implications for understanding pathophysiological AT1R signaling. | 25,170,081 | [
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Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, Cys-XX-Cys-His. | Mitochondrial cytochrome c assembly requires the covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1. The enzyme holocytochrome c synthase (HCCS) binds heme and apocytochrome c substrate to catalyze this attachment, subsequently releasing holocytochrome c for proper folding to its native structure. We address mechanisms of assembly using a functional Escherichia coli recombinant system expressing human HCCS. Human cytochrome c variants with individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions (of CXXCH) were co-purified with HCCS. Single and double mutants form a complex with HCCS but not the triple mutant. Resonance Raman and UV-visible spectroscopy support the proposal that heme puckering induced by both thioether bonds facilitate release of holocytochrome c from the complex. His-19 (of CXXCH) supplies the second axial ligand to heme in the complex, the first axial ligand was previously shown to be from HCCS residue His-154. Substitutions of His-19 in cytochrome c to seven other residues (Gly, Ala, Met, Arg, Lys, Cys, and Tyr) were used with various approaches to establish other roles played by His-19. Three roles for His-19 in HCCS-mediated assembly are suggested: (i) to provide the second axial ligand to the heme iron in preparation for covalent attachment; (ii) to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation; and (iii) to aid in release of the holocytochrome c from the HCCS active site. Only H19M is able to carry out these three roles, albeit at lower efficiencies than the natural His-19. | 25,170,082 | [
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The association between dialysis modality and the risk for dialysis technique and non-dialysis technique-related infections. | Infections are a major cause of morbidity and mortality among dialysis patients. Dialysis modality has been hypothesized to be a potential immunomodulatory factor. The objective of this study was to determine the influence of the first dialysis modality on the risk for infections on dialysis. Our study was conducted utilizing the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) cohort of incident dialysis patients. Medical records of all patients from two tertiary care university hospitals and three regional hospitals were reviewed using pre-specified criteria. Information about infections was collected from the start of dialysis until death, modality switch, study withdrawal, kidney transplantation or at the end of the study. Age-standardized incidence rates for infections were calculated. Poisson regression analysis was used to calculate adjusted incidence rate ratios (IRRs). In total, 452 patients, of whom 285 started with haemodialysis (HD) and 167 with peritoneal dialysis (PD), were included. The median follow-up time on the first dialysis modality was similar for HD and PD, 1.8 and 2.0 dialysis years, respectively. During the first 6 months, the age-standardized infection incidence rate was higher on HD compared with PD patients (P = 0.02). Overall, PD patients had a higher infection risk [adjusted IRR: 1.65, 95% confidence interval (CI): 1.34-2.03], which could be attributed to a 4-fold increased risk for dialysis technique-related infections. The risk for non-dialysis technique-related infections was lower in PD patients (adjusted IRR: 0.56, 95% CI: 0.40-0.79). Overall, PD patients carry a higher risk for infections. Interestingly, the risk for non-dialysis technique-related infections was higher in HD patients. The links between dialysis modality and the immune system are expected to explain this difference, but future studies are needed to test these assumptions. | 25,170,096 | [
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Na⁺/H⁺ exchanger 1 participates in tobacco disease defence against Phytophthora parasitica var. nicotianae by affecting vacuolar pH and priming the antioxidative system. | Despite the importance of NHX1 (Na(+)/H(+) exchanger 1) in plant salt tolerance, little is known about its other functions. In this study, intriguingly, it was found that NHX1 participated in plant disease defence against Phytophthora parasitica var. nicotianae (Ppn) in Nicotiana benthamiana. NbNHX1 was originally isolated from N. benthamiana, and characterized. The subcellular localization of NbNHX1 with its C-terminus fused with green fluorescent protein indicated that NbNHX1 localized primarily to the tonoplast. Tobacco rattle virus-induced NbNHX1 silencing led to reduced H(+) efflux from the vacuole to cytoplasts, and decreased Ppn resistance in N. benthamiana. After attack by Ppn, NbNHX1-silenced plants exhibited impaired ability to scavenge reactive oxidative species (ROS) induced by the pathogen. Pea early browning virus-mediated ectopic expression of SeNHX1 (from Salicornia europaea) or AtNHX1 (from Arabidopsis thaliana) both conferred enhanced Ppn resistance to N. benthamiana, with a lower H2O2 concentration after Ppn inoculation. Further investigation of the role of NHX1 demonstrated that transient overexpression of NbNHX1 improved the vacuolar pH and cellular ROS level in N. benthamiana, which was coupled with an enlarged NAD(P) (H) pool and higher expression of ROS-responsive genes. In contrast, NbNHX1 silencing led to a lower pH in the vacuole and a lower cellular ROS level in N. benthamiana, which was coupled with a decreased NAD(P) (H) pool and decreased expression of ROS-responsive genes. These results suggest that NHX1 is involved in plant disease defence; and regulation of vacuolar pH by NHX1, affecting the cellular oxidation state, primes the antioxidative system which is associated with Ppn resistance in tobacco. | 25,170,102 | [
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<i>Corallina</i> and <i>Ellisolandia</i> (Corallinales, Rhodophyta) photophysiology over daylight tidal emersion: interactions with irradiance, temperature and carbonate chemistry. | The photophysiology of three geniculate coralline algal species (<iCorallina officinalis</i, <iC. caespitosa</i and <iEllisolandia elongata</i) was determined in intertidal rock pools in the south-west UK at Combe Martin (51°12'31N 4°2'19W) and Heybrook Bay (50°31'66N 4°11'41W), at the start, middle and end of summer (September 1 and 2) and winter (February 9 and 10) daylight tidal emersion periods, in relation to prevailing irradiance, temperature and carbonate chemistry conditions. Algal photophysiology was assessed from rapid light curves performed using pulse amplitude modulation fluorometry. <iCorallina</i and <iEllisolandia</i experienced significant fluctuations in irradiance, temperature and carbonate chemistry over seasonal and tidal cycles. Rock pool carbonate chemistry was predictable (<iR</i<sup2</sup = 0.82, <iP</i < 0.0001) by photodose (summed irradiance) plus water temperature, but not significantly related to photophysiology. In contrast, <iCorallina</i and <iEllisolandia</i relative maximum electron transfer rate showed a significant negative relationship (<iR</i<sup2</sup = 0.65, <iP</i < 0.0001) with irradiance plus water temperature. At a seasonal resolution, photoacclimation to maximize both light harvesting during winter months and photoprotection during summer months was observed for all species. Dynamic photoinhibition was apparent over both summer and winter tidal emersion, in relation to irradiance fluctuations. More effective photoinhibition was apparent during summer months, with greater sensitivity to irradiance and slower recovery in <iF</i<subv</sub/<iF</i<subm</sub, observed during winter. With sustained high irradiance over tidal emersion, the establishment of high pH/low inorganic carbon conditions may impact photochemistry. This study represents the first assessment of <iC. officinalis</i, <iC. caespitosa</i and <iE. elongata</i photophysiology underpinned by clear species concepts and highlights their ability to adapt to the dramatically fluctuating conditions experienced in intertidal rock pools. | 25,170,177 | [
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... |
The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. | Injectable blood persistent particulate carriers have important therapeutic application in site-specific drug delivery or medical imaging. However, injected particles are generally eliminated by the reticuloendothelial system within minutes after administration and accumulate in the liver and spleen. To obtain a coating that might prevent opsonization and subsequent recognition by the macrophages, sterically stabilized nanospheres were developed using amphiphilic diblock or multiblock copolymers. The nanospheres are composed of a hydrophilic polyethylene glycol coating and a biodegradable core in which various drugs were encapsulated. Hydrophobic drugs, such as lidocaine, were entrapped up to 45 wt% and the release kinetics were governed by the polymer physico-chemical characteristics. Plasma protein adsorption was drastically reduced on PEG-coated particles compared to non-coated ones. Relative protein amounts were time-dependent. The nanospheres exhibited increased blood circulation times and reduced liver accumulation, depending on the coating polyethylene glycol molecular weight and surface density. They could be freeze-dried and redispersed in aqueous solutions and possess good shelf stability. It may be possible to tailor "optimal" polymers for given therapeutic applications. | 25,170,183 | [
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... |
A red tide of Alexandrium fundyense in the Gulf of Maine. | In early July 2009, an unusually high concentration of the toxic dinoflagellate <iAlexandrium fundyense</i occurred in the western Gulf of Maine, causing surface waters to appear reddish brown to the human eye. The discolored water appeared to be the southern terminus of a large-scale event that caused shellfish toxicity along the entire coast of Maine to the Canadian border. Rapid-response shipboard sampling efforts together with satellite data suggest the water discoloration in the western Gulf of Maine was a highly ephemeral feature of less than two weeks in duration. Flow cytometric analysis of surface samples from the red water indicated the population was undergoing sexual reproduction. Cyst fluxes downstream of the discolored water were the highest ever measured in the Gulf of Maine, and a large deposit of new cysts was observed that fall. Although the mechanisms causing this event remain unknown, its timing coincided with an anomalous period of downwelling-favorable winds that could have played a role in aggregating upward-swimming cells. Regardless of the underlying causes, this event highlights the importance of short-term episodic phenomena on regional population dynamics of <iA. fundyense</i. | 25,170,191 | [
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0.1399406,
... |
Role of moxibustion in inflammatory responses during treatment of rat ulcerative colitis. | To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-κB p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 ± 0.54 vs 1.20 ± 0.44, 0.60 ± 0.54 vs 1.80 ± 0.45, 0.60 ± 0.54 vs 3.0 ± 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 ± 8.75 vs 76.61 ± 3.58, 105.46 ± 8.75 vs 69.78 ± 1.87, 105.46 ± 8.75 vs 67.41 ± 1.84, respectively, P < 0.01 for IL-8; and 30.83 ± 1.29 vs 75.64 ± 1.90, 30.83 ± 1.29 vs 80.90 ± 3.16, 30.83 ± 1.29 vs 83.46 ± 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-κB p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 ± 0.026 vs 0.380 ± 0.022, 0.492 ± 0.026 vs 0.355 ± 0.005, 0.492 ± 0.026 vs 0.327 ± 0.015, respectively, P < 0.05 for TLR9; and 0.436 ± 0.041 vs 0.326 ± 0.022, 0.436 ± 0.041 vs 0.293 ± 0.006, 0.436 ± 0.041 vs 0.265 ± 0.017, respectively, P < 0.05 for NF-κB p65). Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-κB p65 in UC rats. | 25,170,214 | [
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Gastrointestinal symptoms: a comparison between patients undergoing peritoneal dialysis and hemodialysis. | To compare the prevalence and diversity of gastrointestinal (GI) symptoms in patients undergoing peritoneal dialysis (PD) and hemodialysis (HD). Two hundred and ninety-four end-stage renal disease patients participated in the study, including 182 HD and 112 PD patients. Dimension scores were calculated from a modified gastrointestinal symptom rating scale (GSRS) 18-item questionnaire, including items concerning eating dysfunction, and were used for measuring GI symptoms. Information on patient age, condition contributing to end-stage renal disease and the most recent dialysis adequacy assessment (serum Kt/V urea value) was obtained from the follow-up database and by interviewing patients and/or reviewing the medical records. Differences between the HD and PD groups were evaluated using Student's t, Pearson's χ(2) or Fisher's exact tests. The overall prevalence of GI symptoms, defined by a GSRS > 1, in end-stage renal disease patients was 70.7% (208/294), which differed between HD and PD patients (76.4% vs 61.6%, P < 0.01). HD patients had a higher prevalence of constipation, abdominal pain and diarrhea compared to PD patients (36.3% vs 17.9%, 32.4% vs 5.4%, 17.6% vs 4.5%, respectively, P < 0.05). PD patients had a higher prevalence of reflux compared to HD patients (32.1% vs 24.2%, P < 0.05). Additionally, reflux and eating dysfunction were more severe in PD patients (GSRS: 1.71 ± 1.15 vs 1.30 ± 0.67, 1.57 ± 0.84 vs 1.39 ± 0.61, respectively, P < 0.05), whereas HD patients had greater abdominal pain, diarrhea and constipation (GSRS: 1.22 ± 0.39 vs 1.04 ± 0.19, 1.19 ± 0.53 vs 1.07 ± 0.35, 1.51 ± 0.83 vs 1.23 ± 0.58, respectively, P < 0.05). Finally, 14.8% (27/182) of HD patients presented with more than three GI symptoms, compared to 7.2% (8/112) of PD patients (P < 0.01). HD and PD patients differ in prevalence, severity and diversity of GI symptoms. | 25,170,224 | [
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Glutamine prevents oxidative stress in a model of mesenteric ischemia and reperfusion. | To evaluate preventative effects of glutamine in an animal model of gut ischemia/reperfusion (I/R). Male Wistar rats were housed in a controlled environment and allowed access to food and water ad libitum. Twenty male Wistar rats were divided into four experimental groups: (1) control group (control) - rats underwent exploratory laparotomy; (2) control + glutamine group (control-GLU) - rats were subjected to laparotomy and treated intraperitoneally with glutamine 24 and 48 h prior to surgery; (3) I/R group - rats were subjected to occlusion of the superior mesenteric artery for 30 min followed by 15 min of reperfusion; and (4) ischemia/reperfusion + glutamine group (G + I/R) - rats were treated intraperitoneally with glutamine 24 and 48 h before I/R. Local and systemic injuries were determined by evaluating intestinal and lung segments for oxidative stress using lipid peroxidation and the activity of superoxide dismutase (SOD), interleukin-6 (IL-6) and nuclear factor kappa beta (NF-κB) after mesenteric I/R. Lipid peroxidation of the membrane was increased in the animals subjected to I/R (P < 0.05). However, the group that received glutamine 24 and 48 h before the I/R procedure showed levels of lipid peroxidation similar to the control groups (P < 0.05). The activity of the antioxidant enzyme SOD was decreased in the gut of animals subjected to I/R when compared with the control group of animals not subjected to I/R (P < 0.05). However, the group that received glutamine 24 and 48 h before I/R showed similar SOD activity to both control groups not subjected to I/R (P < 0.05). The mean area of NF-κB staining for each of the control groups was similar. The I/R group showed the largest area of staining for NF-κB. The G + I/R group had the second highest amount of staining, but the mean value was much lower than that of the I/R group (P < 0.05). For IL-6, control and control-GLU groups showed similar areas of staining. The I/R group contained the largest area of IL-6 staining, followed by the G + I/R animals; however, this area was significantly lower than that of the group that underwent I/R without glutamine (P < 0.05). These results demonstrate that pretreatment with glutamine prevents mucosal injury and improves gut and lung recovery after I/R injury in rats. | 25,170,229 | [
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There is Room for Even More Doublethink: The Perilous Status of Psychoanalytic Research. | The opposition between psychoanalysis and systematic interdisciplinary research is to be regretted. The target article attempts to bridge the intellectual divide and for this aim as well as the intellectual adroitness shown it is to be celebrated. Much harder to understand is the high level of affect generated by the debate. Accusations of "doublethink" are helpful. The present paper, like the target paper it follows, attempts to develop an understanding of the position of those who are categorically opposed to interdisciplinary systematic research linked to psychoanalysis. Appreciating the perspective of those deeply opposed to such work could help to create a shared agenda from which our troubled discipline could benefit. This is predicated on the possibility of an open collegial dialogue which this journal was founded to create. | 25,170,240 | [
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0.009643099,
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