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pubmed_1095_3962 | Detection of HER2-overexpression in tumors and metastases is important for the selection of patients who will benefit from trastuzumab treatment. Earlier investigations showed successful imaging of HER2-positive tumors in patients using indium- or gallium-labeled Affibody molecules. The goal of this study was to evaluate the use of (99m)Tc-labeled Affibody molecules for the detection of HER2 expression. The Affibody molecule Z(HER2:342) with the chelator sequences mercaptoacetyl-Gly-Glu-Gly (maGEG) and mercaptoacetyl-Glu-Glu-Glu (maEEE) was synthesized by peptide synthesis and labeled with technetium-99m. Binding specificity, cellular retention, and in vitro stability were investigated. The biodistribution of (99m)Tc-maGEG-Z(HER2:342) and (99m)Tc-maEEE-Z(HER2:342) was compared with (99m)Tc-maGGG-Z(HER2:342) in normal mice, and the tumor targeting properties of (99m)Tc-maEEE-Z(HER2:342) were determined in SKOV-3 xenografted nude mice. The results showed that the Affibody molecules were efficiently labeled with technetium-99m. The labeled conjugates were highly stable in vitro with preserved HER2-binding capacity. The use of glutamic acid in the chelator sequences for (99m)Tc-labeling of Z(HER2:342) reduced the hepatobiliary excretion 3-fold with a single Gly-to-Glu substitution and 10-fold with three Gly-to-Glu substitutions. (99m)Tc-maEEE-Z(HER2:342) showed a receptor-specific tumor uptake of 7.9 +/- 1.0 %IA/g and a tumor-to-blood ratio of 38 at 4 h pi. Gamma-camera imaging with (99m)Tc-maEEE-Z(HER2:342) could detect HER2-expressing tumors in xenografts already at 1 h pi. It was concluded that peptide synthesis for the coupling of chelator sequences to Affibody molecules for (99m)Tc labeling is an efficient way to modify the in vivo kinetics. Increased hydrophilicity, combined with improved stability of the mercaptoacetyl-triglutamyl chelator, resulted in favorable biodistribution, making (99m)Tc-maEEE-Z(HER2:342) a promising tracer for clinical imaging of HER2 overexpression in tumors. | 10.1021/bc7002617 |
pubmed_424_8761 | Hepatitis A virus (HAV) infection results in a debilitating, multi-week illness in older children and adults that can be avoided with pre-exposure immunisation. Inactivated HAV vaccines are safe, highly effective and induce long-lasting protection. Immunisation has typically been recommended only for groups at highest risk of infection or complications, with variable success. This paper reviews the outcomes of several new programmes of universal HAV immunisation of children and/or adolescents. These programmes were associated with substantial disease rate reductions, extending beyond the immunised individuals and age groups (herd immunity), and promise additional benefits as immunised cohorts enter adulthood risk groups. Universal programmes are cost-effective, especially when a combined hepatitis A and B vaccine can be used to minimise incremental costs, and deserve wider consideration in developed countries. | 10.1517/14656566.6.2.157 |
pubmed_702_11707 | OBJECTIVE
To investigate the value of Doppler tissue imaging (DTI) in evaluation the changes of cardiac function after neonatal asphyxia.
METHODS
Sixty-two full-term neonates suffering from asphyxia at birth were divided into 2 groups according to Apgar scores: severe asphyxia group with the Apgar scores < or = 3 (n = 31) and mild asphyxia group with the Apgar scores > 3 and < or = 7 (n = 31). Thirty normal neonates were used as control group. DTI was conducted 24, 48, and 72 hours after birth to measure the values of systolic peak myocardial motion velocity (DTIs), early diastolic peak myocardial motion velocity (TDIe), late diastolic peak myocardial motion velocity (DTIa) and DTI e/a of anterior leaflet of mitral valve, and the values were compared with the left ventricular ejection fraction (LVEF) measured by M-mode ultrasound and the values of E, A, and E/A of mitral valve shown in pulsed Doppler echocardiography.
RESULTS
The LVEF of the severe asphyxia group measured 24 h after birth was (62 +/- 4)cm/s, significantly lower than that of the control group (P < 0.05), while the values of DTIs 24, 48, and 72 hours of the severe asphyxia group were all significantly lower than those of the control group (all P < 0.05). In the severe asphyxia group the DTIs value 24 hours [(3.9 +/- 0.4) cm/s] after the birth was significantly lower than those 48 and 72 hours after birth [(5.3 +/- 0. 8)cm/s, (5.0 +/- 0.9)cm/s,both P < 0.01]. The values of E and E/A of the severe asphyxia group (55 +/- 12, 0.94 +/- 0.25) 72 h after birth of the mild asphyxia group (51 +/- 10, 0.89 +/-0.20) were both significantly lower than those of the control group (both P < 0.01), the value of A 72 h after birth of the mild asphyxia group (60 +/- 7) was significantly higher than that of the control group (P < 0.01). The values of DTIe and DTIe/a 24, 48, and 72 h after birth of the mild asphyxia group were all significantly lower than those of the control group, and the values of DTIa 24, 48, and 72 h after birth of the mild asphyxia group were all significantly higher than those of the control group (all P < 0.01).
CONCLUSION
After neonatal asphyxia, both the systolic function and the diastolic function of the left ventricle decrease; and the DTI indexes can reflect the cardiac function changes more sensitively than M-mode ultrasound indexes. | pubmed_702_11707 |
pubmed_748_23101 | Having digital literacy requires more than just the ability to use software or to operate a digital device; it includes a large variety of complex skills such as cognitive, motoric, sociological, and emotional that users need to have in order to use digital environments effectively. A conceptual model that was recently described by the authors suggests that digital literacy comprises five major digital skills: photo-visual skills ("reading" instructions from graphical displays), reproduction skills (utilizing digital reproduction to create new, meaningful materials from preexisting ones), branching skills (constructing knowledge from non-linear, hypertextual navigation), information skills (evaluating the quality and validity of information), and socio-emotional skills (understanding the "rules" that prevail in cyberspace and applying this understanding in online cyberspace communication). The present paper presents results from a performance-based pioneer study that investigated the application of the above digital literacy skills conceptual model among different groups of scholars. Results clearly indicate that the younger participants performed better than the older ones, with photo-visual and branching literacy tasks, whereas the older participants were found to be more literate in reproduction and information literacy tasks. Research results shed light on the cognitive skills that users utilize in performing with digital environments, and provide educators and software developers with helpful guidelines for designing better user-centered digital environments. | 10.1089/cpb.2004.7.421 |
pubmed_9_12806 | The project 'Efficacy of Support Groups for Mexican American Widows' was evaluated by triangulating results collected from different points of view. These included changes after one year in (1) measurement scores of standardized instruments, (2) assessment of adjustment to role of widow by the outsider and (3) evaluation by the widow herself. When subjects were categorized by their assignment to experimental or control groups, the scores on standardized instruments including the Beck Depression Inventory (BDI), the Center for Epidemiologic Study of Depression (CES-D), Anxiety State, Life Satisfaction and new scales measuring Somatic symptoms and Emotional symptoms had decreased from time 1 to time 5 for all widows. However, the widows participating in support groups showed significantly improved changes in these scores. The outsiders found the women who participated in the support groups to have a far better change to the role of widow than the control widows. The support group widows themselves described more positive changes in themselves than did control widows. | 10.1016/0277-9536(93)90343-3 |
pubmed_1132_24244 | Chlorination is the most widely used method for disinfection of drinking water, but there are concerns about the formation of by-products, such as trihalomethanes (THMs), since the chronic exposure to them may pose risks to human health. For these reasons regulations fix maximum acceptable THMs levels throughout distribution networks, so it is very important to be able to correctly reproduce their formation. In the literature many models for predicting THMs formation have been developed, both based on empirical relationships and on kinetics involved during chlorine reactions. In this work the use of some of these models and their reliability in real situations is investigated through the application to the Aurunci-Valcanneto Water Supply System in Southern Lazio (Italy). The comparison of the performances of 18 selected literature empirical models furnishes interesting observations, indicating that the formula, developed using field data, results in being more suitable for reproducing THMs formation for the presented case study. Other considerations are also offered from the comparison with the results obtained using a simple first order kinetic model, calibrated using measured data. | 10.1080/09593330.2012.679702 |
pubmed_611_5172 | Education and instruction in the care of the patient with peripheral vascular diseases is, at best, fragmented during the first years of medical training. Attention to the issues of peripheral arterial, venous, and lymphatic disorders deserves a more formal approach with respect to physician education, patient evaluation and treatment, knowledge and application of various diagnostic modalities, and involvement of our physician colleagues in complementary disciplines. The vascular medicine internist is an invaluable resource in these areas. The aging of our general population will lead to an increase in manifest peripheral vascular disease within our patient population. Having received additional comprehensive training in the management of the complex patient with peripheral vascular disease, the vascular medicine internist may serve as a complete resource for their care. | pubmed_611_5172 |
others_314_4382 | Accurate gene tree inference is an important aspect of species tree estimation in a summary-coalescent framework. Yet, in empirical studies, inferred gene trees differ in accuracy due to stochastic variation in phylogenetic signal between targeted loci. Empiricists should therefore examine the consistency of species tree inference, while accounting for the observed heterogeneity in gene tree resolution of phylogenomic datasets. Here, we assess the impact of gene tree estimation error on summary-coalescent species tree inference by screening ~2000 exonic loci based on gene tree resolution prior to phylogenetic inference. We focus on a phylogenetically challenging radiation of Australian lizards (genus Cryptoblepharus, Scincidae) and explore effects on topology and support. We identify a well-supported topology based on all loci and find that a relatively small number of high-resolution gene trees can be sufficient to converge on the same topology. Adding gene trees with decreasing resolution produced a generally consistent topology, and increased confidence for specific bipartitions that were poorly supported when using a small number of informative loci. This corroborates coalescent-based simulation studies that have highlighted the need for a large number of loci to confidently resolve challenging relationships and refutes the notion that low-resolution gene trees introduce phylogenetic noise. Further, our study also highlights the value of quantifying changes in nodal support across locus subsets of increasing size (but decreasing gene tree resolution). Such detailed analyses can reveal anomalous fluctuations in support at some nodes, suggesting the possibility of model violation. By characterizing the heterogeneity in phylogenetic signal among loci, we can account for uncertainty in gene tree estimation and assess its effect on the consistency of the species tree estimate. We suggest that the evaluation of gene tree resolution should be incorporated in the analysis of empirical phylogenomic datasets. This will ultimately increase our confidence in species tree estimation using summary-coalescent methods and enable us to exploit genomic data for phylogenetic inferen | 10.1101/056085 |
pubmed_697_541 | Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction. | 10.3760/cma.j.issn.0253-9624.2016.11.017 |
pubmed_570_1967 | PURPOSE
Regular exercise is inversely related to markers of chronic inflammation, but we do not know to what extent these changes are the product of recent exercise behavior. The aim of the present investigation was to examine the stability of markers of chronic inflammation in the face of short-term positive and negative changes in physical activity in middle-aged men.
METHODS
Two studies were conducted using a randomized counterbalanced design. In the first study (Study 1), eight highly active men (age = 56 ± 5 yr, body mass index (BMI) = 23.3 ± 3.2 kg·m(-2), VO(2max) = 50.7 ± 7.0 mL·kg(-1)·min(-1)) undertook two trials; withdrawal of exercise for 1 wk versus control (normal exercise behavior). In the second study (Study 2), 10 sedentary men (age = 57 ± 2 yr, BMI = 27.9 ± 3.6 kg·m(-2), VO(2max) = 30.4 ± 4.6 mL·kg(-1)·min(-1)) undertook 30 min of daily walking at 60% VO(2max) for 1 wk versus control (normal sedentary behavior).
RESULTS
The withdrawal of exercise for 1 wk in highly active men (Study 1) and the imposition of 1 wk of daily exercise in sedentary men (Study 2) did not elicit any substantial changes in the inflammatory proteins C-reactive protein (CRP), IL-6, and TNF-α and circulating leukocyte concentration. The differences in inflammatory proteins between active (Study 1) and sedentary (Study 2) men were marked; for example, baseline CRP was 0.85 ± 0.79 and 3.02 ± 2.30 mg·L(-1), respectively.
CONCLUSIONS
The inflammatory markers CRP, IL-6, and TNF-α are stable and not affected by large short-term positive or negative alterations in exercise behavior. This stability strengthens the use of these markers in clinical and research settings because differences and changes are not simply the product of recent exercise behavior. | 10.1249/MSS.0b013e3181f59dc4 |
pubmed_876_22171 | Arginase, which exists as the isoforms arginase I and II, catalyzes the hydrolysis of arginine to ornithine and urea. Ornithine is the principal precursor for production of polyamines, which are required for cell proliferation. Rat aortic smooth muscle cells (RASMC) contain constitutive arginase I, and arginase inhibitors cause inhibition of cell proliferation. The objective of this study was to determine whether the elevated expression of arginase I in RASMC causes increased cell proliferation. RASMC were stably transfected with either rat arginase I cDNA or a beta-galactosidase control expression plasmid. Western blots and arginase enzymatic assays revealed high-level expression of cytosolic arginase I in arginase I-transfected RASMC. Moreover, this observation was associated with the increased production of urea and polyamines and higher rates of RASMC proliferation. The two selective inhibitors of arginase, N(G)-hydroxy-l-arginine and S-(2-boronoethyl)-l-cysteine, inhibited arginase and decreased the production of urea and polyamines in arginase I-transfected RASMC, all of which were associated with the inhibition of cell proliferation. This study demonstrates that elevated arginase I expression increases RASMC proliferation by mechanisms involving increased production of polyamines. These observations suggest that arginase I plays a potentially important role in controlling RASMC proliferation. | 10.1073/pnas.161294898 |
pubmed_614_13565 | BACKGROUND
Previous studies in patients with multiple sclerosis (MS) have shown an association between high serum 25-hydroxyvitamin D (25[OH]D) levels and decreased inflammatory activity.
OBJECTIVE
The purpose of this study was to examine the association between 25(OH)D levels and axonal injury in MS. Cerebrospinal fluid neurofilament light (CSF-NFL) was used as a marker for axonal injury.
METHODS
Patients were identified through clinical practice at the Department of Neurology in Umeå University Hospital, Sweden. Blood draw, magnetic resonance imaging, scoring of disability and lumbar puncture were performed at inclusion in 153 patients, and also at median 12 months follow-up in 87 patients. For analyses of serum 25(OH)D levels and CSF-NFL, enzyme-linked immunosorbent assays were used.
RESULTS
There was an inverse association between serum 25(OH)D and CSF-NFL levels in categorical (dichotomized at 75 or 100 nmol/l) analyses. A dose-response effect for 25(OH)D levels on CSF-NFL levels (p for trend=0.034) was also present. Serum 25(OH)D levels above 100 nmol/l were associated with lower CSF-NFL levels independently of ongoing MS treatment.
CONCLUSION
High 25(OH)D levels are associated with decreased axonal injury in MS. | 10.1177/1352458515606986 |
pubmed_1034_18974 | Vulvovaginal lichen planus is a type of chronic inflammatory dermatosis of the vulva, usually seen as a part of widespread lichen planus. The common clinical types of vulval lichen planus include papulosquamous, erosive and pigmented types. Hypertrophic lichen planus of the vulva is a rare entity. We report a case of hypertrophic lichen planus of the vulva which clinically simulated genital warts. | 10.1177/0956462417695052 |
pubmed_27_19528 | OBJECTIVES
The study was carried out to assess the effect of nitric oxide (NO) generation or inhibition of NO synthase on the cardiac response to beta- and alpha 1-adrenergic agonists. In addition, we determined the effects of the cell-permable analogue of cGMP, 8-bromo-cGMP (8Br-cGMP).
METHODS
Experiments were done in electrically-paced isolated perfused rat hearts as well as in ventricular myocytes. Hearts were exposed to either the beta-adrenoceptor agonist, isoproterenol (0.1 microM), or the alpha 1-adrenoceptor agonist, phenylephrine (2 microM in the presence of equimolar concentrations of propranolol), either with each drug alone or in the presence of the NO donors S-nitrosoacetylpenicillamine (SNAP, 10 microM) and 3-morpholino-sydnonimine (SIN-1, 10 microM), the NO synthase inhibitor L-NAME (10 microM) or 8Br-cGMP (50 microM). These concentrations of SNAP and 8Br-cGMP increase tissue cGMP levels approximately 3-fold after 15 min treatment. Myocardial contractility was assessed by determining left ventricular pressure with a fluid-filled balloon inserted into the left ventricle. Similar experiments were performed in myocytes in which cell shortening and intracellular calcium transients were determined although concentrations of isoproterenol and phenylephrine in myocytes were higher (1 and 5 microM, respectively) than those used in isolated hearts in order to achieve optimum responses.
RESULTS
In isolated hearts isoproterenol increased developed pressure by about 50%, which was totally prevented by SNAP and SIN-1 and unaffected by L-NAME. 8Br-cGMP, however, did not significantly diminish the positive inotropic effect of isoproterenol. Phenylephrine increased developed pressure of isolated hearts by about 30%, but this was totally unaffected by either SNAP, SIN-1 or 8Br-cGMP. In myocytes, isoproterenol significantly increased the calcium transient by more than 50% and cell shortening by about 70%. Both effects were significantly attenuated by SNAP, SIN-1 and 8Br-cGMP but unaffected by L-NAME. Phenylephrine significantly increased cell shortening and the calcium transient, but these responses were unaffected either by SNAP or 8Br-cGMP.
CONCLUSION
The present study demonstrate that NO as well as guanylate cyclase inhibitors and, to a lesser extent, 8Br-cGMP attenuate beta-receptor-mediated cardiac responses and supports the concept that NO serves as an endogenous regulator of beta-mediated effects of catecholamines in the heart. In addition, our findings suggest that the antiadrenergic effects of NO are restricted to these receptors but likely do not involve alpha 1-mediated effects. | pubmed_27_19528 |
others_314_103235 | To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and pow | 10.1101/2020.11.17.387779 |
pubmed_455_12469 | OBJECTIVE
To evaluate the feasibility of an aggressive surgical approach incorporating major hepatic resection after biliary drainage and preoperative portal vein embolization for patients with hilar bile duct cancer.
SUMMARY BACKGROUND DATA
Although many surgeons have emphasized the importance of major hepatectomy in terms of curative resection for patients with hilar bile duct cancer, this procedure results in a high incidence of postoperative morbidity and mortality in patients with cholestasis-induced impaired liver function.
METHODS
A retrospective cohort study was conducted in 140 patients with hilar bile duct cancer treated from 1990 through 2001. Resectional surgery was performed in 79 patients, 69 of whom underwent major hepatic resection. Thirteen patients underwent concomitant pancreaticoduodenectomy. Preoperative biliary drainage was carried out in all 65 patients who had obstructive jaundice. Portal vein embolization was conducted in 41 of 51 patients undergoing extended right hepatectomy. Short- and long-term outcomes were evaluated.
RESULTS
No patient experienced postoperative liver failure (maximum total bilirubin level, 5.4 mg/dL). The in-hospital mortality rate was 1.3% (1 in 79, resulting from cerebral infarction). A histologically negative resection margin was obtained more frequently when the scheduled extended hepatic resection was conducted (75% vs 44%, P = 0.0178). The estimated 5-year survival rate was 40% when histologically negative resection margins were obtained, but only 6% if the margins were positive. Multivariate analysis identified the resection margin and nodal status as independent factors predictive of survival.
CONCLUSIONS
Extensive resection, mainly extended right hemihepatectomy, after biliary drainage and preoperative portal vein embolization, when necessary, for patients with hilar bile duct cancer can be performed safely and is more likely to result in histologically negative margins than other resection methods. | 10.1097/01.SLA.0000074984.83031.02 |
pubmed_51_20177 | National/ethnic mutation databases aim to document the genetic heterogeneity in various populations and ethnic groups worldwide. We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe. Although this database has recently been upgraded, we continuously try to enhance its functionality by providing more advanced visualization tools that would further assist effective data querying and comparisons. We are currently experimenting in various visualization techniques on the existing FINDbase causative mutation data collection aiming to provide a dynamic research tool for the worldwide scientific community. We have developed an interactive web-based application for population-based mutation data retrieval. It supports sophisticated data exploration allowing users to apply advanced filtering criteria upon a set of multiple views of the underlying data collection and enables browsing the relationships between individual datasets in a novel and meaningful way. | 10.1016/j.ygeno.2012.05.009 |
pubmed_1029_1454 | Histamine (300 microM), bradykinin (2 microM), prostaglandin E2 (PGE2) (30 microM), or the leukotrienes (LT) C4 and E4 (1 microM) but not D4 (1 microM) applied in vitro have been shown to change the shape of endothelial cells lining the guinea pig isolated thoracic inferior vena cava. All caused the formation of inter-endothelial cell gaps. Pre-treatment with either indomethacin (100 microM) or verapamil (20 microM) reduced the effects of these compounds. It is suggested that indomethacin and verapamil act by reducing the amount of intracellular calcium available for the shortening of contractile protein filaments within endothelial cells. | 10.1007/BF02028293 |
pubmed_148_6406 | A congenital coagulation defect was suspected in 10 male French bulldogs, independently referred to the Small Animal Clinic of the Utrecht State University by private pet owners from all over the country. The cases are described in this report. Coagulation studies, performed in 8 of these dogs, revealed a factor VIII (anti-hemophilic globulin) deficiency in 5, and a factor IX (Christmas factor) deficiency in 3 propositi. A pedigree analysis revealed that all of the 10 propositi were lineal descendants, in the female line, of one and the same female ancestor. An inquiry by letter among the owners of 210 male descendants, in the female line, of this common ancestor revealed hemorrhagic episodes in at least another 10 male offspirng. The presence of a large number of carriers can be expected among the French bulldog population in the Netherlands, since the officially registered female offspring in the female line of the ancestor bitch, comprised over 170 dogs as of January, 1971. The possible mechanisms responsible for the simultaneous occurrence of hemophilia A and B in one canine family are discussed. | pubmed_148_6406 |
pubmed_108_13056 | Primary health care is well known to be the cornerstone for the health of the society. Furthermore, efficient health care at the secondary and tertiary levels is entirely dependent on effective primary health care. The Kingdom of Saudi Arabia (KSA) is currently building up a rigorous primary health care system with a large number of well-equipped primary health care centers. However, there is an acute shortage of Saudi family physicians throughout the country; both in urban and rural areas. There is no evidence in the literature supporting the relatively long 7 years' traditional duration of medical programs in the KSA. Rather, several US and Canadian medical schools have established accelerated programs in Internal Medicine and Family Medicine with graduates comparable with those of the traditional curricula in terms of standardized tests, initial resident characteristics, and performance outcomes. In response to the challenges the KSA is facing in primary health care, Unaizah College of Medicine at Qassim University is proposing to establish an accelerated Doctor of Family Medicine Program that would run for total duration of 6 years. Herein, we describe a concise outline of this program. | 10.1177/2382120518818844 |
pubmed_470_17316 | OBJECTIVE
To test whether amniotic fluid (AF) glucose levels in 15-18 weeks of pregnancy can predict birthweight and duration of pregnancy.
STUDY DESIGN
In this prospective study, 66 non-diabetic pregnant women underwent amniocentesis between 15 and 18 weeks of pregnancy and glucose levels were measured immediately by using the enzymatic method of hexocinase. They were all followed up and delivered in our department and neognological parameters were recorded.
RESULTS
AF glucose values ranged from 12 to 69mg/dl (mean 44.2mg/dl, S.D. 11.6mg/dl). No linear relationship was found between AF glucose and either birthweight or duration of pregnancy.
CONCLUSION
AF glucose values between 15 and 18 weeks of pregnancy did not correlate with either birthweight or duration of pregnancy. A single measurement of this value cannot be used for the prediction of the factors studied. | 10.1016/s0301-2115(02)00230-0 |
pubmed_746_5385 | INTRODUCTION
Accrual rates for a randomized trial of decongestive therapy in breast cancer patients with lymphedema were lower than anticipated. In two centres, patients presenting to lymphedema clinic were screened for eligibility to understand the accrual process and help define the patient population.
MATERIALS AND METHODS
All breast cancer patients presenting to two lymphedema clinics in regional cancer centres were screened for study entry. Circumferential arm measurements were taken and volumes calculated. Patients were then screened for trial eligibility. All report forms were sent to the trial coordinating centre.
RESULTS
A total of 408 patients were screened. Median arm volume excess was 239 ml (9.5%). One third of patients had little or no excess volume. Only 28.3% of patients had sufficient excess volume for trial eligibility. Of these, a significant number of patients were excluded because of active malignancy or previous decongestive therapy.
CONCLUSIONS
The finding of moderate to severe lymphedema observed in clinics screening for trial eligibility was less than expected. The natural history of lymphedema in breast cancer patients is potentially changing. Some patients may be presenting with sensory changes suggestive of lymphedema but due to other causes, such as nerve disruption following axillary dissection. | 10.1007/s10549-007-9727-0 |
others_314_174162 | Congenital heart disease (CHD) affects nearly 1% of births annually, and CHD pregnancies carry increased risk of developing pathologies of abnormal placentation. We previously reported significant developmental impacts of disrupting Hand1, a gene associated with CHD, expression in placenta trophoblast and endothelial cells in multiple mouse models. In this study, we aimed to build upon this knowledge and characterize the mechanistic impacts of disrupting HAND1 on human placenta trophoblast and vascular endothelial cell gene expression. HAND1 gene expression was silenced in BeWo cells, a choriocarcinoma model of human cytotrophoblasts, (n=3-9 passages) and isolated human placental microvascular endothelial cells (HPMVEC; n=3 passages), with HAND1 siRNA for 96 h. Cells were harvested, mRNA isolated and RNA sequencing performed using the Illumina NextSeq 550 platform. Normalization and differential gene expression analyses were conducted using general linear modeling in edgeR packages. Statistical significance was determined using a log2 fold change of >1.0 or <-1.0 and unadjusted p-value [≤]0.05. Panther DB was used for overrepresentation analysis, and String DB for protein association network analysis. There was downregulation of 664 genes, and upregulation of 59 genes in BeWo cells with direct HAND1 knockdown. Overrepresentation analysis identified disruption to pathways including cell differentiation, localization, and cell projection organization. In contrast, only 7 genes were changed with direct HAND1 knockdown in HPMVECs. Disruption to HAND1 expression significantly alters gene expression profile in trophoblast but not endothelial cells. This data provides further evidence that future studies on genetic perturbations in CHDs should consider the extra-embryonic tissue in addition to the fetal hear | 10.1101/2022.11.01.514704 |
pubmed_673_14322 | In order to assess the effectiveness of the agar plate dilution method for susceptibility testing of N. gonorrhoeae, different media were used. A total of 2,210 N. gonorrhoeae strains were tested on eight different media. The best results were obtained with G.C. base medium (Difco) enriched with 0.1% Isovitalex and 1.5% lysed horse blood and by using a bacterial inoculum with the opacity of No. 1 McFarland nephelometric standard. This medium yielded constant results and 98.6% of the N. gonorrhoeae strains grew well on the control plates. | pubmed_673_14322 |
pubmed_352_14362 | The thickness and area of rat sciatic endoneurial microvessel components (endothelial cells, basement membranes and wall) were assessed to test whether collapse or vasoconstriction was typical of immersion (I) as compared to perfusion (P) or in situ (S) fixation and to determine whether area, but not thickness, would be unaffected by collapse or vasoconstriction. In S and in P fixation there was no apparent collapse or vasoconstriction; in fact, none of the measurements were significantly different between themselves except for index of circularity (IC), which was a little lower in S than in P fixation. By contrast to S or P, in I fixation, the lumen was much smaller and more irregular and the wall was thicker. Area of wall (and of its components) was not significantly different among I, P or S fixation, but thickness was significantly greater in I than in P or S fixation. For comparison to such properties of vessels as permeability, thickness may be the appropriate measurement, but for other purposes, such as determining the amount of basement membrane in diabetes mellitus, area may be a better measurement as it is less affected by collapse or vasoconstriction. | 10.1016/0006-8993(87)91058-4 |
pubmed_135_12181 | Clostridium perfringens type A and C are the primary etiological agents associated with necrotic enteritis (NE) in poultry. The predisposing factors implicated in the incidence of NE changes the physical properties of the gut, immunological status of birds, and disrupt the gut microbial homeostasis, causing an over-proliferation of C. perfringens. The principal virulence factors contributing to the pathogenesis of NE are the α-toxin, β-toxin, and NetB toxin. The immune response to NE in poultry is mediated by the Th1 pathway or cytotoxic T-lymphocytes. C. perfringens type A and C are also pathogenic in humans, and hence are of public health significance. C. perfringens intoxications are the third most common bacterial foodborne disease after Salmonella and Campylobacter. The restrictions on the use of antibiotics led to an increased incidence of NE in poultry. Hence, it is essential to develop alternative strategies to keep the prevalence of NE under check. The control strategies rely principally on the positive modulation of host immune response, nutritional manipulation, and pathogen reduction. Current knowledge on the etiology, pathogenesis, predisposing factors, immune response, effect on the gut microbial homeostasis, and preventative strategies of NE in this post-antibiotic era is addressed in this review. | 10.3390/microorganisms10101958 |
others_290_1154 | Dactylorhiza hatagirea, a terrestrial orchid endemic to North-Western Himalayas has immense medicinal importance attributed to dactylorhin. Inspite of therapeutic relevance, quantification of dactylorhin from this orchid has not been reported so far. Also, there is tremendous need to conserve D. hatagirea through in vitro approaches to harness its various bio-constituents. In the current study, it was found that flowers/inflorescences were enriched with dactylorhin along with tubers in D. hatagirea. Other aerial parts such as stem and leaves were not contributing towards the accumulation of active secondary metabolites collectively in whole plant. Also, the protocol for regeneration of multiple shoots with tubers/roots and callus initiation in D. hatagirea was optimized. BM2 terrestrial orchid media supplemented with 1 mg/L indole-3-butyric acid (IBA) and 6 mg/L 6-Benzylaminopurine (BAP) promoted shoot and root regeneration rapidly and efficiently. Moreover, Murashige Skoog (MS) media containing 0.5 mg/L 1-Naphthaleneacetic acid (NAA) and 1 mg/L BAP was suitable with a high frequency rate and a shorter duration for callus initiation. Further, it was observed that there was less enrichment of dactylorhins in in vitro cultures compared to naturally grown plant parts, but can be exploited alternatively if needed. © 2022 SAA | 10.1016/j.sajb.2022.12.024 |
pubmed_1128_20040 | N-Monomethylformamide (MMF) is a chemical intermediate with potential for inhalation exposure in humans. Human exposures to MMF have occurred in cancer chemotherapy but have been limited due to liver damage. To assess the toxicity of MMF, groups of 15 male rats each were exposed by nose-only inhalation, 6 hr/day, 5 days/week, for 2 weeks to either 0 (control), 50, 130, or 400 ppm MMF. Five rats per group were killed following the 10th exposure, five were killed after a 14-day postexposure recovery period, and five rats were used to determine urinary MMF excretion. Parameters investigated were clinical observations and body weights, clinical pathology, and gross and microscopic pathology including organ weights. Liver damage occurred in rats exposed to either 130 or 400 ppm. This was detected both by increases in serum enzyme activity indicative of liver injury and by microscopic changes in the liver. The changes were more severe in the 400-ppm rats and were partially reversible. Other organs were not adversely affected by inhalation of MMF. The amount of MMF excreted in the urine was dependent on the exposure concentration and MMF was present 14 days postexposure at the higher exposure levels. The no-observed-effect level under the conditions of this experiment was 50 ppm. | 10.1016/0272-0590(90)90305-4 |
pubmed_737_3766 | The objective of this research was to identify the influence of applied force (AF) and the compressive strength (CS) of concrete on particle exposure concentrations during concrete cutting processes. Five cutting conditions were selected with AF varied between 9.8 and 49 N and CS varied between 2500 and 6000 psi. For each selected cutting condition, the measured total dust concentrations (C(tot)) were used to further determine the corresponding three health-related exposure concentrations of the inhalable (C(inh)), thoracic (C(thor)), and respirable fraction (C(res)). Results show that particle size distribution was consistently in a bimodal form under all selected cutting conditions. An increase in CS resulted in an increase in coarse particle generations leading to an increase in the four measured particle exposure levels. An increase in AF resulted in an increase in exposure concentrations with a higher fraction of fine particles (i.e., C(tho) and C(res)) However, for particle exposure concentrations with a higher fraction of coarse particles (i.e., C(tot) and C(inh)), an increase in AF resulted in an initial increase, followed by a decrease in concentration. Finally, the above inferences were further confirmed through the use of fixed-effect models to determine the influence of both CS and AF on the four exposure concentrations. These results provide a reference for industries to initiate appropriate control strategies to reduce the exposure levels encountered by workers. | 10.1016/j.scitotenv.2011.05.016 |
pubmed_678_12080 | Having a greater than average number of older biological brothers is a robust correlate of male androphilia (i.e., sexual attraction and arousal to adult males). Previous investigations have sought to understand whether this fraternal birth order (FBO) effect is also systematically related to recalled indicators of childhood gender nonconformity (CGN). However, these investigations have relied on data from low-fertility Western populations in which expressions of femininity in male children are routinely stigmatized and consequently, suppressed. The present study examined the FBO effect (among other sibship characteristics) and recalled indicators of CGN in Samoa, a high-fertility population, whose members are relatively tolerant of male femininity. Indeed, Samoans identify feminine androphilic males as belonging to an alternative gender category, known locally as fa'afafine. The present study compared the sibship characteristics of 231 fa'afafine and 231 opposite-sex attracted men from Samoa, as well as how these characteristics related to recalled CGN. Results replicated the well-established FBO effect for predicting male sexual orientation, with each older brother increasing the odds of being androphilic by 21%. However, no relationship was found between the number of older brothers (or other siblings) a participant had and their recalled CGN. Although fa'afafine reported significantly more CGN than Samoan men, CGN did not mediate the FBO effect, nor did the FBO effect and CGN interact to predict male sexual orientation. These findings are consistent with previous studies suggesting that the FBO effect is associated with male sexual orientation, but not childhood female-typical gender expression among androphilic males. | 10.1002/dev.21498 |
pubmed_948_993 | The authors examined 41 shoulder joints by arthrography after the patients had undergone surgery for rotator cuff tears. In 26 cases the arthrographic findings were negative; that is to say the region of the tendon suture was tightly closed. In 10 of these 26 cases the underside of the rotator cuff had a rather irregular border. The arthrograms were positive for 12 of the other 15 patients who had undergone surgery. In 3 cases contrast medium leakage into tendinous tissue on the joint side was seen. The postoperative results, ascertained with reference to the assessment guidelines proposed by Neer and Patte, were largely unrelated to the arthrographic findings. In patients with contrast medium leakage from the rotator cuff only the muscular strength was slightly reduced. There was no correlation with the clinical symptoms. In the comparison of all patients who had undergone postoperative arthrography with the total study population a lower number in the index was striking. It may be that patients with symptoms persisting after surgery were more prepared to undergo control arthrography. | pubmed_948_993 |
pubmed_788_1736 | AIMS OF THE STUDY
To examine the patterns of use, complication rates, and survival in elderly recipients of implantable cardioverter defibrillators (ICD).
METHODS AND RESULTS
We followed 500 consecutive patients included in the Marburg Defibrillator database for 48+/-39 months. There were 40 patients (8%) >/= 75 and 460 (92%) < 75 years of age at the time of implant. The 5-year Kaplan-Meier estimate for appropriate treatment of VT or VF by ICD was 49% among patients < 75- versus 57% among patients >/= 75-years-old (P = 0.17). The 5-year sudden death rate was similarly low in both groups of patients (2% versus 3%). The 5-year overall mortality rate was significantly higher in patients >/= 75 than in patients < 75 years of age (55% versus 21%, P = 0.001), due to a higher mortality from heart failure (HF). All procedure-related, lead-related, and pulse generator-related complications were similar in both patient groups (23% versus 25%).
CONCLUSIONS
ICD therapy was equally effective in patients >/= 75 and patients < 75 years of age in the prevention of sudden cardiac death. While the complication rates were similar in both age groups, the long-term mortality was considerably higher in elderly patients, due to a higher mortality from HF. The current ICD therapy guidelines appear applicable to elderly patients who are otherwise medically stable and without advanced HF. | 10.1111/j.1540-8159.2007.00623.x |
pubmed_1018_15866 | OBJECTIVE
To investigate the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in cells from synovial fluid (SF) of patients with acute or chronic arthritis.
METHODS
SF was obtained from eight patients with acute crystal-induced arthritis, nine with rheumatoid arthritis and four with psoriatic arthritis. COX-1 and COX-2 gene expression was studied by reverse transcriptase-polymerase chain reaction (RT-PCR). Protein expression was detected by Western blotting and immunocytochemistry.
RESULTS
There was expression of COX-1 mRNA in all and COX-2 mRNA in most of the SF samples from acute or chronic arthritis. By immunocytochemistry, both COX-1 and COX-2 immunoreactivity was restricted to a variable fraction of mononuclear cells. COX-1 staining was observed in 10-fold more cells than COX-2. By Western blotting, COX-1 protein was detected in 60% of the SF samples and COX-2 in none. There were no differences in the pattern of COX-1 and COX-2 expression between chronic and acute SF samples.
CONCLUSION
In arthritis, both COX-1 and COX-2 isoforms are expressed by SF cells. COX-1 is the most abundant isoform. Since the strong COX-1 immunostaining observed in a fraction of mononuclear SF cells is not observed in peripheral blood leucocytes, it may be the result of either the activation or recruitment of a subset of mononuclear cells with a high COX-1 expression level. | 10.1093/rheumatology/37.7.773 |
pubmed_325_18968 | On the basis of the continuum theory of micromagnetics, the correlation function of the spin-misalignment small-angle neutron scattering cross section of bulk ferromagnets (e.g. elemental polycrystalline ferromagnets, soft and hard magnetic nanocomposites, nanoporous ferromagnets, or magnetic steels) is computed. For such materials, the spin disorder which is related to spatial variations in the saturation magnetization and magnetic anisotropy field results in strong spin-misalignment scattering dΣM/dΩ along the forward direction. When the applied magnetic field is perpendicular to the incoming neutron beam, the characteristics of dΣM/dΩ (e.g. the angular anisotropy on a two-dimensional detector or the asymptotic power-law exponent) are determined by the ratio of magnetic anisotropy field strength Hp to the jump ΔM in the saturation magnetization at internal interfaces. Here, the corresponding one- and two-dimensional real-space correlations are analyzed as a function of applied magnetic field, the ratio Hp/ΔM, the single-particle form factor and the particle volume fraction. Finally, the theoretical results for the correlation function are compared with experimental data on nanocrystalline cobalt and nickel. | 10.1107/S1600576715013187 |
pubmed_621_25182 | This article utilizes a theoretical framework of policy innovation, diffusion, and reinvention to investigate the evolving nature of Medicaid managed care programs over time. By estimating two separate models, one for primary care case management (PCCM) and a second for risk-based program enrollment, this study seeks to disentangle two different paths of learning (internal and external), investigate the potential effects of vertical diffusion of policy, and examine the impact of internal state characteristics on the extent of Medicaid managed care. With respect to diffusion and learning, the data reveal that earlier adopters implement more extensive programs. The data fail to reveal much internal learning, although there is evidence of some. External impacts are clear: managed care enrollments in neighboring states and changes in the federal waiver process affect states' decisions. Other policy choices are important: states with more generous Medicaid eligibility rules implement more extensive managed care programs. Complementing other studies of Medicaid, we find that politics and economics make a difference for the extent of managed care programs; unlike other Medicaid studies, we find no effect of race and ethnicity. | 10.1215/03616878-1672727 |
pubmed_216_13851 | Thymoma exhibiting extensive necrosis is extremely rare and remains a diagnostic challenge for both radiologists and pathologists. We describe such a thymoma in an 18-year-old African-American female. Core needle biopsy contained only necrotic tumor tissue. A well-encapsulated 13-cm anterior mediastinal thymoma with extensive necrosis and areas of hemorrhage was resected. Microscopically, the thymus was almost completely replaced by tumor composed of plump epithelial cells with vesicular nuclei and prominent nucleoli in a background of lymphocytes and extensive necrosis. The clinical, immunohistochemical and diagnostic pitfalls of this tumor in core needle biopsies is discussed. | pubmed_216_13851 |
pubmed_357_13438 | Depression is a mental disorder characterized by low mood as the main pathological feature. Current medications for depression have long treatment cycles and serious side effects. Aromatherapy can alleviate depression in a "moistening things silently" way, but the fast evaporation rate of aromatic drugs weakens the effect of aromatherapy. In this study, we designed and prepared nano-aromatic drugs with slow release for anti-depressant application. We first synthesized rod-shaped mesoporous silica nanoparticles (MSNs) and encapsulated bergamot essential oil. These nanoaromatic drugs were named BEO@MSNs. Subsequently, we analyzed the pore properties of MSNs and BEO@MSNs. Further, we explored the thermal stability, encapsulation efficiency, and slow-release properties of bergamot essential oil in BEO@MSNs. Finally, we used BEO@MSNs to alleviate depression in mice while constructing depression model mice via corticosterone. The results showed that BEO@MSNs had excellent anti-depressant effects and biosafety. | 10.1166/jbn.2021.3100 |
pubmed_464_17807 | Invasive fungal infection often complicates patients with severe viral infection, especially those admitted to critical care units. Severe SARS-CoV-2 infection has been no exception and a significant association with Aspergillus spp. has been documented, resulting in high patient mortality. In this summary we describe the clinical presentation, the underlying diseases most commonly linked with this association, radiological manifestations and therapeutic management of CAPA. | 10.37201/req/s01.21.2021 |
pubmed_407_3811 | Research of the past 25 years has shown that astrocytes do more than participating and building up the blood-brain barrier and detoxify the active synapse by reuptake of neurotransmitters and ions. Indeed, astrocytes express neurotransmitter receptors and, as a consequence, respond to stimuli. Within the tripartite synapse, the astrocytes owe more and more importance. Besides the functional aspects the differentiation of astrocytes has gained a more intensive focus. Deeper knowledge of the differentiation processes during development of the central nervous system might help explaining and even help treating neurological diseases like Alzheimer's disease, Amyotrophic lateral sclerosis, Parkinsons disease, and psychiatric disorders in which astrocytes have been shown to play a role. Specific differentiation of neural stem cells toward the astroglial lineage is performed as a multi-step process. Astrocytes and oligodendrocytes develop from a multipotent stem cell that prior to this has produced primarily neuronal precursor cells. This switch toward the more astroglial differentiation is regulated by a change in receptor composition on the cell surface and responsiveness to Fibroblast growth factor and Epidermal growth factor (EGF). The glial precursor cell is driven into the astroglial direction by signaling molecules like Ciliary neurotrophic factor, Bone Morphogenetic Proteins, and EGF. However, the early astrocytes influence their environment not only by releasing and responding to diverse soluble factors but also express a wide range of extracellular matrix (ECM) molecules, in particular proteoglycans of the lectican family and tenascins. Lately these ECM molecules have been shown to participate in glial development. In this regard, especially the matrix protein Tenascin C (Tnc) proved to be an important regulator of astrocyte precursor cell proliferation and migration during spinal cord development. Nevertheless, ECM molecules expressed by reactive astrocytes are also known to act mostly in an inhibitory fashion under pathophysiological conditions. Thus, we further summarize resent data concerning the role of chondroitin sulfate proteoglycans and Tnc under pathological conditions. | 10.3389/fphar.2012.00120 |
pubmed_626_8978 | The concept of a group is ubiquitous in biology. It underlies classifications in evolution and ecology, including those used to describe phylogenetic levels, the habitat and functional roles of organisms in ecosystems. Surprisingly, this concept is not explicitly included in simple models for the structure of food webs, the ecological networks formed by consumer-resource interactions. We present here the simplest possible model based on groups, and show that it performs substantially better than current models at predicting the structure of large food webs. Our group-based model can be applied to different types of biological and non-biological networks, and for the first time merges in the same framework two important notions in network theory: that of compartments (sets of highly interacting nodes) and that of roles (sets of nodes that have similar interaction patterns). This model provides a basis to examine the significance of groups in biological networks and to develop more accurate models for ecological network structure. It is especially relevant at a time when a new generation of empirical data is providing increasingly large food webs. | 10.1111/j.1461-0248.2009.01321.x |
pubmed_781_21667 | BACKGROUND
Next generation sequencing (NGS) data treatment often requires mapping sequenced reads onto a reference genome for further analysis. Mapped data are commonly visualized using genome browsers. However, such software are not suited for a publication-ready and versatile representation of NGS data coverage, especially when multiple experiments are simultaneously treated.
RESULTS
We developed 'VING', a stand-alone R script that takes as input NGS mapping files and genome annotations to produce accurate snapshots of the NGS coverage signal for any specified genomic region. VING offers multiple viewing options, including strand-specific views and a special heatmap mode for representing multiple experiments in a single figure.
CONCLUSIONS
VING produces high-quality figures for NGS data representation in a genome region of interest. It is available at http://vm-gb.curie.fr/ving/. We also developed a Galaxy wrapper, available in the Galaxy tool shed with installation and usage instructions. | 10.1186/s13104-015-1404-5 |
pubmed_36_20738 | BACKGROUND
Overexpression of NUSAP1 is associated with poor prognosis in prostate cancer, but little is known about what leads to its overexpression. Based on previous observations that NUSAP1 expression is enhanced by E2F1, we hypothesized that NUSAP1 expression is regulated, at least in part, by loss of RB1 via the RB1/E2F1 axis.
METHODS
Using Significance Analysis of Microarrays, we examined RB1, E2F1, and NUSAP1 transcript levels in prostate cancer gene expression datasets. We compared NUSAP1 expression levels in DU145, LNCaP, and PC-3 prostate cancer cell lines via use of cDNA microarray data, RT-qPCR, and Western blots. In addition, we used lentiviral expression constructs to knockdown RB1 in prostate cancer cell lines and transient transfections to knockdown E2F1, and investigated RB1, E2F1, and NUSAP1 expression levels with RT-qPCR and Western blots. Finally, in DU145 cells or PC-3 cells that stably underexpress RB1, we used proliferation and invasion assays to assess whether NUSAP1 knockdown affects proliferation or invasion.
RESULTS
NUSAP1 transcript levels are positively correlated with E2F1 and negatively correlated with RB1 transcript levels in prostate cancer microarray datasets. NUSAP1 expression is elevated in the RB1-null DU145 prostate cancer cell line, as opposed to LNCaP and PC-3 cell lines. Furthermore, NUSAP1 expression increases upon knockdown of RB1 in prostate cancer cell lines (LNCaP and PC-3) and decreases after knockdown of E2F1. Lastly, knockdown of NUSAP1 in DU145 cells or PC-3 cells with stable knockdown of RB1 decreases proliferation and invasion of these cells.
CONCLUSION
Our studies support the notion that NUSAP1 expression is upregulated by loss of RB1 via the RB1/E2F1 axis in prostate cancer cells. Such upregulation may promote prostate cancer progression by increasing proliferation and invasion of prostate cancer cells. NUSAP1 may thus represent a novel therapeutic target. | 10.1002/pros.22938 |
pubmed_904_21589 | Hypertrophic cardiomyopathy (HCM) is a hereditary primary myocardial disease that is most commonly due to mutations within genes encoding sarcomeric contractile proteins and is characterised by left ventricular hypertrophy in the absence of a cardiac or systemic cause. Although the overall prognosis is relatively good with an annual mortality rate <1 %, the propensity to potentially fatal ventricular arrhythmias is the most feared complication. The identification of patients at risk of arrhythmogenic sudden cardiac death (SCD) is an essential component in disease management. Aborted SCD and malignant ventricular arrhythmias are the most powerful risk factors for SCD and ICD implantation is recommended in such circumstances. The selection of patients who may benefit from ICD therapy for primary prevention purposes is more challenging. The heterogeneous nature of the disease and the variation in trigger factors provides an adequate explanation for the low predictive accuracy of most conventional risk factors in isolation. A new risk model for risk stratification proposed by the European Society of Cardiology HCM outcome group shows promise but requires validation in different cohorts. The ICD is the only effective therapy in preventing SCD for the disease with a relatively low adverse event rate, but most deaths occur in relatively young patients. However, it is also difficult to ignore the complications with the ICD, therefore, the strive to perfect risk stratification in HCM should continue to ensure that only the most high-risk patients receive an ICD. | 10.15420/ecr.2015.10.01.31 |
pubmed_976_10326 | HISTORY AND ADMISSION FINDINGS
A 54-year-old man was admitted because of intermittent fever for 2 days. Ten days earlier he had returned from Kenya. He had not taken any antimalarial drugs prophylactically.
INVESTIGATIONS
Initial blood smears showed Plasmodium falciparum in 10.4% of erythrocytes. Laboratory tests indicated hyponatremia and disseminated intravascular coagulation. Also, laboratory markers of infection and hemolysis were clearly positive and accompanied by a low-grade normocyticanaemia. Chest radiograph showed the heart size to be at the upper limit of normal and no signs of congestion, pleural effusion or inflammatory infiltrates. Sonography demonstrated hepatosplenomegaly with diffusely increased echogenicity of the liver.
TREATMENT AND COURSE
Falciparum malaria [corrected] with quartan fever was diagnosed and treatment with quinine and doxycycline was initiated. Despite the successful elimination of parasites and a negative fluid balance the patient died two days after admission from pulmonary edema and heart failure.
CONCLUSIONS
A negative fluid balance failed to prevent acute pulmonary edema in this case of severe malaria,supporting the view that fluid imbalance is not an essential feature in malaria-induced lung injury and that cytokines play and important role. | 10.1055/s-2003-38702 |
pubmed_1089_12393 | Epithelioid mesenchymal malignancies represent a major diagnostic challenge. Epithelioid morphology can be observed in a variety of soft tissue neoplasms, however there exist specific subtypes in which an epithelioid apperance constitutes the most distinctive morphological feature. Moving from epithelioid sarcoma of Enzinger (the prototype of sarcoma with epithelioid morphology), this review will focus on the most relevant entities: namely epithelioid haemangioendothelioma and angiosarcoma, pseudomyogenic haemangioendothelioma, epithelioid malignant peripheral nerve sheath tumour, epithelioid sclerosing fibrosarcoma, epithelioid pleomorphic liposarcoma, alveolar soft part sarcoma, and undifferentiated soft tissue sarcoma with epithelioid morphology. Differential diagnoses and major pitfalls will be discussed in detail. | 10.1097/PAT.0000000000000063 |
pubmed_241_9199 | CONTEXT
Data concerning the safety for pregnancy of cabergoline treatment in hyperprolactinaemic women are still scarce.
OBJECTIVE
To exclude a higher than normal risk for miscarriage and congenital malformation in pregnancies initiated under cabergoline treatment.
DESIGN
A retrospective study of 100 pregnancies in 72 hyperprolactinaemic women treated with cabergoline at the time of conception and follow-up of the 88 newborn children.
METHODS
Cabergoline was interrupted in 99 pregnancies and continued in one case. Foetal exposure dose to cabergoline was calculated for each pregnancy. Complications of pregnancy and neonatal status were compared to those observed in an age-and delivery time-matched control group of 163 women.
RESULTS
The mean foetal exposure dose to cabergoline was 3.6 +/- 4.7 mg. The rate of spontaneous miscarriages was 10%. Three medical terminations of pregnancy were performed for a foetal malformation (3%). Minor to moderate complications were observed in 31% of the pregnancies, a figure similar to that found in the control group. An increase in tumour size (2-8 mm) was observed in 17/37 evaluated cases, needing reintroduction of cabergoline during pregnancy in five patients. The 84 deliveries resulted in 88 infants, three of them presenting with a malformation (3.4%). Neonatal status was comparable to the control group, where a malformation rate of 6.3% was observed. Postnatal development of the children was normal.
CONCLUSION
Cabergoline treatment at the time of conception appears to be safe for both the pregnancy and the neonate, although more data are still needed on a larger number of pregnancies. | 10.1111/j.1365-2265.2010.03808.x |
pubmed_770_7448 | The survey took the form of a mailed questionnaire that was filled out anonymously. Eighty-five returns made up a 77% response rate. Overall, respondents felt that there were more heavy drinkers in the gay community than in the general, that sexual orientation should be taken into account when intervention takes place, and that the situation is not one that encourages gays to come for treatment. By and large comments disapproved of homophobia rather than of homosexuality. Not many respondents showed that they knew much on lesbian-male gay differences, but there were a few whose open-ended answers showed that they were insightful on homosexuals in general. | 10.3109/10826088809033071 |
pubmed_1052_23785 | BACKGROUND
Sclerosing stromal tumors are extremely rare sex cord stromal tumors of the ovary, with approximately 100 cases reported since first described in 1973. These tumors present predominantly in the 2nd and 3rd decades of life, typically present with pelvic/abdominal pain and tenderness, mass, and/or abnormal menses, and with hormonal activity reported predominantly in postmenarchal females. Only 5 cases of these tumors have been reported in premenarchal girls, with age ranging from 7 months to 12 years. Only 2 demonstrated hormonal manifestations, with vaginal bleeding due to hyperestrogenism in the 7 month old, and virilization in an 11-year-old female.
CASE
We report a 9-year-old female who was diagnosed with this ovarian tumor, and who presented with virilization.
SUMMARY AND CONCLUSION
This report is remarkable as our patient not only was diagnosed with an ovarian tumor that is extremely rare in this age group but is the youngest reported patient with this tumor who presented with virilization. | pubmed_1052_23785 |
pubmed_99_1299 | Quantitative relationship between the proton diffusion potential in the unstirred layers near BLM and NH4Cl was investigated. It has been found that in the range of low concentrations of NH4Cl the potential value depends on the difference of salt concentrations on different sides of the membrane. At higher concentrations the potential value is the function of the ratio of salt concentrations at different BLM sides. In the limiting case the potential value equals 58 mV with NH4Cl concentrations ratio equaling ten. A model is suggested which quantitatively describes the experimental data. It has been shown that the results obtained can be used in determining BLM permeability for weak acids and bases. | pubmed_99_1299 |
pubmed_105_14411 | Objective
To assess the TNFAIP3 and nuclear factor κB (NFκB) protein expressions in colorectal cancer (CRC) tissue and to analyze the association of these proteins with the clinical pathological characteristics of CRC.
Methods
The following methods should be used in clinical trials: information collection and immunohistochemical methods. The following methods are used for cell experiment: cell transfection, CCK8 detection method, transwell experiment, and western blot experiment. Explore the TNFAIP3 expression in CRC cells, and assess the effect of upregulated TNFAIP3 expression on CRC cell proliferation, invasion, and migration. In clinical experiment, we selected the tumor tissues of 39 CRC patients as our experimental samples. We also collected corresponding patient demographics, such as sex, age, cell differentiation, tumor type, and lymph node metastasis. We also analyzed the TNFAIP3 and NFκB protein expressions in 20 experimental and 20 control samples and evaluated potential correlations between these two proteins and clinical pathological characteristics of CRC. For basic experiment, we established CRC cell lines with elevated TNFAIP3 expression and then randomly divided the cells into three groups, namely, TNFAIP3, NS, and Con groups. Using the transwell and CCK8 methods, we detected the CRC migration abilities and cell proliferation, respectively. We also employed western blot analysis to assess protein expression in the three groups.
Results
NFκB was highly expressed, and TNFAIP3 was scarcely expressed in the experimental group versus control. The expression of both these proteins were strongly related to the degree of tumor differentiation (P < 0.05). The TNFAIP3 and NFκB protein expressions were significantly associated with lymph node metastasis and tumor differentiation (P < 0.05). For basic experiment, compared to the Con and NS groups, TNFAIP3 protein expression levels, cell proliferation, invasion, and migration were significantly increased in the TNFAIP3 group (P < 0.05).
Conclusion
TNFAIP3 overexpression strongly inhibited CRC proliferation, invasion, and migration. Enhanced NFκB protein expression in CRC tissues was associated with elevated malignant degree, metastasis, and TNFAIP3 protein expression in patients who demonstrated high malignant degree and metastasis. Our evidences suggest the promising potential of utilizing TNFAIP3 and NFκB as important reference indices for determining the prognostic outcome of CRC. Furthermore, we revealed that TNFAIP3 overexpression inhibited CRC cell proliferation, invasion, and migration. | 10.1155/2022/1263530 |
pubmed_368_24937 | AIM
To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population.
METHODS
Data were obtained from the population-based digestive cancer registry of Burgundy over a 34-year period. Age-standardized incidence rates were computed using the world standard population. Average annual variations in incidence rates were estimated using a poisson regression. A univariate and multivariate relative survival analysis was performed.
RESULTS
Age-standardized incidence rates were 0.46 and 0.30 per 100000 inhabitants for men and women, respectively. Incidence rate increased from 0.26 (1976-1984) to 0.58 (2003-2009) for men and remained stable for women. Resection for cure was performed in 48.3% of cases. This proportion was stable over the study period. Among cases with curative resection, pancreatico-duodenectomy was performed in 94.0% of cases and ampullectomy in 6.0% of cases. A total of 50.8% of cancers of the ampulla of Vater were diagnosed at an advanced stage. Their proportion remained stable throughout the study period. The overall 1- and 5-year relative survival rates were 60.2% and 27.7%, respectively. Relative survival did not vary over time. Treatment and stage at diagnosis were the most important determinants of survival. The 5-year relative survival rate was 41.5% after resection for cure, 9.5% after palliative surgery and 6.7% after symptomatic treatment. In multivariate analysis, only stage at diagnosis significantly influenced the risk of death.
CONCLUSION
Cancer of the ampulla of Vater is still uncommon, but its incidence increased for men in Burgundy. Diagnosis is often made at an advanced stage, dramatically worsening the prognosis. | 10.3748/wjg.v20.i29.10144 |
pubmed_39_8935 | We present novel clinical observations on negative dysphotopsia (ND) in eyes that have undergone cataract surgery. In the past, shadow effects were alleged to be located in the far peripheral temporal visual field 50° to 100° away from the optical axis. In a small series of eight patients we found evidence of photic effects, described by the patients as shadows in the periphery that were objectively located much more centrally. In all cases, we could find an association of these phenomena with the blind spot. We hypothesize that the memory effect of the blind spot which is dislocated and changed in magnification due to replacement of the crystalline lens could be one determinant for pseudophakic ND. The scotoma of the optic nerve head and the main arteries and veins of the phakic eye are displaced in the pseudophakic eye depending on the specific characteristics and position of the intraocular lens within the eye. | 10.1155/2015/786579 |
pubmed_505_18571 | A patient with ALL on anticancer chemotherapy developed fever which was later attributed to be due to Fusarium fungemia. The details of the case & a review of literature follows. | pubmed_505_18571 |
pubmed_1020_26119 | Many behavioural tasks require the manipulation of mathematical vectors, but, outside of computational models1-7, it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation7-10, performs vector arithmetic. First, we describe a neural signal in the fan-shaped body that explicitly tracks the allocentric travelling angle of a fly, that is, the travelling angle in reference to external cues. Past work has identified neurons in Drosophila8,11-13 and mammals14 that track the heading angle of an animal referenced to external cues (for example, head direction cells), but this new signal illuminates how the sense of space is properly updated when travelling and heading angles differ (for example, when walking sideways). We then characterize a neuronal circuit that performs an egocentric-to-allocentric (that is, body-centred to world-centred) coordinate transformation and vector addition to compute the allocentric travelling direction. This circuit operates by mapping two-dimensional vectors onto sinusoidal patterns of activity across distinct neuronal populations, with the amplitude of the sinusoid representing the length of the vector and its phase representing the angle of the vector. The principles of this circuit may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required. | 10.1038/s41586-021-04067-0 |
pubmed_849_20452 | Acne is a chronic disease of the pilosebaceous unit which is most common during adolescence. Four factors are believed to play a key role in the development of acne lesions: excess sebum production, disturbed keratinization within the follicle, colonization of the pilosebaceous duct by Propionibacterium acnes, and the release of inflammatory mediators into the skin. Consequently, in order to effectively and rapidly reduce acne lesions, treatments need to address as many of these underlying factors as possible. Currently, about half of patients have poor adherence to acne treatments. To overcome this limitation, treatments need to be developed which are well tolerated by patients, and easy for them to use, handle and apply. Topical monotherapies for acne such as retinoids and antimicrobials by themselves have a restricted range of actions against the pathogenic factors of acne. Instead, the Global Alliance to Improve Outcomes in Acne Group recommends combination therapy with a topical retinoid and an antimicrobial agent as the preferred approach for almost all acne patients. The principal advantage of such combinations is that they target more of the underlying pathogenic factors of acne than individual monotherapies and this results in faster and more complete clearing of acne lesions. Fixed-dose combinations are also more convenient than applying two medications separately, which leads to improved adherence with the regimen. By normalizing desquamation, the retinoid component of these combinations allows entry of the antimicrobial agent into the pilosebaceous unit resulting in faster clearance of P. acnes. In conclusion, topical retinoid/antimicrobial fixed-dose combinations represent a rational approach for the treatment of acne. They should be considered as the cornerstone of acne management and should be used much more in the future. | 10.1111/jdv.13186 |
pubmed_551_418 | BACKGROUND
Dengue virus (DENV) is described as the most prevalent arbovirus, infecting at least 50 million people worldwide. During infection, an intricate network of cytokines, a group of substances closely related to disease severity, is released. Recently, it was observed that both DENV-infected epithelial cells undergoing necrosis and dendritic cells (DCs) are able to release a non-classical pro-inflammatory cytokine called high mobility group box 1 (HMGB1).
OBJECTIVES
The aim of this study was to evaluate whether HMGB1 levels were altered in DENV-infected patients' sera and whether this augment correlated with disease pathogenesis.
STUDY DESIGN
Samples from DENV-infected patients were collected from different days after the onset of symptoms and from patients experiencing primary or secondary infection. The circulating HMGB1 concentration was measured in healthy blood donors as well as in donors with primary and secondary cases of DENV infection by a quantitative capture ELISA assay.
RESULTS
We observed that the HMGB1 concentration in DENV-infected patients was significantly higher than in healthy patients. HMGB1 levels reached the highest concentration in the first day after the onset of symptoms and decreased throughout the course of the infection. Moreover, we observed that the HMGB1 concentration was augmented during secondary infection as well.
CONCLUSION
We hypothesize that HMGB1 levels correlate with disease pathogenesis, specifically with the clinical symptoms and secondary infection, implicating a pro-inflammatory cytokine role for HMGB1 in DENV infection. This is the first report assessing the circulating levels of HMGB1 during DENV infection. | pubmed_551_418 |
pubmed_779_3111 | This study aims to evaluate energy and electrode consumption for Acid Red 18 (AR18) removal and the operating costs employing alternating current (AC) and direct current (DC) in an electrocoagulation (EC) system. As the novelty of this study, the effects of AC/DC mode and electrode type were scrutinized through a series of designed experiments in a batch EC reactor to remove a globally used Azo dye from wastewater. In this regard, by designing the experiments with response surface methodology (RSM), four series of 30 experiments were separately conducted employing DC and AC for iron (Fe) and aluminum (Al) electrodes. In each series, quadratic models were achieved for the removal efficiency and operating costs; by confirming the accuracy of the models, two responses were simultaneously optimized accordingly. As a result, the AR18 removal efficiency with Al electrodes had no significant difference using AC and DC (on average 0.2% difference); however, for Fe electrode, the EC performance in DC was more significant than AC (on average 13.8% difference). Also, the operating costs of Fe electrode were more economical in comparison with the Al; on average, the operating costs in the case of applying DC for Fe and Al were achieved 14.6 and 39.8 (US$/kg dye removed), respectively; whereas, for AC, this amount was calculated 9.3 and 36.0 (US$/kg dye removed) for Fe and Al, respectively. | 10.1007/s11356-021-15345-9 |
pubmed_904_5388 | BACKGROUND/PURPOSE
Colectomy with ileal pouch-anal anastomosis (IPAA) is the standard of care for patients with familial adenomatous polyposis (FAP) and refractory ulcerative colitis (UC). The rates of postoperative complications are not well established in children. The objective of this systematic review is to establish benchmark data for morbidity after pediatric IPAA.
METHODS
PubMed, Embase, and The Cochrane Library were searched for studies of colectomy with IPAA in patients ≤21 years old. UC studies were limited to the anti-tumor necrosis factor-α agents era (1998-present). All postoperative complications were extracted.
RESULTS
Thirteen studies met the inclusion criteria (763 patients). Compared to patients with FAP, UC patients had a higher prevalence of pouch loss (10.6% vs. 1.5%). Other major complications such as anastomotic leak, abscess, and fistula were uncommon (mean prevalence 4.9%, 4.2%, and 5.0%, respectively, for patients with UC; 8.7%, 4.2%, and 4.3% for FAP). The most frequent complication was pouchitis (36.4% of UC patients).
CONCLUSIONS
Devastating complications from colectomy and IPAA are rare, but patients with UC have poorer outcomes than those with FAP. Much of the morbidity may therefore stem from patient or disease factors. Multicenter, prospective studies are needed to identify modifiable risks in patients with UC undergoing IPAA.
LEVEL OF EVIDENCE
Prognostic, level II. | 10.1016/j.jpedsurg.2018.08.047 |
pubmed_611_5464 | Capillary electrophoresis coupled with tandem mass spectrometry was used to indirectly separate and quantify the active metabolite of the anti-human immunodeficiency virus (anti-HIV) didanosine drug. The influence of several parameters (pH and ionic strength of volatile formic acid-ammonia buffer) upon electroosmotic flow, electrophoretic mobility and peak efficiency of several nucleosides (A, dA, ddA, C) has been studied. This paper illustrates the current importance in CE-MS technique as a complementary or substituted method to the known HPLC-radioimmunoassay or HPLC-UV method to measure levels of anti-HIV drugs. The limit of detection for 2',3'-dideoxyadenosine by this method is 2 microg 1(-1) in a formic acid-ammonia buffer (pH 2.5, 10 mM ionic strength). This methodology could be used to perform simultaneous detection of two or more anti-HIV nucleosides, such as stavudine or didanosine in combination therapy. | 10.1016/s0021-9673(00)00524-0 |
pubmed_1094_24461 | Health literacy is recognized as an integral component of high-quality health care. However, health literacy has been understudied in the context of cancer care delivery and surgical decision making. The goal of this article is to outline a process for implementation of a health literacy screening assessment within the routine practices of an academic breast surgical oncology clinic. The self-reported health literacy assessment is feasible, particularly with integration of the health literacy screen in the electronic health record. The authors' estimated clinic prevalence of low health literacy was 22%, which has numerous implications for communication and shared decision-making processes.
. | 10.1188/17.CJON.384-386 |
pubmed_298_10737 | OBJECTIVE
The purpose of this study was to examine the effectiveness of a patient-provider educational intervention in reducing at-risk drinking among older adults.
METHOD
This was a cluster-randomized controlled trial of 31 primary care providers and their patients ages 60 years and older at a community-based practice with seven clinics. Recruitment occurred from July 2005 to August 2007. Eligibility was determined by telephone and a baseline mailed survey. A total of 1,186 at-risk drinkers were identified by the Comorbidity Alcohol Risk Evaluation Tool. Follow-up patient surveys were administered at 3, 6, and 12 months after baseline. Study physicians and their patients were randomly assigned to usual care (n = 640 patients) versus the Project SHARE (Senior Health and Alcohol Risk Education) intervention (n = 546 patients), which included personalized reports, educational materials, drinking diaries, physician advice during office visits, and telephone counseling delivered by a health educator. Main outcomes were alcohol consumption, at-risk drinking (overall and by type), alcohol discussions with physicians, health care utilization, and screening and intervention costs.
RESULTS
At 12 months, the intervention was significantly associated with an increase in alcohol-related discussions with physicians (23% vs. 13%; p ≤ .01) and reductions in at-risk drinking (56% vs. 67%; p ≤ .01), alcohol consumption (-2.19 drinks per week; p ≤ .01), physician visits (-1.14 visits; p = .03), emergency department visits (16% vs. 25%; p ≤ .01), and nonprofessional caregiving visits (12% vs. 17%; p ≤ .01). Average variable costs per patient were $31 for screening and $79 for intervention.
CONCLUSIONS
The intervention reduced alcohol consumption and at-risk drinking among older adults. Effects were sustained over a year and may have been associated with lower health care utilization, offsetting screening and intervention costs. | 10.15288/jsad.2014.75.447 |
pubmed_708_22782 | Broad guidelines for the design, implementation, analysis, and reporting of results of clinical trials are given. The use of randomization, concurrent controls, and blinding is justified. Basic principles of the design of clinical trials are outlined and include the areas of specification of the hypothesis, definition of the outcome and the logistics of protocol design, and safeguards to ensure its proper implementation. | pubmed_708_22782 |
pubmed_457_2262 | Long-read sequencing technology promises to greatly enhance de novo assembly of genomes for nonmodel species. Although the error rates of long reads have been a stumbling block, sequencing at high coverage permits the self-correction of many errors. Here, we sequence and de novo assemble the genome of Drosophila serrata, a species from the montium subgroup that has been well-studied for latitudinal clines, sexual selection, and gene expression, but which lacks a reference genome. Using 11 PacBio single-molecule real-time (SMRT cells), we generated 12 Gbp of raw sequence data comprising ∼65 × whole-genome coverage. Read lengths averaged 8940 bp (NRead50 12,200) with the longest read at 53 kbp. We self-corrected reads using the PBDagCon algorithm and assembled the genome using the MHAP algorithm within the PBcR assembler. Total genome length was 198 Mbp with an N50 just under 1 Mbp. Contigs displayed a high degree of chromosome arm-level conservation with the D. melanogaster genome and many could be sensibly placed on the D. serrata physical map. We also provide an initial annotation for this genome using in silico gene predictions that were supported by RNA-seq data. | 10.1534/g3.116.037598 |
pubmed_1107_20652 | Famotidine is a specific, long-acting histamine2-receptor antagonist. It is indicated for the treatment of duodenal ulcer, gastric ulcer, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. Since its introduction for the treatment of acid-related disorders in 1985, an estimated 18.8 million patients worldwide have been treated with famotidine. We present a comprehensive safety profile of oral famotidine, incorporating data from investigational trials, postmarketing studies, and reports of marketed use. The excellent tolerability profile of famotidine observed during investigational trials has remained substantially unchanged during postmarketing experience. Famotidine does not notably bind to cytochrome P-450 or gastric alcohol dehydrogenase and therefore has not been associated with clinically significant drug interactions. It is generally well tolerated in patients with cardiovascular, renal, or hepatic dysfunction or with Zollinger-Ellison syndrome who have tolerated doses up to 800 mg daily. | 10.1016/s0149-2918(96)80177-9 |
pubmed_667_13440 | The genes responsible for the development of neuroblastoma following in vivo deletion or mutation are largely unknown. We have performed loss of heterozygosity studies on a series of 24 Portuguese primary neuroblastomas using 6 polymorphic markers located at chromosome 9p21 spanning the p16/MTS1/CDKN2, p15/MTS2/CDKN2B, and the interferon alpha and beta genes. Loss of heterozygosity was observed in 4 of the 24 tumors (17%), a somewhat lower percentage than a previous study that identified patients by a mass screening program. A correlation was also observed between 9p21 LOH and 1p36 LOH in our group of tumors. Two distinct regions of 9p21 deletion were observed: one located in the region adjacent to the markers D9S162 and D9S1747 and a second located centromerically of the p16 gene near the D9S171 marker. The latter region is exclusive of the p16 gene. This result suggests the presence of at least one other tumor suppressor gene at 9p21, apart from the p16 and p15 genes, which may be of importance to the development of neuroblastoma. | 10.1016/s0165-4608(96)00300-7 |
pubmed_270_20763 | Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively in skeletal muscle, where it is required for formation of the neuromuscular junction. MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. Here, we report the crystal structure of the agrin-responsive first and second immunoglobulin-like domains (Ig1 and Ig2) of the MuSK ectodomain at 2.2 A resolution. The structure reveals that MuSK Ig1 and Ig2 are Ig-like domains of the I-set subfamily, which are configured in a linear, semi-rigid arrangement. In addition to the canonical internal disulfide bridge, Ig1 contains a second, solvent-exposed disulfide bridge, which our biochemical data indicate is critical for proper folding of Ig1 and processing of MuSK. Two Ig1-2 molecules form a non-crystallographic dimer that is mediated by a unique hydrophobic patch on the surface of Ig1. Biochemical analyses of MuSK mutants introduced into MuSK(-/-) myotubes demonstrate that residues in this hydrophobic patch are critical for agrin-induced MuSK activation. | 10.1016/j.jmb.2006.09.019 |
pubmed_319_1809 | A detailed study of the biotransformation of 6- and 7-methoxyflavones by four fungal strains (Aspergillus niger strains MB, KB, and SBP; Penicillium chermesinum 113) was carried out. Products of demethylation and also demethylation combined with hydroxylation at C-4' were identified. The biotransformation products were stronger antioxidants than the substrates. | 10.1515/znc-2012-7-809 |
pubmed_81_14414 | This work addresses the controversial topic of the exploration of the contralateral side in the presence of a one-sided inguinal hernia in infancy. In a prospective study of 368 children with one-sided inguinal hernia, we demonstrated the consecutive development of a contralateral hernia in 22 (6%) of the children. We found that the child's age at first operation represents a risk factor for the development of a consecutive hernia. At an age of less than two months we found a highly significant (P < 0.0001) accumulation of consecutive hernias. These consecutive contralateral hernias appear significantly often (P < 0.0009) within the first two post-operative months in children at least two months old. In view of these findings, we see an indication for routine simultaneous repair on both sides for children aged less than two months at first presentation. | 10.1007/s10029-008-0403-z |
pubmed_271_16021 | A retrospective study was conducted, and 576 human immunodeficiency virus-infected children with total lymphocyte count (TLC) and CD4 count were recruited from China. Spearman rank order correlation and receiver-operating characteristic were used. An overall positive correlation was noted between TLC and CD4 count (prehighly active antiretroviral therapy [pre-HAART], r = 0.789, 6 months of HAART, r = 0.642, 12 months of HAART, r = 0.691, P = 0.001). TLC ≤ 2600 cells/mm(3) predicted a CD4 count of ≤ 350 cells/mm(3) with 82.9% sensitivity, 79.6% specificity pre-HAART. Meanwhile, the optimum prediction for CD4 count of ≤ 350 cells/mm(3) was a TLC of ≤ 2400 cells/mm at 6 months (73.6% sensitivity and 74.1% specificity) and 12 months (81.7% sensitivity and 76.5% specificity) of HAART. TLC can be used as a surrogate marker for predicting CD4 count of human immunodeficiency virus-infected children before and during HAART in resource-limited countries. | 10.1097/INF.0b013e318241d07e |
pubmed_664_3063 | This paper reports the first direct measurements of static friction force and interfacial shear strength between silicon (Si) nanowires (NWs) and poly(dimethylsiloxane) (PDMS). A micromanipulator is used to manipulate and deform the NWs under a high-magnification optical microscope in real time. The static friction force is measured based on "the most-bent state" of the NWs. The static friction and interface shear strength are found to depend on the ultraviolet/ozone (UVO) treatment of PDMS. The shear strength starts at 0.30 MPa without UVO treatment, increases rapidly up to 10.57 MPa at 60 min of treatment and decreases for longer treatment. Water contact angle measurements suggest that the UVO-induced hydrophobic-to-hydrophilic conversion of PDMS surface is responsible for the increase in the static friction, while the hydrophobic recovery effect contributes to the decrease. The static friction between NWs and PDMS is of critical relevance to many device applications of NWs including NW-based flexible/stretchable electronics, NW assembly and nanocomposites (e.g., supercapacitors). Our results will enable quantitative interface design and control for such applications. | 10.1021/nn202343w |
pubmed_922_5928 | Genomic DNA is framed by additional layers of information, referred to as the epigenome. Epigenomic marks such as DNA methylation, histone modifications, and histone variants are concentrated on specific genomic sites, where they can both instruct and reflect gene expression. How this information is maintained, notably in the face of transcription, is not completely understood. Specifically, the extent to which modified histones themselves are retained through RNA polymerase II passage is unclear. Here, we show that several histone modifications are mislocalized when the transcription-coupled histone chaperones FACT or Spt6 are disrupted in Saccharomyces cerevisiae. In the absence of functional FACT or Spt6, transcription generates nucleosome loss, which is partially compensated for by the increased activity of non-transcription-coupled histone chaperones. The random incorporation of transcription-evicted modified histones scrambles epigenomic information. Our work highlights the importance of local recycling of modified histones by FACT and Spt6 during transcription in the maintenance of the epigenomic landscape. | 10.1016/j.celrep.2019.06.097 |
pubmed_687_2751 | OBJECTIVE
Recent studies indicated that long non-coding RNA is involved in the formation of atherosclerosis, which is the pathological basis of coronary heart disease. Here, we reported the function and regulatory mechanism of RMRP in coronary atherosclerosis.
MATERIALS AND METHODS
qPCR was used to investigate the expression of IL-6, IL-8, RMRP, and miR-128-1-5P in coronary atherosclerosis and human vascular smooth muscle cells. Luciferase reporter assay confirmed the direct target effect of RMRP with miR-128-1-5P and miR-128-1-5P with Gadd45g on HEK293T. Western blot was used to detect protein expression in coronary atherosclerosis and human vascular smooth muscle cells.
RESULTS
RMRP expression and Gadd45g protein level were up-regulated in coronary atherosclerosis and human vascular smooth muscle cells, while miR-128-1-5P was down-regulated. RMRP downregulation remarkably inhibited the expression of IL-6, IL-8, and apoptosis related protein in human vascular smooth muscle cells after ox-LDL treatment. In addition, bioinformatics analysis and Luciferase report experiments confirmed that RMRP was the direct target of miR-128-1-5P. Moreover, miR-128-1-5P inhibitor reserved evidently the effect of IL-6, IL-8, and apoptosis related protein induced RMRP-si after treatment of human vascular smooth muscle cells with ox-LDL, implying RMRP negatively and directly regulated miR-128-1-5P in coronary atherosclerosis. More importantly, RMRP silencing increased Gadd45g protein level in human vascular smooth muscle cells. The same results were found when miR-128 was upregulated. Meanwhile, Gadd45g-si extremely reversed the result of IL-6, IL-8, and apoptosis related protein induced miR-128-1-5P inhibitor after treatment of human vascular smooth muscle cells with ox-LDL and Luciferase report experiments showed that Gadd45g was a direct target of miR-128-1-5P, implying Gadd45g negatively and directly regulated miR-128-1-5P in coronary atherosclerosis. Furthermore, liraglutide restrained evidently the expression of IL-6, IL-8, and apoptosis related protein in coronary atherosclerosis. After all, these results showed that liraglutide could regulate RMRP/miR-128-1-5P/Gadd45g signal pathway to improve coronary atherosclerosis.
CONCLUSIONS
Liraglutide could curb the expression of inflammatory cytokines and apoptosis related protein in coronary atherosclerosis by regulating RMRP/miR-128-1-5P/Gadd45g signaling pathway, providing a new potential strategy for the treatment of coronary atherosclerosis. | 10.26355/eurrev_202003_20545 |
pubmed_291_22414 | The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma and tumours, a new and important cause has been identified as being responsible for the so-called idiopathic male infertility: oxidative stress. Oxidative Stress (OS) is a condition that occurs when the production of Reactive Oxygen Species (ROS) overwhelms the antioxidant defense produced against them. In male reproductive pathological conditions, the OS significantly impairs spermatogenesis and sperm function, which may lead to male infertility. Reactive Oxygen Species (ROS) known as free radicals are oxidizing agents generated as a result of metabolism of oxygen and have at least one unpaired electron that make them very reactive species. Spermatozoa generate Reactive Oxygen Species (ROS) in physiological amounts, which play a role in sperm functions during sperm capacitation, Acrosome Reaction (AR) and oocyte fusion, but they need to be controlled and their concentrations maintained at a level that is not deleterious to the cells. Administration of antioxidants in patients with 'male factor' infertility has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the role of free radicals in normal and abnormal sperm function leading to male infertility. The purpose of the present review is to address the relationship between ROS and idiopathic male factor infertility. | 10.3923/pjbs.2010.413.422 |
pubmed_515_694 | A mass balance study was performed under controlled field conditions to investigate the phytoremediation of perchloroethylene (PCE) by hybrid poplar trees. Water containing 7-14 mg L(-1) PCE was added to the test bed. Perchloroethylene, trichloroethylene, and cis-dichloroethylene were detected in the effluent at an average of 0.12 mg L(-1), 3.9 mg L(-1), and 1.9 mg L(-1), respectively. The total mass of chlorinated ethenes in the water was reduced by 99%. Over 95% of the recovered chlorine was as free chloride in the soil, indicating near-complete dehalogenation of the PCE. Transpiration, volatilization, and accumulation in the trees were all found to be minor loss mechanisms. In contrast, 98% of PCE applied to an unplanted soil chamber was recovered as PCE in the effluent water or volatilized into the air. These results suggest that phytoremediation can be an effective method for treating PCE-contaminated groundwater in field applications. | 10.1016/j.envpol.2009.02.033 |
pubmed_1027_13363 | Vernier acuity for illusory line targets induced by gaps in a horizontal grating was measured in the presence of real and illusory flanks. In a 500 msec presentation forced choice task, observers judged the position of a comparison illusory line positioned 3 min arc below the target. The results show that illusory lines are capable of interacting with real lines in spatial localization. Thus, they provide psychophysical evidence for a common localization mechanism that supports real and illusory contour definitions. The results further show a sensitivity of the visual system to the contrast polarity of real lines. This sensitivity was absent for illusory lines. The present findings are discussed in terms of their relationship to physiological findings, and in terms of their potential to constrain computational models that account for illusory contour brightness. | 10.1016/s0042-6989(96)00186-1 |
pubmed_269_18918 | The metro engineering is in an environment rich in stray current and groundwater, which will accelerate concrete corrosion. In this study, the corrosion of cement-based materials, under stray current, consisting of direct current, was investigated, and the effects of stray current magnitude, water-binder ratio, fly ash, and silica fume on its corrosion were analyzed. The results show that, as the energisation duration of the stray current increases, the mass of the cathode side leachables increases, and the compressive strength of the cement-based materials decreases overall; at 120 d of stray current, the water-binder ratio of 0.50 shows the least reduction in strength, compared to the others; the mass of cathode side leachables decrease significantly with the increase in fly ash content; when fly ash content is 15%, the mass of cathode side leachables is the least, and the decrease in the compressive strength at 120 d of stray current is the smallest. At 10% silica fume content, the mass of the cathode side leachables is the least, and the decrease in the compressive strength of the cement-based materials at 120 d of stray current is the smallest. In general, the corrosion resistance is relatively good at 15% fly ash content and 10% silica fume content under stray current. | 10.3390/ma15062279 |
pubmed_521_7567 | The interaction of antibodies from blood sera of patients with autoimmune pathology, systemic lupus erythematosus with oligoribonucleotides was studied. The RNA-hydrolyzing activity was shown to be an intrinsic property of autoantibodies. Enzymic activity of antibodies in hydrolysis of poly(U) was estimated at 20-40% of that of RNase A. In contrast to known eukaryotic RNases, the autoantibodies possess a specific RNA-hydrolyzing activity for oligo r(A). The RNA-nicking activity of antibodies in hydrolysis of oligoadenylates was more higher than with hydrolysis of oligo d(A). Optimal conditions of r(pA)13 hydrolysis were selected, including the optimal of pH = 8.7. | pubmed_521_7567 |
pubmed_499_22879 | BACKGROUND
Current guidelines consider T-DM1 the standard 2nd line therapy for HER2 positive metastatic breast cancer (MBC) patients following trastuzumab (T) + pertuzumab (P) and taxane 1st line treatment. Despite this, there are no prospective studies supporting this sequence.
METHODS
We performed a meta-analysis using real world data to determine the efficacy of T-DM1 after 1st line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the EMILIA phase III pivotal trial.
RESULTS
Seven studies were eligible. The meta-analysis showed a combined 1-year PFS risk difference for T-DM1 efficacy after TP in 2nd or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p = 0.07), with low heterogeneity among studies (I2 0.01%, p = 0.836). Considering the four studies on T-DM1 in 2nd line setting, 1-year PFS risk was -0.034 (95% CI -0.207 - 0,139; p = 0.701) (I2 0.01%, p = 0.91).
CONCLUSION
Overall, the efficacy of T-DM1 after TP seems to be similar to that previously reported in the EMILIA trial. In the second line setting, data are not mature enough to confirm T-DM1 efficacy in TP pre-treated population. | 10.1186/s12885-022-09556-7 |
pubmed_215_15345 | Sjögren's syndrome is a multisystem inflammatory rheumatic disease that is classified into primary and secondary forms, with cardinal features in the eye (keratoconjunctivitis sicca) and mouth (xerostomia). The aetiology behind this autoimmune exocrinopathy is probably multifactorial and influenced by genetic as well as by environmental factors that are as yet unknown. A genetic predisposition to Sjögren's syndrome has been suggested on the basis of familial aggregation, animal models and candidate gene association studies. Recent advances in molecular and genetic methodologies should further our understanding of this complex disease. The present review synthesizes the current state of genetics in Sjögren's syndrome. | 10.1186/ar599 |
pubmed_1050_7414 | We retrospectively investigated the pharmacokinetics and exposure-efficacy/safety relationships of single-agent atezolizumab based on tissue tumor mutational burden (tTMB) status (high vs low [≥16 vs <16 mutations/megabase]) in a pan-tumor population from seven clinical trials. Data sources included the OAK, POPLAR, BIRCH, FIR, IMvigor210, IMvigor211, and PCD4989g studies; 986 of 2894 treated patients (34%) had TMB data. Exposure metrics were obtained using a prior two-compartment intravenous-infusion population-pharmacokinetics model, merged with prognostic, biomarker, efficacy, and safety variables. Baseline demographic/clinical characteristics and prognostic factors were well balanced between patients with high (n = 175) and low (n = 811) tTMB. Exposure was similar in the high- and low-tTMB subgroups, with no difference seen in the evaluable vs total treated populations. The objective response rate (ORR) was 29.7% vs 13.4%, complete response rate was 6.9% vs 3.2%, and median duration of response (95% CI) was 29.0 (18.6-NE) months vs 15.9 (12.5-20.5) months for patients with high-tTMB vs low-tTMB tumors, respectively. A flat exposure-efficacy relationship was seen for ORR in patients with high-tTMB based on the cycle 1 minimum atezolizumab concentration and area under the serum concentration time curve (AUC). A nonsignificant exposure-safety profile was seen for grade 3/4 adverse events and adverse events of special interest based on the AUC of atezolizumab in the high-tTMB population. tTMB is an additional predictive biological factor affecting response to atezolizumab, and quantitative investigations of atezolizumab exposure and relationships of exposure with safety and efficacy support the use of a 1200-mg, every 3-week regimen in a tumor-agnostic high-tTMB population. | 10.1002/prp2.685 |
pubmed_56_10245 | Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. | 10.1096/fj.201500042 |
pubmed_684_2972 | The cumulus-oocyte-complexes (COCs) recovery rates with respect to reproductive status per sei (Balaenoptera borealis) and Bryde's (B. edeni) whales were determined in Experiment 1. The number of COCs recovered ranged from 16.0 to 30.6 and from 6.7 to 26.8 per sei and Bryde's whales, respectively. The effects of COCs grades and protein supplementation in embryo culture medium on development of in vitro fertilized (IVF) embryos were evaluated in sei and Bryde's whales in Experiment 2. The COCs were classified into either Grade A (COCs with five or more layers of compact cumulus cells) or Grade B (COCs with less than five layers of compact or expanded cumulus cells) before being cultured for IVM. The cleavage (12.0 to 19.5%), 4-cell (8.0 to 12.0%) and 8-cell (4.0 to 8.0%) formation rates in sei whales did not vary significantly between embryos derived from either grade A or B oocytes and between embryos cultured in either fetal whale serum (FWS)- or bovine serum albumin (BSA)-supplemented medium. The cleavage (4.0 to 14.8%), 4-cell (0.0 to 7.5%) and 8-cell (0.0 to 2.6%) formation rates in Bryde's whales did not vary significantly between embryos derived from either grade A or B oocytes and between embryos cultured in either FWS- or BSA-supplemented medium. The grade B oocytes cultured in FWS-supplemented medium developed to morula stage (1.1%) in sei whales. In conclusion, the present study indicates that IVF in sei whales is possible to achieve cleaved embryos developing to morula stage. This is the first in vitro embryo production attempt in sei and Bryde's whales. | 10.1017/S0967199408004887 |
pubmed_257_14870 | The paper describes the technique of 'LLETZ' (large loop excision of the transformation zone), a new method of management for women with an abnormal cervical smear which offers the advantages of conization with those of local destruction. A large loop of thin wire forms a diathermy electrode that allows deep excision of the transformation zone with minimal tissue damage. The tissue removed can be examined histologically. The technique was used to investigate and treat 111 women with abnormal smears referred to the Bristol Royal Infirmary during 1986. Microinvasive disease was revealed in one woman where it was not suspected by cytology or colposcopic examination. Of 102 women followed up for at least 1 year by cytology, colposcopy and, where appropriate, histology, two women were found to have residual/recurrent cervical intraepithelial neoplasia. | 10.1111/j.1471-0528.1989.tb03380.x |
pubmed_389_24312 | Developing and managing measures of quality of life (QoL) require attention to a range of broader concepts, in addition to meeting validation requirements. The aim of this review is to describe development and experience in Cardiff of these concepts and to inform users of Cardiff quality of life tools of aspects of their origin, for the benefit of developers of novel QoL measures or other patient reported outcome measures. Publications from the Cardiff team over the last three decades are used to illustrate descriptions of concepts involved in developing and managing QoL measures. The concepts are grouped into three main themes: (A) Design of tools: measurement ability turns ideas into science, QoL measurement based on patient experience, the need for tools to be clinically practical and useful with meaningful scores, different ages need tailored tools. (B) Practical management of tools: enabling ease of access, maintenance of single version, translation validity, enabling access to postpublication experience and further validation. (C) Promoting wider understanding of QoL: examples include educate thinking with disease severity definition; heighten awareness of broader burden, family impact, the time dimension and the new word quimp. The development and management of QoL and other outcome measures involves attention to a wide range of other issues, in addition to meeting validation requirements. | 10.1111/jdv.14254 |
pubmed_1105_5188 | Metabolic syndrome, indicated by insulin resistance/hyperinsulinemia, obesity, central obesity, atherogenic dyslipidemia, and hypertension, contributes to atherosclerotic cardiovascular disease. However, it is controversial whether the indicators of metabolic syndrome are related to subclinical atherosclerosis collectively or individually. Whether there is any gender-based difference in the mechanisms of metabolic syndrome-induced atherosclerosis progression is also unknown. Two models were compared in this study. Model 1 assumes that a latent factor, metabolic syndrome per se, impacts subclinical atherosclerosis (collective effects model); Model 2 assumes the effect of the syndrome is mediated through its indicators (individual effects model). Data were obtained from the Los Angeles Atherosclerosis Study. The cohort consists of 573 adults (age, 40-60 years) who were asymptomatic for cardiovascular disease. Subclinical atherosclerosis was assessed by measuring common carotid artery intima-media thickness (CCA-IMT) using B-mode ultrasound. Three examinations were completed at 1.5-year intervals from 1995-1999. The analyses were performed with SAS 8.2 and AMOS 4.0. The results showed that atherogenic effects of metabolic syndrome were mediated through its indicators; there were gender-based differences in the mechanisms of metabolic syndrome-induced atherosclerosis. Central obesity was significantly associated with the baseline IMT for men only, whereas triglycerides were significantly associated with the progression of IMT for women only. Systolic blood pressure was significantly associated with the baseline and progression for both men and women. However, fasting insulin was not found to be significantly associated with the baseline and progression of IMT in the multivariate model, although it was significantly associated with other components of metabolic syndrome. | 10.5551/jat.13.46 |
pubmed_789_3795 | In Huntington's disease (HD), the mutant huntingtin (mhtt) protein is associated with striatal dysfunction and degeneration. Excitotoxicity and early synaptic defects are attributed, in part, to altered NMDA receptor (NMDAR) trafficking and function. Deleterious extrasynaptic NMDAR localization and signalling are increased early in yeast artificial chromosome mice expressing full-length mhtt with 128 polyglutamine repeats (YAC128 mice). NMDAR trafficking at the plasma membrane is regulated by dephosphorylation of the NMDAR subunit GluN2B tyrosine 1472 (Y1472) residue by STriatal-Enriched protein tyrosine Phosphatase (STEP). NMDAR function is also regulated by calpain cleavage of the GluN2B C-terminus. Activation of both STEP and calpain is calcium-dependent, and disruption of calcium homeostasis occurs early in the HD striatum. Here, we show increased calpain cleavage of GluN2B at both synaptic and extrasynaptic sites, and elevated extrasynaptic total GluN2B expression in the YAC128 striatum. Calpain inhibition significantly reduced extrasynaptic GluN2B expression in the YAC128 but not wild-type striatum. Furthermore, calpain inhibition reduced whole-cell NMDAR current and the surface/internal GluN2B ratio in co-cultured striatal neurons, without affecting synaptic GluN2B localization. Synaptic STEP activity was also significantly higher in the YAC128 striatum, correlating with decreased GluN2B Y1472 phosphorylation. A substrate-trapping STEP protein (TAT-STEP C-S) significantly increased VGLUT1-GluN2B colocalization, as well as increasing synaptic GluN2B expression and Y1472 phosphorylation. Moreover, combined calpain inhibition and STEP inactivation reduced extrasynaptic, while increasing synaptic GluN2B expression in the YAC128 striatum. These results indicate that increased STEP and calpain activation contribute to altered NMDAR localization in an HD mouse model, suggesting new therapeutic targets for HD. | 10.1093/hmg/dds154 |
pubmed_1031_12310 | Atrial fibrillation (AF) is the most common observed cardiac arrhythmia and is the most frequent condition associated with thromboembolic events in patients with or without mitral valve disease. The source of cardiac emboli is the left atrium, the left atrial appendage or, less frequently, the left ventricle. Emboli may also originate from aortic atherosclerotic plaques. It is important to identify patients at risk in order to perform the appropriate therapy. Risk stratification is multiparametric, being based on clinical, laboratory, and echocardiographic data. Several trials have pointed out the role of echocardiography in the evaluation of anatomic and functional parameters associated with thromboembolic risk. Transthoracic echocardiography (TTE) does not provide sufficient information regarding posterior cardiac structures, being its sensitivity in detecting thrombi relatively low (33-72%). Transesophageal echocardiography (TEE) in contrast, has an almost 100% sensitivity; this technique is, therefore, mandatory in patients with AF for an adequate prevention of thromboembolism. The echocardiographic information joined with clinical features allow to stratify, in a proper way, the risk of every single patient. | pubmed_1031_12310 |
pubmed_528_11026 | Most variables associated with survival after cancer surgery are fixed when we see the patient. One variable over which we have control is the surgical margin. We begin by reviewing the definitions of a positive surgical margin, and then explore potential inaccuracies in obtaining a biopsy and reasons for recurrence after obtaining a free surgical margin. Research in improving the diagnostic accuracy of surgical margins is discussed. Finally, the prognostic significance of surgical margins is reviewed. | 10.1097/01.coc.0000264178.06004.46 |
pubmed_675_26175 | BACKGROUND INFORMATION
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces an alteration in the endomembrane system of the mammalian cells. In this study, we used transmission electron microscopy and electron tomography to investigate the main structural alterations in the cytoplasm of Vero cells infected with a SARS-CoV-2 isolate from São Paulo state (Brazil).
RESULTS
Different membranous structures derived from the zippered endoplasmic reticulum were observed along with virus assembly through membrane budding. Also, we demonstrated the occurrence of annulate lamellae in the cytoplasm of infected cells and the presence of virus particles in the perinuclear space.
CONCLUSIONS AND SIGNIFICANCE
This study contributes to a better understanding of the cell biology of SARS-CoV-2 and the mechanisms of the interaction of the virus with the host cell that promote morphological changes, recruitment of organelles and cell components, in a context of a virus-induced membrane remodelling. | 10.1111/boc.202000146 |
pubmed_444_5371 | The TabZIP15 gene encoding a 396 amino acid (aa) polypeptide in the fungus Trichoderma asperellum ACCC30536 was cloned and characterised. The protein includes a basic region motif (NR-x2-QR-x2-R) and has a pillar-like structure. The 25 basic region/leucine zipper transcription factors (TFs) identified in the T. asperellum genome were divided into YAP (14 TFs), ATF2 (5), GCN4 (2), Zip1 (2), BRLZ (1) and u1 (1) subfamilies based on conserved domains. T. asperellum was cultured in minimal media (MM) control, C-Hungry and N-Hungry medium (to simulate nutrient competition and interaction with pathogens, respectively), and differential expression analysis showed that 14 TabZIP genes (including TabZIP15) were significantly altered under both conditions; TabZIP23 responded strongly to N-Hungry media and TabZIP24 responded strongly to C-Hungry media. However, only YAP genes TabZIP15, TabZIP12 and TabZIP2 were significantly upregulated under both conditions, and expression levels of TabZIP15 were highest. T. asperellum was also cultured in the presence of five fungal pathogenic toxins, and RT-qPCR results showed that TabZIP15 was significantly upregulated in four of the five toxin stress conditions (MM + Rhizoctonia solani, MM + Fusarium oxysporum, MM + Alternaria alternata and MM + Cytospora chrysosperma). | 10.1038/s41598-020-72226-w |
pubmed_765_25729 | Rice (Oryza sativa L.) is a staple crop with agricultural traits that have been intensively investigated. However, despite the variety of mutant population and multi-omics data that have been generated, rice functional genomic research has been bottlenecked due to the functional redundancy in the genome. This phenomenon has masked the phenotypes of knockout mutants by functional compensation and redundancy. Here, we present an intuitive tool, CRISPR applicable functional redundancy inspector to accelerate functional genomics in rice (CAFRI-Rice; cafri-rice.khu.ac.kr). To create this tool, we generated a phylogenetic heatmap that can estimate the similarity between protein sequences and expression patterns, based on 2,617 phylogenetic trees and eight tissue RNA-sequencing datasets. In this study, 33,483 genes were sorted into 2,617 families, and about 24,980 genes were tested for functional redundancy using a phylogenetic heatmap approach. It was predicted that 7,075 genes would have functional redundancy, according to the threshold value validated by an analysis of 111 known genes functionally characterized using knockout mutants and 5,170 duplicated genes. In addition, our analysis demonstrated that an anther/pollen-preferred gene cluster has more functional redundancy than other clusters. Finally, we showed the usefulness of the CAFRI-Rice-based approach by overcoming the functional redundancy between two root-preferred genes via loss-of-function analyses as well as confirming the functional dominancy of three genes through a literature search. This CAFRI-Rice-based target selection for CRISPR/Cas9-mediated mutagenesis will not only accelerate functional genomic studies in rice but can also be straightforwardly expanded to other plant species. | 10.1111/tpj.14926 |
pubmed_288_6235 | Focal dermal hypoplasia (FDH) is an X-linked dominant disorder characterized by patchy dermal hypoplasia with digital, ocular and dental abnormalities. Very recently, mutations in the PORCN gene were demonstrated to cause FDH. Here, we described three unrelated Thai girls who were sporadic cases of FDH. One of them had unilateral athelia, which has never been described in FDH. Mutation analysis by polymerase chain reaction sequencing the entire coding regions of PORCN successfully revealed three potentially pathogenic mutations, c.373+1G>A, c.737_738insA and c.1094G>A (p.R365Q). One was found in each of three patients. In addition, another sequence variant c.682C>T (p.R228C) with an inconclusive role was found in one patient and her unaffected mother. The two missense mutations were not detected in at least 100 ethnic-matched control chromosomes, and all four mutations had never been previously described. X chromosome inactivation studies showed random patterns in all of them. This study demonstrates that PORCN is the gene responsible for FDH across different populations and extends the total number of confirmed mutations to 26. | 10.1111/j.1399-0004.2008.00975.x |
pubmed_861_11435 | Firefly luciferase has been widely used in biotechnology and biophotonics due to photon emission during enzymatic activity. In the past, the effect of amino acid substitutions (mutants) on the enzymatic activity of firefly luciferase has been characterized by the Michaelis constant, KM. The KM is obtained by plotting the maximum relative luminescence units (RLU) detected for several concentrations of the substrate (luciferin or luciferyl-adenylate). The maximum RLU is used because the assay begins to violate the quasi-steady state approximation when RLU decays as a function of time. However, mutations also affect the time to reach and decay from the maximum RLU. These effects are not captured when calculating the KM. To understand changes in the RLU kinetics of firefly luciferase mutants, we used a Michaelis-Menten model with the non-steady state approximation. In this model, we do not assume that the amount of enzyme-substrate complex is at equilibrium throughout the course of the experiment. We found that one of the two mutants analyzed in this study decreases not only the dissociation rate ( koff) but also the association rate ( kon) of luciferyl-adenylate, suggesting the narrowing of the structural pocket containing the catalytic amino acids. Furthermore, comparative analysis of the nearly complete oxidation of luciferyl-adenylate with wild-type and mutant firefly luciferase reveals that the total amount of photons emitted with the mutant is 50-fold larger than that with the wild type, on average. These two results together indicate that the slow supply of luciferyl-adenylate to the enzyme increases the total number of photons emitted from the substrate, luciferyl-adenylate. Analysis with the non-steady state approximation model is generally applicable when enzymatic production kinetics are monitored in real time. | 10.1021/acs.biochem.9b00272 |
pubmed_525_21327 | An electrostatic truck-mounted spray system (Spectrum, Houston, TX) and a nonelectrostatic spray system (Micro-Gen G-4, San Antonio, TX) were tested to determine the feasibility of electrostatically charging Aqua Reslin, a water-based permethrin insecticide, and ascertain whether an electrostatic charge would increase the efficiency of Aqua Reslin against Anopheles quadrimaculatus adults. Parameters tested for both machines included mean mass median diameter (MMD) of droplets, number of drops per cm2, and posttreatment percent mortality at 1, 12, and 24 h. Results indicated that the electrostatically charged droplets produced greater mortality at each distance and hour posttreatment. Correlation coefficients and linear equations were calculated for distance-mortality, MMD-mortality, drops per cm2-mortality, distance-drops per cm2, distance-MMD, and MMD-drops per cm2. Results indicated that the electrostatic drops demonstrated strong correlations between each paired variable, whereas the nonelectrostatic drops showed poor correlation between drops per cm2-mortality, distance-drops per cm2, and MMD-drops per cm2. However, from this trial, these differences cannot be attributed purely to the electrostatic charge because significant differences in droplet size can affect spray performance. | pubmed_525_21327 |
pubmed_543_17734 | This study examined the presence of rhythmic fluctuations in vigilance tasks. The hypothesis was that individual attentional performance is subject to rhythmic variation beyond a linear decrease over time. In the first study the reaction times to an acoustic stimulus were recorded. The analysis of the individual periodograms indicated a rhythm in attentional capacity with periods ranging from 5 to 30 min. These findings indicate that considerable individual variation can be accounted for by considering individual periodicity in performance. Although marked individual differences between subjects are present, the rhythmic fluctuations are stable within each subject and between experimental sessions. | 10.1016/0301-0511(94)00962-W |
pubmed_292_24055 | The effect of different ultraviolet radiation (UVR) treatments combining PAR (P), UVA (A) and UVB (B) on the molecular physiology of Dunaliella tertiolecta was studied during 6 days to assess the response to chronic UVR exposure. UVR reduced cell growth but did not cause cell death, as shown by the absence of SYTOX Green labeling and cellular morphology. However, caspase-like enzymatic activities (CLs), (regarded as cell death proteases), were active even though the cells were not dying. Maximal quantum yield of fluorescence (Fv /Fm ) and photosynthetic electron transport rate (ETR) dropped. Decreased nonphotochemical quenching (NPQ) paralleled a drop in xanthophyll cycle de-epoxidation under UVB. Reactive oxygen species (ROS) and D1 protein accumulation were inversely correlated. PAB exhibited elevated ROS production at earlier times. Once ROS decayed, D1 protein recovered two-fold compared with P and PA at later stages. Therefore, PsbA gene was still transcribed, suggesting ROS involvement in D1 recovery by its direct effect on mRNA-translation. We add evidence of an UVB-induced positive effect on the cells when P is present, providing photoprotection and resilience, by means of D1 repair. This allowed cells to survive. The photoprotective mechanisms described here (which are counterintuitive in principle) conform to an important ecophysiological response regarding light stress acclimation. | 10.1111/php.12502 |
pubmed_792_7191 | Acute hyperoxic lung injury remains a major factor in the development of chronic lung disease in neonates. A critical step in the repair of acute lung injury is the proliferation of type II alveolar epithelial cells. Type II cell proliferation is stimulated by keratinocyte growth factor (KGF), an epithelial cell-specific mitogen. We sought to investigate KGF mRNA expression in relation to type II cell proliferation during hyperoxic lung injury. We studied a previously described newborn (NB) rabbit model of acute and chronic hyperoxic injury [C. T. D'Angio, J. N. Finkelstein, M. B. LoMonaco, A. Paxhia, S. A. Wright, R. B. Baggs, R. H. Notter, and R. M. Ryan. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L720-L730, 1997]. NB rabbits were placed in 100% O2 for 9 days and then recovered in 60% O2. RT-PCR was used to synthesize and amplify a 267-bp fragment of rabbit KGF cDNA from whole lung RNA. KGF mRNA expression was analyzed by ribonuclease protection assay, and mRNA abundance was quantified by phosphorimaging. Proliferating cell nuclear antigen immunohistochemistry was used on lung sections to identify proliferating cells. The rabbit partial cDNA sequenced was >95% homologous to human cDNA, and all amino acids were conserved. Whole lung KGF mRNA expression was increased 12-fold after 6 days of hyperoxia compared with control lungs, and remained increased throughout the 100% O2 exposure period. Proliferating cell nuclear antigen immunohistochemistry showed an increase in type II cell proliferation after 8-12 days of hyperoxia. NB rabbits exposed to hyperoxic injury exhibit increased whole lung KGF mRNA expression preceding type II cell proliferation. KGF may be an important mitogen in the regulation of alveolar epithelial repair after hyperoxic lung injury. | 10.1152/ajplung.1999.276.1.L105 |
pubmed_1039_3590 | Acridine orange (AO), ethidium bromide (EB), ethyl methanesulfonate (EMS) and 8- ethoxycaffeine ( EOC ) were fed to larvae of Drosophila melanogaster in order to test their capacity for the induction of meiotic recombination in males. Our results show that AO and EB increase significantly the male recombination frequencies. No relationship between chromosome breakage ability and male recombination induction was found since EMS and EOC , two effective chromosome-breaking agents, were unable to increase the male recombination. | 10.1016/0027-5107(84)90003-4 |
others_416_1421 | : Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. Methods: The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. Results: Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1β, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. Conclusion: In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling. © 2023, The Author(s) | 10.1186/s10020-022-00599-x |
pubmed_371_14555 | The prognostic implication of a right ventricular aneurysm after a first acute myocardial infarction (AMI) was assessed on a series of 137 AMI patients 12 of whom had a right ventricular aneurysm detected at radionuclide angiocardiography. The follow-up lasted 36 months. Mortality was 50 and 18.4% in patients with and without right ventricular aneurysm, respectively (p less than 0.02). Groups did not differ in age, male-to-female ratio, AMI site, left ventricular ejection fraction (LVEF), peak filling rate (PFR), left ventricular size. A multivariate logistic analysis showed that only three out of ten clinical and functional variables qualified to be independent predictors of death: right ventricular aneurysm (odd ratio = 2.48, confidence limits = 1.21-4.98), LVEF less than 52% (odd ratio = 1.91, confidence limits = 1.03-3.48), abnormal terminal P wave forces (odd ratio = 1.72, confidence limits = 1.07-2.75). The analysis of single case histories did not provide a clue to clarify the reasons accounting for the negative prognostic implication of a right ventricular aneurysm. In conclusion, a significant positive relationship between right ventricular aneurysm and mortality after AMI has been demonstrated; further study is needed to clarify the relevant mechanisms. | 10.1159/000174869 |
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