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pubmed_815_7110 | The autoimmune syndrome in MRL/lpr mice resembles human lupus, both in its serologic and immunopathologic characteristics. The contribution of IL-1 to high-level Ig production in the MRL/lpr model is poorly understood. We investigated the effect of treating B-cell-enriched, or, B plus T cell suspensions derived from either pre-disease or diseased lupus-prone MRL/lpr mice with IL-1 beta or IL-1 receptor antagonist (IL-1Ra). Disparate patterns of IgG production by B cells and B plus T cells derived from diseased versus pre-diseased MRL/lpr mice was observed following treatment with IL-1 beta. Remarkably, IL-1 beta caused significant suppression in IgG production by B cells derived from diseased MRL/lpr mice as compared to B cells derived from pre-disease mice. In mix-and-match experiments with B plus T cells from pre-disease and diseased MRL/lpr mice, both T cell help and B cell hyperactivity, originating in diseased MRL/lpr mice were found to be important factors in high-level IgG production in diseased MRL/lpr mice. Furthermore, IL-1Ra treatment of B plus T cell co-cultures derived from diseased MRL/lpr mice was able to significantly suppress IgG production, whereas, IL-1Ra treatment of B plus T cell co-cultures derived from pre-disease MRL/lpr mice demonstrated virtually no suppression in IgG production. Collectively, these results indicate a potentially important but complex role for IL-1 in influencing high-level IgG production in MRL/lpr mice with established disease. | 10.3109/08820139409066824 |
pubmed_611_18248 | Following uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial phagosome and become available for immune recognition by CD1-restricted T cells. The aim of this study was to explore the possibility that lipoproteins might similarly escape from the phagosome and act as immune targets in cells infected with live mycobacteria. We have focused on a 19-kDa lipoprotein from Mycobacterium tuberculosis that was previously shown to be recognized by CD8(+) T cells. The 19-kDa Ag was found to traffic separately from live mycobacteria within infected macrophages by a pathway that was dependent on acylation of the protein. When expressed as a recombinant protein in rapid-growing mycobacteria, the 19-kDa Ag was able to deliver peptides for recognition by MHC class I-restricted T cells by a TAP-independent mechanism. Entry into the class I pathway was rapid, dependent on acylation, and could be blocked by killing the mycobacteria by heating before infection. Although the pattern of 19-kDa trafficking was similar with different mycobacterial species, preliminary experiments suggest that class I presentation is more efficient during infection with rapid-growing mycobacteria than with the slow-growing bacillus Calmette-Guérin vaccine strain. | 10.4049/jimmunol.166.1.447 |
pubmed_279_13051 | With the recent pressure to control health care expenditures, the costs of patient participation in clinical trials, especially in their earliest phases, have come under increasingly intense scrutiny. We therefore reviewed our experience in patients with acute promyelocytic leukemia (APL) who were treated during the first US trial of a new experimental drug, all-trans retinoic acid (RA). The purpose of the review was to evaluate parameters of patient morbidity and financial cost associated with the use of all-trans RA compared with standard chemotherapy for induction of complete remission in newly-diagnosed patients with APL. We retrospectively compared outcomes of consecutive patients treated during the first 2 years of our studies that used all-trans RA for remission induction (1990-1992) with an identical number of patients consecutively treated with standard chemotherapy (cytosine arabinoside plus an anthracycline) during the immediately preceding period (1985-1990). Responding patients in both groups received post-remission chemotherapy. Evaluation parameters included transfusions of packed red blood cells and platelets, use of anti-bacterial and anti-fungal drugs, duration of fever, time to remission, length of hospital stay, hospital charges, and both overall and relapse-free survival. Thirty patients were evaluated in each group. Complete remission was achieved in 26 patients (87%) treated with all-trans RA, and 24 patients (77%) treated with chemotherapy (p = 0.5). In the chemotherapy group, there were five early deaths (four from hemorrhage, one from sepsis); one other patient was resistant to treatment and died at 6 months. Four patients in the all-trans RA group died prior to response from complications of the 'retinoic acid syndrome'. The median time to complete response by all criteria was 41 days (range, 18-78) for the all-trans RA group and 50 days (range, 24-121) for patients who received conventional chemotherapy (p = 0.2). Looking only at patients who achieved remission, chemotherapy-treated patients required a significantly greater number of platelet transfusions (medians, 14 vs. 4; p < 0.001) and packed red blood cell transfusions (15 vs. 4; p < 0.001). Patients who received chemotherapy also experienced a significantly larger number of days with fever (13 vs. 6; p = 0.01) that was reflected in a greater median number of days on combination antibiotics (35 vs. 21; p = 0.001) and Amphotericin B (20 vs. 0; p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) | pubmed_279_13051 |
pubmed_615_2291 | Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposing roles in control of DNA methylation status. Members of the miR-29 family directly inhibited DNA methyltransferases and two major factors involved in DNA demethylation, namely tet methylcytosine dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29 upregulated the global DNA methylation level in some cancer cells and downregulated DNA methylation in other cancer cells, suggesting that miR-29 suppresses tumorigenesis by protecting against changes in the existing DNA methylation status rather than by preventing de novo methylation of DNA. | 10.3390/ijms140714647 |
pubmed_809_22615 | The use of multi-channel coils can efficiently increase the signal-to-noise ratio (SNR) of magnetic resonance spectroscopy data if the signals from multiple channels are optimally combined. Combining multi-channel signals requires proper alignment of the phases of the signals from each of the elements of the coil and then accurately weighting the summation of those signals. We present a procedure for acquiring proton magnetic resonance spectroscopic imaging (MRSI) data using an eight-channel coil without water suppression and a rapid and robust method that uses unsuppressed water signal as a reference both for aligning the phases and for weighting the summation of signals that originate in the multiple coil elements. We use both computer simulation and in vivo proton MRSI data to demonstrate the advantages of our method for optimizing the SNR of the combined signal compared with the SNRs of signals that were acquired either using a standard volume head coil or using an eight-channel coil with a metabolite signal as the reference for combination. | 10.1016/j.mri.2007.01.005 |
pubmed_647_5633 | This paper reports a facile method for the preparation of lyso-GM1 [Gal beta1-->3GalNAc beta1--> 4(Neu5Ac alpha2-->3)Galbeta1-->4Glc beta1-->1'-sphingosine] and lyso-GM2 [GalNAc beta1-->4(Neu5Ac alpha2-->3)Gal beta1-->4Glc beta1-->sphingosine], respectively, from GM1 [Galbeta1-->3GalNAc beta1-->4(Neu5Ac alpha2-->3)Galbeta1-->4Glc beta1-->1'-Cer] and GM2[GalNAc beta1-->4(Neu5Ac alpha2-->3)Galbeta1-->4Glc beta1-->1'-Cer], using sphingolipid ceramide deacylase and high performance anion-exchange chromatography (HPAEC). The enzymatically released lyso-GM1 and/or lyso-GM2 was effectively separated from its parent ganglioside by HPAEC using a Mono Q HR 5/5 column with an Amersham Biosciences fast protein liquid chromatography system. The yield was almost quantitative and the separation completed in approximately 3 h. This method is more convenient and effective than the conventional method using alkaline hydrolysis and silicic acid chromatography to generate and purify lyso-gangliosides. | 10.1016/j.chroma.2005.04.058 |
others_413_38829 | Animal to human transmission of SARS-CoV-2 has not previously been reported in a zoo setting. A vaccinated African lion with physical limitations requiring hand feeding tested positive for SARS-CoV-2 after development of respiratory signs. Zoo employees were screened, monitored prospectively for development of symptoms, then re-screened as indicated, with confirmation by RT-PCR and whole-genome virus sequencing when possible. Trace-back investigation narrowed the source of infection to one of five people. Three exposed employees subsequently developed symptoms, two with viral genomes identical to the lions. Forward contact tracing investigation confirmed probable lion-to-human transmission.
Close contact with large cats is a risk factor for bidirectional zoonotic SARS-CoV-2 transmission that should be considered when occupational health and biosecurity practices at zoos are designed and implemented. SARS-CoV-2 rapid testing and detection methods in big cats and other susceptible animals should be developed and validated to facilitate timely implementation of One Health investigations | 10.1101/2023.01.29.23285159 |
pubmed_244_8331 | Immune checkpoint inhibitor (ICI) immunotherapy improved the survival of head and neck squamous cell carcinoma (HNSCC) patients. However, more than 80% of the patients are still resistant to this therapy. To test whether the efficacy of ICI therapy can be improved by vaccine-induced immunity, we investigated the efficacy of a tumor membrane-based vaccine immunotherapy in murine models of HNSCC. The tumors, grown subcutaneously, are used to prepare tumor membrane vesicles (TMVs). TMVs are then incorporated with glycolipid-anchored immunostimulatory molecules GPI-B7-1 and GPI-IL-12 by protein transfer to generate the TMV vaccine. This TMV vaccine inhibited tumor growth and improved the survival of mice challenged with SCCVII tumor cells. The tumor-free mice survived for several months, remained tumor-free, and were protected following a secondary tumor cell challenge, suggesting that the TMV vaccine induced an anti-tumor immune memory response. However, no synergy with anti-PD1 mAb was observed in this model. In contrast, the TMV vaccine was effective in inhibiting MOC1 and MOC2 murine oral cancer models and synergized with anti-PD1 mAb in extending the survival of tumor-bearing mice. These observations suggest that tumor tissue based TMV vaccines can be harnessed to develop an effective personalized immunotherapy for HNSCC that can enhance the efficacy of immune checkpoint inhibitors. | 10.3390/vaccines8020182 |
pubmed_257_901 | The homozygote deficit of alpha 1 antitrypsin (alpha 1 PI-ZZ) in patients frequently results in a premature development of emphysema in the lung due to incomplete protection against proteases. An active inhibitor substitution appears to be useful. The presented study proves the biological effect of alpha 1 antitrypsin infused into 8 patients. The results were an activity increase of leukocyte elastase and trypsin inhibition in serum as well as doubling of alpha 1 antitrypsin in sputum. This therapeutical conception (with a dose of 60 mg/kg body weight/week) results in an efficient protection. Inhibitors specific for mucosa are not influenced. An improvement of lung function during 6 weeks of intravenous therapy was not achieved. The progressive destruction of lung parenchyma can be probably prevented, however. | 10.1007/BF01741387 |
pubmed_353_14973 | PURPOSE OF REVIEW
The glomerular filtration barrier consists of fenestrated glomerular endothelium, podocyte foot processes/slit diaphragms, and intervening glomerular basement membrane. Its characterization as both a size and charge-selective barrier emerged from studies conducted decades ago. The charge selectivity phenomenon is receiving renewed attention now that the identities and mechanisms of synthesis of relevant molecules are known. Here we summarize studies employing genetic or other in-vivo strategies to investigate glomerular charge.
RECENT FINDINGS
Attention has focused on glomerular basement membrane heparan sulfate proteoglycans, long considered primary charge barrier components. Agrin contributes significantly to glomerular basement membrane charge but, like perlecan and collagen XVIII, is dispensable for glomerular structure and function. Disruption of glomerular heparan sulfate through transgenic methods or administration of heparanase in vivo provides further evidence against a role for heparan sulfate in glomerular function. Disruption of glomerular sialoproteins, however, causes proteinuria and indicates a critical role for these cell-associated glycoproteins in glomerular filtration.
SUMMARY
Recent in-vivo manipulations of glomerular heparan sulfate proteoglycans fail to reveal a crucial role for either them or their anionic charge in glomerular filtration. In contrast, cell-associated sialoproteins are clearly important, but whether their functions actually involve contributions to the charge barrier is unknown. | 10.1097/MNH.0b013e32830464de |
pubmed_28_15055 | Neutron diffraction techniques permit direct determination of the hydrogen (H) and deuterium (D) positions in crystal structures of biological macromolecules at resolutions of ∼1.5 and 2.5 Å, respectively. In addition, neutron diffraction data can be collected from a single crystal at room temperature without radiation damage issues. By locating the positions of H/D-atoms, protonation states and water molecule orientations can be determined, leading to a more complete understanding of many biological processes and drug-binding. In the last ca. 5 years, new beamlines have come online at reactor neutron sources, such as BIODIFF at Heinz Maier-Leibnitz Zentrum and IMAGINE at Oak Ridge National Laboratory (ORNL), and at spallation neutron sources, such as MaNDi at ORNL and iBIX at the Japan Proton Accelerator Research Complex. In addition, significant improvements have been made to existing beamlines, such as LADI-III at the Institut Laue-Langevin. The new and improved instrumentations are allowing sub-mm3 crystals to be regularly used for data collection and permitting the study of larger systems (unit-cell edges >100 Å). Owing to this increase in capacity and capability, many more studies have been performed and for a wider range of macromolecules, including enzymes, signalling proteins, transport proteins, sugar-binding proteins, fluorescent proteins, hormones and oligonucleotides; of the 126 structures deposited in the Protein Data Bank, more than half have been released since 2013 (65/126, 52%). Although the overall number is still relatively small, there are a growing number of examples for which neutron macromolecular crystallography has provided the answers to questions that otherwise remained elusive. | 10.1042/ETLS20170083 |
pubmed_330_18190 | Erectile dysfunction (ED) is a sexual disorder mainly caused by decrease in cellular concentration of cyclic guanosine monophosphate (cGMP), which is degraded by phosphodiesterase type-5 (PDE-5). As a potent therapeutic target, inhibitors such as Viagra , Cialis, and Levitra have already been developed to target PDE-5 for treating ED; traditional Chinese medicine, Epimedium sagittatum, also has shown prominent results as well. To developed new PDE-5 inhibitors, we performed a virtual screening of traditional Chinese medicine (TCM) database and docking analyses to identify candidates. Known PDE-5 inhibitors were used to construct a three dimensional quantitative structure-activity relationship (3D QSAR) model by HypoGen program. From docking analyses, isochlorogenic acid b was identified as the most potential inhibitory compound. De novo evolution designed 47 derivatives. Of the 47 derivatives, seven were able to map into the pharmacophore model, and these seven compounds were suggested to be the most promising leads for inhibiting PDE-5. An analysis of the hydrogen bond interactions formed between the docked ligands and PDE-5 identified ASN662, SER663 and GLN817 as the most frequently interacting residues. A total of eight novel leading compounds were identified to have favorable interaction with PDE-5. These compounds all had hydrogen bond interactions with three key residues that could be further investigated for understanding of PDE-5 and ligands interaction. | 10.1080/07391102.2010.10508577 |
pubmed_306_12406 | OBJECTIVES
This study aims to investigate biomechanically positive and negative aspects of arthroplasties in combination with diaphyseal cement support as an alternative to calcar supported prosthesis on the proximal femoral load distribution, using finite element analysis method in a virtual environment in intertrochanteric fractures with calcar femoral defect.
MATERIALS AND METHODS
Three femur models were created using the ANSYS method. These were named as a intertrochanteric fracture model without calcar defect, an intertrochanteric fracture model with thick cement mantle and calcar defect, and an intertrochanteric fracture model with thin cement mantle and calcar defect. In the finite element analysis setting, two regions were analyzed for load distributions. The first one was the whole femur, while the other one was the region starting from trochanter minor and extending distally to the 5 cm area.
RESULTS
In the trochanteric fracture model without calcar defect, the stress value in the whole femur was found to be 22.9 MPa; whereas it was 29.2 MPa in the 5 cm long section starting at the trochanter minor. The stress values were 23.6-29.9 MPa in the intertrochanteric fracture model with thick cement mantle and 24.2-32.1 MPa in the intertrochanteric fracture model with thin cement mantle and calcar defect. The statistical analysis was performed using t-test and a p value of >0.005 was found in all.
CONCLUSION
Our study results showed that forming a type of calcar to be used in a hemiarthroplasty surgery and shaping of this region with bone cement does not produce further stress on the cement/bone intersection in intertrochanteric fractures with defected calcar region. | pubmed_306_12406 |
pubmed_442_6945 | AIM
Cricopharyngeal achalasia (CPA) is a rare clinical condition that is characterized by aspiration, choking, and nasopharyngeal regurgitation. The aim of this study is to introduce the outcomes of dilatation alone in children with CPA.
PATIENTS AND METHOD
After the evaluation of upper esophageal sphincter with endoscopy, dilatation was performed. All patients underwent videofluoroscopic evaluation and swallowing therapy after the surgical procedure. A retrospective chart review was performed in children with CPA.
RESULTS
Thirty children who were videofluoroscopically proven to have CPA were included in the study. Their age range was 15days-7years (median 11months). Twenty-one of them were neurologically impaired. Two children were lost to follow-up. Nineteen patients (68%) had a total resolution of CPA and were symptom-free with 1-6 dilatations (median 2). Three of the children (11%) who were severely neurologically impaired had resistant CPA. Three children (11%) treated recently with short follow-up were added to the group. Their VFS evaluations demonstrated improvement, thus we accepted their result as successful. There were two perforations in the series. Three patients died; one 2-month-old (2500g) baby who was accepted from the intensive care unit passed away on postoperative on the 7th day. Two other babies who were unresponsive to dilatation therapy died on follow-up.
CONCLUSION
Dilatation can be a safe and effective method on children who are correctly diagnosed to have CPA. | 10.1016/j.jpedsurg.2016.06.022 |
pubmed_904_2082 | Longitudinal studies enable researchers to distinguish within-person (i.e., time-varying) from between-person (i.e., time invariant) effects by using the person mean to model between-person effects and person-mean centering to model within-person effects using multilevel models (MLM). However, with some exceptions, the person mean tends to be based on a relatively small number of observations available for each participant in longitudinal studies. Unreliability inherent in person means generated with few observations results in downwardly biased between-person and cross-level interaction effect estimates. This manuscript considers a simple, easy-to-implement, post-hoc bias adjustment to correct for attenuation of between-person effects caused by unreliability of the person mean. This correction can be applied directly to estimates obtained from MLM. We illustrate this method using data from a panel study predicting adolescent alcohol involvement from perceived parental monitoring, where parental monitoring was disaggregated into within-person (i.e., person-mean-centered) and between-person (i.e., person-mean) components. We then describe results of a small simulation study that evaluated the performance of the post-hoc adjustment under data conditions that mirrored those of the empirical example. Results suggested that, under a condition in which parameter bias is known to be problematic (i.e., moderate ICCX, small n, presence of a compositional effect), it is preferable to use the bias-adjusted MLM estimates over the unadjusted MLM estimates for between-person and cross-level interaction effects. | 10.1016/j.addbeh.2018.09.031 |
pubmed_704_6417 | In view of the harm of diabetes to the population, we have introduced an ensemble learning algorithm-EXtreme Gradient Boosting (XGBoost) to predict the risk of type 2 diabetes and compared it with Support Vector Machines (SVM), the Random Forest (RF) and K-Nearest Neighbor (K-NN) algorithm in order to improve the prediction effect of existing models. The combination of convenient sampling and snowball sampling in Xicheng District, Beijing was used to conduct a questionnaire survey on the personal data, eating habits, exercise status and family medical history of 380 middle-aged and elderly people. Then, we trained the models and obtained the disease risk index for each sample with 10-fold cross-validation. Experiments were made to compare the commonly used machine learning algorithms mentioned above and we found that XGBoost had the best prediction effect, with an average accuracy of 0.8909 and the area under the receiver's working characteristic curve (AUC) was 0.9182. Therefore, due to the superiority of its architecture, XGBoost has more outstanding prediction accuracy and generalization ability than existing algorithms in predicting the risk of type 2 diabetes, which is conducive to the intelligent prevention and control of diabetes in the future. | 10.3390/healthcare8030247 |
others_308_1034 | : Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. Funding: AstraZeneca. © 2020 Elsevier L | 10.1016/S1470-2045(20)30541-6 |
pubmed_122_18367 | AIM
Dementia is a chronic, costly disease affecting millions of people worldwide. Effective, affordable person-centered interventions are required to improve the lived experiences of individuals with dementia and their caregivers in various care settings. The present study examined the effects of a person-centered music listening intervention on mood, agitation and social engagement for individuals living with dementia.
METHODS
This quasi-experimental study was carried out with participants at five community-based adult day health centers (n = 51). Standardized instruments were used to measure mood and agitation, and in-person and video-recorded observations of participant behavior were used to analyze changes before, during and after the intervention across four domains: mood, agitation, connecting to music and engaging socially. Within-person differences were examined using the Wilcoxon signed rank test, and between-group differences were examined using the Mann-Whitney U-test.
RESULTS
Although standardized instruments did not yield statistically significant results, the behavioral observations showed a positive change in mood and a decrease in agitation. From pre- to post-intervention, there were statistically significant increases in joy, eye contact, eye movement, being engaged and talkativeness, and a decrease in sleeping and moving or dancing.
CONCLUSIONS
Behavioral observations show the positive impact a person-centered music listening intervention might have on individuals living with dementia and attending adult day health centers. This affordable intervention provides a useful tool for caregivers that might improve the day-to-day experience of individuals living with dementia. Geriatr Gerontol Int 2019; 19: 30-34. | 10.1111/ggi.13563 |
pubmed_22_9152 | BACKGROUND
The incidence of skin cancer appearing on the head and neck areas is higher in elderly patients. Although free flap reconstruction is the mainstay after tumor excision, it is challenging to complete in elderly patients, owing to the high risk of complications and/or mortality rates associated with the use of general anesthesia. In this study, we used only local anesthesia in free tissue reconstruction of the head and neck in five elderly patients.
MATERIALS AND METHODS
From 2013 to 2016, 5 elderly patients with high risk of general anesthesia underwent reconstruction with either anterolateral thigh free flaps or groin free flap under local anesthesia, after wide excision of malignant tumors at head and neck. For each patient, the following information was collected: age, gender, body weight, anesthesia agents, intravenous fluid, blood loss, site of lesion, flap size, operation time, complications, and follow-up time.
RESULTS
All flaps survived completely. The mean age of 5 patients (3 male patients and 2 female patients) was 84 years (range, 68-100 years), and mean flap size was 199.6 cm (range, 120-330 cm). The mean follow-up period was 26.6 months (range, 5-38 months). No complications were found.
CONCLUSIONS
With proper local anesthesia, successful head and neck reconstruction with free flap was possible, and patient prognosis was positive. There are numerous advantages, including: (1) a safer and inexpensive operation; (2) no complications from general anesthesia; (3) the fact that free flap transfer can be performed in elderly patients, even if they cannot tolerate general anesthesia; and (4) allowance of the performance of free tissue transferring in countries without adequate medical resources. | 10.1097/SAP.0000000000001303 |
pubmed_339_15229 | Early gastric cancer can be macroscopically classified into elevated and depressed types. To clarify the relationship between macroscopic appearance of early gastric cancer and apoptosis or cell proliferation, formalin-fixed paraffin-embedded tissue specimens of 44 intestinal-type early gastric cancers were investigated by the TUNEL method and immunohistochemical techniques. Diffuse type was excluded in this study. When tissue sections of gastric cancer were vertically classified into the 3 compartments of luminar, intermediate and basal, the apoptosis index (%) was significantly higher in the basal compartment of depressed type (1.76 +/- 2.04, mean +/- SD) than in the basal compartment of elevated type (0.63 +/- 0.81, P = 0.01). In depressed type, the apoptosis index (%) was significantly higher in the basal compartment than in the luminar compartment (0.76 +/- 0.85, P = 0.03). Apoptosis-inducing protein, Bax, was expressed more in each of the compartments of depressed type than in those of elevated type, while there were no significant differences in expression of anti-apoptotic protein, Bcl-2, between the two types. Moreover, the apoptosis index (%) of Bax-positive gastric cancer was significantly higher in the basal compartment (P = 0.03), compared to that of Bax-negative gastric cancer, while there were no significant differences in apoptosis index (%) in any compartment between Bcl-2-positive and Bcl-2-negative gastric cancers. There were no significant differences in Ki-67 expression, either between the two types, or among the compartments of depressed type. These results indicate that increased apoptosis with excessive expression of Bax in the basal compartment is involved in the morphogenesis of the depressed type in intestinal-type early gastric cancer. | 10.1111/j.1349-7006.2001.tb02142.x |
pubmed_688_5214 | Single unit recordings from dorsal column neurons were made during application of mechanical somatic stimuli moving at controlled velocities across the neuron's receptive field. The neurons responded in stereotypic patterns which changed with altered stimulus parameters of velocity, direction and intensity. Spatial analysis of the response patterns indicates that the neurons generate action potentials when the stimulus probe activated particular discrete locations within the receptive field. | 10.1016/0006-8993(85)90868-6 |
pubmed_1052_21746 | We present here a review of the mechanistic studies of the Wacker process stressing the long controversy about the key reaction steps. We give an overview of the previous experimental and theoretical studies on the topic. Then we describe the importance of the most recent Ab Initio Molecular Dynamics (AIMD) calculations in modelling organometallic reactivity in water. As a prototypical example of homogeneous catalytic reactions, the Wacker process poses serious challenges to modelling. The adequate description of the multiple role of the water solvent is very difficult by using static quantum chemical approaches including cluster and continuum solvent models. In contrast, such reaction systems are suitable for AIMD, and by combining with rare event sampling techniques, the method provides reaction mechanisms and the corresponding free energy profiles. The review also highlights how AIMD has helped to obtain a novel understanding of the mechanism and kinetics of the Wacker process. | 10.1039/c3cs60469a |
pubmed_689_20796 | Expansion microscopy enables conventional diffraction limit microscopy to achieve super-resolution imaging. However, the enlarged tissue lacks an objective lens with sufficient working distance that can image tissues with whole-brain-scale coverage. Here, we present expansion tomography (ExT) to solve this problem. We have established a modified super-absorbent hydrogel (ExT gel) that possesses high mechanical strength and enables serial sectioning. ExT gel enables tissue and cell imaging and is compatible with various fluorescent labeling strategies. Combining with the high-throughput light-sheet tomography (HLTP) system, we have shown the capability of large volume imaging with nanoscale resolution of mouse brain intact neuronal circuits. The ExT method would allow image samples to support super-resolution imaging of intact tissues with virtually unlimited axial extensions. | 10.1364/BOE.431696 |
pubmed_647_2578 | The beta-adrenoceptor subtype that mediates adrenaline-induced relaxation was pharmacologically identified in smooth muscle cells of the isolated guinea-pig trachea. Adrenaline produced a concentration-dependent relaxation with a pD(2) value of 7.1. The concentration-response curve for adrenaline was shifted rightwards in a competitive fashion by the beta(1)-/beta(2)-nonselective antagonists propranolol and bupranolol, with pA(2) values of 8.85 and 8.97, respectively. Adrenaline-induced relaxation was not affected by the beta(1)-selective antagonists atenolol and CGP-20, 712A within the concentration ranges supposed to antagonize the beta(1)-subtype (atenolol, <or=10(-6) M; CGP-20, 712A, <or=10(-8) M). By contrast, the concentration-response curve for adrenaline was shifted rightwards in a competitive fashion by atenolol at concentrations >or=3x10(-6) M with a pA(2) value of 5.77. The concentration-response curve for adrenaline was also competitively antagonized by the beta(2)-selective antagonists butoxamine and ICI-118,551 with pA(2) values of 6.86 and 8.73, respectively. The pA(2) values of beta-adrenoceptor antagonists (propranolol, bupranolol, atenolol, butoxamine and ICI-118,551) tested against adrenaline were consistent with the values when tested against salbutamol, a beta(2)-selective adrenoceptor agonist. The present findings provide evidence that the relaxant response of the smooth muscle of the guinea-pig trachea to the adrenal medulla hormone, adrenaline, is mainly mediated through beta(2)-adrenoceptors. | 10.1540/jsmr.41.153 |
pubmed_769_344 | Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production of the antiviral drug remdesivir. Compound 1 was produced through a newly developed synthetic methodology utilizing simple building blocks such as pyrrole, chloramine, and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine 1 was obtained in 55% overall yield in a two-vessel-operated process. This work describes the safety of the process, impurity profiles and control, and efforts toward the scale-up of triazine for the preparation of kilogram quantity. | 10.1021/acs.oprd.1c00071 |
pubmed_1132_19312 | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the degeneration of upper and lower motor neurons. Recent advances in our understanding of some of the genetic causes of ALS, such as mutations in SOD1, TARDBP, FUS and VCP have led to the generation of rodent models of the disease, as a strategy to help our understanding of the pathophysiology of ALS and to assist in the development of therapeutic strategies. This review provides detailed descriptions of TDP-43, FUS and VCP models of ALS, and summarises potential therapeutics which have been recently trialled in rodent models of the disease. This article is part of a Special Issue entitled: Animal Models of Disease. | pubmed_1132_19312 |
pubmed_129_18656 | Heat stress (hs) treatment of cell cultures of Lycopersicon peruvianum (Lp, tomato) results in activation of preformed transcription factor(s) (HSF) binding to the heat stress consensus element (HSE). Using appropriate synthetic HSE oligonucleotides, three types of clones with potential HSE binding domains were isolated from a tomato lambda gt11 expression library by DNA-ligand screening. One of the potential HSF genes is constitutively expressed, the other two are hs-induced. Sequence comparison defines a single domain of approximately 90 amino acid residues common to all three genes and to the HSE--binding domain of the yeast HSF. The domain is flanked by proline residues and characterized by two long overlapping repeats. We speculate that the derived consensus sequence is also representative for other eukaryotic HSF and that the existence of several different HSF is not unique to plants. | 10.1002/j.1460-2075.1990.tb07900.x |
pubmed_787_11132 | BACKGROUND
There is a paucity of population-based studies on Staphylococcus aureus bacteremia (SAB) in the United States. We determined the incidence of and trends in SAB in Olmsted County, Minnesota, over an 8-year period.
METHODS
A retrospective, population-based, cohort study was done to evaluate the initial episodes of SAB occurring in adult residents of Olmsted County, Minnesota, from 1 January 1998 through 31 December 2005, using the microbiology databases at Mayo Clinic and Olmsted Medical Center in Rochester, Minnesota.
RESULTS
Of 247 evaluable adult patients with SAB who were included in the incidence calculation, 143 (57.9%) were males, and the median age was 72.1 years (range, 19.5-98.5 years). Episodes of bacteremia were classified according to acquisition type: 58 (23.5%) were nosocomial (N-SAB), 145 (58.7%) were healthcare-associated (HCA-SAB), and 44 (17.8%) were community-acquired (CA-SAB). Methicillin-resistant S. aureus (MRSA) constituted 31.6% of the cases. No community-acquired MRSA bacteremia was noted. The age-adjusted incidence of SAB was 28.3 episodes/100,000 person-years for females and 53.5 episodes/100,000 person-years for males, with an age- and sex-adjusted rate of 38.2 episodes/100,000 person-years. The age- and sex-adjusted incidence of N-SAB, HCA-SAB, and CA-SAB was 9.0, 22.6, and 6.6 episodes/100,000 person-years, respectively. The age- and sex-adjusted incidence of methicillin-susceptible S. aureus was 25.4 episodes/100,000 person-years, and that of MRSA was 12.4 episodes/100,000 person-years. Overall, the incidence rate increased with age but not over the calendar year. The exception was MRSA bacteremia, which increased at a rate of 19.8% (standard error, +/-5.5%) per year during the study.
CONCLUSIONS
The incidence of SAB in adults remained stable in Olmsted County, Minnesota, from 1998 to 2005, but the proportion of episodes due to MRSA significantly increased over the 8-year period. | 10.1086/648442 |
pubmed_526_18532 | BACKGROUND
Accruing evidence suggests that positive imagery-based cognitive bias modification (CBM) could have potential as a standalone targeted intervention for depressive symptoms or as an adjunct to existing treatments. We sought to establish the benefit of this form of CBM when delivered prior to Internet cognitive behavioral therapy (iCBT) for depression
METHODS
A randomized controlled trial (RCT) of a 1-week Internet-delivered positive CBM vs. an active control condition for participants (N=75, 69% female, mean age=42) meeting diagnostic criteria for major depression; followed by a 10-week iCBT program for both groups.
RESULTS
Modified intent-to-treat marginal and mixed effect models demonstrated no significant difference between conditions following the CBM intervention or the iCBT program. In both conditions there were significant reductions (Cohen׳s d .57-1.58, 95% CI=.12-2.07) in primary measures of depression and interpretation bias (PHQ9, BDI-II, AST-D). Large effect size reductions (Cohen׳s d .81-1.32, 95% CI=.31-1.79) were observed for secondary measures of distress, disability, anxiety and repetitive negative thinking (K10, WHODAS, STAI, RTQ). Per protocol analyses conducted in the sample of participants who completed all seven sessions of CBM indicated between-group superiority of the positive over control group on depression symptoms (PHQ9, BDI-II) and psychological distress (K10) following CBM (Hedges g .55-.88, 95% CI=-.03-1.46) and following iCBT (PHQ9, K10). The majority (>70%) no longer met diagnostic criteria for depression at 3-month follow-up.
LIMITATIONS
The control condition contained many active components and therefore may have represented a smaller 'dose' of the positive condition.
CONCLUSIONS
Results provide preliminary support for the successful integration of imagery-based CBM into an existing Internet-based treatment for depression. | pubmed_526_18532 |
pubmed_1121_5045 | Vestibular Evoked Myogenic Potentials (VEMP) are commonly recorded in patients experiencing vertigo or chronic instability. This test evaluates the patient's otolith function and is often combined with both Videonystagmography and Video Head Impulse Test. VEMP is a simple, reproducible test, in the absence of any pre-existing conductive hearing loss. Cervical VEMP explore both saccular function and the inferior vestibular nerve, whereas ocular VEMP assess utricular function and the superior vestibular nerve. In combination with previously described tests, VEMP allows characterization of vertigo and provides support for the diagnosis of superior semicircular canal dehiscence syndrome, Menière's disease, vestibular neuritis, vestibular schwannoma or idiopathic bilateral vestibulopathy. A good knowledge of these electrophysiological tests is essential in order to precisely assess the presence or absence of vestibular function impairment. We describe the test recording technique and the most common pitfalls in interpretation of the results. We then outline the results observed in various diseases impacting vestibular function. | 10.1016/j.anorl.2021.01.001 |
others_389_9550 | Structural and functional characteristics of the photosynthetic apparatus in 15-day old Brassica rapa plants grown aboard the space shuttle Columbia (STS-87) have been studied. Maintaining of the same growth conditions for control plants was realized using the Orbiter Environmental Simulator in Kennedy Space Center. The main differences in spaceflight plants in comparison with control ones have been shown to be the following. An average volume of one mesophyll palisade cell increased approximately twice and the chloroplast number per cell by 69.8%. Partial volumes of stromal thylakoids, starch grains and plastoglobuli also increased by 19.4%, 20.6% and 2 times accordingly. At the same time, the grana number per chloroplast decreased. Greater diversity of the thylakoid length in grana and a decrease in thylakoid membrane stacking were revealed. A decrease of PSII and PSI light-harvesting antennae has been detected, for PSII by an increase of Chl a/b ratio and kinetics delay in chlorophyll fluorescence induction, and for PSI by a decrease of integral intensity in the excitation spectrum of fluorescence at 735 nm, which indicated a decline of PSI absorption cross-section. Some distortion of PSI complexes have been displayed by fluorescence spectra. A slight decrease in PSII photochemistry yield was detected for the spaceflight material. PSI is concluded to be more susceptible to the microgravity conditions | 10.1080/11263500410001684062 |
pubmed_670_10283 | Models for the activation of the myosin subfragment-1 (S-1) ATPase activity by actin describe transitions that occur between kinetic intermediate states during steady state hydrolysis of ATP. These states consist of myosin-nucleotide complexes in rapid equilibrium binding with actin, but steady state measurements of actin binding during hydrolysis lead only to a weighted average of the individual binding constants involved. In the current work, in order to determine the individual binding constants involved in the activation process, we have investigated the presteady state kinetics of the dissociation of actomyosin by ATP. We find that an actin flow artifact appears to dominate the time course of dissociation, and characterization of this artifact reveals that its magnitude rises linearly (approximately) with the concentration of bound S-1. Attempts to subtract the actin flow artifact from the actoS-1 dissociation signal were not entirely successful due at least partially to the transient nature of the bound S-1 concentration in the first few milliseconds. However, further studies reveal that if the order of addition of actin, ATP, and S-1 are varied, the observed light scattering transients are essentially superimposable. One possible explanation of these data is that the binding constants for myosin-ATP and myosin-ADP-Pi to actin are equal. However, it is also possible that the flow artifact is so large that further analysis is precluded. In addition, we show that the actin flow artifact has little effect on the fluorescence measurements of the phosphate burst reported previously. Therefore, the prior interpretation of the fluorescence data remains unchanged. | 10.1016/0003-9861(91)90408-b |
pubmed_1050_15994 | Recent studies emphasize on developing immune tolerance by an interim administration of various immunosuppressive drugs. In this study, a robust protocol is reported for local immunomodulation using a single-dose of FK506 microspheres and clodronate liposomes (mFK+CLO) in a xenogeneic model of islet transplantation. Surprisingly, the single-dose treatment with mFK+CLO induce tolerance to the islet xenograft. The recipient mice display tolerogenic dendritic cells (tDCs) with decreased antigen presenting ability and T cell activation capacity. Furthermore, a reduced percentage of CD4+ and CD8+ T cells and an impaired differentiation of naïve CD4+ T cells into interferon-γ producing Th1 and interleukin-17 producing Th17 cells are observed. In addition, the immunosuppressive protocol leads to the generation of Foxp3+ regulatory T cells (Tregs) which are required for the long-term graft survival. The enhanced generation of tDCs and Tregs by the single treatment of mFK+CLO cause xenograft tolerance, suggesting a possible clinical strategy which may pave the way towards improving therapeutic outcomes of clinical islet transplantation. | 10.1002/adhm.202001157 |
pubmed_204_14986 | OBJECTIVE
To assess the perspectives of adults with neurofibromatosis 1 (NF1) regarding cutaneous neurofibroma (cNF) morbidity, treatment options, and acceptable risk-benefit ratio to facilitate the design of patient-centered clinical trials.
METHODS
An online survey developed by multidisciplinary experts and patient representatives of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) cNF Working Group was distributed to adults with NF1 (n = 3,734) in the largest international database of individuals with any form of NF. Eligibility criteria included self-reported NF1 diagnosis, age ≥18 years, ≥1 cNF, and ability to read English.
RESULTS
A total of 548 adults with NF1 responded to the survey. Respondents ranked appearance, number, and then location as the most bothersome features of raised cNF. Seventy-five percent of respondents considered a partial decrease of 33%-66% in the number or size of cNF as a meaningful response to experimental treatments. Most respondents (48%-58%) were willing to try available cNF treatments but were not aware of options outside of surgical removal. Regarding experimental agents, respondents favored topical, then oral medications. Most individuals (>65%) reported being "very much" or "extremely willing" to try experimental treatments, especially those with the highest cNF burden. Many respondents were not willing to tolerate side effects like nausea/vomiting (51%) and rash (46%). The greatest barriers to participation in cNF clinical trials were cost of participation and need to take time off work.
CONCLUSIONS
Most adults with NF1 are willing to consider experimental therapies for treatment of cNF. These data will guide the design of patient-centered clinical trials for adults with cNF. | 10.1212/WNL.0000000000012425 |
pubmed_1091_10799 | The purpose of this study was to estimate the population of sexual minority or LGB (lesbian, gay and bisexual) children and youth involved with the child welfare system, and to compare their health, mental health, placement and permanency outcomes to those of non-LGB youth. Data were drawn from the Second National Survey of Child and Adolescent Well-Being (NSCAW-II), a nationally representative sample of children who were referred to child welfare due to a report of abuse or neglect over a fifteen month period. This sample included youth ages eleven and older who self-identified their sexual orientation (n = 1095). Results indicate that approximately 15.5% of all system involved youth identified as lesbian, gay or bisexual, and that lesbian and bisexual females, and LGB youth of color are both overrepresented within child welfare systems. Although no substantive difference in risk factors, permanency and placement were found between LGB and Non-LGB youth, LGB youth were significantly more likely to meet the criteria for adverse mental health outcomes. Implications for child welfare practice and policy are presented, along with recommendations for future research in this area. | 10.1016/j.chiabu.2018.03.009 |
pubmed_687_12614 | Nicotinic acetylcholine receptors (nAChRs) participate in diverse biological processes, such as mood, learning, and addiction. Glycosylphosphatidylinositol-linked lynx1 is an allosteric modulator of nAChR function, including shifts in agonist sensitivity, reduced desensitization, and slower recovery from desensitization. This modulation is thought to be achieved by lynx1's interaction with nAChR subunits, particularly at the α4:α4 interface. In this study, we used molecular modeling and simulation to study the structure, dynamics, and interactions of lynx1 when bound to nAChRs, as well as unbound, monomeric lynx1 in membranes. Though lynx1 structures are similar in both states, its dynamics is more restricted in the bound state than in the unbound one. When bound, interactions between lynx1 and nAChR are observed to be maintained throughout the simulations. Of particular note, lynx1 demonstrates prolonged interactions with the receptor C-loop in one of the nAChR α4 subunits, a region important for agonist binding and possibly the transition between open/closed states. During interactions with lynx1, an α4 C-loop tends to be restricted in either a closed or open state, whereas the C-loop state transitions are more evident when lynx1 is unbound. Interestingly, the conformational change of the C-loop is stochastic, suggesting that lynx1 can influence nAChR (critical for its multimodal action), for instance, by shifting its agonist sensitivity and recovery from desensitization. | 10.1021/acs.jpcb.0c00159 |
pubmed_460_20615 | The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data. | 10.1203/01.PDR.0000139428.77791.3D |
others_87_5239 | Echium vulgare is a gynodioecious species; hermaphrodite and female individuals occur in the same population. Flowers of the female individuals are smaller and produce less nectar. Female and hermaphrodite plants were equally frequently approached by bumblebees. After an approach the bumblebees visited more flowers on hermaphrodite plants. As a result, individual flowers on hermaphrodite plants received 50% more visits. In contrast, flowers on female plants produced more seeds, suggesting that the relation between seed set and number of visits was influenced by resource availability. Per visit bumblebees removed 16.5% of the pollen present in the anthers. In contrast to the common assertion in the literature, our data do not indicate that the number of bumblebee visits was limiting pollen transport to other plants in this situation. © 1990, Brill. All rights reser | 10.1163/156854291X00081 |
pubmed_680_5562 | The acetamide moiety is a general functional group present in many natural and pharmaceutical products. Herein, we report two new reagents, p-methoxybenzyl N-acetylcarbamate potassium salt (PM-BENAC-K) and 2,4-dimethoxybenzyl N-acetylcarbamate potassium salt (2,4-DM-BENAC-K), which are refined versions of the benzyl N-acetylcarbamate potassium salt (BENAC-K). These compounds, which we reported as simple equivalents of N-acetamide nucleophiles, are stable and easy-to-handle powders that react with a variety of alkyl halides and sulfonates to afford substituted products in good yields. The products were transformed into N-alkylacetamides after p-methoxybenzyloxycarbonyl (Moz) or 2,4-dimethoxybenzyloxycarbonyl (Dmoz) cleavage under mild acidic conditions. The acetyl groups in the substituted products of PM- and 2,4-DM-BENAC-Ks were removed using K2CO3 in methanol to afford Moz- and Dmoz-protected amines, respectively. Hence, the new BENAC-Ks acted as versatile equivalents of both N-acetamide and Moz/Dmoz-protected nitrogen nucleophiles and can be used in synthetic studies of natural and pharmaceutical products. | 10.1248/cpb.c22-00413 |
pubmed_524_2416 | Although non-alcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM), the diagnosis of NAFLD for T2DM patients remains a challenge.This study aimed to investigate the prevalence and risk factors for the NAFLD in T2DM outpatients.This is a retrospective, cross-sectional study that included 2405 T2DM patients treated and admitted for glucose control into the Endocrinology Department of our hospital from April 2017 to March 2019. Using strict exclusion criteria, the target patients were screened and divided into two groups: NAFLD patients (study group) and non-NAFLD patients (control group). Subsequently, 34 factors were compared between the two groups. Furthermore, multivariate analysis of the NAFLD risk factors was performed using logistic regression. Finally, the diagnostic significance of individual biochemical predictors, as well as the combined predictive indicator (CPI), for NAFLD was estimated using receiver operating characteristic (ROC) curve analysis.In this study, the overall prevalence of NAFLD in T2DM patients was 58.67%. Of the target patients, 17 factors were identified by univariate analysis to be associated with NAFLD, and 8 factors were found to be significant predictors for NAFLD using binary logistic regression modeling. Furthermore, the CPI and C-Peptide represent high diagnostic value for NAFLD in T2DM patients.This study provides a more comprehensive risk factor analysis for NAFLD in T2DM patients. These data can be used to provide timely diagnosis and effective management of NAFLD. | 10.1097/MD.0000000000024940 |
pubmed_973_6526 | BACKGROUND
Ventricular premature contractions (VPCs) are common in the occult stage of cardiomyopathy in Doberman Pinschers. Although the gold standard for detecting arrhythmia is the 24-hour ambulatory electrocardiography (ECG) (Holter), this method is more expensive, time-consuming and often not as readily available as common ECG.
OBJECTIVES
Comparison of 5-minute ECGs with Holter examinations.
ANIMALS
Eight hundred and seventy-five 5-minute ECGs and Holter examinations of 431 Doberman Pinschers.
METHODS
Each examination included a 5-minute ECG and Holter examination. A cut-off value of > 100 VPCs/24 hours using Holter was considered diagnostic for the presence of cardiomyopathy. Statistical evaluation included calculation of sensitivity, specificity, positive predictive value, and negative predictive value.
RESULTS
Holter examinations revealed > 100 VPCs/24 hours in 204/875 examinations. At least 1 VPC during a 5-minute ECG was detected in 131 (64.2%) of these 204 examinations. No VPCs were found in the 5-minute ECG in 73 (35.8%) examinations of affected Doberman Pinschers. A 5-minute ECG with at least 1 VPC as cut-off had a sensitivity of 64.2%, a specificity of 96.7%, a positive predictive value of 85.6% and a negative predictive value of 89.9% for the presence of > 100 VPCs/24 hours.
CONCLUSIONS AND CLINICAL IMPORTANCE
A 5-minute ECG is a rather insensitive method for detecting arrhythmias in Doberman Pinschers. However, the occurrence of at least 1 VPC in 5 minutes strongly warrants further examination of the dog, because specificity (96.7%) and positive predictive value (85.6%) are high and could suggest occult cardiomyopathy. | 10.1111/j.1939-1676.2010.0477.x |
pubmed_597_12775 | OBJECTIVES
The aim of this hospital-based prospective study was to evaluate the diagnostic ability of breast cancer screening in Korean middle-aged women using age, ultrasonography, mammography, and magnification mammography, which are commonly used in most hospitals.
METHODS
A total of 21 patents were examined using ultrasonography, mammography, and magnification mammography, and their data were prospectively analyzed from August 2011 to March 2013. All patients were divided into benign and malignant groups and the screening results were classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). The final pathology report was used as the reference standard and the sensitivity and specificity of ultrasonography, mammography, and magnification mammography were evaluated using receiver-operating characteristics (ROC) analysis.
RESULTS
The analysis included 21 patients who underwent biopsy. Among them, three (14.3%) were positive and 18 (85.7%) negative for breast cancer. The average age was 50.5 years (range = 38-61 years). The sensitivity was the same for ultrasonography and magnification mammography and the specificity of magnification mammography was higher than that of ultrasonography. The highest area under the ROC curve (AUC) was observed in the combination of age and magnification mammography (1.000) and the decreasing order of AUC in others was magnification mammography (0.833), ultrasonography (0.787), mammography (0.667), and age (0.648).
CONCLUSIONS
In Korean women, the diagnostic accuracy of magnification mammography was better than that of ultrasonography and mammography. The combination of age and magnification mammography increased the sensitivity and diagnostic accuracy. | 10.1016/j.phrp.2013.06.002 |
pubmed_584_14774 | The dewetting dynamics of ultrathin films containing potentially surface-active nanoparticles is considered in the presence of evaporation. Evolution equations for the film height and particle surface and bulk concentration are derived using a lubrication model coupled by a constitutive relation for the dependence of the viscosity on local particle concentration. A linear stability analysis and numerical simulations are used to determine how particle mass distribution depends on the various physical parameters such as equilibrium film separation distance, initial packing concentration, rate of evaporation, and particle surface activity. Our results show that when starting from an initially uniform distribution the particles become aligned into distinct "bands" in rectilinear geometry, or "rings" in cylindrical geometry. The functional dependence of the pattern spacing on relevant system parameters is studied and detailed herein. | 10.1016/s0021-9797(03)00640-4 |
pubmed_923_8561 | Renal epithelial cells resistant to oxidant stress mediated by hydrogen peroxide have been isolated and characterized. African green monkey kidney epithelial cell line, BSC-1 cells, chronically exposed to 50 microM hydrogen peroxide for 15 passages exhibited increased catalase (1.5-fold) and glutathione peroxidase (2.4-fold) activity, as well as increased total cellular glutathione (1.6-fold). This was associated with the acquisition of resistance to hydrogen peroxide cytotoxicity, as judged by nuclear staining with ethidium homodimer and clonogenic survival assay. H2O2-adapted and wild-type BSC-1 cells were used to examine the role of elevated cytosolic calcium concentration and the activation of phospholipase A2 in the development of lethal cell injury. Despite dramatic differences in resistance to oxidative stress, both cell types showed similar kinetics of cytosolic calcium increase in response to challenge with hydrogen peroxide. In contrast to this, oxidant-induced release of arachidonic acid correlated with the resistance of both types of BSC-1 cells to oxidative stress. A mechanism-based inhibitor of calcium-independent phospholipase A2 (Hazen et al., J. Biol. Chem. 266, 7227, 1991) reduced oxidant-induced lethal cell injury, suggesting that this class of phospholipases contributes to damage of BSC-1 cells exposed to hydrogen peroxide. H2O2-adapted BSC-1 cells may represent a valuable tool to study adaptation to oxidative stress and various mechanisms of cell injury. | 10.1006/abbi.1993.1123 |
pubmed_743_1702 | With aging worldwide population and the high incidence of cancer in the population of people over 75 years old, there is a need for oncologists and geriatricians to strengthen their collaboration to improve elderly patients care. Complexity of cancer and aging issues must be considered simultaneously to establish a personalized care plan. Thus, the G8 is a screening tool that allows to identify patients who should benefit from a geriatric assessment, which is a key step in the management process. This specific evaluation offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status and has demonstrated its prognostic value in terms of choice of treatment but also in terms of patient survival. In nearly 20% of cases, the geriatric assessment leads to a change in the choice of treatment, and at one year the initial care plan is not carried out in a quarter of cases. The presence of malnutrition and functional impairment leading to dependence on basic activities of daily living had a significant impact on this change in therapeutic choice. Survival is not only impacted by malnutrition and functional impairment but also by the presence of severe comorbidities and thymic and neurocognitive impairment. The patient's choice must remain at the center of the elaboration of the care plan with the oncologists and geriatricians in order to propose the most appropriate treatment for his or her situation. | 10.1016/j.revmed.2021.10.006 |
pubmed_1055_6060 | Tumor development driven by inflammation is now an established phenomenon, but the role that complement plays remains uncertain. Recent evidence has suggested that various components of the complement (C) cascade may influence tumor development in disparate ways; however, little attention has been paid to that of the membrane attack complex (MAC). This is despite abundant evidence documenting the effects of this complex on cell behavior, including cell activation, protection from/induction of apoptosis, release of inflammatory cytokines, growth factors, and ECM components and regulators, and the triggering of the NLRP3 inflammasome. Here we present a novel approach to this issue by using global gene expression studies in conjunction with a systems biology analysis. Using network analysis of MAC-responsive expression changes, we demonstrate a cluster of co-regulated genes known to have impact in the extracellular space and on the supporting stroma and with well characterized tumor-promoting roles. Network analysis highlighted the central role for EGF receptor activation in mediating the observed responses to MAC exposure. Overall, the study sheds light on the mechanisms by which sublytic MAC causes tumor cell responses and exposes a gene expression signature that implicates MAC as a driver of tumor progression. These findings have implications for understanding of the roles of complement and the MAC in tumor development and progression, which in turn will inform future therapeutic strategies in cancer. | 10.1074/jbc.M115.708446 |
pubmed_229_23373 | PURPOSE
Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy.
METHODS
A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy.
RESULTS
Among 60 patients (20 females) there was a mean age of 58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only).
CONCLUSIONS
Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy. | 10.1007/BF02234632 |
pubmed_1127_17568 | OBJECTIVE
Cognitive behavior therapy (CBT) and medication can be administered in combination in treating tic disorders but there are no studies evaluating the effectiveness of CBT with and without medication. The current study compares the efficacy of CBT in combination with medication and without medication.
METHOD
CBT was administered in a consecutively referred sample of 76 people diagnosed either with Gilles de la Tourette Syndrome or chronic tic disorder. The sample was divided into a medicated and a non-medicated group. Twenty three were stabilized on medication and 53 were not receiving medication. Measures administered pre- and post-CBT in both groups included: main outcome measure of Tourette Syndrome Global Scale and measures of mood.
RESULTS
Repeated measures analysis of variance on the initial sample revealed no difference between medicated and non-medicated groups in outcome. A further analysis comparing the 23 receiving medication with 23 not receiving medication matched on baseline clinical variables also yielded no significant group differences, either in treatment outcome on main tic outcome measures or on other clinically relevant questionnaires.
DISCUSSION
CBT for tic disorders is an effective treatment administered either in combination with medication or alone. | 10.1016/j.brat.2009.07.021 |
pubmed_993_231 | The X-ray induction of 8-azaguanine (AG) resistent mutants in two sets of diploid and tetraploid Chinese hamster cells (DON and V79) was investigated. It was found that (i) the induced mutant frequencies in diploid and tetraploid cells appeared to be of the same order of magnitude and (ii) all mutants showed almost complete loss of hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) activity except that in the tetraploid V79 cells 50--100% of activity was retained. The gene--dosage effect for glucose-6-phosphate dehydrogenase (G6PD) in these cells make it possible to determine the number of chromosomes bearing the HGPRT-gene in mutants by measuring the G6PD activity per cell. The results show that the spontaneous and induced mutants from the diploid V79 and DON as well as the tetraploid DON cells retained the G6PD activity of the parental cells, whereas the induced mutants from the tetraploid V79 cells had about 35% of the parental G6PD activity. With 6-thioguanine (TG) as selective agent, the induced mutant frequencies in diploid and tetraploid DON cells and in diploid V79 cells appeared to be of the same order of magnitude but no mutants could be recovered from tetraploid V79 cells in a single step. TG-resistant tetraploid V79 cells could only be obtained from the AG-resistant mutants after a second selection. The HGPRT activity was lost in these mutants and some of them showed an increase in G6PD activity. The combined data cannot be explained on the basis of a single genetic mechanism. | 10.1016/0027-5107(75)90102-5 |
pubmed_480_12888 | Fusarium oxysporum is one of the few filamentous fungi capable of fermenting ethanol directly from plant cell wall biomass. It has the enzymatic toolbox necessary to break down biomass to its monosaccharides and, under anaerobic and microaerobic conditions, ferments them to ethanol. Although these traits could enable its use in consolidated processes and thus bypass some of the bottlenecks encountered in ethanol production from lignocellulosic material when Saccharomyces cerevisiae is used-namely its inability to degrade lignocellulose and to consume pentoses-two major disadvantages of F. oxysporum compared to the yeast-its low growth rate and low ethanol productivity-hinder the further development of this process. We had previously identified phosphoglucomutase and transaldolase, two major enzymes of glucose catabolism and the pentose phosphate pathway, as possible bottlenecks in the metabolism of the fungus and we had reported the effect of their constitutive production on the growth characteristics of the fungus. In this study, we investigated the effect of their constitutive production on ethanol productivity under anaerobic conditions. We report an increase in ethanol yield and a concomitant decrease in acetic acid production. Metabolomics analysis revealed that the genetic modifications applied did not simply accelerate the metabolic rate of the microorganism; they also affected the relative concentrations of the various metabolites suggesting an increased channeling toward the chorismate pathway, an activation of the γ-aminobutyric acid shunt, and an excess in NADPH regeneration. | 10.3389/fmicb.2016.00632 |
pubmed_125_14405 | Toll-like receptor 4 (TLR4) recognizes various endogenous and microbial ligands and is an essential part in the innate immune system. TLR4 signaling initiates transcription factor NF-κB and production of proinflammatory cytokines. TLR4 contributes to the development or progression of various diseases including stroke, neuropathic pain, multiple sclerosis, rheumatoid arthritis and cancer, and better therapeutics are currently sought for these conditions. In this study, a library of 140 000 compounds was virtually screened and a resulting hit-list of 1000 compounds was tested using a cellular reporter system. The topoisomerase II inhibitor mitoxantrone and its analogues pixantrone and mitoxantrone (2-hydroxyethyl)piperazine were identified as inhibitors of TLR4 and NF-κB activation. Mitoxantrone was shown to bind directly to the TLR4, and pixantrone and mitoxantrone (2-hydroxyethyl)piperazine were shown to inhibit the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNFα) in primary microglia. The inhibitory effect on NF-κB activation or on TNFα production was not mediated through cytotoxity at ≤ 1 µM concentration for pixantrone and mitoxantrone (2-hydroxyethyl)piperazine treated cells, as assessed by ATP counts. This study thus identifies a new mechanism of action for mitoxantrone, pixantrone, and mitoxantrone (2-hydroxyethyl)piperazine through the TLR4. | 10.1016/j.ejps.2020.105493 |
pubmed_1090_5537 | "SUNCT" is a recently reported head pain syndrome characterized by shortlasting, unilateral neuralgiform paroxysms with conjunctival injection and tearing, and to a lesser extent nasal secretion, and (subclinical) sweating. Another case--that of a 56 year old male--is reported herein. The attacks lasted 1/2-1 min. and occurred only infrequently, i.e. once or twice in 1-4 weeks, except for a week recently when there were up to 20 or more typical attacks per day, with the usual ipsilateral, autonomic accompaniments. Due to the benign nature and low frequency of attacks, the diagnosis would have been most difficult to establish prior to the occurrence of this shortlasting period with more marked symptoms. A variety of precipitation mechanisms were present, partly concerning the V 2-3 areas, partly concerning the neck. Precipitation mechanisms in "SUNCT" to some extent seem to differ from those in trigeminal neuralgia. It is remarkable that all four hitherto reported cases are males. | 10.1111/j.1526-4610.1991.hed3103175.x |
pubmed_297_4251 | Inline sludge treatment using free nitrous acid (FNA) was recently shown to be effective in establishing the nitrite pathway in a biological nitrogen removal system. However, the effects of FNA treatment conditions on the nitrite pathway performance remained to be investigated. In this study, three different FNA treatment frequencies (daily sludge treatment ratios of 0.22, 0.31 and 0.38, respectively), two FNA concentrations (1.35 mgN/L and 4.23 mgN/L, respectively) and two influent feeding regimes (one- and two-step feeding) were investigated in four laboratory-scale sequencing batch reactors. The nitrite accumulation ratio was positively correlated to the FNA treatment frequency. However, when a high treatment frequency was used e.g., daily sludge treatment ratio of 0.38, a significant reduction in ammonia oxidizing bacteria (AOB) activity occurred, leading to poor ammonium oxidation. AOB were able to acclimatise to FNA concentrations up to of 4.23 mgN/L, whereas nitrite oxidizing bacteria (NOB) were limited by an FNA concentration of 1.35 mgN/L over the duration of the study (up to 120 days). This difference in sensitivity to FNA could be used to further enhance nitrite accumulation, with 90% accumulation achieved at an FNA concentration of 4.23 mgN/L and a daily sludge treatment ratio of 0.31 in this study. However, this high level of nitrite accumulation led to increased N2O emission, with emission factors of up to 3.9% observed. The N2O emission was mitigated (reduced to 1.3%) by applying two-step feeding resulting in a nitrite accumulation ratio of 45.1%. Economic analysis showed that choosing the optimal FNA treatment conditions depends on a combination of the wastewater characteristics, the nitrogen discharge standards, and the operational costs. This study provides important information for the optimisation and practical application of FNA-based sludge treatment technology for achieving the mainstream stable nitrite pathway. | 10.1016/j.scitotenv.2018.06.346 |
pubmed_199_6706 | Congo red binding by virulent A-layer-containing (A+) and avirulent A-layer-deficient (A-) strains of Aeromonas salmonicida was examined. Congo red binding to A+ cells was enhanced by salt and thus hydrophobically driven, but at low Congo red concentrations binding was salt independent. Congo red was bound by A+ cells by a kinetically distinct mechanism (Kd, 0.25 microM) which was absent in A- isogenic strains. Purified A-layer protein ("A protein") protein A also bound Congo red with similar affinity (Kd, 0.40 microM). Congo red binding was structurally specific; it was not influenced by a wide variety of compounds including amino acids and nucleotides and only weakly inhibited by structurally similar dyes. However, protoporphyrin IX and hemin were strong competitive inhibitors of Congo red binding. Protoporphyrin and hemin were bound only by A+ strains (KdS of 0.41 and 0.63 microM, respectively). Furthermore, binding of these porphyrins was strongly inhibited by Congo red but weakly inhibited by hematoporphyrin. Purified A protein also bound protoporphyrin IX and hemin with affinities similar to those of A+ cells (KdS of 0.94 and 0.41 microM, respectively. | 10.1128/jb.164.3.1332-1336.1985 |
pubmed_166_1232 | OBJECTIVES
To identify reasons for prostate cancer stage being recorded as 'unknown' in Australia's largest population-based cancer registry.
DESIGN
Prospective population-based cohort.
SETTING
New South Wales (NSW) is the most populous state in Australia, with almost one third of the total national population.
PARTICIPANTS
NSW Cancer Registry (NSWCR) records for prostate cancer cases diagnosed in 2001-2009 were linked to the NSW Admitted Patient Data Collection (APDC) for 2000-2010. All patients in this study had a minimum of 12 months follow-up in the hospital episode records after their date of diagnosis as recorded by the NSWCR.
MAIN OUTCOME MEASURES
Incidence of 'unknown' stage prostate cancer and cancer-specific survival.
RESULTS
Of 50 597 prostate cancer cases, 39.9% were recorded as having 'unknown' stage. Up to 4 months after diagnosis, 77.2% of cases without a hospital-reported cancer diagnosis were recorded as having 'unknown' stage. Among those patients with a hospital-reported cancer diagnosis, stage was 'unknown' for 7.6% of cases who received a radical prostatectomy (RP) and for 34.0% of cases who had procedures other than RP. In the latter group, the factors that were related to having 'unknown' stage were living in disadvantaged areas (adjusted OR (aOR) range: 1.13 to 1.20), attending a private hospital (aOR range: 1.25 to 2.13), having day-only admission for care (aOR=1.23, 95% CI 1.11 to 1.36), or having procedures other than multiple procedures with imaging (eg, biopsy only, aOR range: 1.11 to 1.45).
CONCLUSIONS
Over half of 'unknown' stage prostate cancer cases did not have a hospital-reported prostate cancer diagnosis within the 4 months after initial diagnosis. We identified differences in the likelihood of cases being recorded as 'unknown' stage based on socioeconomic status and facility type, which suggests that further investigation of reporting practices in relation to diagnostic and treatment pathways is required. | 10.1136/bmjopen-2016-014259 |
pubmed_862_24237 | The P element is one of the best-studied DNA transposons as a model system to study evolution of mobile DNAs. The P element is a causative factor for P-M hybrid dysgenesis in Drosophila melanogaster and the P-M phenotype (P, Q, or M) has been thought to reflect genomic P elements content. Recent survey of natural populations showed that full-size P (FP) and KP elements are predominant in almost all current populations, irrespective of their phenotype variation. It was also suggested that some P elements are functionally inactive and their inactivation plays an important role in determining P-M phenotype. In order to know how the genomic P elements are inactivated, we characterized molecular features and insertion sites of them in an M' strain. We isolated 20 P elements, one FP, 15 KP, and four other internally deleted defective elements, all of which appeared thoroughly inactive. These FP and KP elements had canonical sequences in each case, but no mutations abolishing their function. In addition, they were mostly located in or within the vicinity of presumably active genes. Our results suggest that inactivation of P elements is associated with neither mutations nor constitutional suppression by heterochromatinization in M' strains and that only a few elements inserted in some special chromosomal regions are likely to be involved in determination of the phenotype of individual flies. Existence of many copies of canonical, but inactive, KP elements in the M' strain is inconsistent with the assumption that type II repression of the KP element is the main reason for its increase in the wild populations of D. melanogaster. | 10.1266/ggs.83.67 |
pubmed_137_4648 | Little is known about the types of social organization characterizing the pre-Roman Celtic populations of Italy. Here, we explore the funerary variability characterizing the late Iron Age site of Seminario Vescovile (SV: Verona, Italy, 3rd-1st c. BC), and test its possible correlation to diet and relative exposure to developmental stressors. Patterns on funerary treatment (N = 125), δ13C and δ15N (N = 90), and linear enamel hypoplasia (N = 47) from SV are compared, and their possible association with sex and age-at-death further discussed. Results point to the presence at SV of variable funerary customs while at the same time demonstrating a rather homogenous diet and exposure to developmental stressors: funerary treatment is mainly correlated to age-at-death but do not appear to be associated to either isotopic patterns or hypoplasia frequencies. Accordingly, even if some weak social differentiation may have characterized the individuals buried at SV, this was not reflected in markedly differing living conditions. Our study is the first to attempt an exploration of the links between age, sex, funerary variability, and diet in a pre-Roman Celtic community from Italy. While highlighting the potential of a multifaceted approach in bioarcheology, it also points to a series of analytical and theoretical issues relevant when trying to disentangle the cultural and biological dimensions of social differentiation in the past. | 10.1371/journal.pone.0214372 |
pubmed_950_11218 | Toxoplasma gondii is a globally-distributed intracellular parasitic protozoon with wide host range. Chronic infection is the most prevalent form of T. gondii infection, which can lead to significant damage. CD44 plays an important role in body's immune response, however, little is known about the function and mechanism of CD44 in T. gondii infection until now. In the present study, total RNA isolated from four groups including C57BL/6 mouse (C57), C57BL/6△CD44 mouse(C57△CD44), C57BL/6 mouse infected with T. gondii (C57-TG) and C57BL/6△CD44 infected with T. gondii (C57△CD44-TG)were subjected to comparative transcriptome analyses using RNA-seq techniques to explore the possible function of CD44 in mouse brain during chronic Toxoplasma infection. The results indicated a total of 35,908, 54,428, 51,473 and 22,387 unigenes were annotated in KOG, Swissprot, GO and KEGG databases by transcriptome analysis, respectively, and all the databases shared 9,833 unigenes. Subsequently, differentially expressed GO terms and enriched KEGG Pathways showed 20,303 unigenes were annotated belonging to three main GO categories (namely biological process, cellular component and molecular function) and six main KEGG categories (cellular processes, environmental information processing, genetic information processing, human diseases, metabolism and organismal systems) between normal C57 and C57△CD44 mice, as well as for C57-TG and C57△CD44-TG mice. For up-regulated genes, Mid1, Ttr and Cd4 were significantly up-regulated in the C57△CD44 mouse compared with the C57 mouse, and Pcp2, Ppp1r17 and Nrk were significantly up-regulated in the C57△CD44-TG mouse compared with the C57-TG mouse. As to down-regulated genes, AC114588.1, Cbln3 and Pmch were significantly down-regulated in the C57△CD44 the mouse compared with the C57 mouse, and down-regulated genes were enriched for immunoglobulins, major histocompatibility complex (MHC) class II antigens, chemokines ligands and interferon (IFN)-inducible GTPase families in the C57△CD44-TG mouse compared with the C57-TG mouse. The present study is the first trial for exploring the function of CD44 in the mouse brain during chronic infection with T. gondii at the transcriptional level, which can provide a basis for the study of the host immune defense mechanism against T. gondii infection. | 10.1016/j.actatropica.2020.105589 |
others_206_1405 | Alteplase (recombinant tissue plasminogen activator [rt-PA]) label approval by the Food and Drug Administration remarks the contraindication of its use with known intracranial neoplasm because of potential bleeding complications. Despite this concern, the real risk of intracerebral bleeding in patients with intracranial neoplasms treated with rt-PA is unknown, and there are few reports of thrombolysis in patients with brain tumors. We report a case of a 78-year-old man who was seen in our emergency department within 2 hours from sudden onset of aphasia, right-sided hemiplegia, hypoesthesia, and homonymous hemianopsia. The National Institutes of Health Stroke Scale (NIHSS) score at admission was 20. Intra-arterial thrombolysis was performed with administration of.3 mg/kg of alteplase combined with mechanical thrombectomy. At discharge, his NIHSS score was 1, and after 90 days, his modified Rankin score was 1. To our knowledge, this is the first report of intra-arterial thrombolysis in a patient with acute ischemic stroke with an intracranial tumor. © 2013 Elsevier B.V. All rights reser | 10.1016/j.jstrokecerebrovasdis.2013.05.009 |
pubmed_886_238 | Cenani-Lenz syndrome (CLS) is an autosomal-recessive congenital disorder affecting distal limb development. It is characterized mainly by syndactyly and/or oligodactyly and is now shown to be commonly associated with kidney anomalies. We used a homozygosity-mapping approach to map the CLS1 locus to chromosome 11p11.2-q13.1. By sequencing candidate genes, we identified recessive LRP4 mutations in 12 families with CLS. LRP4 belongs to the low-density lipoprotein (LDL) receptor-related proteins (LRPs), which are essential for various developmental processes. LRP4 is known to antagonize LRP6-mediated activation of canonical Wnt signaling, a function that is lost by the identified mutations. Our findings increase the spectrum of congenital anomalies associated with abnormal lipoprotein receptor-dependent signaling. | 10.1016/j.ajhg.2010.03.004 |
pubmed_310_15767 | In the early visual system, neuronal responses can be extremely precise. Under a wide range of stimuli, cells in the retina and thalamus fire spikes very reproducibly, often with millisecond precision on subsequent stimulus repeats. Here we develop a mathematical description of the firing process that, given the recent visual input, accurately predicts the timing of individual spikes. The formalism is successful in matching the spike trains from retinal ganglion cells in salamander, rabbit, and cat, as well as from lateral geniculate nucleus neurons in cat. It adapts to many different response types, from very precise to highly variable. The accuracy of the model allows a compact description of how these neurons encode the visual stimulus. | 10.1016/s0896-6273(01)00322-1 |
pubmed_828_13489 | Decrease in stratospheric ozone absorption and increase in oxygen absorption with decreasing wavelength combine to produce a window of maximum atmospheric transmission near 210 nm. Since solar radiation in this spectral region dissociates molecular oxygen, the deep atmospheric penetration at this wavelength is of particular aeronomical interest. High resolution calculations of the transmittance down to 28.65 km were made for the 200-243-nm spectral range in this window region, in support of a stratospheric balloon flight from Fort Churchill in July 1974. The calculations were made by dividing the atmosphere into layers which were chosen so that each could be assumed homogeneous; optical depths were calculated separatelyfor each of these layers and then summed to obtain the over-all transmittance of the atmosphere. Absorptionby molecular oxygen (line and continuum) and by ozone was included, as well as extinction through Rayleigh scattering by air molecules. The calculated transmittances were combined with hig h altitude(above 100-km) rocket measurements of the sun-center spectrum and center-to-limb variations to give residual high resolution solar spectral flux for several altitudes and solar zenith angles. | 10.1364/AO.18.000964 |
pubmed_312_1375 | The study was carried out using 12 noninbred male cats and 14 white rats. In response to vestibulo-autonomic disorders the rats showed a decrease of beta-endorphin in the midbrain, medulla oblongata and hypothalamus as well as a reduction of met-enkephalin in the hypothalamus and medulla oblongata. The concentration of met-enkephalin in the adrenals increased and that of beta-endorphin in blood did not change. This may be attributed to the intraneuronal redistribution of opioids and their transfer to the pituitary or release into the cerebrospinal fluid. Opioid variations give evidence that vestibuloautonomic disorders in rats do not stimulate the pituitary-adrenal system. The cats were exposed to vestibulo-autonomic disorders and subsequent intracerebroventricular administration of regulatory peptides or injection of opiate receptor blockers into the chemoreceptor trigger zone. It was demonstrated that naloxone, gamma-endorphin and des-Tyr-gamma-endorphin were effective in protecting the vestibular function whereas ICI 154, 129 (a selective antagonist of delta-receptors) was practically ineffective. | pubmed_312_1375 |
others_76_9544 | A method has been developed to study aluminium (A1) toxicity towards Rhizobium. This involves growth in broth followed by washing and measurement of cell viability in deionized distilled water plus A1. The results illustrate the high degree of sensitivity and rapid response of Rhizobium leguminosarum biovar trifolii and R. loti to A1 under acid conditions but confirm earlier results on the relative tolerance of these two species. Copyright © 1987, Wiley Blackwell. All rights reser | 10.1111/j.1472-765X.1987.tb01601.x |
pubmed_970_16189 | BACKGROUND
Antimicrobial resistance is becoming increasingly important in both human and veterinary medicine. According to the One Health concept, an important step is to monitor the resistance patterns of pathogenic bacteria. In this study, the antimicrobial susceptibility patterns and trends of bacteria isolated from stray cats, hospital-admitted cats, and veterinary staff in South Korea between 2017 and 2018 were investigated.
RESULTS
The minimum inhibitory concentrations of different antibiotics for Staphylococcus spp., Enterobacteriaceae, and Enterococcus spp. were determined to establish representatives of different antibiotic classes relevant for treatment or surveillance. For Coagulase-positive and Coagulase-negative Staphylococci, resistance to fluoroquinolones was below 13%, but resistance to ampicillin and penicillin was high (20-88%). A total of 9.5, 12.1, and 40.3% of staphylococcal isolates from stray cats, hospital-admitted cats, and veterinary staff, respectively, were confirmed to be mecA positive. For Enterobacteriaceae, resistance to carbapenems, fluoroquinolones, and 3rd generation cephalosporins was low (0-11.1%). The Enterococcus spp. isolates showed no resistance to vancomycin. The antimicrobial resistance rates of the Staphylococcus spp. and Enterobacteriaceae isolates from stray cats were usually lower than those of isolates from hospital-admitted cats and veterinary staff, but the Enterococcus spp. isolates revealed the opposite. Thus, the antimicrobial resistance varied across bacterial species according to the source from which they were isolated.
CONCLUSIONS
Resistance to critically important compounds were low. However, the presence of antimicrobial resistance in cat isolates is of both public health and animal health concern. | 10.1186/s12917-020-02326-2 |
pubmed_733_16108 | The value of an APN in a role such as for the management of patients requiring LTMV is easily recognized. There are few healthcare providers who are as uniquely qualified to ensure the successful resolution of the many complex clinical and system issues that affect these patients' outcomes. Similar models of care using APNs in similar roles have been used successfully in other populations of patients at our institution. We hope that other hospitals will implement models using the APN to manage and monitor complex patient populations and continue to report the results so that the true value of the APN is recognized. | 10.1016/s0899-5885(02)00003-5 |
pubmed_10_9364 | Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls. Intriguingly, FL-VASP/239D abrogated the stimulatory effects of FL-VASP/WT and FL-VASP/239A cells on PKG activity. In turn, pharmacologic blockade of PKG in the presence of BAY60 reversed the inhibitory effect of BAY60 on naïve ASM cell migration. Taken together, we demonstrate for the first time that BAY60 inhibits ASM cell migration through cGMP/PKG/VASP signaling yet through mechanisms independent of pVASP·S239 and that FL-VASP overexpression regulates PKG activity in rat ASM cells. These findings implicate BAY60 as a potential pharmacotherapeutic agent against aberrant ASM growth disorders such as CAD and also establish a unique mechanism through which VASP controls PKG activity. | 10.1016/j.cellsig.2016.06.012 |
pubmed_405_10661 | MOTIVATION
High-throughput reverse-phase protein array (RPPA) technology allows for the parallel measurement of protein expression levels in approximately 1000 samples. However, the many steps required in the complex protocol (sample lysate preparation, slide printing, hybridization, washing and amplified detection) may create substantial variability in data quality. We are not aware of any other quality control algorithm that is tuned to the special characteristics of RPPAs.
RESULTS
We have developed a novel classifier for quality control of RPPA experiments using a generalized linear model and logistic function. The outcome of the classifier, ranging from 0 to 1, is defined as the probability that a slide is of good quality. After training, we tested the classifier using two independent validation datasets. We conclude that the classifier can distinguish RPPA slides of good quality from those of poor quality sufficiently well such that normalization schemes, protein expression patterns and advanced biological analyses will not be drastically impacted by erroneous measurements or systematic variations.
AVAILABILITY AND IMPLEMENTATION
The classifier, implemented in the "SuperCurve" R package, can be freely downloaded at http://bioinformatics.mdanderson.org/main/OOMPA:Overview or http://r-forge.r-project.org/projects/supercurve/. The data used to develop and validate the classifier are available at http://bioinformatics.mdanderson.org/MOAR. | 10.1093/bioinformatics/btu736 |
pubmed_563_3870 | PURPOSE
To demonstrate the biological function of Secreted Phosphoprotein 1(SPP1) and its immune suppressive role in the progression intrahepatic cholangiocarcinoma (ICC).
METHODS
We collected 62,770 cells' published transcriptome data of nine patients whose paired adjacent liver and tumor tissues were both available. We applied differential gene expression analysis to screen potential ICC marker genes, survival analysis to verify the prognostic value of SPP1, and correlation analysis to decipher factors that are related to SPP1 expression. The CellChat was used to distinguish interactions between cancer and T cells. CytoSig was applied to query cytokines that modulate CD44. Further, we established a proliferation score and correlated the score with inhibitory signals to determine the proliferation-suppressive function of SPP1-CD44.
RESULTS
SPP1 expression is significantly upregulated in tumoral epitheliums, and patients with higher SPP1 expression have worse survival (P < 0.05). Tumor cells communicate with T cells via SPP1-CD44 interactions. The average expression of SPP1 in malignant cells (SPP1m) and CD44 in T cells (CD44t) is moderately negatively correlated with T cell proliferation score. Immunosuppressive cytokine TGFβ-3 identified as an inducer of CD44 and was significantly negatively correlated with proliferation score (R = - 0.88, P < 0.01), and the negative correlation was aggravated in samples with high CD44 expression.
CONCLUSION
SPP1 is a prognostic marker of ICC and is associated with the genome heterogeneity. SPP1-CD44 hinders sustained proliferation of T cells, but immunosuppressive T cells in the tumor microenvironment may evade this inhibition by reducing CD44 expression. | 10.1007/s00432-022-04498-w |
pubmed_497_15090 | The aim of this report was to document the practice of vascular surgery for graduates of 4 general surgery training programs.Graduating residents from 1991 to 1995 were surveyed by phone to document the number of reconstructive vascular and dialysis access procedures that they performed during the most recent 12 months. Those who pursued additional training beyond general surgery or who did not successfully complete the certifying examination of the American Board of Surgery (ABS) were excluded. In addition, the Resident Review Committee for Surgery (RRC-S) defined category report for these same general surgeons during their residency was examined.Fifty-five percent (26 of 47) of the board-certified general surgeons do either reconstructive or dialysis access vascular surgery. The average number of procedures in the RRC-S defined category for this cohort was 76. During the focused 12 months, 1986 vascular procedures were done by these 26 surgeons (76 cases per surgeon).In certain regions of this country, a significant volume of vascular surgery is done by general surgeons who have an ABS primary certificate alone. The technique of control and repair of major arteries and veins, the consequences of distal organ ischemia, reperfusion injury, thrombosis, and embolization are important anatomic and physiologic principles that must be taught in the curriculum to general surgeons, regardless of their future surgical careers. (Curr Surg 57:381-383. Copyright 2000 by the Association of Program Directors in Surgery.) | 10.1016/s0149-7944(00)00271-3 |
others_196_7700 | Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF. Copyright © 2020 by The American Society of Tropical Medicine and Hygien | 10.4269/ajtmh.20-0122 |
pubmed_58_6381 | INTRODUCTION
To compare the ability of Body Mass Index (BMI), waist circumference (WC) and waist to height ratio (WHtR) to estimate cardiovascular disease (CVD) risk levels in adolescents.
EVIDENCE ACQUISITION
A systematic review and meta-analysis was performed after a database search for relevant literature (Cochrane, Centre for Review and Dissemination, PubMed, British Nursing Index, CINAHL, BIOSIS citation index, ChildData, metaRegister).
EVIDENCE SYNTHESIS
The study included 117 records representing 96 studies with 994,595 participants were included in the systematic review, 14 of which (13 studies, N.=14,610) were eligible for the meta-analysis. The results of the meta-analysis showed that BMI was a strong indicator of systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and insulin; but not total cholesterol, low-density lipoprotein or glucose. Few studies were eligible for inclusion in the meta-analysis considering WC or WHtR (N.≤2). The narrative synthesis found measures of central adiposity to be consistently valid indicators of the same risk factors as BMI.
CONCLUSIONS
BMI was an indicator of CVD risk. WC and WHtR were efficacious for indicating the same risk factors BMI performed strongly for, though there was insufficient evidence to judge the relative strength of each measure possibly due to heterogeneity in the methods for measuring and classifying WC. | 10.23736/S0026-4946.18.05175-7 |
pubmed_122_22893 | Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) plays a key role in multiple events during infection including virus entry, cell-to-cell spread, and virus-induced syncytia formation. Here, we provide evidence that an arginine/lysine cluster located at the transmembrane-cytoplasm interface of gD critically contributes to viral spread and cell-cell fusion. Our studies began with the discovery that packaging of gD into virions is almost completely blocked in the absence of tegument protein UL16. We subsequently identified a novel, direct, and regulated interaction between UL16 and gD, but this was not important for syncytia formation. However, a mutational analysis of the membrane-proximal basic residues of gD revealed that they are needed for the gBsyn phenotype, salubrinal-induced fusion of HSV-infected cells, and cell-to-cell spread. Finally, we found that these same gD tail basic residues are not required for cell fusion induced by a gKsyn variant. | 10.1016/j.virol.2018.09.018 |
pubmed_948_2419 | Changes in bioelectric properties of alveolar epithelial cell monolayers due to pharmacological agents such as beta-agonists, amiloride and ouabain have recently been reported. In order to determine specifically which ionic species contribute to these changes, fluxes of Na+ and Cl- across primary cultured monolayers of rat type II pneumocytes were directly measured. Monolayers were mounted in modified flux chambers and short-circuited. Unidirectional fluxes of 22Na (or 36Cl) and [14C]-mannitol were measured simultaneously. Experimental maneuvers included apical (A) exposure to 10 microM amiloride, basolateral (B) exposure to 1 mM ouabain, or basolateral exposure to 20 microM terbutaline. Results show that baseline monolayers actively reabsorb Na+ (about 0.14 micro Eq.cm-2.h-1) from the apical fluid, while mannitol and Cl- appear to traverse the alveolar epithelium passively. Active Na+ reabsorption was abolished by amiloride or ouabain, while Cl- and mannitol fluxes were unaffected. Terbutaline, on the other hand, markedly increased net absorption of Na+ and caused active transport of Cl- in the A to B direction. Passive mannitol flow was somewhat increased with terbutaline. These data indicate that active Na+ reabsorption across alveolar epithelial monolayers is dependent on intact Na+,K(+)-ATPase activity and cell Na+ entry (probably via Na+ channels), and can be stimulated by beta-agonists. Beta-agonists also cause active reabsorption of Cl- (passive under other conditions). | 10.1016/0034-5687(91)90065-q |
pubmed_530_22166 | Meningioma's account for around 15% of all primary brain tumors with some 10% of meningiomas arising in the posterior fossa. In rare cases, a meningioma can form around the endolymphatic sac. When formed in the posterior fossa, meningioma tumors can produce vague, non-specific vertiginous symptoms. Research has observed that a subset of these lesions could produce symptoms indistinguishable from those of Meniere's disease. Therefore, we described the clinical features of a case of posterior petrous meningioma with recurrent vertigo as well as the substantial resolution of symptoms after tumor removal via transmastoid approach. | 10.3342/ceo.2012.5.4.234 |
pubmed_16_3689 | Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, was identified in the rat stomach. This peptide acts through nitric oxide (NO) by expressing endothelial nitric oxide synthase (eNOS) and down regulating inducible nitric oxide synthase (iNOS) at its gastroproprotective effect against restraint stress induced damage. Recently the ghrelin receptor has also been detected in peripheral systems including immune tissue. We have investigated the possible effect of ghrelin on phagocytic activity of peritoneal macrophages in acute cold-restraint stress (ACRS) exposed rats. The rats were divided into control, stress and ghrelin groups. In ghrelin groups, single dose and three days consecutive dose of ghrelin (20 microg/kg. i.p.) were applied to rats that were exposed to ACRS for 4 h. 1 ml of saline was injected i.p. after ACRS for 3 consecutive days to the rats of the stress groups. Ghrelin administration reduced the increased phagocytic activity induced by ACRS. We conclude that ghrelin exerts an important role at macrophage phagocytic activity in ACRS exposed rats. | 10.1016/j.regpep.2006.08.010 |
pubmed_26_2819 | Intestinal T-cell lymphoma is a heterogenous group. These tumors differ in their association with enteropathy, intraepithelial or nonintraepithelial origin, primary or secondary involvement, and T-cell or natural killer-like T-cell immunophenotype. There are also nonneoplastic conditions, such as celiac disease, refractory sprue, and reactive T-cell infiltration that mimic intestinal T-cell lymphoma. Therefore, the differential diagnosis requires extensive morphologic, immunophenotypic, and molecular genetic studies. A subset of primary intestinal intraepithelial T-cell lymphoma has emerged in recent years that is distinguished from enteropathy-type T-cell lymphoma in terms of clinical presentation (nonenteropathic), morphology (monomorphic small to medium-sized cells), immunophenotype (CD3(-)CD8(+)CD56(+)), and cytogenetics. We report such a case with a unique immunophenotype (CD3(-), cytoplasmic CD3(+), CD4(-), CD8(+), CD5(-), CD7(+), CD16(-), CD56(+), CD57(-), CD103(+), T-cell intracellular antigen 1(+), and betaF1(+)) that is comparable to that of a newly identified subset of intraepithelial T cells. The tumor progressed rapidly and the patient died within 6 months after the onset of the disease. We recommend a large monoclonal antibody panel for the differential diagnosis of this heterogeneous group of T-cell lymphoma. | 10.1043/1543-2165-133.1.133 |
pubmed_447_20975 | On the basis of literature review the article makes an appreciation of various methods for tuberculosis serological diagnostics. The authors mark a high information level of immunofermental analysis (IFA). 126 tuberculosis patients, 122 patients with non-tuberculosis etiology and 410 donors were examined with the aid of IFA (phosphide antigen). The min. diagnostic titer in pulmonary tuberculosis is 1:320, in nonpulmonary--1:160. The max. antigen titers in IFA (optical density unit of measurement) were in the cases of disseminated tuberculosis 1.32 0.12; the min.--in uterine tube tuberculosis--0.92 0.08. The titers of donors were 0.20 0.03, and of patients with non-tuberculosis diseases--0.25 0.04. IFA is recommended for practical application in tuberculosis and infectious clinics. | pubmed_447_20975 |
pubmed_504_7629 | BACKGROUND/AIMS
Several studies have shown that colorectal neoplasms (CRN) including colorectal cancer (CRC) may be prevalent in patients with gastric cancer. However, in most of these studies, colonoscopy to investigate the prevalence of CRN was performed prior to surgery. We aimed to investigate whether CRN was more prevalent in postgastrectomy gastric cancer patients than in healthy individuals.
METHODS
We reviewed the medical records of those patients within a cohort of gastric cancer patients with gastrectomy who underwent colonoscopy between 2016 and 2017. Controls age- and sex-matched with gastric cancer patients at a 2:1 ratio were identified among those who underwent colonoscopy at a health-promotion center. The frequencies of CRN, advanced CRN (ACRN), and CRC among patients with gastrectomy were compared with those in the control subjects. A total of 744 individuals (gastric cancer, 248; control, 496) were included.
RESULTS
The rates of CRN and ACRN in the gastric cancer group were higher than those in the healthy individuals (CRN, 47.6% vs. 34.7%, P< 0.001; ACRN, 16.9% vs. 10.9%, P= 0.020). The rate of CRC was comparable between the 2 groups (2.0% vs. 0.6%, P= 0.125). Multivariate analysis identified previous gastrectomy for gastric cancer and male sex as significant risk factors for (A)CRN.
CONCLUSIONS
CRN and ACRN were more prevalent in patients who underwent surgery for gastric cancer than in the control group. Regular surveillance colonoscopy at appropriate intervals is indicated after gastrectomy. | 10.5217/ir.2020.00009 |
pubmed_367_6246 | Behavioural performance in the Go/NoGo task was compared with caregiver and teacher reports of inattention and hyperactivity-impulsivity in 1,151 children (N = 557 boys; N = 594 girls) age 9- 10-years-old. Errors of commission (NoGo errors) were significantly correlated with symptom counts of hyperactivity-impulsivity, while errors of omission (Go errors) were significantly correlated with symptom counts for inattention in both caregiver and teacher reports. Cross-correlations were also evident, however, such that errors of commission were related to inattention symptoms, and errors of omission were related to hyperactivity-impulsivity. Moreover, hyperactivity-impulsivity and inattention symptoms were highly intercorrelated in both caregiver (r = .52) and teacher reports (r = .70), while errors of commission and omission were virtually uncorrelated in the Go/NoGo task (r = .06). The results highlight the difficulty in disentangling hyperactivity-impulsivity and inattention in questionnaires, and suggest that these constructs may be more clearly distinguished in laboratory measures such as the Go/NoGo task. | 10.1348/026151008X314919 |
pubmed_732_13840 | Using innovative data with objective and subjective measures of stress collected from 122 employed men and women, this paper tests the thesis of the Time Bind by asking whether people report lower stress levels at work than at home. The study finds consistent support for the Time Bind hypothesis when examining objective stress data: when participants were at work they had lower values of the stress hormone cortisol than when they were at home. Two variables moderated this association - income and children at home - such that the work as haven effect was stronger for those with lower incomes and no children living at home. Participants also, however, consistently reported higher subjective stress levels on work days than on non-work days, which is in direct contrast to the Time Bind hypothesis. Although our overall findings support Hochschild's hypothesis that stress levels are lower at work, it appears that combining work and home increases people's subjective experience of daily stress. | pubmed_732_13840 |
pubmed_1127_5077 | Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest, terminal differentiation, and apoptosis in a broad spectrum of human tumors and animal xenograft models. JNJ-26481585 is a hydroxamic acid derivative, second-generation pan-HDAC inhibitor that has demonstrated high potency in preclinical studies. In the current study, we demonstrated that JNJ-26481585 has antileukemia and molecular activity in leukemia cell lines and primary human leukemia cells. We also observed a synergistic effect between treatment with decitabine and JNJ-26481585. In conclusion, JNJ-26481585 is a potent second-generation pan-HDAC inhibitor with activity in human leukemia, and it is currently in clinical development. | 10.1016/j.leukres.2009.07.024 |
pubmed_1019_116 | Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide, and favours vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation and develops portal hypertension. Portal hypertension, in turn, causes endothelial dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike dysfunction in LSECs, endothelial dysfunction in the splanchnic and systemic circulation causes overproduction of vasodilator molecules, leading to arterial vasodilation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathological consequences, such as oesophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension has been elucidated, the underlying cellular and molecular mechanisms causing endothelial dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on endothelial dysfunctions found during the development of cirrhosis and portal hypertension with a focus on the intra- and extrahepatic circulations. The article ends by discussing the future directions of the study for endothelial dysfunction. | 10.1111/j.1478-3231.2011.02579.x |
pubmed_114_12156 | Following a short and selective summary of findings from psychological studies on lead-induced cognitive dysfunction in man, our own studies in lead-exposed children are briefly described in more detail. These studies, run in the cities of Duisburg and Stolberg, were based on tooth lead levels as the principal indicator of long-term cumulative lead exposure. From a comprehensive sample of neuropsychological outcome measures, only few significant findings emerged, namely lead-related deficits of visual-motor integration and of reaction performance, but not of general intelligence. Without exception, the observed lead effects were small compared to those of social background. An interesting interaction was found between lead exposure and social background for visual-motor integration and for reaction performance: for both these measures, but not for intelligence, the degree of association between performance deficit and lead exposure was more pronounced in socially disadvantaged children than in those from a more middle-class background. This finding was tentatively discussed within a transactional model of development. The common practice of simply controlling the effects of confounding social factors by analysis of covariance or related techniques appears doubtful in this context. | 10.1159/000118077 |
pubmed_612_17387 | AIM
Extrahepatic biliary atresia is a rare disorder. This creates challenges in the quality and quantity of research conducted. This issue is exacerbated by the potential heterogeneity in the reported outcomes in research examining the management of biliary atresia. A core outcome set is required to standardise reporting on the management of biliary atresia in research, facilitate systematic reviews that include outcomes of greatest importance to patients and clinicians, and to evaluate the quality of the existing evidence base on the management of biliary atresia.
METHODS
A list of all potential outcomes will be developed through a systematic review of the literature. This list will be refined through a three-stage Delphi approach, involving key stakeholders in the management of biliary atresia. This will include patients and their parents, clinicians, nurses and allied health professionals. In this way, outcomes will be prioritised into a set of consensus core outcomes.
CONCLUSION
The development of a core outcome set in biliary atresia management is needed to guide future research and assist in evaluating the quality of existing research.
ETHICS AND DISSEMINATION
Ethical approval has been granted by the Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC), Ref: HREC/20/QCHQ/62448. Results of the study will be published in an open access format. | 10.1136/bmjopen-2020-047224 |
pubmed_734_5994 | Many tools that explore models of protein complexes are also able to analyze interactions between specific residues and atoms. A comprehensive exploration of these interactions can often uncover aspects of protein-protein recognition that are not obvious using other protein analysis techniques. This paper describes DiffBond, a novel method for searching for intermolecular interactions between protein complexes while differentiating between three different types of interaction: hydrogen bonds, ionic bonds, and salt bridges. DiffBond incorporates textbook definitions of these three interactions while contending with uncertainties that are inherent in computational models of interacting proteins. We used it to examine the barnase-barstar, Rap1a-raf, and Smad2-Smad4 complexes, as well as a subset of protein complexes formed between three-finger toxins and nAChRs. Based on electrostatic interactions established by previous experimental studies, DiffBond was able to identify ionic and hydrogen bonds with high precision and recall, and identify salt bridges with high precision. In combination with other electrostatic analysis methods, DiffBond can be a useful tool in helping predict influential amino acids in protein-protein interactions and characterizing the type of interaction. | 10.1109/bibm52615.2021.9669850 |
others_15_2016 | The Diving Committee of the Undersea and Hyperbaric Medical Society has reviewed available evidence in relation to the medical aspects of rescuing a submerged unresponsive compressed-gas diver. The rescue process has been subdivided into three phases, and relevant questions have been addressed as follows. Phase 1, preparation for ascent: If the regulator is out of the mouth, should it be replaced? If the diver is in the tonic or clonic phase of a seizure, should the ascent be delayed until the clonic phase has subsided? Are there any special considerations for rescuing rebreather divers? Phase 2, retrieval to the surface: What is a "safe" ascent rate? If the rescuer has a decompression obligation, should they take the victim to the surface? If the regulator is in the mouth and the victim is breathing, does this change the ascent procedures? If the regulator is in the mouth, the victim is breathing, and the victim has a decompression obligation, does this change the ascent procedures? Is it necessary to hold the victim's head in a particular position? Is it necessary to press on the victim's chest to ensure exhalation? Are there any special considerations for rescuing rebreather divers? Phase 3, procedure at the surface: Is it possible to make an assessment of breathing in the water? Can effective rescue breaths be delivered in the water? What is the likelihood of persistent circulation after respiratory arrest? Does the recent advocacy for "compressiononly resuscitation" suggest that rescue breaths should not be administered to a non-breathing diver? What rules should guide the relative priority of in-water rescue breaths over accessing surface support where definitive CPR can be started? A "best practice" decision tree for submerged diver rescue has been proposed. Copyright © 2012 Undersea & Hyperbaric Medical Society, I | others_15_2016 |
pubmed_854_7241 | Fifty three children were referred following community needlestick injuries, August 1995 to September 2003. Twenty five attended for serology six months later. None were positive for HIV, or hepatitis B or C. Routine follow up after community needlestick injury is unnecessary. HIV post-exposure prophylaxis should only be considered in high risk children. | 10.1136/adc.2004.055624 |
pubmed_278_8318 | BACKGROUND
We aim to develop a population pharmacokinetics (PopPK) model of vancomycin for the treatment of septicemia in infants younger than one year. Factors influence of the PK was investigated to optimize vancomycin dosing regimen.
METHODS
The nonlinear mixed effects modelling software (NONMEM) was used to develop the PopPK model of vancomycin. The stability and predictive ability of the final model were assessed by using normalized prediction distribution errors (NPDE) and bootstrap methods. The final model was subjected to Monte Carlo simulation in order to determine the optimal dose.
RESULTS
A total of 205 trough and peak concentrations in 94 infants (0-1 year of age) with septicemia were analyzed. The interindividual variability of the PK parameter was described by the exponential model. Residual error was better described by the proportional model than the mixed proportional and addition models. Serum creatinine concentration and body weight are the major factors that affect the PK parameters of vancomycin. The clearance was shown to be higher when ceftriaxone was co-treated. More than two model evaluation methods showed better stability than the base model, with superior predictive performance, which can develop individualized dosing regimens for clinical reference. Through prediction of final model, the trough concentration was more likely < 5 mg/L when a routine dose of 10 mg/kg is administered every 6 h to 3-9-month-old infants. Therefore, the dose should be increased in the treatment of infant septicemia.
CONCLUSIONS
The stable and effective PopPK model of vancomycin in Chinese infants with septicemia was established. This model has satisfactory predictive ability for clinically individualized dosing regimens in this vulnerable population. | 10.1186/s40360-021-00489-8 |
pubmed_0_10017 | Our study provides a promising alternative of biomimetic coating which functionalizes the dental implant with adhesion peptides and may be useful for enhancing the bone remodeling around Ti implants. A chimeric peptide consisting of an Arg-Gly-Asp (RGD) sequence (mediating cell adhesion) and a RKLPDA (minTBP-1) sequence (specifically recognizing and binding to Ti substrate) was designed and synthesized. The chimeric peptide affinity to Ti disks, as well as its role in mediating MC3T3-E1 cell attachment and afterwards spreading on pre-coated Ti disks, was investigated. The chimeric peptide not only showed favorable affinity to Ti surfaces but also facilitated the adhesion of MC3T3-E1 cells. | 10.1007/s10529-010-0411-9 |
pubmed_227_9616 | [reaction: see text] A diammonium salt of chiral 1,1'-binaphthyl-2,2'-diamine and trifluoromethanesulfonimide (Tf(2)NH) shows excellent catalytic activity and enantioselectivity for the Diels-Alder reaction of alpha-acyloxyacroleins with cyclic dienes. For example, in the presence of 5 mol % of the ammonium catalyst, the Diels-Alder reaction of alpha-(cyclohexanecarbonyloxy)acrolein with cyclopentadiene proceeded in EtCN at -75 degrees C to give the adducts in 88% yield with 92% exo and 91% ee. This catalyst can be easily prepared in situ by mixing the commercially available chiral diamine and Tf(2)NH. | 10.1021/ol060490l |
pubmed_322_25359 | INTRODUCTION
The literature data indicate that bacterial vaginosis (BV) increases the risk of development of lower urinary tract infections (LUTI). Thus, it is reasonable to assume that the use of probiotics, in particular Lactoginal, can be effective in preventing relapses of LUTI.
AIM
To study the efficiency of probiotics, particularly Lactoginal, for the prevention of recurrent LUTI and BV.
MATERIALS AND METHODS
A total of 120 women with chronic recurrent bacterial cystitis in the acute stage and concomitant bacterial vaginosis were randomized into two groups of 60 patients. In group 1, standard antibacterial therapy was used according to guidelines of professional societies. In group 2, vaginal probiotic Lactoginal was prescribed after standard treatment.
RESULTS
The results obtained in this study correspond to the literature data. The additional use of probiotics in the complex therapy of chronic lower urinary tract inflammation contributed to the normalization of the lactobacilli concentration in 93% of cases, in contrast to standard antibacterial therapy, after which the normal flora was preserved only in 40% of cases. In addition, a reduction in the number of relapses of BV was seen. Moreover, it was found that in the group of patients treated with Lactoginal, there was 18.3% less recurrence of cystitis within 6 months than in the control group (p<0.05).
CONCLUSION
The use of probiotics, in particular, Lactoginal vaginal capsules, in women with BV after antibacterial therapy contributes to a faster recovery and longer preservation of the normal vaginal flora, which allows to the prolongate the relapse-free period of both chronic bacterial cystitis and BV. | pubmed_322_25359 |
pubmed_34_6063 | BACKGROUND
The aim of this study was to determine the overall survival, progression-free survival, and toxicity associated with adjuvant administration of docetaxel and gemcitabine for completely resected patients with stage II and IIIA non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS
Thirty-nine eligible patients had surgical resection for pathological stage II or IIIA disease and received postoperative gemcitabine 1000 mg/m2 followed by docetaxel 80 mg/m2 on days 1 and 14. Cycles were repeated every 28 days.
RESULTS
Treatment compliance was acceptable, at 83%. The median duration of follow-up, time to disease progression, and overall survival was 36.7 months, 17 months and 21 months, respectively. Toxicities were acceptable. Treatment failure revealed brain metastasis (15%), intrathoracic recurrence (24%) and systemic metastasis (36%).
CONCLUSION
The biweekly administration of docetaxel and gemcitabine is a safe, well-tolerated and convenient chemotherapy regimen in the adjuvant setting of completely resected NSCLC stage II and III, with efficacy similar to that reported in other regimens. Hence, this nonplatinum based regimen appears promising and warrants further evaluation. | pubmed_34_6063 |
pubmed_167_26016 | BACKGROUND
Spalax, the blind mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 years of Spalax research, no spontaneous cancer development has been observed. The mechanisms underlying this resistance are still not clarified. We investigated the genetic difference between Spalax and mice that might enable the Spalax relative resistance to cancer development. We compared Spalax and mice responses to a treatment with the carcinogen 3-Methylcholantrene, as a model to assess Spalax' cancer-resistance.
RESULTS
We compared RNA-Seq data of untreated Spalax to Spalax with a tumor and identified a high number of differentially expressed genes. We filtered these genes by their expression in tolerant Spalax that resisted the 3MCA, and in mice, and found 25 genes with a consistent expression pattern in the samples susceptible to cancer among species. Contrasting the expressed genes in Spalax with benign granulomas to those in Spalax with malignant fibrosarcomas elucidated significant differences in several pathways, mainly related to the extracellular matrix and the immune system. We found a central cluster of ECM genes that differ greatly between conditions. Further analysis of these genes revealed potential microRNA targets. We also found higher levels of gene expression of some DNA repair pathways in Spalax than in other murines, like the majority of Fanconi Anemia pathway.
CONCLUSION
The comparison of the treated with the untreated tissue revealed a regulatory complex that might give an answer how Spalax is able to restrict the tumor growth. By remodeling the extracellular matrix, the possible growth is limited, and the proliferation of cancer cells was potentially prevented. We hypothesize that this regulatory cluster plays a major role in the cancer resistance of Spalax. Furthermore, we identified 25 additional candidate genes that showed a distinct expression pattern in untreated or tolerant Spalax compared to animals that developed a developed either a benign or malignant tumor. While further study is necessary, we believe that these genes may serve as candidate markers in cancer detection. | 10.1186/s12864-018-5417-z |
pubmed_306_3528 | We evaluated Aedes atlanticus Dyar and Knab, Aedes infirmatus Dyar and Knab, Aedes vexans (Meigen), Anopheles crucians Wiedemann, Coquillettidia perturbans (Walker), Culex nigripalpus Theobald, Mansonia dyari Belkin, Heinemann, and Page, and Psorophora ferox (Von Humboldt) from Florida to determine which of these species should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America. Female mosquitoes that had fed on adult hamsters inoculated with RVFV were incubated for 7-21 d at 26 degrees C, then allowed to refeed on susceptible hamsters, and tested to determine infection, dissemination, and transmission rates. We also inoculated mosquitoes intrathoracically, held them for 7 d, and then allowed them to feed on a susceptible hamster to check for a salivary gland barrier. When exposed to hamsters with viremias > or = 10(7.6) plaque-forming units per milliliter of blood, at least some individuals in each of the species tested became infected; however, Cx. nigripalpus, An. crucians, and Ae. infirmatus were essentially incompetent vectors in the laboratory because of either a midgut escape or salivary gland barrier. Each of the other species should be considered as potential vectors and would need to be controlled if RVFV were introduced into an area where they were found. Additional studies need to be conducted with other geographic populations of these species and to determine how environmental factors affect transmission. | 10.1603/me13049 |
pubmed_89_23491 | Multirobot coordination for finding multiple users in an environment can be used in numerous robotic applications, including search and rescue, surveillance/monitoring, and activities of daily living assistance. Existing approaches have limited coordination between robots when generating team plans or do not consider user location probability within these plans. This results in long searches and robots potentially revisiting the same locations in succession. In this article, we present a novel multirobot person search system to generate search plans for multirobot teams to find multiple dynamic users before a deadline. Our approach is unique in that it simultaneously considers the search actions of all robots and user location probabilities when generating team plans, where user location probabilities are represented as conditional spatial-temporal probability density functions. We model this multirobot person search problem as a two-stage optimization problem to maximize the expected number of users found before the deadline. Stage 1 solves the action selection problem to determine a set of team actions, and the second stage solves the action allocation problem to distribute these actions amongst the robots. Namely, in stage 1, a novel conditional multiperiod multiknapsack problem is modeled as a min-flow graph solved sequentially by the Bellman-Ford shortest path algorithm. Stage 2 is a variant of the min-max multitraveling salesperson problem which models the environment topology as a search region network and search times selected by the previous stage. This stage is solved by a novel fuzzy clustering method. Numerous experiments comparing our proposed method to other existing approaches with varying environment sizes, search durations, and the number of users showed that our approach was able to find more target users before a defined deadline. | 10.1109/TCYB.2022.3166481 |
pubmed_762_20530 | BACKGROUND
Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus.
OBJECTIVE
To investigate the association between C-reactive protein (CRP), the classic acute-phase protein, and incident type 2 diabetes mellitus among middle-aged men.
METHODS
A total of 2052 initially nondiabetic men aged 45 to 74 years who participated in 1 of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995 were followed up for an average of 7.2 years. Incidence of diabetes was assessed by questionnaire mailed to participants in 1998. High-sensitive CRP was measured by an immunoradiometric assay.
RESULTS
A total of 101 cases of incident diabetes occurred during the follow-up period. The age-standardized incidence rate was 6.9 per 1000 person-years. Men with CRP levels in the highest quartile (CRP > or = 2.91 mg/L) had a 2.7 times higher risk of developing diabetes (95% confidence interval, 1.4-5.2) compared with men in the lowest quartile (CRP < or = 0.67 mg/L) in a Cox proportional hazards model adjusted for age and survey. After further adjustment for body mass index, smoking, and systolic blood pressure, the observed association was significantly reduced and became nonsignificant.
CONCLUSIONS
Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus in middle-aged men. Inflammation could be one mechanism by which known risk factors for diabetes mellitus, such as obesity, smoking, and hypertension, promote the development of diabetes mellitus. | 10.1001/archinte.163.1.93 |
pubmed_1077_12326 | For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant. Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene--an epoch proposed for the present time interval--island biogeography is dominated by the economic isolation of human populations. | 10.1038/nature13739 |
pubmed_946_10657 | The replantation of amputated extremities is justified only by the ultimate good function and appearance of the replanted part. This paper is a critical review of our clinical experience with forearm replantation and revascularization in 6 patients over the past ten years. All replanted parts survived. The long-term functional results of the forearm replants are analyzed. Return of function depends on nerve regeneration. The functional outcome in the first patient was unsatisfactory due to poor motor and sensory return. Specific attention directed to careful primary neurorrhaphy in subsequent cases yielded favorable results. We believe that two factors in particular are central in achieving good functional results in forearm replantation--careful repair of the severed major peripheral nerves, and postoperative hand rehabilitation programs. | 10.1097/00000637-198301000-00004 |
others_257_14169 | Pre-plant soil fumigation with methyl bromide (MB) is a standard practice for controlling soil-borne diseases especially for strawberry diseases. However, the application of MB will be forbidden in China in the year 2015. For this reason, a bio-product named Kangdi 3 was tested as an alternative to MB in strawberry greenhouses in Mancheng (Hebei Province) and Donggang (Liaoning province), China in 2005 and 2006. Methyl bromide at a normal dosage of 500 kg/hm2 and Kangdi 3 at three dosages of 750, 1500 and 2250 kg/hm 2 were tested. Plots without any treatment were used as the control. During the growing stage, assessments were made on fungal communities in rhizosphere, growth status of strawberry, the disease levels on roots as well as the yields. Results showed that Kangdi 3 significantly reduced the quantity of fungi and the disease index, while enhancing strawberry growth and the yields compared with the untreated control. Therefore, Kangdi 3 is a great potential substitute for methyl bromide to control replant diseases in strawberry. © 2008 Higher Education Press and Springer-Verl | 10.1007/s11703-008-0001-y |
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