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pubmed_742_6110
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Pharmacological levels of zinc oxide can promote growth and health of weaning piglets, but the underlying molecular mechanisms are yet not fully understood. The aim of this study was to determine changes in the global hepatic protein expression in response to dietary zinc oxide in weaned piglets. Nine half-sib piglets were allocated to three dietary zinc treatment groups (50, 150, 2500 mg/kg dry matter). After 14 d, pigs were euthanized and liver samples taken. The increase in hepatic zinc concentration following dietary supplementation of zinc was accompanied by up-regulation of metallothionein mRNA and protein expression. Global hepatic protein profiles were obtained by two-dimensional difference gel electrophoresis following matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. A total of 15 proteins were differentially (P<0.05) expressed between groups receiving control (150 mg/kg) or pharmacological levels of zinc (2500 mg/kg) with 7 down- (e.g. arginase1, thiosulfate sulfurtransferase, HSP70) and 8 up-regulated (e.g. apolipoprotein AI, transferrin, C1-tetrahydrofolate synthase) proteins. Additionally, three proteins were differentially expressed with low zinc supply (50 mg/kg Zn) in comparison to the control diet. The identified proteins were mainly associated with functions related to cellular stress, transport, metabolism, and signal transduction. The differential regulation was evaluated at the mRNA level and a subset of three proteins of different functional groups was selected for confirmation by western blotting. The results of this proteomic study suggest that zinc affects important liver functions such as blood protein secretion, protein metabolism, detoxification and redox homeostasis, thus supporting the hypothesis of intermediary effects of pharmacological levels of zinc oxide fed to pigs.
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10.1371/journal.pone.0081202
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pubmed_434_6990
|
Mathematical models have been used to study the dynamic interaction of many infectious diseases with the host's immune system. In this paper, we study Varicella Zoster Virus, which is responsible for chicken pox (varicella), and after a long period of latency, herpes zoster (shingles). After developing the model and demonstrating that is exhibits the type of periodic behavior necessary for long term latency and reactivation, we examine the implications of the model for vaccine booster programs aimed at preventing herpes zoster.
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10.3934/mbe.2010.7.765
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pubmed_776_11588
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Twenty infertile women with fibroids were treated with luteinizing hormone releasing hormone agonists (LHRHa) to investigate if the use of these drugs, both with and without myomectomy, was effective in contributing to pregnancy in these women. All women had fibroids as their sole cause for infertility. Seven women conceived within 1 year of myomectomy or LHRHa treatment alone without myomectomy. The overall pregnancy rate was 36% and the postmyomectomy pregnancy rate was 50%. Initial fibroid size and extent of fibroid shrinkage on LHRHa therapy made no difference to the subsequent pregnancy rate. We also found no significant interaction between the number of fibroids present and the effect of myomectomy on the proportion of pregnancies. We conclude that the fertility enhancing value of myomectomy in otherwise idiopathic infertility is confirmed, and that the use of LHRHa premyomectomy in infertile women needs to be investigated in randomized controlled trials to assess its value as a preoperative therapy.
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10.3109/09513599309152480
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pubmed_462_14089
|
M.1 monoclonal antibody has previously been shown to passively transfer partial resistance to schistosome infection within mice and to recognize a 28-kDa antigen that has peptide sequence homology with triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1). We have now isolated the complete coding DNA for Schistosoma mansoni TPI and confirmed that this cDNA encodes the 28-kDa antigen recognized by M.1. The predicted translation product has strong homology with other TPIs, particularly from higher eukaryotes, and the sequence homology is greatest in regions known to form the active site. The complete coding DNA has been expressed within an Escherichia coli host to produce high levels of soluble, recombinant S. mansoni TPI protein. The product is recognized and purified by the M.1 antibody and is a functional TPI with an intrinsic specific activity comparable to that of rabbit and yeast TPI.
|
10.1073/pnas.89.5.1842
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pubmed_540_11897
|
Deep learning has been widely utilized for medical image segmentation. The most commonly used U-Net and its variants often share two common characteristics but lack solid evidence for the effectiveness. First, each block (i.e., consecutive convolutions of feature maps of the same resolution) outputs feature maps from the last convolution, limiting the variety of the receptive fields. Second, the network has a symmetric structure where the encoder and the decoder paths have similar numbers of channels. We explored two novel revisions: a stacked dilated operation that outputs feature maps from multi-scale receptive fields to replace the consecutive convolutions; an asymmetric architecture with fewer channels in the decoder path. Two novel models were developed: U-Net using the stacked dilated operation (SDU-Net) and asymmetric SDU-Net (ASDU-Net). We used both publicly available and private datasets to assess the efficacy of the proposed models. Extensive experiments confirmed SDU-Net outperformed or achieved performance similar to the state-of-the-art while using fewer parameters (40% of U-Net). ASDU-Net further reduced the model parameters to 20% of U-Net with performance comparable to SDU-Net. In conclusion, the stacked dilated operation and the asymmetric structure are promising for improving the performance of U-Net and its variants.
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10.1016/j.compbiomed.2022.105891
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pubmed_643_24916
|
BACKGROUND
Functional mitral regurgitation (FMR) is a common finding among patients with heart failure (HF) and it is related to adverse events. Outcomes in patients undergoing transcatheter mitral valve repair (TMVR) are still a matter of debate. We performed a meta-analysis to assess mid- and long-term outcomes of patients with FMR treated with MitraClip® compared to medical management.
METHODS
We conducted an electronic database search of all published data PubMed Central, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar databases. The primary end-point was all-cause mortality. The secondary end-points were hospitalizations for HF, need for heart transplantation or left ventricular assist device, unplanned mitral valve surgery, myocardial infarction and stroke.
RESULTS
Five studies (n = 1513 patients) were included in the analysis. The summary estimate including all the available studies showed a statistically significant reduction in all-cause mortality favoring MitraClip® (HR 0.56, CI 95% [0.38-0.84]) and HF hospitalizations (HR 0.65; CI 95% [0.46-0.92]). A significant reduction in the indication for advanced HF therapies (OR 0.48; CI 95% [0.25-0.90]) or the need for unplanned mitral valve surgery (OR 0.20; CI 95% [0.07-0.57]) was also found in the group of patients that underwent TMVR. No differences in the incidence of myocardial infarction or stroke were found between both groups of treatment. No publication bias was detected.
CONCLUSION
TMVR with MitraClip® system was related to a significant reduction in all-cause mortality, hospitalizations for HF and the need for HF transplant, left ventricular assist device or unplanned surgery beyond 1-year follow up.
|
10.1016/j.carrev.2019.06.008
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pubmed_722_2151
|
OBJECTIVES
Study objectives were to identify groups of older patients with similar patterns of health care use in the 12 months preceding an index outpatient emergency department (ED) visit and to identify patient-level predictors of group membership.
METHODS
Subjects were adults ≥ 65 years of age treated and released from an academic medical center ED. Latent cluster analysis (LCA) models were estimated to identify groups with similar numbers of primary care (PC), specialist, and outpatient ED visits and hospital days within 12 months preceding the index ED visit.
RESULTS
In this sample (n = 308), five groups with distinct patterns of health service use emerged. Low Users (35%) had fewer visits of all types and fewer hospital days compared to sample means. Low Users were more likely to be female and had fewer chronic health conditions relative to the overall sample (p < 0.05). The ED to Supplement Primary Care Provider (PCP) (23%) group had more PCP visits, but also significantly more ED visits. Specialist Heavy (22%) group members had twice as many specialist visits, but no difference in PCP visits. Members of this class were more likely to be white and male (p < 0.05). High Users (15%) received more care in all categories and had more chronic baseline health conditions (p < 0.05) but no differences in demographic characteristics relative to the whole sample. The ED and Hospital as Substitution Care (6%) group had fewer PC and specialist visits, but more ED visits and hospital days.
CONCLUSIONS
In this sample of older ED patients, five groups with distinct patterns of health service use were identified. Further study is needed to determine whether identification of these patient groups can add important information to existing risk-assessment methods.
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10.1111/j.1553-2712.2010.00870.x
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pubmed_724_5611
|
Ozone (O3), a reactive component of air pollution, depresses feeding and voluntary locomotor behavior in laboratory rodents, but the effects of O3 on amphibian behavior are not known. We evaluated the effects of 4 h of exposure to air or ozone (0.6 microl/L), on two ecologically relevant behaviors of the toad Bufo marinus. Toads were offered five mealworms at 1, 24, and 48 h after exposure. One hour after exposure, O3-exposed toads ate fewer mealworms than did air-exposed toads (Fisher exact test, p=0.005). Within 24 h after exposure, all toads ate four or five mealworms. Because movement is a key component of toad feeding behavior, we tested additional toads (n=25) for voluntary locomotor behavior during three 1-h trials in a 2.9-m2 open-field arena. Mean (+/-standard deviation) total distance moved was: pre-exposure, 29+/-19.5 m; 1-h postexposure, 13+/-15.6 m; and 24-h postexposure, 17+/-17.4 m. The means were not statistically different by repeated measures analysis of covariance. Therefore, our results suggest that a single 4-h exposure to O3 depresses toad feeding behavior after exposure but had little effect on voluntary locomotor behavior.
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10.1897/07-388.1
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pubmed_122_1257
|
Recent growth in public bioinformatic databases has facilitated the analysis of genomic and proteomic data. However, the large size of the datasets makes it hard for nonexpert programmers to perform the analysis. In this paper we present B-Log, a high-level query language for bioinformatic data analysis. Based on Datalog, B-Log can simply express graph analysis algorithms; it is extended with nested tables, recursive aggregations, and foreign functions, which helps quick exploratory analyses. We implemented several analysis algorithms in B-Log; we also implemented a prototype system to explore TCGA dataset. We find B-Log to be useful for exploratory analysis and quick prototyping.
|
10.1109/EMBC.2018.8512571
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pubmed_182_15749
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Two up-flow anaerobic sludge blanket (UASB) reactors (RM with 10 g Fe L-1 magnetite, RB without magnetite) feeding with synthetic wastewater were built to investigate the effect of magnetite addition on anaerobic digestion (AD) performance during start-up and starvation recovery stages. With the magnetite addition, the COD removal efficiency and biogas production during the two stages were enhanced, and the recovery time of RM was shortened by about 50%. The reduced synthesis of riboflavin and heme c along with enhanced sludge conductivity of RM indicated that magnetite could replace their roles for efficient extracellular electron transfer (EET), which favors the growth of anaerobes. Microbial community analysis showed that potential syntrophic partners like Syntrophaceae and Methanothrix were enriched in RM during the recovery stage, and the performance was improved with quick responsiveness. Results demonstrated that addition of conductive materials like magnetite could improve the stability and restorability of AD process efficiently.
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10.1016/j.biortech.2018.10.013
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pubmed_495_20904
|
The objective of this work was to study through in the electromyography the upper and lower umbilical rectus abdominis and the anterior and posterior parts of the external oblique muscles of children 8 to 10 years old. The children studied practice artistic and rhythmical gymnastic sports at the training and learning level and the study was made during abdominal exercise in the dorsal decubitus position on the ground and on a board. The children were divided into 2 groups: Group I - ten already trained children; Group II - nineteen learners. The participants in Group I practiced an average of 5 times a week and those in Group II practiced 2 times a week. The exercises analyzed were: on the ground, lifting the legs 30, 20 and 10 cm high with the knees flexed 90 degrees; flexing the trunk while maintaining the legs elevated and the knees flexed; flexing the trunk with homo and heterolateral rotation of the trunk while maintaining the legs elevated and the knees flexed. On the board, flexing the trunk with the knees flexed 90 degrees on top of the board inclined 30, 20 and 10 cm; flexing the trunk with rotation of the trunk homo and heterolateral with the knees flexed on the board inclined 30, 20 and 10 cm. The results showed that the superior umbilical part of the rectus abdominis muscle presented more intense action potential than the inferior-umbilical part; the more intense action potential occurred at the flexing of the trunk and at the flexing of the trunk with homo and heterolateral rotation. The anterior part of the external oblique muscle presented more intense action potential than the posterior part; the more intense action potential occurred at the flexing of the trunk and at the flexing of the trunk with heterolateral rotation. In both of the muscles the more intense action potential occurred between 45 and 60 degrees of flexing the trunk; the children in Group I presented more intense action potential than those in Group II; the exercise of lifting the flexed legs did not prove efficient for strengthening the analyzed abdominal muscle structure.
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pubmed_495_20904
|
pubmed_938_18825
|
Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twenty-one patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo. The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment ended, however, serum aminotransferases usually returned to pretreatment levels; 6 to 12 months after the discontinuation of interferon therapy, only two patients (10 percent) still had normal values. We conclude that interferon alfa therapy is beneficial in reducing disease activity in chronic hepatitis C; however, the beneficial responses are often transient.
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10.1056/NEJM198911303212204
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pubmed_455_1205
|
A case of idiopathic intracranial hypertension (IIH) with visual field loss was decompressed in the intracanalicular segment of the optic nerve transnasally under endoscopic control. Visual functions improved after surgery.
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10.1258/002221503321892406
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pubmed_748_17523
|
The temperature dependence of spin coherence in InGaAs quantum dots is obtained from quantum beats observed in polarization-resolved pump-probe experiments. Within the same sample we clearly distinguish between coherent spin dynamics leading to quantum beats and incoherent long-lived spin-memory effects. Analysis of the coherent data using a theoretical model reveals approximately 10 times greater stability of the spin coherence at high temperature compared to that found previously for exciton states in four-wave-mixing experiments by Borri et al. [Phys. Rev. Lett. 87, 157401 (2001)]]. The data on incoherent polarization reveal a new form of spin memory based on charged quantum dots.
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10.1103/PhysRevLett.93.057401
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pubmed_720_18012
|
Despite a number of benefits, mobile phones can carry many deleterious effects. We aimed to determine the extent of problematic mobile phone use in a sample of college-aged young adults in the United Arab Emirates. We also examined whether a number of factors were correlated with and predicted problematic use. We conducted a cross-sectional, correlational study in which a sample of 350 young adults (M = 20.70, SD = 2.14, range: 18-33 years) completed a survey that included socio-demographic variables, and measures of problematic mobile phone use (MPPUS-10), depression, and low self-esteem. One third of the sample evidenced scores indicative of problematic mobile phone use (M = 47.14, SD = 19.98). Logistic regression identified female gender, increasing daily time using the mobile phone, and elevated depressive symptomology predicted higher MPPUS-10 scores. The MPPUS-10 evidenced acceptable reliability and validity in this sample. The prevalence of problematic mobile phone use was considerable in this sample, higher in comparison to previous reports from Europe and the Far East.
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10.1016/j.abrep.2019.100185
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pubmed_1105_16590
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A Mittelmeier-type ceramic on ceramic total hip arthroplasty (THA) was retrieved because of aseptic loosening 17 years after implantation. The extent of wear was assessed by scanning electron microscopy. The synovial fluid and the tissue surrounding the implant were also examined. Scanning electron microscopy analysis of the ball head showed that the main wear zone had grade IV wear. The stripe wear zones showed grain pullout regions (grade 5 wear). Pathologically, chronic inflammation was observed in the surrounding tissue. The debris particles in the synovial fluid were polygonal and approximately 3 x 4 microm. Thus, the Mittelmeier-type THA proved excellent wear resistance. Further longevity of ceramic on ceramic THA may indeed become a reality with improvement of the design and quality of alumina.
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10.1016/j.arth.2005.05.025
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pubmed_1046_1266
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Student nurses maintain unfavorable views of people with mental health issues. Many continue to perpetuate common stereotypes, are fearful and believe people with mental health problems are in some way dangerous. The impact of placements greatly affects these views. A pre-post survey of 85 student nurses was conducted to establish the opinions and attitudes of student nurses regarding mental health. Groups were allocated to either community or hospital placements. Each group received the same educational preparation prior to placement. Both community and hospital placed students had improved clinical confidence when working with people experiencing mental health problems. Community placed students demonstrated greater positive attitudes towards people experiencing mental health issues across a number of domains. Students in hospital settings demonstrated more confidence when working with people with mental health issues yet had less attitudinal change about mental health. The approach taken by clinical facilitators also influenced student attitudes. It is suggested that offering community opportunities along with exposure to positive instructor beliefs about mental illness will both improve student attitudes prior to the completion of their nursing studies and may encourage entry into mental health as a nursing option post-education.
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10.1016/j.nepr.2018.06.004
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pubmed_750_1725
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Lead halide perovskite nanocrystals have demonstrated their potential as active materials for optoelectronic applications over the past few years. Nevertheless, one issue that hampers their applicability has to do with the observation of photoluminescence intermittency, commonly referred to as "blinking", as in their inorganic counterparts. Such behavior, reported for structures well above the quantum confinement regime, has been discussed to be strongly related to the presence of charge carrier traps. In this work, we analyze the characteristics of this intermittency and explore the dependence on the surrounding atmosphere, showing evidence for the critical role played by the presence of oxygen. We discuss a possible mechanism in which a constant creation/annihilation of halide-related carrier traps takes place under light irradiation, with the dominant rate being determined by the atmosphere.
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10.1021/acsami.8b17122
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pubmed_73_18718
|
Cyberknife (Accuray Inc. Sunnyvale, USA) stereotactic body radiation therapy (SBRT) involves the delivery of a small number of large doses of radiation to a target volume using continuously evolving advanced technology. It has emerged as a novel treatment modality for cancer and modified some concepts of cancer treatment. It is indicated in early-stage primary cancer, sometimes as an alternative to surgery. It is also indicated for patients with oligometastatic disease who have relatively long survival with the aim to optimize disease control with a good quality of life. Although there remain some uncertainties regarding the radiobiology of hypofractionation, local control and tolerance have been promising. Indications are increasing under strict quality assurance programs worldwide and prospective clinical evaluation.
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10.1684/bdc.2010.1141
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pubmed_1095_2027
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Protection of the environment post-mining is a key objective of rehabilitation, especially where runoff and erosion from rehabilitated mine sites could potentially lead to contamination of the surrounding land and watercourses. As part of an overall assessment of the success of rehabilitation at the former Nabarlek uranium (U) mine, an appraisal of stable lead (Pb) isotopes, radionuclides and trace metals within sediments and soils was conducted to determine the off site impacts from a spatial and temporal perspective. The study found localised areas on and adjacent to the site where soils had elevated levels of trace metals and radionuclides. Lead isotope ratios are highly radiogenic in some samples, indicating the presence of U-rich material. There is some indication that erosion products with more radiogenic Pb isotope ratios have deposited in sediments downstream of the former ore body. However, there is no indication that the radiogenic erosion products found on the mine site at present have significantly contaminated sediments further downstream of Cooper Creek.
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10.1016/j.jenvrad.2007.08.015
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pubmed_743_6252
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Olive (Olea europaea) is one of the most extensive crops in the Mediterranean countries, and an important source of extra distinctive compounds that has been widely tested due to its known health benefits. Olive derivatives, such as extra virgin olive oil (EVOO) and olive leaves are rich in antioxidant compounds such as hydroxytyrosol (HXT) and oleuropein and oleic acid, as main monounsaturated fatty acid. Because of HXT molecular structure, its regular consumption reports important beneficial properties such as anti-inflammatory, antimicrobial, antioxidant, and anticancer. As a matter of fact, its antioxidant and antimicrobial effects made this compound a good preservative agent against meat deterioration and spoilage, capable of replacing some synthetic additives whose continued and regular consumption may negatively affect the human health. On the contrary side, this extract has an unpleasant odor and flavor, so a synthetic source of HXT could also be used to improve the sensory quality of the meat products. In this sense, this review exposes the health benefits provided by the consumption of EVOO and HXT, and the newest research about its application on meat, together new trends about its use as functional ingredient in meat and meat products.
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10.3390/foods10112611
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pubmed_935_2166
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In 100 patients (59 males and 41 females) suffering from proximal spinal muscular atrophy, 23 presented with hypertrophy of the calves. These were all males. They all showed an elevation of serum CK-activity. The combination of spinal muscular atrophy, hypertrophy of the calves and elevated serum CK activity was not found in females.
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10.1016/0022-510x(80)90136-7
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pubmed_114_14810
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Normal human serum and plasma were shown to contain a factor inhibiting phospholipase A2. This factor has been separated from human serum and plasma by chromatography on a Blue-Ultrogel column and was eluted by tris-HCl buffer (pH 7.2); the proteins eluted by 1 M NaCl-tris HCl buffer exhibited phospholipase A2 activity. This activity was abolished when the inhibitory factor was added to proteins possessing such activity. The inhibitory factor was not dialysable, sensitive to both heat and trypsin treatment, suggesting that it is a protein. In vitro, the same factor inhibited phospholipase A2 rat serum.
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10.1016/0006-291x(84)91207-5
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pubmed_740_24775
|
The majority of patients with acute myeloid leukemia (AML) are older and exhibit a poor prognosis even after intensive therapy. Inducing differentiation and apoptosis of leukemic blasts by DNA-hypomethylating agents, like e.g. azacytidine (AZA) and decitabine (DAC), represent well-tolerated alternative treatment approaches. Both agents show convincing response as single agents in AML. However, there is a lack of knowledge regarding molecular mechanisms and predictive biomarkers for these agents. Areas covered: This review will (i) provide an overview of the current knowledge of molecular mechanisms underlying the action of these drugs, (ii) report promising predictive biomarkers, (iii) elude on new combined treatment options, and (iv) discuss novel approaches to improve outcomes. A literature search was performed using PubMed to find recent major publications, which provide biological and clinical research about epigenetic therapy in AML patients. Expert commentary: Numerous studies have demonstrated that HMA therapy with AZA or DAC may lead to significant response rates, even in pre-treated patients. Nevertheless, there is still an unmet need to further improve outcome in elderly AML patients. Therefore, novel treatment combinations are needed and some of them, such as AZA plus venetoclax, already show promising results.
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10.1080/17474086.2018.1453802
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pubmed_787_3154
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This study evaluated the marginal sealing ability of six temporary restorative materials. Seventy-six human premolars were extracted and divided into six groups (n = 12); the remaining four teeth were used as a control group. Coronal access and biomechanical preparation were performed and the root canals were sealed. The external dental surfaces were covered and the coronal access cavities were filled with one of the six materials. At that point, the teeth were immersed in 0.2% Rhodamine B solution for 72 hours and subjected to thermal cycling. Samples were rinsed in running water and sectioned longitudinally; at that point, the images of each tooth were digitized and marginal leakage was measured using the Image Tool program. Data were subjected to statistical analysis by ANOVA and Tukey's test for comparison between experimental groups. All of the glass ionomer cements tested, particularly Maxxion R, offered satisfactory sealing ability as temporary restorative materials.
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pubmed_787_3154
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pubmed_1097_12118
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In the present study, the contribution of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] generation on the mechanical-stimulation-induced Ca(2+) response was investigated in HSY-EA1 cells. Mechanical stimulation induced a local increase in the cytosolic concentration of Ins(1,4,5)P(3) ([IP(3)](i)), as indicated by the Ins(1,4,5)P(3) biosensor LIBRAvIII. The area of this increase expanded like an intracellular Ins(1,4,5)P(3) wave as [IP(3)](i) increased in the stimulated region. A small transient [IP(3)](i) increase was subsequently seen in neighboring cells. The phospholipase C inhibitor U-73122 abolished these Ins(1,4,5)P(3) responses and resultant Ca(2+) releases. The purinergic receptor blocker suramin completely blocked increases in [IP(3)](1) and the Ca(2+) release in neighboring cells, but failed to attenuate the responses in mechanically stimulated cells. These results indicate that generation of Ins(1,4,5)P(3) in response to mechanical stimulation is primarily independent of extracellular ATP. The speed of the mechanical-stimulation-induced [IP(3)](i) increase was much more rapid than that induced by a supramaximal concentration of ATP (1 mM). The contribution of the Ins(1,4,5)P(3)-induced Ca(2+) release was larger than that of Ca(2+) entry in the Ca(2+) response to mechanical stimulation in HSY-EA1 cells.
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10.1242/jcs.064410
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pubmed_561_19013
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CD34+ hematopoietic stem cells are used clinically to support cytotoxic therapy, and recent studies raised hope that they could even serve as a cellular source for nonhematopoietic tissue engineering. Here, we examined in 18 volunteers the gene expressions of 1185 genes in highly enriched bone marrow CD34+ (BM-CD34+) or granulocyte-colony-stimulating factor-mobilized peripheral blood CD34+ (PB-CD34+) cells by means of cDNA array technology to identify molecular causes underlying the functional differences between circulating and sedentary hematopoietic stem and progenitor cells. In total, 65 genes were significantly differentially expressed. Greater cell cycle and DNA synthesis activity of BM-CD34+ than PB-CD34+ cells were reflected by the 2- to 5-fold higher expression of 9 genes involved in cell cycle progression, 11 genes regulating DNA synthesis, and cell cycle-initiating transcription factor E2F-1. Conversely, 9 other transcription factors, including the differentiation blocking GATA2 and N-myc, were expressed 2 to 3 times higher in PB-CD34+ cells than in BM-CD34+ cells. Expression of 5 apoptosis driving genes was also 2 to 3 times greater in PB-CD34+ cells, reflecting a higher apoptotic activity. In summary, our study provides a gene expression profile of primary human CD34+ hematopoietic cells of the blood and marrow. Our data molecularly confirm and explain the finding that CD34+ cells residing in the bone marrow cycle more rapidly, whereas circulating CD34+ cells consist of a higher number of quiescent stem and progenitor cells. Moreover, our data provide novel molecular insight into stem cell physiology.
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10.1182/blood.v99.6.2037
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pubmed_201_25765
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Acute gastric lesions induced by stress are frequent occurrences in medical establishments. The gastric dramatic downrelated gene (GDDR) is a secreted protein, which is abundantly expressed in normal gastric epithelia and is significantly decreased in gastric cancer. In our previous study, it was found that GDDR aggravated stress‑induced acute gastric lesions. However, the role of GDDR in acute gastric lesions remains to be fully elucidated. In the present study, RNA sequencing was performed in order to examine the gene expression profile regulated by GDDR in acute gastric lesions. The dataset comprised four stomach samples from wild-type (WT) mice and four stomach samples from GDDR‑knockout mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the differentially-expressed genes (DEGs). Weighted correlation network analysis was used to identify clusters of highly correlated genes. Cytoscape was used to construct a protein‑protein interaction network (PPI) of the DEGs. Based on the GO analysis, the upregulated DEGs were distinctly enriched in muscle contraction and response to wounding; and the downregulated DEGs were significantly enriched in the regulation of nitrogen compound metabolic process and regulation of RNA metabolic process. The results of the KEGG pathway analysis showed that the upregulated DEGs were enriched in ECM‑receptor interaction and the signaling pathway of cGMP‑PKG, and the downregulated DEGs were enriched in the renin‑angiotensin system and glycerolipid metabolism. The co‑expression network revealed a group of genes, which were associated with increased wound healing in the WT mice. Significant pathways were identified through the PPI network, including negative regulation of the signaling pathway of glucocorticoid receptor, regulation of cellular stress response, and regulation of hormone secretion. In conclusion, the present study improves current understanding of the molecular mechanism underlying acute gastric lesions and may assist in the treatment of gastric lesions.
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10.3892/mmr.2017.7687
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pubmed_108_8491
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The homeostasis of iron is of fundamental importance in the central nervous system (CNS) to ensure biological processes such as oxygen transport, mitochondrial respiration or myelin synthesis. Dyshomeostasis and accumulation of iron can be observed during aging and both are shared characteristics of several neurodegenerative diseases. Iron-mediated generation of reactive oxygen species (ROS) may lead to protein aggregation and cellular toxicity. The process of misfolding and aggregation of neuronal proteins such as α-synuclein, Tau, amyloid beta (Aβ), TDP-43 or SOD1 is a common hallmark of many neurodegenerative disorders and iron has been shown to facilitate protein aggregation. Thus, both, iron and aggregating proteins are proposed to amplify their detrimental effects in the disease state. In this review, we give an overview on effects of iron on aggregation of different proteins involved in neurodegeneration. Furthermore, we discuss the proposed mechanisms of iron-mediated toxicity and protein aggregation emphasizing the red-ox chemistry and protein-binding properties of iron. Finally, we address current therapeutic approaches harnessing iron chelation as a disease-modifying intervention in neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis.
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10.3389/fnins.2019.00015
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pubmed_1133_5348
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Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare clinicoradiological syndrome that is characterized by neurological symptoms, including seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of the posterior white matter observed on neuroimaging. Sorafenib is an inhibitor of pro-angiogenic receptor tyrosine kinases, such as vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and vascular endothelial growth factor receptor 3. In the previous research literature, only one case of sorafenib-induced RPLS, in a patient with hepatocellular carcinoma, has been reported. The current report presents two cases of sorafenib-induced RPLS in patients with metastases from a renal cell carcinoma. In the first case, a 75-year-old female patient developed a fever, fell down and was unable to move her limbs as instructed after 11 days of sorefenib treatment. Brain magnetic resonance imaging (MRI) demonstrated no typical RPLS findings. As all of the symptoms were resolved after sorafenib discontinuation, sorafenib was restarted. However, the patient remained unable to walk steadily and to articulate properly after 10 days. MRI again demonstrated no notable findings, and her condition improved only after discontinuation of the sorafenib. In the second case, a 75-year-old male patient experienced a fall due to loss of consciousness. T2-weighted and fluid-attenuated inversion recovery MRI revealed high-intensity signals on both sides of the cerebellar hemisphere and pons, and also partially on both sides of the frontal lobe. At 33 days after sorafenib discontinuation, he had recovered sufficiently to walk by himself with a walker, and a repeat MRI revealed a significant improvement. Although one case took a longer time, both cases were fortunately reversible by discontinuation of sorafenib treatment and administration of combined-modality therapy (including oxygen, steroids, verapamil, digoxin and nicardipine hydrochloride). The oncology community should be alerted to this uncommon and life-threatening adverse event.
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10.3892/mco.2017.1291
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pubmed_118_14003
|
The prevalence of gout increases with age. Once serum concentration of urate exceeds the saturation/solubility point, it deposits in and around the joints. Clinical presentation in the elderly often has "atypical" features and is challenging to diagnose. Treatment depends on the stage of the disease and the patient's health status and comorbidities. Elderly patients often have several confounding issues; thus, treatment decisions can be complicated and therapeutic options limited. To prevent the recurrence of gout attacks, serum concentration of urate should be maintained well below the saturation threshold of 6.8 mg/dL, leading to dissolution of urate deposits and prevent recurrence.
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10.1016/j.cger.2016.08.010
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pubmed_836_22670
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Receptor-interacting protein (RIP) 140 interacts with several nuclear receptors, but its function in regulation of nuclear receptor action has been debated. Here we have examined the role of RIP140 in regulation of Steroidogenic factor-1 (SF-1)-dependent transcription. SF-1 interacts with RIP140 through its activation function-2 (AF-2) domain. Several domains of RIP140 interact directly with SF-1, but the carboxyl-terminal region containing 4 of its 9 LXXLL motifs showed the strongest SF-1 interaction. Coexpression of RIP140 and SF-1 in different cell types demonstrated that RIP140 acts as a potent corepressor of transcription from the SF-1 responsive cAMP regulatory sequence 2 (CRS2) element of the CYP17 gene and a variety of SF-1 responsive promoter genes. RIP140 also counteracted the stimulatory action of p160/SRC coactivators. The inhibitory effect of RIP140 was partially reversed by Trichostatin A, suggesting a role of histone deacetylase (HDAC) activity in RIP140-mediated repression of SF-1. Quantitation of endogenous coregulator mRNA levels revealed cell type specific differences that could affect the repressor action by overexpressed RIP140.
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10.1016/s0303-7207(03)00097-2
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pubmed_348_10873
|
Voltage-gated L- and N-type calcium channels (VOCs) are implicated in the activity of morphine, but their contribution to the expression of opioid tolerance remains uncertain. L- and N-type VOCs are heteropentamers of alpha(1), alpha(2)delta, beta, and gamma subunits. The alpha(1) subunit forms both the ion pore and the binding site for ligands. The Ca(v)1.2 and Ca(v)1.3 are the neuronal dihydropyridine (DHP)-sensitive L-type channel subunit types. The Ca(v)2.2 subunit is found in omega conotoxin GVIA-sensitive N-type calcium channels. Ca(v)1.2 VOC gating properties are phosphorylation-dependent with many kinases implicated. We hypothesized that changes in channel subunit structure or phosphorylation state, induced by chronic opioid exposure, may in part explain changes in calcium regulation observed both in vivo and in vitro. Antibodies, specific for the Ca(v)1.2, Ca(v)1.3, and Ca(v)2.2 subunits of VOCs were employed with Western immunoassays to access whether chronic morphine treatment had an effect on receptor protein levels. The L-type channel Ca(v)1.3 protein, but not the Ca(v)1.2 protein or phosphorylation state, significantly decreased upon chronic morphine treatment. The Ca(v)2.2 subunit protein of the N-type channel of VOCs remained unchanged. The Ca(v)1.3 subunit modification may represent one of many potential adaptive changes in tolerance to morphine-induced changes in intracellular calcium.
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10.1016/j.ejphar.2007.09.003
|
pubmed_469_3829
|
Lactic acid bacteria (LAB) are part of the microbiota that inhabit several environmental niches, including foods and the gastrointestinal tract of animals and humans [...].
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10.3390/foods11111579
|
pubmed_942_21150
|
The complex apoptotic functions of the p53 tumor suppressor are central to its antineoplastic activity in vivo. Besides its well-known action as a transcriptional activator of apoptotic genes, p53 exerts a direct proapoptotic role at the mitochondria via protein-protein interactions with Bcl2 family members, thus executing the shortest known circuitry of p53 death signaling. We recently reported that exclusive delivery of p53 to mitochondria exerts a significant in vivo tumor suppressor activity in p53-null lymphomas. However, it was unknown whether mitochondrially targeted p53 has suppressor activities in tumors harboring missense mutants, which constitute the vast majority of p53 alterations in human tumors. Here, we show that targeting p53 to mitochondria does confer a significant growth disadvantage in B-lymphomas expressing various point mutants of p53, resulting in efficient apoptosis induction in vitro and in vivo in mice.
|
10.1038/sj.onc.1209641
|
pubmed_708_6485
|
The photosensitizer flavin mononucleotide (FMN), in conjunction with the reducing agents diethylenetriaminepentaacetic acid (DTPA), hydrazine and hydroxylamines derived from nitroxides, generates superoxide radicals in a strictly light-dependent reaction in aerobic solution. Addition of superoxide dismutase (SOD) converts this system to a hydrogen peroxide generator. In the presence of horseradish peroxidase the latter system becomes a phenoxyl radical generator with appropriate phenolic substrates. Under anaerobic conditions FMN, hydrogen peroxide and an iron chelate generate ferryl and when this system is combined with dimethylsulfoxide, methyl radicals are produced. All the radicals can be generated with little contamination from other radicals, in high yields and the reaction can be terminated immediately upon cessation of illumination. Useful applications of this photochemical system include ESR studies of transient free radical species.
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10.3109/10715769009148581
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pubmed_548_19646
|
PURPOSE
This study examines the analytic validity of a software tool designed to provide individuals with risk assessments for colorectal cancer based on personal health and family history information. The software is compatible with the US Surgeon General's My Family Health Portrait (MFHP).
METHODS
An algorithm for risk assessment was created using accepted colorectal risk assessment guidelines and programmed into a software tool (MFHP). Risk assessments derived from 150 pedigrees using the MFHP tool were compared with "gold standard" risk assessments developed by three expert cancer genetic counselors.
RESULTS
Genetic counselor risk assessments showed substantial, but not perfect, agreement. MFHP risk assessments for colorectal cancer yielded a sensitivity for colorectal cancer risk of 81% (95% confidence interval: 54-96%) and specificity of 90% (95% confidence interval: 83-94%), as compared with genetic counselor pedigree review. The positive predictive value for risk for MFHP was 48% (95% confidence interval: 29-68%), whereas the negative predictive value was 98% (95% confidence interval: 93-99%). Agreement between MFHP and genetic counselor pedigree review was moderate (κ = 0.54).
CONCLUSION
The analytic validity of the MFHP colorectal cancer risk assessment software is similar to those of other types of screening tools used in primary care. Future investigations should explore the clinical validity and utility of the software in diverse population groups.Genet Med 17 9, 753-756.
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10.1038/gim.2014.179
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pubmed_800_15189
|
Between January and October 1994, a study of the prevalence, intensity and clinical manifestations of onchocerciasis in nine communities of Toro local government area of Bauchi State, Nigeria was undertaken using the skin-snip method. Of the 1117 inhabitants examined, 188 (16.8%) were positive for microfilariae of Onchocerca volvulus. The prevalence of onchocerciasis was significantly higher (P < 0.05) among males than females, in subjects 21 years of age and above than in those in the first two decades of life, in nomads, farmers, hunters and fishermen than smiths and traders. Intensity of infection was light, not exceeding a geometric mean of 5.3 microfilaria per 2 mm skin bite. Preponderance of positive cases below 20 years presented no chronic signs. Conversely, persons above 20 years had higher microfilaria counts which coincides with the period when most clinical signs manifest. Microfilarial-rate and -density in relation to age were closely associated (r = 0.75, P < 0.001). The need for a sustained mass distribution of Mectizan in these communities is highlighted.
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10.1078/1438-4639-00052
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pubmed_782_6431
|
Cytomegalovirus (CMV) retinitis is a late complication of organ and hematopoietic stem cell transplant, the risk of which depends on the degree of immunosuppression. With the institution of preemptive ganciclovir therapy early after transplant, most patients survive episodes of life-threatening CMV infection during the early months (usually the first 3 months) after transplant and hence late onset of CMV disease, such as CMV retinitis, is being recognized more frequently. Direct involvement of the macula or optic head remains the leading cause of visual loss in patients with CMV retinitis, but there are few studies investigating the management of this condition. Herein, we present the case of 28-year-old man who had acute myeloid leukemia and developed CMV retinitis with bilateral cystoid macular edema and optic swelling in the right eye 6 months after bone marrow transplant. He received treatment with intravitreal methotrexate in the right eye in combination with oral valganciclovir. Visual acuity improved 1 month after four weekly injections of intravitreal methotrexate 400 µg/0.1 mL. Resolved disc swelling and regression of macular edema were also observed. By comparing binocular outcome, we present our findings and discuss the possible efficacy and safety of this treatment with respect to regression of anatomical damage and improvement in visual acuity.
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10.1016/j.tjo.2015.07.004
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pubmed_731_5463
|
Grasslands across the globe are undergoing expansive degradation due to human impacts and climate change. If restoration of degraded native grassland is to be achieved at the scale now required, cost-effective means for seed-based establishment of grass species is crucial. However, grass seeds present numerous challenges associated with handling and germination performance that must be overcome to improve the efficiency of seeding. Previous research has demonstrated that complete removal of the palea and lemma (husk) maximises germination performance, hence we investigated the effects of complete husk removal on seed handling and germination of four temperate Australian grass species. Three techniques were tested to remove the husk - manual cleaning, flaming or acid digestion (the latter two followed by a manual cleaning step); these techniques were refined and adapted to the selected species, and germination responses were compared. The complete removal of the husk improved seed handling and sowability for all species. Germination was improved in Microlaena stipoides by 19% and in Rytidosperma geniculatum by 11%. Of the husk removal methods tested, flaming was detrimental to seed germination and fatal for one species (R. geniculatum). Compared to manual cleaning, sulphuric acid improved the overall efficacy of the cleaning procedure and increased germination speed (T50) in Austrostipa scabra, Chloris truncata and M. stipoides, and improved final germination in R. geniculatum by 13%. The seed processing methods developed and tested in the present study can be applied to grass species that present similar handling and germination performance impediments. These and other technological developments (seed coating and precision sowing) will facilitate more efficient grassland restoration at large scale.
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10.1111/plb.12885
|
pubmed_1065_5504
|
A new, simple and fast spectrophotometric method for the determination of the H(2)S concentration is reported. This method, based on the 1:1 reaction between H(2)S and the ferric derivative of hemoglobin I (HbI) from the bivalve mollusc Lucina pectinata, allows the quantitative determination of H(2)S dissolved in a given solution even at concentrations as low as 1 x 10(-6) M. Note that L. pectinata HbI is considered the physiological receptor of H(2)S.
|
10.1016/s0304-4165(00)00123-9
|
pubmed_754_3729
|
The GAL4 gene encodes a positive regulator of the galactose-inducible genes in Saccharomyces cerevisiae. Recently, GAL4 has been cloned and its 2.8-kilobase mRNA has been identified. We report here the DNA sequence of GAL4 and the mapping of the 5' and 3' ends of its transcripts. The region sequenced contains a single open reading frame, 881 codons long, which could encode a 99,350-dalton protein. The 5' ends of the GAL4 transcripts fall into two clusters. Transcripts which begin at the upstream cluster would encode the 99,350-dalton protein, whereas those starting at the downstream cluster may result in the synthesis of a shorter, 91,600-dalton protein. The putative GAL4 proteins contain an amino acid sequence near their amino termini which resembles a DNA-binding motif found in bacterial and phage repressors and gene activator proteins.
|
10.1128/mcb.4.2.260-267.1984
|
pubmed_480_8079
|
We report nickel-catalyzed cross-coupling of methoxyarenes with alkylmagnesium halides, in which a methoxy group is eliminated. A wide range of alkyl groups, including those bearing β-hydrogens, can be introduced directly at the ipso position of anisole derivatives. We demonstrate that the robustness of a methoxy group allows this alkylation protocol to be used to synthesize elaborate molecules by combining it with traditional cross-coupling reactions or oxidative transformation. The success of this method is dependent on the use of alkylmagnesium iodides, but not chlorides or bromides, which highlights the importance of the halide used in developing catalytic reactions using Grignard reagents.
|
10.1021/jacs.6b03253
|
pubmed_98_4893
|
Two articles hypothesized that exposure to the color red would induce a state of avoidance motivation and reported that snack food consumption was decreased when the food was served on red plates, relative to white and blue plates. The current experiment combined their procedures and approximately tripled their group sizes. Participants were provided with pretzels on red, white, or blue plates in a mock sensory analysis task. The results indicated that more pretzels were consumed when presented on red plates, in direct contradiction of previous results. Alternative explanations, such as group differences in hunger or preference for pretzels, could not account for the results. The facilitation effect of red indicates that the color red does not always reduce snack food consumption and suggests that the reported inhibitory effect of red on snack consumption may not be reliable.
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10.1027/1618-3169/a000524
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pubmed_245_22362
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Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxide (plumbagin) or nitric oxide (NOR-1) to assess the capacity to eliminate them. Under basal conditions, MHE patients show reduced superoxide and peroxynitrite levels and increased nitric oxide (NO) and nitrotyrosine levels. In patients without MHE plumbagin strongly increases cellular superoxide, moderately peroxynitrite and reduces NO levels. In MHE patients, plumbagin increases slightly superoxide and strongly peroxynitrite levels and affects slightly NO levels. NOR-1 increases NO levels much less in patients with than without MHE. These data show that the mechanisms and the capacity to eliminate cellular superoxide, NO and peroxynitrite are enhanced in MHE patients. Superoxide elimination is enhanced through reaction with NO to form peroxynitrite which, in turn, is eliminated by enhanced reaction with biological molecules, which could contribute to cognitive impairment in MHE. The data show that basal free radical levels do not reflect the oxidative stress status in MHE.
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10.1080/10715762.2017.1420183
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pubmed_923_20502
|
OBJECTIVE
To investigate whether various types of ovarian stimulation induce differences in endometrial development at the midluteal phase in infertile women.
DESIGN
Assessment of stromal and glandular compartments in endometrial biopsies using morphometric criteria.
SETTING
Institute for Hormone and Fertility Research, Hamburg, Germany.
PATIENTS
The study included 18 women after treatment with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) (group I), 23 women after clomiphene citrate (CC)/hMG/hCG treatment (group II), and 12 women after CC stimulation (group III).
INTERVENTIONS
Endometrial biopsies and blood samples were taken simultaneously in the early to midluteal phase. To assess the time of ovulation, hormone analysis and regular checks by ultrasonography were performed.
MAIN OUTCOME MEASURES
Morphometric evaluation of glandular and stromal structures revealed an impaired endometrial development after various treatment protocols.
CONCLUSION
Ovarian stimulation in infertile women results in most cases in an elevation of steroid levels; however, the occurrence of an inadequate endometrial development might have an unfavorable influence on the outcome of implantation. Therefore, these findings may be of importance to the choice of treatment for infertility.
|
10.1016/s0015-0282(16)55800-2
|
pubmed_687_9504
|
INTRODUCTION
Old unreduced elbow dislocation is not uncommon in developing countries. Many authors have reported outcome of open reduction in the management of this problem. However, we did not find any study that document patient reported outcome.
OBJECTIVE
the objective of this study was to determine the patients' perspectives of outcome of open reduction in the management of old unreduced elbow dislocation.
METHODS
This was a prospective interventional study of 49 consecutive patients with old unreduced simple elbow dislocation who were treated with open reduction at the National Orthopaedic Hospital, Dala - Kano, Nigeria and Albarka Clinic Kano, Nigeria between January 2015 and December 2019.
RESULTS
Fourty nine patients were studied with median age of 31.0 years (range: 19-60 years). The majority of the patients were within 31-40 years age group. The male to female ratio was 6:1. Using the Mayor Elbow Performance Scale (MEPS) and Patients specific Functional scale (PSFS); there are significant improvements in postoperative functional capability of the patients (P = 0.000). With the short assessment for patient satisfaction (SAPS), 93.3% of patients were either satisfied or very satisfied with the outcome of open reduction.
CONCLUSION
The outcome of open reduction for old unreduced elbow dislocation is good and is well accepted by the patients.
|
10.1016/j.surge.2020.03.001
|
pubmed_978_15711
|
In order to evaluate which cytogenetic evolutionary patterns take place during the in vitro establishment of a permanent glioma cell line, cytogenetic follow-up was performed on direct preparations and primary cultures from a malignant astrocytoma and on serial passages for more than 2 years of in vitro propagation. Sixteen passages were studied, and the presence of a marker chromosome in direct preparations and after in vitro growth permitted us to identify the clonal evolution of the resulting permanent cell line. Near-triploid cells present in the direct study became the main cell population in vitro; chromosomal losses and the acquisition of a few new marker chromosomes were also characteristic features, leading to a stable modal number of around 60 chromosomes in the last passages analyzed. The results provide new evidence of the existence of more than one pattern of chromosomal evolution during the in vitro establishment of human gliomas.
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10.1016/0165-4608(89)90244-6
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pubmed_456_18402
|
KEY POINTS
Ninety-eight per cent of patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy, with 40% developing heart failure. While increased propensity for mitochondrial induction of cell death has been observed in left ventricle, it remains unknown whether this is linked to impaired mitochondrial respiratory control and elevated H2 O2 emission prior to the onset of cardiomyopathy. Classic mouse models of DMD demonstrate hyper-regeneration in skeletal muscle which may mask mitochondrial abnormalities. Using a model with less regenerative capacity that is more akin to DMD patients, we observed elevated left ventricular mitochondrial H2 O2 and impaired oxidative phosphorylation in the absence of cardiac remodelling or overt cardiac dysfunction at 4 weeks. These impairments were associated with dysfunctions at complex I, governance by ADP and creatine-dependent phosphate shuttling, which results in a less efficient response to energy demands. Mitochondria may be a therapeutic target for the treatment of cardiomyopathy in DMD.
ABSTRACT
In Duchenne muscular dystrophy (DMD), mitochondrial dysfunction is predicted as a response to numerous cellular stressors, yet the contribution of mitochondria to the onset of cardiomyopathy remains unknown. To resolve this uncertainty, we designed in vitro assessments of mitochondrial bioenergetics to model mitochondrial control parameters that influence cardiac function. Both left ventricular mitochondrial responsiveness to the central bioenergetic controller ADP and the ability of creatine to facilitate mitochondrial-cytoplasmic phosphate shuttling were assessed. These measurements were performed in D2.B10-DMDmdx /2J mice - a model that demonstrates skeletal muscle atrophy and weakness due to limited regenerative capacities and cardiomyopathy more akin to people with DMD than classic models. At 4 weeks of age, there was no evidence of cardiac remodelling or cardiac dysfunction despite impairments in ADP-stimulated respiration and ADP attenuation of H2 O2 emission. These impairments were seen at both submaximal and maximal ADP concentrations despite no reductions in mitochondrial content markers. The ability of creatine to enhance ADP's control of mitochondrial bioenergetics was also impaired, suggesting an impairment in mitochondrial creatine kinase-dependent phosphate shuttling. Susceptibly to permeability transition pore opening and the subsequent activation of cell death pathways remained unchanged. Mitochondrial H2 O2 emission was elevated despite no change in markers of irreversible oxidative damage, suggesting alternative redox signalling mechanisms should be explored. These findings demonstrate that selective mitochondrial dysfunction precedes the onset of overt cardiomyopathy in D2.mdx mice, suggesting that improving mitochondrial bioenergetics by restoring ADP, creatine-dependent phosphate shuttling and complex I should be considered for treating DMD patients.
|
10.1113/JP277306
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pubmed_501_6200
|
Previous attempts to extract erythropoietin from the kidneys have not been uniformly successful and have yielded only small amounts. Attempts were therefore made to extract erythropoietin from renal extracts prepared from the supernatant obtained after homogenizing kidneys in various liquids and centrifuging at 2300 x g. Detectable amounts of erythropoietin were recovered from kidneys of nonhypoxic male but not female rats. After exposure to hypoxia, the amounts increased to levels greater than 6.0 U/kidney from males after 8 hr of hypoxia. Erythropoietin became detectable in extracts from kidneys obtained from females after 2 hr of hypoxia and rose to levels of 0.54 U/kidney after 4 hr of hypoxia. The amount of plasma trapped in the kidneys at the time of extraction was not sufficient to account for a significant amount of this erythropoietin, and erythropoietin was not detected in extracts made from livers or spleens. Severalfold larger titers of erythropoietin were detected in renal extracts, by a simple extraction procedure, than was the case in previous attempts. The reasons for this difference are discussed.
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pubmed_501_6200
|
pubmed_525_9464
|
We introduce a method to efficiently detect rare mutations for individual subjects in a large population by pooling samples and retesting subgroups of positive pooled samples. We conducted computer simulations of this method and discovered that it seems efficient for mutation prevalences less than 0.1, regardless of the number of samples. The simulations also indicate that splitting the pooled samples into three to five subgroups at each level is optimal. The expected number of necessary tests and relative efficiency of this method are given, by mutation prevalence and sample size.
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10.1089/gte.1998.2.315
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pubmed_1010_8758
|
Leptospirosis is a globally distributed zoonosis with a broad clinical spectrum. This disease mostly affects liver and kidney tissues. Other organs such as the pancreas, can be affected by leptospirosis-induced vasculitis. In addition, cardiac manifestations are common, and the presence of transient ECG abnormalities can be found in 70% of the patients. We report a male patient who presented with an atypical leptospirosis that progressed with severe acute pancreatitis, acute kidney injury and atrial fibrillation. Early diagnosis and adequate supportive therapy are crucial for the appropriated management of symptoms.
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10.1590/S1678-9946201961063
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pubmed_1023_1370
|
A study of 138 patients with psoriasis--74 with psoriasis alone and 64 with psoriatic arthritis--revealed a significantly increased frequency of the HLA antigens A1, A28, B13, DR7 and MT3 in those with psoriasis alone and of Bw39 in those with psoriatic arthritis. The frequency of B17 was higher in both patient groups than in a control group of healthy individuals. The frequency of DRw6 was slightly higher in the patients with psoriasis alone (17.8%) than in the controls (4.7%), and that of DR7 was higher in the patients with psoriatic arthritis (52.9%) than in the controls (32.6%). Elevated levels of serum IgG and IgA along with positive results of tests for antinuclear antibody or rheumatoid factor or both were present in less than a tenth of the patients with psoriatic rash alone and in up to a third of those with psoriatic arthritis. Psoriatic arthritis was found to be less likely to develop in patients with purely guttate psoriasis than in those with other types of psoriasis. Clinical subtypes of psoriatic rash or psoriatic arthritis were not associated with the presence of particular HLA antigens.
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pubmed_1023_1370
|
pubmed_771_3227
|
Human-induced environmental changes differ from most natural changes in which they happen at a faster rate and require quicker responses from populations. The first response of populations is usually phenotypically plastic alterations of morphology, physiology and behaviour. This plasticity can be favourable and move the population closer to an adaptive peak in the altered environment and, hence, maintain a viable population, or be maladaptive and move the population further from the peak and increase the risk of extinction. The radiation of the three-spined stickleback Gasterosteus aculeatus from the ocean to different freshwater habitats has provided much information on adaptation to new environmental conditions. Currently, human-induced eutrophication is changing the breeding areas of these fish, which creates a model system for investigation of responses to rapid environmental disturbance. Results show that a primary reaction is plastic alterations of behaviour, with some adjustments being adaptive while others are not. At the same time, the strength of sexual selection on several traits is relaxed, which could increase the relative importance of survival selection. Whether this will restore population viability depends on the amount of standing genetic variation in the right direction. Human disturbances can be dramatic and resolution of the limit of flexibility and the possibility of genetic adaptation should be important targets of future research.
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10.1111/j.1095-8649.2009.02405.x
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pubmed_362_13638
|
Labeled ammonium cations with pKa ∼7.4 accumulate in acidic organelles because they can be neutralized transiently to cross the membrane at cytosolic pH 7.2 but not at their internal pH<5.5. Retention in early endosomes with less acidic internal pH was achieved recently using weaker acids of up to pKa 9.8. We report here that primary ammonium cations with higher pKa 10.6, label early endosomes more efficiently. This maximized early endosome tracking coincides with increasing labeling of Golgi networks with similarly weak internal acidity. Guanidinium cations with pKa 13.5 cannot cross the plasma membrane in monomeric form and label the plasma membrane with selectivity for vesicles embarking into endocytosis. Self-assembled into micelles, guanidinium cations enter cells like arginine-rich cell-penetrating peptides and, driven by their membrane potential, penetrate mitochondria unidirectionally despite their high inner pH. The resulting tracking rules with an approximated dynamic range of pKa change ∼3.5 are expected to be generally valid, thus enabling the design of chemistry tools for biology research in the broadest sense. From a practical point of view, most relevant are two complementary fluorescent flipper probes that can be used to image the mechanics at the very beginning of endocytosis.
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10.1002/cbic.202200192
|
pubmed_540_24391
|
Many studies have disentangled the perceived benefits of vegetation on subjective well-being (SWB). Yet, scant attention has been paid to the joint effect of vegetation and building density on SWB. This study explores the relationship between streetscape vegetation (SV), building density and SWB in Beijing, China. Our analysis relies on rich measures of street view data to assess SV exposure at the neighbourhood level. Notably, we distinguish between trees (SV-tree) and grasses (SV-grass) when evaluating SV metrics. The results suggest that streetscape trees and grasses are positively associated with SWB, though estimated effects are dependent upon tree and grass density exposures. We also find that the effects of streetscape trees and grass are moderated by building density in the neighbourhood. Additional decomposition analysis provides the insight that the well-being implications of street vegetation and building density are varied significantly by individual sociodemographic characteristics such as sex, age and income. The findings of this study suggest the importance of considering density in SV planning and land use policies to enhance people's quality of life.
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10.1111/hsc.13968
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pubmed_784_549
|
Carbamazepine is a first line drug in the treatment of epilepsy and trigeminal neuralgia, but may exert negative chronotropic and dromotropic effects on the cardiac conduction system. Bradyarrhythmias of different types and severity have been described, especially in the elderly, but the prevalence of arrhythmias in a larger group of carbamazepine treated patients is unknown. Forty-eight patients, 40 years of older, on continuous carbamazepine treatment because of various neurologic disorders were investigated by interview, physical examination, 12-lead surface electrocardiogram, and 24-h long-term electrocardiogram recording. The prevalence of bradyarrhythmias was compared with that in an age-stratified reference group. There was no differences between the two groups, either in the number or the duration of pauses or in the type of pauses. In conclusion, carbamazepine does not increase the risk of bradyarrhythmias in the vast majority of patients.
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10.1016/0920-1211(92)90069-6
|
pubmed_597_12237
|
BACKGROUND
Bone bruising is commonly observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) injury.
OBJECTIVES
The primary objective of this study was to determine if the location and prevalence of tibial and femoral bone bruises after ACL injury can be explained by specific injury mechanism(s). The secondary objective was to determine whether the bone-bruise literature supports sex-specific injury mechanism(s). We hypothesized that most studies would report bone bruising in the lateral femoral condyle (LFC) and on the posterior lateral tibial plateau (LTP).
METHODS
MEDLINE, PubMed, and SCOPUS were searched for studies that reported bone bruise prevalence and location in ACL-injured subjects. Sex differences in bone-bruise patterns were assessed. Time from injury to imaging was assessed to account for confounding effects on bone-bruise size and location.
RESULTS
Thirty-eight studies met the inclusion/exclusion criteria. Anterior-posterior location of bone bruises within the tibiofemoral compartment was assessed in 11 studies. Only five of these studies reported bone-bruise locations on both the tibia and the femur. The most common bone-bruise combination in all five studies was on the LFC and the posterior LTP. Sex differences were only assessed in three studies, and only one reported significantly greater prevalence of LTP bruising in females.
CONCLUSION
Bone-bruise patterns in the current literature support a valgus-driven ACL injury mechanism; however, more studies should report the specific locations of tibial and femoral bone bruises. There is insufficient evidence in the literature to determine whether there are sex-specific bone-bruise patterns in ACL-injured subjects.
|
10.1007/s40279-013-0116-z
|
pubmed_63_12537
|
Genetic variation plays an important role in osteoporosis and a prime candidate gene is Collagen alpha2(I) (COL1A2). A coding polymorphism (rs42524) in COL1A2 has previously been associated with intracranial aneurysms. Here the effects of this polymorphism have been studied in relation to bone mineral density (BMD) and prevalences of stroke and myocardial infarction (MI). rs42524 was genotyped in elderly men (n = 2004) from the Swedish MrOS cohort. Genotypes were analysed for association to BMD and certain health parameters. Significant associations (overall P < 0.05), were observed between rs42524 genotype and BMD at several skeletal sites. Surprisingly, the heterozygote genotype class exhibited lower BMD than either homozygote group. When subjects were classified as heterozygotes or homozygotes, the heterozygous genotype was found to confer a lower BMD at total hip, femoral neck and trochanter Furthermore, the heterozygote genotype had an increased risk of stroke and MI, with population Attributable Risks being 0.12 and 0.08, respectively.
|
10.1016/j.bbrc.2009.05.006
|
pubmed_272_12975
|
PURPOSE
To determine the concentration of netilmicin in tears after eye drop administration.
METHODS
A clinical study was carried out on 32 healthy volunteers. Subjects were divided into four groups and underwent tear collection at 5, 10, 20, and 60-minutes after drug administration, respectively. Tear samples were collected through capillary suction from the inferior conjunctival "cul-de-sac" and analyzed by high-pressure liquid chromatography (HPLC).
RESULTS
Netilmicin concentration in tears decreased after a first order kinetics, a best-fit curve was drawn and the minimum inhibitory concentration (MIC90) intersection for the most common ocular pathogens was calculated.
CONCLUSIONS
The extrapolation of the curve shows that the concentration of netilmicin on the ocular surface can be effective against microorganisms more than 120 minutes after eye drop instillation.
|
10.1097/00003226-200201000-00011
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pubmed_641_13492
|
Adolescents of today inherit the conflicting legacies of the sexual reformation of the 1960s and the counter-reformation of the 1980s/1990s. Sexual mores are influenced by a younger age of puberty than in earlier generations and by the availability of effective contraception and antibiotics to combat sexually transmitted diseases. In the era of acquired immune deficiency syndrome, however, absolutely safe sex cannot be guaranteed, only relative degrees of safety and risk. Masturbation may be one way of achieving safe sex. Advancing technology also allows greater equality of opportunity and economic emancipation for women, enabling men and women to share equally in the care of older infants and children, also influencing sexual roles. Sex education for adolescents is provided sporadically and inconsistently, being seen by opposing factions as either encouragement to early pregnancy or a means of preventing it. In particular, the images delivered by the mass media are blatantly contradictory, ranging from endorsement of teenage sexual expression to condemnation of abortion and teenage pregnancy. Cultural traditions have strong influences on the acceptability of early pregnancy and on family structure. Black American culture is based on the three-generational family as opposed to the white tradition of the nuclear, two-generational family. It is important to realize a social policy that will respect not only the sexual rights of young people, but also the sexual health of the community.
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10.1159/000183959
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pubmed_265_17480
|
Two PCR primer sets for the nitrous oxide reductase gene (nosZ) were developed. The initial primers were based on three sequences in GenBank and used to amplify nosZ from continental shelf sediments and from two denitrifiers in culture, Thiosphaera pantotropha and Pseudomonas denitrificans. Three unique marine sediment nosZ genes were identified and sequenced. The marine nosZ genes were most closely related to the nosZ genes of Paracoccus denitrificans or to Rhizobium meliloti. Alignment of all nosZ sequences currently available (n = 10) facilitated redesign of the PCR primers. Three new primer sets which amplify 1100 bp, 900 bp and 250 bp regions of the nosZ gene were designed and tested. The new primers robustly amplified nosZ fragments from samples in which the initial nosZ primers were only marginally successful.
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10.1111/j.1574-6968.1998.tb12979.x
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pubmed_551_18801
|
Attempts to explain differences in the size and structure of primate groups have argued that they are a consequence of variation in the intensity of feeding competition caused by contrasts in food distribution. However, although feeding competition can limit the size of female groups, many other factors affect the costs and the benefits of sociality to females and contribute to differences in group size. Moreover, interspecific differences in social relationships between females, in female philopatry, and in kinship between group members appear to be more closely associated with variation in life-history parameters, reproductive strategies, and phylogeny than with contrasts in food distribution or feeding competition. The mismatch between predictions of socioecological theory and observed variation in primate social behavior has led to protracted arguments about the future of primate socioecology. We argue that future attempts to understand the diversity of primate societies need to be based on an approach that explores separate explanations for different components of social organization, combines ecological and phylogenetic information, and integrates research on primates with similar studies of other groups of mammals.
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10.1002/evan.21316
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pubmed_40_24393
|
Recently, Clostridium difficile has been isolated from a wide variety of animals, particularly production animals, mainly cattle and pigs. Concurrently, the incidence of C. difficile infection (CDI) in humans has increased in the community, with some suggestions that food-borne transmission of C. difficile is occurring. Interestingly, sheep and lambs appear not to have been investigated for carriage/colonization with C. difficile. The aim of this project was to determine the prevalence of carriage of C. difficile in sheep and lambs in Australia by culturing fecal samples. A total of 371 sheep and lamb fecal samples were received in seven batches from three different geographic areas in eastern Australia and two in Western Australia. The overall rate of detection in sheep and lambs was low (4.0%); however, carriage/colonization in lambs (6.5%) was statistically significantly higher than that in sheep (0.6%) (P = 0.005). Seven distinct PCR ribotype patterns were observed, three of which were known international ribotypes (UK 056 [n = 1], UK 101 [n = 6], and UK 137 [n = 2]), while the remainder were unable to be matched with our available reference library. This low rate of carriage/colonization in Australian ovines suggests they are unlikely to be a major source/reservoir of human infections.
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10.1128/AEM.01888-13
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pubmed_1064_12394
|
Aortic dissection, which typically manifests as sudden tearing or migratory pain, is a well-known medical emergency. However, in 5% of aortic dissection patients, there is no pain. In these patients, the diagnosis depends on the development of neurologic complications. After analyzing the initial symptoms of a series of patients with aortic dissection, we found 4/211 (1.9%) patients suffered from paraparesis. We suggested that the mid- or low thoracic cord be most vulnerable site during acute aortic dissection. This report highlighted the importance of considering the diagnosis of aortic dissection in a patient with a history of acute onset of transient or permanent neurological symptoms in the lower limbs. Whether paraparesis can be an indicator of the prognosis of aortic dissection requires further researches.
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pubmed_1064_12394
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pubmed_1050_7951
|
BACKGROUND
Although health care professionals' increased job demands and strain have generated much public debate in recent years, the way in which occupational therapists' job strain has developed remains unknown.
OBJECTIVE
To examine how Finnish occupational therapists working in municipalities experienced job demands and control in 2014-2018 compared with physiotherapists and registered nurses.
MATERIAL AND METHODS
Occupational therapists (OT, n = 107), physiotherapists (PT, n = 331) and registered nurses (RN, n = 1389) responded to repeated surveys in the Finnish Public Sector Study in 2014-2018. We used the Job Content Questionnaire and analyzed the data using repeated measures analysis of variance and multiple linear regression with generalized estimating equations to identify the trends and differences.
RESULTS
More OTs had lower job demands and higher job control than PTs and RNs in each year of study. These differences were statistically significant. Most OTs had low job strain. The changes in job control and job demands of participants in different years were not statistically significant.
CONCLUSIONS
The OTs consistently experienced low job strain as compared to the PTs and RNs. Developing good practices in OT's work may be beneficial for improving employee health and well-being and high-quality client care.
|
10.1080/11038128.2020.1849396
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pubmed_191_11426
|
We have looked for genetic predictors of life span in a sibship of mice created as a four-way cross among inbred grandparental strains BALB/cJ, C57BL/6J, C3H/HeJ, and DBA/2J. To minimize the potential confounding effects of loci that influence early-life illnesses only, we conducted two analyses: one involving all the mice, and the other using a data set from which the first 20% of the deaths were excluded. The two strongest associations reach experimentwise significance levels (p <.01) when tested on the 80% of the mice with the longest life spans. Surprisingly, three of the four strongest associations showed sex-specific effects, with an influence on life span of either male or female mice, but not both. Epistatic interactions among the loci were also identified. The life-span effect of a locus on chromosome 10 (D10Mit15) exhibited epistatic interactions with loci on chromosomes 9 and 16 (D9Mit10 and D16Mit182). In a second example, a locus on chromosome 12 (D12Mit167) depended on the specific combination of alleles inherited from both male and female parents. Our results show that the common laboratory mouse strains are polymorphic at loci that produce substantial differences in life span and that these effects can be sex specific and conditional on alleles inherited at other loci.
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10.1093/gerona/57.1.b9
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pubmed_430_837
|
1. The effects of in vivo exposure to various concentrations of petroleum refinery wastewater on gill ATPase, plasma protein, plasma osmolarity, and hematocrit were measured in the euryhaline fish, Leptocottus armatus. 2. The extent of the reduction in Na,K-ATPase activity resulting from the exposure to the two refineries wastewaters may be related to wastewater chemical composition. 3. Changes in the blood chemistry parameters did not follow a consistent or easily explainable pattern.
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10.1016/0306-4492(82)90011-9
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pubmed_438_1017
|
An innovative, experimental, medical out-reach initiative, using a fully-equipped mobile medical van with a staff of 2 part-time physicians, a physician assistant, a social worker, and a driver/medical aid serving the needs of 1048, mostly male, minority group, high-level, homeless New York City substance users with infectious diseases is described. The study sample (N = 250) was divided into experimental S's who received Intensive case management and a control group who could choose to refer themselves to the SW. Biological tests revealed high rates of cocaine use and infectious diseases. Preliminary 4-month outcomes (N = 128) showed reductions in drug use, homelessness and health complaints in both groups; experimental subjects compared with controls received more Public Assistance and had fewer emergency room visits.
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10.1081/ja-120004184
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pubmed_1012_20320
|
Most patients with trichuriasis have light worm burdens. Data regarding the inflammatory response to Trichuris worms in the colon of lightly infected persons are scant. Nine patients whose Trichuris infection was found by colonoscopy had biopsies taken from a site adjacent to visible worms and from a second site some 20 cm distally. The biopsies were studied by routine and immunohistochemical methods. None of the biopsies showed mucosal ulceration, significant congestion, fibrosis, gland distortion or goblet cell mucin depletion. There was no difference between worm and worm-free sites in terms of edema, lymphoid follicles or epithelial slough. Worm sites had higher numbers of eosinophils, neutrophils and total inflammatory cells and lower numbers of plasma cells. However there was no difference in lymphocyte, mast cell, and B- and T-cell counts between the two sites. This suggests that the T. trichiura worm incites a local inflammatory response involving eosinophils and neutrophils, even when the colon has only a light burden of worms.
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pubmed_1012_20320
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pubmed_634_21304
|
Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described slowly progressive ataxia with severe imbalance due to the compromise of three of the four sensory inputs for balance, leaving only vision unaffected. Bilateral vestibulopathy is present but saccular and utricular function, measured by vestibular evoked myogenic potentials (VEMPs), has not been widely studied in these patients. Dysautonomia has been reported but is not among the diagnostic criteria. We performed a database analysis to identify patients evaluated between 2003 and 2019 with probable diagnosis of CANVAS by using key words "bilateral vestibulopathy and/or cerebellar ataxia and/or sensory polyneuropathy." Five out of 842 met all conditions. Patients underwent neurological/neurootological exam, brain MRI, visually enhanced vestibulo-ocular reflex (VVOR) exam by high-speed video-oculography using video-Head Impulse Test (vHIT), VEMPs, neurophysiological studies, and genetic tests to exclude other causes of ataxia. Dysautonomia was addressed by the standardized survey of autonomic symptoms. All patients had clinically definite CANVAS as brain MRI showed vermal cerebellar atrophy, neurophysiological studies showed a sensory neuronopathy pattern (absent sensory action potentials), VVOR was abnormal bilaterally, and genetic tests ruled out other causes of ataxia including SCA 3 and Friedreich ataxia. Patients had at least 3 dysautonomic symptoms, including xerostomia/xerophthalmia (5/5). VEMP results varied among patients, ranging from normal to completely abnormal. We found inconsistent results with VEMPs. The utilization of VEMPs in more CANVAS cases will determine its utility in this syndrome. Dysautonomia may be included in the diagnostic criteria.
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10.1007/s12311-019-01061-1
|
pubmed_731_18425
|
Vapor phase infiltration (VPI) is a new approach for transforming polymers into organic-inorganic hybrid materials with unique properties. Here, we combine experimental measurements with phenomenological theory to develop a universal strategy for measuring, modeling, and predicting the processing kinetics of VPI. We apply our approach to the well-studied VPI system of trimethylaluminum (TMA) infiltrating poly(methyl methacrylate) (PMMA) because the system undergoes both precursor-polymer diffusion and reaction. By experimentally measuring aluminum concentration profiles as a function of film depth with secondary ion mass spectrometry (SIMS) and film swelling with ellipsometry, we have extracted equilibrium solubility and effective diffusivity as a function of process temperature. Fitting these values to appropriate Van't Hoff and Arrhenius relationships, we can then extract enthalpies for precursor sorption and diffusion. We observe an abrupt mechanistic change in both the sorption and diffusion processes around 95 °C, where greater chain mobility at higher processing temperatures lead to greater reactivity between TMA and PMMA. With new understanding of this VPI process, we demonstrate precise control of inorganic infiltration depth and loading fraction into PMMA.
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10.1039/c8cp04135k
|
pubmed_1127_15678
|
Two complications are reported from excessively taut application of percutaneous endoscopic gastrostomy (PEG) external bumpers against the abdominal wall skin. First, a 55-year-old woman status post PEG developed a gastric ulcer, complicated by acute gastric bleeding, directly underneath the internal gastric PEG bumper. This complication was associated with replacement by an unknown healthcare worker of the standard flexible external (cutaneous) PEG bumper with an unauthorized rigid external clamp (bumper) and with excessively taut application of this clamp against the abdominal wall skin. No other causes or risk factors for gastric ulcers were present. The pathophysiology of this ulcer, similar to that of a decubitus ulcer, appears to be mucosal ischemia and pressure necrosis. Second, a 37-year-old man status post PEG developed a buried internal gastric bumper that caused PEG malfunction and abdominal pain from excessively taut application of the external PEG bumper. These case reports should alert healthcare workers that replacing a flexible external bumper with a rigid one and that tightening the external bumper excessively may cause pressure necrosis manifesting either as gastric or cutaneous ulcers or as a buried internal bumper. This alert is particularly important for nurses as they are likely to be the first healthcare workers to notice or be told of PEG failure because of their close involvement in the day-to-day care of the patient and their typically close rapport with the patient's family.
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10.1097/SGA.0b013e3181b0a1af
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pubmed_238_15548
|
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. At present, surgery is the first-line treatment for primary resectable GISTs; however, the recurrence rate is high. Imatinib mesylate (IM) is an effective first-line drug used for the treatment of unresectable or metastatic recurrent GISTs. More than 80% of patients with GISTs show significantly improved 5-year survival after treatment; however, approximately 50% of patients develop drug resistance after 2 years of IM treatment. Therefore, an in-depth research is urgently needed to reveal the mechanisms of secondary resistance to IM in patients with GISTs and to develop new therapeutic targets and regimens to improve their long-term prognoses. In this review, research on the mechanisms of secondary resistance to IM conducted in the last 5 years is discussed and summarized from the aspects of abnormal energy metabolism, gene mutations, non-coding RNA, and key proteins. Studies have shown that different drug-resistance mechanism networks are closely linked and interconnected. However, the influence of these drug-resistance mechanisms has not been compared. The combined inhibition of drug-resistance mechanisms with IM therapy and the combined inhibition of multiple drug-resistance mechanisms are expected to become new therapeutic options in the treatment of GISTs. In addition, implementing individualized therapies based on the identification of resistance mechanisms will provide new adjuvant treatment options for patients with IM-resistant GISTs, thereby delaying the progression of GISTs. Previous studies provide theoretical support for solving the problems of drug-resistance mechanisms. However, most studies on drug-resistance mechanisms are still in the research stage. Further clinical studies are needed to confirm the safety and efficacy of the inhibition of drug-resistance mechanisms as a potential therapeutic target.
|
10.3389/fonc.2022.933248
|
pubmed_414_11601
|
Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85+/-0.63 microg/g wet lung weight and 0.58+/-0.30 microg/mL, with low dose group lung and plasma concentrations of 0.38+/-0.01 microg/g wet lung weight and 0.09+/-0.06 microg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.
|
10.1016/j.ijpharm.2009.06.003
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pubmed_279_6153
|
The morphological effects of drug treatment with atovaquone in the brains of mice chronically infected with Toxoplasma gondii was examined by light and electron microscopy. As early as 1 and 2 weeks of treatment there appeared to be fewer tissue cysts compared to untreated controls and this reduction was more significant after 4 weeks treatment. There also appeared to be a decrease in the number of inflammatory nodules and the severity of the meningitis. Ultrastructurally, the cysts of both treated and control animals were located within host cells. There was a marked increase in both the number of cysts with lysed bradyzoites and the number of degenerate bradyzoites after 4 weeks treatment. It is probable that the drug is more active against the metabolically active immature bradyzoites than the mature organisms. Drug treatment does not appear to result in rupture of tissue cysts or release of Toxoplasma antigens since there is a reduction rather than an increase in the inflammatory response. This drug may be useful in treating chronic toxoplasmosis since it appears to be active against the bradyzoites reducing the parasite burden (cyst number) without initiating a destructive inflammatory response.
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pubmed_279_6153
|
pubmed_498_19174
|
BACKGROUND
Iron-folic acid (IFA) intake for the recommended period during pregnancy reduces the risk of anemia and congenital anomalies. However, IFA intake for the recommended period is still very low in low-income countries including Ethiopia. Thus, the aim of this study was to assess both individual-and community-level determinants of IFA intake for the recommended period among pregnant women in Ethiopia.
METHODS
Data were retrieved from the Demographic and Health Survey program's official database website (http://dhsprogram.com). A two-stage stratified cluster sampling technique was employed to conduct the 2016 Ethiopian Demographic and Health Survey. A sample of 3088 pregnant women who had received at least one dose of IFA in Ethiopia were included in this study. A multivariable multilevel logistic regression analysis model was fitted to identify the determinants of IFA intake below the recommended period [< 90 days] during pregnancy. Akaike's Information Criterion (AIC) was used during the model selection procedure.
RESULTS
This study revealed that 87.6% [95% CI; 86.3%, 88.6%] of the women took IFA below the recommended period during the index pregnancy. After adjusting for the covariates: living in rural areas [AOR = 1.74: 95% CI 1.37, 2.50], and women's illiterate proportion [AOR = 1.43: 95% CI 1.06, 1.70] were community level factors. Whereas, primary education level [AOR = 0.63: 95% CI 0.40, 0.78], poorer wealth index [AOR = 1.53: 95% CI 1.08, 3.09], 4 + antenatal care visits [AOR = 0.43: 95% CI 0.31, 0.69], and receive nutritional counseling during pregnancy [AOR = 0.63: 95% CI 0.37, 0.84] were the individual-level factors of IFA intake below the recommended period during pregnancy.
CONCLUSIONS
In this study, nearly nine out of ten pregnant women did not take IFA for the recommended period. Thus, promoting recommended ANC visits, enhancing the quality of nutritional counseling, strengthening the expansion of media, and educate rural women towards the importance of optimal intake of IFA during pregnancy. Besides, the policymakers should design essential strategies based on identified barriers to improve the IFA intake for the recommended period.
|
10.1016/j.heliyon.2021.e07521
|
pubmed_497_19864
|
Human vascular adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are thought to play a critical role in the homing of leukocytes to sites of atherosclerotic lesions. However, very little is known about the expression of adhesion molecules in the vasculature of mice models, such as apolipoprotein E knockout (apoE(-/-)) mice, the lesions of which closely mimic human atherosclerotic lesions. This study has first quantitatively characterized the mean expression of endothelial adhesion molecules, lining the whole vessel intimal circumference, over a period of time (0 to 20 weeks of diet) in aortic arch lesions of male apoE-deficient compared with wild-type (C57BL/6) mice. These animals were fed a chow or a cholesterol-rich diet. ApoE(-/-) animals showed first an increase (at 6 weeks) and then a reduction (at 16 weeks) in the mean expression of ICAM-1 (P<0.05) and PECAM-1 (P<0.05) but not VCAM-1 levels. Such modulation of the mean expression of adhesion molecules was not observed in wild-type mice. Confirmation of immunohistochemistry results on ICAM-1 was obtained by Northern blots performed on the aortic arch of apoE and C57BL6 chow-fed mice over a period of 20 weeks. Moreover, the presence of VCAM-1 was also confirmed at the RNA level, on aortas of control and apoE mice, by reverse transcription-polymerase chain reaction. In the second part of the study, we assayed the levels of adhesion molecules, in different types of histologically defined atherosclerotic lesions, in apoE(-/-) animals fed for 20 weeks. All 3 adhesion molecules (ICAM-1, PECAM-1, and VCAM-1) were observed to be reduced in fibrofatty and complex lesions but not in fatty streaks or in areas without lesions. These results indicate that the expression of these adhesion molecules in apoE-deficient animals varies with the evolution of the plaque from a fatty to a fibrous stage.
|
10.1161/01.atv.20.10.2288
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pubmed_172_13639
|
In an effort to devise an alternative treatment for human ovarian cancer, we have isolated a monoclonal antibody (OVB-3) that reacts with all ovarian cancers tested (10/10) but few normal tissues. An immunotoxin produced by coupling OVB-3 to Pseudomonas exotoxin kills ovarian cancer cells in tissue culture and prolongs the life of animals bearing human ovarian cancers. These data suggest that this immunotoxin should be evaluated as a treatment for ovarian cancer in women.
|
10.1073/pnas.84.8.2474
|
pubmed_840_8505
|
Adherence to a complex medical regimen in patients with chronic heart failure is an important problem. In the Medicare population, patients with heart failure take an average of 7-8 distinct medications that require >11 separate doses on a daily basis. Nonadherence to these regimens accounts for a significant proportion of hospital admissions. Simplification of the medical regimen for patients with heart failure is likely to be associated with improved adherence and, in parallel, may lead to greater satisfaction and potentially improved outcomes. Therefore, the Compliance and Quality of Life Study Comparing Once-Daily Controlled-Release Carvedilol CR and Twice-Daily Immediate-Release Carvedilol IR in Patients with Heart Failure (CASPER) trial has been designed to rigorously test the hypothesis that a once-daily formulation of carvedilol will result in better compliance and increased patient satisfaction relative to the twice-daily formulation. The background, methods, and statistical approaches used in this trial are reviewed in this article.
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10.1016/j.amjcard.2006.08.004
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pubmed_1064_20755
|
Glucagon-like peptide 1 (GLP-1) is a physiological stimulus of pancreatic beta-cell function. This enteroendocrine hormone is produced by intestinal L cells, and is delivered via the bloodstream to GLP-1 receptors (GLP-1Rs) on pancreatic beta-cells. In addition, there is evidence that beta-cell GLP-1Rs maintain sustained basal activity even in the absence of intestinal peptide, an observation that has raised the question whether these receptors have some degree of ligand-independent function. Here, we provide an alternative explanation for basal receptor activity based on our finding that biologically relevant amounts of fully processed GLP-1 are locally generated by insulinoma cell lines, as well as by alpha-cells of isolated rat islets in primary culture. Presence of GLP-1 was established by immunocytochemistry, as well as by selective ELISAs and bioassays of cell supernatants. A GLP-1R antagonist significantly reduced insulin secretion/production in beta-TC-6 insulinoma cells and isolated rat islets, suggesting a functionally important loop between locally produced GLP-1 and its cognate receptor. Treatment with this antagonist also inhibited the growth of beta-TC-6 cells. These observations provide novel insight into the function of insulin-producing cell lines and native beta-cells during in vitro culture, and they support the idea that locally produced GLP-1 may play a role in intra-islet regulation.
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10.1210/me.2004-0350
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pubmed_1070_23956
|
There is still a lack of a high potent and low toxic immunosuppressive drug. We accidentally found that a quite low dose of anisomycin was sufficient to block proliferation of T cells. In this study, carboxy-fluorescein diacetate-succinimidyl ester staining showed that over 10.0 ng/mL of anisomycin markedly inhibited the proliferation of T cells induced by ConA. Propidium iodide staining revealed that anisomycin led to G0/G1 arrest and blocked S phase entry stimulated by ConA or phorbol 12, 13-dibutyrate plus ionomycin. Anisomycin down-regulated remarkably the CD69 and CD25 expression on the surface of T cells. The response of T cells was repressed by treatment of anisomycin, which was partly restored by adding exogenous interleukin-2, and there was no difference between anisomycin and dexamethasone, although the used dose of the latter was 100-fold of the former. The inhibition of cytotoxicity of T cells against 7919 cells by anisomycin was observed without the direct cytotoxicity to T cells or 7919 cells. The level of transforming growth factor-beta1 fell by <80.0 ng/mL in vitro and 30.0 mg/kg of anisomycin in vivo and enhanced by more than the doses. The treatment of anisomycin prolonged the survival of the transplanted skin and depressed the delayed type hypersensitivity development and the T-cell response in the skin-transplanted mice. Moreover, the effect of its restraining allograft rejection might be superior to cyclosporine A, with relatively slight toxic signs. These results indicate anisomycin significantly inhibits the behaviors of T cells and the transplantation rejection, providing important evidence for anisomycin as a novel immunosuppressant.
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10.1097/CJI.0b013e3181869873
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pubmed_1048_5670
|
The impact of point and diffuse sources for 26 per- and polyfluoroalkyl substances (PFASs) in northern Europe were investigated by studying Swedish rivers (n = 40) and recipient seawater (Baltic Sea and Kattegat; n = 18). Different composition profiles were observed in the rivers, with ten rivers having a remarkably high fraction of perfluoroalkane sulfonic acids (PFSAs; 65% of the ƩPFASs) as compared to other rivers (19%) suggesting major impact of one or several source types dominated by PFSAs. Population density and low latitude (south) were strongly correlated to the widely used perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA) as well as to perfluorohexanesulfonic acid (PFHxS). Significant relationships between several PFCAs and PFSAs (i.e. perfluorobutanoic acid (PFBA), perfluoroheptanoic acid (PFHpA), PFOA, perfluorobutanesulfonic acid (PFBS), and PFHxS) and dissolved organic carbon (DOC) were detected (p < 0.05), indicating chemical binding and co-transport with DOC in fresh water and seawater. Partial least squares regression analysis showed that perfluoroalkyl carboxylic acids (PFCAs) were related to latitude according to their perfluorocarbon chain length (C3, C7, C8, C9, C10 and C11), with longer chains associated with higher latitudes. This suggests the presence of mechanisms promoting higher prevalence of longer chained PFCAs in the north, e.g. precursor degradation, and/or aerosol associated stabilization of PFCAs and their precursors.
|
10.1016/j.envpol.2016.10.089
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pubmed_1008_790
|
The cells giving rise to colonies in the spleen of a lethally irradiated recipient after their transplantation (exogenous CFUs) have a higher self-maintaining ability than those that repopulate their own hemopoietic territory after irradiation, due to the migration of these cells from screened territories (endogenous CFUs). The number of exogenous CFUs and their self-maintaining ability do not change with animals ageing.
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pubmed_1008_790
|
pubmed_902_18838
|
In 2005, Tajikistan joined the Move of Elimination of Tropical Malaria in 2010 and Tertian Malaria to 2015 (Tashkent Declaration, WHO European Office for European). To achieve the targets and goals, it is necessary to evaluate the efficiency of therapeutic and preventive measures in 2000-2007, i.e. in the postepidemic period preceding elimination (pre-elimination according to the WHO terminology). Investigations were conducted in the Gorno-Badakhstan Autonomous Region, Khatlon and Sogdiysk Regions, in the districts under the Republic's jurisdiction, and in the city of Dushanbe. The results of the investigations has shown that a small proportion of the population has red blood cell glucose-6-phosphate dehydrogenase deficiency, which does not preclude mass preventive treatment with primaquine that is responsible for a 2.5-fold reduction in the number of foci (783 foci of different types). Foci should be typified for the rational use of a package of therapeutic and preventive measures in the endemic areas. Differentiated packages of therapeutic and preventive measures correspondingly to the National Malaria Strategy of the Republic of Tajikistan should be implemented depending on the type of a focus.
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pubmed_902_18838
|
pubmed_815_14088
|
A map-based cloning technique for crop plants is being developed using tomato as a model system. The target gene jointless is a recessive mutation that completely suppresses the formation of flower and fruit pedicel abscission zones. Previously, the jointless locus was mapped to a 3 cM interval between the two molecular markers TG523 and RPD158. Physical mapping of the jointless region by pulsed-field gel electrophoresis demonstrated that TG523 and RPD158 reside on a 600 kb SmaI fragment. In this study, TG523 was used as a probe to screen a tomato yeast artificial chromosome (YAC) library. Six tomato YAC (TY) clones were isolated, ranging from 220 to 380 kb in size. Genetic mapping of YAC ends demonstrated that this set of overlapping YACs encompasses the jointless locus. Two YAC ends, TY159L (L indicates left end) and TY143R (R indicates right end), cosegregate with the jointless locus. Only one of the six YACs (TY142) contained single-copy DNA sequences at both ends that could be mapped. The two ends of TY142 were mapped to either side of the jointless locus, indicating that TY142 contains a contiguous 285 kb tomato DNA fragment that probably includes the jointless locus. Physical mapping of the TY142 clone revealed that TY159L and TY143R reside on a 55 kb SalI fragment. Southern blot hybridization analysis of the DNAs of tomato lines nearly isogenic for the jointless mutation has allowed localization of the target locus to a region of less than 50 kb within the TY142 clone.
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10.1007/BF00282751
|
pubmed_851_5776
|
AIM
Hypoglycaemia is a common complication in diabetes patients. However, its relationship with retinopathy has not been well documented in patients with type 2 diabetes (T2D). This study aimed to investigate the associations between hypoglycaemia and the incidence and progression of diabetic retinopathy (DR).
METHODS
In this longitudinal cohort study, which was part of the Japan Diabetes Complications Study (JDCS), adult patients with T2D were recruited at 59 diabetes clinics across Japan. Their history of hypoglycaemia was assessed by standardized self-reported questionnaires. Severe hypoglycaemia was defined as having at least one episode with coma requiring an outpatients visit or hospitalization. Adjusted hazard ratios (HRs) for incidence and progression of DR over 8 years of follow-up were determined.
RESULTS
Of 1221 patients without DR, 127 (10.4%) had experienced non-severe hypoglycaemia within the previous year, whereas 10 (0.8%) reported severe hypoglycaemia episodes. During the 8-year follow-up involving 8492 person-years, 329 patients developed DR. In 410 patients with prevalent DR, the adjusted HRs for incident DR were 4.35 (95% CI: 1.98-9.56; P<0.01) and, for progression of DR, 2.29 (95% CI: 0.45-11.78; P=0.32) with severe hypoglycaemia.
CONCLUSION
Having a history of severe hypoglycaemia was one of the strongest predictors of incident DR in patients with T2D, with a fourfold increased risk. Identifying patients with greater risks of DR based on their history of hypoglycaemia may help to personalize risk evaluation in patients with diabetes.
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10.1016/j.diabet.2017.06.002
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pubmed_1027_3254
|
Insulin-like growth factor (IGF)-I is one of the most potent mitogens to many breast cancer cell lines in vitro. Effective growth inhibition in vitro may be achieved by antibodies to the type I IGF receptor (IGF-IR) or by using antisense strategies. Most human breast cancers express IGF-IR in vivo. Thus, different therapeutic strategies aimed at inhibiting ligand stimulation of the IGF-IR may be an attractive treatment option against breast cancer. Several drugs commonly used in breast cancer influence the IGF system both in vitro and in vivo. While antioestrogens such as tamoxifen and droloxifene reduce the expression of IGF-IR in vitro and suppress plasma levels of IGF-I but elevate IGF-binding protein-1 in vivo, megestrol acetate may reduce the delivery of IGFs to the tissues by inhibition of IGFBP-3 protease activity.
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10.3109/02841869609083963
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pubmed_719_3429
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A growing stream of literature at the interface between economics and psychology is currently investigating 'behavioral spillovers' in (and across) different domains, including health, environmental, and pro-social behaviors. A variety of empirical methods have been used to measure behavioral spillovers to date, from qualitative self-reports to statistical/econometric analyses, from online and lab experiments to field experiments. The aim of this paper is to critically review the main experimental and non-experimental methods to measure behavioral spillovers to date, and to discuss their methodological strengths and weaknesses. A consensus mixed-method approach is then discussed which uses between-subjects randomization and behavioral observations together with qualitative self-reports in a longitudinal design in order to follow up subjects over time. In particular, participants to an experiment are randomly assigned to a treatment group where a behavioral intervention takes place to target behavior 1, or to a control group where behavior 1 takes place absent any behavioral intervention. A behavioral spillover is empirically identified as the effect of the behavioral intervention in the treatment group on a subsequent, not targeted, behavior 2, compared to the corresponding change in behavior 2 in the control group. Unexpected spillovers and additional insights (e.g., drivers, barriers, mechanisms) are elicited through analysis of qualitative data. In the spirit of the pre-analysis plan, a systematic checklist is finally proposed to guide researchers and policy-makers through the main stages and features of the study design in order to rigorously test and identify behavioral spillovers, and to favor transparency, replicability, and meta-analysis of studies.
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10.3389/fpsyg.2019.00342
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pubmed_648_7055
|
Professional networks support health care providers in implementing evidence based knowledge. The German Network for Early Mobilization in Intensive Care Units (ICU) was founded in 2011 and serves for more than 300 critical care team members today. The mobilization network is connected to other professional networks and contributed to the development of national guidelines and quality indicators. Several research projects were conducted. Members of the mobilization network perceived benefits for themselves and their workplace. The network increased participants' knowledge and contributed to quality improvement projects on ICUs. Without having significant resources, this network development may serve as an example for other networks.
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10.1016/j.hrtlng.2019.12.004
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pubmed_573_264
|
BACKGROUND
The developments of peripheral blood stem cells in autologous hematopoietic stem cell transplantation (auto-HCT), and of reduced-intensity conditioning (RIC) regimens in allogeneic HCT (allo-HCT), have considerably changed the transplant approach. Prolonged neutropenia combined with severe mucosal damage and organ dysfunction is no longer the rule in the early post-HCT pancytopenic phase. Although strict isolation during pancytopenia was followed by most HCT units in the past, this may not be the current practice.
METHODS
In 2008, a questionnaire was sent out to the 463 European Group for Blood and Marrow Transplantation centers, enquiring about their current environmental protection procedures; 89 (20%) returned the questionnaire.
RESULTS
Most centers housed auto-HCT recipients in high-efficiency particulate air (HEPA)-filtered rooms without (52%) or with laminar air flow (LAF) (29%) after total body irradiation (TBI), whereas HEPA-filtered rooms were used in 53% of auto-HCT conditioned without TBI. During the initial pancytopenic phase after allo-HCT, patients were housed in HEPA/LAF rooms in 50% and 42% of the centers, if a high-dose myeloablative conditioning regimen or a RIC regimen was used, respectively. Surprisingly, 8-24% of the centers reported that no isolation procedures were used in patients colonized or infected with highly transmissible pathogens (i.e., Clostridium difficile, respiratory viruses, and varicella zoster virus).
CONCLUSION
In conclusion, universal recommendations for infected or colonized patients may be poorly known or applied in many HCT units.
|
10.1111/tid.12064
|
pubmed_847_6351
|
BACKGROUND
High-flow nasal cannula (HFNC) is a new type of oxygen therapy, but its application in surgery remains unclear, we tried to describe the application of HFNC in microlaryngoscopic surgery for the Chinese population.
METHODS
Nineteen adults, American society of anesthesiology class (ASA) 1-2 patients with body mass index < 30 kg.m-2 underwent microlaryngoscopic surgery using HFNC for airway management. Outcomes included apnoea time, intraoperative oxygenation, carbon dioxide value, lactate value, and the relationship between the duration of apnoea time and carbon dioxide levels.
RESULTS
A total of 19 patients underwent vocal cord tumor resection under a microlaryngoscope with HFNC as the sole method of ventilation. The mean age was 39.7 years old, and the mean BMI was 23.9 kg.m-2. The mean apnea time was 21.5 min. The SpO2 of 18 patients remained above 90%, and only 1 patient dropped to 88%. The average basal lactate and highest lactate value was 0.58 mmol. L-1 and 0.68 mmol.L-1. The difference between basal and highest lactate values was statistically significant (P < 0.05). The average highest PaCO2 value was 79.4 mmHg. The PaCO2 increased by 1.68 ± 0.12 mmHg every minute linearly.
CONCLUSIONS
In the case series we have observed that HFNC would be safe and effective oxygenation and ventilation technique for selected Chinese patients undergoing non-laser microlaryngoscopic surgery within 30 min. The tubeless technology reduces the complications of tracheal intubation and jet ventilation and clears the surgical field of vision.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ( ChiCTR100049144 ).
|
10.1186/s12871-022-01627-3
|
pubmed_666_1397
|
: Recently the use of food by-products as natural sources of biologically active substances has been extensively investigated especially for the development of functional foods fortified with natural antioxidants. Due to their content of bioactive compounds, such as carotenoids, flavonoids and limonoids, citrus peels could be suitable to formulate enriched olive oils able to boost healthy nutrition. The aim of this study was: (i) to determine the compositional and sensory profiles of citrus olive oil; and (ii) to evaluate its nutraceutical properties in rats with high fat diet-induced metabolic syndrome and oxidative stress. The results obtained show the potential of using citrus peels as a source of bioactive compounds to improve the sensory profile as well as the phytochemical composition of olive oil. We demonstrated that the production system of Citrus x aurantium olive oil and Citrus limon olive oil improves its organoleptic properties without altering its beneficial effects, which, like control extra virgin olive oil, showed protective effects relating to glucose and serum lipid levels, metabolic activity of adipocytes, myocardial tissue functionality, oxidative stress markers and endothelial function at blood vessel level.
|
10.3390/nu12061557
|
pubmed_1074_23899
|
OBJECTIVE
To describe the diagnostic procedures, therapeutic management and successful outcome of a case of anaphylaxis induced by the inadvertent intravenous (IV) administration of mare's milk to a neonatal foal.
CASE SUMMARY
A 3-day-old Thoroughbred colt was presented for treatment of bilateral flexural limb deformities of the forelimbs. Because the foal was unable to ambulate initially, mare's milk was administered via nasoesophageal tube feedings during treatment of the musculoskeletal disorder. Anaphylaxis resulted after unintentional administration of a bolus of 150mL of mare's milk through a jugular catheter. Aggressive therapy for anaphylaxis and careful monitoring resulted in the successful recovery of the foal after 9 days of intensive care.
NEW OR UNIQUE INFORMATION PROVIDED
This case is the first published report to describe the effects of accidental IV administration of mare's milk to a neonatal foal. Medical errors are commonly reported in pediatric medicine; the intent of this report is to raise awareness of medical errors and student education in equine medicine as well as describe the therapy and outcome of anaphylaxis induced by IV administration of mare's milk in a neonatal foal.
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10.1111/j.1476-4431.2010.00586.x
|
pubmed_3_21053
|
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates producing the Panton-Valentine leukocidin (PVL) have been reported worldwide. We describe the molecular characteristics of PVL-positive CA-MRSA strains isolated in Madrid, Spain, and analyze the clinical features of patients infected with these isolates. From 2004 to 2007, we collected 13 PVL-positive MRSA isolates from patients attending to the emergency department. The isolates were genotyped by pulsed-field gel electrophoresis, SCCmec typing, agr polymorphism, and multilocus sequence typing. Susceptibility to 29 antimicrobials was determined by the broth microdilution and by the E-test methods. The isolates belonged to 3 genotypes: ST8-SCCmec IVc (n = 11), ST5-SCCmec IVa (n = 1), and ST80-SCCmec IVc (n = 1). The corresponding agr types were I, II, and III, respectively. Five isolates were resistant to tetracycline and doxycycline, and 1 was resistant to fusidic acid (ST80). The isolates were from children (n = 9) and adults (n = 4), and were associated with skin and soft tissue infections (n = 9), otitis (n = 1), and bacteremia (n = 1). Nine patients were from South America. Our results indicate the transcontinental importation and recent emergence in Spain of PVL-positive CA-MRSA strains belonging to 3 distinct lineages, including 1 predominant (ST8-SCCmec IVc).
|
10.1016/j.diagmicrobio.2008.01.001
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pubmed_795_9230
|
Knowledge of mechanisms of rheumatic diseases has a continuing influence on the introduction of many laboratory tests to be used for establishing diagnosis or monitoring the activity of rheumatic disease. In the article presented are autoantibodies characteristic for distinct inflammatory rheumatic diseases, the role of serum complement activity, immune complexes, HLA-typing as well as other laboratory parameters needed for the diagnosis of rheumatic disease. The methods of synovial fluid analysis are described. Presented are laboratory investigations used by rheumatologists for the evaluation of activity of inflammatory rheumatic diseases and successful treatment together with investigations necessary for the evaluation of side-effects of treatment.
|
pubmed_795_9230
|
pubmed_58_3883
|
Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson's disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6-1.8 Å resolution) showed that they all bind in the active site cavity of the protein with the chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3',4'-dimethylphenyl)-4-oxo-4 H-chromene-3-carboxamide (1), N-(3'-chlorophenyl)-4-oxo-4 H-chromene-3-carboxamide (2), and N-(3'-fluorophenyl)-4-oxo-4 H-chromene-3-carboxamide (3), respectively. These compounds were also 1000-fold more effective than l-deprenyl in reducing the cellular levels of reactive oxygen species (ROS).
|
10.1021/acs.jmedchem.8b00357
|
pubmed_654_3419
|
This article describes a patient who exhibited taurodontism, relatively short roots, external resorption of the roots of the anterior teeth, and a marked tendency toward microcephalic dwarfism. This case is similar to that reported previously by Sauk and Delaney.
|
10.1016/0030-4220(77)90279-1
|
pubmed_630_1009
|
It is acknowledged internationally that chronic disease management (CDM) for community-living older adults (CLOA) is an increasingly complex process. CDM for older adults, who are often living with multiple chronic conditions, requires coordination of various health and social services. Coordination is enabled through interprofessional collaboration (IPC) among individual providers, community organizations, and health sectors. Measuring IPC is complicated given there are multiple conceptualisations and measures of IPC. A literature review of several healthcare, psychological, and social science electronic databases was conducted to locate instruments that measure IPC at the team level and have published evidence of their reliability and validity. Five instruments met the criteria and were critically reviewed to determine their strengths and limitations as they relate to CDM for CLOA. A comparison of the characteristics, psychometric properties, and overall concordance of each instrument with salient attributes of IPC found the Collaborative Practice Assessment Tool to be the most appropriate instrument for measuring IPC for CDM in CLOA.
|
10.3109/13561820.2015.1123233
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pubmed_469_9757
|
We characterize absorption-time distributions for birth-death Markov chains with an absorbing boundary. For "extinction-prone" chains (which drift on average toward the absorbing state) the asymptotic distribution is Gaussian, Gumbel, or belongs to a family of skewed distributions. The latter two cases arise when the dynamics slow down dramatically near the boundary. Several models of evolution, epidemics, and chemical reactions fall into these classes; in each case we establish new results for the absorption-time distribution. Applications to African sleeping sickness are discussed.
|
10.1103/PhysRevLett.128.218301
|
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