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pubmed_293_22816
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BACKGROUND & AIMS
The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation.
METHODS
We conducted a retrospective, multicentre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. The primary endpoint was HEV-associated mortality; the secondary endpoint was HEV-associated liver-related morbidity.
RESULTS
The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in 8 (16%) patients, including 1 patient with iNHL and 1 patient >100 days after alloHSCT in complete remission, and was associated with male sex (p = 0.040), cirrhosis (p = 0.006) and alloHSCT (p = 0.056). Blood-borne transmission of hepatitis E was demonstrated in 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 79.2%. Ribavirin treatment was associated with lower mortality (p = 0.037) and by trend with lower rates of chronicity (p = 0.407) when initiated <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%).
CONCLUSION
Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction of immunosuppressive treatment requires caution.
LAY SUMMARY
Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective.
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10.1016/j.jhep.2019.04.022
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pubmed_590_18514
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OBJECTIVE
Torque teno virus (TTV) infects patients at risk for parenteral exposure and chronic blood transfusion, such as those with β-thalassemic. This study aimed to assess the prevalence of TTV infection and co-infection of TTV and hepatitis C virus (HCV) in pediatric thalassemia patients receiving chronic blood transfusion.
MATERIAL AND METHODS
The study included 90 pediatric thalassemia patients receiving chronic blood transfusion that presented to the Mofid Children's Hospital, Tehran, Iran. The control group included 90 healthy volunteer children. Serum TTV DNA detection via semi-nested PCR and HCV Ab were performed in all the participants. Demographic characteristics and clinical data were collected from each participant for statistical analysis.
RESULTS
In all, 64.4% of the patients had TTV infection, versus 24.4% of the controls (P < 0.01). The thalassemia patients had a greater probability of having TTV and HCV infections than the controls, with a common OR of 5.60 (95% CI: 2.94-10.69) and 2.15 (95% CI: 1.83-2.50), respectively. In total, 17.2% (10/58) of the patients that were TTV positive were also HCV positive, whereas 6.3% (2/32) of the TTV-negative patients were anti-HCV antibody (Ab) positive (P = 0.14).
CONCLUSION
The prevalence of TTV and HCV infection was higher in the Iranian thalassemia patients on chronic transfusion therapy than in the controls. The high prevalence of TTV in pediatric thalassemia patients on chromic transfusion therapy may indicate the superiority of the parenteral route compared to other routs of TTV transmission.
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10.5505/tjh.2012.20280
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pubmed_431_24517
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Genital human papillomavirus (HPV) infection with both low- and high-risk types is common, but most infections resolve as a result of a cell-mediated immune response. Failure to induce an effective immune response is related to inefficient activation of innate immunity and ineffective priming of the adaptive immune response; this defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. This milieu becomes operationally HPV antigen tolerant, and the host's defenses become irrevocably compromised. HPV antigen-specific effector cells are poorly recruited to the infected focus and their activity is downregulated; neoplastic HPV containing cervical keratinocytes expressing high levels of E6 and E7 oncoproteins are not killed in this immunosuppressive, tolerant milieu, and progression to high-grade disease and cancer can result. Highly efficacious prophylactic HPV L1 virus-like particle (VLP) vaccines circumvent viral epithelial evasion strategies since they are delivered by intramuscular injection. The stromal dendritic cells of the muscle that encounter the highly immunogenic repeat structure of the VLP then migrate with their cargo to the lymph node, initiating an immune cascade that results in a robust T-cell dependent B-cell response, which generates high levels of L1-specific serum neutralizing antibodies and immune memory.
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10.1016/j.ygyno.2008.02.003
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pubmed_1_13480
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There is considerable interindividual variation in the response to antiplatelet and anticoagulant therapies. It has been proposed that this variability in drug response may be attributable to genetic variants. Thus, pharmacogenetics may help to accurately predict response to cardiovascular disease (CVD) therapies in order to maximize drug efficacy, minimize drug toxicity, and to tailor personalized care for these patients. Although the clinical utility of pharmacogenetics is promising, its adoption in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies. Thus, this review focuses on the genetic determinants of commonly used platelet antagonists and anticoagulants including aspirin, clopidogrel, dabigatran, and warfarin. We also explore the clinical translation of pharmacogenetics in the management of patients with CVD.
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10.1111/jth.12924
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pubmed_778_657
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PURPOSE
Bladder pressure during voiding can be estimated by a noninvasive technique using controlled inflation of a penile cuff. This test provides a valid and reliable estimate of isovolumetric bladder pressure but to our knowledge the role of the test for the routine clinical treatment of patients with lower urinary tract symptoms (LUTS) has yet to be demonstrated. As a first step, we evaluated a proposed nomogram for the diagnosis of bladder outlet obstruction in men with LUTS using noninvasive measurements of pressure and flow.
MATERIALS AND METHODS
Using a combination of theoretical calculation and experimental data the existing International Continence Society pressure flow nomogram was modified to allow noninvasive measurement of isovolumetric bladder pressure in place of detrusor pressure at maximum urine flow. Accuracy of the nomogram for classifying obstruction was then tested in a group of 144 men with LUTS who underwent an invasive and a noninvasive pressure flow study.
RESULTS
The modified nomogram identified men with obstruction with 68% positive predictive value and 78% negative predictive value. Predictive accuracy could be improved by adding an additional criterion of obstruction, that is maximum urine flow less than 10 ml second, whereby an identifiable 69% of all cases could be classified as obstructed (88% positive predictive value) or not obstructed (86% negative predictive value). In the remaining 31% of patients invasive pressure flow studies would provide additional information, although some results would remain equivocal.
CONCLUSIONS
The proposed nomogram combined with the additional flow rate criterion can classify more than two-thirds of cases without recourse to invasive pressure flow studies. We must now evaluate the usefulness of this classification for the treatment of men with LUTS.
|
10.1097/01.ju.0000173637.07357.9e
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pubmed_900_12710
|
This study analysed the drinking patterns and motivation to change drinking behaviours among injury patients who acknowledged alcohol as a factor in their injuries. A cross-sectional study was conducted over 18 months at a Swedish emergency department. A total of 1930 injury patients aged 18 - 70 years were enrolled in the study (76.8% completion rate). Of those who reported drinking, 10% acknowledged alcohol as a factor in their injury. A patient was more likely to report a causal attribution of the injury to alcohol the higher the weekly intake and the higher the frequency of heavy episodic drinking. The motivation to change variables showed a similar pattern of increased likelihood of attributing a causal link of alcohol and injury with increasing discontent with drinking behaviours and increasing desire to change drinking behaviours. The findings suggest that the ability to measure causal attribution of alcohol to injuries could be a promising tool to help patients explore the association between their injuries and alcohol use and motivate patients to modify drinking behaviours in order to avoid future injuries.
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10.1080/17457300701374759
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pubmed_419_5407
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BACKGROUND
Mammalian inositol 1,4,5-trisphosphate receptor (ITPR) genes encode ubiquitously expressed endoplasmic reticulum Ca2+ channels that have recently been shown to be closely linked to the pathogenesis of several cancers. However, few studies to date have explored associations between ITPR gene family single nucleotide polymorphisms (SNPs) and breast cancer risk.
METHODS
In the present case-control study, 12 SNPs in the potential functional regions of the ITPR1, ITPR2, and ITPR3 genes were genotyped using an Illumina Infinium® Beadchip in 2095 Chinese women (1032 cases and 1063 controls).
RESULTS
Multivariate logistic regression analyses indicated that a missense SNP in the ITPR3 coding region (rs2229642) was significantly related to breast cancer risk when using an additive model in this study (rs2229642-adjusted odds ratio = 1.40, 95% confidence interval = 1.12-1.74, p = 2.97 × 10-3 ). Expression quantitative trait loci analyses indicated that the SNP rs2229642 was associated with reduced ITPR3 expression levels (p = 3.2 × 10-7 ) and with marked reductions in the expressions of several proximal genes, including BAK1, GRM4, HLA-DOB, and UQCC2 (p = 0.013, 0.018, 3.4 × 10-3 , 3.8 × 10-5 ), suggesting that it may further regulate other genes associated with oncogenic susceptibility. Kaplan-Meier analyses indicated that the patients with higher ITPR3 expression exhibited significantly poorer outcomes compared to the patients with lower expression of this gene (hazard ratio = 1.11, 95% confidence interval = 1-1.23, p = 0.046).
CONCLUSIONS
The results indicated that genetic variant in the coding region of ITPR3 gene may regulate the expressions of its host and some other cancer-related genes, as well as act as potential predictive biomarker for susceptibility to breast cancer in the Chinese population.
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10.1002/jgm.3463
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pubmed_1043_11923
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The seminal plasma of eight males with normospermia, seven with oligozoospermia, and eight with azoospermia was examined for the presence of IgG and IgM by means of double-gel immunodiffusion. IgG was present in every seminal plasma sample. The highest titers of IgG were found in azoospermic and normospermic samples, but the lowest IgG titers were seen only in normospermic samples. IgM was detected only in some cases, mainly in the azoospermic group. Testicular biopsy was performed in all the azoospermic patients, but IgM was found only in the cases demonstrating spermatogenic arrest and was not found in the cases with complete spermatogenesis. It is concluded that the IgM present in the seminal plasma was of testicular origin and was associated with injury of the male genital system.
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10.3109/01485017908985046
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pubmed_871_13965
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OBJECTIVE
Neointimal hyperplasia is a central feature in the pathogenesis of a variety of vascular pathologies. Mitogen-activated protein kinases (MAPK) are involved in the downstream transduction of signals from receptors for many of the molecules known to be instrumental in this process and thus represent a potential target for the modification of the proliferative response. We examined the hypothesis that down-regulation of MAPK would inhibit neointima formation in a porcine coronary injury model.
METHODS
Balloon angioplasty was performed on 38 coronary arteries from 23 large white pigs. Antisense oligonucleotides to the p42 and p44 MAPK were locally delivered to the site of injury immediately after balloon injury. At 7 or 21 days, arteries were harvested for morphometry, determination of cell proliferation and assessment of MAPK protein levels.
RESULTS
At 7 days, neointima formation was significantly reduced compared to controls (corrected intima/media ratio (IMR) 1.01+/-0.13 vs. 1.61+/-0.07, P<0.01) and this was associated with a 58% and 23% down-regulation of p42 and p44 protein levels, respectively. Intimal and medial proliferation rates were also reduced by 32% and 26%, respectively. At 21 days however, the effect of the treatment on MAPK protein levels was no longer significant and this correlated with a loss of the effects on IMR and cell proliferation.
CONCLUSIONS
Down-regulation of MAPK inhibits early smooth muscle cell (SMC) proliferation and neointimal thickening in response to arterial injury, implying that it plays an important role in determining the early vascular response to injury. Inhibitory effects were less apparent at 21 days after a single delivery of oligonucleotide, implying that more sustained local delivery may be required to achieve longer term therapeutic benefit.
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10.1016/s0008-6363(02)00335-8
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pubmed_528_14564
|
Ozonation and treatment of wastewaters with oxalic acid-assimilating bacterium was attempted for the complete degradation of reactive dyes. Oxalic acid-assimilating bacterium, Pandoraea sp. strain EBR-01, was newly isolated from soil under bamboo grove and was identified to be a member of the genus Pandoraea by physicochemical and biochemical tests including 16S rDNA sequence analysis. The bacterium was grown optimally at pH 7 and temperature of 30 degrees C under the laboratory conditions. Reactive Red 120 (RR120), Reactive Green 19 (RG19), Reactive Black 5 (RB5) and Remazol Brilliant Blue R (RBBR) were used in degradation experiments. At the initial reactive dye concentrations of 500 mg/l and the ozonation time of 80 min, it was confirmed that 75-90 mg/l oxalic acid was generated from reactive dyes by ozonation. Microbial treatment using EBR-01 greatly decreased the amount of oxalic acid in the mixture after 48 h, but it was not removed completely. TOC/TOC(0) of reactive dye solutions was also decreased to 80-90% and 20-40% by ozonation and microbial treatment using EBR-01, respectively. The study confirmed that consecutive treatments by ozone and microorganisms are efficient methods to mineralize reactive dyes.
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10.1007/s10532-007-9153-3
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pubmed_187_21135
|
Since 1996 a picture archiving and communications system (PACS) is installed at the university hospital of Freiburg. The PACS is integrated in the hospital information system (HIS) and several modalities of different vendors are attached to it. During the implementation phase three critical factors to the success of our PACS installation where identified: the support of the workflow, the interface of the radiological information system (RIS) to the modalities, and the security policy to allow hospital-wide access to the images and results in the PACS.
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pubmed_187_21135
|
pubmed_40_4776
|
Extracellular domains of cell surface receptors and ligands mediate cell-cell communication, adhesion, and initiation of signaling events, but most existing protein-protein "interactome" data sets lack information for extracellular interactions. We probed interactions between receptor extracellular domains, focusing on a set of 202 proteins composed of the Drosophila melanogaster immunoglobulin superfamily (IgSF), fibronectin type III (FnIII), and leucine-rich repeat (LRR) families, which are known to be important in neuronal and developmental functions. Out of 20,503 candidate protein pairs tested, we observed 106 interactions, 83 of which were previously unknown. We "deorphanized" the 20 member subfamily of defective-in-proboscis-response IgSF proteins, showing that they selectively interact with an 11 member subfamily of previously uncharacterized IgSF proteins. Both subfamilies interact with a single common "orphan" LRR protein. We also observed interactions between Hedgehog and EGFR pathway components. Several of these interactions could be visualized in live-dissected embryos, demonstrating that this approach can identify physiologically relevant receptor-ligand pairs.
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pubmed_40_4776
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pubmed_436_19278
|
Circadian rhythms are normal variations in physiological processes that occur over the period of a day. These rhythms are essential for the organism since they allow anticipatory metabolic regulations to prepare for the up-coming feeding or rest period. Disturbances of the biological clock predispose to metabolic disorders such as dyslipidaemia, insulin resistance and obesity. Moreover, certain pathological events, such as cardiovascular accidents (myocardial infarction, stroke) occur more frequently at specific times of the day. The nuclear receptors Rev-erbalpha and RORalpha are clock components involved in the regulation of the core clock circuitry. They are also important regulators of lipid and lipoprotein metabolism, adipogenesis and vascular inflammation. Moreover, they cross-talk with several other nuclear receptors controlling energy homeostasis. Therefore, Rev-erbalpha and RORalpha may play a central role in the coordination of metabolic processes and circadian outputs.
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10.3132/dvdr.2008.0014
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pubmed_633_24543
|
BACKGROUND
Microvesicles are involved in different pathological processes such as inflammation, coagulation and tumor progression. We intended to establish an immunoaffinity capture method for detecting microvesicles and bioactive effectors carried on them using a specific homemade monoclonal antibody AD-1. By this method we investigated the association of inflammation with platelet activation in patients with nonvalvular atrial fibrillation (NVAF).
METHODS
A case-control study of 90 Chinese subjects selected in 3 groups: control, paroxysmal AF, and persistent AF. After capturing the microvesicles of serum using a specific monoclonal antibody AD-1, the amounts of LAP, IL-1β and P-selectin loaded on these microvesicles were quantified by either enzyme activity assay (LAP) or ELISA respectively.
RESULTS
Compared with normal controls, the patients with persistent AF showed significantly increased serum levels of microvesicles (P<0.001), microvesicle-bound IL-1 β (P=0.019) and microvesicle-bound P-selectin (P=0.001). The latter two were significantly correlated with each other (r(2)=0.371, r=0.616, P<0.001). The microvesicle-bound IL-1β (β=0.570, P<0.001) and body weight (β=0.427, P=0.002) were as independent predictors of platelet activation.
CONCLUSIONS
The method was easy and reproducible. Inflammation may be involved in the activation of platelets in NVAF.
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10.1016/j.cca.2010.07.005
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pubmed_418_24447
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Land plants co-speciate with a diversity of continually expanding plant specialized metabolites (PSMs) and root microbial communities (microbiota). Homeostatic interactions between plants and root microbiota are essential for plant survival in natural environments. A growing appreciation of microbiota for plant health is fuelling rapid advances in genetic mechanisms of controlling microbiota by host plants. PSMs have long been proposed to mediate plant and single microbe interactions. However, the effects of PSMs, especially those evolutionarily new PSMs, on root microbiota at community level remain to be elucidated. Here, we discovered sesterterpenes in Arabidopsis thaliana, produced by recently duplicated prenyltransferase-terpene synthase (PT-TPS) gene clusters, with neo-functionalization. A single-residue substitution played a critical role in the acquisition of sesterterpene synthase (sesterTPS) activity in Brassicaceae plants. Moreover, we found that the absence of two root-specific sesterterpenoids, with similar chemical structure, significantly affected root microbiota assembly in similar patterns. Our results not only demonstrate the sensitivity of plant microbiota to PSMs but also establish a complete framework of host plants to control root microbiota composition through evolutionarily dynamic PSMs.
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10.1007/s11427-019-9521-2
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pubmed_453_20553
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The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex. Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However, most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey.
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10.1002/(SICI)1098-1063(1997)7:2<146::AID-HIPO4>3.0.CO;2-L
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pubmed_271_579
|
BACKGROUND AND OBJECTIVE
To assess the effectiveness of currently recommended daily intakes of vitamin D (25[OH]D) to bring optimal serum concentrations (30ng/ml) in postmenopausal osteoporotic women.
PATIENTS AND METHODS
We reviewed 25(OH)D serum concentrations in 165 consecutive osteoporotic postmenopausal women who were taking oral vitamin D daily supplements above 800IU during at least 3 months. The proportion of patients who achieved 25(OH)D levels of 20, 30 and 40ng/ml were compared according to daily vitamin D intakes (group 1: 800-1,000IU, group 2: 1,001-1,600IU, group 3:>1,600IU).
RESULTS
Mean patient age was 69 (10) years. Percentage of patients with serum 25(OH)D levels above 20ng/ml was 79.5% (63.5-88.5%), 92.7%(78.7-96%) and 97.6% (90.6-100%) in group 1, 2, and 3 patients, respectively (P=.009). Serum levels above 30ng/ml were achieved in 27.7% (14.7-44.7%), 53.6% (37.6-70%) and 90.2% (81.2-96.6%), respectively (P<.001). Serum levels above 40ng/ml were reached in 7.2% (1-20%), 24.4% (12-40%) and 61% (49-72%), respectively (P<.001).
CONCLUSION
Daily reference intakes of vitamin D supplements (800-1,000IU) may be insufficient to achieve optimal serum levels of vitamin D in postmenopausal osteoporotic women.
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10.1016/j.medcli.2011.07.024
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pubmed_621_17859
|
BACKGROUND
The aim of this study was to report the long-term clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer.
MATERIALS AND METHODS
Between March 2004 and July 2007, 26 patients with locally advanced, medically inoperable head and neck cancer or gross residual tumors in close proximity to critical structures following head and neck surgery were treated with SBRT as a boost treatment. All patients were initially treated with standard external beam radiotherapy (EBRT). SBRT boost was prescribed to the median 80% isodose line with a median dose of 21 (range 10-25) Gy in 2-5 (median, 5) fractions.
RESULTS
The median follow-up after SBRT was 56 (range 27.6 - 80.2) months. The distribution of treatment sites in 26 patients was as follows: the nasopharynx, including the base of the skull in 10 (38.5%); nasal cavity or paranasal sinus in 8 (30.8%); periorbit in 4 (15.4%); tongue in 3 (11.5%); and oropharyngeal wall in 1 (3.8%). The median EBRT dose before SBRT was 50.4 Gy (range 39.6 - 70.2). The major response rate was 100% with 21 (80.8%) complete responses (CR). Severe (grade ≥ 3) late toxicities developed in 9 (34.6%) patients, and SBRT boost volume was a significant parameter predicting severe late complication.
CONCLUSIONS
The present study demonstrates that a modern SBRT boost is a highly efficient tool for local tumor control. However, we observed a high frequency of serious late complications. More optimized dose fractionation schedule and patient selection are required to achieve excellent local control without significant late morbidities in head and neck boost treatment.
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10.1186/1748-717X-7-85
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pubmed_483_5007
|
PURPOSE
The purpose of this study was to evaluate the biomechanical effects of bone loss on peri-implant bending strain underneath overdentures.
MATERIALS AND METHODS
One mandibular and one maxillary edentulous model were created and covered with 2 to 4 mm of silicone rubber to simulate the oral mucosa. Four strain gauges were attached to four sides of each implant. In the mandibular model, two implants were inserted, and the implant was placed bilaterally in the area between the mandibular canines and lateral incisors. A maxillary conventional denture and mandibular overdenture were fabricated with acrylic resin to fit the edentulous models. Five bone loss levels were created: no bone loss, 0.8 mm bone loss on only the left implant, 0.8 mm bone loss bilaterally, 1.5 mm bone loss on only the left implant, and 1.5 mm bone loss bilaterally. Magnetic attachments were used to retain the denture. The bending strains generated from three types of unilateral loading were measured by a sensor interface, and the data were analyzed using the Kruskal-Wallis test and Bonferroni's post hoc test.
RESULTS
Bending strain increased with decreasing bone levels on the loading side. On the nonloading side, bending strains were greater at even bone loss (0.8 mm or 1.5 mm bone loss bilaterally) than at uneven bone loss (0.8 mm or 1.5 mm bone loss on only the left implant). Strains under loading at the left first premolar were approximately equal to that under loading with a cotton roll; these strains were higher than those generated with loading at the left first molar.
CONCLUSION
Peri-implant bending strains rapidly increased on the loading side as bone loss levels increased. Peri-implant bending strains on the nonloading side were higher at bilaterally even bone loss than at unilateral bone loss.
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10.11607/jomi.6596
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pubmed_400_3792
|
Substituted benzoic acid anions undergo decarboxylation in the medium-pressure region of an electrospray ion source yielding in most cases the correspondingly substituted phenide anions in high yield. The location of the anionic center is specified by the position of the carboxylic group. The only exceptions are compounds with substituents containing acidic hydrogen atoms, like OH and NH(2) groups. For such compounds, either an intra- or an intermolecular (mediated by the molecules of methanol or water) proton transfer from the more acidic position to the benzene ring is observed. The generated anions can be selected using the first quadrupole for studying their ion-molecule chemistry in the second quadrupole of a triple quadrupole mass spectrometer. Their reactions with CO(2), O(2), CH(3)COCH(3) and CCl(4) may serve as typical examples. The general applicability of this method for the generation of phenide anions has been confirmed on three different mass spectrometers. Experiments performed using carboxylic acids other then benzoic acid and its derivatives show that this method is not limited to phenide anions and can be used for the generation of a much wider range of carbanions in the gas phase.
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10.1002/rcm.969
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pubmed_1112_19843
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A multireaction monitoring method using high-performance liquid chromatography-tandem mass spectrometry was developed for 12 target peptides for determination of endogenous peptide concentrations in human serum. Chromatographic separation conditions were optimized and recoveries for liquid-liquid extraction, solid-phase extraction (SPE), and ultrafiltration of endogenous peptides from human serum were compared, and the SPE method was selected for 12 targeted peptide extractions. The optimized SPE method gave recoveries higher than 60 % for all targeted peptides. The limit of detection was 10 ng/ml for most peptides, except for N-formyl-methionyl-leucyl-phenylalanine (NFMLP) and adrenocorticotropic hormone (ACTH) (18-39). The limit of detection for these two peptides was 1 ng/ml. The real serum samples of 25 elderly and 23 young people were analyzed using the optimized extraction and analysis method. Half of the 12 peptides were below the limit of quantification, and B-type natriuretic peptide, cholecystokinin, ACTH(7-38), substance P, NFMLP, and valyl-glutamyl-prolyl-isoleucyl-prolyl-tyrosine were quantified in the concentration range from 0.1 to 50 ng/ml. The concentration of ACTH(7-38) was significantly higher in elderly people and that of NFMLP was significantly lower in elderly people compared with young people (p < 0.0001). This result implies that there be a possible relationships between ACTH, NFMLP and lowered immunity.
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10.1007/s00216-012-6344-5
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pubmed_258_10803
|
BACKGROUND
Traditional angiography only displays two-dimensional images of the coronary arteries during stent implantation. However, intravascular imaging can show the structure of the vascular wall, plaque characteristics. This article aims to evaluate the efficacy of intravascular imaging-guided drug-eluting stent (DES) implantation.
METHOD
We conducted a systematic review and meta-analysis of randomized controlled trials of intravascular imaging-guided, including patients with DES implantation guided by intravascular ultrasound or optical coherence tomography and traditional angiography. The databases of PubMed, EMBASE, web of science, and Cochrane Library were searched. The primary outcome was target lesion revascularization (TLR). The secondary outcomes included the target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), cardiac death, all-cause death, and the major adverse cardiac events (MACE) during the 6-24 months follow-up. The fixed-effects model was used to calculate the relative risk (RR) and 95% confidence interval of the outcome event. Meanwhile, the trial sequence analysis was employed to evaluate the results.
RESULT
This meta-analysis included fourteen randomized controlled trials with 7307 patients. Compared with angiography-guided, intravascular imaging-guided DES implantation can significantly reduce the risk of TLR (RR 0.63, 0.49-0.82, P = 0.0004), TVR (RR 0.66, 0.52-0.85, P = 0.001), cardiac death (RR 0.58; 0.38-0.89; P = 0.01), MACE (RR 0.67, 0.57-0.79; P < 0.00001) and ST (RR 0.43, 0.24-0.78; P = 0.005). While there was no significant difference regarding MI (RR 0.77, 0.57-1.05, P = 0.10) and all-cause death (RR 0.87, 0.58-1.30, P = 0.50).
CONCLUSIONS
Compared with angiography, intravascular imaging-guided DES implantation is associated with better clinical outcomes in patients with coronary artery disease, especially complex lesions (Registered by PROSPERO, CRD 42021289205).
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10.1186/s12872-022-02772-w
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pubmed_1006_1242
|
An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression. The interdependence of host immunity with antiviral efficacy is underscored by the increased antiviral drug resistance in persons with advanced degrees of chronic immunosuppression, related to the higher level of viral replication and viraemia which occurs in the absence of an effective host immune response. Further definition of the precise mechanisms of these interactions should facilitate the rational design of antiviral agents and immunomodulatory therapies to improve treatment of viral infections.
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10.1017/s0031182000075399
|
pubmed_1107_22535
|
The marked increases at the national and state level of preteen and teenage sexual activity and childbearing are reviewed in an effort to make dental practitioners aware of extent of the problem.
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pubmed_1107_22535
|
pubmed_979_12303
|
Although much has been written in recent years on the virtues of collaboration, the reality often does not match the rhetoric. Many sponsors have been caught in a "schizophrenia of spirit," in which their actions do not accord with the values they profess. One reason for this contradiction is that the institutional Church has given sponsors a control model with which to operate. According to such a model, sponsors set the mission, appoint boards, control assets, approve dissolutions, approve bylaws, appoint the chief executive officer, and approve the auditor. Maintaining this much control makes it difficult for sponsors to initiate effective collaborative ventures. On the contrary, effective collaboration requires a willingness to cooperate and use influence, rather than to exert control. An influence model also calls on sponsors to trust others and believe in their commitment to achieving a greater good. For many reasons, religious community leaders find an influence model difficult to implement. However, as resources become more scarce and as the numbers of poor continue to rise, sponsors will be increasingly called on to find creative ways to work with others. In such an environment, they must be willing to take the risks necessary to fulfill the healing ministry of Jesus.
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pubmed_979_12303
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pubmed_20_20164
|
BACKGROUND
The data on the histology of cutaneous lesions of drug reaction with eosinophilia and systemic symptoms (DRESS) is limited.
AIMS
To study the histopathology of cutaneous lesions of drug reaction with eosinophilia and systemic symptoms (DRESS) and to identify any features with diagnostic or prognostic significance.
METHODS
All patients admitted to the dermatology ward of government medical college, Kozhikode from January 1, 2014 to December 31, 2014 with probable or definite DRESS as per the RegiSCAR scoring system and who were willing to undergo skin biopsy were included in this prospective study.
RESULTS
The study population comprised of nine patients. The consistent histological finding documented was the predominantly lymphocytic dermal inflammatory infiltrate. Four of the five patients whose histology revealed focal interface dermatitis and keratinocyte vacuolation with or without apoptotic keratinocytes, had elevated liver transaminases. Tissue eosinophilia was associated with disease flares. The presence of atypical lymphocytes in peripheral smear and histological evidence of dense dermal inflammatory infiltrate showed an association with hepatic involvement.
LIMITATIONS
The main limitations of our study were the small sample size and our inability to carry out a detailed immunohistochemistry work-up.
CONCLUSIONS
In the appropriate setting, varying combinations of epidermal hyperplasia, spongiosis, parakeratosis and individually necrotic keratinocytes in the background of lymphocyte predominant dermal infiltrate (with some atypia) favor a diagnosis of drug reaction with eosinophilia and systemic symptoms. Female sex, the presence of atypical lymphocytes in peripheral smear, dense dermal inflammatory infiltrate, tissue eosinophilia and interface dermatitis with or without keratinocyte necrosis was associated with a poor prognosis.
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10.4103/0378-6323.168934
|
pubmed_211_8457
|
Pharmaceuticals are an important input in health care. As a complement to other modes of treatment and as a substitute for hospitalisation, they affect the health of individuals and populations. Enormous public financial resources are spent on pharmaceuticals, and halting the growth in expenditures is a political objective. Factors with room for improvement include drug use efficiency, cost-efficient prescription, purchasing prices and distribution. High distribution costs affect prices and, thus, the assessment of product cost vs. utility. Changes in the distribution system may be important, for three reasons: First, increased capital costs call for higher efficiency. Second, increased competition requires improved logistics. And third, information technology has opened up for new supply chain solutions. Direct sales solutions are being considered, and were discussed in a Norwegian public report on the matter, but no final conclusion has been reached. This article discusses changes in the supply of pharmaceuticals and the development of the market. Alternative supply chains are outlined, including what role the postal service may play in a deregulated pharmaceutical market.
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pubmed_211_8457
|
pubmed_591_19746
|
Current findings from intervention in bilingual aphasia are inconclusive regarding the extent to which levels of language proficiency and degree of linguistic distance between treated and non-treated languages influence cross-language generalisation and changes in levels of language activation and inhibition following treatment. In this study, we enrolled a 65-year-old multilingual speaker with aphasia and administered treatment in his L1, Dutch. We assessed pre- and post-treatment performance for seven of his languages, five of high proficiency and two of lower proficiency. We asked whether treatment in L1 would generalise to his other languages or increase interference among them. Forty hours of treatment were completed over the course of five weeks. Each language was tested three times at pretreatment and at post-treatment. Testing included measures of narrative production, answering questions, picture description and question generation. Dependent measures examined language efficiency, defined as Correct Information Units (CIUs)/min, as well as language mixing, defined as proportion of code-mixed whole words. We found that our participant's improved efficiency in Dutch was mirrored by parallel improvement in the four languages of high proficiency: English, German, Italian and French. In contrast, in his languages of lower proficiency, Norwegian and Spanish, improved efficiency was limited. An increase in code-mixing was noted in Spanish, but not in Norwegian. We interpret the increased code-mixing in Spanish as indication of heightened inhibition following improvement in a language of close linguistic proximity, Italian. We conclude that an interaction of language proficiency and linguistic similarity affects cross-language generalisation following intervention in multilingual aphasia.
|
10.1080/02699206.2018.1435723
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pubmed_957_3144
|
Covalent organic frameworks (COFs) are a novel type of crystalline porous organic polymer materials recently developed. It has several advantages in chromatographic separation field, such as high thermal stability, porosity, structural regularity, and large specific surface area. Here, a novel spherical COF 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 2,5-bis(2-propyn-1-yloxy)-1,4-benzenedicarboxaldehyde (BPTA) was developed as an electrochromatographic stationary phase for capillary electrochromatography separation. The COF TAPB-BPTA modified capillary column was fabricated via a facile in situ growth method at room temperature. The characterization results of scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD) confirmed that COF TAPB-BPTA were successfully modified onto the capillary inner surface. The electrochromatography separation performance of the COF TAPB-BPTA modified capillary was investigated. The prepared column demonstrated outstanding separation performance toward alkylbenzenes, phenols, and chlorobenzenes compounds. Furthermore, the baseline separations of non-steroidal anti-inflammatory drugs (NSAIDs) and parabens with good efficiency and high resolution were achieved. Also, the prepared column possessed satisfactory precision of the intra-day runs (n = 5), inter-day runs (n = 3), and parallel columns (n = 3), and the relative standard deviations (RSDs) of the retention times of tested alkylbenzenes were all less than 2.58%. Thus, this new COF-based stationary phase shows tremendous application potential in chromatographic separation field.
|
10.1016/j.jpha.2022.06.005
|
pubmed_897_13012
|
Myocilin is an eye protein found in the trabecular extracellular matrix (TEM), within the anatomic region that controls fluid flow. Variants of myocilin, localized to its olfactomedin (OLF) domain, have been linked to inherited forms of glaucoma, a disease associated with elevated intraocular pressure. OLF domains have also been implicated in psychiatric diseases and cancers by their involvement in signaling, neuronal growth, and development. However, molecular characterization of OLFs has been hampered by challenges in recombinant expression, a hurdle we have recently overcome for the myocilin OLF domain (myoc-OLF). Here, we report the first detailed solution biophysical characterization of myoc-OLF to gain insight into its structure and function. Myoc-OLF is stable in the presence of glycosaminoglycans, as well as in a wide pH range in buffers with functional groups reminiscent of such glycosaminoglycans. Circular dichroism (CD) reveals significant β-sheet and β-turn secondary structure. Unexpectedly, the CD signature is reminiscent of α-chymotrypsin as well as another ocular protein family, the βγ-crystallins. At neutral pH, intrinsic tryptophan fluorescence and CD melts indicate a highly cooperative transition with a melting temperature of ∼55 °C. Limited proteolysis combined with mass spectrometry reveals that the compact core structural domain of OLF consists of approximately residues 238-461, which retains the single disulfide bond and is as stable as the full myoc-OLF construct. The data presented here inform new testable hypotheses for interactions with specific TEM components, and will assist in design of therapeutic agents for myocilin glaucoma.
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10.1371/journal.pone.0016347
|
pubmed_976_7630
|
In general, most fishes maintain a swimming posture with the dorsal side towards the water surface under normal gravity condition. In contrast to normal fishes, a catfish Synodontis nigriventris, shows a unique postural control. The catfish keeps its posture with the ventral side towards the water surface and the dorsal side towards water bottom under normal gravity. This evidence leads one to assume that the upside-down posture of the catfish is controlled by gravity sensation in a manner different from that of other fishes. However, it has remained unclear to date whether the gravity sensation contributes to the unique postural control of this catfish. We examined its postural control in intact and labyrinth-removed catfish using a clinostat which generates a specific gravity environment (pseudo-microgravity) on earth. In addition, we examined its postural control under microgravity during parabolic flights.
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pubmed_976_7630
|
pubmed_211_1520
|
Erythrocyte Na+-Li+ countertransport shows an increased activity in essential hypertension and diabetic nephropathy, but its nature remains unknown. This amiloride-insensitive membrane transport may not be a mode of operation of the amiloride-sensitive NHE1, the only Na+-H+ exchange isoform found in human erythrocytes. Whether an independent, although unknown, amiloride-insensitive isoform mediates Na+-Li+ countertransport is unclear. Na+-H+ exchange activity was measured in acid-loaded erythrocytes. Dimethylamiloride, a specific inhibitor of Na+-H+ exchange and phloretin, a known inhibitor of Na+-Li+ countertransport, gave a reduction in H+-driven Na+ influx (by 31 and 37%, respectively). This effect was additive, and a 66% reduction in H+-driven Na+ influx was found in the presence of both inhibitors. Internal acidification, a stimulus for Na+-H+ exchange, enhanced Na+-Li+ countertransport activity (from 287 +/- 55 to 1213 +/- 165 micromol x Lcell(-1) h(-1), mean +/- SEM, P = 0.003). This transport remained sensitive to phloretin under both conditions. Conversely, external acidification decreased Na+-Li+ countertransport activity (as expected for a Na+-H+ exchanger). Competition between internal H+ and Li+ or Na+ for a common binding site was present. Finally, similar kinetic parameters for external Na+ characterized Na+-Li+ countertransport and the phloretin-sensitive component of H+-driven Na+ influx. These findings suggest that both Na+-Li+ countertransport and the amiloride-insensitive, phloretin-sensitive component of H+-driven Na+ influx can be mediated by a previously unrecognized novel amiloride-insensitive Na+-H+ exchange isoform in human erythrocytes.
|
10.1681/ASN.V9122203
|
pubmed_530_14873
|
Phanerochete chrysosporium, the white-rot fungus, (a best source for lignolytic enzymes system) was used in the biological pretreatment of rice husk for reducing sugars production. Usually reducing sugar production through biochemical process involves two steps: solid state fermentation (SSF) of fungal pretreatment for delignification, subsequently pretreated biomass subjected to enzymatic hydrolysis. During the fungal pretreatment of rice husk for reducing sugar production along with cellulase and xylanse, the activities of lignin degradation-related enzymes such as lignin peroxidases (LiP), GLOX (glyoxidase), and aryl alcohol oxidases (AAO), were observed. The fungal pretreated rice husk produced highest (895.9 mg/ml/2g of rise husk) reducing sugars on 18th day of fungal treatment. This method may be good alternative to avoid operational costs associated with washing and the removal of inhibitors during the conventional pretreatment methods.
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pubmed_530_14873
|
pubmed_1080_15973
|
The authors made a retrospective analysis of late ineffectiveness of sulphonylurea derivatives and its correlation with the age of diabetes onset, duration of the disease, sex, body mass, smoking cigarettes, diabetes history in the family, coexistence with some diabetic complications as retinopathy, ischemic heart disease, arterial hypertension and vascular diseases in lower limbs. The study was carried out in a group of 220 patients with diabetes type 2 lasting from 1 up to 25 years, aged 30-77 undergoing therapy in the Department of Gastroenterology and Metabolic Diseases in the years 1976-1987 in whom a late ineffectiveness appeared to sulphonylurea derivatives. The average time of effective therapy by means of sulphonylurea derivatives in the group examined was 8.7 +/- 4.9 years (9.2 +/- 5.2 in men and 8.3 +/- 4.6 in women). The time of effective therapy by means of the above drugs was inversely proportional to the age of patients when diabetes type 2 appeared. The time of effective therapy by means of sulphonylurea derivatives in obese men was significantly longer than in obese women. No correlation was found between the appearance of late ineffectiveness of sulphonylurea derivatives and diabetes history in the family, smoking ischemic heart disease, arterial hypertension, retinopathy and vascular diseases of lower limbs.
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pubmed_1080_15973
|
pubmed_399_16396
|
An observed case of leiomyosarcoma of the small intestine triggered a review of the literature that highlights the difficulties encountered in the radical treatment of such lesions in view of both their extreme variety and their tardive and unclear symptoms.
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pubmed_399_16396
|
pubmed_175_9018
|
The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.
|
10.3390/ijms21031106
|
pubmed_177_17986
|
It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed.
|
10.3389/fimmu.2017.01636
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pubmed_505_16110
|
DSA metal oxide electrodes such as the RuO(2)/IrO(2)/TiO(2) mixed system are widely studied for their excellent electrocatalytic activity. In order to understand their catalytic properties, the comprehension of the surface chemistry involved during electrochemical treatments is crucial. With this aim, RuO(2)/IrO(2)/TiO(2) mixed-oxide electrodes having various noble metal contents were studied by means of secondary ion mass spectrometry (SIMS). In particular, cathodic and anodic polarization and O(2) evolution reactions were carried out to test the electrode behaviour and SIMS analyses were performed after all these treatments. In this way, surface changes induced by electrochemical treatments and depending on electrode composition were widely investigated by SIMS, revealing, for example, the presence of hydration or preferential dissolution phenomena induced by electrochemical processing.
|
10.1002/rcm.1326
|
pubmed_403_24522
|
Liver transplantation is an exemplar model of complex surgery and the only curative option for patients with end-stage liver disease. Although historically associated with poor outcomes, liver cancer management has also been revolutionised with liver transplantation and in some instances, survival outcomes are comparable to surgical resection. As such, the key elements underpinning the major advances in surgical technique, immunological therapies and allocation policies combined with improved patient and graft survival outcomes have created a huge demand for organ donation. Despite improvements in donor and recipient selection, there is a persistent disparity between organ supply and demand. Candidate wait-list mortality and dropout rates remain problematic and this concern has resulted in increased efforts to expand the donor pool to meet the unmet needs of the population. This is even more challenging when coupled with an ever-growing recipient pool, candidate waiting lists and an ageing population. Over the past two decades, there has been a considerable focus on extended criteria organs, donations after cardiac death and alternative avenues for marginal liver use. With careful donor selection and recipient matching, these livers may help bridge the gap between supply and demand and placate the ever-expanding recipient pool. Here, we present a summary of recent developments by the transplant community addressing the issues of a growing donor and recipient pool.
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10.21037/cco-20-212
|
pubmed_970_3155
|
Paratuberculosis, a chronic and sometimes fatal disease of ruminants, is caused by Mycobacterium avium subsp. paratuberculosis (MAP). In this study, we examined paratuberculosis cases among 2-4-year-old dairy cows at farms in Shandong Province, China. Paratuberculosis cases were diagnosed based on clinical symptoms, pathological autopsy, and histopathological inspection. Characteristics of paratuberculosis in the affected dairy cattle included poor body condition, persistent diarrhea, subcutaneous edema, granulomatous ileitis (multibacillary), mesenteric lymphadenitis, and hepatitis. Acid-fast bacilli from fecal specimens and lymphocytes were putatively identified as MAP based on Ziehl-Neelsen staining, then confirmed using polymerase chain reaction-based testing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses. Overall, only one MAP strain was isolated from a herd with symptomatic diarrhea. However, analysis of 586 serum samples from nine herds in Tai'an City revealed that 66.7% of herds and 14.2% of animals were seropositive for MAP. Our findings suggest that paratuberculosis is widely prevalent and therefore a significant threat to the dairy industry in Tai'an City, Shandong Province, China.
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10.1155/2020/3896754
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pubmed_666_9528
|
Plant respiration plays a critical role in the C balance of plants. Respiration is highly temperature sensitive and small temperature-induced increases in whole-plant respiration could change the C balance of plants that operate close to their light-compensation points from positive to negative. Nonstructural carbohydrates are thought to play an important role in controlling respiration and its temperature sensitivity, but this role has not been studied at the whole-plant level. We measured respiration of whole Ardisia crenata Sims. seedlings and tested the hypothesis that darkness-induced C starvation would decrease the temperature sensitivity of whole-plant respiration. Compared with control plants, sugar and starch concentrations in darkened plants declined over time in all organs. Similarly, whole-plant respiration decreased. However, the temperature sensitivity of whole-plant respiration, expressed as the proportional increase in respiration per 10°C warming (Q10), increased with progressive C starvation. We hypothesise that growth respiration was suppressed in darkened plants and that whole-plant respiration represented maintenance respiration almost exclusively, which is more temperature sensitive. Alternatively, changes in the respiratory substrate during C starvation or increased involvement of alternative oxidase pathway respiration may explain the increase in Q10. Carbohydrates are important for respiration but it appears that even in C-starved A. crenata plants, carbohydrate availability does not limit respiration during short-term warming.
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10.1071/FP14329
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pubmed_269_16145
|
The inclusion of family members in the acute care of older persons with complex needs results in better coordination of care and reduces the frequency and/or duration of rehospitalisation. Therefore, healthcare professionals need a tool to assess the collaboration with family members on acute hospital wards. The aims were to test the psychometric properties of the Swedish version of the Family Collaboration Scale (FCS), to investigate family members' perception of collaboration with healthcare professionals on acute medical wards in Sweden and to compare the data with the corresponding Danish results. Three hundred and sixty family members of frail patients aged 65 or older from 13 acute medical wards answered the FCS questionnaire. In addition to descriptive statistics, psychometric methods were applied. The internal consistency of the Swedish version of the FCS was excellent, and confirmatory factor analysis revealed that its factor structure was equivalent to that of the original Danish FCS. The respondents' ratings indicated better perceived collaboration than in the Danish case. Older age than 60 was associated with worse collaboration with healthcare professionals regarding Influence on discharge than younger respondents. Those with compulsory and health or nursing education showed better collaboration. The Swedish version of the FCS should be further evaluated for its retest reliability and as an outcome measure in intervention studies.
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10.3390/healthcare10030478
|
pubmed_170_7308
|
NK cell-mediated murine cytomegalovirus (MCMV) resistance (Cmv(r)) is under H-2(k) control in MA/My mice, but the underlying gene(s) is unclear. Prior genetic analysis mapped Cmv(r) to the MHC class I (MHC-I) D(k) gene interval. Because NK cell receptors are licensed by and responsive to MHC class I molecules, D(k) itself is a candidate gene. A 10-kb genomic D(k) fragment was subcloned and microinjected into MCMV-susceptible (Cmv(s)) (MA/My.L-H2(b) x C57L)F(1) or (B6 x DBA/2)F(2) embryos. Transgenic founders, which are competent for D(k) expression and germline transgene transmission, were identified and further backcrossed to MA/My.L-H2(b) or C57L mice. Remarkably, D(k) expression delivered NK-mediated resistance in either genetic background. Further, NK cells with cognate inhibitory Ly49G receptors for self-MHC-I D(k) were licensed and critical in protection against MCMV infection. In radiation bone marrow chimeras, NK resistance was significantly diminished when MHC-I D(k) expression was restricted to only hematopoietic or nonhematopoietic cells. Thus, MHC-I D(k) is the H-2(k)-linked Cmv(r) locus; these findings suggest a role for NK cell interaction with D(k)-bearing hematopoietic and nonhematopoietic cells to shape NK-mediated virus immunity.
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10.1073/pnas.0913126107
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pubmed_702_19387
|
The original Wolff's vascular theory of migraine was supported by the discovery of a class of drugs, the triptans, developed as a selective cephalic vasoconstrictor agents. Even in the neurovascular hypothesis of Moskowitz, that is the neurogenic inflammation of meningeal vessels provoked by peptides released from trigeminal sensory neurons, the vasodilatation provoked by calcitonin gene-related peptide (CGRP) is considered today much more important than oedema. The role of cephalic vasodilatation as a cause of migraine pain was recently sustained by studies showing the therapeutic effect of CGRP receptor antagonists. We discuss the evidence against vasodilatation as migraine pain generator and some findings which we suggest in support of a central (brain) origin of pain.
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10.1007/s10194-009-0130-6
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pubmed_462_12111
|
STUDY OBJECTIVES
To determine the frequency of, and patient population requiring involuntary treatment orders in the emergency department.
DESIGN
Retrospective review of all patients requiring involuntary treatment orders during a one-month study period.
SETTING
An urban, university hospital, adult emergency department with 45,000 annual patient visits.
RESULTS
Three hundred fourteen of 3,637 patients (8.5%) required involuntary treatment orders. Orders used were observation and detention (57%), seclusion only (9%), restraint only (26%), or seclusion plus restraint (7%). Forty-six percent of patients arrived through the emergency medical services system; the remainder were brought by police or family or were self-referred. More patients required these interventions on the second shift. Most detained and secluded patients had psychiatric diagnoses and dispositions, whereas 100% of restrained patients had medical or surgical diagnoses, and nearly 50% required medical or surgical admissions.
CONCLUSION
The frequent need for involuntary treatment orders for patients in an urban ED is reported. The patient population described, especially among restrained patients, differs significantly from those of studies performed in psychiatric settings. Legal doctrines pertinent to involuntary treatment are reviewed.
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10.1016/s0196-0644(05)82232-2
|
pubmed_675_6602
|
A high-reliability organization must have high-performing teams. Core teams in healthcare should include the patient and, where possible, the patient's family. Everyone on the team should understand what is expected of them in terms of expertise, leadership, communication, mutual support, and awareness of the situation. One test of the excellence of a clinical team is having high-quality handoffs of patients.
|
10.1097/RLU.0000000000003529
|
pubmed_862_18441
|
A simple FI-fluorimetric analytical methodology for the continuous and sequential determination of rhodamine B (RhB) in cosmetic products has been developed and evaluated in terms of sensibility and selectivity. The influence of several surfactant solutions on RhB fluorescence signal has been studied; particular attention was paid in the aggregation behavior of RhB-SDS system. Linear response has been obtained in the range of 1.6 x 10(-9) and 1 x 10(-6) mol L(-1), with a detection limit of 5 x 10(-10) mol L(-1). The novel technique provides a simple dissolution of sample, on-line filtration with sampling rate higher than 100 samples h(-1) and has been satisfactorily applied to the RhB determination in commercial lipsticks.
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10.1016/j.talanta.2007.10.041
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pubmed_434_4212
|
Computed tomography (CT) arthrography of the shoulder is an imaging modality of great diagnostic accuracy with regard to glenohumeral instability and in particular labral lesions. Interpretation of the scans is made difficult by the frequent occurrence of normal anatomic variants and the complexity of injuries to the bone and soft tissues. We selected a continuous sample of 50 CT arthrograms of the shoulder and they were reported by two consultant musculoskeletal radiologists. The results were collated and analysed for the level of agreement. Hill-Sachs showed Kappa (K) statistic to be 0.37 (fair agreement), soft tissue Bankart 0.32 (fair agreement), bony Bankart 0.61 (substantial agreement), anterior capsular laxity 0.41 (moderate agreement) and glenohumeral osteoarthritis 0.20 (slight agreement). All the results were significant with a p value of <0.05. Nine (18%) of the 50 scans were in complete agreement. The results demonstrate that there can be considerable interobserver variation (IOV) in the reports of a CT arthrogram of a shoulder. They highlight the potential difficulties in reporting such images and suggests ways in which the report could be more focussed to provide a clinically reliable report and one which matches the surgical findings accurately.
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10.1016/j.ejrad.2010.10.009
|
pubmed_1104_22659
|
Work-related falls from roofs remain a significant problem for workers in the construction industry. Knowledge about the main causative or initiating factors leading to fall incidents is desperately needed for fall prevention intervention. From biomechanical and psychophysiological perspectives the majority of occupational falls, including falls from roofs, can be regarded as loss-of-balance incidents. The primary objective of this paper is to summarize the current knowledge from multiple fields about factors that are related to the control of balance during roofing work. An extensive literature review identified a number of environmental, task-related and personal factors that degrade the control of balance and could be associated with the initiation of falls from roofs. These factors include visual exposure to elevation; unstable visual cues and inadequate visual information in the work environment; 'confined' and inclined support surfaces; unexpected changes in roof surface properties; load handling; physical exertion; fatigue; task complexity that diverts workers' attention; individual differences; work experience and training; and personal protective equipment. Current measures to reduce falls from roofs focus mainly on fall protection procedures, such as the use of covers, guardrails, safety nets, and personal fall-arrest systems, or the application of warning-line systems, safety monitoring systems, and fall protection plans. In many instances, these procedures are not practical for the industry and current regulations allow the use of alternative means of fall protection, such as slide guards. Future research on preventing falls from roofs should consider the main effects and interactions of the environmental, task-related and personal factors that affect the balance control of workers. Research-supported improvements in the visual and physical characteristics of the roof work environment, the construction materials and methods, and work procedures and practices may result in improved workers' balance control as well as overall safety performance, and would ultimately reduce incidents of falling from a roof.
|
10.1080/00140130110034480
|
pubmed_410_23864
|
Tunable temperature alarm sensors were prepared using multilayer graphene and nitrocellulose (NC) to reliably monitor early high temperature risks. The graphene/NC alarm sensor keeps in a state of electrical insulation, however, turns electrically conductive at high temperatures, such as encountering a flame attack. Its response time is limited to only a few seconds because of a quick chemical reaction of NC. The 90% graphene/NC (wt % ratio 1:9) composite alarm sensor stably remains insulated at an ambient temperature of 200 °C, resulting in a satisfactory responsive temperature (232 °C), instant response time (4.4 s), and sustained working time in the flame below the ignition temperature of most combustibles. Furthermore, the response temperature and time of the alarm sensor can be tuned by graphene/NC ratios to reduce the fire risk of various combustible materials in different fire-prone scenarios and thus has promising applications in both indoor and outdoor environments. The sensor has also proven to work in the form of paint, wallpaper, and other composites due to its superior flame retardancy property, as well as under extreme conditions (i.e., underwater and vacuum).
|
10.1021/acsami.2c02340
|
pubmed_14_538
|
This research tested the hypothesis that shared or related neurophysiological processes are required for treating (a) non-linguistic abstract structure and (b) some aspects of linguistic syntactic structure. In language, one syntactic structure can be used to create an open class of sentences. We have previously proposed a relation between this generative aspect of syntactic structure and the abstract structure of non-linguistic sequences. For instance, the sequences 'ABCBAC' and 'DEFEDF' have different serial order or serial structure, but share the same abstract structure '123213'. Our recent studies of neuropsychology, simulation and ERPs argued that similar neurophysiological processes are involved in treating non-linguistic abstract structure and certain aspects of linguistic syntactic structure. The current research tests this hypothesis by examining the ERP profile evoked during the processing of non-linguistic sequences vs. sentences. Ten healthy subjects were trained to discriminate between syntactically correct and incorrect sequences and sentences presented visually on a video screen. During the subsequent ERP recording, subjects discriminated between correct and incorrect sequences and sentences presented visually on the screen. This discrimination task yielded, for anomalies in both the abstract and syntactic conditions, a late positivity around 550 ms with partially overlapping topography. These results support our hypothesis that shared or related neurophysiological processes are required for treating non-linguistic abstract structure and aspects of linguistic syntactic structure. However, they also suggest that the overlap between these two types of processing is not complete.
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10.1016/s0987-7053(01)00291-x
|
pubmed_329_7256
|
OBJECTIVE
Prospective memory (PM) is a cognitive function defined as the ability to perform an intention at an appropriate moment in the future. In the aging population, PM is essential for maintaining independent daily living. Introduced as a simple and quick way to assess PM in clinical settings, the envelope task has to date received very limited empirical and practical interest.
METHODS
The present study investigated the task's clinical utility in detecting PM impairment in a sample composed of 49 healthy older adults (OA), 41 patients with Alzheimer's disease, and 64 individuals with amnestic and nonamnestic mild cognitive impairment (MCI) of heterogeneous etiology: 17 of idiopathic nature, 20 presenting an idiopathic rapid-eye movement sleep behaviour disorder, and 27 patients diagnosed with idiopathic Parkinson's disease.
RESULTS
The envelope task was highly sensitive and specific in discriminating Alzheimer's disease patients from OA. Although it was specific in distinguishing MCI individuals from OA, its sensitivity was modest, especially in patients presenting a nonamnestic MCI subtype.
CONCLUSIONS
Given its high specificity and simple low-cost administration procedure, the envelope task is a promising instrument for clinicians who seek to rapidly assess PM impairment in their daily practice.
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10.1017/cjn.2016.298
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pubmed_472_19718
|
OBJECTIVE
To evaluate whether there was a change in prevalence of human papillomavirus (HPV) in the United States correlated with the introduction of HPV vaccines in both vaccinated and unvaccinated women.
METHODS
We performed a retrospective review of prevalence data for women aged 18-29 years living in the United States using the National Health and Nutrition Examination Surveys, which is an ongoing series of cross-sectional surveys. Participants provided responses to standardized questions and self-collected cervicovaginal swabs in which a Linear Array HPV Assay was used to determine HPV prevalence. A total of 783 women from the prevaccine era (2003-2004) and 1,526 from the postvaccine era (2007-2012) were analyzed.
RESULTS
Among women aged 18-29 years, the prevalence of vaccine-type HPV declined among women receiving one or more doses of vaccine (P=.003): 10.1% (95% confidence interval [CI] 7.1-13.8%) in the prevaccine era to 4.2% (95% CI 3.3-10.9%) in the postvaccine era. There was no change in prevalence of nonvaccine-type HPV among women receiving one or more doses of vaccine (P>.05). There was also no change in prevalence of vaccine-type HPV among unvaccinated women from the prevaccine era 10.1% (95% CI 7.1-13.8%) to 8.8% (95% CI 5.6-12.9%) in the postvaccine era (P=.4). Vaccine coverage increased to 31.5% of eligible women aged 18-29 years as of 2011-2012.
CONCLUSION
Six years after introduction of HPV vaccination in the United States, there has been a decrease in the prevalence of vaccine-type HPV among women correlated with receiving one or more vaccine doses with no change in nonvaccine-type HPV. Furthermore, there has been no change in prevalence of vaccine-type HPV among unvaccinated women.
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10.1097/AOG.0000000000001760
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pubmed_400_10684
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A simple approach to several cyclopeptidmimetics containing an N-alkylated amino acid was found via a multicomponent reaction followed by a ring-closing metathesis starting from readily available precursors. The combinatorial technique has the advantage that different polar, hydrophilic or hydrophobic moieties can be placed at any position in the cycles and unnatural amino acids can also be incorporated.
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pubmed_400_10684
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pubmed_312_11033
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The participation of glutathione reductase in the process of nutrient-stimulated insulin release was investigated in rat pancreatic islets exposed to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU caused a time-and dose-related, irreversible inhibition of glutathione reductase activity. This coincided with a fall in both GSH/GSSG ratio and the thiol content of the islets. Pretreatment of the islets with BCNU inhibited the oxidation of glucose and its stimulant action upon both 45Ca net uptake and insulin release. Although BCNU (up to 0.5 mM) failed to affect the oxidation of L-leucine and L-glutamine, it also caused a dose-related inhibition of insulin release evoked by the combination of these two amino acids. The latter inhibition was apparently not fully accounted for by the modest to negligible effects of BCNU upon 45Ca uptake, 45Ca efflux, 86Rb efflux and cyclic AMP production. Since BCNU failed to inhibit insulin release evoked by the association of Ba2+ and theophylline, these results support the view that glutathione reductase participates in the coupling of metabolic to secretory events in the process of nutrient-stimulated insulin release. However, the precise modality of such a participation, for example the control of intracellular Ca2+ distribution, remains to be elucidated.
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10.1016/0167-4889(85)90098-9
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pubmed_842_4732
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Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Maternal and Infant Nutrition Interventions, Matlab) in rural Bangladesh, free 8-iso-prostaglandin F(2α) (lipid peroxidation) was analysed in pregnancy week 14 and 30 and 8-Hydroxy-2 -Deoxyguanosine (DNA oxidation) in week 19. We found that higher levels of lipid peroxidation in early pregnancy were associated with larger infant size (birth length and chest circumference). In late pregnancy, no clear pattern of associations was found. Increasing level of DNA oxidation was associated with lower birth length in girls but no other associations were found. In conclusion, a higher level of lipid peroxidation in early (but not late) pregnancy was associated with a favourable larger birth size suggesting that timing of lipid peroxidation is of importance.
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10.3109/10715762.2011.651467
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pubmed_34_5254
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BACKGROUND
Carotid artery stenting is an alternative method to surgical endarterectomy for treatment of carotid artery stenosis.
METHODS AND RESULTS
Three hundred and seventy-one consecutive patients (71+/-9 years) undergoing 405 carotid artery interventions at a single cardiologic center were studied prospectively within a therapy registry. In general, the interventional procedure was performed using neuroprotective devices to prevent distal embolization. Stents were used routinely whenever possible. Independent neurological assessment took place prior to and after carotid stenting. The neurological event rate was assessed in the early (<30 days) and late post interventional period. In asymptomatic patients, 286 interventions were done with a 30-day stroke rate of 1.3% (ipsilateral 1.0%). In symptomatic patients, strokes occurred in a significantly (p<0.005) higher rate of 5.0% after 119 interventions (all ipsilateral). At long-term follow-up (mean 728+/-548 days) additional strokes occurred ipsilateral to the side of carotid intervention in 0.4% of asymptomatic patients (1.7% of symptomatic patients); contralateral strokes were seen at long-term follow-up in 1.1% of asymptomatic (1.7% of symptomatic) patients. Due to their comorbidities, 1.6% of patients died early, and an additional 11.1% late after carotid stenting.
CONCLUSION
Carotid artery stenting with the general use of neuroprotective devices yields acceptable shortterm results with respect to neurological events. Asymptomatic patients have significantly less periprocedural strokes than symptomatic patients. Neurological events during long-term follow-up are rare, in particular ipsilateral to the side of carotid stenting. Thus, carotid artery stenting with neuroprotection is a safe method for carotid revascularization, with acceptable periprocedural events, particularly in asymptomatic patients, and a good long-term neurologic outcome.
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10.1007/s00392-007-0561-5
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pubmed_840_11048
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We demonstrate that in ultraintense ultrafast laser-matter interaction, the interplay of laser-induced oscillating space-charge fields with laser E and B fields can strongly affect whether the interaction is relativistic or not: stronger laser fields may not in fact produce more relativistic plasma interactions. We show that there exists a regime of interaction, in the relation of laser intensity and incident angle, for which the Brunel effect of electron acceleration is strongly suppressed by AC gyromagnetic fields, at a frequency different from the laser field. Analytically and with 1.5D particle-in-cell modeling, we show that from gyromagnetic effects, even in the absence of usual J x B second-harmonic contributions, there are strong effects on the harmonic emission and on the generation of attosecond pulses.
|
10.1103/PhysRevLett.97.085001
|
pubmed_933_20422
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Endocannabinoids (eCB) such as 2-arachidonylglycerol (2-AG) are lipid metabolites that are synthesized in a postsynaptic neurons and act upon CB(1) cannabinoid receptors (CB(1)R) in presynaptic nerve terminals. This retrograde transmission underlies several forms of short and long term synaptic plasticity within the CNS. Here, we constructed a model system based on isolated rat sympathetic neurons, in which an eCB signaling cascade could be studied in a reduced, spatially compact, and genetically malleable system. We constructed a complete eCB production/mobilization pathway by sequential addition of molecular components. Heterologous expression of four components was required for eCB production and detection: metabotropic glutamate receptor 5a (mGluR5a), Homer 2b, diacylglycerol lipase alpha, and CB(1)R. In these neurons, application of l-glutamate produced voltage-dependent modulation of N-type Ca(2+) channels mediated by activation of CB(1)R. Using both molecular dissection and pharmacological agents, we provide evidence that activation of mGluR5a results in rapid enzymatic production of 2-AG followed by activation of CB(1)R. These experiments define the critical elements required to recapitulate retrograde eCB production and signaling in a single peripheral neuron. Moreover, production/mobilization of eCB can be detected on a physiologically relevant time scale using electrophysiological techniques. The system provides a platform for testing candidate molecules underlying facilitation of eCB transport across the plasma membrane.
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10.1523/JNEUROSCI.2244-09.2009
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pubmed_1007_21465
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New diaryl substituted 2-azabicyclo[3.2.2]nonane derivatives have been synthesized in order to investigate the influence of the aromatic substitution and of N substitution on the antiprotozoal activities of those compounds. Following a manual method for the Hansch approach, different 4-substituted aryl rings were systematically inserted, and moieties with varying basicity and polarity were attached to the ring nitrogen. All compounds were investigated for their activities against Trypanosoma brucei rhodesiense (STIB 900) and the K(1) strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) and for their cytotoxicity using microplate assays. Some of the new compounds are amongst the most active antitrypanosomal agents in this series, and the selectivity index of a single derivative is superior in the 2-azabicyclo-nonane series.
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10.1016/j.bmc.2008.05.007
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pubmed_531_11488
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The in vivo effects of methomyl, thiodicarb and metaldehyde on total soluble proteins, total lipids and glycogen content, in addition, the activity of glutamic oxaloacetic transaminase, (GOT), (GPT) glutamic pyruvic transaminase and catalase (CAT) enzymes of terrestrial E. vermiculata snails was studied. The experimental snails were treated with low concentration of 0.2% brain bait w/w of the pesticides for a period of 1,3,5,7 and 10 days. The results showed that methomyl and thiodicarb lead to significant reduction in total soluble proteins, lipids, and glycogen content, while significant increases in the activity of all enzymes tested were noted. Metaldehyde treatment showed no significant effect on total soluble proteins, lipids and GOT level, whereas a significant increase in GPT and CAT enzymes was observed. Also, metaldehyde resulted a significant reduction in glycogen content of snails.
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10.1080/03601239109372750
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pubmed_828_12699
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The objective was to establish the extent to which physical functioning capacity and self-report measures are able to predict the habitual walking performance in ambulatory persons with multiple sclerosis. Fifty persons with multiple sclerosis (Expanded Disability Status Scale, EDSS, 1.5-6.5) were tested on leg muscle strength as well as walking and balance capacity, and completed self-report indices on perceived physical functioning. Habitual walking performance, that is, the real amount of steps that is performed in the customary living environment, was registered by means of an ambulant accelerometer-based monitor during seven consecutive days. Mild (EDSS 1.5-4.0, n = 29) and moderate (EDSS 4.5-6.5, n = 21) multiple sclerosis subgroups were additionally distinguished as predictor variables and values were hypothesized to differ depending on multiple sclerosis severity and concomitant ambulatory function. Multiple regression analyses yielded a single most significant predictor for each (sub)group with other variables making no independent contribution to the variation in habitual walking performance. For the total study sample, this was the 6-Minute Walking Test (R(2) = 0.458, p < 0.01). In the mild multiple sclerosis subgroup, the 6-Minute Walking Test was again most predictive, yet to a modest degree (R(2) = 0. 187, p = 0.02). In the moderate multiple sclerosis subgroup, the 2-Minute Walking Test explained over half of the variance (R(2) = 0.532, p < 0.01). Habitual walking performance is best reflected by longer walking capacity tests. The extent to which it can be predicted based on clinical testing is larger in a multiple sclerosis patient sample with more severe walking disability. Ambulatory monitoring, however, includes aspects of community ambulation not captured in the clinic, and must be considered as an additional outcome for evaluating interventions in multiple sclerosis.
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10.1177/1352458510361357
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pubmed_1057_16142
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BACKGROUND
Multiple sclerosis (MS) relapses are often treated with short pulses of high dose corticosteroids. Previous literature demonstrates corticosteroids can increase blood pressure (BP). There are few studies regarding effects of high dose, pulse corticosteroids on BP when treating MS relapses.
OBJECTIVE
To investigate the effect of high dose pulse corticosteroids for MS relapses on BP and determine factors that may influence development of acute hypertension.
METHODS
In this open-label pilot study, adult patients with a diagnosis of MS were enrolled if determined to be having a relapse that would meet criteria for corticosteroid treatment. BP was monitored sequentially over the course of their corticosteroid treatment and correlations were made with demographic data, including past medical and family history.
RESULTS
22 subjects contributed data. Higher daytime BP was noted in subjects with a past personal (p = 0.007) or family history of hypertension (p = 0.037). Nighttime BP recordings did not show the normal 10% drop and nocturnal diastolic BP was within a hypertensive range during corticosteroid treatment.
CONCLUSION
MS patients may be at risk of increased BP when treated with corticosteroids for relapses. Those with a past or family history of hypertension may be at higher risk and may warrant more frequent monitoring.
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10.1016/j.msard.2020.102401
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pubmed_328_23472
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A highly selective palladium-catalyzed hydroborylative carbocyclization of bisallenes to afford seven-membered rings has been established. This ring-closing coupling reaction showed good functional group compatibility with high chemo- and regioselectivity, as seven-membered ring 3 was the only product obtained. The extensive use of different linkers, including nitrogen, oxygen, malononitrile, and malonate, showed a broad substrate scope for this approach. A one-pot cascade reaction was realized by trapping the primary allylboron compound with an aldehyde, affording a diastereomerically pure alcohol and a quaternary carbon center by formation of a new C-C bond. A comprehensive mechanistic DFT investigation is also presented. The calculations suggest that the reaction proceeds via a concerted hydropalladation pathway from a Pd(0)-olefin complex rather than via a pathway involving a defined palladium hydride species. The reaction was significantly accelerated by the coordination of the pendant olefin, as well as the introduction of suitable substituents in the bridge, due to the Thorpe-Ingold effect.
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10.1021/jacs.8b08708
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pubmed_124_10084
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The testes of the spiny mice showed asymmetry, the left being significantly heavier than the right (P = 0.025). Histological studies indicated that spermatozoa were first present in the testes of animals 35--45 days of age but the maturation of the accessory glands, especially the lateral prostates and coagulating glands, occurred later. The highest fructose concentration in the adult was in the lateral prostates (126.97 +/- 22.23 mg fructose/100 g, n = 5) and coagulating glands (99.38 +/- 17.65 mg fructose/100 g gland weight, n = 5). Coagulation tests of mixtures of extracts of seminal vesicles and coagulating glands from spiny mice and rats indicated that the vesiculase of the spiny mouse was active on rat substrates and vice versa. Cross-reactions of extracts of house mouse (Mus musculus), hamster (Mesocricetus auratus), gerbil (Meriones unguiculatus), and guinea-pig (Cavia porcellus) seminal vesicles (substrate) and coagulating glands (vesiculase) with those of rats and spiny mice showed that although the substrates of rat and spiny mouse were readily coagulated by vesiculase from all the other species, rat and spiny mouse vesiculase were not equally active on substrates of the other species.
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10.1530/jrf.0.0570183
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pubmed_920_22685
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Electronic frailty indices based on data from administrative claims and electronic health records can be used to estimate frailty in large populations of older adults with cancer where direct frailty measures are lacking. The objective of this study was to use the electronic Veterans Affairs Frailty Index (VA-FI-10)-developed and validated to measure frailty in the national United States (US) VA Healthcare System-to estimate the prevalence and impact of frailty in older US veterans newly treated for multiple myeloma (MM) with contemporary therapies. We designed a retrospective cohort study of 4924 transplant-ineligible veterans aged ≥ 65 years initiating MM therapy within VA from 2004 to 2017. Initial MM therapy was measured using inpatient and outpatient treatment codes from pharmacy data in the VA Corporate Data Warehouse. In total, 3477 veterans (70.6%) were classified as frail (VA-FI-10 > 0.2), with 1510 (30.7%) mildly frail (VA-FI-10 > 0.2-0.3), 1105 (22.4%) moderately frail (VA-FI-10 > 0.3-0.4), and 862 (17.5%) severely frail (VA-FI-10 > 0.4). Survival and time to hospitalization decreased with increasing VA-FI-10 severity (log-rank p-value < 0.001); the VA-FI-10 predicted mortality and hospitalizations independently of age, sociodemographic variables, and measures of disease risk. Varying data sources and assessment periods reclassified frailty severity for a substantial portion of veterans but did not substantially affect VA-FI-10's association with mortality. Our study supports use of the VA-FI-10 in future research involving older veterans with MM and provides insights into its potential use in identifying frailty in clinical practice.
|
10.3390/cancers13123053
|
pubmed_601_7364
|
The venous compartment plays a critical role in circulatory control. The present series of experiments was conducted to assess simultaneously effects of vasoactive drugs on arterial resistance and venous capacitance vessels of the rat hindquarters perfused with physiological salt solutions (SS). Retrograde infusion of SS into rat hindquarters via the vena cava resulted in an increase in hindquarters venous pressure (Pv). The range of mean volumes required to increase Pv to 20 and 30 mm Hg was 1.7 +/- 0.1 to 2.9 +/- 0.4 and 3.8 +/- 0.3 to 6.9 +/- 0.3 ml, respectively, in various groups of rats during a control period. Perfusion of the hindquarters with an SS containing 80 mM K+ reduced the volume required to increase Pv to 20 and 30 mm Hg to 47 +/- 2 and 42 +/- 2% of control, respectively, indicating venoconstriction. K+ (80 mM) SS also increased aterial perfusion pressure (Pa; measured from a sidearm off of the inflow catheter) to 141 +/- 9 mm Hg, indicating arterial vasoconstriction. Arterial and venous responses to 80 mM K+ were attenuated markedly by perfusion with SS containing zero Ca and 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, indicating dependence on extracellular Ca. Phentolamine (10(-5) M) attenuated the arterial and venous response to 80 mM K+, indicating an alpha adrenergic contribution. Arterial responses to 80 mM K+ were attenuated markedly by the Ca entry blockers nifedipine (10(-6) and 10(-5) M) and verapamil (10(-6) and 10(-5) M). In contrast, venous responses were not affected by nifedipine and were reduced slightly only at the high concentration of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed_601_7364
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pubmed_146_22362
|
BACKGROUND
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for coronary artery disease (CAD) in nontransplant patients. We evaluated the association between Lp-PLA2, cardiac allograft vasculopathy (CAV) assessed by 3D intravascular ultrasound, and incidence of cardiac adverse events in heart transplant recipients.
MATERIALS AND METHODS
Fasting blood samples were obtained and stored from a cross-section of 112 cardiac transplant recipients attending the Mayo cardiac transplant clinic in 2000 to 2001, mean of 4.7 years after transplant. Lp-PLA2 was measured in plasma aliquots using an enzyme-linked immunoassay. Fifty-six of these patients subsequently underwent two 3D intravascular ultrasound studies in 2004 to 2006 12 months apart. Cardiovascular (CV) events included percutaneous coronary intervention, coronary artery bypass grafting (CABG), reduction in left ventricular ejection fraction (LVEF) < or =45% secondary to CAV and CV death.
RESULTS
High Lp-PLA2 level was associated with increase in plaque volume (r=0.43, P=0.0026) and percent plaque volume (r=0.45, P=0.0004). The association remained significant after adjusting for clinical and lipid variables. During follow-up of 5.1+/-1.6 years, 24 CV adverse events occurred in 15 of 112 (13%) heart transplant patients. Lp-PLA2 level>236 ng/mL (higher tertile) identified a subgroup of patients having a 2.4-fold increase of relative risk for combined endpoint of CV events (percutaneous coronary intervention, CABG, LVEF<45%, and CV death; 95% CI 1.16-5.19, P=0.012) compared with patients with Lp-PLA2< or =236 ng/mL.
CONCLUSIONS
Lp-PLA2 is independently associated with progression of CAV and predicts a higher incidence of CV events and CV death in transplant patients. This finding supports the concept that systemic inflammation is an important mediator of CAV. Lp-PLA2 may be a useful marker for risk of CAV and a therapeutic target in posttransplant patients.
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10.1097/TP.0b013e3181684319
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pubmed_661_16465
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The experimental conditions for antibody-binding by the 38.5 kD porin protein of an E. coli 055 strain in immunoblotting were investigated. A non-ionic detergent in the buffer which contained the primary antibody was required for antibody-binding by electroblots of the SDS-denatured protein. Immunoblotting, using antiserum absorbed with bacteria or the outer membrane (OM) of the E. coli 055 strain, showed results concordant with inaccessibility to antibodies of the 38.5 kD porin protein in its native configuration in the bacterial cells, but immunoreactivity when contained in the OM. OM from strains of different genera of the Enterobacteriaceae and antisera against these strains when used in immunoblot analyses showed that the E. coli 055 porin protein harboured antigenic determinants which are common to the various genera of the enteric bacilli. Cross-reactivity with non-enteric Gram-negative bacteria was not observed.
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10.1111/j.1699-0463.1987.tb03131.x
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pubmed_611_21180
|
Infection of the external structures of the eye is one of the commonest types of eye disease worldwide. In addition, although relatively impermeable to microorganisms, infection within the eye can result from trauma, surgery or systemic disease. This article reviews the general biology of viruses, bacteria, fungi and protozoa and the major ocular infections that they cause. In addition, the effectiveness of the various antimicrobial agents in controlling ocular disease is discussed. Because of changes in the normal ocular flora, continuous monitoring of the microbiology of the eye will continue to be important in predicting future types of eye infection. Basic research is also needed into the interactions of microbes at the ocular surface. There is increasing microbial resistance to the antimicrobial agents used to treat ocular infections and hence, new antimicrobial agents will continue to be needed together with new methods of drug delivery to increase the effectiveness of existing antimicrobial agents.
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pubmed_611_21180
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pubmed_359_12458
|
Human T cells are transformed to antigen-independent permanent growth in vitro upon infection with herpesvirus saimiri subgroup C strains. The viral oncoproteins required for this process, StpC and Tip, could be replaced by Tio, the oncoprotein of herpesvirus ateles. Here we demonstrate that proliferation of lymphocytes transformed with Tio-recombinant herpesvirus saimiri required the activity of Src family kinases. Src kinases had previously been identified as interaction partners of Tio. This interaction was now shown to be independent of any of the four tyrosine residues of Tio but to be dependent on an SH3-binding motif. Mutations within this motif abrogated the transforming capabilities of Tio-recombinant herpesvirus saimiri. Furthermore, kinase interaction resulted in the phosphorylation of Tio on a single tyrosine residue at position 136. Mutation of this residue in the viral context revealed that this phosphorylation site, but none of the other tyrosine residues, was required for T-cell transformation. These data indicate that the interaction of Tio with a Src kinase is essential for both the initiation and the maintenance of T-cell transformation by recombinant herpesvirus saimiri. The requirement for the tyrosine phosphorylation site at position 136 suggests a role for Tio beyond simple deregulation of the kinase.
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10.1128/JVI.79.16.10507-10513.2005
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pubmed_1102_15721
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Gastroesophageal adenocarcinomas (GEA) remain difficult to treat with limited targeted therapeutics. Negative results from randomized trials of EGFR inhibitors (EGFRi) in patients with molecularly unselected GEA have hampered the development of EGFRi in the gastroesophageal cancer space. A recent study reopens the game.See related article by Corso et al., p. 3126.
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10.1158/1078-0432.CCR-21-0533
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pubmed_917_6416
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When 5.10(6) hepatocytes were incubated for 40 min with 0.015-0.3 mM (1-14C)-labeled 6,9,12-octadecatrienoic acid or (1-14C)-labeled 6,9,12,15-octadecatetraenoic acid there was a concentration-dependent acylation of radioactive metabolites into both phospholipids and triacylglycerol. However, when the concentration of either substrate exceeded 60-150 microM there was no further increase in the metabolism of either substrate to longer-chain (n-6) and (n-3) acids. When cells were then incubated for various periods of time with 60 microM substrate there was initial rapid removal of the substrate which was accompanied by its acylation into lipids. Over time, the amount of both substrates in lipids declined without an overall drop in specific activity. This decline was accompanied by an increase in long-chain (n-6) and (n-3) fatty acids. Similar results were obtained when the time-dependent metabolism of the two substrates was examined in individual hepatocyte phospholipids. Collectively, these findings suggest that when these two 18-carbon acids are produced by desaturation of dietary linoleate and linolenate that they are in part initially acylated into a labile phospholipid pool. Rapid release and subsequent further metabolism to longer-chain (n-6) and (n-3) acids may explain why these products of the 6-desaturase do not accumulate in membrane lipids.
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10.1016/0005-2760(88)90172-5
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pubmed_615_22056
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Certain plant growth-promoting rhizobacteria (PGPR) elicit induced systemic resistance (ISR) and plant growth promotion in the absence of physical contact with plants via volatile organic compound (VOC) emissions. In this article, we review the recent progess made by research into the interactions between PGPR VOCs and plants, focusing on VOC emission by PGPR strains in plants. Particular attention is given to the mechanisms by which these bacterial VOCs elicit ISR. We provide an overview of recent progress in the elucidation of PGPR VOC interactions from studies utilizing transcriptome, metabolome, and proteome analyses. By monitoring defense gene expression patterns, performing 2-dimensional electrophoresis, and studying defense signaling null mutants, salicylic acid and ethylene have been found to be key players in plant signaling pathways involved in the ISR response. Bacterial VOCs also confer induced systemic tolerance to abiotic stresses, such as drought and heavy metals. A review of current analytical approaches for PGPR volatile profiling is also provided with needed future developments emphasized. To assess potential utilization of PGPR VOCs for crop plants, volatile suspensions have been applied to pepper and cucumber roots and found to be effective at protecting plants against plant pathogens and insect pests in the field. Taken together, these studies provide further insight into the biological and ecological potential of PGPR VOCs for enhancing plant self-immunity and/or adaptation to biotic and abiotic stresses in modern agriculture.
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10.1007/s10886-013-0317-9
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pubmed_247_15782
|
In adult lurcher mice, in which virtually all cerebellar Purkinje cells have degenerated as a direct consequence of mutant gene action, the inferior olivary complex suffers a severe retrograde transneuronal atrophy. Our analysis indicates a 63% cell loss in the lurcher inferior olive, homogeneously distributed between the medial and dorsal accessory, and principal olivary subdivisions. Olivary neurons are reduced in cross-sectional area by 30% in lurcher mice, compared to normal controls. All olivary subdivisions morphologically identifiable in normal mice are also found in the lurcher inferior olive. Analysis of olivocerebellar topography by retrograde transport of lectin-conjugated horseradish peroxidase and fluorogold, in both single and double labeling paradigms, reveals no abnormalities in the general organization of this highly ordered projection. This stability may be based on the initial establishment of the topographic pattern in late embryogenesis or early postnatal periods, prior to the onset of lurcher Purkinje cell degeneration, or, alternatively, the lurcher gene may not alter critical afferent and target characteristics at stages when the topographic relationship is being established. Once established, the olivocerebellar projection is apparently not dependent on the Purkinje cell for long-term maintenance of its general topographic organization.
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10.1002/cne.903120413
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pubmed_927_15032
|
A method is described for the presumptive identification of Legionella pneumophila by the formation of satellite colonies around filter paper discs impregnated with ferric pyrophosphate and L-cysteine hydrochloride on a deficient basal medium. This technique simplifies the differentiation of picked colonies of L pneumophila from other organisms in mixed cultures from environmental and contaminated clinical samples.
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10.1136/jcp.35.12.1353
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pubmed_263_20399
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There is evidence for an unrecognised classical hormone secreted by the mammalian gonad. This postulated hormone--'micrin' (pronounced 'my-crin')--represents the body's brake against tissue overgrowth. When oestrogens are administered in high doses to female rats there is a considerable (non-artefactual) increase in the relative size and weight of organs such as the pituitary, adrenals, uterus and liver--suggesting an organotrophic (organ-building) role for endogenous oestrogens. This effect is exaggerated if the animals are first ovariectomized, indicating the removal of a negative ovarian factor, micrin. These organ enlargements can be reduced by pretreating the rats with large doses of antioestrogens such as clomiphene and tamoxifen. This antiestrogenic blockade of exogenous oestrogens is itself blunted by prior removal of the ovaries. It is proposed that antioestrogens (e.g. tamoxifen in breast cancer treatment) antagonize the organotrophic effects of oestrogens by competing for the oestrogen receptor peripherally and centrally and via an increase in the secretion of ovarian micrin. It is deduced that micrin is the testicular 'inhibin' proposed in the 1930s, not the molecule that now bears that name, which acts at the pituitary tier as a downregulator of follicle-stimulating hormone. The hallmark of micrin deficiency in the male rat is a pituitary hypertrophy that follows castration. This is reversible with a steroid-depleted aqueous bovine testicular extract, the micrin within which suppresses the hypothalamus, normalizing the pituitary. Micrin probably acts as a brake on peripheral tissues directly but also indirectly at the meta-level via the hypothalamic-pituitary axis, resetting a hypothalamic 'organostat' controlling organ and tissue masses, part of the 'organotrophic system' of internal size regulation. Besides endocrine (circulating) micrin from the gonads there is probably paracrine (locally acting) micrin produced in the brain. This is involved in a somatic cueing system for puberty: the brake comes off at an appropriate body tissue mass disinhibiting the hypothalamus and accelerating the organism towards sexual maturity and full adult stature. This suggests the use in reproductive disorders of micrin-related drugs. These could also be inhibitors of breast, prostate and other cancers, while protecting the bone marrow via a trophic effect on the adrenals (the lack of which protection causes lethal bone marrow depression in oestrogen-treated ferrets and dogs). Benign prostatic hyperplasia is asserted to be a micrin deficiency disorder, involving insufficiently opposed androgen. The rise in cancers with age could be associated with a reduction in micrin protection and a relative lack of this hormone could partly explain why men die younger than women. Micrin is dissimilar in activity to any known molecule and could usefully be isolated, characterised and exploited therapeutically.
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pubmed_263_20399
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pubmed_222_12233
|
A new Staphylococcus aureus gene termed scdA was found upstream of the autolysis regulatory genes, lytS and lytR, and was shown to potentially encode a hydrophilic 25 kDa protein. Analysis of scdA transcription revealed that it is transcribed as a monocistronic message and is lytSR-independent. A role in cell wall metabolism was indicated by examination of the scdA mutant S. aureus KB323, which had a grossly aberrant cellular morphology and formed large cell clusters when grown in liquid culture medium. Furthermore, KB323 exhibited a reduced rate of autolysis and had increased peptidoglycan cross-linking compared to the parental strain, NCTC 8325-4. These data suggest that scdA plays an important role in staphylococcal cell division.
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10.1099/00221287-143-9-2877
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pubmed_681_20555
|
Vascular stiffness is a major contributory factor of cardiovascular morbidity and mortality. Tissue Doppler imaging (TDI) could make it possible to evaluate vascular rigidity in a site by the measurement of the arterial wall velocity. The objective of this work is to validate the use of tissue Doppler imaging in the assessment of carotid rigidity. The following parameters were measured with TDI (ATL HDI 5000 and software HDI Lab): maximum velocity and mean acceleration of parietal motion (VMax and AccMax). These measurements were corrected for the arterial diameter and pulse pressure (VMax cor and AccMax cor). These data have been compared to the calculated parameters of elasticity from a mode M echography. Thirty-one subjects aged of 26 to 77 years (41.6 +/- 10.6 years, m +/- ESM), without atheromatous plaque or high blood pressure, have been included. The VMax is correlated very significantly at the parietal velocity calculated with mode M echography (r = 0.77; p = 0.00002). The VMax cor is correlated significantly with the parameters of stiffness following: distensibility coefficient, compliance coefficient, pulse wave velocity, elasticity modulus of Young, coefficient beta. [table: see text] Tissue Doppler imaging allows an easy evaluation of the carotid stiffness correlated with the parameters of elasticity. Therefore it constitutes a method of evaluation of the cardiovascular risk. Further longitudinal studies will be able to assess the involvement of the carotid stiffness as causal agent of the cardiovascular risk.
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pubmed_681_20555
|
pubmed_1115_5960
|
The binding affinities of agonists at heteromeric nicotinic receptors composed of rat alpha2, alpha3 and alpha4 subunits in combination with beta2 or beta4 subunits were examined in stably transfected HEK 293 cells. In most cases, the affinities of agonists were higher at receptors composed of an alpha subunit in combination with the beta2 subunit than the beta4 subunit, and in some cases this difference was quite large (>250 times), suggesting the possibility of developing subtype-selective ligands and therapeutically useful drugs.
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10.1016/j.bmcl.2003.09.105
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pubmed_757_8441
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We report a stereospecific imine reductase from Candida parapsilosis ATCC 7330 (CpIM1), a versatile biocatalyst and a rich source of highly stereospecific oxidoreductases. The recombinant gene was overexpressed in Escherichia coli and the protein CpIM1 was purified to homogeneity. This protein belongs to the Ornithine cyclodeaminase/ μ-crystallin (OCD-Mu) family of proteins which has only a few characterized members. CpIM1 catalyzed the alkylamination of α-keto acids/esters producing exclusively (S)-N-alkyl amino acids/esters e.g. N-methyl-l-alanine with > 90% conversion and > 99% enantiomeric excess (ee). The enzyme showed the highest activity for the alkylamination of pyruvate and methylamine leading to N-methyl-l-alanine with an apparent KM of 15.04 ± 2.8 mM and Vmax of 13.75 ± 1.07 μmol/min/mg. CpIM1 also catalyzed (i) the reduction of imines e.g. 2-methyl-1-pyrroline to (S)-2-methylpyrrolidine with ∼30% conversion and 75% ee and (ii) the dehydrogenation of cyclic amino acids e.g. l-Proline (as monitered by reduction of cofactor NADP+ spectrophotometrically).
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10.1016/j.btre.2021.e00664
|
pubmed_770_48
|
The human enteric protozoan, Giardia lamblia, has surface membrane lectin activity which mediates parasite adherence to erythrocytes. To determine whether an intestinal binding site exists for this lectin we have studied the interaction in vitro between axenically cultured Giardia trophozoites and isolated rat intestinal epithelial cells. Scanning electron microscopy showed that Giardia attached to the apical microvillus membrane and basolateral membrane of rat enterocytes. Any location on the parasite surface could mediate attachment without predeliction for the ventral disc. Trophozoites attached more avidly to jejunal compared with colonic epithelial cells. Attachment was inhibited at 4 degrees C, by sugars and glycoproteins containing D-mannosyl residues and by subagglutinating concentrations of anti-Giardia rabbit serum and two monoclonal antibodies, all with reactivity to parasite surface membrane determinants. Trypsinisation of trophozoites also reduced attachment but the ability to attach was rapidly restored after returning trophozoites to TYI-S culture medium for 4 h at 37 degrees C. Attachment was unaltered by the presence of the microfilament inhibitor cytochalasin B and in the absence of Ca++ and Mg++ ions. These findings support previous work that Giardia possesses a surface membrane mannose binding lectin and indicate that appropriate binding sites are present on rat intestinal epithelial cells. This lectin may play a part in mediating adherence of Giardia to mammalian intestine and could be a target for host immune defence.
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10.1136/gut.29.6.795
|
pubmed_780_17891
|
Phosphorylation of BAD, a pro-apoptotic member of the Bcl-2 protein family, on either Ser112 or Ser136 is thought to be necessary and sufficient for growth factors to promote cell survival. Here we report that Ser155, a site phosphorylated by protein kinase A (PKA), also contributes to cell survival. Ser112 is thought to be the critical PKA target, but we found that BAD fusion proteins containing Ala at Ser112 (S112A) or Ser136 (S136A) or at both positions (S112/136A) were still heavily phosphorylated by PKA in an in vitro kinase assay. BAD became insensitive to phosphorylation by PKA only when both Ser112 and Ser136, or all three serines (S112/136/155) were mutated to alanine. In HEK293 cells, BAD fusion proteins mutated at Ser155 were refractory to phosphorylation induced by elevation of cyclic AMP(cAMP) levels. Phosphorylation of the S112/136A mutant was >90% inhibited by H89, a PKA inhibitor. The S155A mutant induced more apoptosis than the wild-type protein in serum-maintained CHO-K1 cells, and apoptosis induced by the S112/136A mutant was potentiated by serum withdrawal. These data suggest that Ser155 is a major site of phosphorylation by PKA and serum-induced kinases. Like Ser112 and Ser136, phosphorylation of Ser155 contributes to the cancellation of the pro-apoptotic function of BAD.
|
10.1016/s0960-9822(00)00702-8
|
pubmed_559_11860
|
Molecular weight (MW) distributions of organics in the Bei Shenshu landfill leachate and their permeation from membranes were determined and studied by absorption spectrum, and the removal rates of organics with various molecular weight were measured. A new FTIR preparation method of wastewater sample used in the determination of landfill leachate was proposed in the present paper. The results showed that the aromatics in landfill leachate were mainly related to the organics with MW < 2 500, whereas the distribution of total organics was dispersal comparatively. The removal rates of various humic compounds and oils in landfill leachate were estimated in accordance with the change in FTIR absorbance of permeation from membranes at three characteristic wave numbers 2 930, 2 960 and 3 030 cm(-1), indicating that the defined membrane treatment process can removed organics with relevant MW fractions effectively.
|
pubmed_559_11860
|
pubmed_97_5745
|
Coincidence cloning allows the isolation of sequences held in common by two genomic DNA populations. Human DNA from two human-hamster hybrid cell lines was amplified by Alu-repeat primers (Alu PCR) and the products originating from the shared human chromosomal region were cloned. To achieve this, human sequences were amplified with very similar Alu primers from the two different human-hamster hybrid cell lines. The products were then digested with an appropriate restriction enzyme (either BamHI or Sal I), combined, denatured, and reannealed. The derived heteroduplex molecules (originating from the human regions common to both cell lines) had single BamHI and Sal I cohesive ends due to the primers used, so that they could be cloned in a double-digested plasmid vector. We used this method to enrich about 10-fold for Alu PCR products from the human chromosome 19q13.2 region, resulting in a region-specific clone collection. About 90% of the recombinants with BamHI-Sal I inserts are derived from the common region. This approach allows the boundaries for the regional probe isolation to be defined by combinations of hybrids rather than single hybrid cell lines, thus permitting greater flexibility in the selection of regions for probe isolation.
|
10.1073/pnas.88.15.6765
|
pubmed_210_6933
|
Chemotherapy has serious side effects that may be detrimental to the patient, namely complaints of nausea and vomiting. To reduce the side effects of chemotherapy, many patients in our country choose herbal therapy. One such therapy is the intake of ginger. The aim of this article is to explore the effectiveness of ginger to overcome nausea and vomiting caused by chemotherapy in breast cancer patients. The method used is a systematic review. Results of the study suggest that ginger is only effective to reduce nausea, but does not lower the frequency of vomiting caused by chemotherapy in breast cancer patients.
|
10.5737/2368807630135
|
pubmed_830_19808
|
AIM
To investigate the significance of the surgical approaches in the prognosis of hepatocellular carcinoma (HCC) located in the caudate lobe with a multivariate regression analysis using a Cox proportional hazard model.
METHODS
Thirty-six patients with HCC underwent caudate lobectomy at a single tertiary referral center between January 1995 and June 2010. In this series, left-sided, right-sided and bilateral approaches were used. The outcomes of patients who underwent isolated caudate lobectomy or caudate lobectomy combined with an additional partial hepatectomy were compared. The survival curves of the isolated and combined resection groups were generated by the Kaplan-Meier method and compared by a log-rank test.
RESULTS
Sixteen (44.4%) of 36 patients underwent isolated total or partial caudate lobectomy whereas 20 (55.6%) received a total or partial caudate lobectomy combined with an additional partial hepatectomy. The median diameter of the tumor was 6.7 cm (range, 2.1-15.8 cm). Patients who underwent an isolated caudate lobectomy had significantly longer operative time (240 min vs 170 min), longer length of hospital stay (18 d vs 13 d) and more blood loss (780 mL vs 270 mL) than patients who underwent a combined caudate lobectomy (P < 0.05). There were no perioperative deaths in both groups of patients. The complication rate was higher in the patients who underwent an isolated caudate lobectomy than in those who underwent combined caudate lobectomy (31.3% vs 10.0%, P < 0.05). The 1-, 3- and 5-year disease-free survival rates for the isolated caudate lobectomy and the combined caudate lobectomy groups were 54.5%, 6.5% and 0% and 85.8%, 37.6% and 0%, respectively (P < 0.05). The corresponding overall survival rates were 73.8%, 18.5% and 0% and 93.1%, 43.6% and 6.7% (P < 0.05).
CONCLUSION
The caudate lobectomy combined with an additional partial hepatectomy is preferred because this approach is technically less demanding and offers an adequate surgical margin.
|
10.3748/wjg.v18.i29.3904
|
pubmed_154_15328
|
We report on the case of a 24-year-old pregnant woman with acute mechanical mitral valve thrombosis due to a treatment failure of low molecular weight heparin (LMWH) for permanent anticoagulation following mechanical valve replacement. Initially, our patient was put on oral warfarin for anticoagulation, but when her pregnancy was perceived the anticoagulation regimen was switched to daily subcutaneous administration of LMWH in order to minimize the risk of warfarin-induced embryopathy. During her 24th week of gestation she developed acute life-threatening pulmonary edema and hemodynamic instability, which was caused by an acute thrombosis of her artificial mitral valve. In an emergency operation the thrombozed valve was replaced by a porcine biological heart valve. The patient recovered uneventfully and gave birth to a healthy child in her 35th gestational week by cesarean section. In addition we discuss the rationale of different anticoagulation regimens with regard to maternal and fetal outcome with special consideration of LMWH as an alternative strategy to oral anticoagulation during pregnancy in women with mechanical heart valves.
|
10.1007/s003920200030
|
pubmed_424_8297
|
We have quantitatively characterized by FT-IR spectroscopy the contents of secondary structure of beta-lactoglobulin during thermal unfolding and subsequent refolding. Our data clearly indicate that considerable amount of secondary structure, particularly beta-sheet, still remained intact even at 90 degrees C. Noticeable changes in secondary structure of beta-lactoglobulin were observed only above 70 degrees C. The refolded protein regained, within limits of experimental error, all of the secondary structure lost during thermal unfolding. The data also indicate that the refolding mechanism operating at pH 7.0 and 2.0 are the same. Identical secondary structure of native and refolded beta-lactoglobulin was also indicated by far-UV circular dichroic spectra of the two forms of protein. Near UV circular dichroic spectra of the same two forms showed considerable differences indicating less tertiary structure of refolded beta-lactoglobulin. The combined CD and FT-IR data indicated that refolded form of beta-lactoglobulin could be characterized as a molten globule state as it had native-like secondary structure and compromised tertiary structure.
|
10.1007/s10930-004-0603-z
|
pubmed_440_8459
|
The spatial structure of an ultralow-emittance electron bunch in a plasma wakefield blowout regime is studied. The full Liénard-Wiechert potentials are considered for mutual interparticle interactions in the framework of the equilibrium slice model. This model uses the quasistatic theory which allows one to solve the Liénard-Wiechert potentials without knowledge of the electrons' history. The equilibrium structure we find is similar to already observed hexagonal lattices but shows topological defects. Scaling laws for interparticle distances are obtained from numerical simulations and analytical estimations.
|
10.1103/PhysRevE.98.013201
|
pubmed_357_17826
|
The inactivation of p53, a tumor suppressor, and the activation of the RAS oncogene are the most frequent genetic alterations in cancer. We have shown that a unique E. coli MazF-MazE toxin-antitoxin (TA) system can be used for selective and effective eradication of RAS-mutated cancer cells. This out of the box strategy holds great promise for effective cancer treatment and management. We provide proof of concept for a novel platform to selectively eradicate cancer cells using an adenoviral delivery system based on the adjusted natural bacterial system. We generated adenoviral vectors carrying the mazF toxin (pAdEasy-Py4-SV40mP-mCherry-MazF) and the antitoxin mazE (pAdEasy-RGC-SV40mP-MazE-IRES-GFP) under the regulation of RAS and p53, resp. The control vector carries the toxin without the RAS-responsive element (pAdEasy-ΔPy4-SV40mP-mCherry-MazF). In vitro, the mazF-mazE TA system (Py4-SV40mP-mCherry-MazF+RGC-SV40mP-MazE-IRES-GFP) induced massive, dose-dependent cell death, at 69% compared to 19% for the control vector, in a co-infected HCT116 cell line. In vivo, the system caused significant tumor growth inhibition of HCT116 (KRASmut/p53mut) tumors at 73 and 65% compared to PBS and ΔPY4 control groups, resp. In addition, we demonstrate 65% tumor growth inhibition in HCT116 (KRASmut/p53wt) cells, compared to the other two control groups, indicating a contribution of the antitoxin in blocking system leakage in WT RAS cells. These data provide evidence of the feasibility of using mutations in the p53 and RAS pathway to efficiently kill cancer cells. The platform, through its combination of the antitoxin (mazE) with the toxin (mazF), provides effective protection of normal cells from basal low activity or leakage of mazF.
|
10.1038/s41388-021-01792-8
|
pubmed_1077_22884
|
This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of the review will be to determine the efficacy and tolerability of zolmitriptan compared to placebo and other active interventions in the treatment of acute migraine headaches in adults.
|
pubmed_1077_22884
|
pubmed_1021_22461
|
Muscle biopsy specimens taken from the upper lip and perialar area during the time of secondary lip revision and studied by histochemical techniques demonstrate persistent connective-tissue and muscle abnormalities even at a distance from the cleft margins. Some of these changes are consistent with surgically induced denervation-reinnervation of muscle groups in the surgical field. Increased amounts of connective tissue also were found, most likely secondary to the original deformity and the subsequent surgical procedures. Both these changes may be important factors in subsequent abnormal growth and development of the underlying midfacial structures. This study also demonstrated the resolution of previously noted mitochondrial abnormalities found in the primary cleft lip patient.
|
10.1097/00006534-199108000-00003
|
pubmed_929_25421
|
In this Letter, we present a snapshot hyperspectral light field imaging system using a single camera. By integrating an unfocused light field camera with a snapshot hyperspectral imager, the image mapping spectrometer, we captured a five-dimensional (5D) ($x,y,u,v,\lambda $x,y,u,v,λ) ($x,y,$x,y, spatial coordinates; $u,v,$u,v, emittance angles; $\lambda ,$λ, wavelength) datacube in a single camera exposure. The corresponding volumetric image ($x,y,z$x,y,z) at each wavelength is then computed through a scale-depth space transform. We demonstrated the snapshot advantage of our system by imaging the spectral-volumetric scenes in real time.
|
10.1364/OL.382088
|
pubmed_638_6809
|
OBJECTIVE
To evaluate the role of adrenal and thyroid hormones in the prediction of death in a population of critically ill puppies with parvoviral diarrhea by measuring serial daily serum concentrations of cortisol and thyroxine.
DESIGN
Prospective case-control study.
ANIMALS
57 critically ill puppies with parvoviral diarrhea admitted to the hospital and 17 clinically normal control puppies.
PROCEDURES
Basal serum cortisol and thyroxine concentrations were measured for each dog with parvoviral diarrhea at admission (prior to treatment) and daily until death, euthanasia, or discharge.
RESULTS
Median time between admission and death was 48 hours (ie, on day 3). Median serum cortisol concentration on day 1 (admission) in all dogs with parvoviral diarrhea (248 nmol/L) was significantly higher than in control dogs (77 nmol/L). No significant difference was found in the day 1 median serum cortisol concentration of 11 dogs that died (302 nmol/L) and 46 dogs that survived (238 nmol/L). A significantly higher median serum cortisol concentration was, however, found in nonsurvivor group dogs, compared with survivor group dogs, on days 2 and 3. Median serum thyroxine concentration on day 1 in dogs with parvoviral diarrhea was significantly lower than in control dogs (8.12 nmol/L vs 35 nmol/L, respectively). Median serum thyroxine concentration of nonsurvivor group dogs (4.4 nmol/L) was significantly lower than that of survivor group dogs (9.2 nmol/L) at admission and became even lower on days 2 and 3.
CONCLUSIONS AND CLINICAL RELEVANCE
High serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission were associated with death in dogs with parvoviral diarrhea.
|
10.2460/javma.231.10.1534
|
pubmed_349_7654
|
In May, BSN medical hosted two clinical symposia at the 2017 EWMA conference. These described the challenges in reducing the costs of treatment for patients with chronic venous disease (CVD), the importance of compression therapy and physical activity in the management and prevention of leg ulcers, and the obstacles in treating wound infection, among other topics. Camila Fronzo, JWC chief sub editor, was there to summarise the main points of each session.
|
10.12968/jowc.2017.26.6.350
|
pubmed_710_11222
|
Much is known about skeletal adaptation in relation to the mechanical functions that bones serve. This includes how bone adapts to mechanical loading during an individual's lifetime as well as over evolutionary time. Although controlled loading in animal models allows us to observe short-term bone adaptation (epigenetic mechanobiology), examining an assemblage of extant vertebrate bones or a group of fossils' bony structures can reveal the combined effects of long-term trends in loading history and the effects of natural selection. In this survey we examine adaptations that take place over both time scales and highlight a few of the extraordinary insights first published by John Currey. First, we provide a historical perspective on bone adaptation control mechanisms, followed by a discussion of safety factors in bone. We then summarize examples of structural- and material-level adaptations and mechanotransduction, and analyze the relationship between these structural- and material-level adaptations observed in situations where loading modes are either predictable or unpredictable. We argue that load predictability is a major consideration for bone adaptation broadly across an evolutionary timescale, but that its importance can also be seen during ontogenetic growth trajectories, which are subject to natural selection as well. Furthermore, we suggest that bones with highly predictable load patterns demonstrate more precise design with lower safety factors, while bones that experience less predictable loads or those that are less capable of repair and adaptation are designed with a higher safety factor. Finally, exposure to rare loading events with high potential costs of failure leads to design of structures with very high safety factor compared to everyday loading experience. Understanding bone adaptations at the structural and material levels, which take place over an individual's lifetime or over evolutionary time has numerous applications in translational and clinical research to understand and treat musculoskeletal diseases, as well as to permit the furthering of human extraterrestrial exploration in environments with altered gravity.
|
10.1016/j.bone.2019.115114
|
pubmed_467_21267
|
The mechanistic (or mammalian) Target of Rapamycin Complex 1 (mTORC1) is a central regulator of cell growth and metabolism. By integrating mitogenic signals, mTORC1-dependent phosphorylation of substrates dictates the balance between anabolic, pro-growth and catabolic, recycling processes in the cell. The discovery that amino acids activate mTORC1 by promoting its translocation to the lysosome was a fundamental advance in the understanding of mTORC1 signalling. It has since become clear that the lysosome-cytoplasm shuttling of mTORC1 represents just one layer of spatial control of this signalling pathway. This review will focus on exploring the subcellular localisation of mTORC1 and its regulators to multiple sites within the cell. We will discuss how these spatially distinct regions such as endoplasmic reticulum, plasma membrane and the endosomal pathway co-operate to transduce nutrient availability to mTORC1, allowing for tight control of cell growth.
|
10.1016/j.semcdb.2020.02.007
|
pubmed_1_14387
|
Cyclophilins (CYPs) are a family of proteins that bind to cyclosporine and are thought to be involved in the stress response. In dinoflagellate algae, CYPs may function as a survival strategy in cells exposed to environmental stressors. Here, we identified a novel cyclophilin gene (referred to as PmCYP, comprising a 516-bp open reading frame, encoding a 171-aa protein with a molecular mass of 17.5kDa) from the dinoflagellate Prorocentrum minimum, and evaluated the role of dinoflagellate CYP in cells exposed to environmental pollutants copper and polychlorinated biphenyl. In addition, we assessed the cytoprotective role of nitric oxide in relation to the expression of PmCYP. These stressors strongly affected the physiology of the cells, as judged by cell counting, reactive oxygen species (ROS) imaging, and photosynthetic parameters (Fv/Fm and PIABS). PmCYP expression was significantly (P<0.05) induced upon exposure of the cells to all the test pollutants used in this study. These clearly indicate that PmCYP plays a vital role in the oxidative stress response in dinoflagellate survival, although the gene was initially known only for its housekeeping function.
|
pubmed_1_14387
|
pubmed_42_21180
|
The cardiopulmonary effects of romifidine at 80 microg/kg (R80) or 120 pg/kg (R120), and detomidine at 20 pg/kg (D20) when used as premedicants for ketamine/halothane anaesthesia were investigated in six ponies. Using a blinded crossover design, acepromazine (0-04 mg/kg) was administered followed by the alpha-2 agonist. Anaesthesia was induced with ketamine at 2.2 mg/kg and maintained with halothane (expired concentration 1.0 per cent) in oxygen for three hours. During anaesthesia, arterial blood pressure, cardiac index, PaO2 and PmvO2 decreased, and systemic vascular resistance and PaCO2 increased. The cardiac indices for R80, R120 and D20 were, respectively, 39, 39 and 32 ml/kg/minute at 30 minutes and 29, 29 and 26 ml/kg/minute at 180 minutes. The alpha-2 agonists had similar cardiovascular effects, but PaO2 was significantly lower with R120. The quality of anaesthesia was similar in all three groups.
|
10.1136/vr.147.19.535
|
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