index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_12_19123 | The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions. The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points. Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively. Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state. Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state. Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state. Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges. Evidence provided by this study: 1) indicates that pellet erosion and absorption of active erythromycin base begins when the enteric-coated pellets reach the highly vascular mucosa of the jejunum and proximal ileum, and is essentially completed within the ileum, with a significant portion absorbed in the medial-to-distal ileum; 2) confirms that acceptable therapeutic plasma levels of erythromycin are attained in nonfasting subjects (Cmax = 0.94 microgram/mL) and that superior plasma erythromycin concentrations (Cmax = 1.64 micrograms/mL) are achieved by administration of the dose on an empty stomach 1 to 2 hours before or after meals; 3) corroborates other comparative studies reporting greater fasting bioavailability with this multiparticulate dosage form of erythromycin base than with reference single tablet or particle-in-tablet formulations; and 4) indicates that neutron activation of stable isotopes incorporated as a normal excipient in industrially-produced formulations provides an effective means for in vivo evaluation of dosage forms through gamma scintigraphy. | 10.1002/j.1552-4604.1990.tb01865.x |
pubmed_68_356 | BACKGROUND
The aim of this study was to determine whether a conclusion could be obtained through meta-analysis of the published trials on the relative efficacy of rifampicin and doxycycline versus streptomycin and doxycycline or another tetracycline (SD).
METHODS
The comparative and randomized trials identified by a search in the reference data base MEDLINE from 1967 to 1992 and through manual review of the articles cited in these studies or other reviews were included. The evaluation of quality was performed by a standardized scale. The differences in efficacy were expressed as odds ratio and the results were contrasted by the Mantel-Haenszel method. Heterogenicity was graphically analyzed by the Woolf method with an adjustment being made for small subgroups. The confidence intervals were calculated for each trial and for the combined data by the Cornfield method.
RESULTS
Six trials including 581 patients of whom 544 were considered evaluable were analyzed. In the RD treatment group 261 (242 valid) patients were included with 268 (253 valid) being included in the SD group. Five cases of initial therapeutic failure were observed in each group without significant differences. The secondary effects described were very variable. Nonetheless no secondary effects obliging discontinuation of treatment were presented in the RD group with only one in the SD group with no differences between the two groups. Recurrences were presented in 5% and 39% in the RD group and in 0 and 17% in the SD group. In total 37 (16%) in the former group and 13 (5%) in the latter group. The Mantel-Haenszel odds ratio with respect to recurrence was 3.81 (CI 95%, 1.82-8.17; p = 0.00009). The total number of cures was 196 (81%) in the RD group and 232 (92%) in the SD group (Mantel-Haenszel odds ratio 0.36; CI 95%, 1.19-0.64; p = 0.0004). The inclusion of the quality index of the trials did not modify the statistical significance achieved.
CONCLUSIONS
In human brucellosis the treatment of rifampicin and doxycycline presents a greater number of recurrence and lower number of cure than the classical treatment with streptomycin and tetracycline drugs. | pubmed_68_356 |
pubmed_472_24395 | This review considers early factors that interact with development to contribute to later trauma responses, including developmental sensitive periods, the effects of early environment, and the emergence of sex differences. We also describe development of neural substrates that have been associated with posttraumatic stress disorder and specifically focus on fear behavior and circuitry. Emerging evidence suggests that there may be developmental shifts around age 10 in these underlying circuits that may contribute to vulnerability. We also discuss age-related changes in the importance of caregiver availability as positive buffering factors. Hormonal changes later in development with onset during puberty appear to further shape development trajectories toward risk or resilience. We highlight these recent findings as well as the great need for further longitudinal research from middle childhood through early adulthood. | 10.1007/7854_2016_38 |
pubmed_787_7355 | OBJECTIVE
To investigate the rate of pathologically confirmed unfavourable prostate cancers among Korean men who fulfilled the contemporary Epstein criteria for clinically insignificant prostate cancer.
PATIENTS AND METHODS
This was a retrospective study of 131 Korean men who underwent radical prostatectomy (RP) for clinically insignificant prostate cancer as defined by contemporary Epstein criteria. We assessed the percentage of unfavourable prostate cancer (pathological Gleason sum > or = 7 and/or extraprostatic extension [EPE]) among these men and tried to identify useful predictors for such unfavourable tumour profiles using uni- and multivariate analyses.
RESULTS
Among 131 men with clinically insignificant prostate cancer, 40 (30.5%) had pathological Gleason > or = 7 tumours after RP. Of these 40 men, four (3.1%) also had EPE on examination of RP specimen. All those who did not have Gleason score upgrading after RP had organ-confined disease from examination of RP specimen. Overall, 40 (30.5%) of the 131 men who fulfilled the contemporary Epstein criteria for clinically insignificant prostate cancer before RP had pathologically unfavourable disease. Among our patients, no significant preoperative predictor of pathologically unfavourable disease was identified using uni- and multivariate analyses.
CONCLUSION
Our results showed that a significant proportion of contemporary Korean patients who meet all the conditions of the contemporary Epstein criteria for prediction of clinically insignificant prostate cancer might actually harbour prostate cancer with unfavourable pathological features. Such findings should be considered when treatment options are contemplated based upon the Epstein criteria among Asian patients. | 10.1111/j.1464-410X.2009.09070.x |
pubmed_1063_14007 | In this paper, we perform a systematic study about the on-body sensor positioning and data acquisition details for Human Activity Recognition (HAR) systems. We build a testbed that consists of eight body-worn Inertial Measurement Units (IMU) sensors and an Android mobile device for activity data collection. We develop a Long Short-Term Memory (LSTM) network framework to support training of a deep learning model on human activity data, which is acquired in both real-world and controlled environments. From the experiment results, we identify that activity data with sampling rate as low as 10 Hz from four sensors at both sides of wrists, right ankle, and waist is sufficient in recognizing Activities of Daily Living (ADLs) including eating and driving activity. We adopt a two-level ensemble model to combine class-probabilities of multiple sensor modalities, and demonstrate that a classifier-level sensor fusion technique can improve the classification performance. By analyzing the accuracy of each sensor on different types of activity, we elaborate custom weights for multimodal sensor fusion that reflect the characteristic of individual activities. | 10.3390/s19071716 |
pubmed_632_21607 | Activity rhythms and time budgets are two important components of ecological influences on animal individual behaviors. We collected data on activity pattern using instantaneous scan sampling on captive hamadryas baboons (Papio hamadryas) in Hangzhou Wild Animal Zoo in Zhejiang, China from November 2012 to October 2013. The results showed that: 1) In the activity time allocation, the main activities (frequency percentage was more than or equal to 5%) included resting (42.5%), traveling (16.2%), playing (10.0%), feeding (9.8%), grooming (9.4%) and watching (7.3%), and the secondary activities (frequency percentage is lower than 5%) only accounted for a total of 4.8%. 2) Due to increasing in the feeding and watching time, and decreasing in the playing and grooming time in winter, their time budgets showed significant seasonal variation, but the resting and swimming time had no significant difference between the cold season and the warm season. 3) The diurnal activity rhythms of P. hamadryas showed two feeding peaks of morning and afternoon, and as the temperature gradually turned cold, feeding activity gradually increased with three feeding peaks, which might be a strategy of complementary energy against the cold season. 4) P. hamadryas only had a midday resting and grooming peak with multi peaks of traveling and playing in the warm season, and the swimming, playing and watching time rhythm had not obvious difference between the cold winter and the warm season, but there were multi peaks of resting in the cold winter. Therefore, their diurnal activity rhythm was not the same as other many primates (such as Nomascus nasutus, Propithecus verreauxi and Lagothrix sp.), the captive P. hamadryas in winter in Hangzhou area took a strategy of feeding for supplement energy to withstand cold rather than resting to reduce energy consumption. In short, Papio hamadryas reflects obvious rhythm with seasonal differences, which may be an adaptation to the influence of food and temperature changes in captivity. | 10.13287/j.1001-9332.201611.006 |
pubmed_710_4178 | This study assessed the inconsistencies between self-reported alcohol consumption and blood alcohol content (BAC) in trauma patients. We aimed to identify the incidence of positive BAC in trauma patients who reported a zero score on the Alcohol Use Disorders Identification Test (AUDIT). We also sought to identify characteristics of individuals who were likely to negate alcohol use, yet yielded a positive BAC, to improve our ability to provide alcohol screening and healthcare to these at-risk alcohol consumers. Methods: We conducted a retrospective study from 2010 to 2018 at a university-based, level-one trauma emergency department. We identified 2581 adult trauma patients who reported a zero score on the AUDIT from the trauma registry. We collected BAC, age, gender, race, education level, mechanism of injury, language and injury severity score (ISS) from patient charts, and used descriptive analyses and multivariate logistic regression to analyze the data. Results: One hundred and thirty-one (5.08%) trauma patients who reported AUDIT of zero had a positive BAC. We found that being male (OR 1.53), assaulted or injured from a penetrating mechanism (OR 2.29) and having an ISS greater than 25 (OR 3.76) were independent positive predictors of trauma patients who reported an AUDIT of zero and had a positive BAC. Age (OR 0.99) was an independent negative predictor of trauma patients who reported an AUDIT of zero and had a positive BAC in this cohort. Conclusions: Inaccurate self-reporting of alcohol drinking behavior does exist in trauma patients. A composite of objective alcohol screening modalities, in addition to AUDIT, is needed to screen for alcohol use in this population. Healthcare providers should remain highly suspicious of alcohol-related injuries in individuals with the identified characteristics. | 10.1080/08897077.2019.1671936 |
pubmed_260_6344 | BACKGROUND
Proper functioning of the male reproductive axis depends on complex feedback systems between several hormones. In this study, the genetic contribution of various endocrine components of the hypothalamic-pituitary-testicular axis is evaluated and previously observed differences in FSH and inhibin B levels between mono- (MZ) and dizygotic (DZ) twins are re-investigated.
METHODS
Inhibin B, FSH, LH, sex hormone-binding globulin (SHBG) and testosterone levels were assayed in 128 adult males (20 MZ twin pairs, 7 single MZ twins, 10 DZ twin pairs, 27 single DZ twins and 34 siblings of twins, constituting 10 sibling pairs), aged 15.6-68.7 years. Hormone levels were compared across zygosity groups and heritability estimates were obtained using maximum likelihood variance component analysis.
RESULTS
Heritability estimates ranged from 56% (testosterone) to 81% (inhibin B and SHBG). For LH and FSH, the heritability was estimated at 68% and 80% respectively. No mean differences in hormone levels were observed across groups.
CONCLUSIONS
All measured hormones are highly heritable. A difference in the FSH-inhibin B feedback system between DZ twin males and MZ twin males could not be confirmed. | 10.1093/humrep/dem145 |
pubmed_58_15058 | Gene promoters are evolutionarily conserved across holozoans and enriched in CpG sites, the target for DNA methylation. As animals age, the epigenetic pattern of DNA methylation degrades, with highly methylated CpG sites gradually becoming demethylated while CpG islands increase in methylation. Across vertebrates, aging is a trait that varies among species. We used this variation to determine whether promoter CpG density correlates with species' maximum lifespan. Human promoter sequences were used to identify conserved regions in 131 mammals and a subset of 28 primate genomes. We identified approximately 1000 gene promoters (5% of the total), that significantly correlated CpG density with lifespan. The correlations were performed via the phylogenetic least squares method to account for trait similarity by common descent using phylogenetic branch lengths. Gene set enrichment analysis revealed no significantly enriched pathways or processes, consistent with the hypothesis that aging is not under positive selection. However, within both mammals and primates, 95% of the promoters showed a positive correlation between increasing CpG density and species lifespan, and two thirds were shared between the primate subset and mammalian datasets. Thus, these genes may require greater buffering capacity against age-related dysregulation of DNA methylation in longer-lived species. | 10.18632/aging.101413 |
pubmed_43_4959 | Protein dynamics play an essential role in function regulation. In recent years, many experimental and theoretical studies have shown that changes in protein fluctuations in the backbone and side chains fulfill a pivotal role associated with amino acid mutations, chemical modifications, and ligand binding. The dynamic correlations between protein side chains have not been sufficiently studied, and no reliable analysis method has been available so far. Therefore, we developed a method to evaluate the dynamic correlation between protein side chains using mutual information and molecular dynamics simulations. To eliminate the structural superposition errors dealing with conventional analysis methods, and to accurately extract the intrinsic fluctuation properties of the side chains, we employed distance principal component analysis (distPCA). The motion of the side chain was then projected onto the eigenvector space obtained by distPCA, and the mutual information between the projected motions was calculated. The proposed method was then applied to a small protein "eglin c" and the mutants. The results show that even a single mutation significantly changed the dynamic correlations and also suggest that the dynamic change is deeply related to the stability. Those results indicate that our developed method could be useful for analyzing the molecular mechanism of allosteric communication in proteins. | 10.1063/5.0055662 |
pubmed_250_9534 | Epigenetic modifications of histone play important roles for regulation of cell activity, such as cell division, cell death, and cell differentiation. A SET domain consisting of about 130 amino acids has lysine methyltransferase activity in the presence of the cosubstrate S-adenosyl-methionine. More than 60 SET domain-containing proteins have been predicted in various organisms. One of them, the SMYD family genes which contain a SET domain and a zinc-finger MYND domain are reported to regulate cell cycle and muscle formation. Here we examined the expression and function of smyd1 and 2 in Xenopus. smyd1 and 2 were expressed in various muscle tissues. While smyd1 expression was observed mainly in cardiac muscle and skeletal muscle, smyd2 expression was done abundantly in skeletal muscle and face region. Moreover, by loss-of-function experiments using antisense morpholino oligonucleotides, it was suggested that smyd1 and 2 related to muscle cells differentiation. | 10.1007/s10616-008-9128-1 |
pubmed_882_14209 | To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p < 0.05) level of alkaline phosphatase (ALP) activity, osteocalcin production, mineralization capacity and osteoblast-related gene expression among all groups after treatment for 7 or 21 days, respectively. Besides, in vivo studies of micro-CT analysis, routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days, respectively. In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest (p < 0.01) interfacial shear strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016. | 10.1002/jbm.a.35667 |
pubmed_1011_7884 | Human serum high density lipoprotein subfractions 2 and 3, isolated by preparative ultracentrifugation after blocking the enzyme phosphatidylcholine: cholesterol acyl transferase, have been subfractionated further by hydroxyapatite column chromatography. From subfraction 2 we reproducibly obtained 5 and from subfraction 3, 6 fractions differing in chemical composition and apolipoprotein content. The fractions eluting at low salt concentrations were composed primarily of apolipoprotein-A polypeptides while those eluting at high salt concentrations consisted primarily of apolipoprotein-C. From all the 11 subfractions only one contained the "arginine-rich" polypeptide. The apolipoprotein-C-containing fractions were richer in triacylglycerol, phospholipids and free cholesterol as compared to the apolipoprotein-A-containing ones. Although small differences of their partial specific volumes existed, the obtained values indicate that all subfractions belonged to the parent density class. The implications of these results to the current view of lipoprotein metabolism are discussed. | 10.1016/0005-2760(77)90200-4 |
pubmed_845_10503 | OBJECTIVE
To test the hypothesis that incipient Alzheimer disease (AD) may adversely affect hearing and that hearing loss may adversely affect cognition, we evaluated whether genetic variants that increase AD risk also increase problem hearing and genetic variants that increase hearing impairment risk do not influence cognition.
METHODS
UK Biobank participants without dementia ≥56 years of age with Caucasian genetic ancestry completed a Digit Triplets Test of speech-in-noise hearing (n = 80,074), self-reported problem hearing and hearing with background noise (n = 244,915), and completed brief cognitive assessments. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 previously identified AD-related polymorphisms. A genetic risk score for hearing (hearing-GRS) was calculated using 3 previously identified polymorphisms related to hearing impairment. Using age-, sex-, and genetic ancestry-adjusted logistic and linear regression models, we evaluated whether the AD-GRS predicted poor hearing and whether the hearing-GRS predicted worse cognition.
RESULTS
Poor speech-in-noise hearing (>-5.5-dB speech reception threshold; prevalence 14%) was associated with lower cognitive scores (ß = -1.28; 95% confidence interval [CI] -1.54 to -1.03). Higher AD-GRS was significantly associated with poor speech-in-noise hearing (odds ratio [OR] 1.06; 95% CI 1.01-1.11) and self-reported problems hearing with background noise (OR 1.03; 95% CI 1.00-1.05). Hearing-GRS was not significantly associated with cognitive scores (ß = -0.05; 95% CI -0.17 to 0.07).
CONCLUSIONS
Genetic risk for AD also influences speech-in-noise hearing. We failed to find evidence that genetic risk for hearing impairment affects cognition. AD disease processes or a that shared etiology may cause speech-in-noise difficulty before dementia onset. | 10.1212/WNL.0000000000010709 |
pubmed_897_22735 | The dominant pathophysiological and clinical features of myeloproliferative neoplasm (MPN)-associated myelofibrosis are caused by bone marrow fibrosis. It is widely believed this fibrosis is a reaction to the MPN-clone implying the cells causing fibrosis are polyclonal and genetically unrelated to the MPN-clone. We cite recent data illustrating the complexity of cell types comprising the bone marrow micro-environment and showing that at least some of the cells responsible for bone marrow fibrosis are clonal and genetically related to the MPN-clone. | 10.1016/j.leukres.2011.01.013 |
pubmed_894_15252 | Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters male reproductive functions and brain biogenic amines in male and female offspring. Postnatal exposure to THC or CBN reduced body weights, while testicular weights were lower in CBD-exposed mice. Testicular testosterone (T) levels were also lower in CBN- and CBD-exposed animals. Postnatal cannabinoid exposure reduced plasma luteinizing hormone (LH) levels in intact and castrated adults. Although basal T production in vitro was not affected by postnatal cannabinoid exposure, testes from CBD-exposed males were more responsive to gonadotropin stimulation. In contrast, in vivo responsiveness to intratesticular human chorionic gonadotropin (hCG) administration was significantly reduced in THC- and CBD-exposed males. Pituitary weights and their basal LH production in vitro was higher in THC- or CBN-exposed mice. Pituitaries from cannabinoid-exposed males were less responsive to LH releasing hormone (RH) stimulation, however, hypothalamic LHRH content was significantly higher in the THC-exposed males. Hypothalamic dopamine (DA) levels were significantly lower in CBN-exposed castrated mice, compared to castrated controls. The reduction in hypothalmic norepinephrine (NE) in THC- and CBN-exposed castrates after alpha-methylparatyrosine (alpha-MPT) was significantly less than that observed in control castrates. Hypothalamic DA levels were depleted to a greater extent in CBD-exposed males. Brain levels of serotonin (5-HT) and 5-HIAA were significantly higher in castrated, than in intact THC-exposed males. In ovariectomized CBN-exposed females, hypothalamic NE levels were lower, while the alpha-MPT-induced depletion of NE was less in CBD-exposed, compared to control females. Levels of 5-HT were lower only in THC-exposed females. Plasma levels of LH were significantly higher in CBN-exposed, while plasma levels of FSH were reduced in THC- and CBD females. Maternal exposure to psychoactive or non-psychoactive cannabinoids on the day of parturition results in long term alterations in neuroendocrine function in male and female offspring. It is possible that the observed alterations in biogenic amines may mediate the effects of cannabinoids on pituitary and gonadal function. | 10.1016/0091-3057(84)90111-4 |
pubmed_436_16617 | The nanoscale chemical composition variations of the surfaces of thin films of polystyrene- b-poly(methyl methacrylate) (PS- b-PMMA) diblock copolymers are investigated using apertureless near-field IR microscopy. The scattering of the incident infrared beam from a modulated atomic force microscopy (AFM) tip is probed using homodyne detection and demodulation at the tip oscillation frequency. An increase in the IR attenuation is observed in the PMMA-rich domains with a wavenumber dependence that is consistent with the bulk absorption spectrum. The results indicate that even though a small topography-induced artifact can be observed in the near-field images, the chemical signature of the sample is detected clearly. | 10.1021/la703406d |
pubmed_48_16306 | BACKGROUND
Researchers report difficulties in conducting research with children and young people with life-limiting conditions or life-threatening illnesses and their families. Recruitment is challenged by barriers including ethical, logistical and clinical considerations.
AIM
To explore how children and young people (aged 0-25 years) with life-limiting conditions or life-threatening illnesses and their families were identified, invited and consented to research published in the last 5 years.
DESIGN
Systematic review.
DATA SOURCES
MEDLINE, PsycINFO, Web of Science, Sciences Citation Index and SCOPUS were searched for original English language research published between 2009 and 2014, recruiting children and young people with life-limiting conditions or life-threatening illness and their families.
RESULTS
A total of 215 studies - 152 qualitative, 54 quantitative and 9 mixed methods - were included. Limited recruitment information but a range of strategies and difficulties were provided. The proportion of eligible participants from those screened could not be calculated in 80% of studies. Recruitment rates could not be calculated in 77%. A total of 31% of studies recruited less than 50% of eligible participants. Reasons given for non-invitation included missing clinical or contact data, or clinician judgements of participant unsuitability. Reasons for non-participation included lack of interest and participants' perceptions of potential burdens.
CONCLUSION
All stages of recruitment were under reported. Transparency in reporting of participant identification, invitation and consent is needed to enable researchers to understand research implications, bias risk and to whom results apply. Research is needed to explore why consenting participants decide to take part or not and their experiences of research recruitment. | 10.1177/0269216316663856 |
pubmed_922_6488 | BACKGROUND/AIM
The purpose of this retrospective study was to identify the predictive biomarkers of response to pretreatment for patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.
MATERIALS AND METHODS
The subjects were 54 patients treated with nivolumab for mRCC with a clear cell component (mccRCC) between September 2016 and February 2018. We analyzed the impact of serum biomarkers (lactate dehydrogenase [LDH], neutrophil-to-lymphocyte ratio, and C-reactive protein) on patients treated with nivolumab. We adopted the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model using six clinical factors (0=favorable, 1 or 2=intermediate, 3 to 6=poor risk groups, respectively).
RESULTS
The prognostic risk classification (non-poor vs. poor) and serum LDH levels were correlated with the objective response of nivolumab treatment for mccRCC. Elevated serum LDH levels at baseline were an independent biomarker for progression-free survival (PFS) of mccRCC patients receiving nivolumab [HR=2.268 (95%CI=1.014-5.051), p=0.046]. Notably, high LDH levels were associated with a poorer PFS for patients in the favorable-risk group.
CONCLUSION
Serum LDH levels at baseline before nivolumab treatment were associated with the objective response and clinical outcome of nivolumab treatment. | 10.21873/anticanres.13606 |
pubmed_13_22366 | Analysis of drugs in hair differs from their analysis in other tissues due to the extended detection window, as well as the opportunity that segmental hair analysis offers for the detection of changes in drug intake over time. The antipsychotic drug chlorprothixene is widely used, but few reports exist on chlorprothixene concentrations in hair. In this study, we analyzed hair segments from 20 deceased psychiatric patients who had undergone chronic chlorprothixene treatment, and we report hair concentrations of chlorprothixene and its metabolite desmethylchlorprothixene. Three to six 1-cm long segments were analyzed per individual, corresponding to ~3-6 months of hair growth before death, depending on the length of the hair. We used a previously published and fully validated liquid chromatography-tandem mass spectrometry method for the hair analysis. The 10th-90th percentiles of chlorprothixene and desmethylchlorprothixene concentrations in all hair segments were 0.05-0.84 ng/mg and 0.06-0.89 ng/mg, respectively, with medians of 0.21 and 0.24 ng/mg, and means of 0.38 and 0.43 ng/mg. The estimated daily dosages ranged from 28 mg/day to 417 mg/day. We found a significant positive correlation between the concentration in hair and the estimated daily doses for both chlorprothixene (P = 0.0016, slope = 0.0044 [ng/mg hair]/[mg/day]) and the metabolite desmethylchlorprothixene (P = 0.0074). Concentrations generally decreased throughout the hair shaft from proximal to distal segments, with an average reduction in concentration from segment 1 to segment 3 of 24% for all cases, indicating that most of the individuals had been compliant with their treatment. We have provided some guidance regarding reference levels for chlorprothixene and desmethylchlorprothixene concentrations in hair from patients undergoing long-term chlorprothixene treatment. | 10.1093/jat/bky038 |
pubmed_318_532 | The inner ear as an example of a highly specialized sensory organ also possesses a highly specialized vascularisation. This represents an impressive example for a reasonable adaption of the terminal blood vessels to a specific function of the organ fulfilling more than only the nutrition. In this paper the microvascular bed of the cochlea is examined using both the injection method of the vessels and the biomicroscopic observation in vivo. The combination of these technics supported by histologic and stereoscan microscopic examinations has made it possible to give an account of the functional morphology of the inner ear vessels. As a detailed structural analysis of the vessels morphology with the help of dyes that fill the whole of the vessels space (i.e. Berlin blue) is not possible, perfusion experiments with silver nitrate were performed on the inner ear. After the perfusion the vessels are cleaned again, the silver however imbibes the intercellular reticular substances and after exposure produces a continous and sharp framework of the endothelium and--when present--muscular cells, thus showing the angioarchitectural contours. There is a very clear division of the cochlear vessels in a three dimensional space: The arterial and venous vessels are vividly separated from one another, forming two systems of microvascular units in the lateral wall and the spiral lamina. Each unit begins with special blood vessel convoluts in the modiolus, consisting of loops of arterioles. They are weakly muscularized whereas no muscle structures are seen elsewhere in the other parts of the inner ear vessels. There are no a.-v. anastomoses or sphinkters at all. The function of the vessel loops in the modiolus is to flatten the pulse wave as well as to regulate the blood flow in the microvascular bed by vasomotion. This was proved by statistical examinations of 1200 measurements of the widths of the vessels at several points of the cochlea in a blind study with and without vasoactive drugs. The terminology of the vessels is not standardized. The nomenclature in this paper has regard to the classification of the vessels, the course and the topographic localisation. Silver staining reveals changes in the form of the endothelium cells from the arterial towards the venous end. While the arteries show a long stretched spinle or lancet like form they change over blunt, oval, triangular or rhomboid forms into polygonal cells with spiked border lines at the venules. All experiments together give an account that the blood supply of the inner ear is in close correlation with the blood supply of the brain and too possesses autoregulative mechanisms, which must be localized in the convoluts at the beginning of every microvascular unit of the cochlear vessels. | 10.1007/BF00456576 |
pubmed_561_3532 | Work-related musculoskeletal disorders (WMSDs) represent approximately one third of workers' compensation costs in US private industry, yet estimates of acceptable exposure levels for forceful and repetitive tasks are imprecise, in part, due to lack of measures of tissue injury in humans. In this review, the authors discuss the scope of upper-extremity WMSDs, the relationship between repetition rate and forcefulness of reaching tasks and WMSDs, cellular responses to injury in vivo and in vitro, and animal injury models of repetitive, forceful tasks. The authors describe a model using albino rats and present evidence related to tissue injury and inflammation due to a highly repetitive reaching task. A conceptual schematic for WMSD development and suggestions for further research are presented. Animal models can enhance our ability to predict risk and to manage WMSDs in humans because such models permit the direct observation of exposed tissues as well as motor behavior. | 10.1093/ptj/82.2.173 |
pubmed_300_8723 | We examined determinants of symptom severity and response to treatment among 150 patients with cancer participating in a phase II trial of a palliative care team intervention. Patients completed a modified Edmonton Symptom Assessment Scale (ESAS) at baseline and 1 week. Women had a worse baseline ESAS Distress Score (EDS; P = .003) and Total Distress Score (TDS; P = .005); differences were particularly marked for anxiety and appetite. Performance status was inversely associated with EDS, TDS, well-being, appetite, and fatigue (Kruskal-Wallis, all P < .005). Multivariate analysis of covariance (ANCOVA) showed that symptom improvement was independently predicted by worse baseline EDS score and female gender. Performance status, gender, and baseline symptom severity should be accounted for in trials of palliative care interventions; inclusion criteria based on symptom severity should also be considered. | 10.1177/1049909109346307 |
pubmed_801_7761 | Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted. | 10.1634/theoncologist.2010-0249 |
pubmed_111_3689 | The hypothesis that acoustic measures of relative speech timing remain constant across large changes in speaking rate was tested for fluent utterances produced by normal and neurogenically disordered speakers. For all speakers, relative timing tended to be statistically invariable across conversational and fast speaking rates. This finding was considered especially interesting in the case of speakers with dysarthria and apraxia of speech, because absolute measures of speech timing associated with these disorders are typically aberrant. A post hoc analysis of relative variability across speakers showed the ratio measures to be consistently less variable than measures of absolute interval duration. The greater similarity across speakers of ratio measures, as compared to interval measures, was taken to mean that characterizing the temporal structure of articulatory sequences in terms of relative timing is an appropriate way to capture an important aspect of the biological constraints associated with speech production. | 10.1121/1.392453 |
pubmed_247_20859 | In situ steady-state, single-pass small intestine perfusions in rats were carried out to compare the effect of the bicarbonate and citrate World Health Organization oral rehydration solutions and a base precursor-free solution on intestinal water and electrolyte transport after inducing intestinal secretion with purified heat-stable Escherichia coli enterotoxin. When toxin was not perfused, the rates of water, sodium, and bicarbonate absorption were significantly greater from the bicarbonate-containing solution than from the citrate or base precursor-free solutions. Chloride absorption was greater from the base precursor-free solution, but this might reflect the higher chloride concentration of the perfusate. When toxin was perfused, there was no significant difference among the solutions in the rates of water, potassium, or chloride absorption. Sodium absorption occurred at significantly greater rates from both the bicarbonate and the base precursor-free solutions than from the citrate solution. Base precursor-containing solutions may not provide any advantage over a base precursor-free solution in stimulating water and sodium absorption in 5'-cyclic guanosine monophosphate mediated acute diarrhea. | 10.1007/BF01308341 |
pubmed_979_6122 | PTH-related protein (PTHrP) is produced in vascular smooth muscle, where it is postulated to exert vasorelaxant properties by activation of the PTH/PTHrP type 1 receptor. As a model for studying the actions of locally produced PTHrP in vascular smooth muscle in vivo, we developed transgenic mice that overexpress the PTH/PTHrP receptor (PTHrP-R) in smooth muscle. Oocyte injection with a SMP8-PTHrP-R fusion construct yielded six founder mice. F1 offspring were viable and demonstrated selective overexpression of the SMP8-PTHP-R messenger RNA in smooth muscle-rich tissues. Baseline blood pressure measured in conscious mice by tail sphygmomanometry was significantly lower in the receptor-overexpressing mice than that in controls (117 +/- 4 vs. 133 +/- 3 mm Hg; P < 0.05). In anesthetized animals, iv infusion of PTHrP-(1-34)NH2 caused a significantly greater reduction in blood pressure and total peripheral resistance in transgenic mice than in control animals. Vascular contractility was studied in paired, isometrically mounted aortas from 9-week-old transgenic and wild-type mice. The force of contraction in response to phenlyephrine was not significantly different between transgenic and wild-type mice. However, PTHrP-(1-34) NH2 relaxed aortic vessel preparations from transgenic mice to a greater extent than in controls (77.1 +/- 3% vs. 38.4 +/- 4%; P < 0.001). To determine the impact of overexpression of PTH/PTHrP type 1 receptor and its ligand on the development of the cardiovascular system, double transgenic mice were created by crossing SMP8-PTHrP-R transgenic mice with mice overexpressing PTHrP (SMP8-PTHrP). Double transgenic mice died around day E9 with abnormalities in the developing heart. In conclusion, overexpression of PTH/PTHrP type 1 receptor in vascular smooth muscle of transgenic mice reduces blood pressure, probably through sustained activation of the receptor by endogenous ligand. The cardiovascular defects observed in mice overexpressing both PTHrP and its receptor suggest that PTHrP may play a role in the normal development of the cardiovascular system. | 10.1210/endo.140.4.6645 |
pubmed_240_10067 | In the title complex, [Ag(2)(C(12)H(8)N(2)O(4))(C(14)H(14)N(4))](n), one Ag(I) ion, lying on a twofold rotation axis, is coordinated by two N atoms from two 3,5,9,11-tetra-oxo-4,10-diaza-tetra-cyclo-[5.5.2.0(2,6).0(8,12)]tetra-dec-13-ene-4,10-diide (L) ligands in a nearly linear arrangement. The other Ag(I) ion, lying on an inversion center, is coordinated by two O atoms from two L ligands and two N atoms from two 1,4-bis-(imidazol-1-ylmeth-yl)benzene ligands in a distorted square-planar geometry. An additional Ag⋯Ag [3.0119 (3) Å] inter-action links the Ag(I) ions into a chain along [010]. The two types of ligands have mirror symmetry and connect the Ag(I) ions into a layer parallel to (100). | 10.1107/S1600536812039669 |
pubmed_637_13117 | INTRODUCTION
Nanofitins are low molecular weight, single chain and cysteine-free protein scaffolds able to selectively bind a defined biological target. They derive from Sac7d bacterial protein family and are highly stable over a wide range of pH (0-13) and temperature (Tm ~80°C). Their extreme stability, low cost of production and high tolerability for chemical coupling make Nanofitins a very interesting alternative to antibodies and their fragments. Here, a hexahistidine tagged model Nanofitin (H4) directed against hen egg white lysozyme was radiolabelled and injected in mice to provide a baseline biodistribution and pharmacokinetic profiles to support future Nanofitin development programs.
METHOD
A single cysteine residue has been genetically inserted in a model Nanofitin and its regioselective radiolabelling has been performed with 4-[18F]fluorobenzamido-N-ethylamino-maleimide ([18F]FBEM). The synthesis of [18F]FBEM has been completely implemented on a radiosynthesis unit (FastLab) including HPLC purification and formulation. Coupling with the [18F]FBEM has been achieved on a solid support (Ni magnetic beads) allowing rapid purification at room temperature without organic solvent. PET-MRI studies on C57BL/6 mice were conducted after injection of [18F]FBEM-Cys-H4 in order to access the biodistribution of this Nanofitin model.
RESULTS
Radiochemical yield (decay corrected) of 54±7% (n=4) was obtained after optimization for coupling the [18F]FBEM to Nanofitin. Pharmacokinetics results of [18F]FBEM-Cys-H4 revealed a fast clearance through the liver and the kidneys.
CONCLUSION
An efficient new method on Ni magnetic beads was developed to radiolabelled his-tagged biomolecules with [18F]FBEM. This procedure was applied on a Nanofitin model Cys-H4 and biodistribution kinetic studies were achieved to evaluate the potential use of Nanofitin for diagnostic imaging. Fast clearance indicates that Nanofitins represent very interesting tools for diagnostic imaging. | 10.1016/j.nucmedbio.2017.04.006 |
pubmed_345_17918 | We previously showed that a single bolus of "doubly-labeled" water ((2)H2 (18)O) can be used to simultaneously determine energy expenditure and turnover rates (synthesis and degradation) of tissue-specific lipids and proteins by modeling labeling patterns of protein-bound alanine and triglyceride-bound glycerol (Bederman IR, Dufner DA, Alexander JC, Previs SF. Am J Physiol Endocrinol Metab 290: E1048-E1056, 2006). Using this novel method, we quantified changes in the whole body and tissue-specific energy balance in a rat model of simulated "microgravity" induced by hindlimb suspension unloading (HSU). After chronic HSU (3 wk), rats exhibited marked atrophy of skeletal and cardiac muscles and significant decrease in adipose tissue mass. For example, soleus muscle mass progressively decreased 11, 43, and 52%. We found similar energy expenditure between control (90 ± 3 kcal · kg(-1)· day(-1)) and hindlimb suspended (81 ± 6 kcal/kg day) animals. By comparing food intake (∼ 112 kcal · kg(-1) · day(-1)) and expenditure, we found that animals maintained positive calorie balance proportional to their body weight. From multicompartmental fitting of (2)H-labeling patterns, we found significantly (P < 0.005) decreased rates of synthesis (percent decrease from control: cardiac, 25.5%; soleus, 70.3%; extensor digitorum longus, 44.9%; gastrocnemius, 52.5%; and adipose tissue, 39.5%) and rates of degradation (muscles: cardiac, 9.7%; soleus, 52.0%; extensor digitorum longus, 27.8%; gastrocnemius, 37.4%; and adipose tissue, 50.2%). Overall, HSU affected growth of young rats by decreasing the turnover rates of proteins in skeletal and cardiac muscles and adipose tissue triglycerides. Specifically, we found that synthesis rates of skeletal and cardiac muscle proteins were affected to a much greater degree compared with the decrease in degradation rates, resulting in large negative balance and significant tissue loss. In contrast, we found a small decrease in adipose tissue triglyceride synthesis paired with a large decrease in degradation, resulting in smaller negative energy balance and loss of fat mass. We conclude that HSU in rats differentially affects turnover of muscle proteins vs. adipose tissue triglycerides. | 10.1152/japplphysiol.00004.2014 |
pubmed_633_7267 | Clinical endometritis in dairy cows is defined as mucopurulent or purulent vulvar discharge 21 days or more after parturition. The diagnosis of clinical endometritis is commonly based on vaginal examination. Techniques to reduce the proportions of false negative findings have been described. This paper discusses a clinical approach to determine the proportion of false positive findings that might occur by vaginal inspection. The consequences of false positive findings in dairy practice are unnecessary or inadequate treatments. In research, incorrect diagnoses have an impact on the interpretation of studies on the diagnosis and treatment of clinical endometritis. The objective of the present study was to compare intrauterine bacteriology and endometrial cytology in cows diagnosed with clinical endometritis with findings obtained by vaginoscopy. Clinical endometritis was defined as mucopurulent or purulent vulvar discharge. On two commercial dairy farms, cows were examined 21 to 28 d postpartum. Uterine samples (n = 230) were collected from cows with clinical endometritis with the cytobrush technique to determine the proportion of polymorphonuclear neutrophils (PMN) and to culture smears for aerobic bacteria. Two threshold values for the proportion of PMN (5 and 18%) were chosen as possible indicators for an inflamed endometrium. Common uterine pathogens A. pyogenes and E. coli were found in 33.5 and 10.4% of the samples, respectively. With increasing vaginal discharge score, proportion of samples positive for A. pyogenes increased significantly. The proportion of cows exceeding the thresholds for PMN increased with vaginal discharge score and the presence of A. pyogenes. Considering only the presence of aerobic uterine pathogens and a proportion of PMN above the threshold values of 5 and 18% as indicative for endometritis, a proportion of 17.3 and 28.5%, respectively, of diagnoses by vaginoscopy were false positive. | 10.1016/j.theriogenology.2010.05.028 |
pubmed_525_225 | A metalloprotease gene of Brevibacillus brevis (npr) was expressed in Escherichia coli in a soluble form as native Npr precursor. A significant fraction of the precursor was spontaneously processed, producing the N-terminal propeptide and the mature enzyme. A strong inhibition of the mature Npr by its own propeptide in the crude lysate was observed even in the absence of the covalent linkage between them. Pure precursor, propeptide and the mature Npr were isolated and kinetic parameters of the mature enzyme inhibition by the propeptide were determined. The inhibition is of the tight-binding competitive type with Ki 0.17 nM. Inhibition of metalloproteases from Brevibacillus megaterium and thermolysine by the heterologous propeptide of the Npr from B. brevis was much weaker or none. | 10.1016/s0014-5793(99)00791-7 |
pubmed_340_22709 | BACKGROUND AND AIMS
Dental decay remains a major public health problem in Scottish children. The aim of this study was to investigate the relationship between diet, bowel habit, social class, and body mass index (BMI) in children with severe tooth decay.
CHILDREN AND METHODS
A cross sectional study of 165 children aged 3 -11 years attending Glasgow Dental Hospital for extraction of teeth under dental general anaesthesia (DGA), was undertaken. A structured questionnaire was used to obtain information from each child on diet, bowel habit, and social status of their parents. Fibre and sugar scores were calculated from the frequency of consumption of a range of relevant foods.
RESULTS
The children (mean age 5.7 (SD1.8) years) had between 1 and 20 decayed, missing or filled primary teeth (dmft) with a mean dmft of 7.9 (SD 3.5). 37% ate a chocolate bar daily, and 29% regularly drank a sugary drink after brushing their teeth. An excess of children were from the most deprived parts of the city and they had the worst decay. Children with the worst decay were also significantly thinner. No relationship was found between tooth decay and bowel habit.
CONCLUSIONS
In this selected group of children with poor dental health, those from deprived families were over-represented and had significantly more decay. Severe dental decay was also associated with underweight. | 10.1258/RSMSMJ.51.3.26 |
pubmed_324_2040 | A simple, rapid, precise and eco-friendly ion chromatography (IC) method for the determination of hippuric acid (HA) in human urine was proposed in this paper. The separation was carried out an anion exchange column with 2.0 mmol L⁻¹ Na₂CO₃ + 2.0 mmol L⁻¹ NaHCO₃ as mobile phase at the flow-rate 0.7 mL min⁻¹. A suppressed conductivity detector was used and the detection limit was 1.0 μg L⁻¹ (S/N=3) for hippuric acid. The analysis time for one run was 30 min under the optimized IC condition. The recovery of hippuric acid was 93.2-98.0% while the relative standard deviation (RSD) was 1.4-2.3% by seven measurements. | 10.1016/j.jchromb.2010.12.015 |
pubmed_100_18229 | Introgression between genetically modified (GM) crops and wild relatives is considered to potentially modify the genetic background of the wild species. The emergence of volunteer-like feral populations through backcross of hybrids to the crop is also a concern. The progeny of spontaneous hybrids between mutant herbicide-resistant oilseed rape (Brassica napus) and wild B. juncea was obtained. Parents, F(2) and BC(1) to B. napus were planted together in the field so as to study their performance. The chromosome number of BC(1) followed a Normal distribution. Mendelian ratio of the herbicide-resistance gene was found. The F(2) produced less seeds than B. napus, and BC(1) had intermediate production. Herbicide-resistant BC(1) were not different of their susceptible counterparts for plant weight, seed weight and seed number, but most of them exhibited B. napus morphology and larger flowers than the susceptible BC(1). They displayed an important genetic variability allowing further adaptation and propagation of the herbicide-resistance gene. Pollen flow to susceptible plants within the mixed stand was observed. As a consequence, the resistant BC(1) produced with B. napus pollen could frequently occur and easily establish as a false feral crop population within fields and along roadsides. | 10.1016/j.plantsci.2010.07.005 |
pubmed_728_13680 | Anomalohimalaya lotozkyi sp. n., the second species of this genus, was found in Tadzhikistan, Peter I ridge, at the height of 2700 m above the sea level in rocky locality with xerophilous vegetation on Alticola argentatus. In June, 1977 there were found larvae and nymphs of the species. After feeding larvae and then nymphs females and males were obtained. All phases of the life cycle differ distinctly from those of the type species An. lama Hoog., Kais. et Mitch., 1970, from Himalayas. The diagnosis of the genus Anomalohimalaya is specified. This genus combines the characters of Haemaphysalis Koch and Rhipicephalus Koch and is of great significance for more precise definition of phylogeny of the subfamily Amblyomminae Banks. | pubmed_728_13680 |
pubmed_788_4807 | More than half of the nascent B cells in humans initially express autoreactive antibodies. However, most of these autoantibodies are removed from the repertoire at two checkpoints before maturation into naive B cells. A third checkpoint excludes remaining autoantibodies from the antigen-experienced IgM(+) memory B cell pool. Nevertheless, low-affinity self-reactive antibodies are frequently found in the serum of normal humans. To determine the source of these antibodies, we cloned and expressed antibodies from circulating human IgG(+) memory B cells. Surprisingly, we found that self-reactive antibodies including anti-nuclear antibodies were frequently expressed by IgG(+) memory B cells in healthy donors. Most of these antibodies were created de novo by somatic hypermutation during the transition between mature naive and IgG(+) memory B cells. We conclude that deregulation of self-reactive IgG(+) memory B cells may be associated with autoimmunity. | 10.1016/j.immuni.2007.01.009 |
pubmed_885_18629 | The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by "RTK swapping" by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation. | 10.1371/journal.pone.0046738 |
pubmed_495_1907 | UNLABELLED
The aim of this study was to evaluate the prevalence of disordered intragastric meal distribution and the relationships between gastric emptying, intragastric distribution, glycemic control and gastrointestinal symptoms in diabetes mellitus.
METHODS
Eighty-six patients with diabetes mellitus had measurements of gastric emptying and intragastric distribution of a radioisotopically labeled solid/liquid meal (100 g beef and 150 ml 10% dextrose), glycemic control (plasma glucose concentrations), upper gastrointestinal symptoms (questionnaire) and autonomic nerve function (cardiovascular reflexes). Results were compared to those obtained in 20 normal volunteers.
RESULTS
Solid and liquid gastric emptying were delayed in the diabetic patients and correlated weakly. Intragastric meal distribution was also often abnormal, with increased retention of both solid and liquid in the proximal stomach and increased retention of solid but not liquid in the distal stomach. In all patients with increased retention of solid in the proximal stomach, emptying from the total stomach was delayed. Gastric emptying of liquid was slower in those subjects who had a mean plasma glucose > 15 mmol/liter during the gastric emptying measurement, when compared to the remainder of the group.
CONCLUSION
In patients with diabetes mellitus, there is poor relationship between solid and liquid gastric emptying and intragastric meal distribution is frequently abnormal. Interpretation of the results of gastric emptying measurements should consider meal composition and plasma glucose concentrations. | pubmed_495_1907 |
pubmed_170_12853 | This manuscript will be simultaneously published in all Affiliated National Societies Journals that consented to publication. | 10.1007/BF03091762 |
pubmed_1064_1896 | Quantitative PCR (Q-PCR) technology has recently been applied to the measurement of ocular loads of Chlamydia trachomatis. We present an index called the community ocular C. trachomatis load (COCTL) which is similar to the community microfilarial load (CMFL) of onchocerciasis. Our index has the advantage of being scale-independent so that, for example, percentage changes are the same whether calculated per eye swab or per Q-PCR capillary. The COCTL for a population or subgroup is formed by adding the arbitrary concentration of 1 organism per ml to each individual Q-PCR quantification, calculating the geometric mean, and finally subtracting 1 per ml again. The use of the COCTL is illustrated in a study of trachoma in northern Tanzania. The COCTL is higher in people with clinical trachoma than those without (5.8 organisms per swab vs. 0.1), and in children aged six months to ten years than in the overall population (1.1 vs. 0.4). The COCTL index is potentially useful for sentinel sites, operational research and calibration of clinical measures of trachoma. | 10.1016/j.trstmh.2004.05.003 |
pubmed_14_13773 | In this article we describe state-of-the art techniques for magnetic resonance imaging of the liver. T1-weighted, T2-weighted, and heavily T2-weighted pulse sequences are discussed. Gadolinium-enhanced hepatic parenchymal imaging and magnetic resonance angiography are also described. A comprehensive MR imaging examination of the liver affords evaluation of focal and diffuse hepatic parenchymal disease, biliary disease, and vascular pathology. | 10.1016/s1089-3261(03)00066-7 |
pubmed_270_8425 | We report on the second phase of a programme to select a relative of Arabidopsis thaliana for use in large-scale molecular genetic studies of nickel (Ni) and zinc (Zn) hyperaccumulation. We also report on the relatedness among Thlaspi caerulescens accessions and the utility of using O-acetyl-L-serine as a marker for Ni and Zn hyperaccumulation potential. Twenty-seven new accessions of metal-accumulating species collected in the Czech Republic, France, Greece, Italy, Slovenia and the USA during Spring-Summer 2002 were evaluated. The criteria established for selection were hyperaccumulation of metals (Ni and Zn); compact growth habit; reasonable time to flowering; production of > or = 1000 seeds per plant; self-fertility; compact diploid genome; high sequence similarity to A. thaliana; > or = 0.1% transformation efficiency with easy selection. We conclude that the best candidate identified in the first phase was the best candidate overall: T. caerulescens accession St Félix de Pallières. | 10.1111/j.1469-8137.2006.01820.x |
pubmed_681_21904 | Cyclophosphamide (CP) is an anti-tumor drug commonly used in the chemotherapy of human cancer and autoimmune diseases. In our previous studies, we have demonstrated that lactoferrin (LF), given orally to CP-immunosuppressed mice, could reconstitute a T cell mediated immune response by the renewal of the T cell population. The aim of this present study was to evaluate the effects of LF on humoral responses in mice treated with cyclophosphamide. We demonstrate that a single, sublethal dose of cyclophosphamide (400 mg/kg body weight) profoundly inhibited the humoral immune response of CBA mice to sheep red blood cells (SRBC), as measured by the number of antibody forming cells (AFC) in the spleen after 5 weeks following CP treatment. Administration of 0.5% bovine LF in drinking water for 5 weeks partially reconstituted the AFC number (30-40% of the control values, but 7-10x more than in CP-treated controls). Determination of T and B cell levels in the spleens by flow cytometry revealed that the content of CD3+ and CD4+ as well as Ig+ splenocytes was elevated in the immunocompromised mice treated with LF. In addition, the number of peritoneal macrophages was partially restored following LF treatment. Evaluation of the proliferative response to concanavalin A (ConA) and pokeweed mitogen (PWM) demonstrated that the diminished reactivity of splenocytes from CP-treated mice was significantly enhanced by LF. In summary, we conclude that the prolonged, oral treatment of immunocompromised mice with LF led to partial reconstitution of the humoral response, associated with elevation of T and B cell and macrophage content and the proliferative response of splenocytes to mitogens. | 10.1016/s0165-2478(03)00102-0 |
pubmed_851_5090 | AIM/BACKGROUND
Primary motor cortex (M1) organization differs between individuals with and without chronic low back pain (CLBP), in parallel with motor and sensory impairments. This study investigated whether movement behaviour and tactile/pain sensation are related to M1 organisation in CLBP.
METHODS
Transcranial magnetic stimulation (TMS) was used to map the M1 representation of the erector spinae and multifidus muscles in 20 participants with and without CLBP. Cortical organisation was quantified by: map volume; center of gravity (CoG); number of peaks; and primary and secondary peak location. Movement behaviour was assessed as the ability to dissociate lumbar from thorax motion and sensory function as two-point discrimination, pressure pain thresholds, and pain intensity (visual analogue scale).
RESULTS
People with CLBP showed more anterior location of the CoG than controls. Map peaks were more numerous in CLBP participants who performed the movement task good than those with poor performance. In CLBP, smaller map volume correlated with greater pain during the movement task. Movement behaviour was not linearly correlated with M1 features.
CONCLUSIONS
This study confirms that M1 maps differ between people with and without CLBP, but these changes are variable within the CLBP group and are not related to motor and sensory features in a simple manner. | 10.1097/AJP.0000000000000535 |
pubmed_762_17820 | The iProClass database provides comprehensive, value-added descriptions of proteins and serves as a framework for data integration in a distributed networking environment. The protein information in iProClass includes family relationships as well as structural and functional classifications and features. The current version consists of about 830 000 non-redundant PIR-PSD, SWISS-PROT, and TrEMBL proteins organized with more than 36 000 PIR superfamilies, 145 000 families, 4000 domains, 1300 motifs and 550 000 FASTA similarity clusters. It provides rich links to over 50 database of protein sequences, families, functions and pathways, protein-protein interactions, post-translational modifications, protein expressions, structures and structural classifications, genes and genomes, ontologies, literature and taxonomy. Protein and superfamily summary reports present extensive annotation information and include membership statistics and graphical display of domains and motifs. iProClass employs an open and modular architecture for interoperability and scalability. It is implemented in the Oracle object-relational database system and is updated biweekly. The database is freely accessible from the web site at http://pir.georgetown.edu/iproclass/ and searchable by sequence or text string. The data integration in iProClass supports exploration of protein relationships. Such knowledge is fundamental to the understanding of protein evolution, structure and function and crucial to functional genomic and proteomic research. | 10.1093/nar/gkg044 |
pubmed_0_21415 | Diurnal variations of fossil secondary organic carbon (SOC) and nonfossil SOC were determined for the first time using a combination of several carbonaceous aerosol measurement techniques, including radiocarbon (¹⁴C) determinations by accelerator mass spectrometry, and a receptor model (chemical mass balance, CMB) at a site downwind of Tokyo during the summer of 2007. Fossil SOC showed distinct diurnal variation with a maximum during daytime, whereas diurnal variation of nonfossil SOC was relatively small. This behavior was reproduced by a chemical transport model (CTM). However, the CTM underestimated the concentration of anthropogenic secondary organic aerosol (ASOA) by a factor of 4-7, suggesting that ASOA enhancement during daytime is not explained by production from volatile organic compounds that are traditionally considered major ASOA precursors. This result suggests that unidentified semivolatile organic compounds or multiphase chemistry may contribute largely to ASOA production. As our knowledge of production pathways of secondary organic aerosol (SOA) is still limited, diurnal variations of fossil and nonfossil SOC in our estimate give an important experimental constraint for future development of SOA models. | 10.1021/es102392r |
pubmed_76_20349 | U-251 MG, a permanent cell line derived from human glioblastoma multiforme with the capacity to maintain glial fibrillary acidic protein (GFAP) production over repeated in vitro passages, was evaluated for the expression of three neuron-associated proteins (Class III beta-tubulin, MAP2, and tau) in three different in vitro systems: as free-floating suspensions, on coverslips, and on a gelatin foam (Gelfoam) matrix. Cells grown under the three in vitro conditions were analyzed by immunoblotting techniques, whereas immunohistochemical analyses were performed on cells grown on Gelfoam. By immunohistochemistry, cells were positive for Class III beta-tubulin isotype, a neuron-associated beta-tubulin, for microtubule-associated protein 2 (MAP2), but not for tau. Immunoblotting studies confirmed the presence of Class III beta-tubulin in extracts of cells grown under the three in vitro conditions. MAP2 and tau were clearly evident only in cell extracts grown in Gelfoam cultures. GFAP expression was observed in all three in vitro conditions by immunoblotting and also in foam matrix cultures by immunohistochemistry. In matrix cultures, Class III beta-tubulin- and GFAP-positive cells were found immediately adjacent to each other, but coexpression of these proteins was not observed, and the cells were morphologically indistinguishable. Our findings confirm the heterogeneity of malignant gliomas in vitro, and the implications of these observations require further study. | 10.1007/BF03160016 |
pubmed_1123_12281 | OBJECTIVE
We examined the effect of perceived child anxiety status on parental latency to intervene with anxious and nonanxious youth.
METHOD
Parents (68) of anxiety-disordered (PAD) and nonanxiety-disordered (PNAD; 56) children participated. Participants listened and responded to an audio vignette of a parent-child interaction: Half were told the child was anxious, and half were given a neutral description. Participants completed measures of anxiety and emotional responding before and after the audio vignette and signaled when the mother on the vignette should accommodate the child.
RESULTS
Whereas PNAD responded significantly faster when provided with neutral information about the child than when told the child was anxious, PAD did not differ in response latency. However, PAD exhibited a significant increase in state anxiety and negative affect and a decrease in positive affect after the vignette, whereas PNAD did not.
CONCLUSIONS
Results suggest that PNAD are more flexible and adaptable in their parenting behavior than PAD and that the greater anxiety and emotional lability of PAD may influence their parenting. Suggestions for research are discussed. | 10.1037/a0027230 |
pubmed_475_24506 | Background. To identify, upon emergency department (ED) admission, predictors of unexpected death or unplanned intensive care/high dependency units (ICU/HDU) admission during the first 15 days of hospitalization on regular wards. Methods. Prospective cohort study in a medical-surgical adult ED in a teaching hospital, including consecutive patients hospitalized on regular wards after ED visit, and identification of predictors by logistic regression and Cox proportional hazards model. Results. Among 4,619 included patients, 77 (1.67%) target events were observed: 32 unexpected deaths and 45 unplanned transfers to an ICU/HDU. We identified 9 predictors of the target event including the oxygen administration on the ED, unknown current medications, and use of psychoactive drug(s). All predictors put the patients at risk during the first 15 days of hospitalization. A logistic model for hospital mortality prediction (death of all causes) still comprised oxygen administration on the ED, unknown current medications, and the use of psychoactive drug(s) as risk factors. Conclusion. The "use of oxygen therapy on the ED," the "current use of psychoactive drug(s)", and the "lack of knowledge of current medications taken by the patients" were important predisposing factors to severe adverse events during the 15 days of hospitalization on regular wards following the ED visit. | 10.1155/2014/203747 |
pubmed_464_11519 | Internal conversion (IC) between the two lowest singlet excited states, 11B+ and 21A-, of s-trans-butadiene and s-trans-hexatriene is investigated using a series of single- and multi- reference wave function and density functional theory (DFT) methodologies. Three independent types of the equation-of-motion coupled-cluster (EOMCC) theory capable of providing an accurate and balanced description of one- as well as two-electron transitions, abbreviated as δ-CR-EOMCC(2,3), DIP-EOMCC(4h2p){No}, and DEA-EOMCC(4p2h){Nu} or DEA-EOMCC(3p1h,4p2h){Nu}, consistently predict that the 11B+/21A- crossing in both molecules occurs along the bond length alternation coordinate. However, the analogous 11B+ and 21A- potentials obtained with some multireference approaches, such as CASSCF and MRCIS(D), as well as with the linear-response formulation of time-dependent DFT (TDDFT), do not cross. Hence, caution needs to be exercised when studying the low-lying singlet excited states of polyenes with conventional multiconfigurational methods and TDDFT. The multistate many-body perturbation theory methods, such as XMCQDPT2, do correctly reproduce the curve crossing. Among the simplest and least expensive computational methodologies, the DFT approaches that incorporate the contributions of doubly excited configurations, abbreviated as MRSF (mixed reference spin-flip) TDDFT and SSR(4,4), accurately reproduce our best EOMCC results. This is highly promising for nonadiabatic molecular dynamics simulations in larger systems. | 10.1021/acs.jpclett.1c02707 |
pubmed_810_7257 | OBJECTIVE
The objective of this study was to evaluate the effectiveness of the use of irradiation with a low-level laser therapy (LLLT), wavelength 830 nm, for treating pain inherent to tooth movement caused by orthodontic devices, simulated by positioning interdental elastomeric separators.
METHODS
Sixty orthodontic patients were randomly assigned to two groups: GA (ages 12-25 years; mean 17.1 years) was the control, and GB (ages 12-26 years; mean 17.9 years) the intervention group. All patients received elastomeric separators on the mesial and distal surfaces of one of the lower first molars, and immediately after insertion of the separators received irradiation as randomly indicated. The intervention group (GB) received irradiation with LLLT (aluminum gallium arsenide diode), by a single spot in the region of the radicular apex at a dose of 2 J/cm(2) and application along the radicular axis of the buccal surface with three spots of 1 J/cm(2) (wavelength 830 nm; infrared). Control group (GA) received irradiation with a placebo light in the same way. This was a double-blind study. All the patients received a questionnaire to be filled out at home describing their levels of pain 2, 6, and 24 h and 3 and 5 days after orthodontic separator placement, in situations of relaxed and occluded mouth.
RESULTS
The patients in the intervention group (LLLT) had lower mean pain scores in all the measures. The incidence of complete absence of pain (score=0) was significantly higher the intervention group.
CONCLUSIONS
Based on this study, authors concluded that single irradiation with LLLT of wavelength 830 nm efficiently controlled the pain originating from positioning interdental elastomeric separators, to reproduce the painful sensation experienced by patients when fixed orthodontic devices are used. | 10.1089/pho.2012.3338 |
pubmed_955_5728 | Pericardiocentesis and drainage with a silicon rubber line were performed safely in 55 patients via the subxiphoid (80 times) or apical (1 time) approach at the bedside without echocardiographic guidance. The subxiphoid approach, which is close to the posterior of the sternum or the costal cartilage with a small acute-angle (15-30 degrees) to the parietal pericardium in front of the right ventricle, can avoid injuring the heart, liver and lungs. A line with sideholes near the distal end, which provides convenient drainage and has better histocompatibility, can be kept in place for a long period of time (1-82 days). It was also convenient to inject air, drugs or fluid through the line. There were no procedure-related serious complications or deaths. Emergency drainage with the Seldinger technique, especially for small to moderate effusions, is safe and simple. | 10.1536/ihj.35.751 |
pubmed_590_14326 | OBJECTIVE
To evaluate the association between the two single nucleotide polymorphisms located in catechol-O-methyltransferase (COMT) gene and type 2 diabetes mellitus (T2DM)in Han population in Guangdong province.
METHODS
Two tagSNPs (rs4646312 and rs4680) were picked out from COMT gene. Using the SNPscan(TM) Kit, SNP genotyping was then performed, in two cohorts, including 595 cases and 725 controls. Finally, Chi-square test, logistic regression model and other methods were employed for statistical analysis.
RESULTS
The frequencies of TT, CT and CC of rs4646312 appeared to be 304(51.1%), 234(39.3%)and 57 (8.6%) in cases, 323 (44.6%), 319 (44.0%) and 83(11.4%)in controls, respectively. The frequencies of GG,GA and AA of rs4680 were 311(52.4%), 236 (39.8%) and 46(7.8%)in cases, 417(57.7%), 265 (36.6%) and 41 (5.7%) in controls, respectively.
RESULTS
showed that SNP rs4646312 was significantly associated with T2DM both in allelic association analysis (P = 0.020,OR = 1.26, 95%CI:1.04-1.53)and in recessive model (P = 0.022, OR = 1.35, 95% CI:1.05-1.74)after adjustment for sex,BMI and TG. The association between rs4680 and T2DM was not significant, but BMI was remarkably different among the three genotypes of rs4680 after controlling for other factors.
CONCLUSION
SNP rs4646312 of COMT gene was associated with the increased risk of T2DM in Han population in Guangdong province. However, rs4680 was not significantly associated with T2DM. | pubmed_590_14326 |
pubmed_897_4181 | Cortical astrocytes express fast ionotropic receptors for glutamate and ATP, although their role in neurone-glia communication remains controversial. Stimulation of neuronal afferents in mice neocortex triggers complex glial synaptic currents (GSCs) mediated by NMDA, P2X and AMPA receptors and glutamate transporters. In addition, astrocytes demonstrate spontaneous 'miniature' GSCs resulting from quantal release of neurotransmitters. Here, we demonstrate that maturation and aging of the brain of mice (from 1 to 21 months) affect the density of ionotropic receptors in astrocytes and their role in GSCs generation. The AMPA-receptor-mediated component is the largest in young animals and progressively declines with age. The P2X and NMDA components of GSC are smallest in young, maximal in adult (3 and 6 months old) and once more decrease in old mice, probably reflecting the remodelling of neuronal-glial circuitry. Our results demonstrate that fast synaptic transmission between neurones and astrocytes in neocortex that may be involved in information processing in neuronal-glial networks undergoes remodelling during brain maturation and aging. | 10.1111/j.1474-9726.2011.00682.x |
pubmed_661_3310 | The staining characteristics of the enterochromaffin cell system in the human and rat gastrointestinal tract were studied with 3 histochemical procedures--the Masson method, formaldehyde-induced fluorescence (FIF), and immunocytochemical techniques using both monoclonal and polyclonal serotonin antisera. A simple modification of the Masson technique is described and compared with several other modifications of the same technique. The specificities of the 2 antisera were examined with regard to serotonin and other monoamines and their albumin conjugates, monoamine precursors and metabolites, and also to serotonin-related substances. In the intestine, with very few exceptions the same cells reacted positively with the 3 staining methods, but often serotonin immunoreactivity was observed in larger cytoplasmic areas than the other 2 staining reactions. In the antral mucosa, a cell population with the same staining characteristics as mentioned above was seen, but 2 further cell populations were identified--one displaying FIF-argentaffin reactions but no serotonin immunoreactivity, and the other showing the opposite characteristics. At immunostaining, a discrepancy in the staining results between the 2 antisera was noted--a larger number of antral serotonin immunoreactive cells being demonstrated with the polyclonal than with the monoclonal antiserum; this discrepancy disappeared when the polyclonal antiserum was pretreated with C-terminal tetragastrin. A minor discrepancy in the number of stained cells was still observed between the use of immunostaining with monoclonal or with tetragastrin-pretreated polyclonal antiserum, and the use of the FIF-argentaffin reactions. The reason for this discrepancy is unclear. | 10.1016/S0065-1281(86)80077-0 |
pubmed_781_17305 | Hepatitis C virus (HCV) is the world's most common blood-borne viral infection for which there is no vaccine. The rates of vertical transmission range between 3 and 6% with odds 90% higher in the presence of HIV coinfection. Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine. Recently, HCV has been identified as an independent risk factor for preterm delivery, perinatal mortality, and other complications. In this study, we characterized the immune responses that contribute to the control of viral infection at the maternal-fetal interface (MFI) in the early gestational stages. In this study, we show that primary human trophoblast cells and an extravillous trophoblast cell line (HTR8), from first and second trimester of pregnancy, express receptors relevant for HCV binding/entry and are permissive for HCV uptake. We found that HCV-RNA sensing by human trophoblast cells induces robust upregulation of type I/III IFNs and secretion of multiple chemokines that elicit recruitment and activation of decidual NK cells. Furthermore, we observed that HCV-RNA transfection induces a proapoptotic response within HTR8 that could affect the morphology of the placenta. To our knowledge, for the first time, we demonstrate that HCV-RNA sensing by human trophoblast cells elicits a strong antiviral response that alters the recruitment and activation of innate immune cells at the MFI. This work provides a paradigm shift in our understanding of HCV-specific immunity at the MFI as well as novel insights into mechanisms that limit vertical transmission but may paradoxically lead to virus-related pregnancy complications. | 10.4049/jimmunol.1500409 |
pubmed_63_3228 | OBJECTIVES
To investigate the influence of country of residence on depression and well-being among older Europeans, after establishing the between-country measurement invariance of both constructs.
METHODS
We used data from a cross-sectional nationally representative population-based sample of older Europeans, the Survey of Health, Ageing, and Retirement in Europe (SHARE). The analysis sample comprised 13,498 older Europeans from nine countries. The EURO-D was used to measure depression, and a well-being outcome was derived from self-report items available in SHARE. The between-country measurement invariance of both mental health outcomes was established using modern psychometric modeling techniques.
RESULTS
After adjustment for demographic characteristics and the presence of chronic illness, Spain was the country scoring highest on depression and Denmark highest on well-being. Optimal mental health was associated with higher educational attainment and being married.
DISCUSSION
There is considerable between-country heterogeneity in later-life mental health in Europe. The Scandinavian countries, the Netherlands, and Austria, do best (low depression/high well-being), followed by Germany and France, whereas residents of Spain, Italy, and Greece report the worst mental health. | 10.1093/geronb/gbp026 |
pubmed_565_5420 | On the basis of findings emphasizing the role of perceptual consequences in movement coordination, the authors tested the hypothesis that the learning of a new bimanual relative phase pattern would involve the matching of the movement-related sensory consequences (rather than the motor outflow commands) to the to-be-learned pattern. Two groups of participants (n = 10 in each) practiced rhythmically moving their forearms with a phase difference of 30 degrees . In 1 group, a difference in the arms' eigenfrequencies was imposed such that synchronous generation of the left and right motor commands resulted in the required relative phase (30 degrees ), yielding incongruence between the motor commands and their sensory consequences. In the other group, the experimenter imposed no eigenfrequency difference so that the sensory consequences were congruent with the motor commands. Throughout the practice period, performance of both groups was assessed repeatedly for the congruent situation (i.e., no eigenfrequency difference). On those criterion tests, both groups performed the required pattern equally well. The authors discuss that result, which corroborated the hypothesis, from a dynamical systems perspective. | 10.3200/JMBR.37.3.186-196 |
pubmed_698_1114 | At the Ziguinchor regional hospital centre (RHC), the populations participate in the health effort by paying care services and medicines. The financial assessment of the participation of the community at the Ziguinchor RHC, from January 1,1998 to June 30, 2000, did not give good results. CFAF 263,066,092 of receipts have been generated, especially through the sale of medicines (38.85%) and via the obstetrical and gynecological clinic services (13.30%). The expenditures went up to CFAF 267,120,718; 41.87% were given to the staff, and 25.39% were used to buy medicines. Globally, expenditures exceeded receipts. At the beginning of January 1998, CFAF 7,600,524 were left to the Health Committee's budget. At the end of June 2000, there only remained CFAF 3,365,898. The decrease in the budget was expected because the RHC Health Committee board, set since 1984, never been renewed. Its management never followed the present recommendations. The board members, who were arbitrarily elected, didn't respect their commitment and were just represented by the treasurer. The latter had only a financial executive role. The board's decisions, which should have had the agreement of its president, were taken unilaterally by the direction of the RHC. Consequently, expenses evolved in keeping with gains, completely ignoring the use of the state budget. For a successful start of the RHC in the hospital reform, ten recommendations have been put across. The objective is to improve the organization of the Health Committee in order to better answer the population health problems. | pubmed_698_1114 |
pubmed_132_7556 | OBJECTIVE
The "hypothesis-driven interview" was articulated by George Engel as a method of raising and testing hypotheses in the process of building a biopsychosocial formulation and determining the most likely diagnosis. This interview was a forerunner of the modern medical interview as well as the contemporary psychiatric assessment. The objective of this article is to describe the hypothesis-driven interview and to explore its relationship with the contemporary medical interview.
METHOD
The literature on the medical and hypothesis-driven interview was reviewed. Key features of each were identified.
RESULTS
The hypothesis-driven interview shares much with the contemporary medical interview. In addition, it enhances the application of communication skills and allows the interviewer to develop a formulation during the course of the assessment.
CONCLUSION
The hypothesis-driven interview is well suited to the aims of a contemporary psychiatric assessment. | 10.3109/10398562.2011.601462 |
pubmed_697_3133 | BACKGROUND
Assessment of need for intravascular volume resuscitation remains challenging for anesthesiologists. Dynamic waveform indices, including systolic and pulse pressure variation, are demonstrated as reliable measures of fluid responsiveness for mechanically ventilated patients. Despite widespread use, real-world reference distributions for systolic and pulse pressure variation values have not been established for euvolemic intraoperative patients. The authors sought to establish systolic and pulse pressure variation reference distributions and assess the impact of modifying factors.
METHODS
The authors evaluated adult patients undergoing general anesthetics for elective noncardiac surgery. Median systolic and pulse pressure variations during a 50-min postinduction period were noted for each case. Modifying factors including body mass index, age, ventilator settings, positioning, and hemodynamic management were studied via univariate and multivariable analyses. For systolic pressure variation values, effects of data entry method (manually entered vs. automated recorded) were similarly studied.
RESULTS
Among 1,791 cases, per-case median systolic and pulse pressure variation values formed nonparametric distributions. For each distribution, median values, interquartile ranges, and reference intervals (2.5th to 97.5th percentile) were, respectively, noted: these included manually entered systolic pressure variation (6.0, 5.0 to 7.0, and 3.0 to 11.0 mmHg), automated systolic pressure variation (4.7, 3.9 to 6.0, and 2.2 to 10.4 mmHg), and automated pulse pressure variation (7.0, 5.0 to 9.0, and 2.0 to 16.0%). Nonsupine positioning and preoperative β blocker were independently associated with altered systolic and pulse pressure variations, whereas ventilator tidal volume more than 8 ml/kg ideal body weight and peak inspiratory pressure more than 16 cm H2O demonstrated independent associations for systolic pressure variation only.
CONCLUSIONS
This study establishes real-world systolic and pulse pressure variation reference distributions absent in the current literature. Through a consideration of reference distributions and modifying factors, the authors' study provides further evidence for assessing intraoperative volume status and fluid management therapies. | 10.1097/ALN.0000000000001460 |
pubmed_897_859 | Larvae of Aedes albopictus Skuse typically inhabit natural and artificial containers. Since these larval habitats are replenished by rainfall, Ae. albopictus may experience increased loss of immature stages in areas with high levels of rainfall. In this study, we investigated the effects of rainfall and container water level on population density, and oviposition activity of Ae. albopictus. In field and laboratory experiments, we found that rainfall resulted in the flushing of breeding habitats. Excess rain negatively impacted larval and pupal retention, especially in small habitats. When filled with water to overflowing, container habitats were significantly repellent to ovipositing females. Taken together, these data suggest that rainfall triggers population loss of Ae. albopictus and related species through a direct detrimental effect (flushing out) and an indirect effect (ovipositional repellency). | 10.1007/s00484-011-0402-0 |
pubmed_122_3653 | Phenylpropanoids fulfill numerous physiological functions, essential for plant growth and development, as well as plant-environment interactions. Over the last few decades, many studies have shown that exquisite regulatory mechanisms at multiple levels control the phenylpropanoid metabolic pathway. Deciphering this pathway not only provides a greater, basic understanding of plant specialized metabolism, but also enhances our ability to rationally design plant metabolic pathways for future applications. Despite the identification of the participating enzymes of this complex, biosynthetic machinery, we still lack a complete picture of other genes, enzymes, and metabolites essential for regulation and compartmentation/distribution of phenylpropanoids. Compartmentation, as well as distribution, are critical for the fate/functioning of those molecules, and their effective biosynthesis. At the cellular level, we have narrowed down our understanding of these processes to organelles. Furthermore, various, overlapping, but not exclusive scenarios of phenylpropanoid distribution within the cell have also been described. The cross-membrane dynamics, but also intercellular communication of different branches from phenylpropanoid biosynthesis have become an exciting research frontier in plant science. The intra- and intercellular channeling of intermediates by various transport mechanisms and notably membrane transporters could be a meaningful tool that ensures, inter alia, efficient metabolite production. | 10.3389/fpls.2018.01610 |
pubmed_569_19810 | INTRODUCTION
Infective endocarditis is an infection of the endocardial lining of the heart mainly associated with congenital and rheumatic heart disease. Although it is a rare disease in children, it is associated with high morbidity and mortality; death due to infective endocarditis has been reported to be as high as 26% in sub-Saharan Africa.
METHODS
This was a retrospective review of routinely collected data from patient records.
RESULTS
A total of 40 children (71% female) with 41 episodes of infective endocarditis admitted to a general paediatric ward in Addis Ababa, Ethiopia between 2008 and 2013. Age ranged from 7 months to 14 years, with a median of 9 years (Inter quartile Range: 7-12 years). Rheumatic and congenital heart diseases were underlying risk factors in 49% and 51% of cases respectively. Congestive heart failure, systemic embolization and death occurred in 66%, 12% and 7.3% respectively. Death was associated with the occurrence of systemic embolization (P-value=0.03).
CONCLUSION
Rheumatic heart disease was an important predisposing factor for infective endocarditis in Ethiopian children. Late presentations of cases were evidenced by high proportion of complications such as congestive heart failure. A low rate of clinically evident systemic embolization in this study may be a reflection of the diagnostic challenges. High proportion of prior antibiotic intake might explain the cause of significant BCNE. Preventive measures like primary and secondary prophylaxis of rheumatic fever may decrease the associated morbidity and mortality. Early detection and referral of cases, awareness creation about indiscriminate use of antimicrobials, and proper history taking and documentation of information recommended. | 10.11604/pamj.2015.20.75.4696 |
pubmed_537_7648 | The number of patients with methicillin-resistant Staphylococcus aureus (MRSA) before and after discontinuing placement of patients into private rooms was determined. The mean monthly number of patients with MRSA decreased from 34 to 22, and the proportion of S aureus isolates that were MRSA decreased from 34% to 20%. We found no evidence that failure to isolate patients with MRSA resulted in an increased prevalence of MRSA. | 10.1086/647322 |
pubmed_180_4408 | Mycotic aneurysms may arise in the setting of many local or systemic infections. Those of the intracranial circulation are especially worrisome due to their potential to compress vital neural structures and their propensity for rupture with consequent hemorrhage. Mycotic aneurysms of the intracavernous internal carotid artery (ICA) represent an exceedingly rare clinical entity, described in less than fifty published cases. Typically presenting as a cavernous sinus syndrome with signs and symptoms of the underlying infection, they are often missed initially, with diagnosis and treatment commencing for the triggering infection or confused with cavernous sinus thrombophlebitis, which may be additionally coexistent, confounding timely diagnosis of the aneurysmal disease. Compared to non-mycotic aneurysms of the intracavernous ICA, which typically have a benign course, the infectious etiology of the mycotic variety increases their tendency to rupture, precludes surgical clipping as a viable treatment option, and requires institution of prolonged antibiotic therapy prior to definitive intervention. Their critical location, friability, and propensity to occur bilaterally result in an unpredictable risk of rapid neurological decline and death, making the timing and specific nature of treatment a unique dilemma facing the treating physician. This review seeks to discuss the natural history of and management strategies for mycotic aneurysms of the intracavernous ICA with special emphasis on the role, safety, and efficacy of endovascular therapies. | pubmed_180_4408 |
pubmed_131_8394 | The present report describes the first case of well-differentiated nodular lymphocytic lymphoma evolving into Lennert lymphoma of T-cell origin. A 58-year-old white female developed malignant lymphoma, well-differentiated, lymphocytic type, nodular, with focal bone marrow involvement (stage IV) in May 1975. She received 16 cycles of cyclophosphamide and prednisone combination chemotherapy which was completed in October 1976. A complete remission was achieved. In December 1976, she relapsed and was treated with cyclophosphamide, vincristine, bleomycin, and prednisone until May 1977. Lymphadenopathy decreased until August 1978, but then increased again. Biopsy of an axillary lymph node was interpreted as Lennert lymphoma. She received methotrexate, cyclophosphamide, vincristine, adriamycin, and prednisone beginning in September 1978. When last seen in November 1979, she was in partial remission. Lymphoid cells obtained from lymph node which was involved with Lennert lymphoma consisted of 93% standard E-rosettes and 83% gravity E-rosettes. Cytoplasmic immunoglobulin on frozen sections was negative, but acid phosphatase (ACP) and alpha-naphthyl acetate esterase reactions were strongly positive. These findings support a T-cell proliferation in Lennert lymphoma. A review of the literature reveals only four cases of Lennert lymphoma of T-cell origin. | 10.1002/mpo.2950080304 |
pubmed_267_9585 | Lumbar sympathectomy still has an important role in the surgical treatment of occlusive peripheral arterial diseases of the lower limbs located below the inguinal ligament, when the presence of peripheral lesions makes revascularization difficult. A consecutive series of 143 patients who underwent lumbar sympathectomy was considered, and the clinical, angiographic and haemodynamic findings evaluated. Haemodynamic studies on these patients showed a relation between the clinical improvement and the pressure index, measured at the ankle before lumbar sympathectomy. The patients with pressure index values above 0.5 had a symptomatic improvement whereas the patients with a pressure index below 0.3 gave less good results. It is therefore believed that lumbar sympathectomy showed not be considered a second operative choice but an elective operation, especially in patients affected by lesion of the superficial femoral artery, the popliteal artery and its branches, with pressure indices above 0.5 where revascularization is not possible. | pubmed_267_9585 |
pubmed_890_19836 | OBJECTIVE
Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks' with ultrasound parameters at 20±1 weeks' gestation.
METHODS
Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve.
RESULTS
633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks' clinical variables, 15±1 weeks' clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks' were: 0.63 (0.59-0.67), 0.64 (0.60-0.68) and 0.69 (0.66-0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57-0.66), 0.61 (0.56-0.66) and 0.68 (0.64-0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70-0.82), 0.80 (0.75-0.86) and 0.84 (0.78-0.89) with minimal change in the Training datasets.
CONCLUSION
Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry. | 10.1371/journal.pone.0169311 |
pubmed_494_156 | Two cases are reported in which it is suggested that water deprivation in laying hens resulted in urolithiasis as well as acute renal disease. With either condition birds appeared to have died terminally from renal failure with lesions of visceral gout. | 10.1080/03079458208436137 |
pubmed_416_6634 | OBJECTIVE
A high performance liquid chromatographic (HPLC) method was developed for the determination of the amount of ergosterol in house dust, and was examined the feasibility on determination of ergosterol in house dust. According to the established method, different house dusts derived from different functional indoor air was sampled and determined. We expected to regard ergosterol as an indicator of fungal biomass.
METHODS
We picked up dust samples from nine typical functional indoor area to represent different room temperature, ventilation, air conditioning, human activities, pet-feeding, et al, during Dec 2004 to Jan 2005. The house dust was sampled with a dust collector, and filtrated with a filter. Fine house dusts were extracted by ultrasonic blending, filtration, refluxing, saponification and evaporation. High liquid chromatography was carried out and combined with gas chromatography (GC)-mass spectrometry (MS) to analyze the molecular structure.
RESULTS
A linearity association was observed in the range of 0.02 to 0.8 g/L ergosterol. The detection concentration was 0.0005 g/L. The intra-and inter-day relative standard deviations (RSD) were in the range of 10.2% - 11.7% and 4.54% - 7.34%, respectively. The absolute recoveries ranged between 77.1% and 80.1%. Survey results showed the amount of ergosterol differed greatly from the different sampling spots. The amount of ergosterol had a positive correlation with room temperature and people denseness, while had a negative correlation with natural ventilation, briefly. The highest amount was 66.08 microg/g (house dust).
CONCLUSION
The method is sensitive, accurate and feasible. It can examine different ergosterol content in environmental matrix. Followed by GC-MS, the reliability of the results can be further checked. The sampling data show there are different degrees of fungal contamination in typical indoor air of Shanghai City. | pubmed_416_6634 |
pubmed_561_12612 | A 58-year-old woman began to show ataxia at age 45 and dysarthria at age 56. Neurological examination revealed slurred speech, truncal ataxia, and pyramydal sign. Neither history of alcoholism nor hereditary factors were found. The level of serum ammonia was increased. Brain MRI study showed a high signal intensity in the cerebral peduncle and globus pallidus and mild cerebellar atrophy on T1-weighted image. A portal-systemic shunt due to a shunt vessel was found between the left splenic and kidney veins although she did not show any other symptoms or signs due to liver cirrhosis. Her symptoms dramatically improved by an intravenous administration of branched amino acid. The present case suggests an importance in finding a treatable cerebellar ataxia. | pubmed_561_12612 |
pubmed_719_23074 | PURPOSE
To evaluate diabetic retinopathy (DR) outcomes with ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA) treatment in patients with DR and diabetic macular edema (DME) at high risk of progression to proliferative disease.
DESIGN
Post hoc analysis of the phase 3 RIDE (ClinicalTrials.gov identifier, NCT00473382) and RISE (ClinicalTrials.gov identifier, NCT00473330) clinical trials of ranibizumab for the treatment of DME.
PARTICIPANTS
Seven hundred forty-six patients with baseline fundus photographs and randomized for treatment.
METHODS
Diabetic retinopathy outcomes were assessed through month 36 by baseline DR severity level. Diabetic retinopathy severity was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS).
MAIN OUTCOME MEASURES
Two-step or more or 3-step or more improvement or worsening on the ETDRS DRSS and time to new proliferative event (composite end point).
RESULTS
At baseline, most patients were distributed evenly among mild or moderate nonproliferative DR (NPDR; ETDRS DRSS, 35/43), moderately severe or severe NPDR (ETDRS DRSS, 47/53), and proliferative DR (ETDRS DRSS, 60-75; 28.8%, 33.2%, and 31.1%, respectively). At month 24, rates of 2-step or more improvement with ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham treatment were highest among patients with baseline DR levels 47/53 (78.4%, 81.1%, and 11.6%, respectively) compared with patients with baseline DR levels 35/43 (10.3%, 15.8%, and 1.4%, respectively) or 60 through 75 without panretinal photocoagulation (31.0%, 36.4%, and 6.7%, respectively; all ranibizumab vs. sham comparisons, P < 0.05). In patients with baseline DR levels 47/53, ranibizumab treatment reduced the probability of patients experiencing a new proliferative event at month 36 by 3 times compared with sham treatment (12.4% and 11.9% vs. 35.2% for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham, respectively). In patients with baseline DR levels 47/53 who achieved 2-step or more DR improvement, improvements were independent of all assessed baseline characteristics (P > 0.4).
CONCLUSIONS
Ranibizumab treatment resulted in DR improvements in all 3 baseline DR severity subsets examined. The greatest benefits in DR improvement occurred in patients with baseline moderately severe to severe NPDR (DR levels 47/53). Diabetic retinopathy improvements were rapid, clinically meaningful, and sustained through month 36. | 10.1016/j.oret.2018.06.005 |
pubmed_573_10104 | Congenitally corrected transposition of the great arteries is a rare condition accounting for less than 1% of all congenital cardiac diseases. The fundamental nature of this condition involves a blend of atrioventricular as well as ventriculoarterial discordance. Congenitally corrected transposition of the great arteries is classically associated with three additional abnormalities, including ventricular septal defect, right ventricular outflow tract obstruction, and tricuspid valve abnormalities. Patients with this anomaly have been shown to exhibit reduced exercise tolerance as well as reduced health-related quality of life when compared to patients with normal cardiovascular anatomy. We present the case of a 33-year-old active duty lieutenant in the United States Air Force referred to the cardiology clinic for evaluation of valvular heart disease with subsequent discovery of congenitally corrected transposition of the great arteries on cardiac gated computed tomography. | 10.1155/2013/420213 |
pubmed_598_9332 | OBJECTIVES
Animal-assisted therapy (AAT) is a growing field in Australia, and therapy dogs are becoming increasingly common in clinical settings. This paper aims to highlight the current issues facing AAT in Australia and to make recommendations on how to progress the field. We acknowledge that there are several ways that therapy dogs may enhance treatment outcomes for clients, such as reductions in stress and acute anxious arousal, and improvements in engagement and rapport. These psychological and physiological advantages, however, may not be sustained once interaction with the dog ceases. Clinicians require adequate training and support to develop and implement interventions that are based on sound theoretical foundations, and take advantage of the adjunctive benefits of animal presence.
CONCLUSIONS
A series of recommendations are made for the professionalisation of AAT, including the development of consensus definitions, clinical governance, accreditation, research and evaluation. | 10.1177/1039856217749056 |
pubmed_446_2495 | BACKGROUND
Whether hyperbilirubinemia suppresses electrophysiological activity of the neonatal auditory brainstem remains to be investigated.
AIM
To determine whether hyperbilirubinemia suppresses the brainstem auditory electrophysiology in term neonates.
METHODS
Maximum length sequence brainstem auditory evoked response (MLS BAER) was recorded shortly after confirming hyperbilirubinemia in 58 term neonates. Wave amplitudes of the response were analyzed in detail.
RESULTS
Compared with age-matched term controls, the neonates with hyperbilirubinemia showed a significant reduction in the amplitudes of MLS BAER waves III and particularly V at all click rates 91-910/s. The reduction tended to be more significant at higher than lower rates. Wave I amplitude was reduced at 910/s. V/I amplitude ratio was decreased at all click rates. Therefore, the amplitudes of MLS BAER, particularly later, waves were all reduced. The amplitudes of all MLS BAER waves tended to be reduced with the increase in total serum bilirubin level. All wave amplitudes were correlated with the level of total serum bilirubin at some or most click rates.
CONCLUSIONS
Brainstem auditory electrophysiology is suppressed in neonates with hyperbilirubinemia, which related to the severity of hyperbilirubinemia. Wave amplitudes are valuable BAER variables to detect functional impairment of the brainstem and auditory pathway in neonatal hyperbilirubinemia, and are recommended to be used in assessing bilirubin neurotoxicity to the neonatal brain. | pubmed_446_2495 |
pubmed_708_10746 | These experiments examined the responses of articular blood vessels in the rabbit knee to induction of acute joint inflammation by intraarticular injection of 4% kaolin suspension. This produced an inflammatory response, which became evident about four hours after injection. Electrical stimulation of the nerve supply to the knee joint before induction of inflammation produced a biphasic response--an initial vasoconstriction during the stimulation phase followed by dilatation after stimulation stopped. These responses were followed up for eight hours and it was noted that the constrictor response became progressively greater, producing a further 19% decrease in blood flow during nerve stimulation about three hours after the injection of kaolin. The sensitivity of postjunctional alpha adrenoceptors, however, showed still greater increase in the inflamed joint as close intraarterial injection of 10(-6) M adrenaline produced an additional 30% reduction in blood flow four hours after kaolin injection compared with the control response. Possibly, the smaller enhancement of the constrictor response to nerve stimulation in the inflamed joint may reflect sensitisation of prejunctional alpha adrenoceptors in addition to the effects exerted on postjunctional alpha adrenoceptors by the inflammatory process. The dilator response also increased over eight hours, though this rise was less marked. These findings indicate that even over the limited time span of the experiments, significant alterations occurred in factors which influence the calibre of articular blood vessels. | 10.1136/ard.49.7.540 |
pubmed_740_9117 | BACKGROUND
Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma.
METHODS
Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups.
RESULTS
Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group.
CONCLUSIONS
Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid. | 10.1038/s41416-018-0005-1 |
pubmed_254_7425 | Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has been recently identified as a novel inhibitor of multiple tumors; however, its role in glioblastoma (GBM) has not been investigated. This study aimed to evaluate whether LHPP exerts a potential tumor-inhibiting role in GBM. Compared with that in normal tissues, LHPP expression was lower in GBM tissues and various GBM cell lines. LHPP up-regulation in GBM cells markedly reduced their proliferation and invasion, and its knockdown had an oncogenic effect on these cells. Further studies revealed that overexpressed LHPP decreased the levels of Akt and glycogen synthase-3β phosphorylation and down-regulated Wnt/β-catenin signaling. By contrast, LHPP knockdown produced opposite effects. Akt suppression markedly abrogated the activation of Wnt/β-catenin signaling induced by LHPP knockdown. The reactivation of Wnt/β-catenin signaling partially reversed the inhibition of tumor growth in GBM mediated by LHPP overexpression. In addition, LHPP overexpression markedly retarded the tumorigenesis of GBM cells in vivo. These findings revealed that LHPP acts a potential inhibitor of tumor growth in GBM, and its overexpression represses GBM proliferation and invasion by down-regulating Akt and Wnt/β-catenin signaling. This work highlights the crucial role of LHPP in GBM progression and suggests its potential as an anticancer target for the treatment of this disease. | 10.1007/s10863-020-09866-0 |
pubmed_739_283 | Choline acetyltransferase (ChAT, EC 2.3.1.6) is the biosynthetic enzyme for acetylcholine. We have previously shown that multiple ChAT mRNA species with different 5'-noncoding regions are expressed in the rat and mouse. However, the diversity of ChAT mRNA species in human has not completely been elucidated. In this work N1- and N2-type ChAT cDNAs were cloned from a human brain cDNA library and the N-exon located in the human ChAT gene. Polymerase chain reaction analysis indicates that four species of ChAT mRNAs (R-, N1-, N2- and M-types) are produced in human brain and spinal cord. In all human transcripts, the ATG initiation codon in the rat, mouse and pig was replaced by ACG, which does not serve as an initiation codon for translation. In vitro translation and mammalian expression analyses revealed that N1-, N2- and R-type mRNAs give rise to a single 69 kDa enzyme, while M-type mRNA produces both 82 and 69 kDa enzymes. The translation efficiency of M-type mRNA was lower than that of the other mRNA species. Moreover, the translation efficiency of human ChAT mRNAs was considerably lower than that of rat ChAT mRNA, suggesting that the ATG codons for human ChAT are unfavorable for translation initiation compared with the initiation codon for rat ChAT. These results provide rational explanations for the previous reports that human ChAT protein purified from the brain and placenta had 66-70 kDa molecular mass, and that ChAT activity in a single motor neuron of human was far lower than that of other vertebrates. Sequencing of monkey ChAT gene showed that the initiation ATG in rodent ChAT was also replaced by ACA in the monkey. | 10.1016/s0169-328x(96)00231-8 |
pubmed_312_12375 | The intravenous injection of loperamide induced an immediate fall in blood pressure and heart rate in anaesthetized rats. Both effects were inhibited by the opiate antagonists naloxone and MRZ 2266 BS. Bilateral vagotomy also inhibited both effects whereas atropine only reduced the bradycardia, but the combination of atropine and tertatolol suppressed the bradycardia. A high dose of loperamide induced bradycardia in pithed rats. This effect was prevented by MRZ 2266 BS but not by naloxone. It is concluded that loperamide can elicit a vagally mediated reflex involving vagal and sympathetic mechanisms and could stimulate cardiac opiate receptors, probably kappa, both effects leading to bradycardia. | 10.1016/0014-2999(85)90054-8 |
pubmed_9_19021 | Four cases of severe acute Guillain-Barré syndrome (GBS) characterized by severe axonal degeneration are presented. All had electrically inexcitable motor nerves as early as 4 days after onset. The disease was rapid in onset and the residual disability was severe. Two different types of pathology were seen. Nerve biopsies in 3 cases showed severe axonal degeneration without inflammation or demyelination. Autopsy in one of these cases showed that the dorsal and ventral roots were also significantly affected. These cases illustrate the primary axonal form of GBS. Nerve biopsy in the fourth case at day 15 showed marked inflammation and demyelination with axonal degeneration. Contralateral nerve biopsy at day 75 showed almost complete loss of axons. This case illustrates another type of axonal degeneration, that which occurs secondary to inflammation and demyelination. | 10.1016/0022-510x(93)90324-r |
pubmed_361_21818 | Ro 40-5967 is a structurally novel calcium antagonist that binds to the verapamil binding site but has very weak negative inotropic effects compared to verapamil. The goals of the present study were to assess the effects of Ro 40-5967 on myocardial function during ischemia, and to compare them to those of verapamil. For this purpose, in anesthetized dogs where the circumflex coronary artery was cannulated and perfused at controlled pressure, myocardial function was measured using piezo electric crystals implanted into the endocardium. Myocardial distribution of coronary blood flow was assessed using radioactive microspheres. Ischemia was produced by lowering perfusion pressure from 100 to 15 mm Hg in steps. During ischemia, Ro 40-5967 partially prevented the decrease of segmental shortening (p less than 0.01) and increased coronary flow, especially in the endocardium (p less than 0.01). In contrast, verapamil did not improve myocardial function during ischemia. The protective effect of Ro 40-5967 could be partially explained by the decrease of arterial pressure and heart rate induced by Ro 40-5967. However, Ro 40-5967 injected directly inside the coronary artery did not induce systemic effects, but still had protective effects (p less than 0.05). Verapamil injected intracoronary produced severe cardiac depression. We conclude that in the present model during ischemia Ro 40-5967 has no negative inotropic effects, and in contrast to verapamil can improve the myocardial function. | 10.1097/00005344-198911000-00007 |
pubmed_728_10925 | Light responses (ReP) and pre-stimulus membrane potential (PMP) and conductance of photoreceptors of Astacus leptodactylus and Limulus polyphemus (lateral eye) were recorded and changes were observed when the photoreceptor was depolarized by the action of external ouabain of high potassium concentration application. 1 mM/1 ouabain application causes a transient increase of PMP and ReP in Limulus, followed by a decrease which is faster for the ReP (half time time 34 min) than for the PMP (half time 80 min). Irreversible loss of excitability occurs when the PMP is still ca. 40% of the reference value. In both preparations high external potassium concentration leads to total depolarization (beyond zero line to + 10-+ 20 mV) of the PMP and after a time lag of 10 min also to a loss of excitability (intracellular recording). In extracellular recordings (Astacus) the excitability remains at a low level of 15%. The effects are reversible and are similar whether no or 10% external sodium is present. In all experiments the light-induced changes of membrane conductance are about parallel to those of the light response. The fact that the ability of the photosensoric membrane to undergo light-induced conductance changes is membrane potential-dependent is discussed, leading to the explanation that dipolar membrane constituents such as channel forming molecules (probably not rhodopsin) have to be ordered by membrane potential to keep the membrane functional for the photosensoric action. | 10.1515/znc-1977-9-1032 |
pubmed_175_25034 | Resistance to conventional chemotherapy remains a major cause of cancer relapse and cancer-related deaths. Therefore, there is an urgent need to overcome resistance barriers. To improve cancer treatment approaches, it is critical to elucidate the basic mechanisms underlying drug resistance. Increasingly, the mechanisms involving micro-RNAs (miRNAs) are studied because miRNAs are also considered practical therapeutic options due to high degrees of specificity, efficacy, and accuracy, as well as their ability to target multiple genes at the same time. Years of research have firmly established miR-34 as a key tumor suppressor miRNA whose target genes are involved in drug resistance mechanisms. Indeed, numerous articles show that low levels of circulating miR-34 or tumor-specific miR-34 expression are associated with poor response to chemotherapy. In addition, elevation of inherently low miR-34 levels in resistant cancer cells effectively restores sensitivity to chemotherapeutic agents. Here, we review this literature, also highlighting some contradictory observations. In addition, we discuss the potential utility of miR-34 expression as a predictive biomarker for chemotherapeutic drug response. Although caution needs to be exercised, miR-34 is emerging as a biomarker that could improve cancer precision medicine. | 10.1002/jcp.29640 |
pubmed_434_19560 | Stem cells can exist in either active or quiescent states. In the aging hippocampus, adult neural stem cells (aNSCs) shift into a quiescent state, contributing to age-related reductions in hippocampal neurogenesis. Here, we focused on the subventricular zone (SVZ) stem cell niche of the adult forebrain, asking to what extent quiescence-associated changes in aNSCs are initiated between early and middle-age. Immunohistochemical and label retention experiments revealed that the overall output of the SVZ stem cell system was already highly decreased in middle-aged mice (12-months-old) compared with young adult mice (2-month-old), as measured by reduced marker expression for multiple neural precursor sub-populations and diminished addition of SVZ-derived neuroblasts to the olfactory bulbs (OBs). These changes were associated with significant cytological aberrations within the SVZ niche, including an overall atrophy of the SVZ and accumulation of large lipid droplets within ependymal cells, which are key support cells of the SVZ niche. Importantly, the reduced output of the middle-aged SVZ stem cell system correlated with quiescence-associated changes in middle-aged aNSCs. Specifically, while tissue culture experiments showed that young adult and middle-aged forebrains possessed equal numbers of neurosphere-forming aNSCs, the middle-aged neurospheres exhibited differences in their in vitro properties, and middle-aged aNSCs in vivo divided less frequently. These findings demonstrate that aNSCs begin undergoing quiescence-associated changes between early and mid-adulthood in the mouse SVZ, and serve as a useful framework for further studies aimed at defining the early events involved in aging-associated quiescence of aNSCs. | 10.1016/j.neuroscience.2010.11.032 |
pubmed_572_16683 | Resonance Raman spectroscopy (RRS) is a promising technique for investigating samples with low concentrations of single constituents or many different constituents. The wavelength dependent resonance enhancement (resonance profile) of the respective molecule yields information about the targeted species and reveals the optimal wavelength for high resolution RRS. A significant increase of the Raman scattered intensity can already be achieved in the vicinity of the molecules' absorption band (preresonance). Measuring such preresonance and resonance profiles requires precise control of excitation conditions and careful assessment of the spectral accuracy of the setup. We present a comprehensive procedure for the acquisition of preresonance profiles in Raman spectroscopy. An experimental setup for recording the single spectra is combined with an efficient algorithm for data postprocessing. The procedure is demonstrated on amino acids measured in the UV and can be applied to any molecule and wavelength range. | 10.1063/1.4994891 |
pubmed_957_4875 | We derive a quantum version of the classical-optics Wiener-Khintchine theorem within the framework of detection of phase-space displacements with a suitably designed quantum ruler. A phase-space-based quantum mutual coherence function is introduced that includes the contribution of the detector. We obtain an universal equality linking resolution with coherence. This is illustrated with the case of Gaussian states and number states. | 10.1364/OL.467687 |
pubmed_121_15286 | BACKGROUND
Sarcoma of unknown primary (SUP) designates an enigmatic entity with histologic confirmation of a metastatic tumor without an identifiable primary after a thorough diagnostic workup. The term "unknown primary" is heavily debatable given that sarcomas can arise from any tissue that harbors its histological structure. In this review, we discuss the validity of SUP as a distinct entity. Medline/PubMed and Google Scholar were searched from 1990 until April 2020 for publications in the English language reporting on SUP. We excluded articles reporting on cases with sarcomas from known organ sites such as lung or uterine sarcomas as well as synovial sarcomas. The Kaplan-Meier method was used to compute the median overall survival. A total of 26 patients with SUP were identified. The median age at diagnosis was 17.5 years with a similar prevalence among men and women. The tumors most commonly reported were alveolar rhabdomyosarcoma and rhabdomyosarcoma not otherwise specified. Almost two-thirds of the patients were reported to have more than one metastatic site. Among the 13 patients with survival data, the median overall survival was 10.0 months. Two patients underwent autopsy and had their primary culprit identified in the chest wall and paravertebral.
CONCLUSIONS
This review showed that SUP shares with sarcomas of known primary similar clinical features including an aggressive clinical course, generally poor response to chemotherapy, and dismal patient outcomes. Thus, SUP does not appear to display a different natural history and biological properties that would allude to a distinct entity. | 10.1186/s43046-022-00128-1 |
pubmed_784_8066 | Rhizobium species strain NGR234 is the most promiscuous known rhizobium. In addition to the non-legume Parasponia andersonii, it nodulates at least 70 genera of legumes. Here we show that the nodulation genes of this bacterium determine the production of a large family of Nod-factors which are N-acylated chitin pentamers carrying a variety of substituents. The terminal non-reducing glucosamine is N-acylated with vaccenic or palmitic acids, is N-methylated, and carries varying numbers of carbamoyl groups. The reducing N-acetyl-glucosamine residue is substituted on position 6 with 2-O-methyl-L-fucose which may be acetylated or sulphated or non-substituted. All three internal residues are N-acetylated. At pico- to nanomolar concentrations, these signal molecules exhibit biological activities on the tropical legumes Macroptilium and Vigna (Phaseoleae), as well as on both the temperate genera Medicago (Trifoliae) and Vicia (Viciae). These data strongly suggest that the uniquely broad host range of NGR234 is mediated by the synthesis of a family of varied sulphated and non-sulphated lipo-oligosaccharide signals. | 10.1111/j.1365-2958.1992.tb01793.x |
pubmed_210_11747 | OBJECTIVE
To evaluate changes in visual acuity and corneal tomographic outcomes at 6 months after femtosecond-laser assisted implantation of two different types of intracorneal implants in keratoconus.
METHODS
A total of 39 keratoconus eyes implanted with two segments KeraRing (n = 22 eyes) or MyoRing (n = 17 eyes) were enrolled. Tomographic data (Pentacam system, Oculus) were analyzed and correlated with enhancement in uncorrected (UDVA) and corrected distance visual acuity (CDVA). The tomographic indices were front maximum keratometry (Kmax), corneal asphericity (Q-value) on both surfaces, average pachymetric progression indices (PPI), maximum Ambrosio relational thickness (ARTmax), Belin-Ambrósio enhanced ectasia total deviation index (BAD-D), index of surface variance (ISV), vertical asymmetry (IVA), height asymmetry (IHA) and height decentration (IHD).
RESULTS
LogMAR UDVA and CDVA improved 2.1 (p = 0.003) and 0.7 (p = 0.074) lines with KeraRing, and 8 and 2.5 lines with MyoRing (p = 0.001). The highest and lowest mean differences in the tomographic indices between both groups were related to ISV and IHD, respectively. Changes in all indices differed significantly between two groups except for changes in front corneal astigmatism, ARTmax, ISV, IVA, IHD and IHA (p > 0.05). Correlation of changes in CDVA with changes in other parameters was statistically significant only for IHD in the KeraRing group, while changes in in UDVA were significantly correlated with changes in spherical equivalent, back Q-value, ISV, IVA, and IHA only in the MyoRing group.
CONCLUSION
Both implants promote corneal shape regularization and an enhancement in UDVA in keratoconus. A considerable flattening effect and reduction in prolateness in the front corneal surface were observed with MyoRing. | 10.1177/1120672120963449 |
pubmed_675_3416 | The prevalence of and risk factors for uncertainty stress among residents during the COVID-19 pandemic remain unclear. An online cross-sectional survey was conducted to explore and identify the risk factors for high perceived uncertainty stress among the general public in China during the COVID-19 outbreak. Information about the respondents' socioeconomic characteristics, knowledge of and attitudes towards COVID-19, perceived uncertainty stress, social capital, anxiety, and depressive symptoms was collected and analysed. Among the 1205 respondents, 45.3% (546) reported a high level of uncertainty stress. Multiple linear regression analysis indicated that anxiety (β=3.871,P<0.001) and depression symptoms (β=2.458, P<0.001), family residence (in towns or rural areas) (β=0.947, P<0.001), lack of support for local epidemic control strategies (β=1.253, P<0.001), worry about the pandemic (β=1.191, P<0.001), and symptoms of weakness among family members (β=1.525, P=0.002) were positively associated with perceived uncertainty stress. Cognitive social capital (β=-0.883, P<0.001) and social networks (β=-0.726, P<0.001) were negatively, but social participation (β=0.714, P<0.001) was positively associated with perceived uncertainty stress. Our findings identify factors associated with a higher level of uncertainty stress and should be helpful in the consideration of effective policies and interventions for uncertainty stress during the initial phases of public health emergencies. | 10.1080/13548506.2021.1883692 |
pubmed_152_4881 | PURPOSE
The aromatase inhibitors letrozole and anastrozole have been approvedrecently as first-line treatment options for hormone-dependent advanced breast cancer. Although it is established that a proportion of patients who relapse on first-line tamoxifen therapy show additional responses to aromatase inhibitors, it has not been determined whether tumors that acquire resistance to aromatase inhibitors in the first line remain sensitive to second-line therapy with antiestrogens. The aim of this study was to determine whether aromatase-transfected and hormone-dependent MCF-7Ca human breast cancer cells remain sensitive to antiestrogens after: (a) long-term growth in steroid-depleted medium in vitro; and (b) long-term treatment with the aromatase inhibitor letrozole in vivo.
METHODS
In the first approach, a variant of the MCF-7Ca human breast cancer cell line was selected that had acquired the ability to grow in estrogen-depleted medium after 6-8 months of culture. Steroid-deprived UMB-1Ca cells were analyzed for aromatase activity levels, hormone receptor levels, and sensitivity to estrogens and antiestrogens in vitro and in vivo. In the second approach, established MCF-7Ca breast tumor xenografts were treated with letrozole 10 microg/day for 12 weeks followed by 100 microg/day for 25 weeks until tumors acquired the ability to proliferate in the presence of the drug. Long-term letrozole-treated tumors were then transplanted into new mice, and the effects of antiestrogens and aromatase inhibitors on tumor growth were determined.
RESULTS
Steroid-deprived UMB-1Ca breast cancer cells continued to express aromatase activity at levels comparable with the parental cell line. However, compared with MCF-7Ca cells, UMB-1Ca cells expressed elevated levels of functionally active estrogen receptor. The growth of UMB-1Ca cells in vitro was inhibited by the antiestrogens tamoxifen and faslodex and tumor growth in vivo was inhibited by tamoxifen. In the second approach, the time for MCF-7Ca tumor xenografts to approximately double in volume after being treated sequentially with the increasing doses of letrozole was thirty-seven weeks. Long-term letrozole-treated tumors continued to express functionally active aromatase. When transplanted into new mice, growth of the long-term letrozole-treated tumors was slowed by tamoxifen and inhibited more effectively by faslodex. Tumor growth was refractory to the aromatase inhibitors anastrozole and formestane but, surprisingly, showed sensitivity to letrozole.
CONCLUSIONS
Steroid-deprived UMB-1Ca human breast cancer cells selected in vitro and long-term letrozole-treated MCF-7Ca breast tumor xenografts remain sensitive to second-line therapy with antiestrogens and, in particular, to faslodex. This finding is associated with increased expression of functionally active estrogen receptor after steroid-deprivation of MCF-7Ca human breast cancer cells in vitro. | pubmed_152_4881 |
pubmed_347_16524 | Aquatic systems are affected by a variety of anthropogenic activities that decrease water quality through the introduction of organic and inorganic pollutants. To investigate the relationship between fish parasite communities and water quality, metazoan parasites were examined in 140 specimens of the Mozambique tilapia (Oreochromis mossambicus) sampled in three lakes in the Limpopo Province, namely the Luphephe-Nwanedi Dams (regarded as unpolluted), the Flag Boshielo Dam (regarded as moderately polluted) and a return water dam on a mine site (regarded as polluted). The monogenean parasites Cichlidogyrus halli, digenean larval stages of Clinostomum and Diplostomum spp. and a gryporynchid cestode were found in or on O. mossambicus in all the sampled sites. The distribution of monogeneans (Cichlidogyrus sclerosus, Cichlidogyrus dossoui, Cichlidogyrus tilapiae, Scutogyrus longicornis and three Enterogyrus spp.), metacercarial stages of two digeneans (Neascus and Acanthostomum spp.) and nematodes (an unidentified nematode, Contracaecum sp., Paracamallanus cyathopharynx and Procamallanus laevionchus) was limited to the unpolluted and moderately polluted lakes. Larval stages of Diplostomum sp. were present in O. mossambicus collected from the unpolluted and polluted sites. The variability of the calculated infection indices (prevalence, mean abundance and mean intensity) and the parameters of species richness and diversity suggest that the structure of parasite communities are affected by the pollution levels of the water. The unpolluted reference site had the highest species richness and the highest overall parasite abundance values. | 10.4102/ojvr.v79i1.362 |
pubmed_1122_16229 | BACKGROUND
Urea kinetic modeling (UKM) and food records are widely used to assess the dialysis adequacy. Clinicians use these methods in individual patients to decide whether the dialysis prescription should be adjusted. We determined the variation in UKM parameters and dietary intake within individual patients in order to determine the required number of UKM measurements, and the number of food recording days to assess dialysis adequacy and dietary intake reliably.
METHODS
Session-to-session variation in urea reduction ratio (URR), Kt/V, urea distribution volume (UDVDDQ), and protein catabolic rate (PCR) was determined during three mid-week dialysis sessions in 50 stable hemodialysis patients on three-times per week hemodialysis with a Kt/V of 0.98 +/- 0.13 (mean +/- SD). The dialysis prescription was kept constant. The day-to-day variation in dietary protein intake (DPI) and dietary energy intake (DEI) was determined from seven-day food records. The 90th percentile value of the coefficient of variation (CV) was used to determine the number of measurements.
RESULTS
The variation in URR [CV, 2.4% (0.3 to 9.5) median (range)] and in Kt/V [CV, 4.0% (0.6 to 11.6)] was small in the majority of the patients. The variation in UDVDDQ [CV, 4.9% (0.3 to 25.7)] and PCR [CV, 9.3% (0.8 to 28.5)] was considerably larger. The variation in DPI [CV, 17.3% (8.4 to 64.0)] was larger than that in DEI [CV, 12.9% (5.0 to 33.0)]. To assess the URR within +/- 10% of its true value, the average of two measurements was required. Reliable assessment of Kt/V required three measurements. URR and Kt/V could be assessed reliably from a single measurement in 86 and 66% of the patients, but we were not able to distinguish these patients beforehand. Reliable estimation of UDVDDQ required six measurements. The required number of measurements for PCR, DPI, and DEI was determined using a precision of +/- 20%. To assess PCR reliably, three measurements were needed. Estimation of DPI and DEI required seven and five food recording days, respectively.
CONCLUSIONS
The session-to-session variation in URR and Kt/V is small in stable hemodialysis patients. Nevertheless, the averaged value of two to three measurements is required to assess the dose of dialysis reliably. Assessment of dietary intake requires at least three PCR measurements or food records for at least one week. Basing clinical decisions on a single dialysis adequacy assessment is an unjustified practice that should be abandoned. | 10.1046/j.1523-1755.1999.00412.x |
pubmed_286_13072 | Current and emerging issues: psoroptic mange in cattleHighlights from the scanning surveillance networkUpdate on international disease threatsAfrican swine fever in eastern Europe and the risk to the UKThese are among matters discussed in the Animal and Plant Health Agency's (APHA's) disease surveillance report for August 2017. | 10.1136/vr.j4173 |
pubmed_1084_7066 | BACKGROUND
Triple-course vaccination against hepatitis B might sometimes fail to increase antibody titers or maintain it at sufficient levels. The aim of this study was to evaluate the rate of seroprotection in dental students after receiving recombinant hepatitis B vaccine.
METHODS
Anti-HBs levels of 124 dental students who had received triple-course hepatitis B vaccines (scheduled at months 0, 1, and 6) were examined. Titers ≥ 100 mIU/ml were considered as protective. Associations between age, gender and duration of being vaccinated with the titer of anti-HBs were assessed.
RESULTS
The participants' mean age was 24 ± 1.3 years and 93% of them were female. The time passed from receiving the final dose was 3.5 ± 1.4 years. Fifty four percent of the students had protective immune response (95% CI 45.2% to 62.8%), 24.2% had positive but weak immune response (anti-HBs titer was between 10 and 100 mIU/ml), and the rest of the subjects (21.8%) were seronegative after receiving routine HBV vaccination.
CONCLUSION
There was a considerable rate of failure in achieving or maintaining acceptable titer levels following routine vaccination against HBV. Hence, determining serum anti-HBs titer after vaccination is recommended. | pubmed_1084_7066 |
pubmed_336_13701 | OBJECTIVE
The relation between arterial stiffness and atherosclerosis, and specifically the influence of arterial stiffness on plaque composition, is largely unknown. In a population-based study, we investigated the association between arterial stiffness and the presence and composition of carotid atherosclerotic plaques.
APPROACH AND RESULTS
Arterial stiffness was measured in 6527 participants (67.0±8.6 years) using aortic pulse wave velocity (PWV). Presence of carotid atherosclerotic plaques was assessed with ultrasound. Subsequently, 1059 subjects with carotid plaques (>2.5 mm) underwent MRI to assess plaque composition (presence of intraplaque hemorrhage, lipid, and calcification). Generalized estimation equation analyses adjusted for age, sex, mean arterial pressure, heart rate, carotid wall thickening, pulse pressure, and traditional cardiovascular risk factors were used to study the association between PWV and the presence and composition of carotid atherosclerotic plaques. In multivariable analysis, higher PWV was independently related to higher prevalence of carotid atherosclerotic plaque on ultrasound (odds ratio for highest quartile of PWV compared with lowest quartile, 1.24 [95% confidence interval, 1.02-1.51]). Furthermore, higher PWV was associated with intraplaque hemorrhage (age- and sex-adjusted odds ratio per SD increase in PWV, 1.20 [1.04-1.38] and calcification, 1.18 [1.03-1.35]), but not with lipid. After adjustment for cardiovascular risk factors, PWV remained significantly associated with intraplaque hemorrhage (1.20 [1.01-1.43]). Additional adjustment for pulse pressure did not materially affect the effect estimate (1.19 [1.00-1.42]).
CONCLUSIONS
Higher PWV is associated with presence and composition of carotid atherosclerotic plaques, in particular with intraplaque hemorrhage. These findings provide further clues for understanding the development of vulnerable atherosclerotic plaque. | 10.1161/ATVBAHA.113.302603 |
pubmed_177_2177 | This paper describes a cohort study in terms of its design, the research questions answered by cohort studies, common analytic techniques and the strengths and limitations of this type of study. We also describe the main cohort studies of older populations, many of which are available for secondary data analysis. | 10.1093/ageing/afx183 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.