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pubmed_597_10974 | The agranular architecture of motor cortex lacks a functional interpretation. Here, we consider a 'predictive coding' account of this unique feature based on asymmetries in hierarchical cortical connections. In sensory cortex, layer 4 (the granular layer) is the target of ascending pathways. We theorise that the operation of predictive coding in the motor system (a process termed 'active inference') provides a principled rationale for the apparent recession of the ascending pathway in motor cortex. The extension of this theory to interlaminar circuitry also accounts for a sub-class of 'mirror neuron' in motor cortex--whose activity is suppressed when observing an action--explaining how predictive coding can gate hierarchical processing to switch between perception and action. | pubmed_597_10974 |
pubmed_670_12252 | The beta-galactosidases of several mutagenized strains of Escherichia coli K12 which grew on lactobionate were found to be heat labile. Sequence analysis of the lacZ gene (ligated into Bluescript) of one of these strains (E. coli REH4) showed that the only change in the amino acid sequence was a substitution of an Asp for Gly-794. This change caused a dramatic increase of the activity when lactose was the substrate. The kcat of the purified enzyme from E. coli REH4 (G794D-beta-galactosidase) with lactose as the substrate was five to six times as large as the kcat of the normal enzyme with lactose. Purified G794D-beta-galactosidase was, however, less stable to heat and also to chymotrypsin (which cleaves next to Trp-585) than was normal beta-galactosidase. G794D-beta-Galactosidase bound substrates and substrate analog inhibitors less well than did normal beta-galactosidase while planar transition state analog inhibitors were more strongly bound. The ability to bind 2-amino-D-galactose (a positively charged transition state analog inhibitor) was either unaltered or was decreased somewhat. The data showed that the alteration in structure caused an increase in the value of k2 (the rate constant for the step in which the glycosidic bond is cleaved) with each substrate tested (the increase was at least 25-fold when lactose was the substrate) while k3 was decreased about 4-fold (k3 is the rate constant for the common hydrolysis step with each substrate). Since k2 is rate determining when lactose is the substrate of the normal enzyme, the increase in k2 resulted in a large increase in rate despite the fact that the value of k3 decreased. Large rate increases were not found with the other two substrates because the k2 values were not increased by large factors and because the decrease in the value of k3 negated the effects of the increased k2 values. The destabilization of the substrate binding coupled with a stabilization of the binding of a planar transition state is a possible cause of the significant increase in the value of k2 and of the enhanced activity with lactose. | pubmed_670_12252 |
pubmed_1026_19023 | BACKGROUND
Coarctation of the aorta (CoA), presenting with local stenosis of the aorta is involved in many cardiovascular processes. However, there has been little research on the mechanism of coarctation of the aorta.
METHODS
Altered proteins were identified by isobaric tag for relative and absolute quantitation (iTRAQ) technology in 8 participants, and further analysed by heatmap, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Search Tool for the Retrieval of Interacting Gene (STRING). Of these, two vascular structure-related proteins were further validated by using enzyme-linked immunosorbent assay (ELISA) in a new cohort of CoA patients.
RESULTS
39 differentially expressed plasma proteins were first identified in patients with coarctation of the aorta by iTRAQ. Of these, fibulin-1 (FBLN1) and insulin-like growth factor-binding protein complex acid labile subunit (ALS) were considered candidates and further validation also showed that the level of FBLN1 in the CoA group (8.92 ± 2.36 μg/ml) was significantly higher compared with control group (6.13 ± 1.94 μg/ml), and the level of ALS in CoA children (348.08 ± 216.74 ng/ml) was significantly lower than the level in normal children (619.46 ± 274.08 ng/ml).
CONCLUSIONS
The differentially expressed proteins identified in the plasma from CoA patients indicated that they may play critical roles in CoA and that they could potentially be utilized as biomarkers for diagnosis. Altered vascular related proteins were associated with COA. These results provide a foundation for further understanding and studying the aetiology and pathogenesis of coarctation of the aorta. | 10.1186/s13052-020-00830-7 |
pubmed_206_5602 | Percutaneous vertebroplasty (PVP) using polymethylmethacrylate bone cement is frequently used in the treatment of painful osteoporotic vertebral compression fractures in the Netherlands. In three patients there was another indication. A 44-year-old woman suffering from vertebral pain due to an osteolytic lesion caused by multiple myeloma was treated with vertebroplasty of 4 vertebral levels. A 60-year-old woman with progressive complaints of back pain due to an aggressive vertebral haemangioma was treated with vertebroplasty after embolisation had only been partially successful. Lastly, a 50-year-old non-osteoporotic man with back pain persisting for six weeks due to a stable traumatic burst fracture of TIX could not be treated with standard care, i.e. corset and analgesics, because of obesity. He was treated with PVP after a cavity had been created in the vertebral corpus. Vertebroplasty is a minimal invasive procedure resulting in most patients in rapid diminishment of the pain caused by pathological vertebral fractures, which may be present for a longer period and may have different causes. The indication triad for vertebroplasty consists of localised back pain, pain when pressure is applied to the processus spinosus of the fractured level and MRI bone oedema, findings suggestive of microfractures in a pathologically changed vertebral body. The procedure is also suitable in patients with extensive comorbidity or a short life expectancy. | pubmed_206_5602 |
pubmed_222_13061 | OBJECTIVE
To test the hypothesis that aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) may prevent dementia or cognitive impairment.
DESIGN
A two-wave longitudinal study over 3.6 years.
SETTING
A community survey of elderly persons living in Canberra, Australia.
PARTICIPANTS
There were 1045 elderly persons aged 70 at the start of the study; cognitive assessment was obtained at both waves on 588.
MAIN OUTCOME MEASURES
Cognitive functioning was measured using the Mini-Mental State Examination, an episodic memory test, a test of mental speed and the National Adult Reading Test. Dementia was assessed using the Canberra Interview for the Elderly.
RESULTS
On cross-sectional data, those who had been taking NSAIDs or aspirin performed no better on the cognitive tests after account had been taken of other confounding variables. There was no interaction with apolipoprotein E genotype. On longitudinal data, no difference was found between NSAID or aspirin users and controls, either in cognitive decline or incidence of dementia.
CONCLUSIONS
The results do not support the hypothesis that aspirin or NSAIDs have a protective effect, but it remains possible that various sources of measurement error may have attenuated an effect of clinical significance from either type of drug. Conclusive evidence can be obtained only by a prospective trial. | pubmed_222_13061 |
pubmed_1003_8370 | OBJECTIVE
To examine the separate and joint effects of male and female fertility problem (FP) stress and the source of stress (e.g., personal, social, marital) on treatment outcome.
DESIGN
Prospective, epidemiological cohort design.
SETTING
Fertility clinics in Denmark.
PATIENT(S)
Eight hundred eighteen couples who were about to begin a new course of treatment.
INTERVENTION(S)
An FP stress inventory was administered at the start of treatment, and the treatment outcome was evaluated 12 months later.
MAIN OUTCOME MEASURE(S)
Number of treatment cycles in 12-month study period and treatment outcome (i.e., success, no success).
RESULT(S)
Fertility problem stress was associated with a poorer treatment outcome in women (pooled within-groups [WGr] correlation,WGr = .517) and men (WGr = .392) with the effect significantly more pronounced for women (z = 3.19, P<.001). Fertility problem stress arising in the personal and marital domain showed greater associations with treatment outcome than did FP stress from the social domain. Logistic regression indicated that women who reported more marital distress required more treatment cycles to conceive (median 3) than women reporting less marital distress (median 2) (odds ratio [OR] = 1.20: Model chi2(3) = 77.21, P<.001).
CONCLUSION(S)
The findings provide evidence that infertility-related stress has direct and indirect effects on treatment outcome. | 10.1016/j.fertnstert.2004.12.039 |
pubmed_450_17237 | The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase catalyzes the sixth step of the seven-step shikimate pathway. Chorismate, the product of the pathway, is a precursor for the biosynthesis of aromatic amino acids, siderophores and metabolites such as folate, ubiquinone and vitamin K. The shikimate pathway is present in bacteria, fungi, algae, plants and apicomplexan parasites, but is absent in humans. The EPSP synthase enzyme produces 5-enolpyruvylshikimate 3-phosphate and phosphate from phosphoenolpyruvate and shikimate 3-phosphate via a transferase reaction, and is the target of the herbicide glyphosate. The Acinetobacter baumannii gene encoding EPSP synthase, aroA, has previously been demonstrated to be essential during host infection for the growth and survival of this clinically important drug-resistant ESKAPE pathogen. Prephenate dehydrogenase is also encoded by the bifunctional A. baumannii aroA gene, but its activity is dependent upon EPSP synthase since it operates downstream of the shikimate pathway. As part of an effort to evaluate new antimicrobial targets, recombinant A. baumannii EPSP (AbEPSP) synthase, comprising residues Ala301-Gln756 of the aroA gene product, was overexpressed in Escherichia coli, purified and crystallized. The crystal structure, determined to 2.37 Å resolution, is described in the context of a potential antimicrobial target and in comparison to EPSP synthases that are resistant or sensitive to the herbicide glyphosate. | 10.1107/S2053230X16001114 |
pubmed_437_589 | Tumor necrosis factor alpha (TNF-α) plays an important role in the pathogensis of hepatitis C virus (HCV) infection induced liver injury. This study aimed to evaluate the effects of TNF-α inhibition with pentoxifylline (PTX) on concanavalin A (Con A)-induced hepatic injury in rats. The rats were distributed among 3 groups: (i) control group (1 mL saline·week(-1) by intravenous injection (i.v.)); (ii) Con A treatment group (20 mg Con A·(kg body mass)(-1)·week(-1), i.v.), and (iii) rats treated with Con A and with PTX (200 mg PTX·(kg body mass)(-1)·day(-1), per oral) group. Blood samples and livers were collected at the end of weeks 1, 2, 4, and 8 of Con A treatment. Portal pressure (PP) was measured at the end of week 8. The administration of PTX was found to confer significant protection against the injurious effects of Con A on the liver, by reducing serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic TNF-α, and malondialdehyde. Histopathological examination revealed that treatment with PTX significantly suppressed early inflammation, reduced alpha smooth muscle actin, and the apoptosis of hepatocytes induced by Con A. Moreover, PTX significantly (P < 0.05) reduced PP, and quantitative analyses of the area of fibrosis induced by treatment with Con A showed a significant reduction at the end of week 8. We conclude that rats treated with PTX revealed a more or less normal hepatocyte architecture as well as marked improvement in fibrosis and PP. | 10.1139/cjpp-2014-0085 |
pubmed_240_4575 | Octreotide is a widely used synthetic somatostatin analogue that significantly improves the management of neuroendocrine tumours (NETs). Octreotide acts through somatostatin receptors (SSTRs). However, the molecular mechanisms leading to successful disease control or symptom management, especially when SSTRs levels are low, are largely unknown. We provide novel insights into how octreotide controls NET cells. CNDT2.5 cells were treated from 1 day up to 16 months with octreotide and then were profiled using Affymetrix microarray analysis. Quantitative real-time PCR and western blot analyses were used to validate microarray profiling in silico data. WST-1 cell proliferation assay was applied to evaluate cell growth of CNDT2.5 cells in the presence or absence of 1 µM octreotide at different time points. Moreover, laser capture microdissected tumour cells and paraffin embedded tissue slides from SI-NETs at different stages of disease were used to identify transcriptional and translational expression. Microarrays analyses did not reveal relevant changes in SSTR expression levels. Unexpectedly, six novel genes were found to be upregulated by octreotide: annexin A1 (ANXA1), rho GTPase-activating protein 18 (ARHGAP18), epithelial membrane protein 1 (EMP1), growth/differentiation factor 15 (GDF15), TGF-beta type II receptor (TGFBR2) and tumour necrosis factor (ligand) superfamily member 15 (TNFSF15). Furthermore, these novel genes were expressed in tumour tissues at transcript and protein levels. We suggest that octreotide may use a potential novel framework to exert its beneficial effect as a drug and to convey its action on neuroendocrine cells. Thus, six novel genes may regulate cell growth and differentiation in normal and tumour neuroendocrine cells and have a role in a novel octreotide mechanism system. | 10.1371/journal.pone.0048411 |
pubmed_647_4146 | The ability of electrodermal variables to predict negative symptoms and functional outcome over a 1-year period in schizophrenia was investigated in 78 young, recent-onset outpatients. Patients were stabilized on standardized medication and largely free of psychotic symptoms. Higher levels of both tonic (skin conductance level, nonspecific skin conductance response rate) and phasic (number of skin conductance orienting responses) activity were associated with more negative symptoms and with a combination of poorer social and occupational outcome at 1-year follow-up. This pattern was seen in both male and female patients, and in older and younger patients. Results are interpreted as suggesting that high levels of arousal and overreactivity to the environment may interfere with efficient cognitive processing in schizophrenia, contributing to poor outcome, and that negative symptoms might partially serve as a means of coping with overarousal. | 10.1111/j.1469-8986.2005.00300.x |
pubmed_508_10929 | OBJECTIVE
Cardiovascular diseases are the most common cause of death in patients with renal failure. Glomerular filtration rate (GFR) is used for the assessment of the renal functional status. In this study we aimed to examine the association between severity of coronary stenosis and renal function by quantifying the coronary lesions, angiographically and calculating the renal function with the use of GFR.
METHODS
Forty-three patients with decreased renal function (calculated GFR<80 ml/min) with a mean age of 67.8+/-9.0 years and 49 patients without impaired renal function (calculated GFR>/=80 ml/min) with a mean age of 52.5+/-10.3 years were studied consecutively from March 2005 to September 2005. Glomerular filtration rate was calculated according to a given formula. All patients underwent selective coronary artery angiography and Gensini scoring system was used for the detection of severity of coronary atherosclerosis.
RESULTS
In linear regression analysis, a negative correlation was found between renal function and the severity of coronary atherosclerosis (r=0.326, p=0.002). All patients were classified into quartiles of Gensini score level. In multivariate analysis, the multiple-adjusted odds ratio (OR) of the risk of decreased renal function was 0.99 (95% CI 0.24-4.15) for quartile 2, 4.38 (95% CI 1.11-17.20, p=0.03) for quartile 3, and 7.01 (95% CI 1.72-28.61, p=0.007) for quartile 4 of Gensini score level compared with the quartile 1.
CONCLUSION
Coronary atherosclerosis quantified by Gensini score is significantly associated with the severity of decreased renal function and this association is independent of age and other cardiovascular risk factors. | pubmed_508_10929 |
pubmed_835_26443 | The continual discharge of emerging inorganic pollutants into natural aquatic systems and their negative effects on the environment have motivated the researchers to explore and develop clean and efficient water treatment strategies. Electrocoagulation (EC) is a rapid and promising pollutant removal approach that does not require any chemical additives or complicated process management. Therefore, inorganic pollutant treatment via the EC process is considered one of the most feasible processes. The potential developments of EC process may make the process a wise choice for water treatment in the future. Thus, the present study mainly focuses on the use of EC technology to remove nutrients and other emerging inorganic pollutants from water medium. The operating factors that influence EC process efficiency are explained. The major advancement of the EC technique as well as field-implemented units are also discussed. Overall, this study mainly focuses on emerging issues, present advancements, and techno-economic considerations in EC process. | 10.1016/j.chemosphere.2022.135756 |
pubmed_12_16351 | In 1980 the C-terminal pentapeptide LGLAR (C3a 73-77) was described (Caporale, L. H. et al. J. Biol. Chem. 1980, 255: 10758) as the minimal sequence inducing a C3a-specific activity. We have synthesized C3a-analogue peptides connected to non-peptidic acyl residues known to potentiate biological activity. Starting from the acylated hexapeptide fluorenylmethoxycarbonyl(Fmoc)-aminohexanoyl(Ahx)-ALGLAR+ ++, a related series of shorter peptides was synthesized. C3a-specific activity was measured as ATP release from guinea pig platelets. Even the tripeptide LAR, acylated with Fmoc-Ahx, exhibited C3a-specific activity. With 0.34% C3a activity, it was even more potent than the native LGLAR sequence which has 0.01% activity. N-terminal extension of the acylated tripeptide LAR by adding one to three alanines increased activity tenfold up to 3.26% (Fmoc-Ahx-AAALAR), while N-terminal addition of three glycine residues (Fmoc-Ahx-GGGLAR) only increased activity to 0.83% of native C3a. Furthermore, a stimulus-specific desensitization could be observed. Fmoc-Ahx-R and Fmoc-Ahx-AR exhibited neither activity nor desensitizing capacity, but the addition of four alanines to the dipeptide AR led to a sequence (Fmoc-Ahx-AAAAAR) with a C3a-specific activity of 0.14%. Even arginine prolonged N-terminally with five glycines (Fmoc-Ahx-GGGGGR) exhibited some C3a-specific activity so that for biological activity only the appropriate presentation of arginine seems to be essential. | 10.1002/eji.1830200709 |
pubmed_301_12529 | We prospectively studied 2140 clinically healthy men to assess the influence of smoking on longitudinal decline in one-second forced expiratory volume (FEV1.0). All the subjects had annual medical checks including pulmonary function tests from 1995 to 1999. The mean values +/- standard deviations of annual decreases in FEV1.0 (slope) were 22 +/- 49 mL/year in non-smokers, 26 +/- 52 mL/year in former smokers, and 33 +/- 57 mL/year in current smokers (p < 0.01; non-smokers vs. current smokers). The adjusted slope (slope divided by predicted value of FEV1.0, per year) in current smokers was also greater than that in non-smokers (p < 0.01). Multiple regression analysis revealed that initial age, height, FEV1.0, and smoking status were significant parameters for determining the slope. This study clearly showed that smoking is an important risk factor foracceleration of the aging-related longitudinal decline in pulmonary function in Japanese men. | pubmed_301_12529 |
pubmed_214_20499 | Heat-treated succinite modified under air, oxygen or inert gas atmosphere to improve its colour and clarity, was studied with Fourier-Transform Infrared and Raman spectroscopy, and referenced to variously altered untreated samples. For treated amber, the macroscopic observations revealed diagnostic features such as (1) the presence of discoidal " sun sparkles" inside the crumbs; (2) unusual colours (e.g. dark red) for transparent specimens; (3) mottled colour patches in "beeswax" and "dragon's blood" amber; (4) luminescence quenching; and (5) significant reduction of pine-tree resinous smell. On FTIR spectra the heat treatment of succinite is mainly marked by: (1) the intensity decrease of 2932 cm-1 band (>CH2 and -CH3), followed by the intensity increase of line at 1732 cm-1; (2) the shifts of the band from ν(C = O) towards lower wavenumbers (from 1735 cm-1 to 1714 cm-1); (3) the decrease of intensity of the band at 888 cm-1 ((=CH2 or -CH = CH-); (4) some slight distortion of "Baltic shoulder" in the region 1100-1300 cm-1. The Principal Component Analysis applied to FTIR spectra enabled to distinguish not only untreated amber from treated one, but also recognize the modifications made under oxygen conditions from the ones in an inert gas. On RS spectra of the treated Baltic amber, the heat modifications are indicated by: (1) slight value increase of the relative intensity ratio I1650/1445 compared to untreated succinite; (2) the shift of bands near 1650 (C = C) and 1445 cm-1 (CH2, CH3) towards higher wavenumbers. | 10.1016/j.saa.2022.121404 |
pubmed_355_20843 | This review of the empirical literature on the relationship between asthma and emotion presents an explanatory model of the connection between them. Asthmatics tend to report and display a high level of negative emotion, and asthma exacerbations have been linked temporally to periods of heightened emotionality. Causality may be bidirectional. Hypothesized mediators for the relationship between asthma and emotionality include vagal and alpha-sympathetic hyperreactivity, predominant obstruction in the larger airways, individual response stereotypy, direct effects of emotion-related facial muscle tension on the airways, the emotional effects of asthma medications, heightened respiratory drive, and hyperventilation. Predictions are presented for research on this model of asthma and emotion, and for the psychological treatment of asthma. | 10.3109/02770909309066375 |
pubmed_175_7571 | PURPOSE
To determine patterns of failure, clinical outcomes, and prognostic factors among pediatric patients treated with radiation therapy for parameningeal alveolar rhabdomyosarcoma.
METHODS AND MATERIALS
We evaluated clinical and treatment planning records of patients aged ≤21 years with parameningeal alveolar rhabdomyosarcoma treated with definitive or adjuvant radiation therapy at our institution. The Kaplan-Meier product limit method assessed disease control and survival; the log-rank test was used to evaluate prognostic impact.
RESULTS
We identified 24 patients with a median age of 3.5 years (range, 1-20) treated between 2009 and 2016. The median follow-up was 2.4 years for all (range, 0.3-5.6) and 3.2 years for living patients (range, 0.7-5.6). Most patients had group III (96%), node-negative (67%), positive FOX fusion status (63%) disease, and intracranial extension (54%). The paranasal sinus was the most common subsite (29%). All patients were treated with concurrent chemotherapy and proton radiation therapy with a median dose of 50.4 Gy relative biological effectiveness (range, 41.4-59.4) at a median 13 weeks after induction chemotherapy (range, 3-25). The 3-year local control, regional control, disease-free survival, and overall survival rates were 66%, 94%, 40%, and 58%, respectively. Median time to any failure was 0.5 years (range, 0.2-2.1). N1 disease and intracranial extension (ICE) portended inferior overall survival (P = .002 and .02, respectively). Female sex portended better local control (P = .05). All 7 patients with distant metastases as the first site of recurrence had central nervous system metastases. Age <4 years, absence of ICE, N0 disease, and primary tumor <5 cm were associated with a statistically significant improvement in freedom from distant metastases.
CONCLUSIONS
Although regional nodal failures were rare, in-field local recurrences and leptomeiningeal progression in those with ICE suggest the need for modification of local and central nervous system therapies. | 10.1016/j.ijrobp.2020.01.035 |
pubmed_962_20597 | The present study was undertaken to determine whether neutrophilic granulocytes leave the vascular bed and enter body tissues, particularly the lung, in pathogen-free mice under normal steady state conditions and also under inflammatory stress. Tissues from normal mice and from mice with granulocytosis-producing tumor were processed for electron microscopic studies. Neutrophils have not been seen outside the capillary or in the pulmonary epithelium in alveoli under normal steady state or in mice with leukocyte counts of 300,000/mm3 in which capillaries were replete with neutrophils. Emigration of neutrophils outside the capillaries was observed under inflammatory conditions. Granulocytes were also observed to be concentrated for destruction in the spleen, perhaps the major site for removal of granulocytes. In the pathogen-free mice granulocytes did not appear to leave blood vessels and enter tissues. | pubmed_962_20597 |
pubmed_1008_8403 | The acute lymphoblastic leukemia- (ALL) associated membrane antigen is a single glycosylated polypeptide of approximate m.w. of 100,000 (gp100), containing no intrachain disulfide linkages. Approximately 50% of gp100 will bind to lentil lectin, whereas 100% will bind to the lectin from Ricinus communis. Both lentil-binding and lentil nonbinding forms of the antigen appear to be identical by 2-dimensional isoelectric focusing/SDS polyacrylamide gel electrophoresis and peptide mapping. Carbohydrate, although contributing approximately 20 to 25% of the m.w., appears not to be involved in the antigenic site of the ALL antigen as judged by precipitation of a molecule after tunicamycin treatment of cells or glycosidase digestion. Charge shift electrophoresis and labeling with the lipophilic nitrene reagent hexanoyl diiodo-N-(4-azido-2-nitrophenyl)-tyramine suggests that the cALL antigen is probably not an integral membrane protein; however, it remains tightly bound to the plasma membrane after subcellular fractionation. A glycoprotein of the same m.w. has been detected by immunoprecipitation on bone marrow cells of nonleukemic patients. serologic studies indicate that the cALL-associated antigen is found on the terminal transferase-positive lymphoid cells, and it therefore seems likely that the gp100 molecule is a normal gene products of lymphocyte precursors. | pubmed_1008_8403 |
pubmed_1109_9249 | The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed. We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II). Blood was taken once in Control I and 4 times (every month) in Control II. In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively. Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I. In Control II, the similar differences as compared to Control I were observed throughout the study. Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E. COPD is accompanied by oxidative stress. A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters. | 10.1155/2013/897075 |
pubmed_851_10309 | Genetic testing is routinely performed on infants with critical congenital heart disease (CHD). This project reviewed the effect of implementing a genetic testing protocol in this population. Charts of infants with critical CHD were reviewed for genetic testing and results across two time periods: the time before implementation of a genetic testing protocol (pre-protocol) and the time after implementation (post-protocol). The use of karyotype, 22q11.2 Deletion testing, and chromosomal microarray were compared across these two time periods. Records of 891 infants were reviewed. 562 (63%) had at least one of the target genetic tests completed. During the pre-protocol time period, 66% of patients who had genetic testing underwent multiple tests versus 24% during the post-protocol time period (p < 0.01). The rate of patients who underwent genetic testing increased from 60% in the pre-protocol time period to 77% in the post-protocol time period (p < 0.01). The rate of diagnosis of genetic conditions during the pre-protocol period was 26% versus 36% during the post-protocol period (p = 0.01). There was a reduction in cost to patients by $5105.59 per diagnosis during the post-protocol period. Patients with critical CHD in the post-protocol period were less likely to undergo multiple genetic tests and more likely to have a diagnosis of genetic disease. In addition there was a significant reduction in cost per diagnosis during the post-protocol time period. Genetic testing protocols for infants with critical CHD promoted more efficient use of genetic testing and increased the rate of diagnosis of genetic conditions in this population. | 10.1007/s00246-017-1685-7 |
pubmed_257_13363 | Rats were trained to forage 2 h daily in a zigzag alley at -15 degrees C. On experimental days food was placed in large amounts at a 1-, 4-, or 16-m distance from a warm shelter. The mass of food ingested and hoarded in the shelter by the rats was then recorded. The rats' body weights were depressed progressively by spacing the sessions with access to food, and then the animals were allowed to recover their initial body weight. The results showed that 2-h food intake was constant and did not vary as a function of body weight loss or the distance to reach the food (cost). On the other hand, the mass of food hoarded was a linear increasing function of body weight loss below the hypothetical set point for body weight and a decreasing linear function of the distance to the food. The linear regression of the mass of food hoarded on body weight with a negative slope (b) adequately depicted the rat's hoarding behavior: mass hoarded = a + b (body wt). The slope of this function decreased with increasing cost of food procurement. It is concluded that 1) the main response of the rat to starvation is food hoarding rather than ingestion and 2) the estimation of the body weight set point from hoarding is not affected by the costs of food procurement. | 10.1152/ajpregu.1989.257.4.R952 |
pubmed_476_16568 | Batten disease is a rare group of neurological diseases, specifically called neuronal ceroid lipofuscinosis. This is a genetic disorder and usually manifests during childhood. Batten disease is fatal and there is currently no proven cure. However, there are certain treatment methods that show potential in mitigating the aftermath of the disease. This review will explore the application and effectiveness of antiepileptic drugs, anticonvulsants, and vitamin C in multiple scenarios to treat Batten disease. Anticonvulsants are a broad group of medications that are used to treat epileptic seizures. Epileptic seizures are a big indicator of Batten disease, making anticonvulsants a potential treatment for Batten disease patients. Antiepileptic drugs also work to stop seizures by decreasing neurological excitation, thus for the same reason are often grouped alongside anticonvulsants and are being investigated as a promising way to help Batten disease patients. Vitamin C helps maintain the integrity of several intracellular processes in the central nervous system, which makes it a possible candidate for treating Batten disease. The known effects of anticonvulsants, antiepileptic drugs, and vitamin C on Batten disease are very limited and should be considered more often by healthcare professionals because of their potential effects on patients with Batten disease. | 10.7759/cureus.21745 |
pubmed_650_1688 | We have characterized the surface phenotype and function of long-lived, Ag-specific memory CD4+ T cells generated in vivo by immunization with keyhole limpet hemocyanin (KLH). CD4+ T cells from the spleens of mice primed more than 2 mo previously with KLH, produced high levels of IL-2 and IL-3, and low levels of IL-4 and IFN-gamma in response to in vitro restimulation with specific Ag. The KLH-primed T cells mediated carrier-specific helper activity for the antibody production by NIP-primed B cells in secondary in vitro responses to NIP-KLH. Subsets of CD4+ T cells from KLH-primed mice were isolated on the basis of surface CD45RB (23G2) by magnetic separation and were examined for functional capacity in several assays of Ag-specific recall. Virtually all of the secretion of IL-2, IL-3, IL-4, and IFN-gamma in response to restimulation with Ag in vitro was associated with, and considerably enriched in, the CD45RB- subset of CD4+ T cells. Similarly, carrier-specific helper function and Ag-specific proliferation in vitro were also confined to the CD45RB-, CD4+ subset of T cells, confirming the previous association of this surface phenotype with memory Th cell activity. We also examined expression of the lymphocyte homing receptor, MEL-14 (gp90MEL), which is required for lymphocyte extravasation to peripheral lymph nodes and is present in high levels on naive T cells. MEL-14 positive and negative subsets of CD4+ T cells from long term KLH-primed mice were evaluated for Ag-specific memory function in terms of lymphokine production, Ag-induced proliferation, and helper activity. Each of these functions was associated exclusively with the MEL-14- subset of CD4+ T cells, which exhibited responses comparable to the CD45RB- subset. These data indicate that memory Th cell function in the spleen is contained within the MEL-14-, CD45RB- subset of CD4+ T cells and suggest that memory helper cells may have different patterns of recirculation from naive T cells. | pubmed_650_1688 |
pubmed_1097_4274 | Biosurfactants are a group of microbial molecules identified by their unique capabilities to interact with hydrocarbons. Emulsification and de-emulsification, dispersion, foaming, wetting and coating are some of the numerous surface activities that biosurfactants can achieve when applied within systems such as immiscible liquid/liquid (e.g., oil/water), solid/ liquid (e.g., rock/oil and rock/water) and gas/liquid. Therefore, the possibilities of exploiting these bioproducts in oil-related sciences are vast and made petroleum industry their largest possible market at present. The role of biosurfactants in enhancing oil recovery from reservoirs is certainly the best known; however they can be effectively applied in many other fields from transportation of crude oil in pipeline to the clean-up of oil storage tanks and even manufacturing of fine petrochemicals. When properly used, biosurfactants are comparable to traditional chemical analogues in terms of performances and offer advantages with regard to environment protection/conservation. This chapter aims at providing an up-to-date overview of biosurfactant roles, applications and possible future uses related to petroleum industry. | 10.1007/978-1-4419-5979-9_10 |
pubmed_882_3760 | PURPOSE
To compare patient-reported and clinician-reported outcomes, and radiographic results between patients who had had revision ACL reconstruction and those who had had primary ACL reconstruction.
DESIGN
Systematic review and meta-analysis
DATA SOURCES
The MEDLINE, CINAHL, EMBASE and SPORTDiscus electronic databases were searched on 6 August 2015, using 3 main concepts: (1) revision ACL reconstruction, (2) primary ACL reconstruction and (3) treatment outcomes.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Articles that compared patient-reported or clinician-reported outcomes or radiographic results between patients who had had revision ACL reconstruction and those who had had primary surgery with a minimum of 2 years follow-up were included. The outcomes evaluated were the Lysholm Knee Scoring Scale, objective International Knee Documentation Committee (IKDC) classification, Tegner Activity Scale, side-to-side difference in anterior tibial translation measured with KT-1000/2000 arthrometer, pivot shift test, tibiofemoral osteoarthritis grading on plain radiographs and subsequent knee surgeries.
RESULTS
8 studies (300 revision ACL reconstructions and 413 primary ACL reconstructions) were included in the meta-analysis. Patients who had had revision surgery reported inferior Lysholm Knee Scoring Scale scores (mean difference: 7.8 points), had inferior clinician-reported knee function as assessed with the objective IKDC classification (IKDC category A: 27% vs 57%; IKDC category C or D: 22% vs 8%) and pivot shift test (grade II or III: 7% vs 2%), and more radiographic evidence of tibiofemoral osteoarthritis (50% vs 25%) compared with patients who had had primary surgery.
CONCLUSIONS
Revision ACL reconstruction restored similar anterior-posterior knee laxity compared with primary ACL reconstruction. Patients who had had revision surgery reported inferior Lysholm Knee Scoring Scale scores, had inferior clinician-reported knee function and more radiographic signs of tibiofemoral osteoarthritis compared with patients with primary ACL reconstruction. | 10.1136/bjsports-2015-094948 |
pubmed_832_13472 | AIMS
We sought to determine the diagnostic performance, clinical profiles and outcomes of anomalous aortic origin of coronary arteries (AAOCA) using a standardised echocardiographic approach in young adults and athletes.
METHODS
In 2015-2019, we screened 5998 outpatients (age 16 years (Q1-Q3: 11, 36)), referred for routine echocardiography, using four specific echocardiographic windows: parasternal short/long axis and apical 4/5-chambers view. Coronary CT confirmed AAOCA. For the performance analysis, 300 coronary-CT scans were available; two independent and double-blinded physicians retrospectively reviewed echocardiographic images.
RESULTS
A total of 47 AAOCA was diagnosed; the overall prevalence was 0.0078%. Over 5 years, we found a significant increment of AAOCA diagnostic rate (P for trend=0.002). Syncope (n=17/47) and palpitations (n=6/47) were prevalent symptoms. All patients suspended sports activity at the diagnosis. Twenty-seven patients underwent surgery, while 20 underwent a conservative medical treatment. All patients are alive at a median follow-up of 3±1.6 years; only surgical repairs restarted their activity. Our method showed better sensitivity than traditional short-axis evaluation: 93% vs 83%, p=0.0030 (AUC 0.96 (95% CI 0.92, 0.99) and AUC 0.89 (95% CI 0.83, 0.95), respectively), with a good interobserver agreement (95%, k=0.83, p<0.001).
CONCLUSIONS
The application of a standardised echocardiographic approach for AAOCA detection led to a significantly increased rate of identified anomalies. This approach demonstrated higher sensitivity than the traditional echocardiographic assessment. Implementing this protocol in clinical practice may help improve the AAOCA diagnosis in young adults and athletes.
TRIAL REGISTRATION NUMBER
NCT04224090. | 10.1136/openhrt-2020-001495 |
pubmed_351_13499 | This in vitro study compared the antimicrobial effect of several at-home bleaching agents and an oral antiseptic against anaerobic bacteria that are commonly found in the oral cavity. Zones of inhibition produced by Rembrandt Lighten Bleaching Gel, Opalescence, and Peroxyl were measured and compared. All the materials produced zones of inhibition with the five bacteria used in the study. | 10.1111/j.1708-8240.1992.tb00668.x |
pubmed_329_15967 | BACKGROUND
Women are an increasing minority of prisoners worldwide, and most are of childbearing age. Prisons offer unique opportunities for improving the pregnancy outcomes of these high-risk women, and no systematic review to date has looked at their care. This systematic review identified studies describing models of perinatal health care for imprisoned women which report maternal and child health and care outcomes.
METHODS
We systematically searched for literature published between 1980 and April 2014. Studies were eligible if they included a group of imprisoned pregnant women, a description of perinatal health care and any maternal or infant health or care outcomes. Two authors independently extracted data. We described relevant outcomes in prisons (including jails) under models of care we termed PRISON, PRISON+ and PRISON++, depending on the care provided. Where outcomes were available on a comparison group of women, we calculated odds ratios with 95 % confidence intervals.
RESULTS
Eighteen studies were reported, comprising 2001 imprisoned pregnant women. Fifteen were in the US, two in the UK and one in Germany. Nine contained a comparison group of women comprising 849 pregnant women. Study quality was variable and outcome reporting was inconsistent. There was some evidence that women in prisons receiving enhanced prison care, PRISON+, were less likely to have inadequate prenatal care (15.4 % vs 30.7 %, p < 0 · 001), preterm delivery (6.4 % vs 19.0 %, p = 0 · 001) or caesarean delivery (12.9 % vs 26.5 %, p = 0 · 005) compared to women in prisons receiving usual care (PRISON). Women participating in two PRISON++ interventions, that is, interventions which included not only enhanced care in prisons but also coordination of community care on release, demonstrated reductions in long term recidivism rates (summary OR 0 · 37, 95 % CI 0 · 19-0 · 70) compared to pregnant women in the same prisons who did not participate in the intervention.
CONCLUSIONS
Enhanced perinatal care can improve both short and long-term outcomes but there is a lack of data. Properly designed programmes with rigorous evaluation are needed to address the needs of this vulnerable population. The cost to mothers, children and to society of failing to address these important public health issues are likely to be substantial.
TRIAL REGISTRATION
PROSPERO registration: CRD42012002384 . | 10.1186/s12884-016-1080-z |
pubmed_648_7962 | Programmable nonuniform deformation is of great significance for self-shape-morphing systems that are commonly seen in biological systems and also has practical applications in drug delivery, biomedical devices and robotics, etc. Here, we present a novel gradient four-dimensional (4D) printing method toward biomimetic nonuniform, dual-stimuli self-morphing. By modeling and printing graded active materials with water swelling properties, we can configure continuously smooth gradients of volume fraction of the active material in bilayer structures. The variation of swelling ratio mismatch between the two layers can be delicately regulated, which results in the programmable nonuniform shape transformation. The shape-shifting results can be predicted by the established mathematical model and computational simulations. Furthermore, we demonstrate dual-stimuli self-morphing structures by printing the graded water-responsive elastomer materials onto a heat-shrinkable shape memory polymer, which could produce different shape changes in response to humidity and different temperatures. This method pioneers a versatile approach to broaden the design space for 4D printing and will be compatible with a wide range of active materials meeting various requirements in diverse potential applications. | 10.1021/acsami.9b17577 |
pubmed_425_14571 | BACKGROUND
Artificial intelligence (AI)-based technologies develop rapidly and have myriad applications in medicine and health care. However, there is a lack of comprehensive reporting on the productivity, workflow, topics, and research landscape of AI in this field.
OBJECTIVE
This study aimed to evaluate the global development of scientific publications and constructed interdisciplinary research topics on the theory and practice of AI in medicine from 1977 to 2018.
METHODS
We obtained bibliographic data and abstract contents of publications published between 1977 and 2018 from the Web of Science database. A total of 27,451 eligible articles were analyzed. Research topics were classified by latent Dirichlet allocation, and principal component analysis was used to identify the construct of the research landscape.
RESULTS
The applications of AI have mainly impacted clinical settings (enhanced prognosis and diagnosis, robot-assisted surgery, and rehabilitation), data science and precision medicine (collecting individual data for precision medicine), and policy making (raising ethical and legal issues, especially regarding privacy and confidentiality of data). However, AI applications have not been commonly used in resource-poor settings due to the limit in infrastructure and human resources.
CONCLUSIONS
The application of AI in medicine has grown rapidly and focuses on three leading platforms: clinical practices, clinical material, and policies. AI might be one of the methods to narrow down the inequality in health care and medicine between developing and developed countries. Technology transfer and support from developed countries are essential measures for the advancement of AI application in health care in developing countries. | 10.2196/15511 |
pubmed_743_22236 | INTRODUCTION
MicroRNAs (miRs) may be important regulators of risk for type 2 diabetes (T2D). Circulating miRs may provide information about which individuals are at risk for T2D. The purpose of this study was to assess longitudinal associations between circulating miR expression and variability in fasting blood glucose (FBG) and to identify miR-targeted genes and biological pathways.
METHODS
Variability in FBG was estimated using standard deviation from participants (n = 20) in a previously completed yoga trial. Expression of 402 miRs was measured using hydrogel particle lithography. MirTarBase was used to identify mRNAs, and miRPathDB was used to identify pathways targeted by differentially expressed miRs.
RESULTS
Six circulating miRs (miR-192, miR-197, miR-206, miR-424, miR-486, and miR-93) were associated with variability in FBG and targeted 143 genes and 23 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Six mRNAs (AKT1, CCND1, ESR1, FASN, SMAD7, and VEGFA) were targeted by at least two miRs and four of those were located in miR-targeted KEGG pathways.
CONCLUSIONS
Circulating miRs are associated with variability in FBG in individuals at risk for T2D. Further studies are needed to determine whether miRs may be prodromal biomarkers that can identify which individuals are at greatest risk to progress to T2D and which biological pathways underlie this risk. | 10.1177/14791641211055837 |
pubmed_720_24957 | An exopolysaccharide producing strain AK103T was isolated from Sambharlake, Rajasthan, India. Based on polyphasic taxonomy, the strain AK103T was found to be a novel species for which the name Natronotalea sambharensis sp. nov. is proposed. The strain was able to secrete (1.2 gL-1) EPS under optimum conditions. The FT-IR spectroscopy revealed that EPS had carboxyl, hydroxyl, carbonyl and sulfate ester groups. The high performance liquid chromatography (HPLC), gel permeation chromatography (GPC) and NMR revealed that the exopolysaccharide was composed of mannose, glucose and glucuronic acid with a molecular weight of 4.6 × 106 KDa. This novel EPS was designated as Nat-103. Interestingly, the EPS was found to have antioxidant activity and in vitro antioxidant studies showed that DPPH (2,2-diphenyl-1-picrylhydrazyl) activity increased in a dose dependent manner. Furthermore, EPS Nat-103 was able to produce gold nanoparticles which were further characterized by FT-IR, DLS and Zeta potential (ZP). | 10.1016/j.ijbiomac.2019.06.080 |
pubmed_152_15722 | Estrogen, if it is produced in the gastrointestinal tract, may overflow into the systemic circulation in the case of increased portal-systemic shunting. This idea is in accord with a significant step-up in serum estradiol (E2) concentration in the portal vein of rats, compared with that in the artery. Gene expression of aromatase, estrogen synthetase, was demonstrated by RT-PCR in the gastric mucosa of male and female adult rats, equivalent to that in the ovary. Aromatase activity and production of E2 in the gastric mucosa were demonstrated by (3)H(2)O assay and gas chromatography-mass spectrometry, and they were inhibited by aromatase inhibitor, 4-hydroxyandrostenedione. Conversion of (14)C-androstenedione to (14)C-E2 through (14)C-testosterone in cultured gastric mucosa was also demonstrated. Parietal cells exhibited strong signals for aromatase mRNA and immunoreactive protein by in situ hybridization histochemistry and immunohistochemistry. Estrogen receptor alpha mRNA and immunoreactive protein were demonstrated in hepatocytes by RT-PCR, in situ hybridization histochemistry, and immunohistochemistry. Total gastrectomy reduced portal venous E2 concentration, without changing systemic E2 concentration, together with down-regulation of estrogen receptor alpha mRNA level in the liver. These findings indicate that gastric parietal cells play a potent endocrine role in secreting estrogen that may function as a regulator of the gastro-hepatic axis. | 10.1210/endo.143.8.8974 |
pubmed_3_8907 | The mammalian Target Of Rapamycin (mTOR) is a nutrient-sensing protein kinase that regulates numerous cellular processes. Fetal rat metatarsal explants were used as a physiological model to study the effect of mTOR inhibition on chondrogenesis. Insulin significantly enhanced their growth. Rapamycin significantly diminished this response to insulin through a selective effect on the hypertrophic zone. Cell proliferation (bromodeoxyuridine incorporation) was unaffected by rapamycin. Similar observations were made when rapamycin was injected to embryonic day (E) 19 fetal rats in situ. In the ATDC5 chondrogenic cell line, rapamycin inhibited proteoglycan accumulation and collagen X expression. Rapamycin decreased content of Indian Hedgehog (Ihh), a regulator of chondrocyte differentiation. Addition of Ihh to culture medium reversed the effect of rapamycin. We conclude that modulation of mTOR signaling contributes to chondrocyte differentiation, perhaps through its ability to regulate Ihh. Our findings support the hypothesis that nutrients, acting through mTOR, directly influence chondrocyte differentiation and long bone growth. | 10.1002/dvdy.21464 |
pubmed_26_11255 | PURPOSE
To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm(3) in volume.
PATIENTS AND METHODS
Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 +/- 6.3 cm(3) (mean +/- SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method.
RESULTS
At the time of the second and third fractions, mean tumor volumes were 14.3 +/- 6.5 (18.8% reduction) and 10.6 +/- 6.1 cm(3) (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively.
CONCLUSIONS
The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases. | 10.1016/j.ijrobp.2008.10.035 |
pubmed_670_10835 | Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes. Its plasma activity is enhanced by intravenous heparin which releases the enzymes from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly lower in patients with malabsorption and villous atrophy, thus suggesting that PHD reflects the mature enterocytic mass. In this study we have assayed PHD in five patients with small bowel lymphoma (two with immunoproliferative small intestinal disease [IPSID] and three with non-IPSID lymphoma) associated with malabsorption syndrome and small bowel mucosa atrophy. The PHD test was performed at diagnosis, after partial or complete remission induced by chemotherapy, and during the follow-up. The PHD values, very low at diagnosis (0.66 +/- 0.12 U/ml), increased during chemotherapy and reached the normal range (greater than 3.7 U/ml) when complete remission occurred. The PHD values rapidly and consistently decreased whenever the disease relapsed. Our data indicate that in patients with small bowel lymphoma PHD test is a sensitive marker of small bowel mucosa damage and suggest that it could be useful in monitoring the recovery of mucosal lesions induced by chemotherapy. | 10.1002/1097-0142(19910115)67:2<511::aid-cncr2820670232>3.0.co;2-0 |
pubmed_694_33 | Stern notes that infants attempt to enliven their depressed mothers. The reconstructed childhood of a patient who was the daughter of a depressed mother is discussed. The treatment of this 31-year-old single woman whose talk was rapid, whose comments were studded with high-powered names, and whose checks bounced is described. The intensity of this patient's attempts to connect with the therapist illustrated her need to enliven the therapist. This adult charmer is reminiscent of the infants that Stern observed in interaction with their depressed mothers. | pubmed_694_33 |
pubmed_464_14957 | WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?
Malaria control was affected by the coronavirus disease 2019 (COVID-19) pandemic. This study conducted active case finding for key flights and key populations to determine malaria transmission.
WHAT IS ADDED BY THIS REPORT?
Surveillance for malaria was conducted for entry personnel coming from areas affected by malaria. It is estimated that at least 100,000 tests were conducted in Guangdong Province; 154 cases were confirmed during the surveillance.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
To maintain the malaria elimination status, comprehensively maintaining a sensitive and effective surveillance response system is especially important. | 10.46234/ccdcw2021.180 |
pubmed_214_26330 | Vascular calcification (VC) is an independent risk factor for cardiovascular events and all-cause mortality with the absence of current treatment. This study aimed to investigate whether eIF2alpha phosphorylation inhibition could ameliorate VC. VC in rats was induced by administration of vitamin D3 (3×10(5) IU/kg, intramuscularly) plus nicotine (25 mg/kg, intragastrically). ISRIB (0.25 mg/kg·week), an inhibitor of eIF2alpha phosphorylation, ameliorated the elevation of calcium deposition and ALP activity in calcified rat aortas, accompanied by amelioration of increased SBP, PP, and PWV. The decreased protein levels of calponin and SM22alpha, and the increased levels of RUNX2 and BMP2 in calcified aorta were all rescued by ISRIB, while the increased levels of the GRP78, GRP94, and C/EBP homologous proteins in rats with VC were also attenuated. Moreover, ISRIB could prevent the elevation of eIF2alpha phosphorylation and ATF4, and partially inhibit PERK phosphorylation in the calcified aorta. These results suggested that an eIF2alpha phosphorylation inhibitor could ameliorate VC pathogenesis by blocking eIF2alpha/ATF4 signaling, which may provide a new target for VC prevention and treatment. | 10.33549/physiolres.934797 |
pubmed_438_19699 | Direct stenting (DS) is a novel approach in percutaneous treatment of coronary artery lesions. Several studies confirmed the safety and feasibility of the procedure with success rates greater than 90%. However, the data regarding the incidence of sidebranch occlusion (SBO) after DS are scarce. The purpose of this study was to evaluate SBO (> 1 mm) after DS and compare it to conventional stenting (CS) with balloon predilation. The study population consisted of 151 patients (88 underwent DS, 63 underwent CS) with 185 sidebranches jailed by the stent (110 in DS group, 75 in CS group). SBO was observed in 20 out of 110 patients in the DS group (18.2%) and 18 out of 75 patients in the CS group (24%). Although the incidence of SBO was higher in the CS group compared to the DS group (24% vs. 18.2%, respectively), these values did not reach statistical significance (p > 0.05). Most of the SBOs were observed in cases with type D sidebranch morphology (p < 0.001) and in cases with sidebranch ostial diameter stenosis 50% (p = 0.019). None of the other clinical and angiographic variables predicted the SBO. To the best of our knowledge, this is the first report comparing incidence of SBO between two different PCI methods (CS vs DS). Randomized studies with larger patient populations should be conducted to compare this approach with conventional stenting. | pubmed_438_19699 |
pubmed_888_12592 | It was established, while making blood tests for healthy males and for patients with glomerular nephritis at exacerbation, that there is a statistically reliable interrelation between the erythrocyte electrophoretic mobility and their sedimentation velocity. Its nature is subject to modifications as the functional body state and the investigated range of concurrently altering parameters are changing. Such hierarchy, in neuropathy, can be also the case at the level of mean parameters; and in health, it can be observed only as a conjugated reconstruction of the erythrocyte population structure. | pubmed_888_12592 |
pubmed_220_2617 | Through a process of protein fractionation and vaccination we previously identified four native antigens that confer a degree of protection against challenge with Anaplasma marginale. One of these, Ana 29 has been successfully cloned and sequenced using degenerate primers designed to N-terminal and internal peptide sequences. The full-length gene codes for a protein with a theoretical molecular weight of 27 kDa and pI 8.6. The sequence is highly conserved, showing 99% identity between two Australian and an American isolate of A. marginale. The gene sequences from these isolates also share 99% identity with the strain of Anaplasma centrale used in the commercial Australian vaccine. Protein prediction algorithms suggest the native protein is an integral membrane protein. This protein has been over-expressed and purified from Escherichia coli and used in vaccination trials in cattle using two adjuvants. The initial results from the trial show a significant level of protection was obtained with one adjuvant; in comparison, the second adjuvant slightly aggravated the disease. Preliminary data suggests a good correlation between the induction of an IgG2 response and protection. | 10.1016/j.vaccine.2003.07.006 |
pubmed_115_8650 | We described a family of nicotinic acetylcholine receptor (nAChR) subunits underlying cholinergic transmission in the central nervous system (CNS) of the mollusc Lymnaea stagnalis. By using degenerate PCR cloning, we identified 12 subunits that display a high sequence similarity to nAChR subunits, of which 10 are of the alpha-type, 1 is of the beta-type, and 1 was not classified because of insufficient sequence information. Heterologous expression of identified subunits confirms their capacity to form functional receptors responding to acetylcholine. The alpha-type subunits can be divided into groups that appear to underlie cation-conducting (excitatory) and anion-conducting (inhibitory) channels involved in synaptic cholinergic transmission. The expression of the Lymnaea nAChR subunits, assessed by real time quantitative PCR and in situ hybridization, indicates that it is localized to neurons and widespread in the CNS, with the number and localization of expressing neurons differing considerably between subunit types. At least 10% of the CNS neurons showed detectable nAChR subunit expression. In addition, cholinergic neurons, as indicated by the expression of the vesicular ACh transporter, comprise approximately 10% of the neurons in all ganglia. Together, our data suggested a prominent role for fast cholinergic transmission in the Lymnaea CNS by using a number of neuronal nAChR subtypes comparable with vertebrate species but with a functional complexity that may be much higher. | 10.1074/jbc.M508571200 |
pubmed_68_3369 | Cytosol and crude nuclear extracts of brains from female Diploptera punctata were found to contain a juvenile hormone-binding protein. The binding kinetics of the cytosol and nuclear juvenile hormone-binding proteins toward racemic [3H]JH III were determined using the dextran-coated charcoal assay. Both proteins show reversible and saturable binding toward JH III. The mean dissociation constant (Kd) of the brain cytosol binding protein was 66.5 +/- 7.2 nM, whereas the nuclear-binding protein had a lower affinity, with a mean Kd of 170 +/- 22.1 nM. The specificity of both the cytosol and the nuclear binding proteins was determined by competitive displacement experiments with [3H]JH III. For the cytosol binding protein, the order of relative affinity was JH II > (10R)-JH III > (10RS)-JH III approximately JH I. For the nuclear binding protein the order of relative affinity was JH II > JH I > (10R)-JH III > (10RS)-JH III. The JH analog hydroprene (ZR 512) had > 100-fold lower affinity than JH III for both proteins. | 10.1006/gcen.1994.1055 |
pubmed_147_6336 | OBJECTIVES
To (1) evaluate the relationships between several indices of obesity with obesity-related risk factors; (2) compare the accuracy of body composition estimates derived from anthropometry and bioimpedance analysis (BIA) to estimates of body composition assessed by doubly-labeled water (DLW); and (3) establish equations for estimating fat mass (FM), fat-free mass (FFM), and percent body fat (PBF) in Yup'ik people.
DESIGN AND METHODS
Participants included 1,056 adult Yup'ik people from 11 communities in Southwestern Alaska. In a sub-study of 30 participants, we developed population-specific linear regression models for estimating FM, FFM, and PBF from anthropometrics, age, sex, and BIA against criterion measures derived from total body water assessed with DLW. These models were then used with the population cohort and we analyzed the relationships between obesity indices and several health-related and disease status variables: (1) fasting plasma lipids, (2) glucose, (3) HbA1c, (4) adiponectin, (5) blood pressure, (6) diabetes (DM), and (7) cerebrocoronary vascular disease (CCVD) which includes stroke and heart disease.
RESULTS
The best model for estimating FM in the sub-study used only three variables-sex, waist circumference (WC), and hip circumference and had multiple R(2) = 0.9730. FFM and PBF were calculated from FM and body weight.
CONCLUSION
WC and other anthropometrics were more highly correlated with a number of obesity-related risk factors than were direct estimates of body composition. Body composition in Yup'ik people can be accurately estimated from simple anthropometrics. | 10.1002/oby.20125 |
pubmed_258_3103 | Gallbladder mucocele (GM) is a common extrahepatic biliary disease recognized in dogs and is defined as the expansion and extension of the gallbladder by an accumulation of semi-solid bile or bile acid. Histopathological diagnosis of necrotizing cholecystitis and transmural coagulative necrosis of the gallbladder wall shows poor prognosis. Conversely, histopathological diagnosis with partial necrotic findings is often achieved. We hypothesized that histopathological partial necrosis of the gallbladder wall is the primary lesion of necrotic cholecystitis or transmural ischemic necrosis. Therefore, we investigated the relationship between histopathological necrosis/ partial necrosis findings and their clinical conditions. We retrospectively analyzed 55 dogs diagnosed with GM that had undergone cholecystectomy at the Yamaguchi University Animal Medical Center. The group with histopathological necrosis/partial necrosis of the gallbladder wall showed elevated levels of preoperative white blood cells, alanine transaminase, alkaline phosphatase, γ-glutamyltransferase, total bilirubin, and C-reactive protein compared to the non-necrotic group. Partial necrosis of the gallbladder wall may affect the progression of the disease and hematological abnormalities. Additionally, all death cases until 2 weeks were included in the histopathological necrosis/partial necrosis group. In this study, we found that poor prognosis factors were associated with partial necrosis of the gallbladder wall. Furthermore, these cases of partial necrosis showed elevated levels of blood test parameters. These results suggest that necrosis of the gallbladder wall is associated with poor prognosis and poor pathophysiological conditions. | 10.24425/pjvs.2022.141806 |
pubmed_20_14358 | BACKGROUND
Bone marrow examination is regarded as one of the most important diagnostic procedure to assess various haematological disorders. The uses and advantages of bone marrow aspiration are numerous. This study was conducted with the aim to evaluate the frequency of involvement of bone marrow with malignant and non-malignant haematological and other clinical disorders and to observe the significance of bone marrow in establishing primary diagnosis of the same condition.
METHODS
This was descriptive carried out at the Department of Pathology, Women Medical College, Abbottabad. A total of 570 successful bone marrow examinations were performed. Patients of all age groups and genders were included in the study. After history, clinical examination and blood complete counts, bone marrow was aspirated from posterior superior iliac spine, sternum or tibia. Smears were made, stained and examined under microscope.
RESULTS
Total numbers of cases were 570. Ages ranged from 6 months to 70 years. Male to female ratio was 2:1. The common clinical presentation for bone marrow examination were progressive pallor, fever of unknown origin and bleeding. Total numbers of non-malignant haematological conditions were 417 (73.2%) while the numbers of malignant conditions were 153 (27.8%).
CONCLUSION
Bone marrow examination remains a simple, reliable and effective technique in the diagnosis of many important clinical conditions. It is a reliable accessible tool for diagnosing various haematological malignant and non-haematological conditions. The importance of bone marrow examination is further highlighted in cases where routine investigations fail to reach a conclusive diagnosis. Treatable conditions like visceral leishmaniasis and malaria are diagnosed and the result is decreased mortality from these diseases. | pubmed_20_14358 |
pubmed_992_22952 | The significance of diet-induced thermogenesis (DIT) for metabolic control is still debated. Although obesogenic diets recruit UCP1 and adrenergically inducible thermogenesis, and although the absence of UCP1 may promote the development of obesity, no actual UCP1-related thermogenesis identifiable as diet-induced thermogenesis has to date been unambiguously demonstrated. Examining mice living at thermoneutrality, we have identified a process of facultative (directly elicited by acute eating), adaptive (magnitude develops over weeks on an obesogenic diet), and fully UCP1-dependent thermogenesis. We found no evidence for UCP1-independent diet-induced thermogenesis. The thermogenesis was proportional to the total amount of UCP1 protein in brown adipose tissue and was not dependent on any contribution of UCP1 in brite/beige adipose tissue, since no UCP1 protein was found there under these conditions. Total UCP1 protein amount developed proportionally to total body fat content. The physiological messenger linking obesity level and acute eating to increased thermogenesis is not known. Thus UCP1-dependent diet-induced thermogenesis limits obesity development during exposure to obesogenic diets but does not prevent obesity as such. | 10.1152/ajpendo.00097.2017 |
pubmed_621_19932 | Surgeons conventionally use electrocautery dissection and surgical clip appliers to harvest free flaps. The ultrasonic Harmonic Scalpel is a new surgical instrument that provides high-quality dissection and hemostasis and minimizes tissue injury. The aim of this study was to evaluate the effectiveness and advantages of the ultrasonic Harmonic Scalpel compared to conventional surgical instruments in free flap surgery. This prospective study included 20 patients who underwent head and neck reconstructive surgery between March 2009 and May 2010. A forearm free flap was used for reconstruction in 12 patients, and a fibular flap was used in 8 patients. In half of the patients, electrocautery and surgical clips were used for free flap harvesting (the EC group), and in the other half of the patients, ultrasonic dissection was performed using the Harmonic Scalpel (the HS group). The following parameters were significantly lower in the HS group compared to the EC group: the operative time of flap dissection (35% lower in the HS group), blood loss, number of surgical clips and cost of surgical materials. This study demonstrated the effectiveness of the Harmonic Scalpel in forearm and fibular free flap dissections that may be extended to other free flaps. | 10.1155/2012/302921 |
pubmed_416_17616 | Peroxisomal proliferator-activated receptor (PPAR)-alpha is a ligand-activated transcriptional factor that regulates genes involved in lipid metabolism and energy homeostasis. PPAR-alpha activators, including fibrates, have been used to treat dyslipidemia for several decades. In contrast to their known effects on lipids, the pharmacological consequences of PPAR-alpha activation on cardiac metabolism and function are not well understood. Therefore, we evaluated the role that PPAR-alpha receptors play in the heart. Our studies demonstrate that activation of PPAR-alpha receptors using a selective PPAR-alpha ligand results in cardiomyocyte necrosis in mice. Studies in PPAR-alpha-deficient mice demonstrated that cardiomyocyte necrosis is a consequence of the activation of PPAR-alpha receptors. Cardiac fatty acyl-CoA oxidase mRNA levels increased at doses in which cardiac damage was observed and temporally preceded cardiomyocyte degeneration, suggesting that peroxisomal beta-oxidation correlates with the appearance of microscopic injury and cardiac injury biomarkers. Increased myocardial oxidative stress was evident in mice treated with the PPAR-alpha agonists coinciding with increased peroxisomal biomarkers of fatty acid oxidation. These findings suggest that activation of PPAR-alpha leads to increased cardiac fatty acid oxidation and subsequent accumulation of oxidative stress intermediates resulting in cardiomyocyte necrosis. | 10.2353/ajpath.2006.051110 |
pubmed_954_5840 | Primary angiitis of the central nervous system is a rare idiopathic inflammation of vessels. We report on a 75-year-old male with primary angiitis of the central nervous system and cerebral amyloid angiopathy. He presented with subacute onset of progressive decline in cognitive functions, followed by confusion and coma. Initial brain magnetic resonance imaging favored meningoencephalitis. There was no improvement after treatment with antibiotics. Final diagnosis was proven by brain biopsy. Corticosteroids were given, but without significant improvement. This case is reported because of its rarity and its clinical presentation. | 10.1097/NRL.0000000000000014 |
pubmed_976_22388 | Allgrove's syndrome, i.e., achalasia, addisonianism, alacrima (OMIM 231550) is an autosomal recessive disorder recently associated with the AAAS gene coding for the Aladin protein. However, the pathophysiology of achalasia in Allgrove's syndrome remains obscure. Here we investigated the histopathology of the cardia in Allgrove's syndrome. Myectomy specimens from 10 children with Allgrove's syndrome and four normal cardia were studied by routine staining and by immunohistochemistry for the pan-neuronal marker PGP9.5, neuronal NO synthase, interstitial cells of Cajal, and CD3+ lymphocytes. In the normal cardia, myenteric ganglia, intramuscular nerve fibers, and interstitial cells of Cajal were numerous, whereas myenteric fibrosis and lymphocyte infiltrates were absent. In Allgrove's syndrome, fibrosis of the intermuscular plane was prevalent in all patients. Myenteric ganglia were absent, decreased, or apparently normal in 1 of 10, 8 of 10, and 1 of 10, respectively. Neuronal NO synthase was absent in 7 of 10 and decreased in 3 of 10, whereas interstitial cells of Cajal appeared normal in 7 of 10 and decreased in 3 of 10. Lymphocytes infiltrating the myenteric plexus were present in 6 of 10. Pyloromyectomy specimens available for six patients showed normal histopathologic features. In conclusion, the lack of neuronal NO synthase and fibrosis of the intermuscular plane can be linked to the defective cardia relaxation. Other features were less constant and may reflect the variability of disease expression and progression among patients with Allgrove's syndrome. | 10.1097/00000478-200305000-00010 |
pubmed_934_15900 | This study was aimed to investigate the effect of salidroside on proliferation of bone marrow mesenchymal stem cells (MSC) and their secretion of stem cell factor (SCF). MSC were isolated and amplified in vitro via density gradient centrifugation and adherence screening method. MCS were identified by flow cytometry and osteogenic/adipogenic induction. The effects of salidroside on cell proliferation, cell cycle and the SCF secretion of MSC were detected by flow cytometry. The results showed that the salidroside could induce the proliferation of MSC, peaked at the concentration of 1.5 mg/ml and in a time-dependent manner (in 24 h, 48 h and 72 h). Salidroside at 1.5 mg/ml could more effectively increase the percentage of cells in S and G1/M phase. Co-cultured with salidroside at the concentration of 1.5 mg/ml for 48 h, the SCF and the expression levels of SCF mRNA in co-culture supernatant were both significantly increased (P < 0.01). It is concluded that salidroside in a range of certain concentration can obviously promote the proliferation of MSC and increase the expression and secretion of SCF. | 10.7534/j.issn.1009-2137.2014.04.035 |
pubmed_574_4498 | Following in situ renaturation and assay of protein kinase activity after denaturing electrophoresis of relatively impure samples of maize phosphoenolpyruvate carboxylase (PEPC) kinase, a approximately 30-kDa polypeptide was implicated as the best candidate for the PEPC kinase catalytic subunit. This kinase's apparent native molecular weight was estimated at 28,000 by gel filtration on a calibrated Superose 12 column (HR 10/30), suggesting that the isolated PEPC kinase is monomeric. This protein-serine kinase was partially purified about 4000-fold from illuminated maize leaves by ammonium sulfate precipitation and sequential chromatography on Ultrogel AcA 54, hydroxylapatite, blue dextran-agarose, and an analytical AcA 54 column. Analysis by denaturing electrophoresis revealed that a 30-kDa polypeptide copurified with PEPC kinase activity during the final step. This highly purified kinase had an apparent Km (PEPC subunit) of 2.5 microM and a Km (total ATP) of 40 microM at pH 8.0, its pH optimum. Upon in vitro phosphorylation of darkform (dephospho) C4 PEPC at Ser-15 (maize PEPC) or Ser-8 (sorghum), the malate sensitivity of the target enzyme decreased significantly. The maize PEPC kinase activity was markedly inhibited by L-malate, a negative allosteric effector of its protein substrate, in a concentration- and pH-dependent manner. Comparative phosphorylation studies with the catalytic subunit of mammalian cAMP-dependent protein kinase and casein revealed that a significant part of the malate inhibition of PEPC kinase activity in vitro was due to this effector's interaction with PEPC. The activity of both the highly purified PEPC kinase and a less pure sample prepared rapidly in the presence of various protease inhibitors was insensitive to Ca2+ chelation or addition. It is concluded that the approximately 30-kDa maize PEPC kinase is a low abundance, Ca(2+)-independent protein-serine kinase that activates its target enzyme by the exclusive phosphorylation of the regulatory serine residue near the N terminus and the resulting decrease in feedback inhibition by L-malate. | 10.1006/abbi.1993.1381 |
pubmed_1132_13692 | Elevated blood pressure is associated with diminished pain sensitivity. While this finding is well established in adults, it is less clear when the relation between blood pressure and pain sensitivity emerges across the life course. Evidence suggests this phenomenon may exist during childhood. Children (N = 309; 56% boys) aged 10-15 years and their parents participated. Blood pressure readings were taken during a resting baseline. Maximum pain intensity was rated using a visual analogue scale (rated 0-10) in response to a finger prick pain induction. Parent-measured resting blood pressure was inversely associated with boys' pain ratings only. Cross-sectionally, lower pain ratings were related to higher SBP, univariately. Longitudinally, pain ratings predicted higher DBP, even after controlling for covariates. Determining when and how the relation between blood pressure and pain sensitivity emerges may elucidate the pathophysiology of hypertension. | 10.1111/psyp.12036 |
pubmed_897_12705 | A fiber-optic Fabry-Perot interferometer was constructed by splicing a short length of photonic crystal fiber to a standard single-mode fiber. The photonic crystal fiber functions as a Fabry-Perot cavity and serves as a direct sensing probe without any additional components. Its pressure and temperature responses in the range of 0-40 MPa and 25°C-700°C were experimentally studied. The proposed sensor is easy to fabricate, potentially low-cost, and compact in size, which makes it very attractive for high-pressure and high-temperature sensing applications. | 10.1364/OL.36.000412 |
pubmed_293_20278 | Among the different species of flower beetles, there is one of particular notoriety: the Goliath beetle. This large insect can grow up to 11 cm long and is well-known for its distinctive black and white shield. In this paper, we focus on a particular Goliathus species: G. orientalis (Moser, 1909). We investigated the variations in properties of both the black and white parts of the upper face of G. orientalis; more precisely, the variation in surface properties with respect to the wettability of these two parts. This work reveals that the white parts of the shield have a higher hydrophobic character when compared to the black regions. While the black parts are slightly hydrophobic (θ = 91 ± 5°) and relatively smooth, the white parts are highly hydrophobic (θ = 130 ± 3°) with strong water adhesion (parahydrophobic); similar to the behavior observed for rose petals. Roughness and morphology analyses revealed significant differences between the two parts, and, hence, may explain the change in wettability. The white surfaces are covered with horizontally aligned nanohairs. Interestingly, vertically aligned microhairs are also present on the white surface. Furthermore, the surfaces of the microhairs are not smooth, they contain nanogrooves that are qualitatively similar to those observed in cactus spines. The nanogrooves may have an extremely important function regarding water harvesting, as they preferentially direct the migration of water droplets; this process could be mimicked in the future to capture and guide a large volume of water. | 10.3390/biomimetics3020006 |
pubmed_920_9377 | Aggressive angiomyxoma (AA) is a rare mesenchymal tumour that is characterised by increased incidence in women compared with men, local invasion to the surrounding tissue and high recurrence rate. A premenopausal woman presented to clinic with pelvic pressure, intermittent tingling in the thigh and pressure emptying the bladder. CT scan, vaginal and gluteal biopsies, and MRI scan were performed to conclude a final diagnosis of AA. The patient underwent complete resection of the mass. The mass tested positive for oestrogen receptor and progesterone receptor. The patient received leuprolide postoperatively to prevent recurrence. AA should be considered as a differential diagnosis for a pelvic and perineal mass. Patients should be warned of high recurrence rate, necessity of surgical removal and long-term hormonal treatment. | 10.1136/bcr-2021-241550 |
pubmed_854_12655 | The "8020" objective seems difficult to achieve, but at least 20 teeth are needed based on difficult cases of defective dentition. Our clinical experience shows that at least 18 teeth are needed to keep 4 occlusal supports. If the number of occlusal supports falls below 4, defective dentition may easily deteriorate to more clinically difficult cases. From our long-term experience, patients over 80 years old who still have 20 teeth usually have stabilized occlusal supports, while many cases who have partially lost their occlusal support do not achieve the 8020 goal. Prevention of partial defects of teeth for restoration of caries and active prosthesis for defects are important to achieve the 8020 goal. Furthermore, continuous follow-up and preventive support are important. If continuous clinical correspondence is possible, 8020 may be achievable in about 80% of all cases. | 10.2186/jjps.49.199 |
pubmed_228_20973 | Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. Emerging evidence indicates that amyloid-β (Aβ) peptides enter mitochondria and may thereby disrupt mitochondrial function in brains of AD patients and transgenic model mice. However, it remains to be determined whether the β-cleaved C-terminal fragment (C99), another neurotoxic fragment of amyloid precursor protein (APP), may accumulate in mitochondria of neurons affected by AD. Using immunoblotting, digitonin fractionation and immunofluorescence labeling techniques, we found that C99 is targeted to mitochondria, in particular, to the mitoplast (i.e., inner membrane and matrix compartments) in brains of AD transgenic mice (5XFAD model). Furthermore, full-length APP (fl-APP) was also identified in mitochondrial fractions of 5XFAD mice. Remarkably, partial deletion of the β-site APP-cleaving enzyme 1 (BACE1(+/-)) almost completely abolished mitochondrial targeting of C99 and fl-APP in 5XFAD mice at 6 months of age. However, substantial amounts of C99 and fl-APP accumulation remained in mitochondria of 12-month-old BACE1(+/-)·5XFAD mouse brains. Consistent with these changes in mitochondrial C99/fl-APP levels, BACE1(+/-) deletion age-dependently rescued mitochondrial dysfunction in 5XFAD mice, as assessed by cytochrome c release from mitochondria, reduced redox or complex activities and oxidative DNA damage. Moreover, BACE1(+/-) deletion also improved memory deficits as tested by the spontaneous alternation Y-maze task in 5XFAD mice at 6 months but not at 12 months of age. Taken together, our findings suggest that mitochondrial accumulation of C99 and fl-APP may occur through BACE1-dependent mechanisms and contribute to inducing mitochondrial dysfunction and cognitive impairments associated with AD. | 10.1016/j.nbd.2011.09.001 |
pubmed_573_15751 | LIS1 (PAFAH1B1) mutation can impair neuronal migration, causing lissencephaly in humans. LIS1 loss is associated with dynein protein motor dysfunction, and disrupts the actin cytoskeleton through disregulated RhoGTPases. Recently, LIS1 was implicated as an important protein-network interaction node with high-risk autism spectrum disorder genes expressed in the synapse. How LIS1 might participate in this disorder has not been investigated. We examined the role of LIS1 in synaptogenesis of post-migrational neurons and social behaviour in mice. Two-photon imaging of actin-rich dendritic filopodia and spines in vivo showed significant reductions in elimination and turnover rates of dendritic protrusions of layer V pyramidal neurons in adolescent Lis1(+/-) mice. Lis1(+/-) filopodia on immature hippocampal neurons in vitro exhibited reduced density, length and RhoA dependent impaired dynamics compared to Lis1(+/+) . Moreover, Lis1(+/-) adolescent mice exhibited deficits in social interaction. Lis1 inactivation restricted to the postnatal hippocampus resulted in similar deficits in dendritic protrusion density and social interactions. Thus, LIS1 plays prominently in dendritic filopodia dynamics and spine turnover implicating reduced dendritic spine plasticity as contributing to developmental autistic-like behaviour. | 10.1002/emmm.201202106 |
pubmed_69_21261 | A man is his 50s experienced epigastric discomfort and body weight loss from 60 to 56 kg over 3 months. A lesion was diagnosed as type 3 advanced gastric cancer (group 5, tub2) with para-aortic lymph node and multiple liver metastases. Pretreatment hemoglobin(Hb), albumin(Alb), and C-reactive protein(CRP) levels were 11.0 mg/dL, 3.0 g/dL, and 2.40 mg/dL, respectively. S-1+cisplatin (CDDP) combined chemotherapy (S-1 120 mg/day, day 1-21, CDDP 60 mg/ m2, day 8, q35 days) with nutritional supportive care using enteral nutrition (EN) agent (Prosure) enriched with eicosapentaenoic acid (EPA) was initiated. After 6 weeks, body weight, Hb, Alb, and CRP improved to 60 kg, 13.6 mg/dL, 4.6 g /dL, and 0.14 mg/dL, respectively. Moreover, a marked reduction in para-aortic lymph node and multiple liver metastases was seen on computed tomography (CT) scans 12 weeks after treatment initiation. Accordingly, nutritional supportive care using EN agent enriched with EPA during chemotherapy might be an effective treatment for patients with gastric cancer who show increased CRP and decreased albumin levels. | pubmed_69_21261 |
pubmed_960_18233 | PURPOSE
To investigate the discrepancy between ICP and MCP caused by orthodontic treatment. to evaluate the treatment effect of the malocclusion with later orthodontic treatment.
METHODS
Nineteen cases were selected and treated with preadjusted appliance and combination headgear appliance.Pre- and post- treatment celphalometric radiographs were analyzed.
RESULTS
Discrepancy between ICP and MCP may be resulted from improper design and operation of orthodontists and poor cooperation of patients; By preadjusted appliance and combination headgear appliance,upper dental arch was moved distally; Molar relationship was changed into Class I by bodily movement; A harmonization between ICP and MCP was rehabilitated.
CONCLUSIONS
The discrepancy between ICP and MCP should be minded; Preadjusted appliance and combination headgear appliance were effective in the correction of the discrepancy between ICP and MCP. | pubmed_960_18233 |
pubmed_159_5452 | The May 2018 rift intrusion and eruption of Kīlauea Volcano, Hawai'i, represented one of its most extraordinary eruptive sequences in at least 200 years, yet the trigger mechanism remains elusive1. The event was preceded by several months of anomalously high precipitation. It has been proposed that rainfall can modulate shallow volcanic activity2,3, but it remains unknown whether it can have impacts at the greater depths associated with magma transport. Here we show that immediately before and during the eruption, infiltration of rainfall into Kīlauea Volcano's subsurface increased pore pressure at depths of 1 to 3 kilometres by 0.1 to 1 kilopascals, to its highest pressure in almost 50 years. We propose that weakening and mechanical failure of the edifice was driven by changes in pore pressure within the rift zone, prompting opportunistic dyke intrusion and ultimately facilitating the eruption. A precipitation-induced eruption trigger is consistent with the lack of precursory summit inflation, showing that this intrusion-unlike others-was not caused by the forceful intrusion of new magma into the rift zone. Moreover, statistical analysis of historic eruption occurrence suggests that rainfall patterns contribute substantially to the timing and frequency of Kīlauea's eruptions and intrusions. Thus, volcanic activity can be modulated by extreme rainfall triggering edifice rock failure-a factor that should be considered when assessing volcanic hazards. Notably, the increasingly extreme weather patterns associated with ongoing anthropogenic climate change could increase the potential for rainfall-triggered volcanic phenomena worldwide. | 10.1038/s41586-020-2172-5 |
pubmed_161_4667 | In virus-positive (V+) C57BL/6 Mov-13 mice, Moloney-murine leukemia virus (M-MuLV) is integrated into the germ line and expressed early in lymphoid and nonlymphoid organs. The pattern of immune reactivity to viral antigens in these mice was studied and compared to that of their virus-negative (V-) counterparts. Using a radioimmuno-binding or -precipitation assay, V- mice showed good antibody production after challenge with Moloney-murine sarcoma virus (M-MSV), but no antibodies were detected in V+ mice. Moreover, Mov-13 V+ mice failed to generate virus-specific cytotoxic T lymphocytes (CTL) in secondary mixed-leukocyte tumor cell culture (MLTC) while V- mice showed a strong cytotoxic response. This lack of activity in mass V+ cultures was due to a very low frequency of CTL precursors which did not increase following in vivo challenge with M-MSV or in vitro stimulation with MBL-2 Moloney leukemia cell line. These findings indicate that early M-MuLV activation in Mov-13 V+ mice induces a state of tolerance to viral antigens involving both the humoral and cellular immune responses and related to the high incidence of T-cell lymphomas. | 10.1016/0008-8749(84)90317-4 |
pubmed_225_10732 | BACKGROUND
HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.
METHODS
To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.
RESULTS
Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.
CONCLUSIONS
HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia. | 10.1056/NEJM199102143240701 |
pubmed_737_18919 | The most common method for calculating Granger causality requires the fitting of a system of autoregressive equations to multiple interrelated signals. Historically, the Levinson, Wiggins, Robinson (LWR) algorithm and the least-squares linear regression (LSLR) approach are the most widely used methods for fitting these autoregressive equations. In this manuscript we compare these algorithms head-to-head. LSLR, as implemented using the Dynamic Autoregressive Neuromagnetic Causal Imaging (DANCI) method, was faster, and produced better residual error, normality, independence, and autocorrelation functions when analyzing real magnetoencephalography signals. Simulations demonstrated that the accuracy of LSLR was much higher than the LWR method and that the LSLR method, at least as implemented by DANCI, could accurately resolve the causal connectivity of 50 interrelated signals. We conclude that the multichannel LSLR method, as implemented by DANCI, can accurately calculate the interdependencies among multiple signals and has the potential to accurately calculate Granger causality for large-scale neurophysiological networks. | 10.1016/j.compbiomed.2011.04.012 |
pubmed_1141_7838 | Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open iup new perspectives in the coming millennium. | pubmed_1141_7838 |
pubmed_434_25033 | At first glance, hoping and willing do not seem to have much to do with one another. They evoke quite disparate turns of mind, in fact. Hope, which Aristotle called a "waking dream," is associated with imagination, daydreams, and wishful thinking. Willing, on the other hand, is aligned with practical effort, discipline, and acting against one's inclinations. Despite their lack of obvious affinity, in some communities-especially in the face of extreme suffering-the two acts may develop a close kinship. Hope as a moral task, even a narrative quest, can demand the arduous cultivation of the will. Hope is not necessarily something people easily acquire-not a matter of mere wishful thinking when life becomes difficult, but a difficult moral obligation that must be assumed as a way to confront pain and despair. | pubmed_434_25033 |
pubmed_191_21931 | Superimposition of serial cephalograms provides a limited description of tooth movement that could be complemented by data obtained from serial dental casts. The aim of this study was to develop a mathematical method for superimposing 3-dimensional data obtained from selected landmarks on longitudinally collected dental casts to describe maxillary first molar movement during headgear treatment. The material consisted of dental casts taken bimonthly from 36 children whose Class II Division 1 malocclusion was treated with straight-pull headgear during a 24-month period. Control data were collected from initial and final models of 38 subjects with a similar malocclusion who were not treated during a 24-month observation period. Spatial data from each subject's initial model were oriented similarly in an anatomically derived coordinate system, and a best-fit superimposition of palatal rugae landmarks from subsequent models allowed the measurement of molar movement. On average, headgear treatment resulted in distal movement of the molars, and the fitted net difference between treated and control subjects was 3.00 mm (SE, 0.37 mm; P < .001). Also, the headgear caused significantly more molar extrusion (0.56 mm; SE, 0.20 mm; P < .006) and buccal expansion (0.58 mm; SE, 0.17 mm; P < .001) on average than in the control group. Poor reliability of the method for measuring molar rotations indicated that they could not be determined accurately. Longitudinal description of molar movement for each subject revealed great individual variability in the amount and pattern of tooth movement. Several reasons could account for the wide range of individual variation and warrant exploration. | 10.1067/mod.2002.120687 |
pubmed_634_5930 | Autophagy is a highly conserved cellular process in which cytoplasmic materials are degraded and recycled as energy sources when nutrient supplies are lacking. Established tumor cells require autophagy for cell growth and tumor promotion. In particular, the survival of pancreatic tumor cells appears to be strongly dependent on autophagy, referred to as autophagy addiction. This dependency of pancreatic tumor cells on autophagy may be a candidate target for pancreatic tumor therapy. EI24 (etoposide-induced gene 2.4 kb; PIG8, p53-induced gene 8) acts as a tumor suppressor, inhibiting cell growth and inducing apoptosis in breast, cervical, and prostate cancer cells. However, recent papers have reported that EI24 is an essential component of the autophagy pathway. This newly discovered role of EI24 as a component of autophagy may act as a tumor promoter, which is contradictory to its known role as a tumor suppressor. We investigated the role of EI24 as a component of autophagy in pancreatic tumor cell proliferation. Here, we demonstrated that knockdown of EI24 using siRNA in pancreatic tumor cells led to impaired autophagy at a late step (increase in LC3-II and accumulation of p62 and autolysosomes). EI24 deficiency in pancreatic tumor cell lines inhibited cell proliferation. We confirmed that loss of EI24 inhibited pancreatic cell proliferation using the CRISPR-Cas9 system. However, loss of EI24 in other cell lines did not affect cell proliferation. Taken together, our results suggest that EI24 acts as a tumor promoter in pancreatic tumor cells, and studying the role of EI24 in reference to its cellular context may lead to a useful therapeutic target. | 10.3389/fonc.2019.00652 |
pubmed_80_19870 | Purpose: The purpose of this study was to examine knowledge, attitudes, barriers, and facilitators for human papillomavirus (HPV) vaccination among Latina mothers of HPV vaccine-eligible children in low-income urban areas, as well as useful strategies to improve HPV vaccination. Methods: The study included 132 Latina mothers of HPV vaccine-eligible children, interviewed in 14 focus groups. Using semi-structured discussions, mothers were asked about their knowledge about HPV infection and vaccine, views toward HPV vaccination, barriers for HPV vaccine initiation as well as completion, and opinions on strategies to improve HPV vaccination. Results: Only 55% of mothers reported having ever heard of the HPV vaccine, 27% of mothers indicated initiating the HPV vaccine, and 14% indicated completing the multi-dose series. Mothers generally lacked knowledge about HPV infection and vaccination, with varying degrees by Latino descent. Health care provider (HCP) recommendation was the strongest barrier/facilitator for HPV vaccination. Useful strategies to improve HPV vaccine initiation and completion that the mothers suggested included strong recommendation from HCPs and addressing side effects and safety concerns. Other useful strategies included community and school-based approaches and the use of text messaging and smartphone technology to educate mothers and send vaccine reminders. Conclusion: The findings provide insight for the development of interventions targeting low-income Latina mothers and the need to improve HCP communication on HPV vaccination. | 10.1089/heq.2018.0058 |
pubmed_506_275 | The clinical use of PRP therapy in the practical setting of orthopaedic fields is increasing partly because of the accessibility of devices that are used in outpatient preparation and delivery. Another reason is the strong advertisement of PRP procedures as the ultimate treatment and novel technology for knee problems by a few orthopaedic surgeons based on claims of abundant scientific evidence. Hence, PubMed articles related to the clinical use of PRP in knee osteoarthritis were searched using the key words: PRP, knee and osteoarthritis in order to study these claims. A total of 20 reports were found directly related to the topic. The aforementioned clinical studies suggest that intraarticular injections of PRP could have preventive effects against osteoarthritis progression. However, presently there is no clear evidence from well-designed clinical trials that intraarticular injections of PRP are efficacious in osteoarthritis. Therefore, at this time the efficacy of PRP requires more investigation, wherein better scientific studies should be performed that include high powered randomized controlled trials. | pubmed_506_275 |
pubmed_854_11315 | We studied clinical courses of 15 cases of Fisher syndrome (FS) and examined therapeutic efficacy of plasma exchange (PE), immunoadsorption (IA), intravenous immune globulin (IVIg), and steroid therapy (ST). Compared with other treatments, PE and IA had shortened the peak period of the symptoms, but had not revealed the difference of the duration of illness between one another. As for PE and IA, the short-term effect was seen, but did not show the long-term effect. Though IVIg was done at the early stage, it did not shorten the peak period. So we conclude IVIg for FS to be effective not so equal as PE. However, clinical manifestations were milder in IVIg cases than PE, and there was a possibility that the symptoms of FS became mild by early treatment with Mg. Compared with Guillain-Barré syndrome, it is rare for FS to leave aftereffects and convalescence is good, so the choice of a therapy should be considered with a severity and complications. | pubmed_854_11315 |
pubmed_305_22642 | Background
Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine.
Patients and methods
Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS.
Results
Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%).
Conclusions
Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC.
ClinicalTrials.gov
NCT01095003. | 10.1093/annonc/mdy063 |
pubmed_975_5480 | The interaction between virus and peripheral blood mononuclear cells (PBMC) required to elicit the production of interferon-alpha (IFN-alpha) by the so-called natural interferon-producing cell is unknown. However, results from inhibition experiments suggest that viral glycoproteins are essential in this IFN induction process. We demonstrate here that cellular glycoproteins also appear to be involved in the initiation of IFN-alpha production. Lectins, that is, sugar binding glycoproteins, inhibited the Aujeszky's disease virus-induced IFN-alpha production of porcine PBMC by up to 99%. The level of inhibition varied with lectin used (concanavalin A, Galanthus nivalis lectin, Helix pomatia lectin, and lentil lectin). Preincubation experiments with porcine cells and concanavalin A (ConA) revealed that the lectin exerted its major effect directly on the PBMC. Although the IFN-alpha production in some cases was reduced by more than 90%, the PBMC were still able to proliferate in response to mitogenic lectins. The ConA-mediated inhibition of the IFN-alpha production was reduced if the lectin was added later than 6-8 h after the start of induction and was not mediated by soluble factors. Both orthovanadate and staurosporine inhibited the IFN-alpha production and did not relieve the ConA-mediated inhibition. Thus, ConA seems to interfere with the early events during IFN-alpha induction, but the mechanisms behind this interference could not be clarified. | 10.1089/jir.1995.15.301 |
pubmed_149_13244 | The need to consider the role of social factors in the efficacy of farm management and, consequently, in the onset and persistence of diseases typical to animal farms is increasingly being realized increasingly worldwide. Many risk analysis studies have been conducted to assess the role of various factors in the development of animal diseases; however, very few have accounted for the role of social factors. The aim of this work was to bridge this gap, with the main hypothesis that different socio-economic factors could be valid indicators for the occurrence of different animal diseases. A socio-economic analysis was performed using demographic characteristics of the farmers and data from 44 social indicators released by the Italian Statistician National Institute of Statistics (ISTAT) database. African swine fever (ASF) in wild boars (WB) and domestic pigs and other endemic animal diseases and zoonoses in Sardinia were considered, such as cistic echinococcosis (CE), contagious agalactia (CA), trichinellosis, West Nile disease (WND), and bluetongue (BT). Seven different negative binomial regression models were fitted using the number of cases between 2011-2017. Three indicators-cultural demand, employment rate, and legality-showed a statistically significant association with risk for all the diseases considered, but with varying effects. Some indicators, such as the age and sex of the farmer, material deprivation index, number of farms and animals, micro-criminality index, and rate of reported thefts were common to ASF, CA, trichinellosis, and CE cases. Others such as the forest surface and the energy produced from renewable sources were common to BT, WND, and ASF in WB. Tourism in seasons other than summer was a valid predictor of ASF and trichinellosis, while out-of-region hospital use had a statistically significant role in CE risk identification. These results may help understand the social context in which these diseases may occur and thus guide the design and implementation of additional risk management measures that go beyond well-known veterinary measures. | 10.1371/journal.pone.0217367 |
pubmed_934_22431 | An improvement to the previously proposed adaptive Canny optimization technique for scanning electron microscope image colorization is reported. The additional feature, called pseudo-mapping technique, is that the grayscale markings are temporarily mapped to a set of pre-defined pseudo-color map as a mean to instill color information for grayscale colors in chrominance channels. This allows the presence of grayscale markings to be identified; hence optimization colorization of grayscale colors is made possible. This additional feature enhances the flexibility of scanning electron microscope image colorization by providing wider range of possible color enhancement. Furthermore, the nature of this technique also allows users to adjust the luminance intensities of selected region from the original image within certain extent. | 10.1002/sca.21152 |
pubmed_861_768 | Gliosarcoma (GSM) is a variant of glioblastoma (GBM), the most common primary malignant brain tumor that occurs in adults. GSM is characterized by its biphasic components: the gliomatous and sarcomatous components and categorized into primary and secondary GSM. Intrinsic to the brain parenchyma, GSM is usually managed by gross total resection, and radiotherapy with/without chemotherapy. While the benefits of treatment remain unclear, cases have always been managed similar to GBM cases yielding different treatment outcomes between the two groups. The scarcity of research done on GSM suggests that further investigation is needed. Genetic studies on tumor samples and an in-depth examination of tumor subtypes and categories could result in identification of certain targetable alterations. The objective of this review is to summarize the available findings on characteristics, prognosis and management of GSM patients. | 10.1016/j.clineuro.2019.05.008 |
pubmed_1102_5337 | INTRODUCTION
Surface electrical impedance myography (sEIM) has the potential for providing information on muscle composition and structure noninvasively. We sought to evaluate its use to predict myofiber size and connective tissue deposition in the D2-mdx model of Duchenne muscular dystrophy (DMD).
METHODS
We applied a prediction algorithm, the least absolute shrinkage and selection operator, to select specific EIM measurements obtained with surface and ex vivo EIM data from D2-mdx and wild-type (WT) mice (analyzed together or separately). We assessed myofiber cross-sectional area histologically and hydroxyproline (HP), a surrogate measure for connective tissue content, biochemically.
RESULTS
Using WT and D2-mdx impedance values together in the algorithm, sEIM gave average root-mean-square errors (RMSEs) of 26.6% for CSA and 45.8% for HP, which translate into mean errors of ±363 μm2 for a mean CSA of 1365 μm2 and of ±1.44 μg HP/mg muscle for a mean HP content of 3.15 μg HP/mg muscle. Stronger predictions were obtained by analyzing sEIM data from D2-mdx animals alone (RMSEs of 15.3% for CSA and 34.1% for HP content). Predictions made using ex vivo EIM data from D2-mdx animals alone were nearly equivalent to those obtained with sEIM data (RMSE of 16.59% for CSA), and slightly more accurate for HP (RMSE of 26.7%).
DISCUSSION
Surface EIM combined with a predictive algorithm can provide estimates of muscle pathology comparable to values obtained using ex vivo EIM, and can be used as a surrogate measure of disease severity and progression and response to therapy. | 10.1002/mus.27240 |
pubmed_529_20255 | BACKGROUND
Extracting structured data from narrated medical reports is challenged by the complexity of heterogeneous structures and vocabularies and often requires significant manual effort. Traditional machine-based approaches lack the capability to take user feedbacks for improving the extraction algorithm in real time.
OBJECTIVE
Our goal was to provide a generic information extraction framework that can support diverse clinical reports and enables a dynamic interaction between a human and a machine that produces highly accurate results.
METHODS
A clinical information extraction system IDEAL-X has been built on top of online machine learning. It processes one document at a time, and user interactions are recorded as feedbacks to update the learning model in real time. The updated model is used to predict values for extraction in subsequent documents. Once prediction accuracy reaches a user-acceptable threshold, the remaining documents may be batch processed. A customizable controlled vocabulary may be used to support extraction.
RESULTS
Three datasets were used for experiments based on report styles: 100 cardiac catheterization procedure reports, 100 coronary angiographic reports, and 100 integrated reports-each combines history and physical report, discharge summary, outpatient clinic notes, outpatient clinic letter, and inpatient discharge medication report. Data extraction was performed by 3 methods: online machine learning, controlled vocabularies, and a combination of these. The system delivers results with F1 scores greater than 95%.
CONCLUSIONS
IDEAL-X adopts a unique online machine learning-based approach combined with controlled vocabularies to support data extraction for clinical reports. The system can quickly learn and improve, thus it is highly adaptable. | 10.2196/medinform.7235 |
pubmed_755_11138 | Two cases of extracardial rhabdomyomata are described. One case was discovered incidentally at autopsy while the other was primarily examined by needle aspiration biopsy. As far as the authors are aware, this is the first case to be reported. | pubmed_755_11138 |
pubmed_292_13927 | Biosensors employ biological molecules to recognize the target and utilize output elements which can translate the biorecognition event into electrical, optical or mass-sensitive signals to determine the quantities of the target. DNA-based biosensors, as a sub-field to biosensor, utilize DNA strands with short oligonucleotides as probes for target recognition. Although DNA-based biosensors have offered a promising alternative for fast, simple and cheap detection of target molecules, there still exist key challenges including poor stability and reproducibility that hinder their competition with the current gold standard for DNA assays. By exploiting the self-recognition properties of DNA molecules, researchers have dedicated to make versatile DNA nanostructures in a highly rigid, controllable and functionalized manner, which offers unprecedented opportunities for developing DNA-based biosensors. In this review, we will briefly introduce the recent advances on design and fabrication of static and dynamic DNA nanostructures, and summarize their applications for fabrication and functionalization of DNA-based biosensors. | pubmed_292_13927 |
pubmed_1108_15036 | Parathyroid hormone (PTH) increases fibroblast growth factor receptor-1 (FGFR1) and fibroblast growth factor-2 (FGF-2) expression in osteoblasts and the anabolic response to PTH is reduced in Fgf2-/- mice. This study examined whether candidate factors implicated in the anabolic response to PTH were modulated in Fgf2-/- osteoblasts. PTH increased Runx-2 protein expression in Fgf2+/+ but not Fgf2-/- osteoblasts. By immunocytochemistry, PTH treatment induced nuclear accumulation of Runx-2 only in Fgf2+/+ osteoblasts. PTH and FGF-2 regulate Runx-2 via activation of the cAMP response element binding proteins (CREBs). Western blot time course studies showed that PTH increased phospho-CREB within 15 min that was sustained for 24 h in Fgf2+/+ but had no effect in Fgf2-/- osteoblasts. Silencing of FGF-2 in Fgf2+/+ osteoblasts blocked the stimulatory effect of PTH on Runx-2 and CREBs phosphorylation. Studies of the effects of PTH on proteins involved in osteoblast precursor proliferation and apoptosis showed that PTH increased cyclinD1-cdk4/6 protein in Fgf2+/+ but not Fgf2-/- osteoblasts. Interestingly, PTH increased the cell cycle inhibitor p21/waf1 in Fgf2-/- osteoblasts. PTH increased Bcl-2/Bax protein ratio in Fgf2+/+ but not Fgf2-/- osteoblasts. In addition PTH increased cell viability in Fgf2+/+ but not Fgf2-/- osteoblasts. These data suggest that endogenous FGF-2 is important in PTH effects on osteoblast proliferation, differentiation, and apoptosis. Reduced expression of these factors may contribute to the reduced anabolic response to PTH in the Fgf2-/- mice. Our results strongly indicate that the anabolic PTH effect is dependent in part on FGF-2 expression. | 10.1002/jcp.21661 |
pubmed_249_16323 | Selected dietary lipids may increase the atherogenic effects of environmental chemicals, such as polychlorinated biphenyls (PCBs), by cross-amplifying mechanisms leading to dysfunction of the vascular endothelium. We have shown previously that the omega-6 parent fatty acid, linoleic acid, or 3,3',4,4'-tetrachlorobiphenyl (PCB 77), an aryl hydrocarbon (Ah) receptor agonist, independently can cause disruption of endothelial barrier function. Furthermore, cellular enrichment with linoleic acid can amplify PCB-induced endothelial cell dysfunction. We hypothesize that the amplified toxicity of linoleic acid and PCBs to endothelial cells could be mediated in part by cytotoxic epoxide metabolites of linoleic acid called leukotoxins (LTX) or their diol derivatives (LTXD). Exposure to LTXD resulted in a dose-dependent increase in albumin transfer across endothelial cell monolayers, whereas this disruption of endothelial barrier function was observed only at a high concentration of LTX. Pretreatment with the cytosolic epoxide hydrolase inhibitor 1-cyclohexyl-3-dodecyl urea partially protected against the observed LTX-induced endothelial dysfunction. Endothelial cell activation mediated by LTX and/or LTXD also enhanced nuclear translocation of the transcription factor NF-kappa B and gene expression of the inflammatory cytokine IL-6. Inhibiting cytosolic epoxide hydrolase decreased the LTX-mediated induction of both NF-kappa B and the IL-6 gene, whereas the antioxidant vitamin E did not block LTX-induced endothelial cell activation. Most importantly, inhibition of cytosolic epoxide hydrolase blocked both linoleic acid-induced cytotoxicity, as well as the additive toxicity of linoleic acid plus PCB 77 to endothelial cells. Interestingly, cellular uptake and accumulation of linoleic acid was markedly enhanced in the presence of PCB 77. These data suggest that cytotoxic epoxide metabolites of linoleic acid play a critical role in linoleic acid-induced endothelial cell dysfunction. Furthermore, the severe toxicity of PCBs in the presence of linoleic acid may be due in part to the generation of epoxide and diol metabolites. These findings have implications in understanding interactive mechanisms of how dietary fats can modulate dysfunction of the vascular endothelium mediated by certain environmental contaminants. | 10.1006/taap.2001.9131 |
pubmed_498_4566 | From the anti-tobacco and anti-marijuana campaigns of the twentieth century to the current controversies surrounding vaporizer use and the opioid epidemic, substances and substance use have been at the forefront of cultural, public health, and legal debates for decades. This work explores treatment outcomes among those with substance use disorders (SUD) by 1) comparing legal, semi-legal, and illegal drug types and their impact on treatment outcomes and 2) evaluating the extent that there exist discrepancies between those who need and those who receive treatment. Methods: Binary logistic regression models were employed with data from the 2018 National Survey on Drug Use and Health (NSDUH) to examine the relationship between type of SUD and treatment outcomes. Results: Results indicate that those with SUD to illegal drugs were generally more likely to report a need and receive treatment than those with SUD to a legal drug (alcohol use disorder). Those with SUD to some types of illegal drugs did not report more need, but in some cases reported more treatment. Additionally, analyses indicated that across treatment outcomes, those with marijuana use disorder (semi-legal drug) were less likely to report needing or receiving treatment than those with alcohol use disorder. Conclusions: This research examined the role of drugs' legal status and type of SUD in need for treatment and treatment received. The discrepancy between needing and receiving treatment suggests those with some types of SUDs may be pushed into treatment at higher rates based on the stigma surrounding the substance they use. | 10.1080/10826084.2021.1949608 |
pubmed_156_3003 | The activity of tigecycline against Staphylococcus epidermidis growing in an in vitro adherent-cell biofilm model was determined. Tigecycline minimum bactericidal concentrations (MBCs) ranged from 1 to 8 microg/ml for S. epidermidis growing in a biofilm of adherent cells, compared to MBCs of 0.12 to >32 microg/ml for freely growing cells. The killing activity of tigecycline against the adherent bacteria was at least fourfold better than that of vancomycin and daptomycin. | 10.1128/AAC.47.12.3967-3969.2003 |
pubmed_324_14502 | Subarachnoid hemorrhage is characterized by the extravasation of blood into the spaces covering the central nervous system which are filled with cerebrospinal fluid. The leading cause of non-traumatic subarachnoid hemorrhage is rupture of an intracranial aneurysm. Computed tomography (CT) scanning of the head should be the first examination performed in any patient with suspected subarachnoid hemorrhage. The characteristic appearance of extravasated blood is hyperdense. Head CT scanning can also demonstrate intraparenchymal hematomas, hydrocephalus and cerebral edema and can help predict the site of aneurysm rupture. | 10.1007/s00117-010-2049-y |
pubmed_115_6336 | Previously, we established the in vivo lung metastasis model of rat HCC induced by two hepatocarcinogens, diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR) at a dose of 120 ppm. This model allows us to investigate modifying factors leading to the inhibition of metastasis formation. However, low survival rates made the evaluation of metastasis formation difficult. The current experiments were conducted to modify the experimental protocol to improve survival and to establish a better animal metastasis model. Lower doses of NMOR (80 or 40 ppm in drinking water) were given to F344 rats for 14 weeks after DEN treatment. Survival rates in the 80 ppm group and in the 40 ppm group were 57% and 81%, respectively and these values were significantly higher than that in 120 ppm. Incidences of lung metastasis in the 40 ppm group steadily increased up to 67% by week 36 while that in the 80 ppm increased sharply up to 86% by week 24. Severity of lung metastases in the 40 ppm group at week 36 was mild compared with the 80 ppm group at week 24. In the second experiment, in order to characterize HCC development and lung metastasis in the 40 ppm group, rats given DEN and then followed with 40 ppm NMOR were killed sequentially. Development of HCC was observed at week 14 and reached 100% incidence at week 20. First lung metastatic lesions were evident at week 22, and incidence of lung metastasis reached 100%. Tumor cells were identified in the blood at week 20 by RT-PCR. The current study revealed that 40 ppm NMOR for 14 weeks after DEN treatment developed HCC without lung metastases at week 22, then HCC with a frequent lung metastasis at week 40. Thus, it can be said that this system is a more appropriate model for elucidation of mechanisms of metastasis and also for analysis of factors to inhibit natural metastasis. | 10.1007/s10585-005-2807-9 |
pubmed_534_6958 | The genome sequences of the plastid and mitochondrion of white spruce (Picea glauca) were assembled from whole-genome shotgun sequencing data using ABySS. The sequencing data contained reads from both the nuclear and organellar genomes, and reads of the organellar genomes were abundant in the data as each cell harbors hundreds of mitochondria and plastids. Hence, assembly of the 123-kb plastid and 5.9-Mb mitochondrial genomes were accomplished by analyzing data sets primarily representing low coverage of the nuclear genome. The assembled organellar genomes were annotated for their coding genes, ribosomal RNA, and transfer RNA. Transcript abundances of the mitochondrial genes were quantified in three developmental tissues and five mature tissues using data from RNA-seq experiments. C-to-U RNA editing was observed in the majority of mitochondrial genes, and in four genes, editing events were noted to modify ACG codons to create cryptic AUG start codons. The informatics methodology presented in this study should prove useful to assemble organellar genomes of other plant species using whole-genome shotgun sequencing data. | 10.1093/gbe/evv244 |
pubmed_840_23466 | We evaluated the effects of immunostimulation in the development of postweaning multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a grower/finisher barn with a history of PMWS. The pigs were allocated to 5 treatment groups: 4 groups received a single intramuscular injection of RespiSure-ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil-based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n = 172), or physiologic saline (n = 218); 1 group received no treatment (n = 171). Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus type 2 (PCV-2) was detected by immunohistochemical testing within lesions of mesenteric lymph node, spleen, Peyer's patch, and lung of affected pigs. There was no significant difference in the incidence of PMWS among the groups. The findings indicate that immunostimulation did not influence the expression of PMWS in this study. Thus, routine vaccination against swine diseases may not significantly contribute to the occurrence of PMWS under field conditions. | pubmed_840_23466 |
pubmed_498_16910 | OBJECTIVE
To explore the existing evidence on patient understanding of and/or participation in infection-related care in surgical specialties.
METHOD
A scoping review of the literature was conducted. PubMed, Web of Science, Scopus, and grey literature sources were searched using predefined search criteria for policies, guidelines, and studies in the English language. Data synthesis was done through content and thematic analysis to identify key themes in the included studies.
RESULTS
The initial search identified 604 studies, of which 41 (36 from high-income and five from low- and middle-income countries) were included in the final review. Most of the included studies focused on measures to engage patients in infection prevention and control (IPC) activities, with few examples of antimicrobial stewardship (AMS) engagement strategies. While patient engagement interventions in infection-related care varied depending on study goals, surgical wound management was the most common intervention. AMS engagement was primarily limited to needs assessment, without follow-up to address such needs.
CONCLUSION
Existing evidence highlights a gap in patient participation in infection-related care in the surgical pathway. Standardization of patient engagement strategies is challenging, particularly in the context of surgery, where several factors influence how the patient can engage and retain information. Infection-related patient engagement and participation strategies in surgery need to be inclusive and contextually fit. | 10.1016/j.ijid.2021.07.039 |
pubmed_862_6006 | Usually, Kurie plots are used to analyze beta-spectra shape-factor functions measured by means of semiconductor and magnetic spectrometers. A drawback of these techniques is the occurrence of self-absorption within the samples through which the emission spectrum is altered. In liquid-scintillation samples self-absorption does not occur, but the poor energy resolution makes the analysis of the spectra difficult. To overcome this problem, two resolution-invariant observables are used for determining the shape-factor function of (90)Sr: (1) the maximum point energy and (2) the cutoff energy yield. The measured shape-factor function of (90)Sr agrees with the one which is predicted by theory for the first-forbidden unique transition. | 10.1016/j.apradiso.2008.02.049 |
pubmed_259_10797 | Electrodeposition is known to be suitable for separation and preconcentration of extremely low concentrations of analyte from bulk samples and is instrumentally is very simple. In this approach a new combined system was designed for in-situ electrodeposition of ultratrace levels of gold from micro samples on to a graphite furnace prior to determination by electrothermal atomic absorption spectrometry (ETAAS). Sediment samples were digested and traces of the gold content were extracted with boiling aqua regia. To prevent the highly corrosive effect of aqua regia media, the graphite tube surface was pre-coated by electrodeposition of ppm amounts of Pd prior to sample introduction. Separation of the analyte from the matrix was achieved by electrodeposition of the analyte in situ on the Pd/C surface of the furnace tube. Vanadium was also used as a modifier to stabilize the analyte from decomposition at charring temperatures. By using the proposed microelectrolysis preconcentration technique a considerable improvement in sensitivity and detection limit was achieved compared with conventional ETAAS. Characteristic masses for ED-ETAAS techniques in both nitric acid and aqua regia were reported to be m(o)=4.1 pg, with %RSD=2.9; the calculated LOD was 0.105 ppb, and typical calibration graphs for this element in nitric acid and aqua regia for both techniques were linear up to 70 microg L(-1) with about 99% recovery. Six reference sediments samples were tested by the proposed technique and by the Conv-ETAAS method. The results were in agreement with recommended values (reported by a reference laboratory using UV-visible spectrometry), demonstrating the efficiency of extraction and preconcentration of ultratrace levels of gold. | 10.1007/s00216-003-1922-1 |
pubmed_776_18011 | A 65-year-old woman was referred to our department because of general fatigue and anorexia for one month. The patient has received anti-rheumatoid therapy with aurothiomalate and bucillamine for the last two years for rheumatoid arthritis diagnosed 11 years earlier. Based on her systemic arthralgia, positive RA factor, and characteristic pleural effusion, the diagnosis of rheumatoid pleural effusion was made and prednisolone was administered. Two weeks later, the pleural effusion had improved. Rapid tapering of the drug over one month resulted in reappearance of pleural effusion. Slow tapering of prednisolone resulted in disappearance of the pleural effusion. One year after discharge, the patient was again referred to our department because of increased arthralgia. Pleural effusion reappeared after similar rapid tapering of the drug. These results suggest that induction of pleural effusion may occur in rheumatoid arthritis patients as a result of rapid tapering of steroids. Tapering of steroids in rheumatoid patients should be performed with care. | pubmed_776_18011 |
pubmed_323_3014 | The adsorption of a colloidal particle at a fluid interface is studied theoretically and numerically, documenting distinctly different relaxation regimes. The adsorption of a perfectly smooth particle is characterized by a fast exponential relaxation to thermodynamic equilibrium where the interfacial free energy reaches the global minimum. The short relaxation time is given by the ratio of viscous damping to capillary forces. Physical and/or chemical heterogeneities, however, can result in multiple minima of the free energy giving rise to metastability. In the presence of metastable states we observe a crossover to a slow logarithmic relaxation reminiscent of physical aging in glassy systems; sufficiently close to equilibrium the slow relaxation becomes exponential. The long relaxation time is determined by the Kramers escape rate from metastable states. Derived analytical expressions yield quantitative agreement with molecular dynamics simulations and recent experimental observations. This work provides new insights on the adsorption of colloidal particles with surface microstructure. | 10.1103/PhysRevLett.111.028302 |
pubmed_435_779 | INTRODUCTION
Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.
METHODS
All paediatric heart transplant recipients (2004-2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.
RESULTS
A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (-18.2 versus -14.1), global circumferential strain (-24.1 versus -19.6), longitudinal strain rate (-1 versus -0.8), circumferential strain rate (-1.3 versus -1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.
CONCLUSIONS
Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function. | 10.1017/S1047951119001185 |
pubmed_570_25093 | The aim of the study was to determine the contemporary socio-clinical profile and perinatal outcome of illicit substance use in pregnancy in a large UK city and compare with published literature. Cases were identified retrospectively from the 'cause for concern' referrals over 5 years (2003-2007). Data was collected on mother-infant pair from medical notes and laboratory records. Chi-square and Mann-Whitney U tests were used where appropriate for statistical analysis. One hundred sixty-eight women were identified as using illicit substance in pregnancy. Smoking (97.4%), unemployment (85.4%) and single status (42.3%) were frequent. Besides controlled use of methadone, heroin, cannabis and benzodiazepines were the most commonly used drugs. Hepatitis C prevalence was high (29.9%) despite low antenatal screening rates (57.7%). Neonatal morbidity was related to prematurity (22.9%), small for dates (28.6%) and neonatal abstinence syndrome (NAS; 58.9%). By day 5 of life, 95.1% of the babies developing NAS and 96.1% of those requiring pharmacological treatment were symptomatic. Of the infants developing NAS, 31.7% required pharmacological treatment. A total of 82.5% babies went home with their mother, and 21.2% were placed on the Child Protection Register. Only 14.3% were breast feeding at discharge. Illicit substance use in pregnancy continues to be associated with significant maternal and neonatal morbidity, and the socio-clinical profile in this decade appears unchanged in the UK. Hepatitis C prevalence is high, and detection should be improved through targeted antenatal screening. Where facility in the community is unavailable, 5 days of hospital stay is sufficient to safely identify babies at risk of developing NAS. Most babies were discharged home with their mother. | 10.1007/s00431-010-1284-6 |
pubmed_536_6669 | RATIONALE
Cytokines are humoral regulatory molecules that act together in immunologic pathways underlying pathogenesis. Grossly elevated blood levels characterize certain diseases; variations within physiologic ranges could also have significance. We therefore evaluated the performance characteristics of a multiplex cytokine immunoassay.
METHODS
We used a fluorescent bead-based (Luminex) immunoassay kit to simultaneously measure interleukin (IL) 1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, IFNgamma, granulocyte colony-stimulating factor, and tumor necrosis factor-alpha. We tested identical aliquots of serum from 38 asymptomatic individuals on three different days and matched sets of serum, heparinized plasma, and acid citrate dextrose plasma from an additional 38 healthy donors expected to have low cytokine concentrations. We applied multiple imputation to calculate unbiased reproducibility estimates for measurements below the limits of detection. Correlations among the cytokines were assessed by Spearman rank order coefficients and principal components analyses.
RESULTS
Of the 13 cytokines, 3 were undetectable (IL1beta, IL2, IL5) in more than half of the serum samples. Coefficients of variation for replicate serum measurements ranged from 18% to 44%, with intraclass correlation coefficients ranging from 55% to 98%. Only IL4, IL6, and IL8 had statistically significant correlations (Spearman rho, 0.42-0.94) between serum and acid citrate dextrose or heparin plasma levels.
CONCLUSIONS
Interindividual differences outweigh substantial laboratory variation for these assays, yielding high intraclass correlation coefficients despite unimpressive coefficients of variation. Plasma measurements generally are not reflective of serum levels and hence are not interchangeable. With their small volume, low cost per test, and multiplex capacity, Luminex-based cytokine assays have potential utility for epidemiologic studies. | 10.1158/1055-9965.EPI-08-0311 |
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