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pubmed_1017_8011 | BACKGROUND
In hospitals, effective and efficient communication among care providers is critical to the provision of high-quality patient care. Yet, major problems impede communications including the frequent use of interruptive and one-way communication paradigms. This is especially frustrating for frontline providers given the dynamic nature of hospital care teams in an environment that is in constant flux.
METHODS
We conducted a pre-post evaluation of a commercially available secured messaging mobile application on 4 hospital units at a single institution for over one year. We included care providers on these units: residents, hospitalists, fellows, nurses, social workers, and pharmacists. Utilization metrics and survey responses on clinician perceptions were collected and analyzed using descriptive statistics, the Kruskal-Wallis test, and Mann-Whitney U test where appropriate.
RESULTS
Between May 2013 and June 2014, 1,021 providers sent a total of 708,456 messages. About 85.5% of total threads were between two providers and the remaining were group messages. Residents and social workers/clinical resource coordinators were the largest per person users of this communication system, sending 9 (IQR 2-20) and 9 (IQR 2-22) messages per person per day, and receiving 18 (IQR 5-36) and 14 (IQR 5-29) messages per person per day, respectively (p=0.0001). More than half of the messages received by hospitalists, residents, and nurses were read within a minute. Communicating using secured messaging was found to be statistically significantly less disruptive to workflow by both nursing and physician survey respondents (p<0.001 for each comparison).
CONCLUSIONS
Routine adoption of secured messaging improved perceived efficiency among providers on 4 hospital units. Our study suggests that a mobile application can improve communication and workflow efficiency among providers in a hospital. New technology has the potential to improve communication among care providers in hospitals. | 10.4338/ACI-2015-11-RA-0151 |
pubmed_705_4661 | OBJECTIVE
The adhesion of monocytes to endothelium, an early event in atherosclerosis is mediated by cell adhesion molecules. Signal-transduction pathways for these binding molecules include the translocation of the transcription factor NF-kappaB; moreover, intracellularly generated oxygen-derived free radicals play a major role in this process. In this study we evaluated the extent to which lacidipine, a calcium antagonist with antioxidant properties, affects the expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells, induced by different pro-oxidant signals such as oxidized low density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-alpha).
METHODS
We incubated 5 micromol/l Cu2+-oxidized LDL and TNF-alpha (2 ng/ml) with human umbilical vein endothelial cells for 48 and 6 h, respectively. ICAM-1, VCAM-1 and E-selectin were measured by flow cytometry. NF-kappaB was evaluated by electrophoretic mobility shift assay.
RESULTS
The incubation of 5 micromol/l Cu2+-oxidized LDL not only caused a dose-dependent increase in ICAM-1, VCAM-1 and E-selectin (P < 0.001), but also synergically increased their TNF-alpha-induced expression (P < 0.001). The addition of lacidipine to human umbilical vein endothelial cells significantly reduced the expression of ICAM-1, VCAM-1 and E-selectin induced by TNF-alpha alone or with oxidized LDL (P < 0.001). The reduction in adhesion molecule expression caused by lacidipine was paralleled by a significant fall in NF-kappaB translocation.
CONCLUSIONS
The results suggest that lacidipine may have prevented NF-kappaB-mediated adhesion molecule expression by exerting its effects on oxygen-derived free radicals. The results support previous observations that lacidipine may have therapeutic effects in atherosclerosis. | 10.1097/00004872-199715120-00065 |
pubmed_569_22251 | MOTIVATION
In the past few years, an increasing number of crystal and cryo electron microscopy (cryo-EM) structures of large macromolecular complexes, such as the ribosome or the RNA polymerase, have become available from various species. These multi-subunit complexes can be difficult to analyze at the level of amino acid sequence in combination with the 3D structural organization of the complex. Therefore, novel tools for simultaneous analysis of structure and sequence information of complex assemblies are required to better understand the basis of molecular mechanisms and their functional implications.
RESULTS
Here, we present a web-based tool, Integrative Biology of Sequences and Structures (IBiSS), which is designed for interactively displaying 3D structures and selected sequences of subunits from large macromolecular complexes thus allowing simultaneous structure-sequence analysis such as conserved residues involved in catalysis or protein-protein interfaces. This tool comprises a Graphic User Interface and uses a rapid-access internal database, containing the relevant pre-aligned multiple sequences across all species available and 3D structural information. These annotations are automatically retrieved and updated from UniProt and crystallographic and cryo-EM data available in the Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB).
AVAILABILITY AND IMPLEMENTATION
The database contains all currently available structures of ribosomes, RNA polymerases, nucleosomes, proteasome, photosystem I and II complexes. IBiSS is available at http://ibiss.igbmc.fr
CONTACT
[email protected]. | 10.1093/bioinformatics/btv347 |
pubmed_584_14202 | Spatial resolution and contrast sensitivity requirements for some types of medical image techniques, including mammography, delay the implementation of new digital technologies, namely, computer-aided diagnosis, picture archiving and communications systems, or teleradiology. In order to reduce transmission time and storage cost, an efficient data-compression scheme to reduce digital data without significant degradation of medical image quality is needed. In this study, we have applied two region-based compression methods to digital mammograms. In both methods, after segmenting the breast region, a region-based discrete wavelet transform is applied, followed by an object-based extension of the set partitioning in hierarchical trees (OB-SPIHT) coding algorithm in one method, and an object-based extension of the set partitioned embedded block (OB-SPECK) coding algorithm in the other. We have compared these specific implementations against the original SPIHT and the new standard JPEG 2000, both using reversible and irreversible filters, on five digital mammograms compressed at rates ranging from 0.1 to 1.0 bit per pixel (bbp). Distortion was evaluated for all images and compression rates by the peak signal-to-noise ratio. For all images, OB-SPIHT and OB-SPECK performed substantially better than the traditional SPIHT and JPEG 2000, and a slight difference in performance was found between them. A comparison applying SPIHT and the standard JPEG 2000 to the same set of images with the background pixels fixed to zero was also carried out, obtaining similar implementation as region-based methods. For digital mammography, region-based compression methods represent an improvement in compression efficiency from full-image methods, also providing the possibility of encoding multiple regions of interest independently. | 10.1109/TMI.2003.817812 |
pubmed_199_13613 | Mutagenicity of three selected series of 2-furylethylene was determined by the Ames test. These included: nine alkylesters and eleven N-alkylamides of 5-nitro-2-furylacrylic acid (NFAA) and ten derivatives differing not only at exocyclic double bond, but also in the position 5 of the furan ring. Mutagenicity of the derivatives depends on the presence of the 5-nitro-furan centre in the molecule; side chains in the position 2 modify the degree of mutagenicity. Among the derivatives of NFAA tested as changing the substituents virtually does not affect chemical properties of the 5-nitrofuran ring. Mutagenicity of the n-alkyl congeners decreases linearly with increasing lipophilicity. Mutagenicity of the derivatives with branched alkyl substituents is lower than expected from the behaviour of the n-alkyl homologues. | 10.1016/s0009-2797(85)80092-2 |
pubmed_378_855 | Deep somatic pain originating in joints and tendons is a major therapeutic challenge. Spontaneous pain and mechanical hypersensitivity can develop as a consequence of sensitization of primary afferents directly involved in the inflammatory process, but also following sensitization of neuronal processing in the spinal cord (central sensitization) or higher centres. Inflammatory pain is linked to sensitization of sensory proteins at the nociceptive endings whereas pain originating from nerve damage (neuropathic pain) has been linked to changes in axonal ion channels producing ectopic discharge in nociceptors as a source of pain. New targets for analgesic therapy include sensory proteins at the nociceptive nerve endings such as the activating TRPV and ASIC channels, but also inhibitory opioid and cannabinoid receptors. Therapeutic targets are also found among the axonal channels that set membrane potential and modulate discharge frequency such as voltage sensitive sodium channels and various potassium channels. | 10.1016/j.addr.2006.01.011 |
pubmed_1100_14754 | Osteopetrois is an inherited bone disease characterized by an excessive accumulation of bone throughout the skeleton. The disease in the ia (incisors absent) rat is the result of reduced bone resorption caused by defective, although numerous osteoclasts. In addition to the bone defects, ia rats have suppressed natural immunity, even though these animals have excessive numbers of natural killer (NK) cells. The osteopetrotic condition also appears to have an associated abnormality in vitamin D metabolism. Because 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] stimulates bone resorption and has a role in the immunoregulation of NK cells, mutant and normal rats were infused with 1,25-(OH)2D3 for 14 days in an attempt to correct the defects in this mutant. Serum levels of osteocalcin, 25-OHD3, and 1,25-(OH)2D3, as well as NK function and parameters of bone resorption, were evaluated after the infusion period. Serum levels of osteocalcin and 1,25-(OH)2D3 were elevated in both ia and normal rats treated with 1,25-(OH)2D3. Serum 25-OHD3 levels were significantly reduced in the treated animals. The elevated percentage of NK cells normally found in ia rats was reduced to normal in the treated mutants, and NK cell function was elevated to normal levels of lytic activity. The percentage of NK cells and NK function remained unchanged in the treated normal rats. The bone marrow cavity size was significantly increased in the 1,25-(OH)2D3-treated mutants, as was the percentage of osteoclasts exhibiting normal morphology. Radiographically, the mutant bones were less dense.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1002/jbmr.5650090419 |
pubmed_697_19295 | Objective: Oral anticoagulants are widely administered to patients with atrial fibrillation in order to prevent the onset of cardiogenic embolisms. However, intracranial bleeding during anticoagulant therapy often leads to fatal outcomes. Accordingly, the use of novel oral anticoagulants (NOACs), which less frequently have intracranial bleeding as a complication, is expanding. A nationwide survey of intracranial bleeding and its prognosis in Japan reported that intracranial bleeding of advanced severity was not common after NOAC administration. In this report, two cases from our institute are presented. Patients: Case 1 was an 85-year-old man with a right frontal lobe hemorrhage while under dabigatran therapy. Case 2 was an 81-year-old man who had cerebellar hemorrhage while under rivaroxaban therapy. Result: In both patients, the clinical course progressed without aggravation of bleeding or neurological abnormalities once anticoagulant therapy was discontinued. Conclusion: These observations suggest that intracranial hemorrhage during NOAC therapy is easily controlled by discontinuation of the drug. NOAC administration may therefore be appropriate despite the risk of such severe complications. Further case studies that include a subgroup analysis with respect to each NOAC or patient background will be required to establish appropriate guidelines for the prevention of cardiogenic embolisms in patients with atrial fibrillation. | 10.2185/jrm.2901 |
pubmed_604_6182 | PPE44 is a member of the Mycobacterium tuberculosis PPE proteins, a polymorphic family of 69 glycine-rich proteins that predictively represent a source of antigenic variation. The genetic diversity of gene ppe44 among clinical isolates has been studied. No genomic polymorphism of ppe44 was found by a PCR-restriction fragment length polymorphism assay using three restriction enzymes. Nucleotide sequencing of gene ppe44 of a number of isolates, selected to represent the major phylogenetic lineages of M. tuberculosis, showed no nucleotide substitution, with the exception of isolates of the Beijing genotype. These findings indicate that gene ppe44 is basically conserved among M. tuberculosis strains. The expression of gene ppe44 was then determined at the transcriptional level by a real-time reverse transcriptase PCR assay. Extremely high quantitative variations in ppe44 expression were found among the isolates; ppe44 expression of the Beijing strains was significantly higher than the non-Beijing strains. To test whether differential expression of gene ppe44 has the potential to provide a dynamic antigen display, antibodies to PPE44 were titered in the sera of M. tuberculosis-infected subjects. Variation of antibody response to PPE44 was found with regard to both antibody titers and the proportion of responding subjects. These results indicate that the differential expression of genes ppe could influence the host's immune responsiveness, thus having implications in the immunopathogenesis of tuberculosis. | 10.1111/j.1574-695X.2007.00315.x |
pubmed_755_14352 | Analysis of surgical treatment of 76 patients with Hashimoto's disease has shown that focal forms of disease are an absolute indication for operation: cancer was diagnosed in 6.6. per cent of patients in intraoperative verification. Progressive thyrotoxicosis or neck compression served as an indication in a diffuse form of lesion. | pubmed_755_14352 |
pubmed_139_7575 | von Willebrand protein was found to promote the incorporation of platelets into evolving fibrin thrombi. Using formalin-treated or fresh platelets, both the initial rate and extent of platelet incorporation into polymerizing fibrin were dependent on von Willebrand protein. von Willebrand protein was incorporated into evolving fibrin thrombi in parallel with platelets. Soluble fibrin monomer covalently linked to acrylonitrile beads (Matrex 102) bound von Willebrand protein specifically and saturably with an apparent approximate dissociation constant (KD) of 15 micrograms/ml. Glycocalicin, the water-soluble proteolytic fragment of glycoprotein Ib, bound to fibrin monomer in this system specifically and saturably, as well, with an apparent approximate KD of 5 micrograms/ml, but only in the presence of saturating concentrations of von Willebrand protein. These data demonstrate that the initial rate and extent of platelet incorporation into evolving fibrin thrombi are dependent on von Willebrand protein; von Willebrand protein serves as a link between polymerizing fibrin and platelet surface glycoprotein Ib; and von Willebrand protein binds to fibrin monomer and is thereby able to bind to platelet surface glycoprotein Ib in the absence of ristocetin. | 10.1172/JCI112668 |
pubmed_919_4819 | The early history of "DNA fingerprinting" in the UK might have been different were it not for the accounts of two dramatic courtroom trials, made by the participants and the media, in the mid-1980s. But these reports, which misrepresented the importance DNA evidence had in the trials, left a strong impression on the British public and on judges on both sides of the Atlantic. These trials, widely considered to be the first "victories" for DNA fingerprinting, have been frequently cited as proof of the utility and reliability of the technique, in both the UK and beyond. But in reality, it was the threat of DNA evidence being used rather than the integrity or validity of it that resolved these cases. At that time, DNA fingerprinting was still in its infancy, an untried and untested technology. | 10.1016/j.endeavour.2005.04.006 |
pubmed_848_18200 | MIIENJ has paid $30,144,636 in indemnity from 1977 through 1988 for medical malpractice suits arising from medication errors. A review of these files revealed that patients incurred death and serious morbidity, and that several specific behavior errors accounted for the majority of patient injury. Among the damages that occurred during that time period were 88 deaths, 15 patients with profound brain damage, 15 patients who alleged that they had become addicted to medications prescribed for pain, 10 patients who required amputations of limbs, and 12 patients who suffered some degree of hearing loss or decreased visual acuity. The predominant categories where insureds incurred difficulty were in disregarding patient allergies to specific drugs (acetylsalicylic acid (aspirin), penicillin and its derivatives); prescribing drugs without consideration of the patient's medical history; failing to monitor therapy with anticoagulants, nonsteroidal anti-inflammatory drugs, digitalis derivatives, theophylline, and aminoglycoside antibiotics; antibiotic therapy; and errors in the writing of prescriptions. In order to reduce the number of patient injuries and accompanying medical malpractice suits from medication errors, the following suggestions are offered: 1. Heed the patient's warning regarding drug allergies and prescribe a substitute drug, especially if the drug is aspirin or penicillin (and derivatives) or if the patient gives a history of having asthma. If the patient gives a history of aspirin sensitivity, make certain the drug you are prescribing does not contain aspirin as one of its components. Often physicians stated that they were not aware that aspirin was contained in the drug they prescribed for patients with a documented allergy to aspirin.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_848_18200 |
pubmed_35_17017 | The surgical outcomes in 149 patients with diabetes and carpal tunnel syndrome who underwent transverse carpal ligament release surgery are reported. Associated factors such as insulin dependence, length of time with diabetes, electrodiagnostic studies, severity of neurological deficit, presence of polyneuropathy, and cervical disc disease were considered. Analysis of preoperative and postoperative symptoms, clinical findings, diagnostic studies, and patient self-assessment indicated that the majority of patients with diabetes experienced a favorable surgical outcome, regardless of any associated factors. Eighty-four percent of the patients reported good to excellent postoperative results in their hands. Further analysis of the subpopulation of insulin-dependent diabetics showed that 81% experienced good to excellent postoperative results. These results compare favorably with those of the control group: 200 nondiabetic patients, of whom 90% rated their results from carpal tunnel release surgery as good to excellent. There were no major complications in any group. | 10.3171/foc.1997.3.4.10 |
pubmed_764_2742 | Two partial chicken POU domain genes were isolated by genomic library screening and reverse transcriptase-polymerase chain reaction (RT-PCR). A cDNA clone encoding the POU domain of Brn-3a, which showed near identity to the human Brn-3a sequence (100% amino acid identity), was isolated and mapped to chicken linkage group E48. A Skn-1/Epoc-1/Oct-11 genomic clone was identified and mapped to chicken linkage group E49. This mapping identified a syntenic group in chicken linkage group E49 that was conserved with human chromosome 11q23 and mouse chromosome 9. | 10.1111/j.1365-2052.1997.00160.x |
pubmed_37_2690 | OBJECTIVE
Knowledge of injuries of earthquake victims is important to plan relief efforts. This cross-sectional study was conducted following the 08 October 2005 earthquake in Northern Pakistan to determine the pattern of injuries sustained and their relationship with age and gender in order to identify the medical needs in an earthquake-affected zone.
METHODS
The study was conducted between 13 October and 23 October 2005 at the Emergency Relief Hospital, Doraha, Mansehra. From the 1,700 patients registered in the hospital, 310 were sampled randomly for the study. Demography and details of the patients' injuries were noted by history and physical examination. Twelve cases were omitted due to incomplete data.
RESULTS
Of the cases, 54% were female. Children less than or equal to 10 years old formed the largest age group. Isolated bone injuries were present in 41%, soft tissue injuries in 36%, and mixed injuries in 23% of the patients. The most common bone injury was lower limb fracture (52%), while the most common non-bone injury was non-infected, soft tissue wounds on the limbs (33%). Among patients with soft tissue injuries, gangrenous wounds were present in 9%, and grossly infected wounds in 30% (20% on limbs and 10% on rest of the body).
CONCLUSIONS
The population injured during the earthquake showed a higher proportion of females and children less than or equal to 10 years old, and lower limb bone injuries. The data highlight the need to address orthopedic, pediatric, and women's health issues, and for logistic arrangement of relevant diagnostic and therapeutic facilities at the initial stages of relief activities after earthquakes. | 10.1017/s1049023x00007470 |
others_280_4648 | Venous plasma histamine levels were measured in 60 asthmatic subjects in order to investigate the role of histamine in naturally occurring asthmatic episodes. The patients were divided into 3 groups of 20 according to the degree of disease activity. Group A consisted of asthmatic patients with severe exacerbations. Flow/volume curves demonstrated a forced expiratory volume in 1 sec to forced vital capacity ratio ( FEV1 FVC) of less than 55% and a maximum expiratory flow at 50% of FVC (MEF50) of less than 1.0 L/sec. Asthmatics in group B were in partial remission. The patients in this group had FEV1 FVC ratios between 55% and 75% and MEF50 values between 1.0 and 4.0 L/sec. The remaining asthmatic patients (group C) were in complete remission. They were asymptomatic and had normal physical examinations and flow/volume curves. Venous plasma histamine levels were also measured in 50 normal control subjects (group D). Every asthmatic subject in group A had plasma histamine above 1.25 ng/ml (mean, 1.9 ng/ml ± 0.5). Only 3 asthmatic patients in group B and 3 in group C had venous plasma histamine levels greater than 1 ng/ml. None of the normal subjects in group D had plasma histamine above 1 ng/ml. These data show a relationship between spontaneously occurring asthmatic attacks and elevated plasma histamine and support previous studies suggesting that histamine may play a role in the mediation of bronchial asthma. © 1977 | 10.1016/0091-6749(77)90111-7 |
pubmed_133_22541 | Agents used to measure glomerular filtration rate (GFR) give a biexponential plasma disappearance curve on multiple peripheral venous sampling between 20 min and 4 h after intravenous injection. These two exponentials are generally regarded to represent equilibration of agent throughout the extracellular fluid (ECF) space and renal clearance, respectively. In seven subjects undergoing diagnostic arteriography, arterial and antecubital venous plasma samples were obtained up to 60 min in five and up to 120 min in two following simultaneous intravenous injection of 99Tcm-diethylene triamine pentaacetate (99Tcm-DTPA) and inulin. The count rate from 99Tcm was simultaneously recorded over the calf with a collimated scintillation probe in five subjects up to 60 min post-injection. The arterial and venous time-concentration curves were interpolated and subtracted to give a curve of the arterio-venous (A-V) concentration difference, which was then integrated. Arterial time-concentration curves display three exponentials, the first of which has the largest amplitude and disappears by about 20 min. The A-V concentration difference becomes zero at about the same time. The integral of the A-V concentration difference, which represents activity in the interstitial space of the forearm, has a time course consistent with the second compartment of a model of two compartments in series (the first being plasma) and a time course that is reciprocally similar to the first exponential of the triexponential arterial plasma curve. The curve externally recorded by scintillation probe has a shape consistent with a signal that is the composite of interstitial 99Tcm-DTPA and plasma 99Tcm-DTPA activities. The arterial plasma clearance curve of GFR agents is triexponential; the first exponential reflects equilibration of agent between plasma and the interstitial space of carcass tissue (mainly muscle and skin). The second exponential is minor compared with the first; it is not clear what it represents. The third exponential reflects renal clearance. | 10.1097/00006231-199911000-00010 |
pubmed_414_12141 | To investigate the molecular mechanisms of bacterial resistance in susceptible and resistant cultivars of tomato, a proteomic approach was adopted. Four cultivars of tomato were selected on the basis of their response to bacterial (Pseudomonas solanacearum) inoculation wherein cultivar Roma and Riogarande, and cultivar Pusa Ruby and Pant Bahr were considered as resistant and susceptible cultivars, respectively. Proteins were extracted from leaves of 3-week-old seedlings of the four cultivars and separated by 2-DE. A total of nine proteins were found to be differentially expressed between the susceptible and resistant cultivars. Amino acid sequences of these proteins were determined with a protein sequencer. The identified proteins belongs to the categories of energy, protein destination and storage, and defense. Of these proteins, a 60kDa chaperonin and an apical membrane antigen were significantly upregulated in resistant cultivars compared with susceptible cultivars. Application of jasmonic acid and salicylic acid resulted in significant changes in levels of apical membrane antigen and protein disulfide-isomerase. Taken together, these results suggest that apical membrane antigen might be involved in bacterial resistance process through salicylic acid induced defense mechanism signaling in tomato plants. | 10.1016/j.peptides.2009.06.005 |
pubmed_37_4345 | Under normal conditions, hepatocyte growth factor (HGF)-induced Met tyrosine kinase (TK) activation is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalisation and degradation. Despite these controls, HGF/Met signalling contributes to oncogenesis and tumour progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumour metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programmes. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signalling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control. | 10.1016/j.ejca.2010.02.028 |
pubmed_1088_15869 | Although many proteins, receptors, and viruses are transported rearward along filopodia by retrograde actin flow, it is less clear how molecules move forward in filopodia. Myosin-X (Myo10) is an actin-based motor hypothesized to use its motor activity to move forward along actin filaments to the tips of filopodia. Here we use a sensitive total internal reflection fluorescence (TIRF) microscopy system to directly visualize the movements of GFP-Myo10. This reveals a novel form of motility at or near the single-molecule level in living cells wherein extremely faint particles of Myo10 move in a rapid and directed fashion toward the filopodial tip. These fast forward movements occur at approximately 600 nm/s over distances of up to approximately 10 microm and require Myo10 motor activity and actin filaments. As expected for imaging at the single-molecule level, the faint particles of GFP-Myo10 are diffraction limited, have an intensity range similar to single GFP molecules, and exhibit stepwise bleaching. Faint particles of GFP-Myo5a can also move toward the filopodial tip, but at a slower characteristic velocity of approximately 250 nm/s. Similar movements were not detected with GFP-Myo1a, indicating that not all myosins are capable of intrafilopodial motility. These data indicate the existence of a novel system of long-range transport based on the rapid movement of myosin molecules along filopodial actin filaments. | 10.1016/j.cub.2009.03.067 |
pubmed_364_2960 | Conveyor belts are the most widespread means of transportation for large quantities of materials in the mining sector. Therefore, autonomous methods that can help human beings to perform the inspection of the belt conveyor system is a major concern for companies. In this context, we present in this work a novel and automatic visual detector that recognizes dirt buildup on the structures of conveyor belts, which is one of the tasks of the maintenance inspectors. This visual detector can be embedded as sensors in autonomous robots for the inspection activity. The proposed system involves training a convolutional neural network from RGB images. The use of the transfer learning technique, i.e., retraining consolidated networks for image classification with our collected images has shown very effective. Two different approaches for transfer learning have been analyzed. The best one presented an average accuracy of 0.8975 with an F-1 Score of 0.8773 for the dirt recognition. A field validation experiment served to evaluate the performance of the proposed system in a real time classification task. | 10.3390/s20205762 |
pubmed_70_2847 | This study was designed to characterize naphthalene metabolism in Polaromonas naphthalenivorans CJ2. Comparisons were completed using two archetypal naphthalene-degrading bacteria: Pseudomonas putida NCIB 9816-4 and Ralstonia sp. strain U2, representative of the catechol and gentisate pathways, respectively. Strain CJ2 carries naphthalene catabolic genes that are homologous to those in Ralstonia sp. strain U2. Here we show that strain CJ2 metabolizes naphthalene via gentisate using respirometry, metabolite detection by GC-MS and cell-free enzyme assays. Unlike P. putida NCIB 9816-4 or Ralstonia sp. strain U2, strain CJ2 did not grow in minimal medium saturated with naphthalene. Growth assays revealed that strain CJ2 is inhibited by naphthalene concentrations of 78 microM (10 p.p.m.) and higher, and the inhibition of growth is accompanied by the accumulation of orange-coloured, putative naphthalene metabolites in the culture medium. Loss of cell viability coincided with the appearance of the coloured metabolites, and analysis by HPLC suggested that the accumulated metabolites were 1,2-naphthoquinone and its unstable auto-oxidation products. The naphthoquinone breakdown products accumulated in inhibited, but not uninhibited, cultures of strain CJ2. Furthermore, naphthalene itself was shown to directly inhibit growth of a regulatory mutant of strain CJ2 that is unable to metabolize naphthalene. These results suggest that, despite being able to use naphthalene as a carbon and energy source, strain CJ2 must balance naphthalene utilization against two types of toxicity. | 10.1099/mic.0.2007/010728-0 |
pubmed_1047_17663 | We have investigated the potential of stirred suspension cultures to support hematopoiesis from starting innocula of normal human bone marrow cells. Initial studies showed that the short-term maintenance of both colony-forming cell (CFC) numbers and their precursors, detected as long-term culture-initiating cells (LTC-IC), could be achieved as well in stirred suspension cultures as in static cultures. Neither of these progenitor cell populations was affected in either type of culture when porous microcarriers were added to provide an increased surface for adherent cell attachment. Supplementation of the medium with 10 ng/ml of Steel factor (SF) and 2 ng/ml of interleukin-3 (IL-3) resulted in a significant expansion of LTC-IC, CFC and total cell numbers in stirred cultures. Both the duration and ultimate magnitude of these expansions were correlated with the initial cell density and after 4 weeks the number of LTC-IC and CFC present in stirred cultures initiated with the highest starting cell concentration tested reflected average increases of 7- and 22-fold, respectively, above input values. Stirred suspension cultures offer the combined advantages of homogeneity and lack of dependence on the formation and maintenance of an adherent cell layer. Our results suggest their applicability to the development of scaled-up bioreactor systems for clinical procedures requiring the production of primitive hematopoietic cell populations. In addition, stirred suspension cultures may offer a new tool for the analysis of hematopoietic regulatory mechanisms. | 10.1038/nbt0994-909 |
pubmed_873_110 | BACKGROUND
Testicular biopsies and ejaculated spermatozoa are routinely cryopreserved in many units but the fate of these samples has not provoked large interest. This prompted us to review our data accumulated during a period of 20 years (1997 to 2016).
METHODS
For patients with biopsies (group 1) or ejaculated spermatozoa (group 2), an attempt was made to evaluate whether the samples stored, had been discarded with the patient's consent or because the patient had died, or whether they had been transported to another laboratory. In each of these categories, a previous use in our program of assisted reproduction was assessed.
RESULTS
The total utilization rate in group 1 (n=95) was 53.7% and only 5.48% in group 2 (n=365). In both groups, deceased patients had not previously used their cryopreserved samples. In detail, the utilization rates for still banked, discarded and transferred samples were 84.2%, 50% and 27.3%, respectively in group 1 and 2.88%, 10.4% and 10%, respectively in group 2.
CONCLUSION
The exact reasons for the low utilization rates of cryopreserved male gametes remain to be explored. A closer contact between sperm banking units and patients might be useful to discuss the need for further storage of the probes, their possible disposal or the prospects when a specific use for assisted reproduction is intended. | pubmed_873_110 |
pubmed_144_686 | OBJECTIVE
To examine the sociodemographic correlates of obesity among Ghanaian women.
DESIGN
The 2003 and 2008 Ghana Demographic and Health Survey data sets were used to examine the sociodemographic characteristics and the BMI of women aged 15-49 years using descriptive statistics, bivariate and multivariate analyses.
SETTING
Ghana is a West African country which is divided into ten administrative regions. The country is further divided into the northern and southern sectors. The northern sector includes the three northern regions (Northern, Upper East and Upper Westen regions) and the seven remaining regions form the southern sector.
SUBJECTS
Women aged 15-49 years whose BMI values were available.
RESULTS
The overall prevalence of obesity and overweight increased from 25·5 % in 2003 to 30·5 % in 2008. Obesity varied directly with age from 20 to 44 years. Women with higher education had the highest rate of obesity. Obesity was more common among women from wealthy households compared to women from poor households.
CONCLUSIONS
Obesity and overweight were found to be more common among older women, urban women, married women, women with higher education and women from rich households. Adoption of healthy lifestyles and the implementation of policies that promote healthy living can help reduce the prevalence of overweight and obesity. | 10.1017/S1368980010002879 |
pubmed_308_7066 | Pyoderma gangrenosum is an unusual cause of skin ulcerations that wound specialists must be prepared to recognize. There is no diagnostic test since it is a diagnosis of exclusion, and if the disease is not recognized it can quickly become much worse. Pathergy, whereby a lesion begins or worsens due to trauma, such as a scrape, bite, debridement, surgery, or biopsy, is seen with pyoderma and requires special consideration. This case series and review will summarize the salient features of pyoderma and its treatment with an emphasis on the controversial role of surgery with pyoderma. | pubmed_308_7066 |
pubmed_30_8211 | In adult rat lung the lectin Maclura pomifera agglutinin (MPA) binds apically to alveolar type II (ATII) cells but not to alveolar type I (ATI) cells. This suggests that the presence of MPA binding glycoproteins might be a criterion by which to distinguish the differentiated state of these two adult alveolar epithelial cells. The authors therefore studied MPA binding glycoproteins of ATII cells, comparing, biochemically and cytochemically, MPA binding glycoproteins in freshly isolated ATII cells with those in cultures of ATII cells that are "dedifferentiating" or have "dedifferentiated" as a result of growth on tissue culture plasticware. A MPA binding glycoprotein (185 kd) that is present in freshly isolated "differentiated" ATII cells and then is subsequently lost as isolated ATII cells "dedifferentiate" in tissue culture has been identified. This 185 kd MPA binding glycoprotein alone, or expressed in conjunction with other proteins, is a candidate for a differentiation marker for ATII cells. Preliminary data suggests that this 185 kd MPA binding glycoprotein is not found in ATI cells. | pubmed_30_8211 |
pubmed_358_4213 | OBJECTIVE
Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model.
METHODS
Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons.
RESULTS
All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons.
CONCLUSIONS
The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental. | 10.1067/mtc.2000.106841 |
pubmed_1031_4093 | Correlations between the chemical structures of agricultural fungicides and mRNA expression levels following exposure of Saccharomyces cerevisiae to toxic doses of thiuram, zineb, maneb, TPN, and PCP were examined. Structurally, thiuram, zineb, and maneb are dithiocarbamate fungicides, whereas TPN and PCP are not. To characterize chemical toxicity, genes expression was classified according to the functional groups used by the MIPS database. However, no correlations between the classification scheme and chemical structures were found. Hierarchical clustering of gene expression profiles was performed to characterize the effects of the five chemicals. According to this analysis the similarity of gene expression profiles depended on the similarity of chemical structures. These results suggest that DNA microarray technology has potential for predicting the major chemicals which will cause environmental toxicity and will provide information on new biomonitoring methods. | 10.1021/es026156b |
pubmed_51_173 | BACKGROUND
On examination of the literature in Latin America and the Caribbean, and in particular Jamaica, no study could be found that investigated the health and health care-seeking behaviour of uninsured people. This study bridges the gap in the literature by evaluating uninsured Jamaicans' medical care-seeking behaviour and good health status. MATERIAL #ENTITYSTARTX00026;
METHOD
The study extracted a sample of 5,203 uninsured respondents 15 years and older from a national probability cross-sectional survey of 6,782 Jamaicans. Descriptive statistics were used to provide background information on the sample; cross-tabulations evaluated bivariate analyses, and logistic regression was used to model health and medical care-seeking behaviour.
RESULTS
Good health of uninsured Jamaicans is correlated -reported biological condition (OR =0.114, 95% CI = 0.090 -0 .145) followed by age (OR =0.952, 95% CI = 0.946- 0.959); gender (OR = 1.501, 95% CI = 1.221-1.845); consumption (OR = 1.000, 95% CI = 1.000-1.000); social class (upper class OR = 0.563, 95% CI = 0.357-0.888); education (secondary and above OR = 0.622, 95%CI = 0.402-0.963), and area of residence (other towns OR = 1.351, 95% CI = 1.026-1.778). Medical care-seeking behaviour is associated with age (OR = 1.020, 95% CI = 1.006 - 1.033); poor health status (OR = 2.303, 95% CI = 1.533-3.461), and marital status (married OR = 0.518, 95% CI = 0.325-0.824).
CONCLUSION
The findings are far reaching and provide an understanding of the uninsured, and the information can be used to aid public health intervention and education programmes. | 10.4297/najms.2010.271 |
pubmed_332_13864 | The title compound, C(18)H(17)NO(6) [systematic name: (2R,3R)-4-benzyl-amino-2-benzo-yloxy-3-hy-droxy-4-oxobutanoic acid], is the first structurally characterized unsymmetrical monoamide-monoacyl tartaric acid derivative. The mol-ecule shows a staggered conformation around the tartramide Csp(3)-Csp(3) bond with trans-oriented carboxyl and amide groups. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds between the carboxyl and amide carbonyl groups, forming translational chains along [001]. Further O-H⋯O and N-H⋯O hydrogen bonds as well as weaker C-H⋯O and C-H⋯π inter-molecular inter-actions extend the supra-molecular assembly into a double-layer structure parallel to (100). There are no directional inter-actions between the double layers. | 10.1107/S1600536812022933 |
pubmed_523_277 | 1. Dopamine was shown to be released from the isolated lung of calves sensitized with horse serum by compound 48/80 and by specific antigen.2. Dopamine contracts the bovine pulmonary artery and pulmonary vein. Phentolamine, the alpha-adrenoceptor blocking agent, inhibits this activity of dopamine and also strongly reduces the Schultz-Dale response of the pulmonary vessels.3. The results are consistent with the suggestion that dopamine (together with histamine and 5-hydroxytryptamine) may participate in the pulmonary vasoconstriction associated with anaphylaxis in cattle. | 10.1111/j.1476-5381.1971.tb07127.x |
pubmed_328_23653 | This paper is concerned with the target tracking of underactuated autonomous surface vehicles with unknown dynamics and limited control torques. The velocity of the target is unknown, and only the measurements of line-of-sight range and angle are obtained. First, a kinematic control law is designed based on an extended state observer, which is utilized to estimate the uncertain target dynamics due to the unknown velocities. Next, an estimation model based on a single-hidden-layer neural network is developed to approximate the unknown follower dynamics induced by uncertain model parameters, unmodeled dynamics, and environmental disturbances. A bounded control law is designed based on the neural estimation model and a saturated function. The salient feature of the proposed controller is twofold. First, only the measured line-of-sight range and angle are used, and the velocity information of the target is not required. Second, the control torques are bounded with the bounds known as a priori. The input-to-state stability of the closed-loop system is analyzed via cascade theory. Simulations illustrate the effectiveness of the proposed bounded controller for tracking a moving target. | 10.1109/TNNLS.2018.2868978 |
pubmed_261_15079 | The 3 study objectives were to compare the activity levels of older people who had received a restorative home care service with those of people who had received "usual" home care, explore the predictors of physical activity in these 2 groups, and determine whether either group met the minimum recommended activity levels for their age group. A questionnaire was posted to 1,490 clients who had been referred for a home care service between 2006 and 2009. Older people who had received a restorative care service were more active than those who had received usual care (p = .049), but service group did not predict activity levels when other variables were adjusted for in a multiple regression. Younger individuals who were in better physical condition, with good mobility and no diagnosis of depression, were more likely to be active. Investigation of alternatives to the current exercise component of the restorative program is needed. | 10.1123/japa.21.2.140 |
pubmed_753_22287 | Several users of a newly built school building in a university (new building) complained about their deteriorating physical health. We measured the air quality in the new building, an old school building and atmosphere in September 2007 and February 2008. We also conducted a questionnaire survey of subjective symptoms of users in the new building in February 2008. The university administrator took some remedial actions to improve the indoor air quality after the first measurement. In September 2007, the concentrations of total volatile organic compounds (TVOCs) and 2-ethyl-1-hexanol in the new building were higher than those in the old building and atmosphere. Moreover, the concentrations of TVOCs exceeded the Japanese recommended guideline values. In February 2008, the concentrations of these substances in the new building were lower than the previous values. Out of the 177 users who were surveyed regarding subjective symptoms, 59 responded to the survey. In September 2007, 21 users felt that their physical health had deteriorated, while in February 2008, 12 users felt no deterioration. However, nine users still complained about the deterioration of their physical health. It was suggested that the improvement in the indoor air quality may be influenced by the decrease in room temperature. Even if the concentrations of VOCs are below the recommended guideline values, users with an enhanced sensitivity towards VOCs may lose their tolerance to low-level VOCs. Our findings suggested that a survey of the changes in the subjective symptoms of users should be conducted to evaluate the improvement in the indoor air quality of newly built buildings. | 10.1265/jjh.66.122 |
pubmed_373_7532 | Two patients with hypertrophic cardiomyopathy (HCM) who underwent non-cardiac surgery were managed successfully using epidural anesthesia as the principal intraoperative anesthesia. Epidural block was induced by inserting an epidural catheter from the lumbar vertebrae toward the caudal side. Epidural anesthesia is usually avoided in HCM patients because of the risk of a decreased preload or afterload causing stenosis in the left ventricular outflow tract. However, in surgery that requires an anesthesia level at L1 or below, which has little effect on sympathetic nerves, epidural anesthesia that maintains a stabilized hemodynamic state appears to be an excellent option. | pubmed_373_7532 |
pubmed_567_306 | We describe a 27-year-old woman with systemic chemoresistant and radioresistant metastatic disease secondary to a recurrence of human papillomavirus (HPV) 18 infected cervical adenocarcinoma of the uterine cervix who received adoptive transfer of peripheral blood T cells stimulated with HPV 18 E7-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells derived from peripheral blood mononuclear cells (PBMC) included phenotypic analysis, cytotoxicity and intracellular cytokine production. High cytotoxicity activity was observed by CD8+T cells against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was significantly inhibited by pretreatment of tumor targets with MAb specific for HLA class I as well as that of effector cells with anti-CD8, anti-LFA-1, but not anti CD3 MAb. Two-color flow cytometric analysis of the cytotoxic T cells revealed that a significant proportion of CD8+ cells was also CD56+. These double positive CTLs were thymically derived, as shown by expression of heterodimeric CD8 molecules (alpha/beta CD8) and were endowed with high cytotoxic activity against tumor cells. Analysis of intracellular cytokine expression showed that the striking majority of E7-pulsed DC activated CD8+ T cells strongly expressed IFN-gamma, TNF-alpha and IL-2 but not IL-4. The patient received two infusions of cytotoxic tumor-specific T cells at 2 week intervals, and in vivo distribution of the T cells was followed by 111 oxine labeling and serial gamma camera imaging. Persistent accumulation of radioactivity in the lungs, which harbored extensive metastatic disease, was detected up to 120 hrs after the infusion. Taken together, these results illustrate the potential of E7-specific and tumor-specific CTL-based immunotherapy for the treatment of patients with invasive cervical cancer. | pubmed_567_306 |
pubmed_617_18210 | Mizoribine (MZB) is an imidazole nucleoside and an immunosuppressive agent. The immunosuppressive effect of MZB has been reported to be due to the inhibition of DNA synthesis in the S phase of the cell cycle. Because of its relative lack of toxicity, during the past decade MZB has been frequently used instead of azathioprine as a component of immunosuppressive drug regimens. MZB is being used to treat renal transplantation patients, IgA nephropathy, lupus erythematosus, and childhood nephrotic syndrome (NS), and some recent studies have assessed the efficacy of oral MZB pulse therapy for severe lupus nephritis, steroid-resistant NS, and frequently relapsing-steroid-dependent NS. This review summarizes the published findings on the efficacy of MZB for renal disease including IgA nephropathy, lupus nephritis, and NS, as well as of oral MZB pulse therapy for severe lupus nephritis and NS, and also the mechanism of the effect of oral MZB pulse therapy on the lymphocyte cell cycle. | 10.1155/2009/681482 |
pubmed_689_11866 | BACKGROUND
Since the novel coronavirus disease (COVID-19) outbreak, the cases of COVID-19 co-infections have been increasingly reported worldwide. Mucormycosis, an opportunistic fungal infection caused by members of the Mucorales order, had been frequently isolated in severely and critically ill COVID-19 patients.
METHODS
Initially, the anamnestic, clinical, and paraclinical features of seven COVID-19-associated mucormycosis (CAM) cases from Egypt were thoroughly reported. Subsequently, an extensive review of the literature was carried out to describe the characteristics of CAM cases globally, aiming to explore the potential risk factors of mortality in CAM patients.
RESULTS
Out of the seven reported patients in the case series, five (71.4%) were males, six (85.7%) had diabetes mellitus, and three (42.9%) had cardiovascular disease. All patients exhibited various forms of facial deformities under the computed tomography scanning, and two of them tested positive for Mucorales using the polymerase chain reaction (PCR) testing. Liposomal amphotericin B (LAmB) was prescribed to all cases, and none of them died until the end of the follow-up. On reviewing the literature, 191 cases were reported worldwide, of which 74.4% were males, 83.2% were from low-middle income countries, and 51.4% were aged 55 years old or below. Diabetes mellitus (79.1%), chronic hypertension (30%), and renal disease/failure (13.6%) were the most common medical comorbidities, while steroids (64.5%) were the most frequently prescribed medication for COVID-19, followed by Remdesivir (18.2%), antibiotics (12.7%), and Tocilizumab (5.5%).
CONCLUSIONS
As the majority of the included studies were observational studies, the obtained evidence needs to be interpreted carefully. Diabetes, steroids, and Remdesivir were not associated with increased mortality risk, thus confirming that steroids used to manage severe and critical COVID-19 patients should not be discontinued. Lung involvement, bilateral manifestation, and Rhizopus isolation were associated with increased mortality risk, thus confirming that proactive screening is imperative, especially for critically ill patients. Finally, surgical management and antimycotic medications, e.g., amphotericin B and posaconazole, were associated with decreased mortality risk, thus confirming their effectiveness. | 10.3390/jof7100837 |
pubmed_884_2892 | To determine the accuracy and reproducibility of cardiac output determination by thermodilution (COT) in children, simultaneous outputs were measured by the Fick technique (COF) (using measured oxygen consumption) and thermodilution in 26 children, ranging in age from 8 to 86 months, who were undergoing cardiac catheterization. There was excellent correlation between mean output by thermodilution and by the Fick technique: COT = 1.10 COF -- 0.2 l/minute, R = 0.91. In three-quarters of the patients with COT differed by 15% or less and in none differed by more than 25%. Serial values of thermodilution outputs were reproducible in each patient with a SD of 5.5%. Our observations indicate that COT is accurate, reproducible, and valuable in the care of critically ill infants and children. | 10.1016/s0022-3476(78)80067-5 |
pubmed_246_1109 | The physical removal of plaque from dentures by brushing is important in the maintenance of oral health. However, there is a danger that brushing will abrade acrylic resin. A machine using a rotary brushing action was therefore utilized for laboratory tests of possible cleaning pastes, employing a toothbrush with good access and adaptability to denture surfaces. Crest toothpaste produced the most abrasion on acrylic resin, Dentu-Creme the least. An experimental paste produced an appreciably lower abrasion rate. Self-cured specimens wore more than heat-cured ones. The rate of abrasion decreased as the temperature was raised. Brushing with water alone, or with a 10% solution of soap, did not produce detectable wear. The wear produced by proprietary cleaners when hand brushing the lingual flanges of dentures and flat blanks of heat-cured acrylic was also measured. Boots denture cleaning paste produced the greatest abrasion, Dentu-Creme the least. The wear measured by reference to a glass plane was at least twice that recorded by the decrease in depth of a groove. The machine did not quantitatively produce the same abrasion as hand brushing, nor did it qualitatively rank the pastes in the same order of abrasiveness. The clinical relevance of these results is discussed. | 10.1111/j.1365-2842.1983.tb00110.x |
pubmed_299_2963 | Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obscure. In this Letter, we investigated the kinetic isotope effect (KIE) of 5-LOX with its physiological substrate, arachidonic acid (AA). The observed KIE is 20±4 on kcat and 17±2 on kcat/KM at 25°C indicating a non-classical reaction mechanism. The observed rates show slight temperature dependence at ambient temperatures ranging from 4 to 35°C. Also, we observed low Arrhenius prefactor ratio (AH/AD=0.21) and a small change in activation energy (Ea(D)-Ea(H)=3.6J/mol) which suggests that 5-LOX catalysis involves tunneling as a mechanism of H-transfer. The measured KIE for 5-LOX involves a change in regioselectivity in response to deuteration at position C7, resulting in H-abstraction form C10 and formation of 8-HETE. The viscosity experiments influence the (H)kcat, but not (D)kcat. However the overall kcat/KM is not affected for labeled or unlabeled AA, suggesting that either the product release or conformational rearrangement might be involved in dictating kinetics of 5-LOX at saturating conditions. Investigation of available crystal structures suggests the role of active site residues (F421, Q363 and L368) in regulating the donor-acceptor distances, thus affecting H-transfer as well as regiospecificity. In summary, our study shows that that the H-abstraction is the rate limiting step for 5-LOX and that the observed KIE of 5-LOX is masked by a change in regioselectivity. | pubmed_299_2963 |
pubmed_1135_24607 | Numerous species have been pushed into extinction as an increasing portion of Earth's land surface has been appropriated for human enterprise. In the future, global biodiversity will be affected by both climate change and land-use change, the latter of which is currently the primary driver of species extinctions. How societies address climate change will critically affect biodiversity because climate-change mitigation policies will reduce direct climate-change impacts; however, these policies will influence land-use decisions, which could have negative impacts on habitat for a substantial number of species. We assessed the potential impact future climate policy could have on the loss of habitable area in biodiversity hotspots due to associated land-use changes. We estimated past extinctions from historical land-use changes (1500-2005) based on the global gridded land-use data used for the Intergovernmental Panel on Climate Change Fifth Assessment Report and habitat extent and species data for each hotspot. We then estimated potential extinctions due to future land-use changes under alternative climate-change scenarios (2005-2100). Future land-use changes are projected to reduce natural vegetative cover by 26-58% in the hotspots. As a consequence, the number of additional species extinctions, relative to those already incurred between 1500 and 2005, due to land-use change by 2100 across all hotspots ranged from about 220 to 21000 (0.2% to 16%), depending on the climate-change mitigation scenario and biological factors such as the slope of the species-area relationship and the contribution of wood harvest to extinctions. These estimates of potential future extinctions were driven by land-use change only and likely would have been higher if the direct effects of climate change had been considered. Future extinctions could potentially be reduced by incorporating habitat preservation into scenario development to reduce projected future land-use changes in hotspots or by lessening the impact of future land-use activities on biodiversity within hotspots. | 10.1111/cobi.12549 |
pubmed_893_21699 | Mood stabilizers are the cornerstone in treatment of mood disorders, but their use is characterized by high interindividual variability. This feature has stimulated intensive research to identify predictive biomarkers of response and disentangle the molecular bases of their clinical efficacy. Nevertheless, findings from studies conducted so far have only explained a small proportion of the observed variability, suggesting that factors other than DNA variants could be involved. A growing body of research has been focusing on the role of epigenetics and metabolomics in response to mood stabilizers, especially lithium salts. Studies from these approaches have provided new insights into the molecular networks and processes involved in the mechanism of action of mood stabilizers, promoting a systems-level multiomics synergy. In this article, we reviewed the literature investigating the involvement of epigenetic mechanisms, noncoding RNAs and metabolomic modifications in bipolar disorder and the mechanism of action and clinical efficacy of mood stabilizers. | 10.2217/pgs-2017-0111 |
pubmed_859_17888 | We investigate the factor structure, concurrent validity, internal consistency, measurement invariance (sex and parents' geographical/cultural background), and practical scoring practices of the Strengths and Weaknesses of Attention-deficit/Hyperactivity Disorder (ADHD)-Symptoms and Normal Behavior scale (SWAN) in junior high school students. With a sample of 650 parents of Mexican junior high school students (55.84% girls; mean age of 13.15 and SD = 0.97 years) who completed the SWAN scale, a bidirectional instrument, and the Barrios and Matute Questionnaire of ADHD symptoms (BMQ-ADHD), a traditional Mexican unidirectional instrument, we obtained SWAN' psychometric properties by a series of confirmatory factor analyses. Two and three-correlated factors of the SWAN and bifactor models fitted well to the data. The bifactor model with one general dimension and two specific dimensions (BF 2S) showed most favorable psychometric properties and was invariant regarding sex and cultural background. The analyses of the BF 2S revealed that only the general factor was sufficiently reliable for scoring. Percentiles divided by sex better approximated SWAN averaged-based scores to the general factor derived from the SWAN bifactor model, measuring the trait with acceptable precision for norms development. The study provides evidence that SWAN measures a trait best represented by a reliable general domain, that the average-based SWAN score is closer to the general SWAN trait when the score is segregated by sex, and that it is invariant with respect to sex and cultural background to be reliable in a culturally diverse population. (PsycInfo Database Record (c) 2022 APA, all rights reserved). | 10.1037/pas0001201 |
pubmed_756_6757 | A disease transmission model of SEIRS type with distributed delays in latent and temporary immune periods is discussed. With general/particular probability distributions in both of these periods, we address the threshold property of the basic reproduction number R0 and the dynamical properties of the disease-free/endemic equilibrium points present in the model. More specifically, we 1. show the dependence of R0 on the probability distribution in the latent period and the independence of R0 from the distribution of the temporary immunity, 2. prove that the disease free equilibrium is always globally asymptotically stable when R0, and 3. according to the choice of probability functions in the latent and temporary immune periods, establish that the disease always persists when R0 < 1 and an endemic equilibrium exists with different stability properties. In particular, the endemic steady state is at least locally asymptotically stable if the probability distribution in the temporary immunity is a decreasing exponential function when the duration of the latency stage is fixed or exponentially decreasing. It may become oscillatory under certain conditions when there exists a constant delay in the temporary immunity period. Numerical simulations are given to verify the theoretical predictions. | 10.1007/s00285-013-0720-4 |
pubmed_284_5051 | To study the effects of acute alterations in heart rate and systemic arterial pressure on the mean velocity of left ventricular circumferential fiber shortening (Vcf) and on mean posterior wall velocity (Vpw), we performed ultrasound studies in 25 normal human subjects between the ages of 21 and 29 years. When heart rate was augmented by the administration of intravenous atropine from 64 +/- 2.2 (SEM) to 98 +/- 2.7 beats/min, mean normalized Vcf increased from 1.22 +/- 0.05 to 1.38 +/- 0.06 circumferences (circ)/sec(P less than 0.001). Mean normalized Vpw increased from 0.76 +/- 0.03 to 0.89 +/- 0.04 sec-1 (P less than 0.001). Mean Vcf and mean Vpw uncorrected for end-diastolic diameter increased in a similar fashion (P less than 0.01). After atropine administration, systemic arterial pressure was augmented by means of a phenylephrine infusion in 23 subjects by an average of 39 mm Hg (range 20-50 mm Hg). During the phenylephrine infusion, average heart rate decreased from 96 +/- 2.6 to 91 +/- 3.1 beats/min (NS), while mean normalized Vcf declined from 1.38 +/- 0.06 to 1.09 +/- 0.05 circ/sec (P less than 0.001) and normalized Vpw from 0.89 +/- 0.04 to 0.65 +/- 0.04 sec-1 (P less than 0.001). Nonnormalized velocities exhibited similar alterations (P less than 0.01). We conclude that in the normal human subject mean Vcf and mean Vpw are sensitive to acute alterations in heart rate and systemic arterial pressure. Thus, when ultrasound measures are used for serial assessment of left ventricular performance, the level of heart rate and systemic arterial pressure at which studies are obtained must be considered. Further, the sequential use of atropine and phenylephrine, as described in this study, provides an experimental model for the evaluation of the effects of drug treatment and other interventions on left ventricular performance in man. | 10.1161/01.cir.52.5.835 |
pubmed_1064_5654 | We have solved the crystal structures of three HLA-B*2705-peptide complexes with the immunodominant viral peptides: EBV EBNA3C 258-266 (RRIYDLIEL), influenza (flu) nucleoprotein NP383-391 (SRYWAIRTR), and HIV gag 264-273 (KRWIILGLNK). Long-term non-progression during HIV infection has been associated with presentation by HLA-B*2705, and T cell recognition, of the highly immunodominant KRWIILGLNK peptide. The tight hydrogen-bonding network observed between the HLA-B*2705 B-pocket and the peptide P2 arginine guanadinium anchor explains why mutation of this residue during HIV infection results in loss of peptide binding, immune escape and progression to AIDS. Prominent, solvent-exposed structures within these peptides may participate in generating T cell responses to these immunodominant epitopes. In the HLA-B*2705 complex with flu NP383-391, the amino acid side chains of residues 4, 7 and 8 are solvent-exposed whilst in the HIV decamer, the main-chain bulges into the solvent around P7. Thus, HLA-B*2705 presents viral peptides in a range of conformations. Tetrameric complexes of HLA-B*2705 with the HIV and flu but not EBV peptides bound strongly to the killer-Ig-like receptor (KIR)3DL1. Substitution of EBV P8 glutamate to threonine allowed recognition by KIR3DL1. In the HLA-B*2705-EBV structure the P8 glutamate side chain is solvent-exposed and may inhibit KIR3DL1 binding through electrostatic forces. | 10.1002/eji.200425724 |
pubmed_487_18874 | We investigated the effect of acupuncture therapy on obese women's body weight and peripheral blood levels of serum immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin E (IgE). Sixty-three healthy women were assigned into 3 groups: placebo electroacupuncture (n = 13; mean age, 40.5 +/- 4.2 years; body mass index [BMI], 33.5 +/- 4.2), diet restriction (n = 23; mean age, 42.9 +/- 4.0 years; BMI, 34.6 +/- 2.9), and electroacupuncture (n = 24; mean age, 40.1 +/- 5.9 years; BMI, 33.9 +/- 2.7). Electroacupuncture was applied to the Hunger and Shen Men ear points and to the LI 4, LI 11, St 36, St 44, and Ren 6 body points for 30 min once daily for 20 days. A restricted diet of 1400 kilocalories was given to participants in all 3 groups for 20 days. Weight was lost significantly in subjects in the electroacupuncture group compared to those in the diet restriction and placebo electroacupuncture groups (p < 0.000, Tukey test). Modulations in serum IgG (p < 0.001) were apparent in women treated with electroacupuncture compared with women treated with placebo electroacupuncture and restricted diet only. No significant changes were seen in serum IgA, IgM, and IgE levels among the 3 groups. Our results suggest that electroacupuncture can be effectively used to treat obesity. We also observed a modulating effect of serum IgG, which is associated with weight loss, in patients in the electroacupuncture group. | 10.1142/S0192415X07005429 |
pubmed_750_6174 | The Wigner high electron correlation regime is characterized in the literature by an electron-interaction energy much greater than the kinetic energy. Via the 'quantal Newtonian' first law, we discover that for a nonuniform electron density system in this regime, there is a 'quantal compression' of the kinetic energy density. The explanation of this compression provides a fundamental understanding for why the kinetic energy is a smaller fraction of the total energy relative to the same ratio in the low correlation regime. We also discover by application of quantal density functional theory, that the contribution of electron correlations to the kinetic energy - the correlation-kinetic effects - and to the total energy is very significant. We propose that in addition to a high electron-interaction energy, the Wigner regime must thus also be characterized by a high correlation-kinetic energy. | 10.1016/j.comptc.2014.02.020 |
pubmed_1007_13073 | Nanobiotechnology is defined as an interdisciplinary field of science that studies the application of fine-sized biological objects (of nanoscale, 1-100 nm) to design the devices and systems of the same size that utilize for new purposes the unusual, known, or previously unknown effects. Analysis demonstrates that the final goals, approaches, solution methods, and applications of nanostructures and biological sensors have much in common. This brief review attempts to systematize a number of the available data and pick out an organic connection of the new research direction with the field of biosensor technology, which have reached the level of sustainable development. | pubmed_1007_13073 |
pubmed_322_3825 | The paper addresses an image processing problem in the field of fine arts. In particular, a deep learning-based technique to classify geometric forms of artworks, such as paintings and mosaics, is presented. We proposed and tested a convolutional neural network (CNN)-based framework that autonomously quantifies the feature map and classifies it. Convolution, pooling and dense layers are three distinct categories of levels that generate attributes from the dataset images by introducing certain specified filters. As a case study, a Roman mosaic is considered, which is digitally reconstructed by close-range photogrammetry based on standard photos. During the digital transformation from a 2D perspective view of the mosaic into an orthophoto, each photo is rectified (i.e., it is an orthogonal projection of the real photo on the plane of the mosaic). Image samples of the geometric forms, e.g., triangles, squares, circles, octagons and leaves, even if they are partially deformed, were extracted from both the original and the rectified photos and originated the dataset for testing the CNN-based approach. The proposed method has proved to be robust enough to analyze the mosaic geometric forms, with an accuracy higher than 97%. Furthermore, the performance of the proposed method was compared with standard deep learning frameworks. Due to the promising results, this method can be applied to many other pattern identification problems related to artworks. | 10.3390/jimaging7080149 |
pubmed_204_17685 | PURPOSE
The aim of this study was to investigate economic inequality in cataract surgery and to decompose it into its determinants using Oaxaca-Blinder decomposition.
METHODS
The Tehran Geriatric Eye Study is a population-based cross-sjal study that was done on individuals above 60 years using stratified cluster random sampling. All subjects underwent full optometric, slit lamp, and fundoscopic examinations. Then, after pupil dilation, the history of cataract surgery, including PC and AC IOL, was determined.
RESULTS
The age and sex-standardized prevalence of cataract surgery was 33.51% (95% CI: 31.45 to 35.62). Cataract surgery had a significant positive association with age (OR: 14.06; p < .001 for >80 vs 60-64 years) and a significant inverse association with education level (OR: 0.55, p: 0.006 for college education vs being illiterate) and economic status (OR: 0.64, p: 0.003 for rich vs poor). A significant difference was found in cataract surgery between the rich and poor (26.22%) disfavoring the poor (p < .001). The explained and unexplained portions comprised 95.99% and 4.01% of the difference (p < .001 and p = .336, respectively). Among study variables, age (p < .001), education (p = .003), economic status (p = .002), insurance (p = .011), and eye examination (p < .001) were significant determinants of inequality in the explained portion.
CONCLUSION
There was a marked difference in the prevalence of cataract surgery between the rich and poor that was mostly caused by the explained portion. Age, economic status, and education had the largest effects on increasing the inequality and history of eye examination by an ophthalmologist and insurance coverage had the largest effects on reducing this inequality. | 10.1080/09286586.2021.1946827 |
pubmed_908_17978 | Despite recent advances, pathogenesis of cholangiocarcinoma, a highly lethal cancer, remains enigmatic. Furthermore, treatment options are still limited and often disappointing. For this reason, in the last few years there has been a mounting interest towards the generation of experimental models able to reproduce the main features associated with this aggressive behavior. Toxic and infestation-induced, genetically engineered and cell implantation rodent models have been generated, contributing to a deeper understanding of the complex cell biology of the tumor, sustained by multiple cell interactions and driven by a huge variety of molecular perturbations. Herein, we will overview the most relevant animal models of biliary carcinogenesis, highlighting the methodological strategy, the molecular, histological and clinical phenotypes consistent with the human condition, their particular strengths and weaknesses and the novel therapeutic approaches that have been developed. | 10.1016/j.clinre.2018.04.008 |
pubmed_315_12201 | This paper discusses the development Mayan linguistics as an authoritative field of knowledge in Guatemala. In particular, it links missionary linguists' and Maya linguists' activities with shifting nationalist agendas from the 1920s in to the late 1980s. It is argued that during the historical and intellectual moment that linguistics becomes an authoritative epistemology, phonetic analysis functions as a creative index that constitutes "expert" knowledge for particular semiotic and ideological reasons tied to competing versions of the Guatemalan imagined community. | pubmed_315_12201 |
pubmed_565_14219 | Our laboratory has purchased four LaCl (3)(Ce) scintillation crystals over the course of the last year for evaluation as part of an environmental management research and development project. In addition to the expected content of naturally radioactive (138)La, we have found that all four of these detectors are contaminated to various degrees with alpha particle emitting nuclides that we have determined to be (227)Ac and its daughters. The impact of these radionuclides on the background spectra and, thus, on the detection sensitivity of these detectors is presented and discussed. | 10.1016/j.apradiso.2005.02.009 |
pubmed_392_15309 | Skin graft surgery is a standard treatment that increases the survival rate of patients with burn injuries; however, it leaves many sequelae. Conventional external preparations for the treatment of burns also have various side effects. In this retrospective case study, we assessed the cases of four patients with topical third-degree burns who did not wish to undergo the skin graft surgeries recommended by medical doctors and were thus treated using traditional medicine alone. A Korean medicine doctor administered integrative traditional medicine treatment to the patients using acupuncture and herbal ointments. Analysis of the patients' treatment photographs, quantitative evaluation indices, and vivid narratives suggested that their skin recovered well without adverse effects. Traditional Korean medicine treatment, including acupuncture and herbal ointment treatment, can be a new alternative therapeutic strategy for the treatment of patients with topical burns who do not want to undergo skin graft surgery or who have higher risks for poor surgical outcomes. | 10.1093/jbcr/irab210 |
pubmed_720_11525 | Natural competence is the term used to describe the uptake of "naked" extracellular DNA by bacteria; it plays a significant role in horizontal genetic exchange. It is associated with type IV pili, and specialized competence pili mediate DNA uptake. Here, we show that the crystal structure of a competence-associated protein from Thermus thermophilus, ComZ, consists of a type II secretion pseudopilin-like domain, with a large β-solenoid domain inserted into the β-sheet of the pilin-like fold. ComZ binds with high affinity to another competence-associated pilin, PilA2, which lies adjacent to the comZ gene in the genome. The crystal structure of PilA2 revealed a similar type II secretion pseudopilin-like fold, with a small subdomain; docking simulations predicted that PilA2 binds between the pseudopilin-like and β-solenoid domains of ComZ. Electrophoretic shift analysis and DNase protection studies were used to show that ComZ alone and the ComZ/PilA2 complex are able to bind DNA. Protection against reductive dimethylation was used in combination with mass spectrometry and site-directed mutagenesis to identify two lysine residues in ComZ which are involved in DNA binding. They are located between the two domains in ComZ, on the opposite side from the predicted PilA2 binding site. These results suggest a model in which PilA2 assists ComZ in forming the competence pilus tip and DNA binds to the side of the fiber. The results demonstrate how a type IV pilin can be adapted to a specific function by domain insertion and provide the first structural insights into a tip-located competence pilin.IMPORTANCEThermus thermophilus is a thermophilic bacterium which is capable of natural transformation, the uptake of external DNA with high efficiency. DNA uptake is thought to be mediated by a competence-associated pilus, which binds the DNA substrate and mediates its transfer across the outer membrane and periplasm. Here, we describe the structural and functional analysis of two pilins which are known to be essential for DNA uptake, ComZ and PilA2. ComZ adopts an unusual structure, incorporating a large β-solenoid domain into the pilin structural framework. We argue on structural grounds that this structure cannot readily be accommodated into the competence pilus fiber unless it is at the tip. We also show that ComZ binds DNA and identify two lysine residues which appear to be important for DNA binding. These results suggest a model in which ComZ and PilA2 form a tip-associated DNA receptor which mediates DNA uptake. | 10.1128/mBio.00614-19 |
pubmed_1072_15874 | Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables. SFN's cytoprotective properties have been demonstrated in several models associated with a variety of disorders. Our recent studies have shown that SFN protects against ethanol-induced oxidative stress and apoptosis in neural crest cells (NCCs), an ethanol-sensitive cell population implicated in Fetal Alcohol Spectrum Disorders (FASD). This study is designed to test the hypothesis that SFN can prevent ethanol-induced apoptosis in NCCs by inhibiting HDAC and increasing histone acetylation at the Bcl-2 promoter. We found that exposure to 50mM ethanol resulted in a significant increase in HDAC activities in NCCs. Treatment with SFN decreased the activities of HDAC in ethanol-exposed NCCs. We also found that SFN treatment significantly increased the expression of acetyl-histone H3 in NCCs treated with ethanol. ChIP-qPCR assay revealed that ethanol exposure significantly decreased acetyl-histone H3 binding to the Bcl-2 promoter while supplementing with SFN reversed the ethanol-induced reduction in acetyl-histone H3 binding to the Bcl-2 promoter. In addition, SFN treatment restored the expression of Bcl-2 in ethanol-exposed NCCs and diminished ethanol-induced apoptosis in NCCs. Treatment with SFN also significantly diminished apoptosis in mouse embryos exposed to ethanol in vivo. These results demonstrate that SFN can epigenetically restore the expression of Bcl-2 and attenuate ethanol-induced apoptosis by increasing histone acetylation at the Bcl-2 promoter and suggest that SFN may prevent FASD through epigenetic regulation of the expression of anti-apoptotic genes. | 10.1016/j.expneurol.2017.10.020 |
pubmed_213_1814 | The effect of chronic administration of morphine and subsequent withdrawal on brain and pituitary receptors for thyrotropin releasing hormone (TRH) was investigated in Sprague-Dawley rats. The rats were implanted subcutaneously with four morphine pellets (each containing 75 mg of morphine free base) during a 3-day period. Placebo pellets, which contained all the excipients of morphine pellets except the morphine, were implanted in rats which served as controls. Both tolerance and physical dependence on morphine have been shown to develop as a result of this procedure. TRH receptors were labeled with 3H-(3-MeHis2) TRH (MeTRH). 3H-MeTRH bound to brain membranes at a single high affinity site with Bmax (receptor density) value of 24.6 +/- 2.2 fmol/mg protein and Kd (apparent dissociation constant) value of 3.7 +/- 0.4 nM. The binding of 3H-MeTRH to five regions of the brain namely, hypothalamus, cortex, striatum, midbrain and pons + medulla, as well as pituitary was also investigated. The binding of 3H-MeTRH to pituitary membranes was increased during the development of tolerance, whereas the binding to membranes prepared from different brain regions was unaffected. Serum concentration of triiodothyronine (T3) and thyroxine (T4) were found to be lower in chronic morphine-treated rats when compared to placebo-treated rats, however, serum TSH level remained unaltered. Twenty-four hours after the removal of morphine pellets (natural withdrawal), the binding of 3H-MeTRH to pons + medulla membranes was greater than in placebo control group. Naloxone-precipitated withdrawal produced results which were qualitatively similar to those obtained in rats from which pellets had been removed. The results suggest that the development of tolerance to morphine may be associated with changes in the pituitary-thyroid axis. | 10.1016/0091-3057(89)90344-4 |
pubmed_476_23668 | Background
The benefits of intravenous immunoglobulin administration are controversial for critically ill COVID-19 patients.
Methods
We analyzed retrospectively the effects of immunoglobulin administration for critically ill COVID-19 patients. The primary outcome was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. Cluster analysis was used to perform phenotype analysis.
Results
Between January 1 and February 29, 2020, 754 patients with complete data from 19 hospitals were enrolled. Death at 28 days occurred for 408 (54.1%) patients. There were 392 (52.0%) patients who received intravenous immunoglobulin, at 11 (interquartile range (IQR) 8, 16) days after illness onset; 30% of these patients received intravenous immunoglobulin prior to intensive care unit (ICU) admission. By unadjusted analysis, no difference was observed for 28-day mortality between the immunoglobulin and non-immunoglobulin groups. Similar results were found by propensity score matching (n = 506) and by IPTW analysis (n = 731). Also, IPTW analysis did not reveal any significant difference between hyperinflammation and hypoinflammation phenotypes.
Conclusion
No significant association was observed for use of intravenous immunoglobulin and decreased mortality of severe COVID-19 patients. Phenotype analysis did not show any survival benefit for patients who received immunoglobulin therapy. | 10.3389/fimmu.2021.738532 |
pubmed_1135_23581 | Hepatocellular carcinoma (HCC) is one of the most life-threatening malignancies worldwide. Defects in DNA repair genes may increase the risk of HCC. X-ray cross-complementing group 1 gene (XRCC1) is a major DNA repair gene involved in base excision re-pair. Recently, several studies have indicated that an association exists between XRCC1 polymorphism and HCC, particularly the Arg280His polymorphism. However, the data is inconsistent and incomplete. In this study, we conducted a meta-analysis to investigate the association between the XRCC1 Arg280His polymorphism and HCC risk. A total of 10 case-control studies included 1848 HCC cases and 1969 controls were examined in this analysis. Our results suggest that variant geno-types of the XRCC1 Arg280His gene are associated with a significantly increased risk of HCC in homozygote comparison (HisHis vs ArgArg, odds ratio, 1.55, 95% confidence interval, 1.10-2.18, P = 0.013); no het-erogeneity was observed (I2 = 0%). Our analysis suggests that the XRCC1 Arg280His polymorphism is associated with a higher risk of HCC. | 10.4238/2015.June.29.5 |
pubmed_306_7790 | Linkage analysis was used to determine the genetic map location of er-1, a recessive gene conditioning resistance to powdery mildew, on the Pisum sativum genome. Genetic linkage was demonstrated between er-1 and linkage group 6 markers after analyzing the progeny of two crosses, an F2 population and a set of recombinant inbred lines. The classes of genetic markers surrounding er-1 include RFLP, RAPD and allozyme markers as well as the morphological marker Gty. A RAPD marker tightly linked to er-1 was identified by bulked segregant analysis. After DNA sequence characterization, specific PCR primers were designed to convert this RAPD marker into a sequence characterized amplified region (SCAR). | 10.1007/BF00220815 |
pubmed_481_8007 | Small DNA viruses (adenoviruses, simian virus 40, or human papillomaviruses) induce S-phase progression but prevent cell division to provide precursors for viral DNA replication. Herpes simplex viruses types 1 or 2 (HSV-1 or HSV-2) contain genes which encode DNA-metabolizing enzymes, for example, ribonucleotide reductase, thymidine kinase and dUTPase, suggesting that S-phase factors are not required for an efficient infection. However, several studies indicated that HSV induces some events that occur during cell-cycle progression. To determine if HSV-2 induces S-phase entry, we examined serum-arrested African green monkey kidney cells (CV-1) after infection. Two hours after infection steady-state levels of the S-phase-specific cyclin, cyclin A, increased. S-phase cyclin-dependent kinase activity (CDK2) was stimulated 10-fold 8 h after infection but decreased at 16 or 24 h after infection. Mitotic CDK activity (CDC2) was not activated after infection, in part due to decreases in CDC2 protein levels and inactivation of enzymatic activity resulting from tyrosine phosphorylation of CDC2. Furthermore, CDK4 activity was not dramatically affected by infection. These studies indicate that HSV-2 infection selectively activates CDK2 after infection but cell-cycle progression does not occur. We hypothesize that infection activates certain components of the cell cycle which enhance viral gene expression and DNA replication. | 10.1099/0022-1317-78-12-3341 |
pubmed_1117_14584 | The characteristics of the train-of-four (TOF) response have been studied electromyographically during the onset and the spontaneous offset of neuromuscular blockade induced with vecuronium or gallamine. During the onset of blockade, at 75% depression of initial twitch height, gallamine was associated with significantly more TOF fade than vecuronium. Both agents were associated with significantly less fade during onset than during spontaneous offset. When the two neuromuscular blocking drugs were compared during spontaneous offset they showed a similar degree of fade during early offset (up to 50% recovery of initial twitch height). However, during late spontaneous offset, when the initial twitch height had recovered to 75% of control values, vecuronium was associated with more fade than gallamine. | 10.1093/bja/60.5.486 |
pubmed_975_10097 | OBJECTIVE
To obtain and contrast the informed opinions of people in five decision-making groups that could have a role in devolved governance of health care and social services.
DESIGN
Deliberative polling.
SETTING
Three rural and three urban communities selected from the 32 areas covered by a district health council in Ontario.
PARTICIPANTS
A total of 280 citizens from five potential decision-making groups: randomly selected citizens, attendees at town-hall meetings, appointees to district health councils, elected officials and experts in health care and social services.
INTERVENTION
Participants' opinions were polled during 29 structured 2-hour meetings.
MAIN OUTCOME MEASURES
Participants' opinions on their personal willingness and their group's suitability to be involved in devolved decision making, desired type of decision-making involvement, information preferences, preferred areas of decision-making involvement and preferred composition of decision-making bodies.
RESULTS
Mean attendance at each meeting was 9.6 citizens. Although there were some significant differences in opinion among the five potential decision-making groups, there were few differences among citizens from different geographic areas. A total of 189 (72%) of people polled were personally willing to take on a role involving responsibility for overall decision-making, but far fewer thought that their group was suited to taking on responsibility (30%) or a consulting role (55%). Elected officials were the most willing (85% personally willing, 50% thought their group was suitable) and randomly selected citizens the least willing (60% personally willing, 17% thought their group was suitable) to take responsibility for overall decision making. Most citizens polled indicated less interest in involvement in specific types of decisions, except for planning and setting priorities, than in overall decision making. Only 24 participants (9%) rated their own group as suitable to take responsibility for raising revenue, 91 (33%) deemed their group suited to distribution of funds and 108 (39%) felt their group was suitable for management of services. People in all five groups ranked health care needs (mean rank 1.5 out of four options) as the most important and preferences (mean rank 3.6) as the least important information. They rated a combination body involving several community groups as the most suitable overall decision-making body (8.8 on 10-point scale). Participants favoured the representation of elected officials, the provincial government and experts on combination bodies responsible for the specific types of decisions. Overall, as the complexity of devolved decision making became clear, participants tended to assign authority to traditional decision makers such as elected officials, experts and the provincial government, but also favoured a consulting role for attendees at town-hall meetings (i.e., interested citizens).
CONCLUSION
There are significant differences among groups in the community in their willingness to be involved, desired roles and representation in devolved decision making on health care and social services in Ontario. | pubmed_975_10097 |
pubmed_265_10576 | Lesions in the oral cavity are often treated with two opposed lateral fields. These include a significant amount of normal healthy tissue whose radiation tolerance is dose-limiting. The tumor dose can be boosted to tumorcidal levels by brachytherapy or by small electron fields directed straight on the lesion. We have developed a simple attachment to the standard electron applicator of the Varian Clinac 1800 that allows irradiation of small electron fields through acrylic tubes-the oral cones. These tubes have been evaluated in terms of depth dose and field profiles for 6, 9, 12, 16, and 20 MeV electrons using film for relative dosimetry. At these small field sizes there are significant changes in output factors, in the depth dose as well as in the effective size of the field, and a thorough dosimetric evaluation is imperative prior to treatment. The attachment can be manufactured locally at low cost. For reasons of patient safety the assembly is collapsible. In clinical practice the cone is directed directly on the tumor. For deep-seated lesions we use a penlight and a mirror for positioning. | 10.1016/s0958-3947(97)00119-2 |
pubmed_803_3194 | The Johns Hopkins Oncology Center has developed and maintains a clinical information system to support patient care, education, research, and administrative functions. It operates on a dedicated minicomputer (PDP-11) programmed in MUMPS. Clinical information collected includes patient medical status and laboratory values. Data are used daily in patient care and also in support of retrospective and prospective research. The use of the system to manage a large blood pheresis program and to study and treat infectious disease is described. Administrative functions include patient and personnel scheduling, program evaluation, and projects directed toward control of costs. | 10.1007/BF00995121 |
pubmed_867_8701 | An adrenocortical carcinoma (15.5 g) secreting excessive amounts of steroids with weak mineralocorticoid activity in a 25-year-old woman was studied with particular reference to its in vivo and in vitro secretions of steroids. Severe hypertension, occasional low serum potassium and suppressed PRA were the major clinical findings, and were improved with removal of the tumor. In the preoperative stage, plasma levels of 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, corticosterone and 18-hydroxycorticosterone were all increased. However, the plasma level of aldosterone was repeatedly normal. Although plasma levels of pregnenolone, 17-hydroxypregnenolone, progesterone and 17-hydroxyprogesterone were very high, those of other late step steroids, i.e. 11-deoxycortisol, cortisol, dehydroepiandrosterone, androstenedione and testosterone were almost normal. From these findings, a major etiological role of weak mineralocorticoids such as 11-deoxycorticosterone, 18-hydroxycorticosterone and corticosterone in her hypertension was suggested. Pregnenolone and 17-hydroxypregnenolone in tumor tissue were increased, but 11-deoxycorticosterone, corticosterone, aldosterone, cortisol and adrenal androgens such as dehydroepiandrosterone, androstenedione and testosterone were below normal or low normal. In vitro production of 11-deoxycorticosterone, aldosterone or cortisol by the tumor tissue slices was very low and scarcely responded to synthetic ACTH. | 10.1507/endocrj1954.34.65 |
pubmed_672_11455 | Four patients, each with a history of myocardial infarction and diffuse coronary artery disease, underwent application of left latissimus dorsi (LD) muscle with intact neurovascular bundle to the anterolateral wall of the left ventricle. The muscle was conditioned over a six-week period subsequent to operation in 3 patients and was conditioned preoperatively with a burst stimulus in the fourth. Biopsy specimens confirm the experimental data that human skeletal muscle can be electrically conditioned over a six- to ten-week period to contain mainly fatigue-resistant type I fibers. All patients survived the procedure, and 3 showed improvement secondary to aneurysmectomy. In Patient 1, a modified resection was performed, and at 28 months after operation, at the 75-W level of exercise, the ejection fraction was 54% paced versus 45% nonpaced. In Patient 2, at 12 months, the ejection fraction at rest was 44% paced versus 30% nonpaced. Doppler echo studies confirmed the presence of the flap and its function in the paced and nonpaced mode. The third patient died of a sudden ventricular arrhythmia 2 months following operation. An infected, nonfunctioning, degenerated flap was found at autopsy. Patient 4 did not have an aneurysm. She received a bypass graft to the right coronary artery and underwent cardiomyopexy in an attempt to relieve medically refractory incapacitating chronic congestive heart failure. Ten months postoperatively, ejection fraction at rest was 33% paced versus 25% nonpaced. Constrictive myopathy has not been encountered in any of these patients. | 10.1016/s0003-4975(10)64761-3 |
pubmed_249_20254 | Penaeus japonicus postlarvae, reared under laboratory conditions, were fed an astaxanthin enriched diet to the investigate carotenoid metabolic capabilities during the postlarval development. Animals fed astaxanthin were found to absorb this carotenoid. The decrease of pigment concentration in the carotenoid starved group is related to the duration of the experimental feeding conditions; the carotenoid depletion depends upon the postlarval status at the starting point. As has been shown for adult prawns, the carotenoid pattern of postlarval stages, regardless of the diet, consists mainly of free and esterified astaxanthin; the relative amounts of these fractions undergo slight variations depending on the diet. | 10.1016/s1095-6433(97)00460-1 |
pubmed_674_16706 | Various endoscopic suturing and tying methods have been reported, but these methods remain imperfect because knots are sometimes not tied completely and additional stitches are needed. To address this problem, we developed the "Figure 4" technique in which the knot can be easily slid to the suture point and tied by pulling suture tail-these knots will never come untied. This technique requires very simple technique and can be used in other surgical procedures such as conventional laparoscopic surgery. | 10.1097/IMI.0000000000000348 |
others_53_9205 | An automated method for maize and weed detection is very important to efficiently remove weeds and precisely calculate the quantity of maize. Color features were used in this study to investigate a simple maize-detection method using a color machine-vision system. Conventional image segmentation methods based on RGB values cannot separate maize from weeds because of the highly similar image RGB values of these plants. Thus, a post-processing algorithm was developed to distinguish maize from weeds after image preprocessing. Color indices were used to develop a classification model. The nine optimal features were selected by principal component analysis to reduce the effect of illumination. Finally, support vector data description was used as a classifier to differentiate maize from the mixes of different species of weeds. Pictures were taken by a commercial camera and used to verify the stability of the algorithm. Results show that the overall accuracy for three years is 90.19%, 92.36% and 93.87%, respectively. And the color indices used in this work were stable under various weather conditions and over time. © 2017 | 10.1016/j.compag.2017.07.028 |
pubmed_906_9780 | We have previously shown that Macaca fascicularis (Cynomologus) monkeys receiving a primary and either one or two booster rabies DNA vaccinations are protected against rabies virus. In this study, we determined whether monkeys that had been vaccinated only once via gene gun or intramuscularly (i.m.) with different concentrations of DNA would be protected against rabies virus challenge. Neutralizing antibody responses were assayed for 1 year before the monkeys were challenged. Neutralizing antibody was detected at least 50 days earlier in gene gun vaccinated as compared to i.m. vaccinated animals. Prior to viral challenge, all (6/6, 100%) gene gun vaccinated animals, but only 3/6 (50%) i.m. vaccinated animals seroconverted. In general, antibody titers of the gene gun vaccinated animals were higher than the titers of the i.m. vaccinated animals. There was no correlation between the concentration of DNA used for vaccination, the neutralizing antibody responses elicited and protection against viral challenge. Seven days after viral challenge, a rapid and strong anamnestic antibody response was elicited in 100% of the gene gun vaccinated monkeys and in four i.m. vaccinated monkeys. Neutralizing antibody remained undetectable in two i.m. vaccinated monkeys. Overall, 60% (3/5) of the gene gun vaccinated animals and 87% (5/6) of the i.m. vaccinated monkeys survived viral challenge. This study is the first, to our knowledge, to show long-term protection of non-human primates against a human viral pathogen using a DNA vaccination protocol that did not include a booster immunization. | 10.1016/s0264-410x(01)00392-9 |
pubmed_444_11820 | In this work, we present the design and synthesis of novel fully synthetic analogues of the bisbenzylisoquinoline tetrandrine, a molecule with numerous pharmacological properties and the potential to treat life-threatening diseases, such as viral infections and cancer. Its toxicity to liver and lungs and the underlying mechanisms, however, are controversially discussed. Along this line, novel tetrandrine analogues were synthesized and biologically evaluated for their hepatotoxicity, as well as their antiproliferative and chemoresistance reversing activity on cancer cells. Previous studies suggesting CYP-mediated toxification of tetrandrine prompted us to amend/replace the suspected metabolically instable 12-methoxy group. Of note, employing several in vitro models showed that the proposed CYP3A4-driven metabolism of tetrandrine and analogues is not the major cause of hepatotoxicity. Biological characterization revealed that some of the novel tetrandrine analogues sensitized drug-resistant leukemia cells by inhibition of the P-glycoprotein. Interestingly, direct anticancer effects improved in comparison to tetrandrine, as several compounds displayed a markedly enhanced ability to reduce proliferation of drug-resistant leukemia cells and to induce cell death of liver cancer cells. Those enhanced anticancer properties were linked to influences on activation of the kinase Akt and mitochondrial events. In sum, our study clarifies the role of CYP3A4-mediated toxicity of the bisbenzylisoquinoline alkaloid tetrandrine and provides the basis for the exploitation of novel synthetic analogues for their antitumoral potential. | 10.1016/j.ejmech.2020.112810 |
pubmed_332_22394 | Mitochondrial oxidative metabolism is the major site of ATP production as well as a significant source of reactive oxygen species (ROS) that can cause damage to critical biomolecules. It is well known that mitochondrial enzymes that scavenge ROS are targeted by stress responsive proteins to maintain the fidelity of mitochondrial function. Manganese superoxide dismutase (MnSOD) is a primary mitochondrial ROS scavenging enzyme, and in 1983 Irwin Fridovich proposed an elegant chemical mechanism/model whereby acetylation directs MnSOD enzymatic activity. He christened it the "electrostatic repulsion model." However, the biochemical and genetic mechanism(s) determining how acetylation directs activity and the reasons behind the evolutionarily conserved need for several layers of transcriptional and posttranslational MnSOD regulation remain unknown. In this regard, we and others have shown that MnSOD is regulated, at least in part, by the deacetylation of specific conserved lysines in a reaction catalyzed by the mitochondrial sirtuin, Sirt3. We speculate that the regulation of MnSOD activity by lysine acetylation via an electrostatic repulsion mechanism is a conserved and critical aspect of MnSOD regulation necessary to maintain mitochondrial homeostasis. | 10.1016/j.freeradbiomed.2012.06.020 |
pubmed_854_16424 | 5-Arylamino-4,7-dioxobenzo[b]thiophenes 3-6 were synthesized and tested for in vitro antifungal activity against Candida and Aspergillus species. 5-Arylamino-6-chloro-2-(methoxycarbonyl)-4,7-dioxobenzo[b]thiophenes 5 showed, in general, more potent antifungal activity against Candida species than the other 4,7-dioxobenzo[b]thiophenes 3, 4 and 6. The results suggest that 5-arylamino-4,7-dioxobenzo[b]thiophenes would be potent antifungal agents. | 10.1016/j.bmcl.2005.03.042 |
pubmed_321_18275 | OBJECTIVE
Functional imaging of synovitis could improve both early detection of rheumatoid arthritis (RA) and long-term outcomes. Given the intersection of inflammation with coagulation protease activation, this study was undertaken to examine coagulation protease activities in arthritic mice with a dual-fluorescence ratiometric activatable cell-penetrating peptide (RACPP) that has a linker, norleucine (Nle)-TPRSFL, with a cleavage site for thrombin.
METHODS
K/BxN-transgenic mice with chronic arthritis and mice with day 1 passive serum-transfer arthritis were imaged in vivo for Cy5:Cy7 emission ratiometric fluorescence from proteolytic cleavage and activation of RACPPNleTPRSFL . Joint thickness in mice with serum-transfer arthritis was measured from days 0 to 10. The cleavage-evoked release of Cy5-tagged tissue-adhesive fragments enabled microscopic correlation with immunohistochemistry for inflammatory markers. Thrombin dependence of ratiometric fluorescence was tested by ex vivo application of RACPPNleTPRSFL and argatroban to cryosections obtained from mouse hind paws on day 1 of serum-transfer arthritis.
RESULTS
In chronic arthritis, RACPPNleTPRSFL fluorescence ratios of Cy5:Cy7 emission were significantly higher in diseased swollen ankles of K/BxN-transgenic mice than in normal mouse ankles. A high ratio of RACPPNleTPRSFL fluorescence in mouse ankles and toes on day 1 of serum-transfer arthritis correlated with subsequent joint swelling. Foci of high ratiometric fluorescence localized to inflammation, as demarcated by immune reactivity for citrullinated histones, macrophages, mast cells, and neutrophils, in soft tissue on day 1 of serum-transfer arthritis. Ex vivo application of RACPPNleTPRSFL to cryosections obtained from mice on day 1 of serum-transfer arthritis produced ratiometric fluorescence that was inhibited by argatroban.
CONCLUSION
RACPPNleTPRSFL activation detects established experimental arthritis, and the detection of inflammation by RACPPNleTPRSFL on day 1 of serum-transfer arthritis correlates with disease progression. | 10.1002/art.40316 |
pubmed_548_5349 | PURPOSE
The aim of the study was to analyse greater tuberosity's (GT) micro-vascularization in the context of rotator cuff tear and to identify factors that could affect the rate and distribution of micro-vessels.
METHODS
Eighty-seven patients with supraspinatus and/or infraspinatus tendon tears were included in a prospective study. Mean age at surgery was 58 years (41-78) and clinical symptoms were lasting from an average of 20 months before surgery. A bone core of 1-cm depth was obtained from the GT during rotator cuff repair at two localizations, medial and lateral within tuberosity. Micro-vascularization was then analysed with an immunohistochemistry technique based on CD34 antigen tracking endothelial cells at two levels of depth for each sample (more and less than 5 mm). Epidemiologic and pathologic data were correlated with the rate of micro-vascularization measured.
RESULTS
Median rate of GT's micro-vascularization was 9.8 %, which ranged from 0.13 % to 33.4 %. This rate decreased with preoperative steroid injection (7.4 % vs 11.2) and with localization close to the cartilage of the humeral head (8.7 % vs 11.9 %). However, it remains almost homogenous along the depth's core. Moreover, no significant correlation was found regarding age at surgery, gender, context of previous trauma, smoking habits, duration of symptoms, and specific data regarding the tendon tear.
CONCLUSIONS
This study highlighted the variability of GT's micro-vascularization in case of rotator cuff tear. A greater rate was observed at the lateral part of the footprint, whereas medical history of steroid injection has a negative influence on micro-vascularization. | 10.1007/s00264-014-2628-z |
pubmed_973_23855 | Replantation of an avulsed ear was completely successful with only arterial repair (to the superficial temporal artery) and the use of medicinal leeches. | 10.3109/02844310701682931 |
pubmed_300_6374 | In a multicentre randomised, unblinded patient preference pilot trial to assess the feasibility of a definitive randomised trial comparing colposuspension with tension-free vaginal tape (TVT) plus anterior repair in women with incontinence and prolapse, we found that 31 of 56 eligible women agreed to participate (55%). Recruitment was more successful face to face (87%) than by letter (16%). Only four of our women agreed to be randomised, 21 (68%) chose anterior repair+TVT and six (19%) chose colposuspension. This study demonstrates the importance of pilot work for complex trials to identify issues likely to adversely affect recruitment. | 10.1111/j.1471-0528.2009.02355.x |
others_287_17324 | The analysis of human short tandem repeats of the Y-chromosome (Y-STRs) provides a powerful tool in forensic cases for male sex identification, male lineage identification and identification of the geographical origin of male lineages. As the commonly used 12 and 17 Y-STR multiplexes do not discriminate between some unrelated males, additional Y-STRs were implemented in the PowerPlex® Y23 System to supplement the existing commercial Y-STR kits. Until today, the forensic value of a (near) 23 versus 17 Y-STR haplotype match between an unknown DNA donor and a certain biological sample in a database is not yet well studied. This will be of huge interest for cases where an autosomal DNA profile yields no match to a DNA database and the database is used for familial searching (male relative(s) of the offender) or for the estimation of the geographical origin of the offender. In order to value (near) 23 Y-STR haplotype matches in a local sample from Western Europe, we selected the region of Flanders (Belgium) due to the already present knowledge on its Y-chromosomal variants. Many Y-chromosomes of this region were previously genotyped with Y-SNPs at a high resolution of the most recently updated Y-chromosomal tree and the deep-rooted genealogy of each DNA donor was already established. By comparing (near) matches of 23 versus 17 Y-STR haplotypes between patrilineal-unrelated males, a substantial lower number of uninformative (near) 23 Y-STR haplotype matches has been observed compared to 17 Y-STR haplotypes. Furthermore, the use of SNP data was informative to discriminate >60% of unrelated males with an (near) identical 17 Y-STR match while SNP data was only necessary to discriminate about 10% of unrelated males with a 23 Y-STR haplotype that differed at only two Y-STRs. This shows the higher value of the Y23 haplotype within familial DNA searching and the estimation of the geographical origin of a DNA donor. Therefore, the use of the PowerPlex® Y23 System instead of the commonly used 12 and 17 Y-STRs by the forensic community is recommended as it will increase the efficiency of Y-STRs in forensic casework. © 2014 Elsevier Ireland L | 10.1016/j.fsigen.2014.04.002 |
pubmed_522_14971 | The 90K solid-state structures, room temperature absorption, and room temperature and 17 K emission spectra of seven different salts of [Cu(I)(bfp)(2)](+) (bfp = 2,9-bis(trifluoromethyl)-1,10-phenanthroline) have been determined. To quantify the distortion of the Cu coordination environment, a distortion parameter zeta is defined that is a combined measure of the flattening, rocking, and wagging distortions of the complex cations. In general, the distortion in the (bfp) cations is less than found previously for Cu(I)(dmp)(2) (dmp = 2,9-dimethyl-1,10-phenanthroline) salts, in particular the flattening is reduced because of the bulkier 2,9-substituents. The 17 K lifetimes range up to 1.8 mus in the series of solids examined and, with the marked exception of the BF(4)(-) salt, correlate linearly with the distortion parameter zeta. The emission wavelength red-shifts with decreasing lifetime, which implies that an increased ground-state distortion is associated with a smaller energy gap. | 10.1021/ic049638s |
pubmed_1133_19961 | Genetic engineering technology has been successfully used in many plant species, but is limited in woody plants, especially in bamboos. Ma bamboo (Dendrocalamus latiflorus Munro) is one of the most important bamboo species in Asia, and its genetic improvement was largely restricted by the lack of an efficient regeneration and transformation method. Here we reported a plantlet regeneration and Agrobacterium-mediated transformation protocol by using Ma bamboo young shoots as explants. Under our optimized conditions, embryogenic calluses were successfully induced from the excised young shoots on callus induction medium and rapidly grew on callus multiplication medium. Shoots and roots were regenerated on shoot induction medium and root induction medium, respectively, with high efficiency. An Agrobacterium-mediated genetic transformation protocol of Ma bamboo was established, verified by PCR and GUS staining. Furthermore, the maize Lc gene under the control of the ubiquitin promoter was successfully introduced into Ma bamboo genome and generated an anthocyanin over-accumulation phenotype. Our methods established here will facilitate the basic research as well as genetic breeding of this important bamboo species. Key achievements: A stable and high efficiency regeneration and Agrobacterium-mediated transformation protocol for Ma bamboo from vegetative organ is established. | 10.3389/fpls.2017.01298 |
pubmed_316_18463 | The authors review the available studies on the use of the dexamethasone suppression test (DST) in children and adolescents with psychiatric disorders. For the purposes of analysis, the authors divided the studies according to the two age groups. Pooled sensitivity, specificity, and positive predictive power were calculated for each age group per diagnostic category. DST nonsuppression among subjects with major depressive disorder (MDD) in the children's group was 69.6%, with a specificity of 69.7%, whereas for adolescent subjects, DST sensitivity was 41.3%, and specificity was 79.3%. The positive predictive power of an abnormal DST result in helping diagnose MDD in the children's group was 69.7%, whereas for the adolescent group, the positive predictive power was 66.6%. The authors conclude that the evidence cannot support the routine clinical use of the DST in children and in adolescents, but there may be a research role for the DST in these patient populations. | pubmed_316_18463 |
pubmed_855_831 | PURPOSE
Transrectal ultrasound is the most accurate means of assessing the degree of invasion for rectal neoplasms. A learning curve for performing and interpreting these studies exists, but it is unknown how long or steep it is. We reviewed our initial results with transrectal ultrasound to determine our accuracy and to define the learning curve.
METHODS
All patients undergoing transrectal ultrasound during our initial 30 months of experience were included. Each patient was staged with transrectal ultrasound and, after resection, the histopathologic stage was compared with transrectal ultrasound staging. The accuracy of transrectal ultrasound was calculated at intervals as experience was gained.
RESULTS
A total of 42 examinations were performed on 41 neoplasms in 41 patients. Comparison between transrectal ultrasound and the pathologic stage could be made in 36 studies. Overall accuracy of degree of wall invasion was 78 percent. Overstaging occurred with eight neoplasms, and one lesion was understaged. Accuracy of transrectal ultrasound staging improved with time: 58 percent of the initial 12 studies were staged correctly compared with 87.5 percent accuracy in the remaining 24 examinations (P = 0.048).
CONCLUSION
A definite learning curve was apparent. We conclude that transrectal ultrasound is a relatively simple procedure to learn and, once a moderate degree of experience is gained, should be routinely incorporated into the evaluation of rectal neoplasms. | 10.1007/BF02236981 |
pubmed_171_3532 | INTRODUCTION
Primary percutaneous coronary interventions (PCI) in acute coronary syndrome include coronary angioplasty (PTCA) and placing stent in occluded coronary artery, representing distinct progress in treating patients with acute coronary syndrome.
PATIENTS AND METHODS
Permanent PCI service is available at Dubrava University Hospital since May 1, 2001. During the 2-year period, 142 patients with acute myocardial infarction with significant electrocardiographic ST-elevation were treated by this method.
RESULTS
Occlusion was found and PCI treatment most often performed on the leading descending artery (46.5%) and right coronary artery (45.5%). The mortality during and immediately after PTC was reduced to 4.2%.
CONCLUSION
Our results of successful recanalization of occluded coronary artery are similar to those reported from most European cardiology centers. | pubmed_171_3532 |
pubmed_78_24020 | OBJECTIVES
Constituents of St John's wort (SJW) in vivo induce the cytochrome P450 (CYP) isozymes 3A4, 2C9, and 2C19 but in vitro were shown to inhibit them. This study investigates both short- and long-term effects of SJW on the antifungal voriconazole, which is metabolized by these enzymes.
METHODS
In a controlled, open-label study, single oral doses of 400 mg voriconazole were administered to 16 healthy men stratified for CYP2C19 genotype before and on day 1 and day 15 of concomitant SJW intake (300 mg LI 160 3 times daily). Plasma and urine concentrations of voriconazole were determined by liquid chromatography with mass-spectrometric detection.
RESULTS
During the initial 10 hours of the first day of SJW administration, the area under the voriconazole plasma concentration-time curve was increased by 22% compared with control (15.5 +/- 6.84 h . microg/mL versus 12.7 +/- 4.16 h . microg/mL, P = .02). After 15 days of SJW intake, the area under the plasma concentration-time curve from hour 0 to infinity was reduced by 59% compared with control (9.63 +/- 6.03 h . microg/mL versus 23.5 +/- 15.6 h . microg/mL, P = .0004), with a corresponding increase in oral voriconazole clearance (CL/F) from 390 +/- 192 to 952 +/- 524 mL/min (P = .0004). The baseline CL/F of voriconazole and the absolute increase in CL/F were smaller in carriers of 1 or 2 deficient CYP2C19*2 alleles compared with wild-type individuals (P < .03).
CONCLUSIONS
Coadministration of SJW leads to a short-term but clinically irrelevant increase followed by a prolonged extensive reduction in voriconazole exposure. SJW might put CYP2C19 wild-type individuals at highest risk for potential voriconazole treatment failure. | 10.1016/j.clpt.2005.01.024 |
pubmed_210_6960 | Control of integrin activity is vital during development and tissue homeostasis, while derailment of integrin function contributes to pathophysiological processes. Phosphorylation of a conserved threonine motif (T788/T789) in the integrin β cytoplasmic domain increases integrin activity. Here, we report that T788/T789 functions as a phospho-switch, which determines the association with either talin and kindlin-2, the major integrin activators, or filaminA, an integrin activity suppressor. A genetic screen identifies the phosphatase PPM1F as the critical enzyme, which selectively and directly dephosphorylates the T788/T789 motif. PPM1F-deficient cell lines show constitutive integrin phosphorylation, exaggerated talin binding, increased integrin activity, and enhanced cell adhesion. These gain-of-function phenotypes are reverted by reexpression of active PPM1F, but not a phosphatase-dead mutant. Disruption of the ppm1f gene in mice results in early embryonic death at day E10.5. Together, PPM1F controls the T788/T789 phospho-switch in the integrin β1 cytoplasmic tail and constitutes a novel target to modulate integrin activity. | 10.1083/jcb.202001057 |
pubmed_448_515 | BACKGROUND
Health service coverage cascades measure the proportion of a population in need of a service that experienced a positive health outcome from the service, and enable tracking of progress in achieving universal health coverage and inequities in care coverage.
OBJECTIVES
To investigate HIV care coverage among HIV-positive adolescent girls and young women (AGYW) living in six South African districts, compare coverage by age and socioeconomic status (SES), and investigate other associated factors including participation in a combination HIV prevention intervention.
METHODS
The HERStory Study was an evaluation of the combination intervention, comprising a representative household survey of AGYW aged 15 - 24 years living in six intervention districts. From September 2017 to November 2018, biological, sociodemographic and behavioural data were collected. HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression were determined through laboratory tests (enzyme-linked immunosorbent assay for HIV antibodies, antiretroviral (ARV) metabolites and viral load (VL) testing). Viral suppression was defined as a VL <1 000 copies/mL. Knowledge of HIV-positive status was self-reported, and participants testing positive for ARV metabolites were assumed to have known their HIV-positive status. Unconditional HIV care cascades were created, stratified by age and SES. We used Pearson's χ2 tests corrected for survey-based analysis to describe factors associated with knowledge of HIV status, and being on ART.
RESULTS
Of the 4 399 participants, 568 were HIV-positive (12.4%), of whom 60.8% (95% confidence interval (CI) 57.1 - 64.5) knew their status, 50.6% (95% CI 46.6 - 54.0) were on ART, and 62.1% (95% CI 58.4 - 65.9) were virally suppressed. Most participants (84.9%) were in the lower SES group, and they had better coverage than the higher SES group: 61.9% (95% CI 58.3 - 65.4) knew their status, 52.1% (95% CI 48.4 - 55.9) were on ART, and 64.9% (95% CI 61.3 - 68.4) were virally suppressed, compared with 55.0% (95% CI 42.1 - 68.0), 40.0% (95% CI 29.2 - 50.8), and 46.6% (95% CI 34.5 - 58.7), respectively. Participants aged 15 - 19 years had slightly inferior coverage to the 20 - 24-year-old group: 57.5% knew their status, 46.1% were on ART and 59.5% were virally suppressed, compared with 62.3%, 52.2% and 63.3%.
CONCLUSIONS
These findings emphasise the need to close the gaps in HIV care coverage among AGYW, of whom only 61% knew their HIV-positive status and only 62% were virally suppressed. There is pro-poor inequality in HIV care coverage, with those in lower socioeconomic groups more likely to be virally suppressed. | 10.7196/SAMJ.2021.v111i5.15351 |
pubmed_43_14744 | OBJECTIVE
Catheters and wires are used extensively in cardiac catheterization procedures. Detecting their positions in fluoroscopic X-ray images is important for several clinical applications such as motion compensation and co-registration between 2D and 3D imaging modalities. Detecting the complete length of a catheter or wire object as well as electrode positions on the catheter or wire is a challenging task.
METHOD
In this paper, an automatic detection framework for catheters and wires is developed. It is based on path reconstruction from image tensors, which are eigen direction vectors generated from a multiscale vessel enhancement filter. A catheter or a wire object is detected as the smooth path along those eigen direction vectors. Furthermore, a real-time tracking method based on a template generated from the detection method was developed.
RESULTS
The proposed framework was tested on a total of 7,754 X-ray images. Detection errors for catheters and guidewires are 0.56 ± 0.28 mm and 0.68 ± 0.33 mm, respectively. The proposed framework was also tested and validated in two clinical applications. For motion compensation using catheter tracking, the 2D target registration errors (TRE) of 1.8 mm ± 0.9 mm was achieved. For co-registration between 2D X-ray images and 3D models from MRI images, a TRE of 2.3 ± 0.9 mm was achieved.
CONCLUSION
A novel and fully automatic detection framework and its clinical applications are developed.
SIGNIFICANCE
The proposed framework can be applied to improve the accuracy of image-guidance systems for cardiac catheterization procedures. | 10.1109/TBME.2021.3102670 |
pubmed_337_19624 | E,E-2,5-bis[2-(3-pyridyl)ethenyl]pyrazine (BPEP) has been prepared by aldol condensation between 2,5-dimethylpyrazine and pyridine-3-carboxaldehyde. It is characterized by IR, (1)H NMR, and (13)C NMR. The electronic absorption and emission properties of BPEP were studied in different solvents. BPEP displays a slight solvatochromic effect of the absorption and emission spectrum, indicating a small change in dipole moment of BPEP upon excitation. The dye solutions (1 × 10(-4) M) in CHCl3, EtOH and dioxane give laser emission in blue region upon excitation by a 337.1 nm nitrogen pulse (λ = 337 nm). The tuning range, gain coefficient (α) and emission cross - section (σe) have been determined. Ground and excited states electronic geometric optimizations were performed using density functional theory (DFT) and time-dependent density functional theory (TD-DFT), respectively. A DFT natural bond analysis complemented the ICT. The simulated maximum absorption and emission wavelengths are in line the observed ones in trend, and are proportionally red-shifted with the increase of the solvent polarity. The stability, hardness and electrophilicity of BPEP in different solvents were correlated with the polarity of the elected solvents. BPEP dye displays fluorescence quenching by colloidal silver nanoparticles (AgNPs). The fluorescence data reveal that radiative and non-radiative energy transfer play a major role in the fluorescence quenching mechanism. | 10.1007/s10895-016-1802-7 |
pubmed_839_1485 | PURPOSE
With the goal of eventually restoring functional vision in patients with retinal degenerative diseases, USC/Second Sight Medical Products, Inc. chronically implanted blind human subjects with a prototype epiretinal prosthesis consisting of a 4 x 4 array of 16 stimulating electrodes. To accurately represent a visual scene, a visual prosthesis must convey luminance information across a range of brightness levels. To achieve this, the brightness of phosphenes produced by an individual electrode should scale appropriately with luminance, and the same luminance should produce equivalently bright phosphenes across the entire electrode array. The goal was to examine how apparent brightness changes as a function of stimulation intensity across electrodes.
METHODS
As described in previous studies, electrical stimulation of intact cells of the neural retina using this prosthetic device reliably elicits visual percepts in human subjects blinded by retinitis pigmentosa. Here, apparent brightness for a range of electrical amplitudes was measured using both subjective magnitude rating and brightness-matching procedures in chronically implanted human subjects.
RESULTS
It was found that apparent brightness can be described as a power function of stimulation intensity. The same model can also predict brightness matching across electrodes.
CONCLUSIONS
These results suggest that a relatively simple model for scaling current across electrodes may be capable of producing equivalently bright phosphenes across an entire array. (ClinicalTrials.gov number, NCT00279500.). | 10.1167/iovs.08-2897 |
pubmed_987_2383 | Systemic sclerosis, also known as scleroderma, is an autoimmune disease characterized by cutaneous and visceral fibrosis, immune dysregulation, and vasculopathy. Generally, the degree of skin fibrosis is associated with an increased likelihood of visceral organ involvement. Its pathogenesis is poorly understood; however, it is clear that changes in both the innate and adaptive immune responses are associated with fibroblast dysfunction and vascular damage. Further, DNA damage has been postulated as one of the triggering factors in systemic sclerosis, although the association of DNA damage with the progression of this disease is more poorly established. Recently, abnormal DNA damage response repair pathways have also been identified in patients with systemic sclerosis, suggesting that cells from patients with this disease may be more susceptible to DNA damaging agents. Chemotherapeutic drugs and other DNA damaging agents have been associated with the development of systemic sclerosis, as these agents may provide additional "hits" that promote abnormal DNA damage responses and subsequent inflammatory changes. Herein, we present the case of a 39-year-old female who developed scleroderma after the treatment of her breast cancer with chemotherapeutic agents. Her scleroderma was subsequently successfully treated with autologous hematopoietic stem cell transplantation. We also completed a literature review for previously published cases of chemotherapy associated with systemic sclerosis and highlighted a role of DNA damage in promoting the disease. Our case is the first case of chemotherapy associated with systemic sclerosis treated with hematopoietic stem cell transplantation. | 10.3389/fmed.2022.855740 |
pubmed_1018_6506 | A model of interaction between biologically active substances and macromolecular structures is proposed. The solutions of kinetic equations of discrete and continuous cases were obtained which predict nonmonotonous dose dependences. | pubmed_1018_6506 |
pubmed_803_14968 | Chlamydia trachomatis was present in cell cultures of specimens from 96 (32%) of 300 men with nongonococcal urethritis, but this organism was not isolated from 100 healthy volunteers matched for sex and age. The prevalence of serum antibodies to C. trachomatis was investigated with the use of a single-antigen, indirect immunofluorescence test; all patients with nongonococcal urethritis due to C. trachomatis had serum antibody against C. trachomatis, whereas only 54% of patients with nonchlamydial, nongonococcal urethritis and 22% of healthy volunteers had serum antibody. C. trachomatis was recovered from only one (0.9%) of 106 women observed in an obstetrical clinic for reasons other than genital tract infections. In a female population selected according to the presence of glandular ectopia of the cervix, C. trachomatis was isolated from nine (5.6%) of 160 women. A significantly (P less than 0.005) higher incidence of histological dysplasia was demonstrated in women presenting both glandular ectopia of the cervix and serum antibody to C. trachomatis than in women with glandular ectopia but no chlamydial antibodies. A seroepidemiological survey of a healthy population showed the presence of antibodies against C. trachomatis in 26% of the controls. The incidence was lowest (16%) among the children younger than ten years of age and highest (37%) among women older than 40 years of age.U | pubmed_803_14968 |
pubmed_871_16036 | Cyclized subunits of the E. coli glucose transporter were produced in vivo by intein mediated trans-splicing. IIA(Glc) is a beta-sandwich protein, IICB(Glc) spans the membrane eight times. Genes encoding the circularly permuted precursors U(Cdelta)-IIA(Glc)-U(Ndelta) and U(Cdelta)-IICB(Glc)-U(Ndelta) were assembled from DNA fragments encoding the 3' and 5' segments of the recA intein of M. tuberculosis and crr and ptsG of E. coli, respectively. A 20-residues long, Ala-Pro rich linker peptide and/or a histidine tag were used to join the native N- and C-termini in the cyclized proteins. The cyclized proteins complemented growth of glucose auxotrophic strains. Purified, cyclized IIA(Glc) and IICB(Glc) had 100 and 25%, respectively, of wild-type glucose phosphotransferase activity. They had an increased electrophoretic mobility, which decreased upon linearization of the proteins with chymotrypsin. Cyclized IIA(Glc) displayed increased stability against temperature and GuHCl-induced unfolding (75 vs. 70 degrees C; 1.52 vs. 1.05 M). | 10.1016/s0301-4622(02)00012-1 |
pubmed_162_18028 | B cells home to the lymph nodes (LNs) via high endothelial venules (HEVs) under the guidance of chemokines, particularly CXCL13. However, as CXCL13 is not directly made in HEVs, the molecular mechanism mediating B-cell homing to LNs has remained unclear. We show here that nuclear factor (NF)-κB-inducing kinase (NIK), a kinase mediating activation of the noncanonical NF-κB pathway, functions in lymphatic endothelial cells (LECs) to regulate B-cell homing to LNs. LEC-conditional deletion of NIK in mice did not affect the integrity or global function of lymphatic vessels but caused a severe reduction in the frequency of B cells in LNs. The LEC-specific NIK deficiency did not affect the survival of B cells or the frequency of B cells in the spleen. B-cell adoptive transfer studies revealed that the LEC-specific NIK deletion impairs the ability of LNs to recruit B cells. We further show that NIK mediates expression of the chemokines CXCL13 and CCL19 in LECs. Although CCL19 is also expressed in blood endothelial cells (BECs), CXCL13 is not produced in BECs. These results suggest that NIK regulates naive B-cell homing to LNs via mediating production of the B-cell homing chemokine CXCL13 in LECs. | 10.1038/cmi.2017.167 |
pubmed_409_12033 | The genotoxicity of 51 epoxides is studied with the SOS-Chromotest using Escherichia coli PQ37 as tester strain. The results obtained with this test system are compared with results of the Ames test. Out of 51 epoxides, 39 are shown to be mutagenic in Salmonella typhimurium whereas only 27 mutagenic epoxides induced the SOS response in Escherichia coli PQ37. | 10.1016/0027-5107(90)90027-2 |
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