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pubmed_978_18920 | A mandelonitrile lyase (EC 4.1.2.10) that catalyzes the dissociation of (S)-(-)-mandelonitrile to benzaldehyde and hydrogen cyanide has been purified to apparent homogeneity from leaves of Ximenia americana L. (Olacaceae). The lyase was purified 122-fold with 38% yield by chromatography on carboxymethyl-cellulose and chromatofocusing. The enzyme had a pH optimum of 5.5, with a Km value of 280 microM. Activity toward 4-hydroxy-(R,S)-mandelonitrile was 77% of that observed with the endogenous substrate; no activity was observed toward the aliphatic substrate acetone cyanohydrin. The enzyme was stable at 4 degrees C and at room temperature for at least 1 month. Native and subunit molecular weights of 38,000 and 36,500, respectively, suggest the enzyme is a monomer. The isoelectric point was pH 3.9 as determined by isoelectric focusing. Staining with periodic acid-Schiff and fluorescein-labeled concanavalin A reagents indicate this enzyme is a glycoprotein. In contrast to (R)-mandelonitrile lyases isolated from Prunus species, the Ximenia lyase does not appear to be a flavoprotein. A second enzyme that eluted from the chromatofocusing column at pH 4.0 was also active toward mandelonitrile. However, this form accounted for less than 10% of the total activity, and its specific activity was only 6% of that of the major component. Additional physical and kinetic studies suggested this activity may be due to a nonspecific enzyme that is active toward mandelonitrile. | 10.1073/pnas.86.18.6978 |
pubmed_994_5373 | Over the last few years multiple studies have been published outlining chloroplast genomes that represent many of the photosynthetic euglenid genera. However, these genomes were scattered throughout the euglenophyceaean phylogenetic tree, and focused on comparisons with Euglena gracilis. Here, we present a study exclusively on taxa within the Euglenaceae. Six new chloroplast genomes were characterized, those of Cryptoglena skujai, E. gracilis var. bacillaris, Euglena viridis, Euglenaria anabaena, Monomorphina parapyrum, and Trachelomonas volvocina, and added to six previously published chloroplast genomes to determine if trends existed within the family. With this study: at least one genome has now been characterized for each genus, the genomes of different strains from two taxa were characterized to explore intraspecific variability, and a second taxon has been characterized for the genus Monomorphina to examine intrageneric variability. Overall results showed a large amount of variability among the genomes, though a few trends could be identified both within Euglenaceae and within Euglenophyta. In addition, the intraspecific analysis indicated that the similarity of a genome sequence between strains was taxon dependent, and the intrageneric analysis indicated that the majority of the evolutionary changes within the Euglenaceae occurred intergenerically. | 10.1111/jeu.12235 |
pubmed_869_1567 | In studies of the biological effects of UV radiation, ozone depletion can be mimicked by performing the study under ambient conditions and adding radiation with UV-B lamps. We evaluated this methodology at three different locations along a latitudinal gradient: Rimouski (Canada), Ubatuba (Brazil) and Ushuaia (Argentina). Experiments of the effect of potential ozone depletion on marine ecosystems were carried out in large outdoor enclosures (mesocosms). In all locations we simulated irradiances corresponding to 60% ozone depletion, which may produce a 130-1900% increase in 305 nm irradiance at noon, depending on site and season. Supplementation with a fixed percentage of ambient irradiance provides a better simulation of irradiance increase due to ozone depletion than supplementation with a fixed irradiance value, particularly near sunrise and sunset or under cloudy skies. Calculations performed for Ushuaia showed that, on very cloudy days, supplementation by the square-wave method may produce unrealistic irradiances. Differences between the spectra of the calculated supplementing irradiance and the lamp for a given site and date will be a function of the time of day and may become more or less pronounced according to the biological weighting function of the effect under study. | 10.1562/2005-09-28-ra-700 |
pubmed_732_13921 | The freshwater shrimp genus Atyaephyra de Brito Capello, 1867 is a complex of cryptic species with morphologically overlapping features, which has led to invalid identifications until recently. The genus is distributed around the entire Mediterranean Basin and surrounding areas. In 2009 we used a molecular approach with 16S and Cox1 genes to identify the European and African populations and to show the existence of different species and groups of haplotypes (García Muñoz et al. 2009). Christodoulou et al. (2012) recently identified four species in Greece (Atyaephyra stankoi, A. thyamisensis, A. strymonensis and A. acheronensis) based on morphology and some partial sequences of Cox1. In the present study we analyse several Greek populations of Atyaephyra spp. using morphology and two mitochondrial markers (16S and Cox1). Our molecular data confirm the taxonomic validity of A. stankoi, A. thyamisensis and A. strymonensis but show that A. acheronensis should be considered a synonym of A. desmarestii. The limited distribution of A. desmarestii in only a few rivers in the Ionian region is probably the result of a posterior introduction from neighbouring European areas. After the genetic identification and as a consequence of the high variability observed within species and between rivers, mainly in A. thyamisensis, we re-describe this species and provide morphological data for the other species. We also give information on the chromatophore pattern in larvae, which could be very useful in the future for recognizing species and their distribution. The distribution of Greek Atyaephyra species seems to be related to the very complex paleogeographical history of the Paratethys and Mediterranean Sea in the Balkan Peninsula. Three areas can be recognized in relation to the distribution of these species: a global region, a western region separated from the eastern region by the Pindos Mountains, and a Macedonia-Thracian region. | 10.11646/zootaxa.3790.3.1 |
pubmed_351_22840 | Several different physics procedures have been tried to mechanize the recording of partograms. Can a measure of impedance of tissue Z using potential difference V, according to Ohm's law V = Z1, and 1 is a constant, be correlated with a measure of cervical dilatation using vaginal examination? This was our hypothesis. The tissue impedance meter was made to our design and applied according to a bipolar procedure. Our work was carried out on 28 patients. 10 patients were registered before labour started in order to test the apparatus and to record the impedance variations without labour taking place, and 18 patients were registered in labour to see whether there was any correlation. The level of impedance in the cervix without labour was 302.7 Ohms with a deviation of 8.2. Using student's t tests it was found that there was a significant correlation (p less than 0.001) in four measurements between the impedance measure and measures obtained by extrapolating the degrees of dilatation calculated from vaginal examination. This is a preliminary study in which we have defined the conditions that are necessary to confirm these first results and to further develop the method. | pubmed_351_22840 |
pubmed_1003_8901 | An extracellular giant hemoglobin of Oligobrachia mashikoi, composed of 24 globins with the molecular mass of approximately 400 kDa was crystallized in its intact form. Two crystal forms were obtained by the vapor-diffusion method. Form I crystals obtained using sodium acetate as a precipitant belong to the space group P6(1)22 or P6(5)22, with unit-cell parameters a=112.41, c=621.25 A, and diffracted X-rays beyond 3.0 A resolution. Form II crystals obtained using PEG 10000 as a precipitant belong to the space group R32, with unit-cell parameters a=111.50, c=276.84 A, and diffracted X-rays beyond 2.9 A resolution. The crystals are suitable for X-ray crystallography to determine the supramacromolecular assembly of this giant hemoglobin. | 10.1016/j.bbapap.2005.05.009 |
pubmed_815_18194 | Sixteen dairy-goat farms were investigated in the centre-west of France for nematode infection. The intensity of infection was assessed by means of faecal egg counts and nematode counts at necropsy for digestive-tract nematodes and faecal larval counts for Muellerius capillaris. The specific diversity and prevalence were estimated by worm counts of 28 necropsied culled goats. The history and breeding management were recorded by means of a questionnaire. Specific diversity was estimated on two culled goats. Specific diversity and prevalence were related to the area of permanent pasture, age of farm, and to the number of goats introduced at the establishment of the farm. The most common species were Teladorsagia circumcincta and Trichostrongylus colubriformis. Teladorsagia trifurcata was absent from zero-grazing farms. Trichostrongylus vitrinus and Oesophagostomum venulosum were present in significant numbers on only one farm out of 16. The importance of Haemonchus contortus varied from farm to farm. The historical and breeding management factors that influenced the proportions of the most common species were the age of farm, size of flock, percentage of Alpine breed, duration of kidding period, age of goats and number of farms of origin. Age of farm and size of flock exerted opposing effects on the proportions of Teladorsagia circumcincta and Trichostrongylus colubriformis, respectively. The historical and breeding management factors were confounded and their respective effects on infection and the proportions of species was difficult to assess. | 10.1016/0304-4017(94)90185-6 |
pubmed_400_16169 | PURPOSE
To assess changes in various functional and satisfaction measures between older persons enrolled in Minnesota Senior Health Options (MSHO), a managed care program for older persons eligible for both Medicare and Medicaid.
DESIGN AND METHODS
We used two sets of matched controls for MSHO enrollees and their families and matched controls living in the community and in nursing homes: Persons in the same county who were eligible to enroll but did not enroll in MSHO and persons in other metropolitan areas where MSHO is not available. For the community sample, we used questionnaires to measure functional status (activities of daily living), pain, unmet care needs, satisfaction, and caregiver burden. Approximately 2 years after the first survey, we resurveyed respondents who lived in the community at the time of the first survey. For the nursing home residents, we used annual assessments to calculate case mix to compare changes in functional levels over time.
RESULTS
There were few significant differences in change over time between the MSHO sample and the two control groups. Out-of-area controls showed greater increases in pain but in-area controls showed less interference from pain. Compared with out-of-area controls, MSHO clients showed greater increase in homemaker use, meals on wheels, and outpatient rehabilitation. Compared with in-area controls, they showed more use of meals on wheels and less help from family with household tasks. There were few differences in satisfaction, but the MSHO families showed significantly lower burden than controls on five items.
IMPLICATIONS
The analyses show only modest evidence of benefit from MSHO compared with the two control groups. The model represented by MSHO does not appear to generate substantial differences in outcomes across function, satisfaction, and caregiver burden. | 10.1093/geront/43.2.165 |
pubmed_899_8306 | INTRODUCTION
Qualitative interviews are used to assess understandability and content validity of patient-reported outcomes. However, the common approach of asking patients to paraphrase items may not be sufficient to completely reveal item content as understood by patients.
OBJECTIVE
We used qualitative interviews to elicit more detailed information about patients' understanding of treatment goal items for the Patient Benefit Index 2.0 (PBI 2.0). This questionnaire measures patient-relevant benefit from treatments for skin diseases by assessing goal importance prior to and goal attainment after treatment.
METHODS
We interviewed 16 patients with psoriasis, atopic dermatitis, leg ulcers, and vitiligo. Patients were asked to elaborate in detail on their understanding of 15 treatment goal items. Subsequently, they were asked to suggest changes in item wording and to name missing treatment goals. Interview transcripts were analyzed according to an adapted approach of content analysis.
RESULTS
The task was easy for the patients to understand, and they shared detailed information on what each goal meant to them. Results of the content analysis induced a range of revisions of the PBI 2.0 items, including changes in wording (four items) and item order (two items). Four items were deleted because they were found to be redundant or irrelevant, and one item was added to the list of treatment goals.
CONCLUSIONS
Asking patients to elaborate on their item understanding in qualitative interviews provided detailed insight into item content and understandability. This method has helped considerably to improve feasibility and content validity of the PBI 2.0. | 10.1007/s40271-015-0149-5 |
pubmed_529_23373 | Routinely recorded health data have evolved from mere by-products of health care delivery or billing into a powerful research tool for studying and improving patient care through clinical epidemiologic research. Big data in the context of epidemiologic research means large interlinkable data sets within a single country or networks of multinational databases. Several Nordic, European, and other multinational collaborations are now well established. Advantages of big data for clinical epidemiology include improved precision of estimates, which is especially important for reassuring ("null") findings; ability to conduct meaningful analyses in subgroup of patients; and rapid detection of safety signals. Big data will also provide new possibilities for research by enabling access to linked information from biobanks, electronic medical records, patient-reported outcome measures, automatic and semiautomatic electronic monitoring devices, and social media. The sheer amount of data, however, does not eliminate and may even amplify systematic error. Therefore, methodologies addressing systematic error, clinical knowledge, and underlying hypotheses are more important than ever to ensure that the signal is discernable behind the noise. | 10.2147/CLEP.S129779 |
pubmed_41_17337 | The molecular mechanism of muscle contraction is based on the ATP-dependent cyclic interaction of myosin heads with actin filaments. Myosin head (myosin subfragment-1, S1) consists of two major domains, the motor domain responsible for ATP hydrolysis and actin binding, and the regulatory domain stabilized by light chains. Essential light chain-1 (LC1) is of particular interest since it comprises a unique N-terminal extension (NTE) which can bind to actin thus forming an additional actin-binding site on the myosin head and modulating its motor activity. However, it remains unknown what happens to the NTE of LC1 when the head binds ATP during ATPase cycle and dissociates from actin. We assume that in this state of the head, when it undergoes global ATP-induced conformational changes, the NTE of LC1 can interact with the motor domain. To test this hypothesis, we applied fluorescence resonance energy transfer (FRET) to measure the distances from various sites on the NTE of LC1 to S1 active site in the motor domain and changes in these distances upon formation of S1-ADP-BeFx complex (stable analog of S1∗-AТP state). For this, we produced recombinant LC1 cysteine mutants, which were first fluorescently labeled with 1,5-IAEDANS (donor) at different positions in their NTE and then introduced into S1; the ADP analog (TNP-ADP) bound to the S1 active site was used as an acceptor. The results show that formation of S1-ADP-BeFx complex significantly decreases the distances from Cys residues in the NTE of LC1 to TNP-ADP in the S1 active site; this effect was the most pronounced for Cys residues located near the LC1 N-terminus. These results support the concept of the ATP-induced transient interaction of the LC1 N-terminus with the S1 motor domain. | 10.1016/j.bbrc.2017.10.172 |
pubmed_1089_17588 | In 1980, more than 376 million persons were age 60 or older in the world. By the year 2000, this figure is expected to increase by 57% to 590.4 million. Approximately 61% of these persons will be living in the lesser developed countries of the world. The growth and distribution of older persons throughout the world will have far reaching consequences for the utilization of national resources, including health resources. | 10.1007/BF00116016 |
pubmed_412_12432 | There is evidence indicating that the area postrema (AP), the most caudal circumventricular organ located on the dorsal surface of the medulla, is involved in several physiological regulations. In this study, we investigated the role of AP in the regulation of arginine vasopressin (AVP) synthesis and release, using rats of which the AP was lesioned 6 weeks previously. The level of plasma AVP in the AP lesioned (APX) group was significantly lower than in the sham operated (Sham) group in the basal state. AVP release induced by either hyperosmolality or hypovolemia was significantly attenuated by APX. To clarify the role of AP in AVP synthesis in the hypothalamus, we examined the AVP gene expression using in situ hybridization. AVP messenger RNA levels in paraventricular (PVN) and supraoptic nuclei (SON) in the APX group were significantly lower than in the Sham group in the basal state. Moreover, the AVP messenger RNA levels in PVN and SON in the APX group were also significantly lower than in the Sham group after water deprivation for 3 days. These results suggest that AVP synthesis and release are tonically stimulated by AP in the basal state and that AVP synthesis and release in stimulated states are also regulated, at least partially, by AP. | 10.1210/endo.139.4.5873 |
pubmed_449_9881 | The basic aims of hygienic standardization of the long-term round-the-clock action of ship noise on the sailors include protection of health, prolonged professional activity, prevention of interference and provision of comfort conditions of rest. Neuro-emotional stress in the work of sailors aboard a ship has been another reason for starting the ship noise standardization. As a result of long-term hygienic, clinical, physiological, experimental and natural studies, there were established the hygienic significance of noise and vibration parameters, a combined increased effect of noise and work strain, as well as that of pitching and rolling, and also the potent combined effect of vibration and noise. During a 3-month voyage the cumulative effect of noise was identified and the physiological significance of acoustic comfort of post-watch rest was ascertained. The relation of sailors' health to ship acoustic conditions was determined. The obtained results served as a scientific motivation for a number of Soviet legislative documents. Unification of physiological and hygienic criteria and methods of assessment of noise and vibration effects meets the interests of protection of seamen's health in CMEA countries. | pubmed_449_9881 |
pubmed_218_20064 | OBJECTIVES
To investigate the effects of androgen administration at different periods of prepubertal life on penile size and potential fertility in hormonally normal rats.
METHODS
Eighty Sprague-Dawley rats were divided into 4 groups; group 1 received weekly injections of testosterone enanthate (8 mg/100 g) at 1-3 weeks group 2 at 3-5 weeks, group 3 at 1-5 weeks, and group 4 was control (n = 20 each). Animals were killed at age 60 days. Penile length, penile, testicular, and epididymal weight, testicular fertility index, serum follicular stimulating hormone, luteinizing hormone, and testosterone levels were measured and quantitative real time polymerase chain reaction of penile androgen receptor messenger ribonucleic acids was performed.
RESULTS
Penile length in the 3-5-week injection group was significantly longer than controls (41.18 vs 39.13 mm, P = .011), and it was smaller than controls in the 1-3 week injection group (37.24 vs 39.13 mm, P = .020). The penile wet weight showed a similar pattern to stretched penile length; however, statistical significance was not found. Testicular weight was significantly less in the testosterone injection group than controls (1.79, 2.16, 2.24, and 2.78 g in groups 1-4, respectively) as well as the epididymal weight (0.48, 0.42, 0.59, and 0.69 in groups 1-4, respectively). The mean tubular diameter and germ cell count were significantly reduced in the testosterone treated group. Total penile androgen receptor messenger ribonucleic acid level was significantly lower in group 3 as compared with controls.
CONCLUSIONS
Testosterone administered during early prepubertal life resulted in smaller penis than controls, as well as having an adverse effect on testicular development which can jeopardize potential fertility. | 10.1016/j.urology.2009.08.064 |
pubmed_121_13316 | INTRODUCTION
There has been increasing interest in using deep parasternal intercostal plane (PIP) block as a supplement to multimodal analgesia regimens in cardiac surgery. The aim of this study was to observe cutaneous sensory block distribution and its duration for deep PIP blocks in patients undergoing open cardiac surgery.
METHODS
This observational, prospective clinical study consisted of 113 participants. All patients received bilateral ultrasound-guided deep PIP block with 40 ml 0.33% ropivacaine. The primary study outcome was cutaneous sensory block distribution of deep PIP blocks in patients undergoing open cardiac surgery. Secondary outcome included block duration in all participants. The area of cutaneous sensory block was tested by using a cold stimulus (ice cube) 30 min after the end of deep PIP block administration. Cutaneous sensory testing was performed once every hour after extubation until the return of normal sensation.
RESULTS
Thirty minutes after bilateral deep PIP block administration, the successful block rate of dermatomes T4 to T6 was almost 100%. However, T2 (percentage of left T2 block: 64.6%; percentage of right T2 block: 42.5%) and T3 (percentage of left T3 block: 88.5%; percentage of right T3 block: 87.6%) had a lower percentage of success. A few patients had blocked dermatomes at T1 or T7 (percentage of left T1 block: 7.08%; percentage of right T1 block: 2.65%; percentage of left T7 block: 6.19%; percentage of right T7 block: 10.6%). The mean effective duration of the deep PIP block was 17 h.
CONCLUSION
Bilateral deep PIP blocks can produce a widespread cutaneous sensory blockade with variable dermatomal distribution in the mid-sternum for a considerable effective duration.
TRIAL REGISTRATION
This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047755). | 10.1007/s40122-022-00403-y |
pubmed_1125_20778 | The purpose of this survey was to investigate the perceptions of health care professionals concerning the development of clinical pathways before the implementation of the regional electronic health record. The data of this study were collected from health care professionals working with conservative heart patients and surgical hip joint patients by means of a questionnaire. The professionals were working at one central hospital and two primary care units. In this hospital region, the process of regional electronic health record implementation is ongoing. The data from this survey were analyzed using statistical methods. The participants in this study set great store by developing and describing the current clinical pathways, and believed it was important to plan the changes in clinical pathways before implementing the electronic health record. However, the clinical pathways development work has not yet fully commenced. | pubmed_1125_20778 |
pubmed_244_19033 | As one of the world's five terminally ills, tumours can cause important genetic dysfunction. However, some current medicines for tumours usually have strong toxic side effects and are prone to drug resistance. Studies have found that farnesyltransferase inhibitors (FTIs) extracted from natural materials have a good inhibiting ability on tumours with fewer side effects. This article describes several FTIs extracted from natural materials and clarifies the current research progress, which provides a new choice for the treatment of tumours. | 10.1080/14756366.2020.1732366 |
pubmed_464_22185 | Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes (P. acnes) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1β (IL-1β) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla's rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1β pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1β/IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 108 CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1β pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1β pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes-induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV. | 10.1155/2021/1821220 |
pubmed_90_2171 | The implication of post-mortem changes such as cell swelling, imbibition and autolysis on the elemental composition of body organs has been studied in rats. Liver has been chosen as an example. Retaining the liver inside the intact dead body for different periods of time at ambient temperature induced significant changes in its weight due to post-mortem tissue degeneration. Livers from animals that were frozen at -15 degrees C also showed significant decreases in weight when they were thawed on the third day. The effect of these changes on the concentrations of various elements depended on the association of the elements with extracellular fluid and intracellular components. For example, concentration of K+ was affected more by the lysis of the cell and sustained losses up to 30 per cent. in relation to the control values, while the total content was reduced by more than 40 per cent. as a result of both lysis and tissue liquefaction. For Na+, differences ranging from +10 to -20 per cent. in concentrations and +20 to -40 per cent. in total content were observed which could be explained by the movement of fluid in and out of the organ. Among trace elements, variation observed for iron ranged from -20 to +40 per cent., while both copper and zinc were found to fluctuate between -20 and +20 per cent. The loss observed in the total content in the liver for the five trace elements studied (Cu, Fe, Mn, Rb and Zn) was found to be about 20 to 40 per cent. | 10.1002/path.1711340302 |
pubmed_163_20416 | The interactions between Emiliania huxleyi and E. huxleyi virus (EhV) regulate marine carbon and sulfur biogeochemical cycle and play a prominent role in global climate change. As a large DNA virus, EhVs have developed a novel "virocell metabolism" model to meet their higher metabolic needs. However, the regulatory mechanism of this metabolic model is still largely unclear. MicroRNAs (miRNAs) can regulate biological pathways through targeting hub genes in the metabolic processes. Here, we performed high-throughput small RNA sequencing to analyse miRNA expression in EhV99B1 infected E. huxleyi BOF92. A total of 26 miRNAs (including 2 virus-derived miRNAs) were identified, including four up-regulated and one down-regulated miRNAs. These results were further validated through quantitative real-time PCR. Functional enrichment analysis showed that five differentially-expressed miRNAs might be involved in the regulation of carbohydrate metabolism, lipid metabolism and amino acid metabolism. Moreover, the expression levels of differentially-expressed miRNAs were negatively correlated with that of several lipid metabolism-related genes, such as ACC-1, SPT, ACOX, ACAT, CERS and ACADS, indicating that these miRNAs might play an important regulatory role in virus-mediated lipid metabolism. | 10.16288/j.yczz.21-164 |
pubmed_263_2215 | More than 27 series of the Japanese general rules of cancer handling, which comprise the basic foundations of cancer diagnosis and treatment, are currently used for routine clinical management in Japan. However, important concerns such as compatibility with the Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification, the lack of unity of revised time, and unsuitable term definitions during consensus have emerged following medical globalization, advances in medical treatment, and legislation regarding cancer registration in hospital, which will begin 2015. To efficiently employ the strong points of the Japanese general rules of cancer handling and conquer the problems associated with cancer treatment globalization in Japan, immediate unification of the current Japanese general rules of cancer handling is thought to be required. In this paper, I would like to propose a method for solving these problems henceforth by clarifying the problems associated with the Japanese general rules of cancer handling and establishing future relationships between the Japanese general rules of cancer handling and the UICC-TNM and American Joint Committee on Cancer (AJCC). More than 27 series of the Japanese general rules of cancer handling, which comprise the basic foundations of cancer diagnosis and treatment, are currently used for routine clinical management in Japan. However, important concerns such as compatibility with the Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification, the lack of unity of revised time, and unsuitable term definitions during consensus have emerged following medical globalization, advances in medical treatment, and legislation regarding cancer registration in hospital, which will begin 2015. To efficiently employ the strong points of the Japanese general rules of cancer handling and conquer the problems associated with cancer treatment globalization in Japan, immediate unification of the current Japanese general rules of cancer handling is thought to be required. In this paper, I would like to propose a method for solving these problems henceforth by clarifying the problems associated with the Japanese general rules of cancer handling and establishing future relationships between the Japanese general rules of cancer handling and the UICC-TNM and American Joint Committee on Cancer (AJCC). | pubmed_263_2215 |
pubmed_899_18928 | An economic and practical AIBN-initiated aerobic oxidation system of benzylic alcohols, hetero aryl alcohols and allyl alcohols was developed for the first time. Moderate to excellent yields were obtained with a broad substrate scope. Moreover, a proposed mechanism of a radical process was assumed and confirmed by the key intermediate detected. | 10.1039/c5ob01834j |
pubmed_936_23973 | Background
The COVID-19 pandemic has undone years of progress in providing essential TB services and controlling the TB burden. Italy, a low TB burden country, has an incidence of 7.1 cases per 100,000 people. To control the TB spreading in Italy is critical to investigate the characteristics of patients with the worst outcomes and the highest risk of adverse events related to antituberculosis therapy. Therefore, we conducted a large retrospective study in TB patients admitted to the Clinic of Infectious Diseases University of Bari, Italy, in order to describe the clinical presentation and the factors associated with adverse events and outcomes.
Methods
We retrospectively evaluated the patients admitted to the Clinic of Infectious Diseases from January 2013 to 15 December 2021. We stratified our cohort into two groups: <65 years of age and ≥65 years in order to assess any differences between the two groups. Two logistic regression models were implemented considering the dependent variables as: (I) the adverse events; and (II) the unsuccessful treatments.
Results
In total, 206 consecutive patients [60% (n = 124) M, median age 39 years, range 16-92] were diagnosed and admitted with TB at Clinic of Infectious Diseases. Of the whole sample, 151 (74%) were <65 years and 55 (26%) were ≥65. Statistically significant differences between the two groups were detected (p-value < 0.05) for nationality (p-value = 0.01), previous contact with TB patient (p-value = 0.00), type of TB (p-value = 0.00), unsuccessful treatment (p-value = 0.00), length of hospitalization (p-value = 0.02) and diagnostic delay (p-value = 0.01). Adverse events related to TB drug regimen were reported in 24% (n = 49). Age < 65 years (O.R. = 3.91; 95% CI 1.72-4.21), non-Italian nationality (O.R. = 4.45; 95% CI 2.22-4.98.), homeless (O.R. = 3.23; 95% CI 2.58-4.54), presence of respiratory symptoms (O.R. = 1.23; 95% CI 1.10-1.90), diagnostic delay (O.R = 2.55; 95% CI 1.98-3.77) resulted associated with unsuccessful treatment outcome (death, failure or lost to follow up). Finally, age < 65 years (O.R. = 1.73; 95% CI 1.31-2.49), presence of pulmonary TB (O.R. = 1.15; 95% CI 1.02-1.35), length of hospitalization (O.R. = 1.82; 95% CI 1.35-2.57) and TB culture positive (O.R. = 1.35; 95% CI 1.12-1.82) were associated with adverse events in our populations.
Conclusions
The pharmacological approach alone seems insufficient to treat and cure a disease whose ethiopathogenesis is not only due to the Mycobacterium tuberculosis, but also to the poverty or the social fragility. Our data suggest that young foreigners, the homeless, and the people with low social and economic status are at higher risk of an unfavorable outcome in low incidence TB countries. Targeted actions to support this highly vulnerable population both in terms of outcome and occurrence of adverse events are needed. | 10.5334/aogh.3677 |
pubmed_245_6391 | Contralateral metastatic axillary lymph nodes in a patient with breast cancer is a rare condition. Here, we present a 55-year-old woman with a second primary breast cancer. The patient underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for staging work-up. Additionally, preoperative lymphoscintigraphy was performed to detect sentinel lymph nodes. FDG PET/CT demonstrated increased FDG uptake in the left nipple and right axillary lymph nodes. Lymphoscintigraphy identified the right axillary lymph nodes which was consistent with the FDG PET/CT findings. This case emphasizes the usefulness of FDG PET/CT and lymphoscintigraphy for identifying unpredictable contralateral axillary lymph node metastasis from a second primary breast cancer. | 10.1007/s13139-017-0485-6 |
pubmed_671_7545 | Urinary infection is found in less than 10% of renal stone formers. It is three times more common in women than in men. Urea-splitting bacteria (Proteus, Klebsiella, pyocyaneus, staphylococcus) leading to stone formation are identified in two thirds of the cases. The percentage of the different bacteria varies depending upon the sex and degree of resistance to therapy. The sensitivity of bacteria to eight commonly used drugs was investigated. | 10.1159/000473309 |
pubmed_773_3253 | Two methods of assessing personal space in young children were examined in a group of 24 boys and 24 girls, aged 3 to 6 yr. When sex of peer figures and affect attributed to them were varied, 3-yr.-olds made distance-cue judgements based on affect but failed to use affect cues in structuring personal space. However, 4- to 6-yr.-olds readily perceived and used distance to communicate the affective quality of peer relations. On both measures, perception of distance cues increased with age. Only girls also used sex of figures as a social cue in depicting appropriate distances. | 10.2466/pms.1976.43.1.107 |
pubmed_921_22644 | The type II iodothyronine deiodinase (D2) catalyzes the 5'-deiodination of thyroxine to yield the biologically active form, 3,3',5,-tri-iodothyronine, and is a member of the selenoproteins. We isolated a 17.5 kb mouse genomic clone containing the entire coding and 5'-untranslated regions of the D2 gene (mdio2). We also isolated the entire 5'-UTR of the mouse D2 cDNA, which was 753 bp in length and contained five ATG codons. An additional 258 bp ORF from the fourth ATG codon was found in the same reading frame as the coding region reported previously, and this additional ORF contained a TGA codon, which could encode selenocysteine. The proximal promoter of mdio2 contained a TATA box and several potential transcription factor-binding sequences, including CRE, C/EBP and GATA binding sites. The 1.3 kb 5'-upstream region exhibited a promoter activity by reporter assay using Mm5MT and JAR cells, which have a D2 transcript, but not HepG2 cells that have no detectable level of D2 transcript. | 10.1016/s0303-7207(00)00246-x |
pubmed_1107_8486 | For about 20 years we have known from cytogenetic studies that there is a clonal cell population in Hodgkin's disease. Most karyotypes are complexly aberrant and chromosome numbers typically lie in the hyperploid range. Some chromosome regions seem to be preferentially involved, but a chromosome aberration specific for Hodgkin's disease has not yet been determined. Although the existence of a clonal cell population is evident from these cytogenetic studies, there is still an ongoing debate, whether in all cases the pathognomonic Hodgkin and Reed-Sternberg cells belong to one single aberrant clone and thus represent a monoclonal proliferation. This article reviews the current knowledge on cytogenetics in Hodgkin's disease. Moreover, our recent data from simultaneous immunophenotyping and interphase cytogenetics (FICTION) are introduced into the passionate discussion on the monoclonality of the Hodgkin and Reed-Sternberg cells. | 10.1093/annonc/7.suppl_4.s49 |
pubmed_229_9139 | OBJECTIVES
To examine the characteristics of evoked and induced gamma band oscillatory responses occurring during P300 development in an auditory oddball paradigm.
METHODS
A time-frequency analysis method was applied to an auditory oddball paradigm in 7 healthy subjects. This method combines a multiresolution wavelet algorithm for signal extraction and the Gabor transform to represent the temporal evolution of the selected frequency components. Phase-locked or evoked activity and also non-phase-locked activity were computed for both standard and target stimuli.
RESULTS
The gamma band frequency components differed between target and non-target stimuli processing. The study showed an early and mainly phase-locked oscillatory response appearing around 26--28 ms after both standard and target stimuli onset. This response showed a spectral peak around 44 Hz for both stimuli. A late oscillatory activity peaking at 37 Hz with a latency around 360 ms was observed appearing only for target stimuli. The latency of this late oscillatory activity had a high correlation (P=0.002) to the latency of the P300 wave.
CONCLUSIONS
EEG signal analysis with wavelet transform allows the identification of an early oscillatory cortical response in the gamma frequency range, as well as a late P300-related response. | 10.1016/s1388-2457(01)00557-0 |
pubmed_58_1544 | BACKGROUND
Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) behave as a novel class of transcription products during multiple cancer processes. However, the mechanisms responsible for their alteration in cholangiocarcinoma (CCA) are not fully understood.
METHODS
The expression of SPRY4-IT1 in CCA tissues and cell lines was determined by RT-qPCR, and the association between SPRY4-IT1 transcription and clinicopathologic features was analyzed. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of SPRY4-IT1 and activate its transcription. The biological function of SPRY4-IT1 in CCA cells was evaluated both in vitro and in vivo. ChIP, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays were performed to determine the molecular mechanism of SPRY4-IT1 in cell proliferation, apoptosis and invasion.
RESULTS
SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.
CONCLUSIONS
Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. | 10.1186/s13046-018-0747-x |
pubmed_332_17580 | BACKGROUND
Cisplatin induced ototoxicity is a serious adverse effect of cisplatin therapy. Cisplatin induced ototoxicity shows significant interindividual variability. This variability is probably based on genetic background. Recent papers describe association of cisplatin ototoxicity with allelic variants of glutathion-S-transferase coding genes.
PATIENTS AND METHODS
We have analyzed 55 patients treated with cisplatin therapy without any previous hearing impairment. Audiometric examination was performed before the start of cisplatin therapy and then before and after each cycle of cisplatin. DNA isolated from peripheral blood samples was used to analyze genetic polymorphisms of selected genes coding for glutathion-S-transferases.
RESULTS
We have demonstrated association of early onset of cisplatin induced hearing impairment with absence of null allele of GSTT1 (p = 0.009). Both GSTM1 gene deletion and single nucleotide polymorphism in GSTP1 gene (rs1695) did not show any association with cisplatin induced ototoxicity.
CONCLUSION
Early onset of cisplatin induced hearing impairment is more probable in persons with two functional alleles of GSTT1 gene. | pubmed_332_17580 |
pubmed_1009_9791 | A well-known feature of Broca's aphasia is the problem of handling "small words." It has been claimed that patients show these problems in both language production and language perception. The traditional dichotomy of "function" words and "content" words is probably not a good description of the classes of words that are affected and intact. It has long been recognized that not only do Broca's aphasics have problems with free closed class morphemes, but that also bound morphemes, such as verb inflections, are often omitted in spontaneous speech. The question arises whether all bound morphemes, being members of the closed class category, are difficult to process for Broca's aphasics. Using a lexical decision task the recognition of derivational word forms was studied in Broca's aphasics and two control groups. The pattern of results is very similar in the three groups. Derivational word forms are recognized as lexical items independent of the stem. It is concluded that Broca's aphasics can process derivational affixes appropriately. The consequences of this conclusion for the characterization of the class of "small" words are discussed. | 10.1016/0093-934x(86)90110-0 |
pubmed_109_6607 | Two classes of mutants, con and tolG, that appeared to be very similar in a number of respects have been shown to be identical and cotransducible with pyrD. By diethylaminoethyl-cellulose chromatography of the outer membranes, we have shown that the mutants are missing only protein 3A and retain protein 3B. Using con mutants, we were thus able to identify protein 3B on the pH 7.2 gel system of Maizel where it runs separately from protein 3A if unheated samples are used. tolG mutants were shown to be identical to con mutants in being conjugation defective with most F-like plasmid donors but not with I-like plasmid donors, and in their resistance pattern to bacteriophages and colicins. During the course of this study, it was observed that the bacteriocin produced by Serratia marcescenc JF246 was identical in its activity spectrum to colicin L-398 and is now considered to be a colicin of type L. | 10.1128/jb.127.3.1070-1079.1976 |
pubmed_357_22279 | Aneurysm of the internal thoracic artery is a rare entity, with variable presentation and a potential risk of fatal rupture. Angiotomography is the diagnostic test of choice and is useful for planning treatment. Considering the morbidity of thoracic access for a direct approach and the unpredictable risk of rupture, an endovascular procedure is the treatment modality of choice for this type of aneurysm. We describe the case of an internal thoracic artery aneurysm discovered incidentally during investigation of syncope and treated by embolization with low-profile and controlled-release microcoils. | 10.1590/1677-5449.200042 |
pubmed_456_18762 | OBJECTIVES
To investigate potential harm and benefits of antiepileptic drugs (AED) given prophylactically to prevent de novo brain tumour-related epilepsy after craniotomy.
METHODS
Randomised controlled trials (RCT) and retrospective studies published before 27 November 2018 were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied. Eligible patients were diagnosed with a brain tumour, were seizure naïve and underwent craniotomy. The random effects model was used for quantitative synthesis. The analysis was adjusted for the confounding effect of including patients with a history of seizure prior to study inclusion.
RESULTS
A total of 454 patients received prophylactic AED whereas 333 were allocated to placebo or no treatment. Two RCTs and four retrospective studies were identified. The OR was 1.09 (95% CI 0.7 to 1.8, p=0.7, I2=5.6%, χ2 p=0.5), indicating study consistency and no significant differences. An additional two RCTs and one retrospective study combined craniotomy and diagnostic biopsy, and were subgroup analysed-which supported no difference in odds for epilepsy.
CONCLUSIONS
A prophylactic effect of AED could not be demonstrated (nor rejected statistically). Levetiracetam was associated with less adverse effects than phenytoin. The potential harm of AED was not balanced by the potential prophylactic benefit. This study suggests that prophylactic AED should not be administered to prevent brain tumour-related epilepsy after craniotomy. | 10.1136/jnnp-2018-319609 |
pubmed_581_11156 | OBJECTIVES
The aim of this study was to investigate the relationship between serum infliximab (IFX) levels and changes of RF and ACPA levels in patients with rheumatoid arthritis (RA).
METHODS
Enzyme-linked immunosorbent assays (ELISA) [Promonitor® IFX R1 (version 2) (Progenika Biopharma, Spain)] were used to measure drug levels and antidrug-antibodies (ADAb) in IFX RA-treated patients (n=19). Disease activity was assessed using DAS28. IgM rheumatoid factor (RF) and IgM, IgA and IgG anti-cyclic citrullinated peptide (ACPA) were determined through ELISA.
RESULTS
A significant decrease in RF (p=0.01), ACPA IgG (p=0.007), IgM (p=0.01) and IgA (p=0.03) was observed in patients presenting adequate levels of serum IFX. No significant changes to RF or ACPA were observed in patients with undetectable IFX.
CONCLUSIONS
Data from this study support the hypothesis that the anti-TNF antagonist IFX downregulates autoantibody levels in RA patients when IFX levels are detectable. Larger-scale studies need to be performed to establish RF and ACPA presence as therapeutic response predictive factors. | pubmed_581_11156 |
pubmed_525_8342 | Gene expression in cultures of Escherichia coli has been determined in situ and on-line by the use of an electrochemical sensor. Intact bacteria were used to monitor the induction of the lacZ gene; the onset of stationary phase was also monitored, using a reporter gene fused to the RpoS-dependent promoter of the osmY gene. The technique described can in principle be used to determine the activity of any promoter, with a variety of reporter genes. This technology is non-intrusive, allows real-time monitoring of gene expression, and will be useful in the study of growth regulation and development. | 10.1099/13500872-145-8-2129 |
pubmed_713_16108 | Physiological determinants of different body weight (BW) broiler chickens under heat stressed conditions were investigated to compare the performance at market age considering medium body weight group as standard. At 5 weeks, broilers were categorized randomly into 3 treatments (N = 24 per group) as high (HBW) (>1050 g), medium (MBW) (900-1050 g) and low (LBW) (<900 g) followed by simultaneous exposure to normal and heat stress (HS) conditions at 40 ± 1 °C and 45 ± 5% RH for 4 h/day for a period of 7 days (D) and sample collection was employed at D0, D3 and D7. Physiological and stress responses, haematological and biochemical profile, intestinal gross and histological aspects were estimated using standard protocols. Heart rate and mean arterial blood pressure were significantly (P = 0.000) higher in HBW broilers followed by low and medium ones. Heat stress exposure indicated significant (P = 0.000) increase in heart rate, arterial blood pressure, respiration rate and comb temperature while cloacal temperature remained unaffected. Lymphocytes, eosinophils, total red blood cell count, haemoglobin, and haematocrit were reduced (P = 0.000) whereas mean corpuscular volume and mean corpuscular hemoglobin, heterophil count and heterophil to lymphocyte ratio were increased (P = 0.000) in response to HS. Circulating corticosterone and tri-iodothyronine concentrations showed inverse relationship with respect to BW variation and HS duration respectively with significant interaction (P = 0.000). Higher protein in LBW was observed on D3. Serum triglycerides remained unaffected till D3 exposure but significantly (P = 0.017) reduced on D7 with lowest content in HBW group. Serum alkaline phosphatase increased in LBW group with significant heat stress interaction (P = 0.000) on D3. HS reduced villi length and crypt depth; but their corresponding ratio increased. In conclusion, HBW broilers are more affected than MBW or LBW groups. This study established interactive roles of BW and HS on physiological responses in broilers. | 10.1016/j.jtherbio.2021.102840 |
pubmed_256_2370 | Detection of cell death throughout embryogenesis demonstrates its importance in the normal form and function of the organism. We have examined cellular death during normal limb development by use of markers that display the morphology of cell death, the presence of phagocytic cells, and lysosomal activity. In addition in situ labeling confirms fragmentation of DNA in the mammalian limb. By these criteria, cell death in the developing limb can be categorized as type 1 or apoptotic cell death. However, the signal(s) responsible for cellular destruction and activation of phagocytosis by neighboring cells or recruited macrophages remain to be identified. The decision for cellular fate during development and regulation of it once the decision is made are key questions. To address the specific question of what determines that one cell will die while its neighbor survives, we have used compounds, such as retinoic acid (RA), that have been shown to alter the pattern of normal development. We and others have shown that RA does indeed alter the pattern of cell death to the extent of inducing malformations in the limb. The mouse mutant Hammertoe (Hm) provides an abnormal system in which the pattern of cell death is specifically altered in the interdigital regions of the limb. Our preliminary data suggest that RA can also introduce cell death between digits 2, 3, 4, and 5 of the Hm mutant where there was no cell death to begin with. Our observations of the effect of RA on mutant limbs suggest that a direct relationship between RA and cell death does exist and that this interaction may be required for correct pattern formation. The alteration in the pattern of cell death in the mutant mouse is of great interest, since it would provide a rare example of specific correction of a birth defect by direct intercession against the physiological effect of the mutation. | 10.1139/o94-080 |
pubmed_52_5396 | Bcl-6 is a transcription factor that is normally expressed in germinal centre B cells. It is essential for the formation of germinal centres and the production of high-affinity antibodies. Transcriptional downregulation of Bcl-6 occurs on terminal differentiation to plasma cells. Bcl-6 is highly expressed in B-cell non-Hodgkin's lymphoma and, in a subset of cases of diffuse large cell lymphoma, the mechanism of Bcl-6 overexpression involves interruption of normal transcriptional controls. Transcriptional control of Bcl-6 is, therefore, important for normal antibody responses and lymphomagenesis, but little is known of the cis-acting control elements. This report focuses on a region of mouse/human sequence homology in the first intron of Bcl-6, which is a candidate site for such a control element. We demonstrate that poly-(ADP-ribose) polymerase-1 (Parp-1) binds in vitro and in vivo to specific sequences in this region. We further show that PARP inhibitors, and Parp-1 knockdown by siRNA induce Bcl-6 mRNA expression in Bcl-6 expressing cell lines. We speculate that Parp-1 activation plays a role in switching off Bcl-6 transcription and subsequent B-cell exit from the germinal centre. | 10.1038/sj.onc.1210434 |
pubmed_67_2157 | Hand, foot, and mouth disease (HFMD) is an important public health problem and has received concern worldwide. Moreover, the coronavirus disease 2019 (COVID-19) epidemic also increases the difficulty of understanding and predicting the prevalence of HFMD. The purpose is to prove the usability and applicability of the automatic machine learning (Auto-ML) algorithm in predicting the epidemic trend of HFMD and to explore the influence of COVID-19 on the spread of HFMD. The AutoML algorithm and the autoregressive integrated moving average (ARIMA) model were applied to construct and validate models, based on the monthly incidence numbers of HFMD and meteorological factors from May 2008 to December 2019 in Henan province, China. A total of four models were established, among which the Auto-ML model with meteorological factors had minimum RMSE and MAE in both the model constructing phase and forecasting phase (training set: RMSE = 1424.40 and MAE = 812.55; test set: RMSE = 2107.83, MAE = 1494.41), so this model has the best performance. The optimal model was used to further predict the incidence numbers of HFMD in 2020 and then compared with the reported cases. And, for analysis, 2020 was divided into two periods. The predicted incidence numbers followed the same trend as the reported cases of HFMD before the COVID-19 outbreak; while after the COVID-19 outbreak, the reported cases have been greatly reduced than expected, with an average of only about 103 cases per month, and the incidence peak has also been delayed, which has led to significant changes in the seasonality of HFMD. Overall, the AutoML algorithm is an applicable and ideal method to predict the epidemic trend of the HFMD. Furthermore, it was found that the countermeasures of COVID-19 have a certain influence on suppressing the spread of HFMD during the period of COVID-19. The findings are helpful to health administrative departments. | 10.1007/s11356-022-23643-z |
pubmed_837_20848 | New information is now provided to the pediatric pathologist through the application of new techniques as immunocytochemistry, cytogenetics, flow cytometry, etc... Their confrontation with better analysis of histopathology and extremely valuable data provided through Electron Microscopy and tissue culture has led to important progress in sub-classification of tumors, and especially definition of histologic patterns correlating with favorable or unfavorable response to therapy. This is especially true in the field of renal tumors. Clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumors (MRTK) have recently been isolated as tumors of unfavorable prognosis. The actuarial 2-year survival rate is 49% for CCSK and 10% for MRTK (versus 95% for Wilms' Tumor). Amongst tumors of good prognosis are congenital mesoblastic nephroma which can be considered as a benign tumor, when no atypia is present, and cystic partially differentiated nephroblastoma, which is potentially malignant but in most cases is related to favorable outcome. Attention should be now focused on minimising the sequela of treatment, which requires different strategies according to extension of disease and histologic subclassification. | pubmed_837_20848 |
pubmed_980_22515 | BACKGROUND
Worldwide research anticipates that a current shortage of rheumatologists will exacerbate over the next decade, whereas the need for arthritis specialists will continue to escalate. Saudi Arabia (SA) also encounters a limited geographical distribution of rheumatologists and rheumatology fellowship training centres.
OBJECTIVE
Reporting the Saudi rheumatologists' advisory meeting conducted in Makkah, SA in January 2020 with the aim to discuss the "Saudi Vision 2030" for rheumatology training programs.
MATERIALS AND METHODS
A meeting of Saudi rheumatology experts and consultants was conducted to address the future directions, challenges, and recommendations of rheumatology training. The 10th Rheumatology Practice Symposium was organised by Alzaidi Chair of Research in Rheumatic Diseases (ZCRD), and conducted in Makkah Commerce Chamber, Makkah, SA on January 28, 2020. More than 30 consultants and rheumatology fellows with five Saudi experts in the field of rheumatology assembled to form 10 recommendations that tackle rheumatology training challenges in SA.
RESULTS
The meeting recommendations shed light on the clinical practice of rheumatology training in SA; challenges and opportunities in rheumatology fellowship programs; efforts of the Saudi Commission for Health Specialties (SCFHS) to design and implement a competent postgraduate rheumatology training; and challenges with trainers, trainee, and within training centres.
CONCLUSION
To address rheumatology challenges in SA, rheumatology consultants and fellows assembled to form 10 recommendations. The recommendations tackled the challenges of rheumatology fellowship programs and the efforts to implement a competent postgraduate rheumatology training. These recommendations are expected to lead us successfully to fulfil our ambition in the "Saudi Vision of 2030". | 10.2147/OARRR.S286285 |
pubmed_693_11289 | Compulsionary and ritual mechanisms show a variety of manifestations specifically in transcultural aspects. Strong feelings to suffer in compulsionary diseases and identical behavior patterns more or less within "normal" personality reactions can be observed. Limitations of free possibilities to behave can be described within creation and freedom of thought in man. Also this can be found in stereotyped patterns within sociodynamic ritus. Learning-psychological data are of great influence in human behavior as well as depth-psychological and sociodynamic features. Compulsionary and transcultural manifestations were to be discussed. | pubmed_693_11289 |
pubmed_121_27220 | The results of ab initio correlated molecular orbital theory electronic structure calculations for low-lying electronic states are presented for UH and UH- and compared to photoelectron spectroscopy measurements. The calculations were performed at the CCSD(T)/CBS and multireference CASPT2 including spin-orbit effects by the state interacting approach levels. The ground states of UH and UH- are predicted to be 4Ι9/2 and 5Λ6, respectively. The spectroscopic parameters Te, re, ωe, ωexe, and Be were obtained, and potential energy curves were calculated for the low energy Ω states of UH. The calculated adiabatic electron affinity is 0.468 eV in excellent agreement with an experimental value of 0.462 ± 0.013 eV. The lowest vertical detachment energy was predicted to be 0.506 eV for the ground state, and the adiabatic ionization energy (IE) is predicted to be 6.116 eV. The bond dissociation energy (BDE) and heat of formation values of UH were obtained using the IE calculated at the Feller-Peterson-Dixon level. For UH, UH-, and UH+, the BDEs were predicted to be 225.5, 197.9, and 235.5 kJ/mol, respectively. The BDE for UH is predicted to be ∼20% lower in energy than that for ThH. The analysis of the natural bond orbitals shows a significant U+H- ionic component in the bond of UH. | 10.1021/acs.jpca.2c03115 |
pubmed_800_16543 | Unstable heavy atomic nuclei not found in nature can be created by fusing two stable nuclei, in a process analogous to colliding charged droplets of liquid. Recently, the formation of a handful of super-heavy nuclei with atomic numbers 114 (ref. 1) and 116 (ref. 2) has been achieved by fusion of heavy nuclei. The electrostatic energy of such systems is very large (which is the reason super-heavy nuclei are unstable), so although the two nuclei may initially be captured by the nuclear potential, rather than fusing, they almost always separate after transfer of mass to the lighter nucleus. This process, called quasi-fission, can inhibit fusion by many orders of magnitude. Understanding this inhibition may hold the key to forming more super-heavy elements. Theoretically, inhibition is predicted (ref. 5 and references therein) when the product Z1Z2 of the charges of the projectile and target nuclei is larger than about 1,600. Here we report measurements of three fusion reactions with Z1Z2 around half this value, each forming 216 88Ra. We find convincing model-independent evidence both of inhibition of fusion, and of the presence of quasi-fission. These results defy interpretation within the standard picture of nuclear fusion and fission. | 10.1038/35093069 |
pubmed_891_14830 | Giardia lamblia is a single-celled eukaryotic parasite with a small genome and is considered an early divergent eukaryote. The pentose phosphate pathway (PPP) plays an essential role in the oxidative stress defense of the parasite and the production of ribose-5-phosphate. In this parasite, the glucose-6-phosphate dehydrogenase (G6PD) is fused with the 6-phosphogluconolactonase (6PGL) enzyme, generating the enzyme named G6PD::6PGL that catalyzes the first two steps of the PPP. Here, we report that the G6PD::6PGL is a bifunctional enzyme with two catalytically active sites. We performed the kinetic characterization of both domains in the fused G6PD::6PGL enzyme, as well as the individual cloned G6PD. The results suggest that the catalytic activity of G6PD and 6PGL domains in the G6PD::6PGL enzyme are more efficient than the individual proteins. Additionally, using enzymatic and mass spectrometry assays, we found that the final metabolites of the catalytic reaction of the G6PD::6PGL are 6-phosphoglucono-δ-lactone and 6-phosphogluconate. Finally, we propose the reaction mechanism in which the G6PD domain performs the catalysis, releasing 6-phosphoglucono-δ-lactone to the reaction medium. Then, this metabolite binds to the 6PGL domain catalyzing the hydrolysis reaction and generating 6-phosphogluconate. The structural difference between the G. lamblia fused enzyme G6PD::6PGL with the human G6PD indicate that the G6PD::6PGL is a potential drug target for the rational synthesis of novels anti-Giardia drugs. | 10.3390/microorganisms9081678 |
pubmed_800_966 | Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, we examined the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial [3H]tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of [3H]tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock. | 10.1016/0197-0186(88)90167-2 |
pubmed_705_1786 | OBJECTIVE
To provide information needed by patients with breast cancer (stages I and II) and their physicians when deciding whether axillary dissection should be carried out.
OPTIONS
No axillary surgery; removal of all axillary lymph nodes; removal of level 1 and 2 nodes; axillary "sampling."
OUTCOMES
Accurate determination of stage of cancer, resulting in better-informed therapeutic decisions; reduction of recurrence in axillary lymph nodes; improved survival.
EVIDENCE
A systematic review of English language literature based on MEDLINE and CANCERLIT databases to September 1996, with nonsystematic review continued to June 1997. The nature of the evidence or opinion is classified as shown on page S2.
BENEFITS
Optimal therapy, with maximal survival and minimal local recurrence.
HARMS
Increased postsurgical morbidity.
RECOMMENDATIONS
Removal and pathological examination of axillary lymph nodes should be standard procedure for patients with early, invasive breast cancer. For accurate staging and to reduce the risk of recurrence in the axilla, level 1 and level 2 nodes should be removed. Patients should be made fully aware of the frequency and severity of the potential complications of axillary dissection. Irradiation of the axilla should carried out with caution after axillary dissection. Omission of axillary dissection may be considered when the risk of axillary metastasis is very low or when knowledge of node status will have no influence on therapy. Patients should be offered the opportunity to participate in clinical trials whenever possible.
VALIDATION
Guidelines were reviewed and revised by the Writing Committee, expert primary reviewers, secondary reviewers selected from all regions of Canada and by the Steering Committee. The final document reflects a consensus of all these contributors. | pubmed_705_1786 |
pubmed_289_2891 | The purpose of this study was to evaluate a 3M Petrifilm-based on-farm culture system for the detection of intramammary infection (IMI) in low somatic cell count (SCC) cows (<200,000 cells/mL) at drying off. The main objectives were to determine the test characteristics and the predictive values of the Petrifilm on-farm culture system. The ability of dairy producers to correctly classify cows as infected or uninfected based on Petrifilm culture and a set colony count threshold was also assessed. A total of 360 cows originating from 16 low bulk tank SCC (<250,000 cells/mL) dairy herds were enrolled at drying off. Enrolled cows had an expected dry period of 30-90 days, a SCC<200,000 cells/mL on the last 3 tests prior to drying off, no clinical mastitis in the same time period, and no antibiotic treatment in the last 14 days. Quarter milk samples were collected on the day prior to drying off, and a composite milk sample was created by combining 5 mL of milk from each quarter sample. Composite milk samples were cultured on-farm using the Petrifilm culture system, which provided results within 24h. Quarter milk samples were cultured in a reference laboratory, and the results were aggregated to the cow level. On the day of drying off, the Petrifilm was read by the producer and cows were classified as positive if ≥5 colonies (equivalent to 50 colony forming units/mL) were present. When read by the producer, 47.8% of the cows cultured negative on Petrifilm and were infused with only an internal teat sealant at drying off. The test characteristics of the Petrifilm on-farm culture system were calculated by comparing the producer-derived Petrifilm results to those obtained by standard laboratory culture. The sensitivity and specificity of the Petrifilm on-farm culture system were 85.2% (78.5-90.5) and 73.2% (66.4-79.3), respectively. The negative predictive value of the Petrifilm test system was high (86.6%) when estimated using the prevalence of IMI in this data set, and the positive predictive value was moderate (70.9%). An automated 3M Petrifilm reader was used to obtain accurate colony counts. The agreement between Petrifilm results obtained by the producer and those obtained by the automated Petrifilm reader was high, with a kappa value of 0.82 (0.75-0.89). | pubmed_289_2891 |
pubmed_528_861 | BACKGROUND
Selegiline orally disintegrating tablet (ODT; Zelapar) is a selective monoamine oxidase B inhibitor developed as an adjunct to levodopa (LD) for Parkinson disease. Most patients on long-term LD therapy eventually experience deterioration at the end of the LD dosing interval, with predictable "wearing off" and "on-off" fluctuations.
METHODS
We conducted a 12-week, double-blind, placebo-controlled, parallel-design trial of selegiline ODT. The primary efficacy point was reduction in the percentage of average daily "off" time. Secondary measures included reductions in daily off hours and total daily off time, Clinical Global Impressions-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I). Patients on LD received selegiline ODT (1.25 mg/d for 6 weeks, then 2.5 mg/d for 6 weeks) or placebo. Safety and tolerability were measured.
RESULTS
The intent-to-treat population included 98 patients receiving selegiline ODT and 50 patients receiving placebo. Combined efficacy results for weeks 10 and 12 revealed an 11.6% reduction in percentage of daily off time for selegiline ODT versus a 9.8% reduction for placebo (NS). PGI-I detected a statistically significant difference between treatment groups in favor of selegiline ODT (P = 0.02), whereas CGI-I detected a strong trend toward improvement (P = 0.06). Selegiline ODT was safe and well tolerated.
CONCLUSIONS
This study showed no significant difference in improvement in percentage of off time with selegiline ODT versus placebo. Some clinical impressions (e.g., PGI-I, CGI-I) improved. This result contrasts with an identically designed study that showed a significant improvement in off time with selegiline ODT. A combined analysis of both studies suggested overall efficacy. | 10.1097/WNF.0b013e3180616570 |
pubmed_937_12716 | A study of the actinosporean fauna of oligochaetes from a freshwater salmon farm in Northern Scotland was carried out from October 1996 to August 1998. Following the examination of 28,387 oligochaete worms belonging to the families Tubificidae, Lumbriculidae, Naididae and Enchytraeidae, five types of echinactinomyxon (four previously described), six types of raabeia (five previously described), three types of synactinomyxon (all previously described), four types of aurantiactinomyxon (three previously undescribed), one type of triactinomyxon (previously described), one type of neoactinomyxum (previously undescribed) and one type of siedleckiella (previously undescribed) were identified. The triactinomyxon type was released from unidentified immature oligochaetes. Of the twenty-one types of actinosporeans found, thirteen types were released from Tubifex tubifex (Müller), three types were released from Lumbriculus variegatus (Müller), three types from both L variegatus and T. tubifex and two types from immature oligochaetes. | 10.14411/fp.2002.036 |
pubmed_332_6568 | OBJECTIVE
The study objective was to establish The American Association for Thoracic Surgery (AATS) lung cancer screening guidelines for clinical practice.
METHODS
The AATS established the Lung Cancer Screening and Surveillance Task Force with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 4 medical oncologists, 1 pulmonologist, 1 pathologist, and 1 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with, and at risk for, lung cancer. The task force reviewed the literature, including screening trials in the United States and Europe, and discussed local best clinical practices in the United States and Canada on 4 conference calls. A reference library supported the discussions and increased individual study across disciplines. The task force met to review the literature, state of clinical practice, and recommend consensus-based guidelines.
RESULTS
Nine of 14 task force members were present at the meeting, and 3 participated by telephone. Two absent task force members were polled afterward. Six unanimous recommendations and supporting work-up algorithms were presented to the Council of the AATS at the 2012 annual meeting in San Francisco, California.
CONCLUSIONS
Annual lung cancer screening and surveillance with low-dose computed tomography is recommended for smokers and former smokers with a 30 pack-year history of smoking and long-term lung cancer survivors aged 55 to 79 years. Screening may begin at age 50 years with a 20 pack-year history of smoking and additional comorbidity that produces a cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Screening should be undertaken with a subspecialty qualified interdisciplinary team. Patient risk calculator application and intersociety engagement will provide data needed to refine future lung cancer screening guidelines. | 10.1016/j.jtcvs.2012.05.059 |
pubmed_289_5831 | In recent years, an aqueous extract of the fungus Trametes robiniophila Murriell 1907 (Huaier) has been commonly used in China for complementary cancer therapy. However, the mechanisms of its anticancer effects are largely unknown. In the present study, we aimed to investigate the effects of Huaier extract on the inhibition of proliferation and promotion of apoptosis in a melanoma cell line, A875, and to explore the possible mechanisms of its anticancer effects. Cell proliferation was measured using a Cell Counting Kit-8 (CCK8) and PCNA-Western blot. The cell cycle distribution, and apoptosis levels were analyzed by flow cytometry, and Western blot was used to test the apoptotic pathways. We found that Huaier extract strongly inhibited cell proliferation of the A875 melanoma cells and induced G2/M arrest and apoptosis in a time- and dose-dependent manner. P53 expression was increased and cell apoptosis executed by caspase-3. Down-regulation of Bcl-2 and up-regulation of Bcl2-associated X protein (BAX) indicated that Huaier extract induced apoptosis through the mitochondrial pathway. As expected, the inhibitor Huaier decreased melanoma cell line A875 proliferation, and induced apoptosis in a time- and dose-dependent manner. Our findings indicate that Huaier extract is an effective complementary agent for cancer treatment of melanoma. | pubmed_289_5831 |
pubmed_1103_21941 | Radial neuropathy is frequently associated with fracture of the middle third of the humerus owing to the course of the nerve adjacent to the humeral shaft. The prevalence varies from 2 to 18% of humeral fractures. The therapeutic management is still controversial. Some authors recommend initial surgical exploration, whereas others prefer observation and intervention only if the injured nerve failed to recover after a period of more than 4 months. According to the literature, verification of an entrapped radial nerve in a fracture gap requires surgical exploration, but diagnostic tools to verify the existence of a pathologic condition are limited. We describe the sonographic findings of an entrapped radial nerve and review the literature regarding diagnosis and treatment of entrapped radial nerve in cases of humeral fracture. | 10.7863/jum.1999.18.10.703 |
pubmed_118_6533 | The present study is related to Dipylidium caninum infection in dogs. Three dogs about 1 year of age with the history of scooting behaviour and passing diarrhoeic stool containing white specks were presented before the clinicians. Physical examination of dogs revealed flea infestation and faecal examination revealed the presence of gravid segments, which were confirmed microscopically to be of cestode, D. caninum. Dogs were treated with Praziquantel@5 mg/kg body wt. orally. Dogs showed marked recovery post treatment. On re-examination after a week, faeces were found negative for any parasitic eggs/gravid segments. | 10.1007/s12639-015-0706-9 |
pubmed_935_14223 | The effects of new non-tricyclic antidepressants, FS32 and its desmethylated compound (FS97), on the uptake of (3H)-dopamine (DA) by rat purified whole brain synaptosomes and the striatal synaptosomes were studied. The uptake into synaptosomes was time- and temperature-dependent and was saturable with a Km value of 9.1 X 10(-8) M. The inhibiting activities of both compounds were comparable to those of amitriptyline, nortriptyline and iprindole, and were nearly twice the activity of imipramine and desipramine. The kinetic constants indicated that both FS32 and FS97 were competitive inhibitors of (3H)-DA uptake. Neither drug caused a significant release of (3H)-DA from the synaptosomes. | 10.1016/0014-2999(80)90271-x |
pubmed_201_7945 | The organization of the human insular cortex has traditionally been considered as an anterior-posterior dichotomy, where anterior and posterior subdivisions have unique structural and functional connections. However, recent functional neuroimaging research proposes a tripartite organization where insular subdivisions have both unique and overlapping functional profiles. Studies examining unique profiles show that the dorsal anterior insula (dAI) has connections with frontal areas supporting higher-level cognitive processes, the ventral anterior insula (vAI) has connections with limbic areas supporting affective processes, and the posterior insula (PI) has connections with sensorimotor areas supporting interoceptive processes. Studies examining overlapping profiles demonstrate that all 3 subdivisions can also have similar functional profiles. The structural organization supporting a functional tripartite insula organization presenting with overlapping and unique connections is currently unknown. We used a large HARDI diffusion magnetic resonance imaging (MRI) dataset (n = 199) to demonstrate novel visualizations of insula white matter tracts supporting a tripartite structure-function insula organization. Overlapping connections of all 3 insula subdivisions consisted of association pathways (inferior fronto-occipital fasciculus, uncinate fasciculus, arcuate fasciculus) while unique connections included the corona radiata, subcortical-cortical tracts, and horizontal and u-shaped tracts. These results generally support a tripartite structure-function organization of the insular cortex, with subdivisions that exhibit both overlapping and unique connectivity profiles. | 10.1093/cercor/bhx211 |
pubmed_701_11308 | Ultraviolet (UV)-induced repair and mutational spectra were analyzed in an inducible marker gene, the metallothionein-l/guamine-xanthine phosphoribosyl transferase (gpt) fusion gene, carried by an Epstein-Barr virus-derived shuttle vector episomically maintained in human cells. The repair rate of UV photodimers from the shuttle-vector molecules was typical of transcriptionally active sequences, 70% of the dimers being removed within 8 h after irradiation. The spectrum obtained under basal gene transcription was compared with that obtained under induced transcription. In both cases, base substitutions at dipyrimidine sequences predominated. Multiple mutations and deletions probably due to recombinational events induced by UV damage were also observed. Most of the UV-mutated dipyrimidine sites were located in the transcribed strand and were independent of the transcriptional activity of the target gene. In contrast, the distribution of mutations throughout the coding region of the gpt gene was affected by transcription, with a preferential clustering of mutations occurring in the 3' half of the gene after transcription induction. The strand bias observed in the UV spectra most likely reflects selection for nonfunctional gpt protein. | 10.1002/mc.2940140311 |
pubmed_1113_13259 | The extracellular accumulation of glutamate and the excessive activation of glutamate receptors, in particular N-methyl-D-aspartate (NMDA) receptors, have been postulated to contribute to the neuronal cell death associated with chronic neurodegenerative disorders such as Parkinson's disease. Findings are reviewed indicating that the tridecaptide neurotensin (NT) via activation of NT receptor subtype 1 (NTS1) promotes and reinforces endogenous glutamate signalling in discrete brain regions. The increase of striatal, nigral and cortical glutamate outflow by NT and the enhancement of NMDA receptor function by a NTS1/NMDA interaction that involves the activation of protein kinase C may favour the depolarization of NTS1 containing neurons and the entry of calcium. These results strengthen the hypothesis that NT may be involved in the amplification of glutamate-induced neurotoxicity in mesencephalic dopamine and cortical neurons. The mechanisms involved may include also antagonistic NTS1/D2 interactions in the cortico-striatal glutamate terminals and in the nigral DA cell bodies and dendrites as well as in the nigro-striatal DA terminals. The possible increase in NT levels in the basal ganglia under pathological conditions leading to the NTS1 enhancement of glutamate signalling may contribute to the neurodegeneration of the nigro-striatal dopaminergic neurons found in Parkinson's disease, especially in view of the high density of NTS1 receptors in these neurons. The use of selective NTS1 antagonists together with conventional drug treatments could provide a novel therapeutic approach for treatment of Parkinson's disease. | 10.1016/j.pneurobio.2007.06.006 |
pubmed_692_23605 | BACKGROUND
Health Related Quality of Life (HRQoL) is an important outcome measure in health economic evaluation that guides health resource allocations. Population norms for HRQoL are an essential ingredient in health economics and in the evaluation of population health. The aim of this study was to produce EQ-5D-3L-derived population norms for Sri Lanka.
METHOD
A population sample (n = 780) was selected from four districts of Sri Lanka. A stratified cluster sampling approach with probability proportionate to size was employed. Twenty six clusters of 30 participants each were selected; each participant completed the EQ-5D-3L in a face-to-face interview. Utility weights for their EQ-5D-3L health states were assigned using the Sri Lankan EQ-5D-3L algorithm. The population norms are reported by age and socio-economic variables.
RESULTS
The EQ-5D-3L was completed by 736 people, representing a 94% response rate. Sixty per cent of the sample reported being in full health. The percentage of people responding to any problems in the five EQ-5D-3L dimensions increased with age. The mean EQ-5D-3L weight was 0.85 (SD 0.008; 95%CI 0.84-0.87). The mean EQ-5D-3L weight was significantly associated with age, housing type, disease experience and religiosity. People above 70 years of age were 7.5 times more likely to report mobility problems and 3.7 times more likely to report pain/discomfort than those aged 18-29 years. Those with a tertiary education were five times less likely to report any HRQoL problems than those without a tertiary education. A person living in a shanty was 4.3 more likely to have problems in usual activities than a person living in a single house.
CONCLUSION
The population norms in Sri Lanka vary with socio-demographic characteristics. The socioeconomically disadvantaged have a lower HRQoL. The trends of population norms observed in this lower middle income country were generally similar to those previously reported in high income countries. | 10.1371/journal.pone.0108434 |
pubmed_90_4665 | Authors report six cases of boutonneuse Mediterranean fever seen in the last two years. All of them presented fever, malaise, generalised maculopapulous rash and a typical black spot or inoculation canker. Diagnosis was done by a positive Weil-Félix test. The treatment used was tetracycline with good results. Incidence of this disease is increasing in our country. | pubmed_90_4665 |
pubmed_597_24453 | Successful realization of planned actions requires the brain to encode intentions over delays. Previous research has indicated that several regions in the rostral or anterior prefrontal cortex (PFC) encode delayed intentions. However, different processes may encode the same future task depending on task load during the delay. This difference may depend on the computational resources available when the delay is occupied with an ongoing task and when it is task-free. Here we directly investigated and compared the representation of delayed intentions in the human brain in the presence and absence of ongoing task load during the delay. We acquired fMRI data in combination with an event-based prospective memory design where human subjects remembered to perform the same future tasks over occupied and task-free delays. We used time-resolved multivoxel pattern classification and found that: (1) rostrolateral PFC (BA 46) encoded the delayed intention during both delay types; (2) rostromedial PFC (BA 10) encoded the intentions during occupied delays; whereas (3) a variety of more posterior regions, including the anterior cingulate cortex (BA 24), the supplementary motor area (BA 6), and the precuneus, encoded intentions during task-free delays. Overall, the medial PFC encoded delayed intentions more rostrally in the presence of an ongoing delay task and more caudally in its absence. Thus, rostromedial PFC may play a specialized role in the encoding of prospective memory that depends on higher computational demands (e.g., given higher task load during the delay). In contrast, the rostrolateral PFC is a more general area that encodes future intentions regardless of task load. | 10.1523/JNEUROSCI.0492-13.2013 |
pubmed_160_24361 | Infrared multiphoton dissociation spectra of protonated p-aminobenzoic acid generated by electrospray ionization (ESI) from aqueous methanol and acetonitrile solutions were recorded in the gas phase from 2800-4000 cm(-1). The O-protonated ion is more stable than the N-protonated structure in the gas phase, whereas the opposite is true in both solutions. When CH(3)OH/H(2)O was used as the ESI solvent, only the O-protonated ion was observed. In contrast, a 70:30 mixture of the O- and N-protonated species were produced from CH(3)CN/H(2)O. These structural assignments are based on an assortment of experimental data (action spectra, photofragments, photofragmentation kinetics, and H/D exchange) and are fully supported by extensive computations. This work shows that ESI can lead to isomerization and that the ionization site may be varied by changing the solvent from which the substrate is analyzed. | 10.1021/jp203829z |
pubmed_687_2475 | The in situ on-surface conversion process from boroxine-linked covalent organic frameworks (COFs) to boronate ester-linked COFs is triggered and catalyzed at room temperature by an electric field and monitored with scanning tunneling microscopy (STM). The adaptive behavior within the generated dynamic covalent libraries (DCLs) was revealed, providing in-depth understanding of the dynamic network switching process. | 10.1021/jacs.0c01270 |
pubmed_1065_356 | OBJECTIVE
To determine the effects of inflammatory mediators on the production of activin A, inhibin A, and the binding protein follistatin in term amnion and choriodecidual tissues.
METHODS
The effects of interleukin-1 beta (IL-1 beta; 1 ng/mL), tumor necrosis factor-alpha (TNF-alpha; 10 ng/mL), and bacterial lipopolysaccharide (LPS; 5 microg/mL) on production rates of activin A, inhibin A, and follistatin by term choriodecidual and amnion membranes in explant culture were determined using specific enzyme-linked immunoabsorbent assays.
RESULTS
All explants (n = 6 placentas) produced detectable amounts of activin A, inhibin A, and follistatin under basal conditions; choriodecidual production rates were more than tenfold higher than amnion rates. In amnion explants, activin A production was stimulated by IL-1 beta and TNF-alpha to 450 +/- 155.4% and 531 +/- 170.8% of control, respectively (mean +/- standard error of the mean; P <.05 by analysis of variance), whereas production of inhibin and follistatin was stimulated to a much more modest extent. Similar responses were observed in the choriodecidual explants. Lipopolysaccharide had no significant effect on amnion activin A production, but stimulated choriodecidual production to 290 +/- 34% of control. Lipopolysaccharide exerted only limited effects on inhibin A and follistatin production.
CONCLUSIONS
Treatment with proinflammatory mediators resulted in a preferential increase in activin A production compared with that of inhibin A or follistatin. These findings suggest that inflammation of the gestational membranes could result in increased local activin A production and bioactivity. | pubmed_1065_356 |
pubmed_864_21904 | UNLABELLED
Neuroblastoma is the most common solid extracranial tumor of childhood. Even though >25% of presentations are orthopaedic in nature, ranging from a limp to lower limb paralysis, neuroblastoma is a rare cause of limping in childhood and can therefore be easily missed by the admitting orthopaedic surgeon. Four cases of metastatic neuroblastoma are reported who all presented with hip pain within the last 3 years at Royal Manchester Children's Hospital. They all posed a diagnostic dilemma and an alternative diagnosis was initially made. A simple screening examination of the abdomen after ultrasonographic hip examination for sepsis would have led to an earlier diagnosis in all 4 cases. We suggest that including the abdomen in children undergoing a hip sonographic examination in those who are slightly atypical in nature or have indications of malignancy may lead to an early diagnosis of this rare cause of hip pain.
LEVEL OF EVIDENCE
IV. | 10.1097/BPO.0b013e318279c636 |
pubmed_739_9409 | Telomeres in somatic cells are progressively shortened with aging. We investigated the relationship between the telomere length and other factors which may affect the frequency of cell divisions, in peripheral blood cells. Shortening of telomeric repeats was correlated with aging (p < 0.0001), but not with white blood cell count, neutrophil count, and smoking habit. Not only the number of cell divisions, but also some other factors, such as upregulation level of telomerase activity concomitant with the cell division in hematopoietic progenitor cells, might affect the length of telomeric repeats in blood cells. | 10.1007/BF01876332 |
pubmed_71_6564 | The present study investigated the correlation between four serum biomarkers of liver fibrosis, liver function and pathological hepatic fibrosis grade in neonatal cholestatic rats. A total of 38 Sprague‑Dawley rats, aged 3 weeks, were randomly assigned to the experimental group (EG), control group (CG) and the blank control group (BCG). EG received intragastric administration of 1% α‑naphthylisothiocyanate, 75 mg/kg, to induce acute cholestasis liver injury, CG and BCG were set as control groups. Blood samples from all groups were collected 48 h following the procedure. The levels of liver function markers, and four biomarkers of liver fibrosis in serum, were measured and sections of liver tissue were stained for pathological analysis. The results of the present study demonstrated that the degree of hepatic fibrosis in EG, in the serum levels or by pathological analysis, was markedly more evident compared with the CG. Several indices of four biomarkers for liver fibrosis in serum were identified and correlated with the levels of liver function markers. The pathological hepatic fibrosis grade was correlated with γ‑glutamyl transferase (γ‑GT) and Hyaluronic acid (HA). Therefore, HA and γ‑GT were positively correlated with the grade of hepatic fibrosis, indicating their efficacy as biomarkers of infantile cholestatic hepatic fibrosis. | 10.3892/mmr.2017.6588 |
pubmed_950_5240 | Multiple myeloma (MM) is an incurable disease with relatively high morbidity and mortality rates. Great efforts were made to develop nuclear factor-kappa B (NF-κB)-targeted therapies against MM disease. However, these treatments influence MM cells as well as normal cells, inevitably causing serious side effects. Further research showed that NF-κB signalling promotes the survival of MM cells by interacting with JNK signalling through growth arrest and DNA damage-inducible beta (GADD45β), the downstream module of NF-κB signalling. The GADD45β-targeted intervention was suggested to be an effective and MM cell-specific treatment. However, the underlying mechanism through which GADD45β promotes the survival of MM cells is usually ignored in the previous models. A mathematical model of MM is built in this paper to investigate how NF-κB signalling acts along with JNK signalling through GADD45β and MKK7 to promote the survival of MM cells. The model cannot only mimic the variations in bone cells, the bone volume and MM cells with time, but it can also examine how the NF-κB pathway acts with the JNK pathway to promote the development of MM cells. In addition, the model also investigates the efficacies of GADD45β- and NF-κB-targeted treatments, suggesting that GADD45β-targeted therapy is more effective but has no apparent side effects. The simulation results match the experimental observations. It is anticipated that this model could be employed as a useful tool to initially investigate and even explore potential therapies involving the NF-κB and JNK pathways in the future. | 10.1098/rsos.192152 |
pubmed_761_15341 | Due to their distinctive physicochemical properties, platinum nanoparticles (PtNPs) have emerged as a material of interest for a number of biomedical therapeutics. However, in some instances NP exposure has been correlated to health and safety concerns, including cytotoxicity, activation of cellular stress, and modification to normal cell functionality. As PtNPs have induced differential cellular responses in vitro, the goal of this study was to further characterize the behavior and toxicological potential of PtNPs within a HepG2 liver model. This study identified that a high PtNP dosage induced HepG2 cytotoxicity. However, lower, subtoxic PtNP concentrations were able to elicit multiple stress responses, secretion of proinflammatory cytokines, and modulation of insulin-like growth factor-1 dependent signal transduction. Taken together, this work suggests that PtNPs would not be overtly toxic for acute exposures, but sustained cellular interactions might produce long term health consequences. | 10.1155/2018/1367801 |
pubmed_507_1401 | The transforming growth factor beta (TGF-beta) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-beta signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case-control study conducted in Poland from 2000 to 2003. TGF-beta signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-beta1 (78%), TGF-beta2 (91%), TGF-beta3 (93%), TGF-betaR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-beta1 was expressed in 32% of tumors. Expression of TGF-beta ligands (beta1, beta2, and beta3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-betaR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-beta. In addition, expression of extracellular-TGF-beta1 (P = 0.005), TGF-betaR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment. | 10.1007/s10549-009-0590-z |
pubmed_18_4158 | Priming research has shown that repeated exposures to first-person singular pronouns (I, my, me, mine) activate an individualistic orientation, whereas first-person plural pronouns (we, our, us, ours) activate a collectivistic orientation. However, little research has been done to explore the opposite direction of influence such that one's cultural orientation determines one's choice between first-person singular versus plural pronouns. The authors conducted three studies to examine the effects of one's cultural orientation on one's use of first-person possessive pronouns. Results show that, compared to their individualistic counterparts, participants who have a collectivistic orientation, chronically or temporarily by priming, preferred to use first-person plural possessive pronouns. | 10.1177/0146167209343810 |
pubmed_92_2611 | It is desired that the same imaging functional modules such as beamformation, envelope detection, and digital scan conversion (DSC) are employed for the efficient development of a cross-sectional photoacoustic (PA) and ultrasound (US) dual-modality imaging system. The beamformation can be implemented using either delay-and-sum beamforming (DAS-BF) or adaptive beamforming methods, each with their own advantages and disadvantages for the dual-modality imaging. However, the DSC is always problematic because it causes blurring the fine details of an image, e.g., edges. This paper demonstrates that the pixel based focusing method is suitable for the dual-modality imaging; beamformation is directly conducted on each display pixel and thus DSC is not necessary. As a result, the artifacts by DSC are no longer a problem, so that the proposed method is capable of providing the maximum spatial resolution achievable by DAS-BF. The performance of the proposed method was evaluated through simulation and ex vivo experiments with a microcalcification-contained breast specimen, and the results were compared with those from DAS-BF and adaptive beamforming methods with DSC. The comparison demonstrated that the proposed method effectively overcomes the disadvantages of each beamforming method. | pubmed_92_2611 |
pubmed_310_5816 | The experiment that was carried out consisted of subjects pushing an external object (a heavy pendulum) using stable and unstable handles of increasing mobility. Using this protocol it was possible to distinguish between the motor and stabilising functions of the muscles of the upper extremity. The motor functions were realised by the extensors of the upper extremity, whereas stabilising functions were effected by the muscles spanning the wrist joint. The experiment involved synchronised measurements of the electromyographic (EMG) activity of the muscles in question together with several mechanical quantities revealed against the external object: force, velocity and power. As a result, the instantaneous and global EMG contributions of the extensor and stabilising muscles were determined. It was found that it is the equilibrium state of the object being set in motion and not its mobility (expressed in terms of the number of degrees of freedom) that influences the forces produced by individual muscles. We also suggest that the realisation of stabilising functions by skeletal muscles is a necessary condition of performing any voluntary and co-ordinated movement. | 10.1007/s004210100401 |
pubmed_988_7656 | As part of a prospective program to use risk-adjusted outcome (operative mortality and morbidity) as a measure of quality of care, we have analyzed perioperative complication data in 10,634 patients representing 73% of all patients undergoing cardiac surgery requiring cardiopulmonary bypass at Veterans Administration medical centers between April 1, 1987, and March 31, 1989. One or more complications occurred in 15% of patients undergoing coronary artery bypass grafting, and in 24% of patients undergoing valve and other cardiac surgery. Patients experiencing one or more complications had an eightfold to 10-fold increase in operative mortality compared with patients with no perioperative complications. The most frequent complication was requirement for mechanical ventilation for at least 48 hours occurring in 8% of patients undergoing coronary artery bypass and in 15% of patients undergoing valve and other cardiac surgery; 24-25% of these patients died within 30 days of surgery or as a direct result of a surgical complication. Previous heart surgery was a strong predictor of development of one or more complications in both groups of patients, being associated with an adjusted relative risk of 1.6-2.0. Other important predictors in both surgical groups were surgical priority, older age, peripheral vascular disease, and higher serum creatinine. Although a number of preoperative risk factors could be identified for the development of renal failure, low cardiac output, and requirement for prolonged mechanical support, few risk factors could be identified for the development of mediastinitis and reoperation for bleeding. This observation suggests that mediastinitis and reoperation for bleeding are more likely the result of technical factors rather than patient-related risk factors. | pubmed_988_7656 |
pubmed_151_25842 | Dystrophin is an important protein within the central nervous system. The absence of dystrophin, characterizing Duchenne muscular dystrophy (DMD), is associated with brain related comorbidities such as neurodevelopmental (e.g., cognitive and behavioural) deficits and epilepsy. Especially mutations in the downstream part of the DMD gene affecting the dystrophin isoforms Dp140 and Dp71 are found to be associated with cognitive deficits. However, the function of Dp140 is currently not well understood and its expression pattern has previously been implicated to be developmentally regulated. Therefore, we evaluated Dp140 and Dp71 expression in human hippocampi in relation to cognitive functioning in patients with drug-resistant temporal lobe epilepsy (TLE) and post-mortem controls. Hippocampal samples obtained as part of epilepsy surgery were quantitatively analyzed by Western blot and correlations with neuropsychological test results (i.e., memory and intelligence) were examined. First, we demonstrated that the expression of Dp140 does not appear to differ across different ages throughout adulthood. Second, we identified an inverse correlation between memory loss (i.e., verbal and visual memory), but not intelligence (i.e., neither verbal nor performance), and hippocampal Dp140 expression. Finally, patients with TLE appeared to have similar Dp140 expression levels compared to post-mortem controls without neurological disease. Dp140 may thus have a function in normal cognitive (i.e., episodic memory) processes. | 10.1002/hipo.23015 |
pubmed_496_622 | Mannose-binding lectin (MBL) insufficiency due to polymorphisms in the MBL2 gene causes an opsonization defect, which has been connected to infections and atopy. We investigated the significance of MBL2 genotypes with regard to persistent asthma and atopy among adults. The genotypes were determined in 243 adults with persistent asthma and 400 controls. Atopy was determined by skin-prick test. As a result, the carriage of -221 base pairs (bp) promoter region variant allele X (nucleotide change G-->C; alleles Y-->X, respectively) causing low MBL expression proved to be a significant risk factor for asthma in non-atopic males [odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23-5.15; P = 0.01]. Furthermore, the X-allele carriage was associated with the decrease in lung function (forced expiratory volume at 1 s, FEV(1)) during follow-up in the patients with asthma (P = 0.033), the effect being strongest for non-atopic asthmatics (P = 0.042). The MBL2 genotype had no clear effect on the occurrence of atopy in adults. In conclusion, our results abrogate the previously suggested predisposing effect of MBL insufficiency on atopy at least in adults. However, as MBL is a complement component participating in immune defence against microbes, and as in the pathogenesis of non-atopic asthma infectious agents are probably involved, the gene-environment interactions between MBL and infections should be assessed further with regard to asthma. | 10.1111/j.1365-2249.2005.02881.x |
pubmed_852_14171 | Aldehyde dehydrogenase 3A1 (ALDH3A1) is a recently characterized corneal crystallin with its exact functions still being unclear. Expressing recombinant human ALDH3A1 has been difficult in Escherichia coli (E. coli) because of low solubility, yield and insufficient purity issues. In this report, we compared different E. coli expression strategies (namely the maltose binding protein; MBP- and the 6-his-tagged expression systems) under conditions of auto-induction and co-expression with E. coli's molecular chaperones where appropriate. Thus, we aimed to screen the efficiency of these expression strategies in order to improve solubility of recombinant ALDH3A1 when expressed in E. coli. We showed that the MBP- tagged expression in combination with lower-temperature culture conditions resulted in active soluble recombinant ALDH3A1. Expression of the fused 6-his tagged-ALDH3A1 protein resulted in poor solubility and neither lowering temperature culture conditions nor the auto-induction strategy improved its solubility. Furthermore, higher yield of soluble, active native form of 6-his tagged-ALDH3A1 was facilitated through co-expression of the two groups of E. coli's molecular chaperones, GroES/GroEL and DnaK/DnaJ/GrpE. Convenient one step immobilized affinity chromatography methods were utilized to purify the fused ALDH3A1 hybrids. Both fusion proteins retained their biological activity and could be used directly without removing the fusion tags. Taken together, our results provide a rational option for producing sufficient amounts of soluble and active recombinant ALDH3A1 using the E. coli expression system for conducting functional studies towards elucidating the biological role(s) of this interesting corneal crystallin. | 10.1371/journal.pone.0056582 |
pubmed_332_688 | Introduction. Despite initial enthusiasm, the use of transanal endoscopic microsurgery (TEM) is still quite limited at present because of the expense of highly specialized equipment and the complexity of the learning curve. Furthermore, some authors report a relevant, although temporary, effect on anorectal function because of the considerable anal dilatation which can even produce a rupture of the internal anal sphincter. The "glove TEM" proposes itself as an alternative to traditional TEM that could settle these problems. Materials and Methods. The technique is accurately described together with the necessary equipment to perform it. Between 2011 and 2012, we operated eight patients with this technique for rectal adenomas or early carcinomas achieving R0 resection in all cases and reporting no early or late complications during the first five months of followup. Discussion. This technique offers multiple advantages compared to the original TEM. (i) It allows the use of all available laparoscopic instruments. (ii) It gives a great manoeuvrability of the instruments in contrast to rigid rectoscope systems. (iii) Given the limited length of the device, it permits to operate on tumors closer to the dentate line. (iv) It is less traumatic to the anal sphincter. It is definitively much cheaper. Conclusions. We believe that this new technique is easy to perform, cost-effective, and less traumatic to the anal sphincter compared to traditional TEM. | 10.1155/2012/383025 |
pubmed_795_21527 | Neoplastic seeding of the leptomeninges often signifies limited life expectancy. Still, patients are frequently offered aggressive multimodality therapies to palliate symptoms, and, one hopes, to prolong survival. Treatment modalities directed at the central nervous system (CNS) include radiotherapy, intra-cerebrospinal fluid (CSF) chemotherapy, standard systemic chemotherapy, and systemic high-dose chemotherapy. Because many of these modalities are used in combination, it is often difficult to discern which mode is the predominant cause of either acute or delayed complications. This review summarizes the incidence, clinical manifestations, laboratory findings, and pathology related to acute and delayed toxicity of treatment. It describes complications associated with radiotherapy, the use of an intraventricular implanted device (ie, Ommaya device), adverse effects of intra-CSF chemotherapy, and neurotoxicity, either associated with high-dose chemotherapy or manifested as delayed and chronic complications of combined therapies. All CNS-directed therapies are associated with a high rate of complications. The adverse effects of therapy profoundly affect the patient's quality of life, both at the acute phase of treatment and in late and chronic complications after therapy is completed. Intra-CSF chemotherapy is associated with a high rate of acute, reversible adverse effects that sometimes evolve into life-threatening medical conditions. Devastating delayed complications, mainly described as leukoencephalopathy, develop in more than 50% of patients who survive for extended periods and often lead to progressive loss of cognitive capacities. Careful assessment of the benefits and potential adverse reactions to a particular therapy regimen is mandated. | 10.1007/s11912-003-0085-8 |
pubmed_362_19481 | Metal-organic framework (MOF)-based derivatives with uniform micro/mesoporous structures have attracted a great deal of interest in various research fields. Herein, we report a simple strategy to design functional mesoporous ternary metal oxides with controlled composition through direct pyrolysis of Co/Cu bimetal-formate frameworks (Co/Cu-MFFs), which were prepared by a facile one-step liquid-phase precipitation method, exhibiting uniform distribution of two different metal species and good structural integrity. The obtained mesoporous ternary metal oxide Cu Co3- O4 (x = 0.5, 1) microcubes exhibit much better performance for CO oxidation than pure Co3O4, which can be mainly attributed to their larger specific surface areas, stronger reducibility, and the synergistic effect of two active metal oxide components. | 10.1039/c8ra04081h |
pubmed_992_16479 | Clarifying the healthcare innovation agenda is critical in order to advance the impact of system innovations. As part of this agenda-setting it is important to address the four conditions within which innovations can enhance system sustainability: 1) the innovation agenda reflects and is aligned with healthcare objectives and policy; 2) planning methodologies for services, workforce and funding are aligned with healthcare objectives and policy; 3) innovations in services are accommodated in systems through innovations in policy, planning and funding; and 4) innovations are systematically monitored and evaluated. In order to illustrate these conditions, the authors present a case study of an evaluation of one Canadian Health Authority's efforts to transform healthcare delivery. This case study reveals that aligning innovations in policy, planning, funding and health services is critical to transforming health systems and that, in the absence of such alignment, sustainable health systems are difficult to achieve. | pubmed_992_16479 |
pubmed_149_24152 | Post-curing is essential to improve the mechanical properties of 3D printed parts fabricated by stereolithography (SLA), since right after 3D printing they remain in a "green state". It means that the 3D printed parts have reached their final shape, but the polymerization reaction has not been yet completed. Herein, we take advantage of the tacky partially polymerized surface of "green state" SLA 3D printed parts to immobilize extraction disks and miniature magnets, which after UV post-curing, become permanently attached to the 3D printed part resulting in a rotating-disk sorptive extraction device (RDSE). The developed "stick & cure" procedure is reagent-free and does not require any additional preparation time, specialized skills, or instrumentation. As proof of concept, 3D printed RDSE devices with immobilized chelating disks have been applied to the simultaneous extraction of 14 trace metals prior to ICP-OES determination, featuring LODs between 0.03 and 1.27 μg L-1, and an excellent device-to-device reproducibility (n = 5, RSD = 2.7-8.3%). The developed method was validated using certified wastewater and soil reference samples, and satisfactory spiking recoveries were obtained in the analysis of highly polluted solid waste treatment plant leachates (89-110%). In addition, exploiting the versatility of 3D printing, nine RDSE devices with different shapes were fabricated. Their performance was evaluated and compared for the fast extraction of the highly toxic Cr (VI) as its 1,5-diphenylcarbazide complex in reversed-phase mode, showing different extraction performance on depending on the shape of the 3D printed RDSE device. | 10.1016/j.talanta.2019.04.026 |
pubmed_368_6464 | The androgen receptor (AR) is a transcription factor that has a pivotal role in the occurrence and progression of prostate cancer. The AR is activated by androgens that bind to its ligand-binding domain (LBD), causing the transcription factor to enter the nucleus and interact with genes via its conserved DNA-binding domain (DBD). Treatment for prostate cancer involves reducing androgen production or using anti-androgen drugs to block the interaction of hormones with the AR-LBD. Eventually the disease changes into a castration-resistant form of PCa where LBD mutations render anti-androgens ineffective or where constitutively active AR splice variants, lacking the LBD, become overexpressed. Recently, we identified a surfaced exposed pocket on the AR-DBD as an alternative drug-target site for AR inhibition. Here, we demonstrate that small molecules designed to selectively bind the pocket effectively block transcriptional activity of full-length and splice variant AR forms at low to sub-micromolar concentrations. The inhibition is lost when residues involved in drug interactions are mutated. Furthermore, the compounds did not impede nuclear localization of the AR and blocked interactions with chromatin, indicating the interference of DNA binding with the nuclear form of the transcription factor. Finally, we demonstrate the inhibition of gene expression and tumor volume in mouse xenografts. Our results indicate that the AR-DBD has a surface site that can be targeted to inhibit all forms of the AR, including enzalutamide-resistant and constitutively active splice variants and thus may serve as a potential avenue for the treatment of recurrent and metastatic prostate cancer. | 10.1074/jbc.M114.553818 |
pubmed_340_24488 | Post-traumatic osteoarthritis is the form of osteoarthritis (OA) that develops following joint injury. Although its end-stage is indistinguishable from idiopathic OA, many patients with post-traumatic OA are younger than those with idiopathic OA, and they have a well-defined precipitating insult. Clinical and experimental studies suggest that excessive acute impact energy or chronic mechanical overload cause the degeneration of the articular surface responsible for post-traumatic OA. Yet, the mechanisms by which excessive mechanical force causes OA remain unknown. For these reasons it has not been possible to develop effective methods of preventing or decreasing the risk of post-traumatic OA. We hypothesized that mechanical loading that exceeds the tolerance of the articular surface causes chondrocyte damage due to oxidative stress. Our in vitro tests of human articular cartilage samples showed that shear stress causes chondrocyte death and that anti-oxidants decrease the shear stress induced cell death. These observations suggest that specific patterns of loading are particularly damaging to articular surfaces and that improved treatments of joint injuries may include mechanical methods of minimizing shear stresses and biologic methods of minimizing oxidative damage. | pubmed_340_24488 |
pubmed_421_9739 | This article examines the America Needs More Family Doctors: 25x2030 Collaborative goal of "25x30"-that 25% of all medical students will enter family medicine residency programs by the year 2030. Filling 25% of all available postgraduate year-1 positions in the match is an important consideration in creating a strong primary care workforce. Data from the National Resident Matching Program (NRMP) matches for 2010 and 2020 are reviewed to examine trends not only in the US MD and DO categories, but also US international medical school graduates (IMGs) and non-US IMG categories over the last 10 years. If the total number of all programs and of all positions offered were held constant in 2030, what shifts in student choices would be required to reach the 25x30 goal in each applicant category as well as for all four categories combined? This discussion explores resources, power, physician income, and other factors that affect student numbers. Until a national health system is developed with national goals and priorities, it is unlikely that 25x30 will become a reality. | 10.22454/FamMed.2021.982403 |
pubmed_517_20254 | The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions. | 10.1182/blood-2011-04-347559 |
pubmed_841_16996 | Fifteen years (1984-1998) of records from a Veterinary Teaching Hospital were analyzed to determine whether antimicrobial drug resistance in coagulase-positive Staphylococcus spp. (S. aureus, S. intermedius) isolated from clinical infections in dogs has increased, and whether there has been a change in the species of bacteria isolated from urinary tract infections in dogs. In coagulase-positive Staphylococcus spp., a complex pattern showing both increases and decreases of resistance to different classes of antimicrobial drugs was observed, reflecting the changing use of different antimicrobial drug classes in the hospital over a similar period (1990-1999). In canine urinary tract infections identified from 1984 to 1998, an increase in the incidence of multiresistant Enterococcus spp. was apparent, with marginal increases also in incidence in Enterobacter spp. and in Pseudomonas aeruginosa, both of which, like Enterococcus spp., are innately antimicrobial-resistant bacteria. A survey of directors of veterinary teaching hospitals in Canada and the United States identified only 3 hospitals that had any policy on use of "last resort" antimicrobial drugs (amikacin, imipenem, vancomycin). Evidence is briefly reviewed that owners may be at risk when dogs are treated with antimicrobial drugs, as well as evidence that some resistant bacteria may be acquired by dogs as a result of antimicrobial drug use in agriculture. Based in part on gaps in our knowledge, recommendations are made on prudent use of antimicrobial drugs in companion animals, as well as on the need to develop science-based infection control programs in veterinary hospitals. | pubmed_841_16996 |
pubmed_744_6483 | The characteristics of the spatial eigenmodes of vertical-cavity surface-emitting lasers with a large circular aperture are considered close to the lasing threshold. Experiments yield patterns based on rotational symmetry ("flowerlike" patterns) or on Cartesian symmetry (stripelike patterns) for very close operating conditions. The former are compatible with the boundary conditions whereas the latter are expected in infinite devices. Theoretically, the problem is considered in the framework of an eigenmode analysis of a linear partial differential equation for the optical field valid at threshold. This formulation allows for a simple implementation of asymmetries due to the reflection properties of Bragg mirrors as well as of transverse variations of gain and refractive index due to the device structure or due to imperfections in the growth process. A sharp transition between flowerlike modes and stripelike modes is shown to occur, if the device aperture is increased. | 10.1103/PhysRevE.69.066205 |
pubmed_756_16778 | BACKGROUND
Although radiological diagnosis of Paget's disease of bone (PD) is usually straightforward, monostotic cases may potentially raise specific problems which lead to performing invasive procedures. Therefore, the purpose of this study is to ascertain whether or not monostotic femoral Paget's disease (MFPD) presentation poses particular diagnostic difficulties which prompt excessive use of excisional biopsies.
METHODS
We retrospectively reviewed the medical records of 24 MFPD patients identified from a series of 412 patients; their clinical features were compared with those of the remaining 164 monostotic cases and the radiological images were systematically assessed.
RESULTS
When compared with the remaining monostotic cases, MFPD patients were more prone to having normal alkaline phosphatase levels (31.8% vs. 16.4%; 0.08) and a significantly higher percentage of patients have PD symptoms (75% vs. 51%; 0.02) and complain of bone pain (73.9% vs. 40.8%; 0.003). Six (25%) MFPD patients evidenced a fracture over the pagetic lesion. This incidence is higher than that of the monostotic cases of other locations (8.4%; p=0.02). The existence of PD lesion was not recognised initially in 10 cases and an excisional bone biopsy was performed in 7 (29%). One patient subsequently experienced a fracture through the biopsy site and another two experienced worsening of their previous bone pain.
CONCLUSION
The femur is a relatively common monostotic PD location which often causes diagnostic confusion, prompting a bone biopsy in many cases. Careful assessment of this lesion by X-ray examination may help attain an early appropriate diagnosis and avoidance of unnecessary surgical morbidity. | pubmed_756_16778 |
pubmed_772_715 | BACKGROUND
Patients with occult metastasis or locally nonresectable pancreatic cancer found during surgical exploration have a limited life expectancy. We sought to define markers in these patients that could predict survival and thus aid decision making for selection of the most appropriate therapeutic palliative option.
METHODS
In a prospective 4-year single-center study, 136 consecutive patients with obstructive pancreatic cancer and intraoperative diagnosis of nonresectable or disseminated pancreatic cancer underwent a palliative surgical bypass procedure. Potential factors predicting survival were evaluated.
RESULTS
Ninety-eight patients had metastatic disease and 38 locally advanced disease. Surgical morbidity rate was 16 %, re-operation rate 1%, and overall in-hospital mortality 4%. Univariate analysis showed American Society of Anesthesiologists (ASA) score, pain, operation time, presence of metastasis, and levels of leukocytes, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were associated significantly with survival. The multivariate analysis identified ASA score, presence of liver metastasis, pain, CA 19-9, and CEA levels as independent indicators for poor survival. Patients with none or 1 of these risk factors had a median survival of 13.5 months, whereas patients with 4 or 5 risk factors had a median survival of 3.5 months.
CONCLUSIONS
The clinical markers identified predict poor outcome for patients with palliative bypass surgery and therefore aid the appropriate selection of either surgical bypass or endoscopic stenting in these patients. | 10.1016/j.amjsurg.2007.02.026 |
pubmed_377_19899 | Considerable evidence indicates that quantitative and/or functional abnormalities of natural killer (NK) cells are associated with reproductive failure. The objective of this study was to determine if peripheral NK percentage and activity are altered in women with reproductive failure after artificial insemination by donor (AID), and which parameters can best discriminate women with AID failure and normal controls. A case-control study of 20 fertile controls, 25 patients undergoing more than four treatment cycles without success (Group I), 25 experiencing biochemical pregnancy loss (Group II), and 25 undergoing embryo growth arrest or miscarriage (Group III) was performed. The peripheral NK percentage and cytotoxicity was evaluated by flow cytometry. Our results showed that a significantly increased percentage of NK cell cytotoxicity (NKCC) was detected in all study groups compared with the controls. The percentage of CD56(+) NK cells was elevated in Groups II and III compared with the controls. The percentage of CD56(+)CD16(+) NK cells in the study groups was higher than that in the controls. By using receiver operating characteristic curve and logistic regression analysis, we found that NKCC combined with CD56(+)CD16(+) NK percentage had good predictive power. The overall predicted percentage correct was 0.89. These results suggest that enhanced NKCC and an elevated cytotoxic NK percentage may be associated with AID failure and can be biomarkers for predicting AID-induced failure. | 10.1016/j.jri.2011.05.009 |
pubmed_313_15568 | Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is difficult to detect the subsurface lesions. In this research, we investigated the feasibility of a novel multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. The C57BL/6J-ApcMin/J mice were imaged using OCT and FLOT, and the correlated histopathological diagnosis was obtained. Quantitative structural (scattering coefficient) and molecular (relative enzyme activity) parameters were obtained from OCT and FLOT images for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 88.23% (82.35%) for sensitivity (specificity) compared to either modality alone. This study suggested that combining OCT and FLOT is promising for subsurface cancer detection, diagnosis, and characterization. | 10.1364/BOE.7.005218 |
pubmed_5_18478 | A 6-year-old boy developed macroscopic haematuria on the 4th day after appendectomy for acute appendicitis, at which the appendix was found to be perforated. During the next few days the urine secretion decreased and malaise, pain in the lower abdomen, nausea and vomiting occurred. On a management of ample fluid administration, the urine secretion recovered and the symptoms subsided in a few days. In the early postoperative stage after appendectomy in children the possibility should be kept in mind of the development of acute renal insufficiency due to bilateral ureteral obstruction as a result of oedema of the posterior bladder wall, even if by means of ultrasonography only mild to moderate abnormalities are noted. Awaiting decompression by means of the introduction of bilateral ureteric stents, in order to prevent irreversible renal damage, supportive therapy with fluid administration depending on the diuresis seems indicated. | pubmed_5_18478 |
pubmed_499_17440 | Quantum flatland i.e., the family of two dimensional (2D) quantum materials has become increscent and has already encompassed elemental atomic sheets (Xenes), 2D transition metal dichalcogenides (TMDCs), 2D metal nitrides/carbides/carbonitrides (MXenes), 2D metal oxides, 2D metal phosphides, 2D metal halides, 2D mixed oxides, etc. and still new members are being explored. Owing to the occurrence of various structural phases of each 2D material and each exhibiting a unique electronic structure; bestows distinct physical and chemical properties. In the early years, world record electronic mobility and fractional quantum Hall effect of graphene attracted attention. Thanks to excellent electronic mobility, and extreme sensitivity of their electronic structures towards the adjacent environment, 2D materials have been employed as various ultrafast precision sensors such as gas/fire/light/strain sensors and in trace-level molecular detectors and disease diagnosis. 2D materials, their doped versions, and their hetero layers and hybrids have been successfully employed in electronic/photonic/optoelectronic/spintronic and straintronic chips. In recent times, quantum behavior such as the existence of a superconducting phase in moiré hetero layers, the feasibility of hyperbolic photonic metamaterials, mechanical metamaterials with negative Poisson ratio, and potential usage in second/third harmonic generation and electromagnetic shields, etc. have raised the expectations further. High surface area, excellent young's moduli, and anchoring/coupling capability bolster hopes for their usage as nanofillers in polymers, glass, and soft metals. Even though lab-scale demonstrations have been showcased, large-scale applications such as solar cells, LEDs, flat panel displays, hybrid energy storage, catalysis (including water splitting and CO2 reduction), etc. will catch up. While new members of the flatland family will be invented, new methods of large-scale synthesis of defect-free crystals will be explored and novel applications will emerge, it is expected. Achieving a high level of in-plane doping in 2D materials without adding defects is a challenge to work on. Development of understanding of inter-layer coupling and its effects on electron injection/excited state electron transfer at the 2D-2D interfaces will lead to future generation heterolayer devices and sensors. | 10.1186/s40580-022-00317-7 |
pubmed_674_22780 | To explore the joint effect of copper (Cu) and flooding on Salix integra Thunb. (S. integra), the physiological and biochemical parameters of the seedlings grown in Cu amended soil (50, 150, 450 mg kg-1) with or without the flooding for 60 days were evaluated. The results suggested that the flooding significantly inhibited the root growth in terms of root length and root tips. The Cu exposures of 50 and 150 mg kg-1 notably enhanced the root growth as compared to the control. Majority of Cu was accumulated in S. integra roots, while flooding significantly reduced the Cu content, except the 150 mg kg-1 Cu treatment, but the iron (Fe) and manganese (Mn) content on the root surface were both markedly increased relative to non-flooded control. The malonaldehyde (MDA) and glutathione (GSH) contents in leaves showed a dose-response upon Cu exposure. Soil flooding enhanced the GSH level, which displayed 4.50-49.59% increases compared to its respective non-flooded treatment, while no difference was evident on MDA contents between the flooding and the non-flooded treatments. Both superoxide dismutase (SOD) and peroxidase (POD) activities were boosted while the catalase (CAT) was suppressed with increasing Cu exposure dose, and soil flooding reduced the POD and CAT activities. The elevated Cu level caused the evident increases of root calcium (Ca), potassium (K), and sulfur (S) concentrations and decreases of root phosphorus (P), sodium (Na), and zinc (Zn) concentrations. Soil flooding increased the concentrations of Fe, S, Na, Ca, and magnesium (Mg) in S. integra root. Taken together, our results suggested S. integra has high tolerance to the joint stress from Cu and flooding. | 10.1016/j.envpol.2017.03.040 |
pubmed_437_22843 | Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status. | 10.1007/s11745-014-3913-8 |
pubmed_999_6720 | Greater gait variability predicts dementia. However, little is known about the neural correlates of gait variability. The aims of this study were to determine (1) grey matter volume covariance patterns associated with gait variability and (2) whether these patterns were associated with specific cognitive domains. Participants (n = 351; mean age 71.9 ± 7.1) were randomly selected from the Southern Tasmanian electoral roll. Step time, step length, step width and double support time were measured using an electronic walkway. Gait variability was calculated as the standard deviation of all steps for each gait measure. Voxel-based morphometry and multivariate covariance-based analyses were used to identify grey matter patterns associated with each gait variability measure. The individual expressions of grey matter patterns were correlated with processing speed, memory, executive and visuospatial functions. The grey matter covariance pattern of double support time variability included frontal, medial temporal, anterior cingulate, insula, cerebellar and striatal regions. Greater expression of this pattern was correlated with poorer performance in all cognitive functions (p < 0.001). The covariance pattern of step length variability included frontal, temporal, insula, occipital and cerebellar regions and was correlated with all cognitive functions (p < 0.05), except memory (p = 0.76). The covariance pattern of step width variability was limited to the cerebellum and correlated only with memory (p = 0.047). No significant pattern was identified for step time variability. In conclusion, different grey matter covariance patterns were associated with individual gait variability measures. These patterns were also correlated with specific cognitive functions, suggesting common neural networks may underlie both gait and cognition. | 10.1007/s10548-021-00841-5 |
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