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pubmed_266_1845 | Pulmonary Embolism (PE) is the third most common cause of cardiovascular mortality in the United States, with 60,000-100,000 deaths per year following myocardial infarction and stroke. During the past 5 years, there has been an introduction of novel interventions as a result of a renewed interest in optimizing PE management, particularly among those individuals with more severe disease of hemodynamic significance. The cornerstone treatment for PE is anticoagulation. More aggressive alternatives have been considered for patients with intermediate and high-risk PE. In general, these options can be grouped into 3 different categories: systemic thrombolysis, catheter-directed interventions, and surgical embolectomy. Systemic thrombolysis has shown statistical benefit in several randomized trials for intermediate- and high-risk PE, however, this benefit has been offset by an elevated risk of major bleeding and intracerebral hemorrhage, limiting their use in clinical practice. Catheter-directed thrombolysis refers to catheter-directed injection of a thrombolytic drug directly into the pulmonary artery. Three interventional devices (EKOSonic endovascular system, FlowTriever embolectomy device and the Indigo thrombectomy system) have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. As of today, catheter-based interventions are limited to small randomized trials and single arm-prospective studies focused on short-term surrogate endpoints. Although single arm studies carry some value establishing the preliminary safety and effectiveness of these devices, they are not sufficient to stratify risk and guide clinical practice. Furthermore, no trials have been performed with enough power to assess potential mortality benefit with the use of catheter-directed thrombolysis or catheter-based embolectomy devices, hence treatment decisions continue to be influenced by individual risk of bleeding, the location of thrombus and operator expertise until additional evidence becomes available. | 10.1016/j.cpcardiol.2020.100650 |
pubmed_109_3037 | DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC. | pubmed_109_3037 |
pubmed_549_10539 | Phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P(3)) accumulates at the leading edge of migrating cells and works, at least partially, as both a compass to indicate directionality and a hub for subsequent intracellular events. However, how PtdIns(3,4,5)P(3) regulates the migratory machinery has not been fully elucidated. Here, we demonstrate a novel mechanism for efficient lamellipodium formation that depends on PtdIns(3,4,5)P(3) and the reciprocal regulation of PtdIns(3,4,5)P(3) itself. LL5beta, whose subcellular localization is directed by membrane PtdIns(3,4,5)P(3), recruits the actin-cross-linking protein Filamin A to the plasma membrane, where PtdIns(3,4,5)P(3) accumulates, with the Filamin A-binding Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2). A large and dynamic lamellipodium was formed in the presence of Filamin A and LL5beta by the application of epidermal growth factor. Conversely, depletion of either Filamin A or LL5beta or the overexpression of either an F-actin-cross-linking mutant of Filamin A or a mutant of LL5beta without its PtdIns(3,4,5)P(3)-interacting region inhibited such events in COS-7 cells. Because F-actin initially polymerizes near the plasma membrane, it is likely that membrane-recruited Filamin A efficiently cross-links newly polymerized F-actin, leading to enhanced lamellipodium formation at the site of PtdIns(3,4,5)P(3) accumulation. Moreover, we demonstrate that co-recruited SHIP2 dephosphorylates PtdIns(3,4,5)P(3) at the same location. | 10.1074/jbc.M109.081901 |
pubmed_153_7183 | BACKGROUND
DNA vaccines provide high tolerability and safety but commonly suffer from suboptimal immunogenicity. We previously reported that a plasmid vector (pATRex), encoding the DNA sequence for the von Willebrand I/A domain of the tumor endothelial marker-8 (TEM8) when given in combination with plasmid-encoded tumor antigens acted as a powerful molecular adjuvant enhancing immunity against breast and melanoma tumors.
AIMS
In the present study we addressed two unsolved issues; would the adjuvant action of pATRex extend to a DNA vaccine against infectious disease and, if so, what is the mechanistic basis for pATRex adjuvant action?
RESULTS
Here we show in a murine malaria vaccine model that co-administration of pATRex potentiates antibody production elicited by an intramuscular injection of plasmid encoding Plasmodium yoelii merozoite surface protein 4/5 (PyMSP4/5). pATRex enhanced the B-cell response and induced increased IgG1 production consistent with TH2 polarization of the DNA vaccine response. To explore the mechanism of adjuvant action, cells were transfected in vitro with pATRex and this resulted in formation of insoluble intracellular aggregates and apoptotic cell death. Using a structural modeling approach we identified a short peptide sequence (α3-β4) within ATRex responsible for protein aggregation and confirmed that transfection of cells with plasmid encoding this self-assembling peptide similarly triggered intracellular aggregates, caspase activation and cell death.
CONCLUSION
Plasmids encoding aggregation-promoting domains induce formation of insoluble intracellular aggregates that trigger caspase activation and apoptotic cell death leading to activation of the innate immune system thereby acting as genetic adjuvants. | 10.2174/1566523214666140509114838 |
pubmed_19_5935 | Vitamin E is well known as an antioxidant, with 8 natural isoforms, such as α-, bgr;-, γ- and δ-tocopherols and α-, β-, gamma;- and δ-tocotrienols. It has been suggested that both tocopherols and tocotrienols have anti-tumor effects due to the antioxidant effect. The results of several studies have indicated that the tocotrienols may have a stronger bioactivity than the tocopherols. Both types have shown antiproliferative, proapoptotic and cyclooxygenase-2- inhibiting effects in in vitro studies. Several animal studies have demonstrated that vitamin E has cancer-preventing effects. However, clinical trials have not shown similar results for the cancer prevention effect of tocopherol. Although the Linxian Trials demonstrated that the supplementation of β-carotene, α-tocopherol and selenium reduced cancer risk, the beneficial effects of α- tocopherol on prostate cancer disappeared after several years in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Vitamin E, especially tocotrienols, seems to be a potent agent for cancer prevention, however no large-scale clinical trial on the cancer prevention effect of tocotrienols has been conducted yet. Therefore it is expected that clinical trials overcoming the lower bioavailability of tocotrienols will be conducted, and it is urgently needed to assess the safety and the efficacy of the administration of the tocotrienols as a part of a cancer prevention regimen. | 10.2174/138920112798868656 |
pubmed_345_14706 | BACKGROUND
There has been substantial interest and emphasis on medical professionalism over the past twenty years. This speaks to the history of the medical profession, but increasingly to a broader understanding of the importance of socialisation and professional identity formation.
METHOD
A literature review was undertaken of professionalism and the role of professions and medical professional organisations.
RESULTS
A key outcome has been the recognition that medical professionalism must be actively taught and assessed. Substantial effort is required to improve the educational environment, so that it nurtures the development of professionalism within the work-place. Although medical colleges have been prominent in identifying and progressing the recent developments within professionalism there is still much to be done to deliver fully on the societal contract between the public and the profession. There are key gaps to address, particularly with regards to self-regulation, civil behaviour and effective leadership and advocacy.
CONCLUSION
Medical colleges need to take direct responsibility for the professionalism of their members. The expectations of the community are increasingly clear in this regard. | pubmed_345_14706 |
pubmed_733_14141 | We report a 72-year-old woman who died of respitory failure. History included onset of diabetes mellitus at the age of 67 years and hypertension at the age of 72 years. The patient had been in good health otherwise until 2000, when she had onset of numbness or tingling of the bilateral lower limbs. On December 3, 2000, she was admitted to a hospital in the vicinity of her home because of the above-mentioned complaints. Neurological examinations revealed progressive paraplegia. Symptoms and signs suggested Guillain-Barré syndrome. Examinations of cerebrospinal fluids revealed cell count of 338/3 (mono 72%, poly 18%) and protein value of 100 mg/dl. Later the patient course deteriorated. On December 15, 2000, she was admitted to Hakujikai Memorial Hospital for the second time. Ten days later, MRI examination showed diffuse swelling of the spinal cord from the cervical (C 3/4) level to the thoracic level. Gd-enhanced T 1-weighted MRI performed 22 days later showed a partially enhanced lesion at the thoracic (Th 5/6) level of the spinal cord. The patient was treated with steroid therapy (methylprednisolone 500 mg/dl). She died of respiratory failure on January 6, 2001. The patient was presented in a neurological CPC. Neurological and imaging findings suggested a transverse myelopathy. However, there were several points in this case that were unusual for a typical transverse myelopathy, such as total sensory loss below spinal segments of thoracic level (Th 5) and motor weakness of the upper limbs of upper segment of the same level. A clinical neurologist concluded that the patient had subacute transverse myelopathy with fused multiple pathy pathologic lesions. We discussed whether this case was a transverse myelopathy or multiple sclerosis. Post mortem examination revealed acute necrotic myelopathy affecting the spinal cord from the second cervical to the tenth thoracic vertebrae, with conspicuous infiltration of CD 68-positive macrophages involving both gray and white matter, partially necrotic associated with scattered UCHL-1 dominants lymphocytic infiltration of T cells around vessels. There were relatively older lesions with demyelinating features in the spinal roots that were particularly dominant in the anterior roots. No demyelinated plaques in the optic chiasm, tracts and nerves, or in the cerebero-cerebellar white matter were found. Systemic pathological diagnosis was lung edema with fresh hemorrhage, pancreatic atrophy consistent with diabetes mellitus and choleductlithiasis. | pubmed_733_14141 |
pubmed_656_16864 | Many studies of split-belt treadmill adaptation have been focused on the biomechanical changes that occur in response to walking on belts at different speeds. This process of adaptation, and the ensuing aftereffects that are present when participants return to typical treadmill walking, have inspired the potential use of the split-belt treadmill as a rehabilitation tool. However, a full systematic review of the current split-belt treadmill literature has not yet been published to consolidate what is known about how the human central nervous system (CNS) controls adaptation to this type of symmetry perturbation. A systematic literature search identified 55 studies that investigated the neural control of human gait adaptation to a split-belt treadmill. Studies of infants and manipulated sensory feedback in healthy adults suggest that the initial gait adjustments to split-belt walking are reliant on proprioceptive feedback to inform central pattern generators to modify lower limb muscle activation patterns appropriately. Simultaneously, this literature suggested that proprioceptive and visual feedback inform supraspinal centres for motor planning and motor output to adapt and store a new and efficient gait pattern to walk on belts at different speeds. However, evidence from participants with brain injury (post-stroke, cerebellar lesions) suggest that injury impedes, but does not completely take away, the ability to adjust and adapt aspects of the gait pattern to split-belts. The model proposed from this review provides the overarching roles of the CNS in the adaptation process, specifically in short-term, and potential sites of focus within the human CNS for future rehabilitation-based work. | 10.1016/j.neuroscience.2020.09.055 |
pubmed_578_4056 | A new cost-effective amperometric proton selective sensor utilizing a single microhole interface between two immiscible electrolyte solutions (ITIES) is developed. The sensing methodology is based on measuring currents associated with proton transfer across the interface assisted by a proton selective ionophore. The ellipse shaped micro-interface was first fabricated by simple mechanical punching with a sharp needle on a thin PVC film (12 μm thick) commercially available as a food wrapping material. The microhole was then filled up with a gellified polyvinylchloride (PVC)-2-nitrophenyloctylether (NPOE) to create a single microhole liquid/liquid interface. Direct ion transfer reactions across the polarized interface serving as ion sensing platforms were studied using cyclic voltammetry. In order to enhance the selectivity of proton sensing, a proton selective ionophore, octadecyl isonicotinate (ETH1778), was incorporated into the organic gel layer and their electrochemical sensing characteristics were investigated using cyclic voltammetry and differential pulse stripping voltammetry. As an example, we employed the proton selective sensor for the determination of glucose concentrations. The detection scheme involves two steps: (i) protons are first generated by the oxidation of glucose with glucose oxidase in the aqueous phase; and (ii) the current associated with the proton transfer across the interface is then measured for correlating the concentration of glucose. | 10.1039/c0cp00750a |
pubmed_996_20565 | OBJECTIVE
The authors' aim was to assess the safety and efficacy of starting clozapine in a structured, long-term, partial hospitalization program that included protocols for detecting and managing side effects and adverse reactions to the drug as well as therapeutic programming to enhance patients' reintegration into community life.
METHODS
Medical records of 47 patients with schizophrenia or schizoaffective disorder who were started on clozapine in the partial hospitalization program were analyzed. Data on incidence and management of adverse reactions, number of hospitalizations, status of symptoms, and changes in patients' social functioning for periods up to 12 months after initiation of clozapine were collected.
RESULTS
Although adverse reactions were common in the first weeks of treatment, they were managed with dosing strategies, monitoring, and concomitant medication so that no patient had to discontinue the medication. Psychotic symptoms and symptoms of tardive dyskinesia decreased significantly during the study period. At 12-month follow-up, most patients were able to attend school, hold paying or volunteer jobs, and live independently.
CONCLUSIONS
Clozapine can be safely initiated outside an inpatient setting. Partial hospitalization programs can enhance patients' reintegration into the community through a combination of treatment with clozapine and rehabilitative and psychotherapeutic programming. | 10.1176/ps.45.3.264 |
pubmed_1142_16443 | INTRODUCTION
Young people in contact with the youth justice system are more likely to present with complex ongoing needs than young people in the general population. To address this, the Framework for Integrated Care (SECURE STAIRS) is being implemented in the Children and Young People's Secure Estate: a 'whole systems' approach to support secure settings to develop trauma-informed and relationally based environments, supporting staff to provide consistent, therapeutic care. This paper aims to present the protocol for a national cohort study examining the impact and implementation of this cultural transformation programme.
METHODS AND ANALYSIS
A mixed-methods realist evaluation will be conducted. Data collection will take place between August 2018 and December 2020. Eighteen sites will collect routine service activity data and questionnaires completed by young people, parents/guardians and staff. Semi-structured interviews and non-participant observations will be conducted across five qualitative focus sites with young people and staff. An economic evaluation will examine value for money. The results will be triangulated at the analysis stage to gain an in-depth understanding of experiences.
ETHICS AND DISSEMINATION
Ethical approval was granted by the Health Research Authority, Her Majesty's Prison and Probation Service and UCL Ethics Committee. Findings will be disseminated via project reports, site feedback, peer-reviewed journal publications and conference presentations. | 10.1136/bmjopen-2020-045680 |
pubmed_324_1137 | Microsatellite markers were used to examine spatio-temporal genetic variation in the endangered eastern freshwater cod Maccullochella ikei in the Clarence River system, eastern Australia. High levels of population structure were detected. A model-based clustering analysis of multilocus genotypes identified four populations that were highly differentiated by F-statistics (F(ST) = 0·09 - 0·49; P < 0·05), suggesting fragmentation and restricted dispersal particularly among upstream sites. Hatchery breeding programmes were used to re-establish locally extirpated populations and to supplement remnant populations. Bayesian and frequency-based analyses of hatchery fingerling samples provided evidence for population admixture in the hatchery, with the majority of parental stock sourced from distinct upstream sites. Comparison between historical and contemporary wild-caught samples showed a significant loss of heterozygosity (21%) and allelic richness (24%) in the Mann and Nymboida Rivers since the commencement of stocking. Fragmentation may have been a causative factor; however, temporal shifts in allele frequencies suggest swamping with hatchery-produced M. ikei has contributed to the genetic decline in the largest wild population. This study demonstrates the importance of using information on genetic variation and population structure in the management of breeding and stocking programmes, particularly for threatened species. | 10.1111/j.1095-8649.2010.02865.x |
pubmed_391_13887 | Forty stainless steel endodontic files were observed at scanning electron microscopy after being subjected to ten disinfection cycles of 10 minutes each one, immersed in different chemical disinfectants. Corrosion was not observed on the surface of the files in circumstances that this study was made. | pubmed_391_13887 |
pubmed_505_23848 | Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that metabolizes methylated arginine to citrulline and methylamine, thus working to produce nitric oxide (NO). We isolated a gene encoding chick DDAH1. In situ hybridization analysis revealed characteristic DDAH1 mRNA expression in the embryonic spinal cord, which was especially strong in the ventral horn and dorsal root ganglion (DRG). DDAH1 was also detected in the brain, kidney, digestive tract, and in other tissues. We examined the expression pattern of DDAH1 in developing rats and compared this with the expression pattern in chicks. The expression pattern in the rats was very similar to that in the chicks, but there were some differences between the chicks and rats in the amount of DDAH1 detected in the heart, liver, lung, and DRG. We also investigated neural nitric oxide synthase (nNOS) mRNA expression patterns in rat embryos. The DDAH1 expression patterns were completely different from nNOS expression patterns. Our study suggests that DDAH1 plays an important role in development. | 10.1016/j.devbrainres.2003.09.021 |
pubmed_259_844 | A Bayesian hierarchical model is proposed for estimating parasitic infection dynamics for highly polymorphic parasites when detectability of the parasite using standard tests is imperfect. The parasite dynamics are modelled as a non-homogeneous hidden two-state Markov process, where the observed process is the detection or failure to detect a parasitic genotype. This is assumed to be conditionally independent given the hidden process, that is, the underlying true presence of the parasite, which evolves according to a first-order Markov chain. The model allows the transition probabilities of the hidden states as well as the detectability parameter of the test to depend on a number of covariates. Full Bayesian inference is implemented using Markov chain Monte Carlo simulation. The model is applied to a panel data set of malaria genotype data from a randomized controlled trial of bed nets in Tanzanian children aged 6-30 months, with the age of the host and bed net use as covariates. This analysis confirmed that the duration of infections with parasites belonging to the MSP-2 FC27 allelic family increased with age. | 10.1002/sim.1274 |
pubmed_73_20811 | The use of chemilumigenic probes to monitor the production of chemically induced reactive oxygen species in situ has been hampered by commonly occurring interference of test compounds with radical intermediates of the probe and by the lack of suitable on-line detection systems. In this study we have explored the ability of the cell-permeable agent luminal to assess reactive oxygen species generated from redox-cycling compounds in cultured rat hepatocytes. Luminol-derived chemiluminescence was induced by exposure of hepatocytes to the 1,4-naphthoquinone drug menadione in a concentration-dependent manner. The luminescence signal was quantitated by integrating the light emission over time using a temperature-controlled luminescence plate reader. The signal was peroxidase-dependent and catalase-sensitive, indicating that extracellular hydrogen peroxide was detected. It was possible to rank a series of cytotoxic quinones according to their potential to undergo redox cycling. This assay includes rigorous controls for possible interference of quinone-containing compounds with light emission from the luminol reaction and for chemical quenching due to a reaction between the compound and a luminol radical intermediate. Taken together, this method, which we developed for use in multiwell plates, offers a fast and reliable tool for detecting the redox-cycling compound-derived production of reactive oxygen species in cultured hepatocytes. | 10.1080/15376510209167938 |
pubmed_1071_20286 | While the uses of block copolymers (BCPs) with a high Flory-Huggins interaction parameter (χ) are advantageous for the improvement of resolution and line edge fluctuations of self-assembled nanoscale patterns, their slow chain diffusion results in a prolonged assembly time. Although solvent vapor annealing has shown great effectiveness in promoting the self-assembly of such BCPs, a practical methodology to achieve a uniform swelling level in wafer-scale BCP thin films has not been reported. Here, we show that a solvent-swollen polymer gel pad can be used as a highly controllable vapor source for the rapid, large-area (>200 mm in diameter) formation of sub-10-nm patterns from a high-χ BCP. The proximal injection of solvent vapors to BCP films and the systematic control of the swelling levels and temperatures can significantly boost the self-assembly kinetics, realizing the formation of well-aligned sub-10-nm half-pitch patterns within 1 min of self-assembly. Moreover, we show that the gel pad can be used for the shear-induced alignment of BCP microdomains in an extremely short time of ~5 s as well as for the generation of three-dimensional crossed-wire nanostructures with controlled alignment angles. | 10.1021/nn401611z |
pubmed_359_422 | Genes play an important role in the development of osteoporosis. Twin and family studies have consistently shown that peak bone mass, ultrasound properties of bone, skeletal geometry, bone turnover, and fracture are heritable. Yet, as we report in this paper, few candidate genes have been implicated without ambiguity. Osteoporosis is thought to be a polygenic disorder, determined by multiple genes and environmental risk factors, each with small to modest effect on bone mass and fracture. Here we argue that future success in finding genes is only possible with improved study design and the use of more rigorous analytic approaches that are now becoming available. | 10.1007/s11914-004-0015-1 |
pubmed_614_7473 | OBJECTIVE
To investigate the effectiveness of the posterior midline approach with complete laminectomy for giant intraspinal tumor (more than 3 cm in diameter) resection and vertebral canal reconstruction.
METHODS
Between March 2009 and February 2012, 21 cases of giant intraspinal tumor underwent the posterior midline approach with complete laminectomy and vertebral canal reconstruction. There were 12 males and 9 females with an average age of 40.5 years (range, 21-62 years). The Japanese Orthopaedic Association (JOA) scores were 0-5 in 4 cases, 6-11 in 9 cases, and 12-17 in 8 cases. The preoperative Cobb angle was less than 10° on the X-ray films. MRI showed that the tumor located at the cervical part in 3 cases, at the cervicothoracic part in 1 case, at the thoracic part in 8 cases, at the thoracolumbar part in 2 cases, and at the lumbar part in 7 cases; the long diameter of tumor on the sagittal view was 3.0-16.5 cm (mean, 8.3 cm). Total resection of tumor was performed in 17 cases, and subtotal resection in 4 cases.
RESULTS
Postoperative pathological examinations showed 9 cases of neurilemmoma, 6 cases of neurofibroma, 3 cases of lipoma, 2 cases of meningioma, and 1 case of bronchogenic cyst. Primary healing of incision was achieved in all patients. The patients were followed up 1-3 years (mean, 2.3 years). Postoperative X-ray film showed that Cobb angle was more than 10° in 3 cases, and no displacement of internal fixator was observed. The JOA scores were 0-5 in 1 case, 6-11 in 10 cases, and 12-17 in 10 cases, showing significant difference when compared with preoperative scores (Z = -3.26, P = 0.02).
CONCLUSION
The posterior midline approach with complete laminectomy for giant intraspinal tumor resection and vertebral canal reconstruction is a safe, simple, and feasible operation way, and it can resect tumor to a maximum extent, relieve the clinical symptoms, and maintain the spinal stability. | pubmed_614_7473 |
pubmed_753_22430 | Diagnosing spondyloarthritis (SpA) early in young patients with inflammatory back pain and normal findings on radiographs of the sacroiliac joints (SIJ) remains a challenge in routine practice. Magnetic resonance imaging (MRI) is regarded as the most sensitive imaging modality for detecting early SpA before the radiographic appearance of structural lesions. The recently published Assessment of SpondyloArthritis International Society classification criteria for axial SpA include for the first time a positive MRI demonstrating sacroiliitis as an imaging criterion indicative of SpA together with at least 1 clinical feature of SpA. A systematic and standardized evaluation of the SIJ in patients with SpA showed that MRI has much greater diagnostic utility than documented previously and allowed a data-driven definition of a positive MRI for SpA. Single MRI lesions suggestive of inflammation can be found in the SIJ and the spine in up to one quarter of healthy controls and young patients with mechanical back pain. | 10.1097/MAJ.0b013e31820f8c59 |
pubmed_518_21702 | In this paper we demonstrate that peptide nucleic acids (PNAs) are excellent probes able to detect the W1282X point mutation of the cystic fibrosis (CF) gene when biospecific interaction analysis (BIA) by surface plasmon resonance (SPR) and biosensor technologies is performed. The results reported here suggest that BIA is an easy, fast, and automatable approach for detecting mutations of CF, allowing real-time monitoring of hybridization between 9-mer CF PNA probes and target biotinylated PCR products generated from healthy, heterozygous subjects and homozygous W1282X samples and immobilized on streptavidin-coated sensor chips. This method is, to our knowledge, the first application of PNAs, BIA, and SPR to a human hereditary mutation, and demonstrates the feasibility of these approaches for discriminating between normal and mutated target DNA. We like to point out that the procedure described in this paper is rapid and informative; results are obtained within a few minutes. This could be of great interest for molecular pre-implantation diagnosis to discriminate homozygous CF embryos from heterozygous and healthy embryos. Other advantages of the methodology described in the present paper are (a) that it is a nonradioactive methodology and (b) that gel electrophoresis and/or dot-spot analysis are not required. More importantly, the demonstration that SPR-based BIA could be associated with microarray technology allows us to hypothesize that the method described in the present paper could be used for the development of a protocol employing multispotting on SPR biosensors of many CF-PCR products and a real-time simultaneous analysis of hybridization to PNA probes. These results are in line with the concept that SPR could be an integral part of a fully automated diagnostic system based on the use of laboratory workstations, biosensors, and arrayed biosensors for DNA isolation, preparation of PCR reactions, and identification of point mutations. | 10.1038/labinvest.3780355 |
pubmed_260_11849 | OBJECTIVE
To determine whether patient-physician communication in obstetrics and gynaecology can be improved by a training program and to investigate if physicians with poorer performance before the training show greater improvement in communication skills scores over the course of the study.
DESIGN
Intervention study with randomisation in training (n = 16) and control group (n = 16) and patient satisfaction and communication skills of physicians as outcome variables. Physicians' communication skills were assessed by independent raters using a standardised evaluation instrument (adapted version of the MAAS-R) to analyse video recorded interviews before and after the training. Patient satisfaction was assessed with a patient satisfaction questionnaire.
RESULTS
Using general linear model (GLM) for repeated measures no group x time interaction nor time effects were found for physicians' communication skills. No group x time interaction was found for patients' satisfaction scores; however the significant time effect was mostly attributable to positive changes in patients' rating of the training group. Physicians with poorer performance at the beginning showed greater improvements over the course of the study, especially in the training group.
CONCLUSIONS
In this randomized controlled trial marginal intervention effects for the improvement of communication skills and only partial changes in patient satisfaction scores from pre to post training were shown. However, physicians with poorer performance at the beginning showed greater improvements, suggesting that competence levels were already relatively high at the beginning of the study. Also, formation of communication training groups should be based on specific skill deficits rather than being implemented unspecifically for an entire team of physicians. | 10.1007/s00404-007-0399-0 |
pubmed_159_15584 | Cognitive impairment is one of the core symptoms of schizophrenia, and patients with schizophrenia are at increased risk of metabolic syndrome (MS). However, the role of MS in cognitive impairment of schizophrenia is not established. This study investigated the correlation between neurocognitive, social cognitive performance and MS with schizophrenia. One hundred and fifty eight (158) schizophrenia patients were divided into 3 groups with ① normal metabolism, ② metabolic disorder (only meeting 1 or 2 MS criteria), and ③ metabolic syndrome (meeting 3 or more MS criteria). MATRICS Consensus Cognitive Battery)MCCB(and the Brief Psychiatric Rating Scale)BPRS(were used to evaluate cognitive performance and clinical symptoms. Blood samples were obtained to detect glucose and lipid metabolic levels. Overall MCCB and subscale T scores in the normal metabolism and metabolic disorder groups were better than in the MS group. After controlling for the confounding factors including age, sex, the usage of hypolipidemic and hypoglycemic drugs, and disease duration, metabolic deficits had effects on the symbol coding and spatial span scores. The results suggest that a defective metabolic state might play a role in neurocognitive performance of schizophrenia patients. | 10.1016/j.psychres.2020.112941 |
pubmed_810_3855 | Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms. | 10.5414/CN107655 |
pubmed_649_1115 | To elucidate the environmental influence on the growth of a tumor, bromodeoxyuridine (BrdU) uptake in multiple tumor foci within the intracranial cavity was studied immunohistochemically with a monoclonal antibody. Walker 256 tumor implanted intracerebrally produced multifocal tumors presented as intraparenchymal solid tumor, tumor in the choroid plexus, and leptomeningeal dissemination. The BrdU-labeling indices, or the S-phase fractions (% of nuclei labeled by BrdU divided by the number of tumor cell nuclei scored; LI), of those tumors were 48.4 +/- 1.1, 59.1 +/- 1.3, and 27.9 +/- 5.9, respectively (mean +/- SEM). These differences in LI, or the tumor growth activity, are discussed in relation to the different environmental conditions in different host structures. These host structure-related modification of tumor growth would be important in evaluating the proliferative activity of tumors growing at various intracranial structures. | 10.1007/BF00687956 |
pubmed_1059_1273 | Premature parturition was successfully induced with a preparation containing 2 dexamethasone esters in 709 out of 716 cows and heifers of gestational periods ranging from 3 to 8 months. A mortality rate of 38.5% was experienced among calves produced by induced cows, while only a 2.7% mortality rate occurred among 4,330 calves from normal parturitions. Approximately 50% of all treated cattle retained foetal membranes, but with apparently no ill-effect. The treatment apparently did not affect milk production, post-calving fertility, and the overall incidence of dystocias in cows and post-calving diseases. Three deaths occurred among induced cattle, but they could not be attributed to the treatment. It was concluded that the technique may prove to be of great value in dairy cattle, in seasonal milking areas. | 10.1111/j.1751-0813.1976.tb05386.x |
pubmed_107_18948 | Two repeated C2-like domains interacting with Ca2+ and phospholipid are found in synaptotagmin and Rabphilin-3A which are implicated in neurotransmitter release. Here we have isolated a cDNA encoding a novel protein having two repeated C2-like domains from a human brain cDNA library. The isolated cDNA encodes a protein with 400 amino acids and a M(r) of 44,071. The purified recombinant protein indeed interacts with Ca2+ and phospholipid. We have named this protein Doc2 (Double C2). Doc2 is exclusively expressed in brain and is highly concentrated in the synaptic vesicle fraction. These results suggest that Doc2 is a novel brain protein and serves as a Ca2+ sensor in neurotransmitter release. | 10.1006/bbrc.1995.1062 |
pubmed_304_18105 | Umbilical cords often become encircled around portions of the fetus, usually the neck. The incidence ranges from 21% in one loop to 0.2% in three loops. In the present study, we assessed the practice of severing the cord, which was encircled once around the neck of the fetus, after delivery of the anterior shoulder and prior to extraction of the body. This was a prospective, randomized, controlled study. The study and the control groups included 30 women each. Cord around the neck was diagnosed during labor by ultrasound. It was cut intentionally in the study group and left intact in the control group. Demographic data were obtained. The course of labor was assessed. Neonatal outcomes measured were cord pH, Apgar scores at 5 minutes, and need for resuscitation. Length of maternal and neonatal hospitalization was determined. No differences were found between the study and the control group before, during, and after labor regarding perinatal variables such as meconium-stained amniotic fluid, fetal heart rate patterns, Apgar scores at 5 minutes, and umbilical cord pH after delivery (7.29 +/- 0.07 [SD] in the study group and 7.32 +/- 0.06 [SD] in the controls; p=0.1). Single nuchal encirclement by the umbilical cord during labor, after delivery of the anterior shoulder, can be severed or left intact. We could not detect any adverse perinatal outcome in such deliveries. | 10.1055/s-2006-958166 |
pubmed_854_19608 | Vascular endothelial growth factor (VEGF) is associated with increased angiogenesis and aggressive tumour growth. We investigated the expression and clinical significance of VEGF and its receptors, flt-1 and KDR/flk-1, in patients with uterine endometrial carcinoma. The series consisted of 115 endometrioid endometrial adenocarcinoma patients with FIGO stage I-IV. Additionally, samples from 3 patients with adenoacanthoma and 12 patients with poor prognostic variants of endometrial carcinoma were examined. Immunohistochemical assessment was classified as negative or positive based on staining intensity. The median follow-up time of patients with endometrioid endometrial adenocarcinoma was 87 months. In endometrioid endometrial carcinomas, the positive immunostaining rate was 39% for VEGF, 65% for flt-1 and 68% for KDR/flk-1. There was a significant correlation between VEGF and both its receptors. Furthermore, this receptor expression was correlated between the two types of receptors. VEGF-, flt-1- and KDR/flk-1-positive immunostainings were not related to poor prognosis. We conclude that VEGF, flt-1 and KDR/flk-1 expressions are not useful prognostic markers for overall survival in patients with endometrioid endometrial carcinoma. | 10.1159/000085589 |
pubmed_1061_23738 | Nonalcoholic fatty liver disease (NAFLD) is a continuous diseases spectrum associated with obesity, type 2 diabetes, insulin resistance, and hyperlipidemia. Simple hepatic steatosis may progress to nonalcoholic steatohepatitis (NASH), even fibrosis and cirrhosis, and finally hepatocellular carcinoma. In recent years, NAFLD has become a public health concern with increasing prevalence. However, the mechanisms underlying the pathogenesis remain incompletely understood, and few effective therapeutic approaches are available. Summary and Key Messages: A myriad of different rodent models has been developed to elucidate pathophysiology of NAFLD/NASH and guide therapeutic strategy. To date, no single rodent model can display the whole disease spectrum and metabolic features associated with human NASH, but can imitate particular characteristics. In this paper, we review the most commonly used dietary, genetic, and chemical rodent models for NAFLD referring to their advantages and disadvantages. Also, we illustrate the status of latest treatment strategy using various NAFLD rodent models. We hope to provide critical guidance for researchers to select appropriate animal models. | 10.1159/000501851 |
pubmed_774_10908 | Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. A series of thiazolyl-pyrazole derivatives (6a-f, 7a-f, 8c, 8e) were screened for antimycobacterial activity against dormant M. tuberculosis H37Ra (D-MTB) and M. bovis BCG (D-BCG). Nine thiazolyl-pyrazole analogs, 6c, 6e, 7a, 7b, 7c, 7e, 7f, 8c and 8e exhibited promissing minimum inhibitory concentration (MIC) values (0.20-28.25 µg/mL) against D-MTB and D-BCG strains of Mtb. Importantly, six compounds (7a, 7b, 7e, 7f, 8c and 8e) exhibited excellent antimycobacterial activity and low cytotoxicity at the maximum evaluated concentration of >250 µg/mL. Finally, the promising antimycobacterial activity and lower cytotoxicity profile suggested that, these compounds could be further subjected for optimization and development as a lead, which could have the potential to treat tuberculosis. | 10.1016/j.bmcl.2019.03.020 |
pubmed_868_24728 | A water-soluble polysaccharide (TOP-2) was isolated from Trametes orientalis, consisting of galactose, glucose, mannose, and arabinose with the molar ratios of 5.79:5.77:3.45:1, having an average molecular weight of 63kDa. The antitumor and immunomodulatory activity of TOP-2 were determined in Lewis lung carcinoma (LLC) tumor-bearing mice. The results revealed that TOP-2 not only could efficaciously restrain the growth of LLC in mice, but also effectively increase the body weight and relative spleen/thymus weight. In addition, TOP-2 remarkably enhanced splenocyte proliferation, notably stimulated phagocytotic function of macrophages, and strikingly promoted the expression of serum cytokines. These findings indicate that TOP-2 exert antitumor activity in vivo potentially by improving immune function. TOP-2 could be empoldered as a potential supplementary agent for cancer treatment. | pubmed_868_24728 |
pubmed_1111_6437 | BACKGROUND
Because of the aging United States population, increase in overall life expectancy, and rising incidence of hepatobiliary tumors, more elderly patients are considered for hepatic resection. The objective of this study was to assess the influence of age on postoperative outcomes after major hepatectomy among a contemporary cohort from 2 high volume centers.
STUDY DESIGN
Demographics, diagnoses, surgical treatments, and postoperative outcomes of patients who underwent major hepatic resection were reviewed.
RESULTS
There were 856 patients who underwent major hepatectomy (resection of 3 or more segments) from 2002 to 2009. Postoperative mortality and morbidity occurred in 53 (6.2%) and 403 (47.1%) patients, respectively. Increasing age was independently associated with postoperative mortality (p = 0.0345). Each 1-year and 10-year increase in age resulted in an odds ratio of mortality after major hepatic resection of 1.036 (95% CI [1.003-1.071]) and 1.426 (95% CI [1.026-1.982]), respectively. This relationship was independent of American Society of Anesthesiology (ASA) score. Increasing age was associated with postoperative sepsis (p = 0.0224, odds ratio for each year 1.025 [range 1.003 to 1.048]) after major hepatic resection, but not overall postoperative morbidity.
CONCLUSIONS
In the contemporary era, increasing age is independently associated with postoperative mortality after major hepatic resection at high volume academic centers. | 10.1016/j.jamcollsurg.2010.12.048 |
pubmed_332_10553 | OBJECTIVE
To supplement the information on the underlying cause of death due to external causes through using news carried in newspapers.
METHODS
This study investigated 153 deaths due to external causes among people living in Belo Horizonte, Southeastern Brazil, in 2008. A database named "press" was constructed using information from large-circulation national and state-level newspapers, and this was correlated with the database of the Brazilian mortality information system. The data were analyzed using the EpiInfo and Link-plus software. The concordance of the results was assessed using the kappa coefficient.
RESULTS
A total of 1,530 news items on accidents and violence were located, and 201 of these items were matched with death certificates in the mortality information system; 153 items referred to people living in Belo Horizonte. The main causes of death identified in the databases were aggression and traffic accidents. In the press database, aggression and traffic accidents accounted for 86.3%, other accidents 7.8%, events of undetermined intent 4.6% and legal intervention cases 1.3%. After supplementation using the press database, there were increases in the numbers of deaths due to car accidents (220.0%) and motorcycle accidents (100.0%), which resulted in a decrease in the numbers of deaths due to indeterminate causes and unspecified traffic accidents notified in the mortality information system.
CONCLUSIONS
News in newspapers has great potential for qualifying and supplementing the information on the underlying cause of death due to external causes in the mortality information system, particularly regarding deaths due to traffic accidents. | pubmed_332_10553 |
pubmed_949_5706 | PURPOSE
To determine if the pattern of release of neurotensin from the enkephalin-, neurotensin- and somatostatin-like immunoreactive amacrine cells in response to light and dark is the same as that of the enkephalins and somatostatin.
METHODS/RESULTS
Both the enkephalins and somatostatin are released at high rates in the dark and at lower rates in the light, and these rate changes are reflected in increasing intracellular levels of the peptides in vivo in the light and decreasing levels in the dark. The levels of neurotensin-like immunoreactivity show a similar diurnal light-driven and non-circadian rhythm in vivo.
CONCLUSION
This implies that the actual release rates of neurotensin follow the same patterns as those demonstrated in vitro for the enkephalins and somatostatin. | 10.1111/j.1442-9071.1997.tb01761.x |
pubmed_578_2990 | The mechanisms of the Myers-Saito cyclization and the Schmittel cyclization of hepta-1,2,4-triene-6-yne are studied by ab initio multireference MO methods (CASSCF and MRMP2 methods). For the Myers-Saito cyclization, two transition states with C(s) and C₁ symmetries are located. The transition state with C1 symmetry is only 1.5 kcal/mol lower in energy than that with C(s) symmetry at the MRMP2 calculation level. The obtained activation energy at the transition state with C₁ symmetry and the reaction energy are 16.6 and 16.2 kcal/mol exothermic, respectively. For the Schmittel cyclization, two transition states with C(s) and C₁ symmetry are also obtained. The transition state with C₁ symmetry is 7.9 kcal/mol lower in energy than that with C(s) symmetry. The transition state with C₁ symmetry for Schmittel cyclization is 6.7 kcal/mol higher in energy than that for the Myers-Saito cyclization. The reaction mechanisms are analyzed by a CiLC-IRC method. The interactions of orbitals for the Myers-Saito and Schmittel cyclizations can be distinguished. | 10.1021/jp105860n |
pubmed_738_5730 | In face-to-face communication there are multiple paralinguistic and gestural features that facilitate recognition of a speaker's intended meaning, features that are lacking when people communicate digitally (e.g., texting). As a result, substitutes have emerged (expressive punctuation, capitalization, etc.) to facilitate communication in these situations. However, little is known about the comprehension processes involved in digital communication. In this research we examined the role of emoji in the comprehension of face-threatening, indirect replies. Participants in two experiments read question-reply sequences and then judged the accuracy of interpretations of the replies. On critical trials the reply violated the relation maxim and conveyed a negative, face-threatening response. On one-third of the trials the reply contained only text, on one-third of the trials the reply contained text and an emoji, and on one-third of the trials the reply contained only an emoji. When the question requested potentially negative information about one of the interactants (disclosures and opinions), participants were more likely to endorse the indirect meaning of the reply, and did so faster, when the reply contained an emoji than when it did not. This effect did not occur when the question was a request for action, a more conventional type of indirect reply. Overall, then, this research demonstrates that emoji can sometimes facilitate the comprehension of meaning. Future research is needed to examine the boundary conditions for this effect. | 10.1371/journal.pone.0232361 |
pubmed_462_18064 | Twenty-seven crossbred calves (1/2 Simmental, 1/4 Hereford, 1/4 Brahman) averaging 257 +/- 11 d of age were either hot-iron-branded (H), freeze-branded (F), or sham-branded (S). Calves were blocked for temperament, weight, and sex and were randomly assigned to day and order in which treatments were applied. To reduce stress from handling at treatment time, each calf was herded through the squeeze chute daily for 5 d before the experiment. Jugular cannulas were inserted in each calf 1 d before application of treatment. Blood samples and heart rate measures were obtained at -5, -3, 0, .5, 1, 3, 5, 10, 15, and 20 min after application of the treatments. Mean concentrations of plasma epinephrine (EPI) were higher for H calves at time .5 min than for either S or F calves (P = .10). To account for individual differences, prebranding heart rates and hormone concentrations were subtracted from subsequent samples and were also used to calculate a proportion for each subsequent sample. Analyses of subtracted values found that EPI concentrations were greater for H calves than for either S or F calves (P = .007) at .5 min postbranding. No other differences were found for the subtracted analyses. Analyses of proportion data also revealed that H calves had greater EPI than did either S or F calves (P = .027) at .5 min postbranding. Only three animals vocalized during branding, one H calf and two F calves. Despite the 5-d acclimation period, handling and restraint elevated plasma cortisol concentrations and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.2527/1992.702330x |
pubmed_1030_8113 | OBJECTIVE
The study objective was to determine the impact of malperfusion syndrome on in-hospital mortality and midterm survival after emergency aortic arch reconstruction for acute type A aortic dissection.
METHODS
This was an observational study of aortic surgeries from 2010 to 2018. All patients with acute type A aortic dissection undergoing open aortic arch reconstruction were included. Patients were dichotomized by the presence or absence of malperfusion syndrome and were analyzed for differences in short-term postoperative outcomes, including morbidity and in-hospital mortality. Kaplan-Meier survival estimation and multivariable Cox analysis were performed to identify variables associated with survival.
RESULTS
A total of 467 patients undergoing aortic arch reconstruction for acute type A aortic dissection were identified, of whom 332 (71.1%) presented without malperfusion syndrome and 135 (28.9%) presented with malperfusion syndrome. Patients with malperfusion syndrome had higher in-hospital mortality (21.5% vs 5.7%) than patients without malperfusion syndrome. After multivariable adjustment, malperfusion syndrome was associated with worse survival (hazard ratio, 2.43, 95% confidence interval, 1.61-3.66, P < .001) compared with patients without malperfusion syndrome. The predicted risk of mortality increased as the number of malperfused vascular beds increased. Patients with coronary malperfusion syndrome and neuro-malperfusion syndrome had reduced survival compared with the rest of the cohort (P < .05).
CONCLUSIONS
Malperfusion syndrome is associated with higher in-hospital mortality and reduced survival for patients with acute type A aortic dissection, with the risk of mortality increasing as the number of malperfused vascular beds increases. Coronary malperfusion syndrome and neuro-malperfusion syndrome may represent a high-risk subgroup of patients presenting with acute type A aortic dissection complicated by malperfusion syndrome. Finally, malperfusion syndrome may benefit from immediate surgical intervention to restore true lumen perfusion, as opposed to operative delay. | 10.1016/j.jtcvs.2022.04.051 |
pubmed_360_4762 | Statistical investigations indicate that disappearance of bile ducts, estimated by a histometric method, was more extensive in symptomatic than in asymptomatic patients with primary biliary cirrhosis. The extent and degree of intrahepatic bile duct disappearance in PBC is related to the degree of copper granule deposition in the hepatocytes, the degree of atypical ductular proliferations and the fibrous septa formation. Bile plug formation and chemically determined copper content are not so well related to the bile duct disappearance, while periportal lymphoid cell infiltration is not related to the degree or extent of bile duct disappearance at all. | pubmed_360_4762 |
pubmed_272_12506 | The Clara cell secretory protein (CCSP, also CC-10/uterglobin) is a 16-kD homodimeric protein abundantly expressed in the airways of mammals. Although the molecular function is unknown, gene-targeting studies indicate CCSP as a regulator of lung inflammation following acute respiratory infection or injury. CCSP is decreased in the lungs of mice following acute Pseudomonas aeruginosa (P.a.) infection. In the present study, the role of decreased promoter function in the regulation of CCSP by P.a. was assessed using an in vitro co-culture system and in vivo studies of transgenic mice. CCSP promoter activity in lung epithelial cells was markedly decreased by P.a. or tumor necrosis factor-alpha (TNF-alpha) in a dose-dependent manner. Regulation of CCSP promoter function by either P.a. or TNF-alpha was localized to the proximal 166 bp flanking region of the CCSP promoter activity. Decreased regulation of the CCSP promoter by P.a. or TNF-alpha was specific to CCSP, as human surfactant protein D (SP-D) promoter activity was unaffected or increased by P.a. or TNF-alpha, respectively. A neutralizing antibody against human TNF-alpha was able to reverse both the TNF-alpha- mediated as well as P.a.-mediated decrease in CCSP promoter function in lung epithelial cells. TNF-alpha secretion by lung epithelial cells coincided with the decrease in CCSP promoter function following P.a. administration. Using a transgenic mouse model, P.a. administration to the lung markedly attenuated CCSP promoter-conferred gene expression in vivo. The attenuation of CCSP promoter activity in lung epithelial cells by P.a. involves, in part, autocrine/paracrine secretion of TNF-alpha, which in turn regulates CCSP transcription through cis-active elements in the proximal promoter region. | 10.1165/ajrcmb.26.2.4718 |
pubmed_777_12948 | Effects of inhibitors of tyrosine kinases (K-252a, genistein) and of phospholipase A2 (bromophenacetyl bromide) on viability of PC12 cells are studied in the presence of hydrogen peroxide and ganglioside GM1. The degree of inhibition of hydrogen peroxide cytotoxic effect by ganglioside GM1 amounted to 52.8 +/- 4.3 %. However, in the presence in the medium of 0.1 and 1 microM inhibitors of tyrosine kinase of Trk-receptors (K-252a) it was as low as 32.7 +/- 6.5 % and 11.7 +/- 9.8 %, respectively. GM1 prevented Na+, K+-ATPase produced by H2O2, but in the presence of 1 microM K-252a this effect was practically not pronounced. In the presence of another inhibitor of tyrosine kinases--genistein, a tendency for a decrease of the GM1 protective effect was observed at its concentrations 0.1 and 1 microM, whereas at a higher concentration 10 microM genistein depressed the GM1 neuroprotective effect statistically significantly. It was found that inhibitor of phospholipase A2 bromophenacetyl bromide did not affect the action of GM1 aimed at increasing the viability of cells under action of hydrogen peroxide on them. It seems that this enzyme is not involved in the cascade of reactions participating in realization of the ganglioside protective effect. Thus, inhibitor of tyrosine kinase of Trk-receptors K-252 decreases or practically prevents the ganglioside GM1 neuroprotective effect of PC12 cells under stress conditions; the same ability is characteristic of genistein--an inhibitor of tyrosine kinases of the wider spectrum of action. | pubmed_777_12948 |
pubmed_599_1130 | The most common oral diseases have a microbial aetiology. Pathogenic bacteria liberate a number of irritating agents including a lipopolysaccharide (LPS) that activates pro-inflammatory cytokines promoting increased activity of polymorphonucleocytes (PMN). Release of PMN-derived free radicals into an infected gingival area affects gums, periodontal ligaments and alveolar bone. Berries of Lonicera caerulea L. (blue honeysuckle) are rich in phenolics, particularly phenolic acids, flavonoids and anthocyanins that have multiple biological activities in vitro and in vivo such as antiadherence, antioxidant and anti-inflammatory. Studies have shown that polyphenols suppress a number of LPS-induced signals and thus could be effective against gingivitis. Here we assessed effects of the polyphenolic fraction of L. caerulea fruits (PFLC; containing 77% anthocyanins) on LPS-induced oxidative damage and inflammation in human gingival fibroblasts. Application of PFLC (10-50mug/ml) reduced reactive oxygen species (ROS) production, intracellular glutathione (GSH) depletion as well as lipid peroxidation in LPS-treated cells. PFLC treatment also inhibited LPS-induced up-regulation of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) and it suppressed expression of cyclooxygenase-2 (COX-2). The effects are presumably linked to its antioxidant and anti-inflammatory activities and suggest its use in attenuating the inflammatory process, including periodontal disease. | 10.1016/j.fct.2010.03.024 |
pubmed_291_463 | BACKGROUND
Treatment of ovarian cancer is still challenging especially in recurrent platinum refractory cases. Sunitinib is a multi tyrosine kinase inhibitor targeting receptors for vascular endothelial growth factor and platelet-derived growth factor which play a role in tumor angiogenesis. It has been approved for the treatment of recurrent gastro intestinal stroma tumors and metastatic renal cancer.
MATERIALS AND METHODS
In this study, sunitinib was tested for its effectiveness as a single agent in an ovarian cancer xenograft mouse model. Skov3 cells stably expressing firefly luciferase were injected into SCID beige mice. Mice received either 40 mg/kg bodyweight sunitinib or vehicle control. Tumor growth was monitored longitudinally by luciferase signal.
RESULTS
Sunitinib significantly reduced tumor growth (p=0.0052) and peritoneal metastases, and was associated with a significantly reduced microvessel density count (p<0.001).
CONCLUSION
These results suggest that clinical trials are warranted for the evaluation of sunitinib for treatment of patients with recurrent or advanced ovarian cancer. | pubmed_291_463 |
pubmed_433_24868 | High-frequency electromagnetic fields can have a negative effect on both the human body and electronic devices. The devices and systems utilized in radio communications constitute the most numerous sources of electromagnetic fields. The following research investigates values of the electric component of electromagnetic field intensification determined with the ESM 140 dosimeter during the flights of four aircrafts-Cessna C152, Cessna C172, Aero AT3 R100, and Robinson R44 Raven helicopter-from the airport in Depultycze Krolewskie near Chelm, Poland. The point of reference for the obtained results were the normative limits of the electromagnetic field that can affect a pilot in the course of a flight. The maximum value registered by the dosimeter was E = 3.307 V/m for GSM 1800 frequencies. | 10.3390/s19245537 |
pubmed_1041_1367 | We present the first report on the synthesis of chiral ureas, (R)- and (S)-2-heptylurea, and their gelling behaviors. The ureas were prepared by the reactions of chiral amines and phenyl carbamate in the presence of triethylamine. On cooling from homogeneous solutions, the chiral ureas form gels in water and various nonpolar organic solvents, such as cyclohexane, toluene, and tetrachloromethane, while the racemate gelatinize only toluene and tetrachloromethane among the solvents we examined. The gelling ability of the enantiomeric urea is higher than the racemate, as the critical gelling concentrations in toluene, for example, were 0.2% and 0.7% (wt/wt), respectively. The enhanced gelling ability of the enantiomeric ureas is due to the 1D supramolecular structure formed during gelation. In contrast, the racemate crystallizes into two-dimensional lamellae, where the (R)- and (S)-2-heptylurea exist alternatingly in a plane (P2(1)/c space group). Powder X-ray diffraction pattern of the enantiomeric urea showed that it has a different crystal lattice from that of the racemate, implying that the steric effect by the methyl group at the chiral center prevents the pure enantiomers from having 2D hydrogen bonding networks, which lead to sheet-like structures for the racemate and the achiral analog. Thus the pure enantiomers self-organize into one-dimensional fibrous structures. The simplicity and the ambidextrous gelling behaviors of the chiral ureas in forming both hydrogels and organogels present numerous possibilities for future applications. | 10.1016/j.jcis.2011.02.006 |
others_293_6749 | In baroreceptor-denervated animals, sympathetic nerve discharge (SND) displays a 2- to 6-Hz rhythm. Current theories suggest that this rhythm is generated by a neural oscillator in the medulla. In urethan-anesthetized rats, we have examined the effect on the 2- to 6-Hz rhythm of lumbar SND produced by 1) altering the firing pattern of a major output of this medullary network [the rostral ventrolateral medulla (RVLM)] and 2) disrupting the interactions between medulla and spinal cord (SC). Microinjection of muscimol [γ-aminobutyric acid (GABA) agonist] unilaterally or a mixture of kynurenic acid (KYN; broad spectrum, excitatory amino acid antagonist) and bicuculline (GABA(A) antagonist) bilaterally into RVLM produced little effect on the 2- to 6-Hz rhythm. Intrathecal injection of KYN or transection of the cervical SC also had little effect once SND had been restored by intrathecal injection of kainic acid (excitatory amino acid agonist). Thus, whereas an excitatory input to the spinal cord is required for the generation of basal SND, patterning of this input is not critical for production of the 2- to 6-Hz SND rhythm that, in this species, may be essentially of spinal orig | 10.1152/ajpregu.1993.264.5.r938 |
pubmed_856_13496 | The discovery of a new gold(I)-catalyzed cascade reaction involving cyclization onto a vinylammonium, 3-aza-Cope rearrangement, and Mannich cyclization is reported. A variety of fused nitrogen heterocycles were prepared from simple cyclic tertiary amines using 1-5 mol % of a AuCl(PPh3)/Ag[C5(CN)5] cocatalyst system. The developed reaction was used in a study aimed at synthesizing cephalotaxine. A five-step operation from norhydrastinine provided demethylcephalotaxinone in 39.1% overall yield, which was transformed to (-)-cephalotaxine in two steps. | 10.1021/acs.orglett.1c01323 |
pubmed_348_24794 | Dextromethorphan (DEM) is a widely used probe drug for human cytochrome P450 2D6 isozyme activity assessment by measuring the ratio between DEM and its N-demethylated metabolite dextrorphan (DOR). DOR is excreted in urine mainly conjugated to glucuronic acid. Prior to quantification, DOR must be deconjugated to avoid variability caused by the polymorphic glucuronosyltransferase enzyme. A chemical hydrolysis method was optimized using a chemometric approach. Three factors (acid concentration, hydrolysis time and temperature) were selected and simultaneously varied to study their effect on conjugated DOR hydrolysis. Hydrolysis conditions that maximize DOR release without significant degradation of both DEM and DOR were chosen and results were compared to those obtained by enzymatic method using beta-glucuronidase. An HPLC method with fluorescence detection was developed for the simultaneous quantitation of DEM, DOR and levallorphan, used as an internal standard. Separation was performed on a phenyl analytical column (150 mmx4.6 mm i.d., 5 microm) with a mobile phase consisting of 18% acetonitrile and 50 mM phosphoric acid (pH 3). The overall analytical procedure was validated and showed good performances in terms of selectivity, linearity, sensitivity, precision and accuracy. Finally, this assay was used to determine DEM/DOR molar ratios in fibromyalgia patients for the purpose of determining phenotype status for the CYP2D6. | 10.1016/j.jchromb.2007.11.019 |
pubmed_878_17614 | Argumentation is presented which indicates that the additive decomposition of the total genetic variation of a population into variation within and between (among) its subpopulations suffers from conceptual inconsistency. While the measurement of variation between subpopulations can be shown to be identical to the measurement of subpopulation differentiation, the notion of variation within subpopulations, when viewed as a single measurement, cannot be derived as an independent and cogent concept. Rather, it appears to be merely technically defined as the arithmetic difference between the total variation and the variation between subpopulations, and this difference happens to be non-negative for concave measures of variation such as the (statistical) variance or certain measures of genetic diversity. In order to overcome the conceptual inconsistency, "variation between subpopulations" could be regarded as subpopulation differentiation and the notion of "variation within subpopulations" could be replaced by measurements of the degree to which the variation in the total population is represented within the subpopulations. A complementary situation with respect to total variation is thus realized once more, and appropriate measures can be directly derived from existing ones. | 10.1007/BF00273686 |
pubmed_325_22203 | Bereavement may bring negative impacts on the mind, body, and spiritual well-being of grieving persons. Some bereaved persons with chronic fatigue syndrome- (CFS-) illness experience a dual burden of distress. This study investigated the effects of bereavement on CFS-like illness by comparing bereaved and nonbereaved participants. It also adopted a random group design to investigate the effectiveness of Qigong on improving the well-being of bereaved participants. The Qigong intervention comprised 10 group sessions delivered twice a week for 5 weeks and home-practice for at least three times a week lasting 15-30 minutes each. The participants' fatigue, anxiety, and depression, quality of life (QoL), and spiritual well-being were measured at baseline and 3 months after treatment. The bereaved participants experienced significantly greater mental fatigue (16.09 versus 14.44, p = 0.017) and lower physical QoL (34.02 versus 37.17, p = 0.011) than their nonbereaved counterparts. After 3 months, the mental fatigue (-8 versus -4, p = 0.010) and physical fatigue (-10 versus -5, p = 0.007) experienced by intervention group had declined significantly, and improvements on their spirituality (14 versus -2, p = 0.013) and psychological QoL (8.91 versus 0.69, p = 0.002) scores exceeded those of the control group. | 10.1155/2015/631410 |
pubmed_495_2455 | A total of 427 patients with major chest trauma were treated in two major hospitals in Abu Dhabi, United Arab Emirates, during a 10-year period. In 64 of 426 patients, flail chest injury was the dominant factor among other injuries that were insignificant. Among 64 cases of flail chest injury, 25 were managed by internal fixation of ribs, whereas the remaining 38 were managed by endotracheal intubation and intermittent positive-pressure ventilation alone. Of the patients treated by internal fixation 80% (21/26) were weaned from the ventilator within an average of 1.3 days, whereas the remaining 20% (5/26) continued to need assisted ventilation for a longer duration; the total average duration of assisted ventilation for the whole group was 3.9 days. In comparison, among 38 patients with flail chest injury treated by endotracheal intubation and ventilation alone, the average duration of assisted ventilation was 15 days. In the group treated by internal fixation 11% (3/26) of the patients ultimately required a tracheotomy, whereas in the patients treated by intubation and ventilation alone tracheostomy was required in 37% (14/38) of the cases. In the group treated by internal fixation, chest infection was documented in 15% (4/26), septicemia in 4% (1/26), and barotrauma in 0%; in the other group these complications occurred in 50% (19/38), 24% (9/38), and 8% (3/38) of the cases, respectively. The mortality rate was 8% (2/26) in the surgically treated patients, whereas it was 29% (11/38) in the other group. All the deaths in both groups were ascribed to adult respiratory distress syndrome. Average stay in the intensive care unit was 9 days for the patients treated by internal fixation, whereas it was 21 days in the group treated by intubation and ventilation alone. The treatment of flail chest injury in our series by internal fixation resulted in speedy recovery, decreased complications, and better ultimate cosmetic and functional results and proved to be cost effective. | 10.1016/S0022-5223(95)70030-7 |
pubmed_824_8224 | BACKGROUND
Trajectories of anxiety symptoms in people with type 2 diabetes (T2D) and their associations with diabetes health outcomes have not been investigated. This study examined latent longitudinal trajectories of anxiety symptoms in adults with T2D and their associations with incident cardiovascular disease (CVD).
METHODS
Data were from the Evaluation of Diabetes Treatment Study, a community-based cohort study of adults aged 40-76years with T2D. Anxiety and CVD were assessed by self-report at baseline and at four annual follow-up assessments. N=832 participants without cardiovascular disease at baseline and 12-month follow-up were included in the present study. Group-based trajectories of anxiety at baseline, 12-month follow-up, and 24-month follow-up were modelled using latent class growth modeling. Associations between anxiety trajectories and CVD reported at 24-, 36-, or 48-month follow-ups were examined with logistic regression analysis adjusted for sociodemographic and lifestyle characteristics.
RESULTS
Four distinct anxiety trajectories were identified, reflecting chronically low (39.4%), chronically moderate-low (47.4%), chronically moderate-high (11.1%), and chronically high (2.2%) anxiety. The likelihood of CVD was greater for the chronically moderate-low (OR=2.23, 95% CI=1.36-3.66), chronically moderate-high (OR=3.05, 95% CI=1.54-6.02), and chronically high (OR=3.61, 95% CI=1.09-12.00) anxiety trajectory groups compared to the chronically low anxiety group.
CONCLUSION
The identified latent trajectories reflected three groups with chronic courses of anxiety symptoms at different levels of severity and one group with chronically low levels of anxiety. Chronic anxiety, even at subthreshold levels, was associated with an increased risk of CVD among people with T2D. | 10.1016/j.jpsychores.2017.11.015 |
pubmed_275_9670 | Human myometrial smooth muscle cells (MSMC) showed high protein kinase C (PKC) activity when a maximal dose of PKC-activating phorbol ester was used, while uterine leiomyomal cells (ULMC) showed only 6-12% of PKC activity. MSMC exhibited a low proliferation rate, whereas ULMC exhibited a high proliferation rate. These different cell types of MSMC and ULMC responded to 10 U/mL thrombin, with a twofold stimulation of PKC activity. Downregulation of PKC activity was found when MSMC were treated with phorbol ester or with transforming growth factor-beta2. We concluded that differences in PKC activity exist between MSMC and ULMC, which may be related to their different proliferative activity. ULMC treated with Euonymus alatus (Thunb.) Sieb (EA), known as "gui-jun woo" in Korea, which is used for leiomyomal tumors, exhibited a much lower proliferation rate than untreated cells, suggesting that EA inhibited the cellular proliferation of ULMC. The PKC activity of MSMC by EA treatment (50 microg/mL) changed little. ULMC showed increased PKC activity by addition of EA, indicating that PKC is activated by EA. The EA-treated ULMC were differentiated into phenotypes characteristic for normal untransformed cells, since the EA-treated cells possess higher PKC activity than untreated cells. | 10.1111/j.1525-1438.2005.15228.x |
pubmed_1073_5849 | We've estimated the cellular and metabolic part of geroprophylactic effects of short synthetic tripeptides vesugen and pinealon for correction of the biological age. 32 people (18 men, 12 women) aged 41-83 years with polymorbidity and the organic brain syndrome in remission participated in the study. The preparations of "Pinealon" and "Vesugen" have had the significant anabolic effect. They have improved the activity of the Central nervous system and other vital organs, which slows the rate of aging by biological age indicators. Vesugen has demonstrated more visible geroprophylactic effect than Pinealon. At the same time we've found the prooxidant activity through chemiluminescence. Decrease of markers CD34+ positive hematopoietic polypotent cells in blood has shown significant inhibition of hemopoiesis. Apparently, the cells have not been involved in the adaptive reactions. Pinealon and Vesugen haven't affected the degree of chromatin condensation, so they are safe on nuclear genetic level. This property should be studied in future. In geriatric practice, we recommend to apply the peptides Pinealon and Vesugen as geroprotectors anabolic neuroprotective and no antioxidant type for reducing the rate of aging in patients with the organic brain syndrome vascular and/or traumatic genesis. | pubmed_1073_5849 |
pubmed_273_2509 | Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking water. The present study was designed to investigate the potential adverse effects of maternal exposure to CAN on fetal liver in mice. Based on an initial dose-response experiment, CAN (25mg/(kgday)) was given orally to pregnant mice at gestation day (GD) 6, till GD 18. Fetuses were collected and fetal livers were used for assessing oxidative status, apoptosis and histopathological changes. Maternal exposure to CAN resulted in observed oxidative stress and redox imbalance in fetal liver tissues as marked by significant decrease in reduced glutathione (GSH) and elevation of oxidized glutathione (GSSG), malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in genomic DNA. Further, CAN induced apoptosis as indicated by a significant increase in binding of Hoechst reagent to damaged DNA fragments of fetal liver and enhancement of the activity of caspase-3 in cytosolic fractions of fetal livers. Histopathological examination of fetal livers of CAN-treated mice showed hepatocytes with vacuolated cytoplasm, karyolysis and karyorrhexis as well as depletion of their glycogen content. In conclusion, maternal exposure to CAN adversely affects mouse fetal livers as evidenced by the induction of oxidative stress, apoptosis and histopathological changes. | 10.1016/j.toxlet.2009.06.867 |
pubmed_724_12807 | INTRODUCTION
Epilepsy and the epileptic syndromes are common neurological diseases and represent an important public health problem that has given rise to marked social and healthcare concerns.
AIM
To analyse the changes in the consumption of antiepileptic drugs in the Basque Country Autonomous Community over a 13 year period (1992-2004).
MATERIALS AND METHODS
The consumption of the N03 subgroup has been studied using data from the ECOM database of the Spanish Ministry of Health and Consumer Affairs, which records the number of drug packets dispensed on National Health Service prescription. The results are expressed as defined daily doses per 1,000 inhabitants per day (DID).
RESULTS
A significant increase is observed in the consumption of antiepileptic drugs over the study period (5.53-9 DID). The most widely used drugs were phenobarbital, carbamazepine, valproic acid and phenytoin and, in recent years, the extensive use of gabapentin is of particular note.
CONCLUSION
Epidemiological studies on epilepsy are difficult to perform due to a number of methodological problems which are caused fundamentally by the heterogeneity of the disease. Pharmacoepidemiological studies constitute a simple, effective, low-cost tool for estimating the prevalence of the disease, and furthermore enumerates the drugs used, thus contributing to a rational use of these drugs. | pubmed_724_12807 |
pubmed_315_17789 | BACKGROUND
Myocardial performance index (MPI) has been used to assess global ventricular function in different types of cardiac disease. Thyroid hormones influence cardiac performance directly and indirectly by changes in peripheral circulation. The aim of this study was to evaluate the possible effect of central hypothyroidism (CH) on MPI.
METHODS
The study included 28 control subjects and 7 patients with CH without cardiac disease. MPI was defined as the sum of isovolumetric contraction time (ICT) and isovolumetric relaxation time divided by ejection time. Patients were submitted to hormonal therapy with thyroxin and the study was repeated after 35 to 42 days.
RESULTS
MPI was significantly higher in patients with CH (0.54 +/- 0.08) than in control subjects (0.40 +/- 0.05) (P =.002). The increase in MPI was caused by the prolongation of ICT without a significant variation of isovolumetric relaxation time and ejection time. After hormonal therapy there was a significant reduction of MPI (0.54 +/- 0.08 vs 0.42 +/- 0.07; P =.028) and ICT.
CONCLUSION
MPI was increased in patients with untreated CH. The increase was related to prolongation of ICT and reverted by hormonal therapy. | 10.1016/j.echo.2004.03.010 |
pubmed_708_6105 | Dot-blot analysis of Chlamydia trachomatis elementary bodies (EBs) with monospecific polyclonal antibodies demonstrated that the 18-kilodalton binding protein is surface exposed. Immunoelectron microscopy with whole serovar L2 EBs and ultrathin sections confirmed this finding. In addition, only the extracellular EBs and not the intracellular reticulate bodies were labeled with immunogold. | 10.1128/jb.172.6.3524-3528.1990 |
pubmed_510_13737 | A study of 72 temporomandibular joints of adults without any gross signs of degenerative changes was made, in order to analyse the stress on individual regions of the joint, and to determine the path of the split line pattern in the articular cartilage. The cancellous architecture and the material distribution in the juxta-articular bone were also investigated. Zones of high-density compact substance in the lateral region of the joint, and the presence of attractive singular points in the split line orientation in this localization, suggest great stress on the lateral part of the temporomandibular joint. This increased stress in the lateral region is confirmed by the fact that arthrotic changes in the temporomandibular joint first almost always appear laterally. Degenerative changes usually originate at the articular disc, affect the articular tubercle after a delay, and finally spread to the condyle. Besides the greater physiological, mechanical stress on the lateral region of the joint, the force acting on every individual temporomandibular joint is influenced by the dental condition. The molars and bicuspids serving as a support zone play a decisive role in this context. | 10.1007/BF00185839 |
pubmed_653_3476 | The reaction of Na(12)[Bi(2)W(22)O(74)(OH)(2)]·44H(2)O, Na(9)[BiW(9)O(33)]·16H(2)O, lanthanide chloride and Na(2)CO(3) in aqueous solution at a pH value of about 7.0 resulted in the three unprecedented giant lanthanide-tungstobismuthate clusters Na(x)H(22-x)[(BiW(9)O(33))(4)(WO(3)){Bi(6)(μ(3)-O)(4)(μ(2)-OH)(3)}(Ln(3)(H(2)O)(6)CO(3))]·nH(2)O {Ln = Pr(3+) (1), Nd(3+) (2), La(3+) (3), x = 22 (1), 22 (2), 20 (3), n = 95 (1), 91 (2), 73 (3)}. These three complexes represent the first examples of lanthanide ions encapsulated in polyoxotungstobismuthates and the largest polytungstobismuthates so far. Furthermore, a [{Bi(6)(μ(3)-O)(4)(μ(2)-OH)(3)}](7+) polyoxo cation was incorporated into the structure of these compounds. All complexes are characterized by single-crystal X-ray diffraction, IR spectra, electronic spectroscopy, thermogravimetric and elemental analysis. Magnetic investigation revealed that the progressive depopulation of excited Stark sublevels of the lanthanide ions at low temperature and the weak antiferromagnetic interaction between the neighboring metal centres are responsible for the magnetic properties of 1 and 2. The original synthesis strategy in this work may open a gateway to assembly of large lanthanide-tungstobismuthates clusters and novel multifunctional solid materials in aqueous solution under mild conditions. | 10.1039/c2dt11478j |
pubmed_48_6631 | This Special Issue on CRISPR comprises a series of nine reviews that cover the development and application of this technology to an array of biological systems. We hope that you will find these pieces to be of interest; we certainly found them to be practically helpful and thoughtfully written, and we are grateful to their authors for taking the time to write for The FEBS Journal. | 10.1111/febs.13823 |
pubmed_286_3235 | In one sense, formal specification and verification have been highly successful: techniques have been developed in pioneering academic research, transferred to software companies through training and partnerships, and successfully deployed in systems with national significance. Altran UK has been in the vanguard of this movement. This paper summarizes some of our key deployments of formal techniques over the past 20 years, including both security- and safety-critical systems. The impact of formal techniques, however, remains within an industrial niche, and while government and suppliers across industry search for solutions to the problems of poor-quality software, the wider software industry remains resistant to adoption of this proven solution. We conclude by reflecting on some of the challenges we face as a community in ensuring that formal techniques achieve their true potential impact on society.This article is part of the themed issue 'Verified trustworthy software systems'. | 10.1098/rsta.2015.0402 |
pubmed_1053_17823 | The specificity of vesicular transport in a cell is determined by the formation of vesicles with specific contents from a donor compartment and their selective fusion with the appropriate acceptor compartment. Several of the latter fusion steps have been investigated in detail using cell-free systems, and work with these systems as well as genetic evidence has revealed a role for GTP-binding proteins in membrane fusion processes. We have reconstituted the formation of constitutive secretory vesicles and immature secretory granules from the trans Golgi network in a cell-free system. We show here that the budding of both types of post-Golgi vesicles is inhibited by non-hydrolysable analogues of GTP, which suggests a more widespread role for GTP-binding proteins in membrane traffic than previously assumed. | 10.1038/347207a0 |
pubmed_852_23228 | Proteomics-based clinical studies have been shown to be promising strategies for the discovery of novel biomarkers of a particular disease. Here, we present a study of hepatocellular carcinoma (HCC) that combines complementary two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography (LC-MS)-based approaches of quantitative proteomics. In our proteomic experiments, we analyzed a set of 14 samples (7 × HCC versus 7 × nontumorous liver tissue) with both techniques. Thereby we identified 573 proteins that were differentially expressed between the experimental groups. Among these, only 51 differentially expressed proteins were identified irrespective of the applied approach. Using Western blotting and immunohistochemical analysis the regulation patterns of six selected proteins from the study overlap (inorganic pyrophosphatase 1 (PPA1), tumor necrosis factor type 1 receptor-associated protein 1 (TRAP1), betaine-homocysteine S-methyltransferase 1 (BHMT)) were successfully verified within the same sample set. In addition, the up-regulations of selected proteins from the complements of both approaches (major vault protein (MVP), gelsolin (GSN), chloride intracellular channel protein 1 (CLIC1)) were also reproducible. Within a second independent verification set (n = 33) the altered protein expression levels of major vault protein and betaine-homocysteine S-methyltransferase were further confirmed by Western blots quantitatively analyzed via densitometry. For the other candidates slight but nonsignificant trends were detectable in this independent cohort. Based on these results we assume that major vault protein and betaine-homocysteine S-methyltransferase have the potential to act as diagnostic HCC biomarker candidates that are worth to be followed in further validation studies. | 10.1074/mcp.M113.028027 |
pubmed_466_6889 | Some cellular immune responses initiate the coagulation protease cascade and promote the formation of fibrin. Local fibrin deposition is requisite for the induration associated with delayed hypersensitivity reactions. The deposited fibrin also is catabolized. In the present study we demonstrate that plasmic cleavage of fibrinogen results in the generation of immunosuppressive activity in vitro that is not expressed by the intact molecule. This property is associated with small dialyzable peptides recovered from advanced plasmic digests of fibrinogen. The peptides inhibit phytohemagglutinin-, pokeweed mitogen-, and allogeneic cell-stimulated blastogenesis as well as proliferation in a dose-dependent fashion. The suppression of lymphocyte responses does not result from loss of cells or their viability. Suppression requires the presence of the peptides at the time of, or immediately after, the exposure of cells to the appropriate stimulus, and is manifest as both a delay and an absolute inhibition of [3H]thymidine uptake. Human peptides inhibit the response of murine spleen cells to mitogens, and B and T lymphocyte classes appear to be equally sensitive to suppression. Thymidine uptake by two continuous lymphoblastoid cell lines also is inhibited by the peptides, indicating a direct effect of the fibrinogen-derived peptides on lymphocytes. In contrast, the peptides stimulate thymidine uptake by a diploid fibroblast line, suggesting selectivity in the biologic effects of the peptides. These observations indicate that in addition to its primary role in hemostasis, the participation of fibrinogen and its derivative fibrin in inflammatory lesions includes the release of lymphocyte-suppressive peptides. This may play a role in regulation of the evolution of immunologic lesions in vivo. | pubmed_466_6889 |
pubmed_878_16018 | OBJECTIVE
Many skills needed to provide patients with safe, timely, and adequate anesthesia care during humanitarian crisis and disaster relief operations are not part of the daily routine before deployment. An exploratory study was conducted to identify preparedness, knowledge, and skills needed for deployment to complex emergencies.
METHODS
Anesthesiologists who had been deployed during humanitarian crisis and disaster relief operations completed an online questionnaire assessing their preparedness, skills, and knowledge needed during deployment. Qualitative data were sorted by frequencies and similarities and clustered accordingly.
RESULTS
Of 121 invitations sent out, 55 (46%) were completed and returned. Of these respondents, 24% did not feel sufficiently prepared for the deployment, and 69% did not undertake additional education for their missions. Insufficient preparedness involved equipment, drugs, regional anesthesia, and related management.
CONCLUSIONS
As the lack of preparation and relevant training can create precarious situations, anesthesiologists and deploying agencies should improve preparedness for anesthesia personnel. (Disaster Med Public Health Preparedness. 2013;0;1-5). | 10.1017/dmp.2013.40 |
pubmed_681_13087 | In the present paper we discuss the possible form and meaning of Fisher, bound, and physical information in some special cases. It seems to us that an unusual choice of bound information may describe the behavior of dissipative processes. | 10.1103/PhysRevE.68.016121 |
pubmed_686_17704 | Process and tubercle fractures of the talus and calcaneus can be a source of significant pain and dysfunction. Successful management requires extensive knowledge of the complex osseoligamentous anatomy of the hindfoot. The large posterior process of the talus is composed of a medial and a lateral tubercle; an os trigonum may exist posterior to the lateral tubercle. The talus has a lateral process that articulates with the fibula and subtalar joint; the calcaneus possesses a frequently injured anterior process that articulates with the cuboid. Injury to these hindfoot structures is caused by inversion and eversion of the ankle, which can occur during athletic activity. These injuries often are misdiagnosed as ankle sprains. A high degree of clinical suspicion is warranted, and specialized radiographs or other imaging modalities may be required for accurate diagnosis. Nonsurgical management with cast immobilization is frequently successful when the fracture is correctly diagnosed acutely. Large fragments may be amenable to open reduction and internal fixation. Untreated, chronic injuries can cause significant pain and functional impairment that may be improved substantially with late surgical intervention. | 10.5435/00124635-200512000-00002 |
pubmed_1115_7075 | BACKGROUND
The purpose of this study was to describe our institutional experience in using inhaled prostacyclin as a selective pulmonary vasodilator in patients with pulmonary hypertension, refractory hypoxemia, and right heart dysfunction after cardiothoracic surgery.
METHODS
Between February 2001 and March 2003, cardiothoracic surgical patients with pulmonary hypertension (mean pulmonary artery pressure >30 mm Hg or systolic pulmonary artery pressure >40 mm Hg), hypoxemia (PaO(2)/fraction of inspired oxygen <150 mm Hg), or right heart dysfunction (central venous pressure >16 mm Hg and cardiac index <2.2 L.min(-1).m(-2)) were prospectively administered inhaled prostacyclin at an initial concentration of 20,000 ng/mL and then weaned per protocol. Hemodynamic variables were measured before the initiation of inhaled prostacyclin, 30 to 60 minutes after initiation, and again 4 to 6 hours later.
RESULTS
One hundred twenty-six patients were enrolled during the study period. At both time points, inhaled prostacyclin significantly decreased the mean pulmonary artery pressure without altering the mean arterial pressure. The average length of time on inhaled prostacyclin was 45.6 hours. There were no adverse events attributable to inhaled prostacyclin. The average cost for inhaled prostacyclin was 150 US dollars per day. Compared with nitric oxide, which costs 3000 US dollars per day, the potential cost savings over this period were 681,686 US dollars.
CONCLUSIONS
Inhaled prostacyclin seems to be a safe and effective pulmonary vasodilator for cardiothoracic surgical patients with pulmonary hypertension, refractory hypoxemia, or right heart dysfunction. Overall, inhaled prostacyclin significantly decreases mean pulmonary artery pressures without altering the mean arterial pressure. Compared with nitric oxide, there is no special equipment required for administration or toxicity monitoring, and the cost savings are substantial. | 10.1016/j.jtcvs.2003.11.035 |
pubmed_622_18162 | The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1-associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1-specific signals are required for the platelet-induced augmentation of polymorphonuclear leukocyte (PMN) effector functions (provoked by LPS). However, TREM-1 interaction with its ligand is not required for platelet/PMN complex formation, which is dependent on integrins and selectins. Taken together, the results indicate that the TREM-1 ligand is expressed by platelets, and the TREM-1/ligand interaction contributes to the amplification of LPS-induced PMN activation. Our results shed new light on our understanding of TREM-1 and its role in the innate inflammatory response in infections and might contribute to the development of future concepts to treat sepsis. | 10.1182/blood-2007-01-069195 |
pubmed_715_8352 | We have characterized a series of mesostructured aluminophosphate (AlPO)-based lamellar materials by several solid-state NMR techniques. In particular, we were able to estimate the average number of Al atoms and identify the nature of other ancillary groups in the second coordination sphere for each P site. Our work has shown that a combination of several dipolar coupling-based (31)P/(27)Al double-resonance techniques such as transfer of population in double-resonance (TRAPDOR), rotational echo double-resonance (REDOR), and heteronuclear correlation spectroscopy (HETCOR) as well as (1)H --> (31)P cross polarization (CP) can provide more detailed structural information regarding the local environments of P and Al atoms in AlPO-based mesostructured materials, which is not readily available from straightforward (31)P and (27)Al magic-angle spinning (MAS) experiments. | 10.1021/ja040167i |
pubmed_340_24282 | Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor with actions that are dependent on circumstances, including dose, target cell type, and context. TGF-beta can elicit both growth-promoting and growth-suppressive activities. In normal tissues, TGF-beta generally acts to restrict growth and maintain differentiation. However, during tumorigenesis, changes in TGF-beta expression and cellular responses can promote tumorigenesis. The present study examines the effects of TGF-beta on the nontumorigenic human prostatic epithelial cell line BPH1 and on three derivative tumorigenic sublines BPH1(CAFTD)1, BPH1(CAFTD)3, and BPH1(CAFTD)5. The data show that TGF-beta has different effects on the nontumorigenic and tumorigenic cells. The nontumorigenic cells are growth inhibited by TGF-beta. In contrast, the tumorigenic sublines are not growth inhibited but instead undergo an epithelial to mesenchymal transformation (EMT) in response to TGF-beta. The tumorigenic lines show constitutively elevated levels of phosphorylated Akt, which modulates their response to TGF-beta by blocking Smad3 and p21 nuclear translocation. On TGF-beta stimulation of the tumorigenic sublines, the activated Akt allows the cell to escape cell cycle arrest. The phosphatidylinositol 3-kinase/Akt pathway is also involved in TGF-beta-induced EMT, defined here by induction of vimentin expression and enhanced cellular motility. In vivo, tumorigenic cells with constitutively active TGF-beta signaling show increased invasion with EMT, which express vimentin, located specifically at the invasive front of the tumor. These data indicate that following malignant transformation TGF-beta can play a direct role in promoting prostatic cancer and further that these responses are context specific in vivo. | 10.1158/0008-5472.CAN-05-4451 |
pubmed_857_9745 | A 35-mm slide scanner digital imaging system was tested for its suitability in digitizing intraoral dental radiographic film for quantitative studies. The system (Nikon model LS-3510AF Nikon Electronic Imaging, Nikon, Inc., Melville, N.Y.) uses a charge-coupled device linear photodiode array. The data content in the original film images was evaluated, and the system performance assessed objectively with the use of specially designed test films. Radiometric and geometric performances for the digitizing system were extracted from measurements and observations, and these were compared with published data for two other film digitizing systems (video camera DAGE MTI, Michigan City, Ind. and Barneyscan 35-mm film digitizer Barneyscan, Berkeley, Calif.). The techniques used to evaluate this system are easy and suitable for evaluation of any digitizing system. This scanner system (Nikon) was superior to previously evaluated systems in transforming and recording radiographic film densities across the range (0.3 to 2.0 optical density units) of clinically relevant optical densities. The scanner offers substantial advantage over the other digitizing systems for gray scale information from clinically important optical densities. | 10.1016/0030-4220(93)90020-5 |
pubmed_891_15952 | In this work we analyze the effectiveness of decoration of nanocrystalline SnO2/TiO2 composites with gold nanoparticles (Au NPs) and platinum nanoparticles (Pt NPs) in enhancing gas sensor properties in low-temperature HCHO detection. Nanocrystalline SnO2/TiO2 composites were synthesized by a chemical precipitation method with following modification with Pt and Au NPs by the impregnation method. The nanocomposites were characterized by TEM, XRD, Raman and FTIR spectroscopy, DRIFTS, XPS, TPR-H2 methods. In HCHO detection, the modification of SnO2 with TiO2 leads to a shift in the optimal temperature from 150 to 100 °C. Further modification of SnO2/TiO2 nanocomposites with Au NPs increases the sensor signal at T = 100 °C, while modification with Pt NPs gives rise to the appearance of sensor responses at T = 25 °C and 50 °C. At 200 °C nanocomposites exhibited high selectivity toward formaldehyde within the sub-ppm concentration range among different VOCs. The influence of Pt and Au NPs on surface reactivity of SnO2/TiO2 composite and enhancement of the sensor response toward HCHO was studied by DRIFT spectroscopy and explained by the chemical and electronic sensitization mechanisms. | 10.3390/nano11082049 |
pubmed_1045_1916 | Hypokalemic paralysis associated with hyperthyroidism (TPP) is a well-known acute electrolyte and muscle function disorder. Lesser known is normokalemic periodic paralysis associated with hyperthyroidism. We describe two cases of young men with acute muscular paralysis and bilateral impairment of sensation over the lower legs who had normal plasma potassium concentrations. They were initially misdiagnosed as having Guillain-Barré syndrome or hysterical paralysis. However, thyroid function tests showed elevated serum T(3) and T(4) and markedly depressed thyroid-stimulating hormone findings consistent with hyperthyroidism. Control of the hyperthyroidism completely abolished their periodic paralysis. Thyrotoxic normokalemic periodic paralysis (TNPP) should be kept in mind as a cause of acute muscle weakness to avoid missing a treatable and curable condition. | 10.1053/ajem.2003.50005 |
pubmed_446_2545 | At present, a number of invasive diagnostic techniques can be used to diagnose the cause of lung infiltrates in patients with hematologic malignancies or hematopoietic stem cell transplantation recipients. Bronchoscopy with measurement of biomarkers in the bronchoalveolar lavage (BAL) will most likely become the preferred method to diagnose infectious causes of pulmonary infiltrates. However, there is no uniform approach regarding the technical parameters of the lavage procedure in cancer patients. Diagnostic protocols vary by region, center, and the expertise of the staff. This mini review discusses the issues surrounding diffuse pulmonary infiltrates and provides some recommendations to deal with these issues. | pubmed_446_2545 |
pubmed_768_4588 | Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) expressed in several mammalian brain areas and activated by "trace amines" (TAs). TAs role is unknown; however, discovery of their receptors provided an opportunity to investigate their functions. In vivo evidence has indicated an inhibitory influence of TAAR1 on dopamine (DA) neurotransmission, presumably via modulation of dopamine transporter (DAT) or interaction with the D2 DA receptor and/or activation of inwardly rectifying K(+) channels. To elucidate the mechanisms of TAAR1-dependent modulation, we used TAAR1 knockout mice (TAAR1-KO), a TAAR1 agonist (RO5166017) and a TAAR1 antagonist (EPPTB) in a set of neurochemical experiments. Analysis of the tissue content of TAAR1-KO revealed increased level of the DA metabolite homovanillic acid (HVA), and in vivo microdialysis showed increased extracellular DA in the nucleus accumbens (NAcc) of TAAR1-KO. In fast scan cyclic voltammetry (FSCV) experiments, the evoked DA release was higher in the TAAR1-KO NAcc. Furthermore, the agonist RO5166017 induced a decrease in the DA release in wild-type that could be prevented by the application of the TAAR1 antagonist EPPTB. No alterations in DA clearance, which are mediated by the DAT, were observed. To evaluate the interaction between TAAR1 and D2 autoreceptors, we tested the autoreceptor-mediated dynamics. Only in wild type mice, the TAAR1 agonist was able to potentiate quinpirole-induced inhibitory effect on DA release. Furthermore, the short-term plasticity of DA release following paired pulses was decreased in TAAR1-KO, indicating less autoinhibition of D2 autoreceptors. These observations suggest a close interaction between TAAR1 and the D2 autoreceptor regulation. | pubmed_768_4588 |
others_257_17045 | In this study, the habitat use by the threatened Cabrera vole, Microtus cabrerae, was assessed in an agricultural landscape of SW Portugal, in order to evaluate agricultural management practices that might favour its populations. Despite the patchy distribution and the sensitivity in relation to human management, average colony size was 1928 m2, and mean nearest neighbour distance was 363 m. Within the selected habitats, the Cabrera vole's activity was concentrated in sites with dense and tall herbs, though appearing to avoid areas where southern water voles, Arvicola sapidus, were present. Activity of Cabrera voles was higher during the winter, confirming the adverse effect of the dry periods for this species. Conservation of the Cabrera vole in agricultural landscapes would require the maintenance of a network of tall and dense herbaceous patches, which could possibly be established along field margins, road verges, and ditches, and supported by agri-environment subsidy schemes. © 2006 Elsevier B.V. All rights reser | 10.1016/j.agee.2005.12.002 |
pubmed_32_21161 | Resistance to lysis by human serum (HS) is an important parameter used to distinguish Trypanosoma brucei brucei from both Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Neither the exact nature of the trypanolytic factor (TLF) nor the mechanism of action by which HS lyses susceptible trypanosomes is well understood. This report tries to elucidate the role played by the variable surface glycoprotein (VSG) coat and trypanosome surface-related processes in the mechanism of HS lysis of HS-sensitive (HSS) and HS-resistant (HSR) trypanosomes. Procyclic forms of T. brucei gambiense transformed from either HSS or HSR bloodstream stages were found to be HSR. These procyclic forms were shown to have lost their VSG coat. However, the addition of excess soluble VSG from HSS trypanosomes did not block lysis of HSS trypanosomes. Human serum lysis was significantly inhibited if the trypanosomes were incubated with membrane stabilizers, i.e., including cytochalasins (B, D, and E specifically), zinc acetate, vinblastine, and benzyl alcohol, or with the lysosomotropic agents ammonium chloride and chloroquine. The inhibition exerted by these compounds was always reversible. The results in this report, taken together, strengthen the hypothesis that the lytic factor interacts with and moves along the trypanosome surface to be internalized eventually. | pubmed_32_21161 |
pubmed_867_5293 | Heparin cofactor II (HC II) levels were measured by electro-immunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established. It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis. | pubmed_867_5293 |
pubmed_1018_12846 | Utilizing a recently developed numerical technique, known as the lattice-Boltzmann method, we study 2D immiscible three-phase flow at the microscopic scale. In this paper, the spreading of a droplet on a fluid-fluid interface has been investigated. Different spreading regimes, depending on the governing forces, are identified. It has been found that the spreading rates derived from simulations agree with analytically obtained spreading rates for both capillary- and gravity-driven flow. In the gravity driven case, a formula can be derived for the drop shape. The numerical results regarding the drop shape turn out to resemble the predicted shape. Copyright 1998 Academic Press. | 10.1006/jcis.1998.5656 |
pubmed_230_2158 | Transmission of pinewood nematode through Monochamus carolinensis oviposition wounds was documented. Nematode transmission was measured as the average number of nematodes isolated per oviposition wound excavated and also as the percentage of oviposition wounds from which nematodes were isolated. The influence of three factors that might affect nematode transmission was investigated: age of the beetle vector, number of nematodes carried per beetle, and egg deposition in the oviposition wound. Only the number of nematodes carried by the beetle was found to have a significant effect on transmission. Nematodes were transmitted more frequently and in slightly greater numbers by beetles carrying more nematodes. The influence of pinewood on nematode exit from beetles were investigated by comparing nematode exit from beetles placed over pine chips with those placed over distilled water. Nematodes exited in greater numbers and at a higher frequency from beetles over pine chips than from beetles over distilled water. Apparently, the nematodes are able to detect a factor from the pine chips that promotes their exit from the beetles. | pubmed_230_2158 |
pubmed_1112_16719 | Objective. Glutamate, an excitatory neurotransmitter in the central nervous system (CNS), may play a role in the development of anxiety. Memantine partially blocks N-methyl-D-aspartate (NMDA) receptors' glutamate channels located in the CNS. This paper evaluates memantine as an augmentation therapy for treatment of anxiety. Methods. 15 consecutive partially responding anxious patients were treated with adjunctive memantine for 10 weeks. Memantine was dosed 5-20 mg/day. Result. Memantine augmentation resulted in clinically relevant reduction in anxiety symptoms when compared to baseline. Forty percent of patients achieved remission (HAM-A ≥ 7). Memantine improved sleep quality. Mean dose was 14 mg/d (range 5-20 mg/d). Typical adverse events included nausea and headache. Conclusion. The NMDA receptor antagonist memantine may be an effective augmentation therapy in patients with treatment-resistant anxiety. | 10.1155/2012/749796 |
pubmed_510_10256 | Uncoupled enzyme IIGlc of the phosphoenolpyruvate (PEP): glucose phosphotransferase system (PTS) in Salmonella typhimurium is able to catalyze glucose transport in the absence of PEP-dependent phosphorylation. We have studied the energetics of glucose uptake catalyzed by this uncoupled enzyme IIGlc. The molar growth yields on glucose of two strains cultured anaerobically in glucose-limited chemostat- and batch cultures were compared. Strain PP799 transported and phosphorylated glucose via an intact PTS, while strain PP952 took up glucose exclusively via uncoupled enzyme IIGlc, followed by ATP-dependent phosphorylation by glucokinase. Thus the strains were isogenic except for the mode of uptake and phosphorylation of the growth substrate. PP799 and PP952 exhibited similar YGlc values. Assuming equal YATP values for both strains this result indicated that there were no energetic demands for glucose uptake via uncoupled enzyme IIGlc. | 10.1007/BF00252206 |
pubmed_230_18607 | We describe the case of a middle-aged woman who presented to us after injury from a clenched fist 3 days previously. The diagnosis was occult scleral perforation, severe conjunctival chemosis, and traumatic aphakia. However, the lens could not be localized during posterior segment examination. An anterior segment optical coherence tomography (AS-OCT) examination showed scleral discontinuity and a heterogeneous reflection in the subconjunctival area, suggesting a possible phacocele. Surgical exploration confirmed these findings. Aphakia was managed using the "glued intraocular lens" technique in the same sitting. This case highlights the use of AS-OCT in noncontact exploration of the traumatized anterior segment and in diagnosis of a possible phacocele along with an occult scleral perforation with uveal prolapse. To our knowledge, this is the first report of successful implantation of a glued IOL as a primary procedure combined with scleral perforation repair. | 10.1016/j.jcrs.2008.09.031 |
pubmed_367_16533 | PURPOSE OF REVIEW
To give an overview of autophagy and its effects on innate and adaptive immunity and touch on some of the roles of autophagy in disease.
RECENT FINDINGS
Precise regulation of autophagy is necessary to maintain metabolic equilibrium, immune homeostasis, delineate cell fate and influence host cell responses to cytosolic pathogens. A growing number of studies have implicated that inactivation of autophagy-selective responses contributes to inflammatory disorders, neurodegeneration and cancer, but the precise steps at which disease-associated autophagy-related (ATG) genes affect autophagy pathways is unknown at present.
SUMMARY
In eukaryotic cells autophagy is constitutively active at low levels, whereas significant up-regulation occurs in response to a multitude of stresses. Autophagy has achieved notoriety as a perturbed biological process in many disease states and an exponential increase of studies attribute roles for autophagy in innate and adaptive immunity. Understanding how individual disease-associated ATG genes function will lead to a better understanding of and potentially novel therapies for treating the diseases in which they are involved. | 10.1097/MOG.0b013e32833104f1 |
pubmed_603_6107 | Heart failure constitutes a major public health problem. Its incidence continues to grow and its prognosis remains poor. Therapeutic approach of chronic heart failure with left ventricular systolic dysfunction is well codified. Recommended medical treatment is presented with the description of the different therapeutic classes. Recent advances are discussed. New therapeutic targets are described. Optimization of recognized treatment and application to heart failure of drugs used for other indications are developed. Therapeutic approach of heart failure with preserved ejection fraction is tackled but stays far less well defined. Many studies concerning treatment of acute heart failure are ongoing. | pubmed_603_6107 |
pubmed_1033_18443 | Although osteopontin (OPN) is highly expressed in osteoclasts, OPN-deficient mice have a near-normal bone phenotype and its role in osteoclast differentiation and function remains uncertain. We used an adenoviral OPN-antisense vector (AdOPN-AS) to down-regulate OPN expression in a human in vitro osteoclastogenesis model employing CFU-GM precursors treated with RANKL and M-CSF. Cultures infected with AdOPN-AS showed reduced secretion of OPN compared to cultures infected with a control adenoviral vector expressing beta-galactosidase. Infection with AdOPN-AS co-incident with exposure to RANKL was associated with substantial (approximately 50%) inhibition of osteoclast formation with a concomitant reduction in dentine resorption. There was also a small reduction in the size of generated osteoclasts but no significant effect on the size of resorption pits/tracks nor on the amount of resorption per osteoclast. When the cultures were infected with AdOPN-AS after 4 days exposure to RANKL only minor effects on osteoclastogenesis were seen. Our data demonstrate that early down-regulation of OPN in vitro inhibits human osteoclastogenesis. Since mice totally lacking OPN do not have reduced osteoclast numbers our results imply the existence in vivo of an alternative molecular pathway(s). | 10.1002/jcb.20247 |
pubmed_285_10879 | Reinforcement learning is a branch of machine learning concerned with using experience gained through interacting with the world and evaluative feedback to improve a system's ability to make behavioural decisions. It has been called the artificial intelligence problem in a microcosm because learning algorithms must act autonomously to perform well and achieve their goals. Partly driven by the increasing availability of rich data, recent years have seen exciting advances in the theory and practice of reinforcement learning, including developments in fundamental technical areas such as generalization, planning, exploration and empirical methodology, leading to increasing applicability to real-life problems. | 10.1038/nature14540 |
pubmed_444_1783 | BACKGROUND
Sexual dysfunction is common among people who are prescribed antipsychotic medication for psychosis. Sexual dysfunction can impair quality of life and reduce treatment adherence. Switching antipsychotic medication may help, but the clinical effectiveness and cost-effectiveness of this approach is unclear.
OBJECTIVE
To examine whether or not switching antipsychotic medication provides a clinically effective and cost-effective method to reduce sexual dysfunction in people with psychosis.
DESIGN
A two-arm, researcher-blind, pilot randomised trial with a parallel qualitative study and an internal pilot phase. Study participants were randomised to enhanced standard care plus a switch of antipsychotic medication or enhanced standard care alone in a 1 : 1 ratio. Randomisation was via an independent and remote web-based service using dynamic adaptive allocation, stratified by age, gender, Trust and relationship status.
SETTING
NHS secondary care mental health services in England.
PARTICIPANTS
Potential participants had to be aged ≥ 18 years, have schizophrenia or related psychoses and experience sexual dysfunction associated with the use of antipsychotic medication. We recruited only people for whom reduction in medication dosage was ineffective or inappropriate. We excluded those who were acutely unwell, had had a change in antipsychotic medication in the last 6 weeks, were currently prescribed clozapine or whose sexual dysfunction was believed to be due to a coexisting physical or mental disorder.
INTERVENTIONS
Switching to an equivalent dose of one of three antipsychotic medications that are considered to have a relatively low propensity for sexual side effects (i.e. quetiapine, aripiprazole or olanzapine). All participants were offered brief psychoeducation and support to discuss their sexual health and functioning.
MAIN OUTCOME MEASURES
The primary outcome was patient-reported sexual dysfunction, measured using the Arizona Sexual Experience Scale. Secondary outcomes were researcher-rated sexual functioning, mental health, side effects of medication, health-related quality of life and service utilisation. Outcomes were assessed 3 and 6 months after randomisation. Qualitative data were collected from a purposive sample of patients and clinicians to explore barriers to recruitment.
SAMPLE SIZE
Allowing for a 20% loss to follow-up, we needed to recruit 216 participants to have 90% power to detect a 3-point difference in total Arizona Sexual Experience Scale score (standard deviation 6.0 points) using a 0.05 significance level.
RESULTS
The internal pilot was discontinued after 12 months because of low recruitment. Ninety-eight patients were referred to the study between 1 July 2018 and 30 June 2019, of whom 10 were randomised. Eight (80%) participants were followed up 3 months later. Barriers to referral and recruitment included staff apprehensions about discussing side effects, reluctance among patients to switch medication and reticence of both staff and patients to talk about sex.
LIMITATIONS
Insufficient numbers of participants were recruited to examine the study hypotheses.
CONCLUSIONS
It may not be possible to conduct a successful randomised trial of switching antipsychotic medication for sexual functioning in people with psychosis in the NHS at this time.
FUTURE WORK
Research examining the acceptability and effectiveness of adjuvant phosphodiesterase inhibitors should be considered.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN12307891.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 44. See the NIHR Journals Library website for further project information. | 10.3310/hta24440 |
pubmed_383_16349 | AIMS
Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF).
METHODS AND RESULTS
In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo.
CONCLUSION
In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure. | 10.1002/ejhf.2138 |
pubmed_1031_21126 | We propose that the isomorphism generally observed between the representations composing our momentary phenomenal experience and the structure of the world is the end-product of a progressive organization that emerges thanks to elementary associative processes that take our conscious representations themselves as the stuff on which they operate, a thesis that we summarize in the concept of Self-Organizing Consciousness (SOC). | 10.1017/s0140525x02000067 |
others_188_8221 | The large and recent migrations of the main vector of the Chikungunya virus, Aedes albopictus, raise questions about the epidemiological impact of possible microevolutionary changes in new territories. Quantitative traits are suitable to detect such changes as induced by environmental adaptations, local competition and founder effects. Using landmark-based geometric morphometrics, we compared the size and shape of 22 populations (1572 females) of Ae. albopictus. The collection sites covered five countries around the world, with special emphasis on Asia, which is assumed to be the origin of the vector. Some collections came from places where an important epidemic outbreak of Chikungunya has recently occurred.Quantitative comparisons were based on 18 anatomical landmarks on the wing. To contrast geographic and possible interspecific shape variation, close species were introduced in the sample, namely five Aedes riversi and nine Ae. flavopictus from Japan. The three species had similar size, but they were clearly separated by shape.Within Ae. albopictus, there was general agreement on size variation with the available climatic data. Shape variation was less related to climatic data than to either geography or a known itinerary of past territorial expansion. Thus, two main clusters were distinguished by wing shape variation: the first one composed of the Southeast Asian sample, the second one grouping Japan, Florida, Hawaii and the Reunion Island samples.The Southeast Asian countries, assumed to be at the origin of the geographic expansion of the mosquito, had similar wings and constituted a distinct group where localities clustered into northern and southern localities. Contrasting with this homogeneous group, very distant localities such as United States (US) and Japan shared a common shape pattern. The US Ae. albopictus samples (Hawaii and Florida) were indeed very similar to the Japanese samples, with Florida behaving exactly like a northern Japanese locality, close to Tokyo and Yokohama. Shape proximity among these distant areas could be explained by a common and relatively recent ancestor, as generally suggested in the literature. The three Reunion Island samples conformed a group external to the Southeast Asian countries, loosely connected to the remaining localities.Thus, areas where recent epidemics took place, the Reunion Island and the southernmost localities of Thailand, did not cluster together, but represented separate groups.In sum, the size of the wing was apparently under the influence of climatic factors, while its shape could contribute information on species and geographic differences. Apparent departures from expectations based on geography were explained by known past and present migratory routes. These patterns of shape variation were compatible with genetic drift, suggesting microevolutionary changes probably induced by the expansion of the Ae. albopictus mosquito. © 2012 Elsevier B.V | 10.1016/j.meegid.2012.08.008 |
pubmed_402_3367 | Universities and colleges have for a long time ignored sexual harassment, hoped it was non-existent or waited for it to disappear. Recently, however, students, professors and university administrators have begun to recognize the perniciousness and pervasiveness of the problem but thus far with little attention to sexual harassment as a health hazard. Based on data collected by questionnaire from 455 women university undergraduate and graduate students and nine follow-up in-depth interviews, this study examines the dimensions and dynamics of sexual harassment as a health hazard for women. Sexual harassment is found to have both direct and indirect health effects, including nausea and sleeplessness, loss of self-esteem, fear and anger, feelings of helplessness and isolation, as well as nervousness and depression. In contributing to the literature on women's culturally and socially determined health problems, this study sheds light on the ways in which women students' economic, political, social and personal well-being can be undermined by sexual harassment. | 10.1300/j013v28n02_03 |
pubmed_436_22710 | The aim of the study was to assess the prevalence of contact allergy to glucocorticosteroids in patients with chronic venous leg ulcers (CVLU), atopic dermatitis (AD) and contact dermatitis (CD), and in a group of healthy individuals; and to estimate differences among these patient groups. Patch tests with the European standard series, antibiotics, glucocorticosteroid contact allergy screening markers and ointment vehicles were performed in a population of 140 patients. Positive patch tests results were recorded in 80% and contact allergy to glucocorticosteroids in 40% of CVLU patients. In the group of AD patients, the respective figures were 30% and 3%. In the group of CD patients, allergic type of disease was detected in 80% and positive patch tests for glucocorticosteroids in 20% of patients. In healthy individuals, allergic contact reaction was observed in 17% of cases. Statistically significant differences among patient groups were found according to the prevalence of contact allergy, polyvalent allergy and contact allergy to glucocorticosteroids. We suggest that glucocorticosteroid contact allergy should be considered as a crucial clinical problem in patients with inflammatory dermatoses like CVLU, AD and CD. | pubmed_436_22710 |
others_46_9125 | Horse health is best served when farriers and veterinarians collaborate in the care of their patients. Veterinary Teaching Hospitals (VTHs) provide an environment that can nurture that collaboration. While VTH veterinary services are well known, VTH farrier activities are undocumented. To characterise farrier services at VTHs in the USA, 27 VTH Diplomates of the American College of Veterinary Surgeons and/or VTH farriers completed a multiple choice questionnaire characterising VTH farrier details, training, certification, remuneration method, and clinical, teaching and research responsibilities; and farrier service prevalence, facilities and financial viability. Questionnaire response rate was 81%. Eighteen of 22 (82%) responding VTHs had in-house farrier services. Twenty-one of 22 (95%) VTH farriers were male. Farriers' ages ranged from <30 years (n = 1, 5%) to >50 years (n = 7, 32%). At 11 (61%) VTHs the farriers were paid by the client and at 7 (39%) by the VTH. Five farriers (23%) received a VTH salary. Eighteen of 22 (82%) farriers had a professional certification. At 5 (28%) VTHs the farrier service made a profit and operational costs were met at 13 (72%). Fifteen (83%) farrier services provided professional education in clinical settings and 13 (72%) in lecture settings. Nine (41%) VTH farriers participated in research activities. the USA, VTH farrier services vary considerably in both nature and extent. The farriers' potential contributions to VTH operations are often recognised but not consistently exploited. VTH farriers are a valuable resource who can contribute effectively toward VTH patient care, veterinary education and research. © 2010 EVJ L | 10.1111/j.0957-7734.2010.00124.x |
pubmed_435_6319 | Canonically the oncogenic kinase AKT is activated by growth signals. Our work suggests apoptotic materials, abundant in tumors, also contribute to AKT activation by stimulating MERTK that in turn phosphorylates Y26 in the AKT PH domain. pY26 reverses binding of an AKT endogenous, WW-domain containing inhibitor, SAV1, allowing AKT responsiveness to classic growth signals. This novel mechanism may contribute to drug resistance. | 10.1080/23723556.2019.1611161 |
pubmed_648_25918 | Interest in the synthesis of Bi(III) and Sb(III) dithiocarbamate complexes is on the rise, and this has been attributed to their wide structural diversity and their interesting application as biological agents and in solid state/materials chemistry. The readily available binding sites of the two sulphur atoms within the dithiocarbamate moiety in the complexes confers a wide variety of geometry and interactions that often leads to supramolecular assemblies. Although none of the bismuth or antimony metals are known to play any natural biological function, their dithiocarbamate complexes, however, have proven very useful as antibacterial, antileishmanial, anticancer, and antifungal agents. The dithiocarbamate ligands modulate the associated toxicity of the metals, especially antimony, since bismuth is known to be benign, allowing the metal ion to get to the targeted sites; hence, making it less available for side and other damaging reactions. This review presents a concise chemistry and some known biological potentials of their trivalent dithiocarbamate complexes. | 10.3390/molecules25020305 |
pubmed_1037_1088 | BACKGROUND
Cancer pain is among the most severe types of pain and is among the most common types of cancer-related problems. Yet, many ambiguities surround the concept of cancer pain and its attributes.
OBJECTIVE
This study aimed to analyze the concept of cancer pain.
METHODS
This concept analysis was conducted using the Rodgers' evolutionary method. Nursing, psychology, social sciences, and medicine literature were reviewed through searching online databases. In total, 52 articles were included and analyzed through thematic analysis.
RESULTS/CONCLUSION
The attributes of cancer pain are known origin, sharp, burning, piercing, or throbbing quality, varying duration (acute, chronic, or breakthrough), intolerability, and moderate to severe intensity. Its antecedents are cognitive system, pain-related beliefs, coping strategies, family and social support, financial status, and cultural, ethnic, racial, and religious values. Its consequences include physical, psychological, existential and spiritual, and social consequences, and reduced quality of life. This concept analysis concludes that cancer pain is different from other types of acute and chronic pain. Thus, specific interventions are needed for its assessment and management.
IMPLICATIONS FOR CASE MANAGEMENT PRACTICE
The results of this concept analysis can broaden the case manager/health care team and other health care providers' knowledge about cancer pain and help them make better decisions and take more effective interventions for its management. The information in the article can be used to inform the case manager/health care team when it may be time to consider palliative care or even hospice care. Also, the information, itself, is crucial for case managers to understand when a patient has cancer pain. | 10.1097/NCM.0000000000000509 |
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