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Rosiglitazone has been proposed as a treatment strategy for type 2 diabetes mellitus (T2DM), and it could provide robust glucose-lowering capability with risk of cardiovascular events. We thus performed a systematic review and meta-analysis of controlled trials to assess the effect of this treatment on glycaemic control and cardiovascular events in patients with T2DM. We systematically search PubMed, Embase, and the Cochrane Central Register of Controlled Trials comparing rosiglitazone to other anti-diabetic treatments. These studies included randomised controlled trials (RCTs), cohort studies, and case-control studies that had treatment with at least six months of follow-up in patients with T2DM. We aimed to evaluate the long-term effect on cardiovascular risk of rosiglitazone compared with a basal insulin drug. The main outcomes included myocardial infarction, heart failure, stroke, cardiovascular mortality, and all-cause mortality. We included 11RCTs and four observational studies involving 20,079 individuals with T2DM allocated to rosiglitazone and a similar number to comparison groups of which only five compared rosiglitazone with placebo and collected data on cardiovascular outcomes. Among patients with T2DM, rosiglitazone is associated with a significantly increased risk of heart failure, with little increased risk of myocardial infarction, without a significantly increased risk of stroke, cardiovascular mortality, and all-cause mortality compared with placebo or active controls. Alternative methods to reduce the uncertainty in long-term pragmatic evaluations, inclusion of rosiglitazone in factorial trials, publication of cardiovascular outcome data from adverse event reporting in trials of rosiglitazone and a cardiovascular endpoint trial of rosiglitazone among people without diabetes. | Rosiglitazone |
There are several forms of pulmonary hypertension that can be considered unusual not solely due to their prevalence but also due to their geographic distribution. The aim of this review is to highlight some of these forms, most of them classified within group 5 of the current pulmonary hypertension classification. This review also discusses on schistosomiasis-associated pulmonary hypertension, a prevalent form of pulmonary hypertension mostly limited to developing countries. | Schistosomiasis |
The purpose of this review was to analyze the current ideas about various techniques and methods for treating epilepsy in patients with hypothalamic hamartomas including microsurgery, endoscopy, radiofrequency thermal destruction, stereotactic laser ablation and radiosurgery. Data characterizing their effectiveness, limitations and complications are considered. CONCLUSION: When choosing the optimal treatment option, it is necessary to take into account patient age and course of disease, anatomical and topographic features of hamartoma location, previous attempts of treatment, opinion of the patient and his guardians, as well as surgical experience. | Hypothalamic Diseases |
TAR DNA-binding protein-43 (TDP-43) is a nuclear protein functioning in the regulation of transcription and mRNA splicing. TDP-43 is accumulated in ubiquitinated inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) diseased brains. However, the pathways involved in the clearance of TDP-43 and its pathogenic form (TDP-25), a truncated form of TDP-43, are still not elucidated. In this study, we demonstrated that the protein levels of TDP-43 and TDP-25 were increased in cells treated with a proteasome inhibitor, MG132, or an autophagy inhibitor, 3-MA, whereas, they were decreased in cells treated with an enhancer of autophagy, trehalose. Furthermore, more protein level changes of TDP-25 than TDP-43 were observed in cells treated with above inhibitors or enhancer. Thus, our data suggest that TDP-43 and TDP-25 are degraded by both proteasome and autophagy with TDP-25 being more regulated. | Pepstatins |
CYP3A4, an important drug-metabolizing enzyme, is known to have genetic variants. We have previously reported that CYP3A4 variants such as CYP3A4.2, 7, 16, and 18 show different enzymatic kinetics from CYP3A4.1 (wild type). In this study, we quantitatively investigated the inhibition kinetics of two typical inhibitors, itraconazole (ITCZ) and cimetidine (CMD), on CYP3A4 variants and evaluated whether the genetic variation leads to interindividual differences in the extent of CYP3A4-mediated drug interactions. The inhibitory profiles of ITCZ and CMD on the metabolism of testosterone (TST) were analyzed by using recombinant CYP3A4 variants. The genetic variation of CYP3A4 significantly affected the inhibition profiles of the two inhibitors. In CYP3A4.7, the K(i) value for ITCZ was 2.4-fold higher than that for the wild-type enzyme, whereas the K(i) value for CMD was 0.64-fold lower. In CYP3A4.16, the K(i) value for ITCZ was 0.54-fold lower than that for wild-type CYP3A4, whereas the K(i) value for CMD was 3.2-fold higher. The influence of other genetic variations also differed between the two inhibitors. Docking simulations could explain the changes in the K(i) values, based on the accessibility of TST and inhibitors to the heme moiety of the CYP3A4 molecule. In conclusion, the inhibitory effects of an inhibitor differ among CYP3A4 variants, suggesting that the genetic variation of CYP3A4 may contribute, at least in part, to interindividual differences in drug interactions mediated by CYP3A4 inhibition, and the pattern of the influences of genetic variation differs among inhibitors as well as substrates." | 14-alpha Demethylase Inhibitors |
An alternative way of teaching informatics, especially health informatics, to health professionals of different categories has been developed and practiced. The essentials of human competence and skill in handling and processing information are presented parallel with the essentials of computer-assisted methodologies and technologies of formal language-based informatics. Requirements on how eventually useful computer-based tools will have to be designed in order to be well adapted to genuine human skill and competence in handling tools in various work contexts are established. On the basis of such a balanced knowledge methods for work analysis are introduced. These include how the existing problems at a workplace can be identified and analyzed in relation to the goals to be achieved. Special emphasis is given to new ways of information analysis, i.e. methods which even allow the comprehension and documentation of those parts of the actually practiced 'human' information handling and processing which are normally overlooked, as e.g. non-verbal communication processes and so-called 'tacit knowledge' based information handling and processing activities. Different ways of problem solving are discussed involving in an integrated human perspective--alternative staffing, enhancement of the competence of the staff, optimal planning of premises as well as organizational and technical means. The main result of this alternative way of education has been a considerably improved user competence which in turn has led to very different designs of computer assistance and man-computer interfaces. It is the purpose of this paper to give a brief outline of the teaching material and a short presentation of the above mentioned results.(ABSTRACT TRUNCATED AT 250 WORDS) | Attitude to Computers |
Halophytic plants growing in harsh desert environments are rich reservoirs of unique endophytic microorganisms. Here, healthy fresh plants of the families Tamaricaceae and Amarantaceae at three saline locations in Iran were investigated for their bioactive endophytic fungi. Among a vast number of isolates, eight isolates were identified as Humicola fuscoatra (Sordariomycetes, Pezizomycotina, Ascomycota) by microscopy and representative DNA sequences of the 5.8S rDNA (ITS) and partial beta-tubulin (TUB2). Those isolates were halotolerant, and highly bioactive, so that their intra- and extra-cellular metabolites possessed in vitro antifungal, antibacterial and antiproliferative activities, against a number of fungal and bacterial plant pathogens including the fungi Arthrobotrys conoides, Pyrenophora graminea, Pyricularia grisea and the bacteria Agrobacterium tumefaciens, Pseudomonas syringae and Xanthomonas oryzae. Chemical analyses of metabolites from the endophytes using HNMR, CNMR, NOESY, COSY, HMBC, HSQC, DEPT, TOCSY and EI MASS techniques identified 3,8-dihydroxy-1-methyl-9,10-anthracenedione (aloesaponarin II; an anthraquinone derivative), 1,8,9-anthracenetriol structure (chrysarobin; an anthranol derivative) and 2,4-di-tert-butylthiophenol in fungal extracts. To the best of our knowledge, this is the first report of endophytic association of halotolerant H. fuscoatra isolates with Tamaricaceae and Amarantaceae, and their bioactivity against plant pathogens. Also, the capability of chrysarobin and aloesaponarin II production is new to the fungal kingdom. These findings may find application in agriculture, pharmacology, and biotechnology. | Tamaricaceae |
Computed tomography is a medical instrument that can be useful not only for diagnostic purposes, but also for surgical planning, thanks to the fact that it offers volumetric information which can be translated in three dimensional models. These models can be visualized, but also exported to Rapid Prototyping (RP) systems, that can produce these structures thanks to the rapidity and versatility of the technologies involved. The literature reports various cases of stereolithographic models used in orthopedic, neurological, and maxillo-facial surgery. In these contexts, the availability of a copy of the real anatomy allows not only planning, but also the practical execution of surgical operations, within the limitations of the materials. Nevertheless, the Rapid Prototyping model also presents some disadvantages that can be reduced if practical simulation is accompanied by virtual simulation, performed on a digital model. The purpose of this work is to examine and present the use of Virtual Reality (VR) and Rapid Prototyping for surgical planning in Maxillo-Facial surgery." | Mandibular Prosthesis Implantation |
Personalized dendritic cell- (DC-) based vaccination has proven to be safe and effective as second-line therapy against various cancer types. In terms of overall survival, there is still room for improvement of DC-based therapies, including the development of more immunostimulatory DC vaccines. In this context, we redesigned our currently clinically used DC vaccine generation protocol to enable transpresentation of interleukin- (IL-) 15 to IL-15Rbetagamma-expressing cells aiming at boosting the antitumor immune response. In this study, we demonstrate that upon electroporation with both IL-15 and IL-15Ralpha-encoding messenger RNA, mature DC become highly positive for surface IL-15, without influencing the expression of prototypic mature DC markers and with preservation of their cytokine-producing capacity and their migratory profile. Functionally, we show that IL-15-transpresenting DC are equal if not better inducers of T-cell proliferation and are superior in tumor antigen-specific T-cell activation compared with DC without IL-15 conditioning. In view of the clinical use of DC vaccines, we evidence with a time- and cost-effective manner that clinical grade DC can be safely engineered to transpresent IL-15, hereby gaining the ability to transfer the immune-stimulating IL-15 signal towards antitumor immune effector cells." | Interleukin-15 Receptor alpha Subunit |
Bispyribac sodium (BS), a pyrimidinyl carboxy herbicide, is a well-known inhibitor of acetolactate synthase (ALS) activity. ALS is an enzyme in the biosynthetic pathway for branched-chain amino acids. A mutant form of rice ALS (OsmALS [W548L/S627I]) that confers resistance to BS can be used as an in vitro selection marker gene for plant transformation. Since indica and indica-derived cultivars are thought to have lower BS sensitivity than japonica rice, the application of BS as a selectable reagent for genetic transformation in indica and indica-derived cultivars is more challenging than for japonica cultivars. In this study, callus and seedlings of eight different rice cultivars (five indica-derived cultivars, two indica cultivars and one japonica cultivar) were tested for BS sensitivity. Our study indicates for the first time that callus shows a higher sensitivity to BS than seedlings in indica and indica-derived cultivars. We used BS with OsmALS [W548L/S627I] to select transformed calli, and transgenic rice plants from indica and indica-derived cultivars were successfully obtained. | Acetolactate Synthase |
Mortality from prostate cancer (PCa) is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor beta (TGFbeta) superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFbeta receptor, activin receptor-like kinase 2 (ALK2), and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFbeta receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA) and bone morphogenetic protein receptor type II (BMPRII). Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact." | Bone Morphogenetic Protein Receptors, Type II |
OBJECTIVE: Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington's disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. RESULTS: We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression. | Cholesterol 24-Hydroxylase |
PREMISE: After deforestation, environmental changes in the remaining forest fragments are often most intense near the forest edge, but few studies have evaluated plant growth or plasticity of plant growth in response to edge effects. METHODS: In a 2-year common garden experiment, we compared biomass allocation and growth of Heliconia acuminata with identical genotypes grown in 50 x 35 m common gardens on a 25-year-old edge and in a forest interior site. KEY RESULTS: Genetically identical plants transplanted to the forest edge and understory exhibited different patterns of growth and biomass allocation. However, individuals with identical genotypes in the same garden often had very different responses. Plants on forest edges also had higher growth rates and increased biomass at the end of the experiment, almost certainly due to the increased light on the forest edge. CONCLUSIONS: With over 70000 km of forest edge created annually in the Brazilian Amazon, phenotypic plasticity may play an important role in mediating plant responses to these novel environmental conditions. | Heliconiaceae |
The Cognitive reserve (CR) hypothesis was put forward to account for the variability in cognitive performance of patients with similar degrees of brain pathology. Compensatory neural activity within the frontal lobes has often been associated with CR. For the first time we investigated the independent effects of two CR proxies, education and NART IQ, on measures of executive function, fluid intelligence, speed of information processing, verbal short term memory (vSTM), naming, and perception in a sample of 86 patients with focal, unilateral frontal lesions and 142 healthy controls. We fitted multiple linear regression models for each of the cognitive measures and found that only NART IQ predicted executive and naming performance. Neither education nor NART IQ predicted performance on fluid intelligence, processing speed, vSTM or perceptual abilities. Education and NART IQ did not modify the effect of lesion severity on cognitive impairment. We also found that age significantly predicted performance on executive tests and the majority of our other cognitive measures, except vSTM and GNT. Age was the only predictor for fluid intelligence. This latter finding suggests that age plays a role in executive performance over and above the contribution of CR proxies in patients with focal frontal lesions. Overall, our results suggest that the CR proxies do not appear to modify the relationship between cognitive impairment and frontal lesions. | Cognitive Reserve |
The molecular chaperone protein HSP60 is mainly distributed in mitochondria and assists protein folding under physiological and pathological conditions. Accumulating evidence suggests abnormally expressed HSP60 in cancer is associated with clinicopathological features and prognosis of cancer patients. HSP60 could be used as a new biomarker for both diagnostic and prognostic purpose and tumor therapy. In this review article, we briefly described the structure, functional cycle, and regulatory mechanism of HSP60, and summarized its functional diversity in cancer as well as recent progress related to the diagnostic application of HSP60 and inhibitors against HSP60, which could provide us a comprehensive understanding about the value of HSP60 in tumor management. | Group I Chaperonins |
A careful history and physical examination is essential in diagnosing and treating salivary gland disorders. This alone may identify congenital lesions, trauma, acute and chronic inflammatory diseases, and a variety of other conditions affecting the salivary glands. The most common presenting complaint is that of a lump in a salivary gland, and the onus is on the physician to prove the presence or absence of malignancy. Laboratory and radiographic studies are of minimum value in making this distinction, and biopsy, under general anesthesia, by a competent head and neck surgeon with microscopic evaluation is often necessary. Office biopsy or large or fine-needle aspiration should not be attempted. Fortunately, most neoplasms are benign, and many malignant forms are low grade and have a good prognosis. | Salivary Gland Diseases |
BACKGROUND: The original Charnley-type negative-pressure body exhaust suit reduced infection rates in randomized trials of total joint arthroplasty (TJA) decades ago. However, modern positive-pressure surgical helmet systems have not shown similar benefit, and several recent studies have raised the question of whether these gowning systems result in increased wound contamination and infections. The gown-glove interface may be one source of particle contamination. QUESTIONS/PURPOSES: The purpose of this study was to compare particle contamination at the gown-glove interface in several modern surgical helmet systems and conventional surgical gowns. METHODS: A 5-mum fluorescent powder was evenly applied to both hands to the level of the wrist flexion crease. After gowning in the standard fashion, the acting surgeon performed a 20-minute simulated TJA protocol. Each of the five gowning systems was run through five trials. The amount of gown contamination at the gown-glove interface then was measured by three observers under ultraviolet light using a grading scale from 0 (no contamination) to 4 (gross contamination). Statistical analysis was carried out with Minitab 15. Friedman's test was used to compare the levels of contamination across trials for each gown and the Mann-Whitney test was used post hoc to perform a pairwise comparison of each gown. RESULTS: All gown-glove interfaces showed some contamination. Friedman's test showed that there was a significant difference in contamination between gowns (p = 0.029). The Stryker T5 Zipper Toga system showed more contamination than the other gowns. The median contamination score and range for each gowning setup was 1.8 (range, 1-4; conventional Kimberly-Clark MicroCool gown without helmet), 4 (range, 3-4; Stryker T5 Zipper Toga), 3.6 (range, 0-4; Stryker helmet with conventional gown), 1.6 (range, 0-2; Stryker Flyte Toga), and 3.0 (range, 2-3; DePuy Toga). A Mann-Whitney test found no difference among any of the gowns except for the Stryker T5 Zipper Toga, which showed more contamination compared directly with each of the other four gowns (p < 0.001 for each gown-to-gown comparison). CONCLUSIONS: Particle contamination occurs at the gown-glove interface in most commonly used positive-pressure surgical helmet systems. The Stryker T5 Zipper Toga exhibited more contamination than each of the other gowning systems. CLINICAL RELEVANCE: The gown-glove interface is prone to particle contamination and all surgeons should be aware of this area as a potential source of surgical site infection. Although future studies are needed to clarify the link between particle contamination through this route and clinical infection, surgeons should consider using gowning systems that minimize the migration of fomites through the gown-glove interface. | Gloves, Surgical |
Clinical trials are a valuable study design for evaluating interventions when it is ethical and feasible for investigators to randomly allocate study animals to intervention groups. Researchers may choose to evaluate the comparative efficacy of intervention groups for their effect on outcomes that are relevant to the specific objectives of their trial. However, the results across multiple trials on the same intervention and with the same outcome should be considered when making decisions on whether to use an intervention, because the results of a single trial are subject to sampling error and do not reflect all biological variability. The objective of this review was to provide an overview of important concepts when selecting intervention groups and outcomes within a randomized controlled trial, and when building a body of evidence for intervention efficacy across multiple trials. Empirical evidence is presented to highlight that integrating and interpreting the efficacy of an intervention across trials is hindered by a lack of replication of interventions across trials. Inconsistency in the outcomes and their measurement among trials also limits the ability to build a body of evidence for the efficacy of interventions. The development of core outcome sets for specific topic areas in dairy science, updated as necessary, may improve consistency across trials and aid in the development of a body of evidence for evidence-based decision-making." | Clinical Trials, Veterinary as Topic |
The prevalence of Barrett's esophagus is increasing in the United States and is a major risk factor for esophageal adenocarcinoma. This review serves to help primary care physicians and family practitioners better understand who should be screened for Barrett's esophagus, know the appropriate surveillance intervals for repeat endoscopy, and understand therapeutic options for the management of Barrett's esophagus. | Barrett Esophagus |
The first reported outbreak of St. Louis encephalitis in Canada occurred in the summer of 1975 in southern Ontario -- in the Windsor-Sarnia-Chatham area, the Niagara region and the city of Toronto. Hemmagglutination inhibition and complement fixation testing of serum samples collected during the outbreak confirmed that St. Louis encephalitis virus was the etiologic agent. Furthermore, this virus was isolated from brain tissue of a patient who died. This outbreak was probably an extension of the outbreak that occurred in the United States that summer. It was the first outbreak of arbovirus encephalitis in the province of Ontario. | Encephalitis, St. Louis |
We report the case of a 62-year-old diabetic man, who was incidentally detected to have extensive calcification in his upper limb arteries, consistent with Monckeberg's sclerosis. The condition was identified when routine radial puncture attempted in the course of coronary angiography was repeatedly unsuccessful. Coronary angiography and angioplasty was subsequently performed through the femoral route. Monckeberg's sclerosis is a poorly understood condition associated with generalised atherosclerosis and chronic kidney disease. The pathogenesis and natural history of Monckeberg's sclerosis are briefly discussed." | Monckeberg Medial Calcific Sclerosis |
The human mitochondrial ribosome (mitoribosome) and associated proteins regulate the synthesis of 13 essential subunits of the oxidative phosphorylation complexes. We report the discovery of a mitoribosome-associated quality control pathway that responds to interruptions during elongation, and we present structures at 3.1- to 3.3-angstrom resolution of mitoribosomal large subunits trapped during ribosome rescue. Release factor homolog C12orf65 (mtRF-R) and RNA binding protein C6orf203 (MTRES1) eject the nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for these factors during mitoribosome rescue. We also report related cryo-electron microscopy structures (3.7 to 4.4 angstrom resolution) of elongating mitoribosomes bound to tRNAs, nascent polypeptides, the guanosine triphosphatase elongation factors mtEF-Tu and mtEF-G1, and the Oxa1L translocase. | Mitochondrial Ribosomes |
Actually, only two pangolin species occur naturally in China, namely the Chinese pangolin (Manis pentadactyla) and the Sunda pangolin (Manis javanica). The Sunda pangolin was found to occur naturally in Yunnan, China, but only with a narrow distribution in the Xishuangbanna and Pu'er City. The Indian pangolin (Manis crassicaudata) did not occur in China. The previous claim that this species is naturally distributed in China was found to originate from a mistake in the book The Mammals of China and Mongolia" written by Allen in 1938." | Pangolins |
This study aimed to evaluate the dynamics of Haemonchus contortus and Haemonchus placei infections and hybridization between these species in grazing sheep without contact with cattle. On January 14, 2014, sixteen young sheep were infected with 4000 infective H. placei third-stage larvae L3; 11 days later, another group n = 16 was infected with 4000 H. contortus L3. The establishment rates of H. contortus and H. placei L3 were, on average, 61.6 % and 56.8 %, respectively, in the permanent sheep. After the establishment of patent infections, all permanent sheep were allocated together in the same clean pasture where they grazed for the next 12 months. Euthanasia of a sample of the permanent sheep was performed every three months: in May, August, November and February. Two weeks before the sheep were removed for euthanasia, 2 worm-free tracer sheep were introduced to the pasture to evaluate the larval population in the field. The tracer sheep grazed alongside the permanent sheep for 2 weeks. Then, they were housed indoors for 20 days; at the end of this period, they were euthanized. Parasites were recovered from the permanent and tracer sheep and identified using morphological and molecular techniques. A total of 432 worms (from permanent and tracer animals) were analyzed by PCR using species-specific primer pairs. Of these specimens, only two (0.46 %) male worms were identified as hybrids: one was recovered from a permanent animal euthanized in August and the other from a tracer sheep that grazed in May. The last detection of adult H. placei worms occurred in sheep euthanized in May (approximately 3.5 months after the beginning of the grazing period). The morphological evaluation of the L3 produced in fecal cultures showed that H. placei were progressively replaced by H. contortus populations starting in March. The last trace of H. placei L3 was found in August, when a small percentage (0.5 %) of infective larvae with H. placei morphology was identified in a fecal culture. In conclusion, hybridization between H. contortus and H. placei can occur in the field during coinfection. It was demonstrated that H. placei established successfully in artificially infected worm-free sheep; however, with concomitant natural reinfection with H. contortus, the H. placei population showed a rapid decrease and was eliminated within a few months in an environment without cattle. | Haemonchus |
Protein biosynthesis in bacteria is controlled by a number of translation factors. Recent data based on comparison of sequence and structure data of translation factors have established a novel hypothesis for their interaction with the ribosome: initiation, elongation, and termination factors may use a common or partly overlapping binding site on the ribosome in a process of macromolecular mimicry of an A-site-bound tRNA. This paper reviews structural knowledge and tRNA macromolecular mimicry involvement of translation initiation factor IF2. Furthermore, a model is proposed for the factor and its interaction with the ribosome during the formation of the translation initiation complex." | Prokaryotic Initiation Factors |
System [Formula: see text] is an antiporter belonging to the hetero(di)meric amino acid transporter family. It is located on astrocytes as well as on blood-brain barrier within the CNS. It plays a pivotal role in free radical neutralization as well as neuronal signalling by regulating the glutathione production which occurs via the exchange of intracellular glutamate with extracellular cystine at 1:1 molar ratio. Understandably, it is a vital component responsible for the maintenance of neuronal homeostasis (e.g. redox state). Hence, it could be postulated that any perturbation in system [Formula: see text] function may contribute, directly or indirectly, to the pathophysiology of a variety of CNS disorders like Alzheimer's disease, schizophrenia, drug addiction, depression, multiple sclerosis, hypoglycemic neuronal cell death, glioma, and excitotoxicity, making system [Formula: see text] a promising target for treating CNS disorders. In recent times, recognizing the potential of this target, variety of inhibitors has been synthesized by modifying commercially available potent inhibitors including sulfasalazine, erastin, and sorafenib. Although, they have demonstrated efficacy, the in-depth data is still lacking to warrant their use for the treatment of aforementioned CNS disorders. In this review, we discuss the in-depth role of system [Formula: see text] transporter in maintaining normal physiology as well as in the pathophysiology of CNS diseases. Additionally, we have also listed some of the potent inhibitors of system [Formula: see text]. In conclusion, the critical role of system [Formula: see text] in multiple CNS disorders and advanced research on its inhibitors have promising future prospects for better management of the CNS ailments." | Amino Acid Transport Systems, Basic |
Here we report a simple and efficient method to produce 3,6-anhydro-l-galactose (l-AHG) and agarotriose (AO3) in one step by a multienzyme system with the coimmobilized beta-agarase AgWH50B and alpha-neoagarobiose hydrolase K134D. K134D was obtained by AgaWH117 mutagenesis and showed improved thermal stability when immobilized via covalent bonds on functionalized magnetic nanoparticles. The obtained multienzyme biocatalyst was characterized by Fourier transform infrared spectroscopy (FTIR). Compared with free agarases, the coimmobilized agarases exhibited a relatively higher agarose-to-l-AHG conversion efficiency. The yield of l-AHG obtained with the coimmobilized agarases was 40.6%, which was 6.5% higher than that obtained with free agarases. After eight cycles, the multienzyme biocatalyst still preserved 46.4% of the initial activity. To the best of our knowledge, this is the first report where two different agarases were coimmobilized. These results demonstrated the feasibility of the new method to fabricate a new multienzyme system onto magnetic nanoparticles via covalent bonds to produce l-AHG. | Disaccharidases |
This study involved a total of 116 samples, 79 taken from pigeon droppings and 37 of atmospheric air taken close to accumulations of excrement. Cryptococcus neoformans var. grubii was isolated from 11 (13.9%) of these samples. Other species of Cryptococcus were also isolated from these samples, such as C. albidus (12.6%) and C. laurentii (8.9%). C. neoformans was not isolated from the air samples, though C. albidus (5.4%) was. All the strains of C. neoformans were found to belong to the A serotype (C. neoformans var. grubii). In regard to the studies with the antifungal agents 5-fluorocytosine, fluconazole, itraconazole, amphotericin B and voriconazole, by means of the microdilution method (EUCAST), we point out that one sample demonstrated resistance to fluconazole, this being especially significant because this is an environmental strain. | Cryptococcus neoformans |
Radioimmunodetection (RaID) of tumors containing human chorionic gonadotropin (hCG; choriogonadotropin) was evaluated in 25 patients by injecting 131I-labeled goat antibody IgG against hCG and performing total-body photoscans with a gamma scintillation camera 24 and 48 hr later. All 10 testicular cancer patients with proven tumor sites had positive RaID results, whereas three cases without known tumor were negative. Four patients with hydatidiform mole and one with degenerative products of conception showed positive RaID results consistent with elevated serum hCG titers. Two putatively false-positive results were obtained in patients with lung or ovarian cancer, whereas a false-negative metastasis to the liver of a patient with lung cancer and an elevated serum hCG titer was observed. Of 14 tumor sites found by RaID in 10 testicular cancer patients, 4 were revealed by RaID prior to any other detection method used and provided a lead time to definitive diagnosis by other measures of a few days to greater than 1 yr. Although a number of patients had high serum hCG levels, even exceeding 3 microgram/ml, the xenogeneic antibody was capable of localizing in tumor. No adverse effects were noted in any of the patients studied. Thus, hCG RaID appears to be a safe and effective method of detecting and locating hCG-producing tumors and has been found to disclose occult testicular cancers. | Hydatidiform Mole, Invasive |
In the era of personalized medicine greatly improved by molecular diagnosis and tailor-made therapies, the survival rate of acute myeloid leukemia (AML) at 5 years remains unfortunately low. Indeed, the high heterogeneity of AML clones with distinct metabolic and molecular profiles allows them to survive the chemotherapy-induced changes, thus leading to resistance, clonal evolution, and relapse. Moreover, leukemic stem cells (LSCs), the quiescent reservoir of residual disease, can persist for a long time and activate the recurrence of disease, supported by significant metabolic differences compared to AML blasts. All these points highlight the relevance to develop combination therapies, including metabolism inhibitors to improve treatment efficacy. In this review, we summarized the metabolic differences in AML blasts and LSCs, the molecular pathways related to mitochondria and metabolism are druggable and targeted in leukemia therapies, with a distinct interest for Venetoclax, which has revolutionized the therapeutic paradigms of several leukemia subtype, unfit for intensive treatment regimens. | Clonal Evolution |
Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 (SNAP23) and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and Kif5, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression. | Qc-SNARE Proteins |
BACKGROUND: As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported that mifepristone may cause cell death in decidual cells and result in hemorrhage of the decidua and insufficient blood supply. However, little is known about the histological effects of mifepristone on human decidua and chorion. METHODS: Histological and subcellular structural changes of decidua and chorionic villi from women taking mifepristone at early pregnancy times were examined by Hematoxylin and eosin (H&E) staining and transmission Electron microscope. The expression of apoptosis-related proteins Bax/Bcl-2 was examined by immunohistochemistry. RESULTS: After 48 h of mifepristone administration, the decidua tissue and chorionic villus structures were altered in women within 39-49 days of gestation and displayed varying degrees of degeneration and necrosis-like features. Apoptotic events were observed in the decidua and chorionic villi of early pregnancy, and mifepristone treatment significantly increases the number of apoptotic cells. The increased apoptotic events were concomitant with the increased expression of Bax and decreased expression of Bcl-2. CONCLUSION: This study provides evidence that mifepristone induces histological and subcellular changes in decidua and chorionic villi. Mifepristone modulates the relative ratio of Bax/Bcl-2 and the increased apoptosis contributes to the pregnancy termination at early stage of pregnancy. | Mifepristone |
Reference is made to the authors' own experience and to evaluated literature in an account of possibilities which so far have been explored for planned control of reproduction processes in industrialised cattle production. Synchronisation of oestrus in heifer has been found to be suitable for reproduction control even under conditions of industrialised production. The method has been in use on several farms. Synchronisation of oestrus in cow is an approach which still is in the process of translation into practice. Obtainable advantages, like those in the context of heifer, will include better job conditions. Systematic puerperal monitoring, too, will yield positive effects in controlling post-partum readiness of cow for reproduction. Results so far achieved include progress towards the introduction of a complex reproduction technology in cattle production. Before such complete system of reproduction control can be used, further studies are required into some fundamental aspects of the problem, including calving control, pregnancy examination, and gravidity hagiene." | Reproductive Physiological Phenomena |
At least some mammalian tissues produce H2S in vitro from L-cysteine at rates sufficient to have physiological effects. To determine whether tissues of macrofaunal invertebrates have the same capacity, we measured H2S production in tissue homogenates of the Manila clam Tapes philippinarum and the lugworm Arenicola marina. Tissue homogenates from both animals produced significant quantities of H2S gas upon addition of L-cysteine and the enzyme cofactor pyridoxal-5PRIME;-phosphate (10 mmol l(-1) and 2 mmol l(-1), respectively), while only tissues from T. philippinarum produced measurable H2S in the absence of added substrate or cofactor. In T. philippinarum tissues, H2S production was completely inhibited by the cystathionine beta-synthase (CBS) inhibitor aminooxyacetic acid (AOAA), suggesting that the majority of H2S production was via CBS pathways, while in A. marina body wall, AOAA inhibited only half of the total H2S production, indicating that the CBS pathway was not the only major source of H2S production. H2S production in tissues of T. philippinarum but not A. marina was doubled by the addition of a second thiol substrate (2.5 mmol l(-1) 2-mercaptoethanol), suggesting the presence of an 'activated serine sulfhydrase pathway', which had previously been demonstrated only in some microfauna. | Aminooxyacetic Acid |
We report our study on the correlation between the types of anastomosis and the incidence of anastomotic stricture formation in the upper gastro-intestinal tract. Our experience with balloon dilatation is also reported. We examined the incidence of stricture formation among patients who had an anastomosis between the esophagus and stomach following subtotal esophagectomy for esophageal cancer, and esophagojejunostomy following proximal or total gastrectomy for gastric cancer in the past 17 years. Among 283 patients undergoing esophagojejunostomy, 7 cases of stricture (excluding 3 cases of cancer recurrence) were observed (conventional anastomosis 1.8%; stapling anastomosis 4.6%). There were 17 cases of stricture among 56 patients who had anastomosis between the esophagus and stomach following subtotal esophagectomy (conventional anastomosis 28.6%; stapling anastomosis 50.0%). One month or more after the operation, the diameter of the esophagojejunostomy was estimated using a barium study. The mean diameter of the anastomosis using the stapling method was 11.9 +/- 2.9 mm, whereas the mean diameter of serosubmucosal single layer hand-sewn anastomosis (Jourdan's) was 19.8 +/- 2.2 mm, and that of vertical mattress hand-sewn anastomosis was 19.0 +/- 2.0 mm. Balloon dilatation was used in 29 patients with anastomotic stricture of the upper gastro-intestinal tract (esophageal cancer, 19 patients, gastric cancer, 10 patients). With repeated dilatation, we were able to obtain satisfactory efficacy for benign strictures and there were no severe complications. We believe that balloon dilatation is an easy, safe and effective therapy for anastomotic stricture of the upper gastro-intestinal tract. | Surgical Staplers |
Dihydropyrimidine dehydrogenase (DHPDase), dihydropyrimidinase (DHPase) and beta-ureidopropionase (betaUPase) are the enzymes that catalyze the first, second, and third steps of the degradation of pyrimidines, respectively. beta-Ureidopropionate (betaUP) and beta-ureidoisobutyrate (betaUIB) are increased in the urine of patients with betaUPase deficiency. The original case in which betaUPase deficiency was discovered by NMR spectroscopy was an 11-month-old patient who presented with hypotonia and dystonic movement. We detected a second but asymptomatic case during a pilot study of neonatal screening with filter-paper urine, urease pretreatment and gas chromatography/mass spectrometry (GC/MS). The urease pretreatment of urine without fractionation resulted in a high recovery of these polar ureide compounds and allowed the highly sensitive GC/MS detection and diagnosis of betaUPase deficiency. betaUP and betaUIB were identified using GC/MS techniques. In the urine of the neonate with betaUPase deficiency, betaUP and betaUIB were persistently increased. Thymine, 5,6-dihydrothymine and 5,6-dihydrouracil were increased only moderately but significantly. It is known that thymine and uracil increase markedly in DHPDase deficiency, and 5,6-dihydrothymine and 5,6-dihydrouracil increase in DHPase deficiency. Therefore, betaUPase deficiency can be differentially diagnosed from the first and second enzyme deficiencies. Application of this specific and sensitive diagnostic procedure will lead to an understanding of the clinical heterogeneity of betaUPase deficiency. Furthermore, the identification of patients with defects in pyrimidine metabolism will enable doctors to avoid cancer chemotherapy with pyrimidine analogues such as 5-fluorouracil, which could be dangerous for these patients." | Purine-Pyrimidine Metabolism, Inborn Errors |
Understanding the mechanisms of ligand binding to enzymes is of paramount importance for the design of new drugs. Here, we report on the use of a novel biased molecular dynamics (MD) methodology to study the mechanism of camphor binding to cytochrome P450cam. Microsecond-long MD simulations allowed us to observe reaction coordinates characterizing ligand diffusion from the active site of cytochrome P450cam to solvent via three egress routes. These atomistic simulations were used to estimate thermodynamic quantities along the reaction coordinates and indicate diverse binding configurations. The results suggest that the diffusion of camphor along the pathway near the substrate recognition site (SRS) is thermodynamically preferred. In addition, we show that the diffusion near the SRS is triggered by a transition from a heterogeneous collection of closed ligand-bound conformers to the basin comprising the open conformations of cytochrome P450cam. The conformational change accompanying this switch is characterized by the retraction of the F and G helices and the disorder of the B' helix. These results are corroborated by experimental studies and provide detailed insight into ligand binding and conformational behavior of the cytochrome family. The presented methodology is general and can be applied to other ligand-protein systems. | Camphor |
A one-pot procedure for the efficient hydroazidation of alkenes involving hydroboration with catecholborane followed by reaction with benzenesulfonyl azide in the presence of a radical initiator is described. The regioselectivity is controlled by the hydroboration step and corresponds in most cases to an anti-Markovnikov regioselectivity. This procedure is applicable to a wide range of alkenes and gives excellent results with 1,2-disubstituted and trisubstituted alkenes. | Azides |
The prevailing sandstorm environment of Lop Nur is a high-risk factor which can induce respiratory diseases. Ephedra can cure the patients or relieve the symptom. These may make ancient Lop Nur peoples worship ephedra. Therefore, viewed it as burial objects. From the point of view of some eastern and western religions, ephedra was the elixir of life. Since ephedrine ephedra contains can excite the sympathetic nerves of human body, it makes people have an illusion.Ephedra can restore their youth. Ancient people of Lop Nur viewed ephedra as a holy item. Both the functions of therapy and youth restoration" from exciting the nerves, meant guarantee for life. For ancient Lop Nur peoples, ephedra has the value of both medicine and religion." | Ephedra |
In addition to acting as diagnosticians, surgical pathologists are increasingly becoming prognosticians. Currently there are 3 staging groups: the International Federation of Gynecology and Obstetrics (FIGO), the American Joint Commission on Cancer (AJCC), and the International Union against Cancer (UICC), each forming its own staging system. However, despite diligent efforts, these classification systems do not yet agree in their reporting of cancer staging. Because having a uniform set of staging guidelines is essential for consistent interpretation and management of patients with cancer, we attempt to review the issues and inconsistencies that exist in the current staging guidelines. Specifically, we compare and contrast the AJCC/UICC and the parallel system formulated by FIGO in the diagnosis of cancers in the gynecologic tract, focusing on the vulva, vagina, cervix, and endometrium/uterus. Our hopes are to clarify the controversies, because a more unified system must be created to eliminate ongoing inconsistencies, and to make communication and treatment even more reliable. | Neoplasm Staging |
Programmed cell death or apoptosis is an essential component of human ovarian function and development. During early fetal life approximately 7 x 10(6) oocytes are formed in the human ovary. However, the number of oocytes is dramatically reduced already before birth through apoptotic cell death. In reproductive life, a number of primordial follicles start growing during each menstrual cycle. Usually only one will ovulate and the fate of the rest of the follicles is atresia through the mechanism of apoptosis. Ultimately, only around 400 follicles will ovulate during a woman's reproductive life. After ovulation, the dominant follicle forms the corpus luteum, a novel endocrine gland that is responsible for the production of progesterone and maintenance of endometrium during early pregnancy. If pregnancy does not occur, corpus luteum action must cease so that new follicles can resume growing during the next menstrual cycle. Apoptosis is also responsible for corpus luteum regression in the human ovary. In recent years, new knowledge of the role and regulation of apoptosis in the ovary has been acquired through the use of knockout and transgenic animals. Apoptosis seems to be the mechanism that makes the female biological clock tick. The following review will discuss the role of apoptosis and its regulation of human ovarian function. | Luteolysis |
The anaphase-promoting complex is composed of eight protein subunits, including BimE (APC1), CDC27 (APC3), CDC16 (APC6), and CDC23 (APC8). The remaining four human APC subunits, APC2, APC4, APC5, and APC7, as well as human CDC23, were cloned. APC7 contains multiple copies of the tetratrico peptide repeat, similar to CDC16, CDC23, and CDC27. Whereas APC4 and APC5 share no similarity to proteins of known function, APC2 contains a region that is similar to a sequence in cullins, a family of proteins implicated in the ubiquitination of G1 phase cyclins and cyclin-dependent kinase inhibitors. The APC2 gene is essential in Saccharomyces cerevisiae, and apc2 mutants arrest at metaphase and are defective in the degradation of Pds1p. APC2 and cullins may be distantly related members of a ubiquitin ligase family that targets cell cycle regulators for degradation." | Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome |
The use of androgen therapy to improve the poor quality of semen was assessed on 69 subfertile men. The men were treated with 2 or 4 mg of fluoxymesterone daily up to 12 months. During the course of treatment, the semen samples were analyzed every 3 months and the overall mean values for various semen characteristics were compared before and after the onset of treatment. The sperm motility and normal sperm morphology showed a significant improvement with treatment. Based on overall evaluation, androgen therapy may benefit some patients, while in others it may not significantly alter the semen quality. | Fluoxymesterone |
We have previously found that leachate from a Swedish refuse dump caused toxicological effects, including endocrine disruption and reproductive failures, in feral female perch (Perca fluviatilis) from Molnbyggen and in brook trout (Salvelinus fontinalis) from Vadbacken. This raised concerns that leachate-induced toxicity might affect fish in other leachate-contaminated lakes. This study looks at female perch from three different regions in Sweden, focusing on toxicological biomarkers (skin lesions, liver-somatic index (LSI), ethoxyresorufin O-deethylase (EROD) activity and DNA adducts) and reproductive biomarkers (number of mature females, gonadosomatic index (GSI), aromatase (P450arom), progesterone, 17alpha-hydroxyprogesterone (17alpha-OHP), testosterone (T) and 17beta-estradiol (E2)). Five out of seven contaminated locations had lower numbers of mature females and most of them exhibited higher frequencies of fin erosion relative to their comparable reference sites. Females from Lake Nedre Vattern exhibited these effects, as well as body sores, high EROD activity, high levels of DNA adducts in the liver and the intestinal mucosa, low GSI and low plasma levels of T and E2, similar to the anti-estrogenic effects earlier found in SM perch from Molnbyggen in 1997 and in brook trout from Vadbacken. No effects on LSI, GSI, aromatase, or circulating steroids were found in mature females from Molnbyggen in this study. This indicated less leachate-contamination, but low numbers of mature females in Lake Siljan, at the sewage treatment plant which now processes the leachate that earlier contaminated Molnbyggen and Vadbacken, suggested insufficient sewage treatment at this site. All females in Lake Simshyttsjon were mature, and their high GSI and LSI, low EROD activity, high level of 17alpha-OHP and low level of T, suggest an estrogenic rather than an anti-estrogenic effect. The results show that our earlier findings in Molnbyggen and Vadbacken are not common, but neither are they unique. This study also shows that refuse dumps should be considered as potential point-sources for environmental pollutants, and that uncontrolled leachate-contamination of lakes and freshwater reservoirs could be a serious environmental hazard for both wildlife and humans. | Perches |
The chiral structure of antibiotic vancomycin (Van) was exploited as an innovative coordination sphere for the preparation of an IrCp* based hybrid catalysts. We found that Van is able to coordinate iridium (Ir(III)) and the complexation was demonstrated by several analytical techniques such as MALDI-TOF, UV, Circular dichroism (CD), Raman IR, and NMR. The hybrid system so obtained was employed in the Asymmetric Transfer Hydrogenation (ATH) of cyclic imines allowing to obtain a valuable 61% e.e. (R) in the asymmetric reduction of quinaldine 2. The catalytic system exhibited a saturation kinetics with a calculated efficiency of K(cat)/K(M) = 0.688 h(-1)mM(-1). | Quinaldines |
BACKGROUND: Although palliative care providers, patients, and their families rely heavily on accurate prognostication, the prognostic value of electrolyte imbalance has received little attention. METHODS: As a retrospective review, we screened inpatients with terminal cancer admitted between January 2017 and May 2019 to a single hospice-palliative care unit. Clinical characteristics and laboratory results were obtained from medical records for multivariable Cox regression analysis of independent prognostic factors. RESULTS: Of the 487 patients who qualified, 15 (3%) were hypernatremic upon admission. The median survival time was 26 days. Parameters associated with shortened survival included male sex, advanced age (> 70 years), lung cancer, poor performance status, elevated inflammatory markers, azotemia, impaired liver function, and hypernatremia. In a multivariable Cox proportional hazards model, male sex (hazard ratio [HR] = 1.53, 95% confidence interval [CI]: 1.15-2.04), poor performance status (HR = 1.45, 95% CI: 1.09-1.94), leukocytosis (HR = 1.98, 95% CI: 1.47-2.66), hypoalbuminemia (HR = 2.06, 95% CI: 1.49-2.73), and hypernatremia (HR = 1.55, 95% CI: 1.18-2.03) emerged as significant predictors of poor prognosis. CONCLUSION: Hypernatremia may be a useful gauge of prognosis in patients with terminal cancer. Further large-scale prospective studies are needed to corroborate this finding. | Hypernatremia |
Autoimmune diseases are characterized by an insufficiency of immune tolerance and, although treated with a number of useful drugs, may need more unconventional therapeutic strategies for their more severe presentations. Among such unconventional therapeutic approaches, stem cell autograft and allograft have been used, with the aim of stimulating disease remission by modifying the pathogenic mechanisms that induce anomalous responses against self-antigens. Autologous transplantation is performed with the purpose of retuning autoimmune cells, whereas allogeneic transplantation is performed with the purpose of replacing anomalous immune effectors and mediators. In this article, we comprehensively review up-to-date information on the autoimmune diseases for which the transplantation of stem cells is indicated. | Autografts |
Colorectal cancer (CRC) screening is widely recommended as part of standard preventive care. All average risk persons over the age of 50 y are eligible. Various authorities have advocated fecal occult blood testing, flexible sigmoidoscopy, barium enema and colonoscopy at varying intervals as acceptable screening options. Despite the array of choices, CRC screening lags in frequency behind other cancer screening maneuvers like mammography or Pap smear. Of late, there is growing interest in CT colonography (CTC) as another screening option. CTC, or virtual colonoscopy, may represent an attractive, non-invasive method of CRC screening that provides images akin to traditional colonoscopy. Improvements in CTC performance, especially when coupled with declining costs, suggest that CTC's role in average risk screening will increase in the future. This review summarizes available data about the efficacy of CTC in average and high risk screening populations. Current indications as well as limitations to this technology are discussed, as are practical issues like the cost-effectiveness of CTC for widespread use. | Colonoscopy |
Cation recognition mechanisms beyond calcium-sensing receptors are still largely unexplored and consequently there is surprisingly little information on linking of this primary event to key metabolic features of different cell systems, such as arachidonic acid metabolism. However, information on the modulatory role of extracellular cations in cellular function is scarce. In this study we have demonstrated, that Ni(2+) and Sr(2+) potentiate endothelin-1 induced prostaglandin E2 formation in the osteoblastic cell line, MC3T3-E1, even in the absence of extracellular calcium. The effect is strictly dependent of receptor-mediated signal transduction processes evoked by endothelin-1 and arachidonate release involves cytosolic phospholipase A2 activity. The ligation sites, at least for Ni(2+) are extracellular. The data suggest a novel activation mechanism for arachidonate release and subsequent prostaglandin formation that does not require calcium. | Group IV Phospholipases A2 |
Colicin E8-J and its immunity protein were characterized with regard to their activities and gene structures. Colicin E8 is a complex of proteins A and B; protein A (the naked E8) exhibits an apparently nonspecific DNase activity that is inhibited by protein B (the immunity protein), as in the case of colicin E2. The nucleotide sequence of the downstream half of the colicin operon of ColE8-J was determined to be highly homologous to that of ColE2-P9, with the exception of the hot spot region of the 3'-terminal segment of the colicin gene and the adjacent immunity gene. The immE2-like gene of ColE3-CA38 was, as assumed previously, extensively homologous to the immE8 gene of ColE8-J, and thus, ColE8-J was shown to be situated between ColE2-P9 and ColE3-CA38 in the evolution of the E-group Col plasmids. | Colicins |
BACKGROUND: The Food and Drug Administration (FDA) became aware of lead fracture and inappropriate shock events related to Sprint Fidelis leads in January 2007. The manufacturer announced a voluntary market withdrawal in October 2007. AIM: Our aim was to retrospectively evaluate this safety signal using disproportionality analysis to estimate whether disproportionality analysis could have detected this particular safety signal earlier than actually occurred. MATERIALS AND METHODS: The Manufacturer and User Facility Device Experience (MAUDE) database contains reports on device-related adverse events, of which, FDA receives several hundred thousand every year. For each manufacturer, a list of the top lead brand names was ranked by frequency of reports. We used the Multi-item Gamma Poisson Shrinker (MGPS) method for analysis. We isolated 11 top-reported implantable cardioverter defibrillator (ICD) lead brand names. Using MGPS methodology, we calculated the one-sided 95% lower confidence bound EB05 on the empirical Bayes geometric mean of the reporting ratio. RESULTS: We performed individual MGPS analysis for each of the top reported adverse events in 2006 for ICD leads. Fidelis had the highest EB05 scores for lead fractures and inappropriate shock. DISCUSSION: Through disproportionality analysis of the MAUDE database, we were able to identify known safety signals associated with the Medtronic Sprint Fidelis lead. CONCLUSION: If utilized at the time, this disproportionality analysis would have identified signals earlier for lead fractures, oversensing, high impedance, and inappropriate shock." | Safety-Based Medical Device Withdrawals |
BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian disorder that involves degeneration of brain regions associated with motor coordination and sensory processing. Combining transcranial direct current stimulation (tDCS) with rehabilitation training has been shown to improve upper-limb performance in other disease models. Here, we describe the protocol investigating whether tDCS with neurologic music therapy (NMT) (patterned sensory enhancement and therapeutic instrumental music performance) enhances functional arm/hand performance in individuals with CBS. METHODS: Study participants are randomly assigned to six 30-min sessions (twice per week for 3 weeks) of NMT + either sham tDCS or active tDCS. We aim to stimulate the frontoparietal cortex, which is associated with movement execution/coordination and sensory processing. The hemisphere contralateral to the more affected arm is stimulated (total stimulation current of 2 mA from 5 dime-sized electrodes). Individualized NMT sessions designed to exercise the upper limb are provided. Participants undergo gross/fine motor, cognitive and emotional assessments at baseline and follow-up (one month after the final session). To investigate the immediate effects of tDCS and NMT training, gross /fine motor, affective level, and kinematic parameter measurements using motion sensors are collected before and after each session. Electroencephalography is used to collect electrical neurophysiological responses before, during, and after tDCS+NMT sessions. The study participants, neurologic music therapist and outcome assessor are blinded to whether participants are in the sham or active tDCS group. CONCLUSION: This noninvasive and patient-centered clinical trial for CBS may provide insight into rehabilitation options that are sorely lacking in this population. | Corticobasal Degeneration |
INTRODUCTION: The safety and efficacy of medications stored on air medical helicopters may be adversely affected by extreme temperatures. The purpose of this study was to determine whether temperatures inside an air medical helicopter drug box were within the U.S. Pharmacopeia recommendations for controlled room temperature. This is defined as a temperature between 15 degrees and 30 degrees C (59 degrees and 86 degrees F) with a mean kinetic temperature of less than 25 degrees C (77 degrees F). An additional goal was to determine whether time/temperature indicator labels can reliably monitor mean kinetic temperatures. METHODS: Temperatures were monitored with miniature electronic temperature recorders and color-changing time/temperature indicator labels. RESULTS: The mean kinetic temperatures for the summer and winter periods were 25.1 degrees C (77.2 degrees F) and 12.7 degrees C (54.8 degrees F), respectively. In the summer, the electronic recorders logged temperatures exceeding 25 degrees C (59 degrees F) 37% of the time and more than 30 degrees C (86 degrees F) 6% of the time. In the winter, temperatures less than 15 degrees C (59 degrees F) were recorded 83% of the time. The mean kinetic temperatures obtained from the electronic recorder and the time/temperature indicator labels differed by less than 0.7 degree C (1.3 degrees F). The results show that medications on an air medical helicopter are subject to temperatures out of the recommended range and that time/temperature indicator labels can reliably monitor mean kinetic temperatures. | Air Ambulances |
BACKGROUND: Otalgia is a common presenting symptom to the ENT clinic. The aetiology of otalgia can be divided into otological and referred depending on its underlying pathology. This article aims to provide a systematic and evidence-based method of managing a patient with referred otalgia. METHODS: The data in this article are based on a literature review performed on MEDLINE and EMBASE in January 2010. The keywords used included otalgia in combination with diagnosis, management, investigations and treatment. Articles in the English language were selected and reviewed. Suitable references from these articles were also reviewed. RESULTS: The majority of published literature on the management of diseases causing referred otalgia is level III/IV evidence. CONCLUSIONS: An understanding of the different causes of referred otalgia is essential as it can be multifactorial in origin. The main concern in a patient with referred otalgia is overlooking a malignant lesion in the upper aerodigestive tract or base of skull/infratemporal fossae. A thorough history followed by a systematic examination usually helps to arrive at a diagnosis. Treatment should be directed towards the underlying pathology. | Earache |
BACKGROUND: Earlier initial antibiotic treatment for febrile neutropenia is associated with improved clinical outcomes. This study was conducted to evaluate the association of an emergency department (ED) intervention protocol with time to initial antibiotic treatment for febrile neutropenia patients. METHODS: We conducted a cohort study of adult ED febrile neutropenia patients before and after implementation of an intervention protocol. Analyses included comparison of means and medians, Kaplan-Meier estimates, multivariable regression analyses, interrupted time-series analyses, and causal mediation analyses. The intervention protocol included specific triage and process-of-care actions to reduce the primary outcome of time to initial antibiotic treatment. RESULTS: There were 69 patients in the 12-month preintervention period and 52 patients in the 8-month postintervention period. The mean (+/-SD) times to initial antibiotics were 197.6 (+/-85.4) min for the preintervention group and 97.7 (+/-51.0) min for the postintervention group (difference of 99.9 min with 95% confidence interval [CI] = 73.5 to 126.4, p < 0.001). The patients' probability for receiving initial antibiotics within 90 min was severalfold greater (adjusted risk ratio = 10.31, 95% CI = 4.99 to 21.30, p < 0.001) for the postintervention group versus preintervention group. ED length of stay, hospital length of stay, 30-day readmissions, and 30-day all-cause mortality were not different between the study groups. The association of the intervention protocol with time to initial antibiotics appeared to be mediated through times to treatment room placement, report of absolute neutrophil count, and initial antibiotic order. CONCLUSIONS: The intervention protocol was associated with a significant reduction in time to initial antibiotics for ED patients with febrile neutropenia. This association appears to be facilitated through specific intermediate process-of-care variables. A larger multicenter study is needed to assess the potential effects of an ED febrile neutropenia protocol on patient-centered clinical outcomes and resource utilization. | Febrile Neutropenia |
Pediatric cardiac arrest presents an infrequent but high-stakes event for emergency clinicians, who need to maintain expertise in this area. Evidence regarding pediatric resuscitations has been accumulating substantially over the past decade and highlights the unique considerations and challenges when resuscitating children. This issue reviews resuscitation principles of children in cardiac arrest while addressing the newest evidence-based and best-practice recommendations by the American Heart Association. | American Heart Association |
The effects of bergapten-containing preparations in sunlight-induced skin pigmentation were evaluated. Oil and lotion vehicles with bergapten/UV-B sunscreen or sunscreen alone were applied to the backs of subjects twice weekly for 4 weeks and the subjects were exposed to gradually increasing doses of midday sunlight. The degree of skin darkening was assessed by clinical examination, reflectometry, and light microscopy of skin biopsy specimens. At 5 weeks, 1 week after the last sunlight exposure, the sites treated with either the bergapten/UV-B sunscreen lotion or the lotion vehicle were significantly darker than the sites treated with the sunscreen lotions without bergapten. Oil preparations produced less clearcut results, possibly because of a less potent sunscreen or because the bergapten did not leave the vehicle and absorb into the epidermis. In type I skin, the bergapten/sunscreen and the oil vehicle alone produced the same amount of tanning; both yielded more tanning than the sunscreen in oil by clinical examination. The findings were not confirmed by reflectometry or by light microscopy. Thus, we conclude that bergapten added to a UV-B sunscreen lotion preparation can increase skin pigmentation over the sunscreen alone when one is exposed to sunlight. The bergapten/UV-B sunscreen combination is a potentially useful product since one can develop a psoralen and UV-A-induced tan while being protected from UV-B-induced sunburn by the UV-B sunscreen incorporated into the formulation. | Methoxsalen |
While the role of trefoil factors (TFF) in the maintenance of epithelial integrity in the gastrointestinal tract is well known, their involvement in wound healing in the conducting airway is less well understood. We defined the pattern of expression of TFF1, TFF2, and TFF3 in the airways of mice during repair of both severe (300 mg/kg) and moderate (200 mg/kg) naphthalene-induced Clara cell injury. Quantitative real-time PCR for tff messenger RNA expression and immunohistochemistry for protein expression were applied to airway samples obtained by microdissection of airway trees or to fixed lung tissue from mice at 6 and 24 h and 4 and 7 days after exposure to either naphthalene or an oil (vehicle) control. All three TFF were expressed in normal whole lung and airways. TFF2 was the most abundant and was enriched in airways. Injury of the airway epithelium by 300 mg/kg naphthalene caused a significant induction of tff1 gene expression at 24 h, 4 days, and 7 days. In contrast, tff2 was decreased in the high-dose group at 24 h and 4 days but returned to baseline levels by 7 days. tff3 gene expression was not significantly changed at any time point. Protein localization via immunohistochemistry did not directly correlate with the gene expression measurements. TFF1 and TFF2 expression was most intense in the degenerating Clara cells in the injury target zone at 6 and 24 h. Following the acute injury phase, TFF1 and TFF2 were localized to the luminal apices of repairing epithelial cells and to the adjacent mesenchyme in focal regions that correlated with bifurcations and the bronchoalveolar duct junction. The temporal pattern of increases in TFF1, TFF2, and TFF3 indicate a role in cell death as well as proliferation, migration, and differentiation phases of airway epithelial repair. | Trefoil Factors |
In six sedated, anesthetized, paralyzed, and mechanically ventilated guinea pigs, total respiratory system (RT,rs), lung, and chest wall resistances and respiratory system (Est,rs), lung, and chest wall (Est,w) elastances were determined before and after longitudinal laparotomy. Furthermore the resistances were also split into their initial and difference components, with the former reflecting the Newtonian resistances and the latter representing the viscoelastic/inhomogeneous pressure dissipations in the system. For such purpose the end-inflation occlusion during constant inspiratory flow method was used. During laparotomy, a statistically significant increase in respiratory system difference resistance (from 0.086 to 0.101 cmH2O.ml-1.s) significantly augmented RT,rs (from 0.157 to 0.167 cmH2O.ml-1.s). The former was entirely secondary to a significant increase in chest wall difference resistance (0.019 to 0.034 cmH2O.ml-1.s), which naturally raised chest wall total resistance (from 0.030 to 0.047 cmH2O.ml-1.s). Est,rs and Est,w also increased (14.7 and 13.1%, respectively) after abdominal incision. It can be concluded that the midline xiphipubic laparotomy accompanied by the bilateral ventrodorsal infracostal incision increases RT,rs as a consequence of augmented chest wall difference resistance and Est,rs as a result of higher Est,w. | Airway Resistance |
Complex interactions between genes and environment result in a sodium-induced elevation in blood pressure (salt sensitivity) and/or hypertension that lead to significant morbidity and mortality affecting up to 25% of the middle-aged adult population worldwide. Determining the etiology of genetic and/or environmentally-induced high blood pressure has been difficult because of the many interacting systems involved. Two main pathways have been implicated as principal determinants of blood pressure since they are located in the kidney (the key organ responsible for blood pressure regulation), and have profound effects on sodium balance: the dopaminergic and renin-angiotensin systems. These systems counteract or modulate each other, in concert with a host of intracellular second messenger pathways to regulate sodium and water balance. In particular, the G protein-coupled receptor kinase type 4 (GRK4) appears to play a key role in regulating dopaminergic-mediated natriuresis. Constitutively activated GRK4 gene variants (R65L, A142V, and A486V), by themselves or by their interaction with other genes involved in blood pressure regulation, are associated with essential hypertension and/or salt-sensitive hypertension in several ethnic groups. GRK4gamma ï 142Vï transgenic mice are hypertensive on normal salt intake while GRK4gammaï 486Vï transgenic mice develop hypertension only with an increase in salt intake. GRK4 gene variants have been shown to hyperphosphorylate, desensitize, and internalize two members of the dopamine receptor family, the D(1) (D(1)R) and D(3) (D(3)R) dopamine receptors, but also increase the expression of a key receptor of the renin-angiotensin system, the angiotensin type 1 receptor (AT(1)R). Knowledge of the numerous blood pressure regulatory pathways involving angiotensin and dopamine may provide new therapeutic approaches to the pharmacological regulation of sodium excretion and ultimately blood pressure control." | G-Protein-Coupled Receptor Kinase 4 |
BACKGROUND: A 1994 National Institutes of Health consensus panel recommended that eradication of Helicobacter pylori should be first-line therapy for persons with duodenal ulcer. OBJECTIVE: To assess the cost-effectiveness of H pylori eradication relative to alternative pharmacologic strategies in the long-term management of persons with confirmed duodenal ulcer. METHODS: Decision analysis model to estimate expected costs and symptomatic ulcer recurrences during a 12-month period for three general treatment strategies: (1) immediate H pylori eradication; (2) H pylori eradication at first ulcer recurrence; and (3) continuous maintenance therapy with a histamine2 receptor antagonist (ranitidine hydrochloride). Two H pylori eradication therapies were compared: classic triple therapy and omeprazole plus amoxicillin. Probabilities for ulcer recurrence are by meta-analysis of published randomized trials. Health care resources used in the management of duodenal ulcer recurrence were by expert physician panel. All costs are in 1993 Canadian dollars. RESULTS: Duodenal ulcer recurrence at 6 months (symptomatic and asymptomatic) with placebo was 65.4% and 12.8% with maintenance ranitidine therapy. Where eradication of H pylori was successful (85% of patients), the ulcer recurrence rate to 12 months was 3.7%. Treatment with ranitidine and triple therapy to eradicate H pylori on first presentation has an expected 1-year cost of $253 with 15 symptomatic recurrences per 100 patients; H pylori eradication by omeprazole plus amoxicillin had similar expected costs ($272) and outcomes (15 recurrences per 100 patients). Both of these early H pylori eradication strategies were dominant (less costly with same or better outcomes) over intermittent or continuous maintenance ranitidine therapy or delayed (after first recurrence) H pylori eradication. CONCLUSION: Our analysis provides economic evidence in support of the recent guidance that for persons with duodenal ulcer, early attempts to eradicate H pylori are recommended. | Duodenal Ulcer |
Theobromine metabolism and clearance were investigated at steady-state under chronic oral dosing conditions in eight healthy volunteers, four of whom were cigarette smokers. The subjects were studied before and after separate 1 week pretreatments with cimetidine (1 g/day) and sulfinpyrazone (800 mg/day). Theobromine plasma clearance (ClTB) was 33% higher in smokers than in non-smokers due to induction of all metabolic pathways (3-demethylation, 7-demethylation, and formation of 6-amino-5-(N-methylformylamino)-1-methyluracil (AMMU]. 7-Demethylation was induced by cigarette smoking to a greater extent than the other pathways. Cimetidine pretreatment inhibited theobromine 3-demethylation and AMMU formation resulting in a 27% decrease in ClTB in the combined smoker/nonsmoker group. The 7-demethylation pathway was unaffected by cimetidine. In contrast, sulfinpyrazone pretreatment increased ClTB by 50% in the whole group by approximately equal induction of each metabolic pathway. The extent of induction due to sulfinpyrazone was 2.4-fold greater in nonsmokers than in smokers. When compared with previous data relating to theophylline, the results suggest that theobromine 3-demethylation is mediated by the same form(s) of cytochrome P-450 involved in theophylline demethylation, while a second form(s) of cytochrome P-450 is involved in theobromine 7-demethylation and theophylline 8-hydroxylation. In addition, since AMMU formation was inhibited by cimetidine and induced by cigarette smoking and sulfinpyrazone, it would appear that the conversion of theobromine to AMMU is also mediated by cytochrome P-450. | Sulfinpyrazone |
Isoprostanes (IsoPs) and neuroprostanes (NeuroPs) are formed in vivo by a free radical non-enzymatic mechanism involving peroxidation of arachidonic acid (AA, C20:4 n-6) and docosahexaenoic acid (DHA, C22:6 n-3) respectively. This review summarises our research in the total synthesis of these lipid metabolites, as well as their biological activities and their utility as biomarkers of oxidative stress in humans. | Neuroprostanes |
Preliminary experiments show that rabbit anti sea star T-like serum recognizes T-like cells from two different geographic regions but not mouse T lymphocytes and man T lymphocytes. On the other hand, cytotoxicity reactions do not occur with this serum. | Antilymphocyte Serum |
This report of a working group established by the Japan Diabetes Society proposes a new classification and diagnostic criteria for insulin resistance syndrome. Insulin resistance syndrome is defined as a condition characterized by severe attenuation of insulin action due to functional impairment of the insulin receptor or its downstream signaling molecules. This syndrome is classified into two types: genetic insulin resistance syndrome, caused by gene abnormalities, and type B insulin resistance syndrome, caused by autoantibodies to the insulin receptor. Genetic insulin resistance syndrome includes type A insulin resistance as well as Donohue and Rabson-Mendenhall syndromes, all of which are caused by abnormalities of the insulin receptor gene; conditions such as SHORT syndrome caused by abnormalities of PIK3R1, which encodes a regulatory subunit of phosphatidylinositol 3-kinase; conditions caused by abnormalities of AKT2, TBC1D4, or PRKCE; and conditions in which a causative gene has not yet been identified. Type B insulin resistance syndrome is characterized by severe impairment of insulin action due to the presence of insulin receptor autoantibodies. Cases in which hypoglycemia alone is induced by autoantibodies that stimulate insulin receptor were not included in Type B insulin resistance syndrome. | Donohue Syndrome |
Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from the hydroxycinnamic acid family. Epidemiological, biological, and biochemical studies concur to support the beneficial role of chlorogenic acid in human health, along with other dietary phenolic compounds. Thus, chlorogenic acid has been reported to exert inhibitory effects on carcinogenesis in the large intestine, liver, and tongue, and a protective action on oxidative stress in vivo, together with anti-inflammatory, antidiabetic and antihypertensive activities. It is also claimed to have antifungal, antibacterial and antiviral effects with relatively low toxicity and side effects, alongside properties that do not lead to antimicrobial resistance. Due to its importance, numerous methods for determining chlorogenic acid (CGA), as well as for its derivatives from coffee beans and other plants, were elaborated. The most frequently used methods are infrared spectroscopy, high performance liquid chromatography (HPLC), capillary electrophoresis, liquid chromatography-mass spectrometry and chemiluminescence. Although these methods proved to be efficient for quantifying CGA and its derived products, a number of deficiencies were identified: they are time consuming, laborious, and require expensive instruments. Therefore, electrochemical methods have been developed and used in the determination of CGA in different nutraceuticals or food products. The present review aims to present the main progresses and performance characteristics of electrochemical sensors and biosensors used to detect CGA, as it is reported in a high number of relevant scientific papers published mainly in the last decade. | Chlorogenic Acid |
During the last few years it has been shown that intensive or continuing chemotherapy of patients with advanced chronic lymphocytic leukemia prolongs survival. In the search for new effective drugs with tolerable toxicity, mitoxantrone was evaluated in this phase 2 study. Seven of 11 previously untreated patients achieved complete or partial remission after single agent treatment with mitoxantrone, and 5 of .16 previously treated patients had the same degree of response. Only minor toxicity was observed. Therefore, it appears likely that mitoxantrone is as effective as chlorambucil, and it would seem justified to evaluate mitoxantrone in future combination chemotherapy regimens in patients with advanced chronic lymphocytic leukemia. | Mitoxantrone |
Di(2-ethylhexyl)phthalate (DEHP) was administered to male rats in the diet at concentrations of 2.0, 0.2, and 0.02% for up to 102 weeks. Low doses resulted in moderate increases in certain hepatic enzymes during the initial phase of exposure and in a continuous increase in the activities of these same enzymes throughout the treatment period. An increased level of dolichol and decreased concentration of dolichyl-P were observed. Furthermore, the rate of protein glycosylation diminished. Liver biopsies from patients subjected to hemodialysis demonstrated an increased number of peroxisomes. Phthalate ester seems to interfere with protein turnover, so that the half-life of total mitochondrial and microsomal protein is considerably increased. | Carnitine O-Acetyltransferase |
Hip and groin injuries are common in ballet dancers, who often begin sport-specific training at a young age. The unique demands of ballet include extreme range of motion, with an emphasis on external rotation and abduction. This creates a distinctive constellation of hip symptoms and pathology in this cohort, which may differ from other flexibility sports. When managing hip symptoms in this cohort, orthopaedic surgeons should consider the unique factors associated with ballet, including ballet-specific movements, morphologic adaptations of the hip, and the culture of the sport. Three common etiologies of hip pain in ballet dancers include femoroacetabular impingement syndrome, hip instability, and extra-articular snapping hip syndrome. First-line treatment often consists of focused physical therapy to strengthen the core and periarticular hip musculature, with surgical management reserved for patients who fail to improve with conservative measures. | Arthralgia |
Proton beam therapy benefits from the Bragg peak and delivers highly conformal dose distributions. However, the location of the end-of-range is subject to uncertainties related to the accuracy of the relative proton stopping power estimates and thereby the water-equivalent path length (WEPL) along the beam. To remedy the range uncertainty, an in vivo measurement of the WEPL through the patient, i.e. a proton-range radiograph, is highly desirable. Towards that goal, we have explored a novel method of proton radiography based on the time-resolved dose measured by a flat panel imager (FPI). A 226 MeV pencil beam and a custom-designed range modulator wheel (MW) were used to create a time-varying broad beam. The proton imaging technique used exploits this time dependency by looking at the dose rate at the imager as a function of time. This dose rate function (DRF) has a unique time-varying dose pattern at each depth of penetration. A relatively slow rotation of the MW (0.2 revolutions per second) and a fast image acquisition (30 frames per second, ~33 ms sampling) provided a sufficient temporal resolution for each DRF. Along with the high output of the CsI:Tl scintillator, imaging with pixel binning (2 x 2) generated high signal-to-noise data at a very low radiation dose (~0.1 cGy). Proton radiographs of a head phantom and a Gammex CT calibration phantom were taken with various configurations. The results of the phantom measurements show that the FPI can generate low noise and high spatial resolution proton radiographs. The WEPL values of the CT tissue surrogate inserts show that the measured relative stopping powers are accurate to ~2%. The panel did not show any noticeable radiation damage after the accumulative dose of approximately 3831 cGy. In summary, we have successfully demonstrated a highly practical method of generating proton radiography using an x-ray flat panel imager. | Radiography |
The brachial plexus sheath was examined in cadavers by using a combination of anatomic dissection, histologic preparations, and x-rays made after injection of x-ray contrast media, and in surgical patients by using computed tomography (CT) dye studies. The connective tissue forming the sheath was organized more densely proximally near its origin and became loosely organized distally as it ended by joining the medial intermuscular septum of the arm. The connective tissue forming the sheath extends inward, forming septa between components of the plexus. Thus, the sheath is a multicompartmented structure, formed by the thin connective tissue sheath surrounding the plexus and by the septa which extend inward from the sheath. A fascial compartment is created for each nerve, and this compartment serves to define the anatomic limits of that nerve. These compartments have potential clinical importance and implication in the techniques for brachial plexus block. They serve functionally to limit the circumferential spread of injected solutions of local anesthetics. These studies also indicate that injected anesthetic solutions spread easily in a longitudinal manner up and down the nerve and remain compartmentalized. The data presented here provide a rational explanation for the not uncommon occurrence of a profound block of rapid onset in one nerve, yet partial or absent block in other nerves, following any of the techniques of brachial plexus anesthesia. | Brachial Plexus |
Paleophysical oceanography is the study of the behavior of the fluid ocean of the past, with a specific emphasis on its climate implications, leading to a focus on the general circulation. Even if the circulation is not of primary concern, heavy reliance on deep-sea cores for past climate information means that knowledge of the oceanic state when the sediments were laid down is a necessity. Like the modern problem, paleoceanography depends heavily on observations, and central difficulties lie with the very limited data types and coverage that are, and perhaps ever will be, available. An approximate separation can be made into static descriptors of the circulation (e.g., its water-mass properties and volumes) and the more difficult problem of determining transport rates of mass and other properties. Determination of the circulation of the Last Glacial Maximum is used to outline some of the main challenges to progress. Apart from sampling issues, major difficulties lie with physical interpretation of the proxies, transferring core depths to an accurate timescale (the age-model problem"), and understanding the accuracy of time-stepping oceanic or coupled-climate models when run unconstrained by observations. Despite the existence of many plausible explanatory scenarios, few features of the paleocirculation in any period are yet known with certainty." | Oceanography |
Here we have examined the composition of free sterols and steryl esters of pollen from selected angiosperm species, as a first step towards a comprehensive analysis of sterol biogenesis in the male gametophyte. We detected four major sterol structural groups: cycloartenol derivatives bearing a 9beta,19-cyclopropyl group, sterols with a double bond at C-7(8), sterols with a double bond at C-5(6), and stanols. All these groups were unequally distributed among species. However, the distribution of sterols as free sterols or as steryl esters in pollen grains indicated that free sterols were mostly Delta(5)-sterols and that steryl esters were predominantly 9beta,19-cyclopropyl sterols. In order to link the sterol composition of a pollen grain at anthesis with the requirement for membrane lipid constituents of the pollen tube, we germinated pollen grains from Nicotiana tabacum, a model plant in reproductive biology. In the presence of radiolabelled mevalonic acid and in a time course series of measurements, we showed that cycloeucalenol was identified as the major neosynthesized sterol. Furthermore, the inhibition of cycloeucalenol neosynthesis by squalestatin was in full agreement with a de novo biogenesis and an apparent truncated pathway in the pollen tube. | Pollen |
In this time of burnout" and high turnover in nursing, we must attend to our own needs for healing. Integration of a spiritual dimension in our lives and work are central to our health. A balanced life allows nurses to give more, not less, to their practice. Spirituality enlarges the purpose and meaning of our lives and work. Nursing practice entails care, comfort, and healing. These nursing actions flow naturally from a peaceful center." | Transactional Analysis |
BACKGROUND: The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period. OBJECTIVES: The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function. METHODS: We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication. RESULTS: (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed. CONCLUSION: Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy. | Betaxolol |
BACKGROUND: Hemorrhoids are an extremely rare condition in children, and data on its incidence and treatment in the pediatric population remains scarce. We retrospectively reviewed children who underwent sclerotherapy for internal hemorrhoids, and analyzed patients' characteristics and outcomes. METHODS: A total of 14 pediatric patients who underwent sclerotherapy were included. Patients' ages and the required amount of polidocanol, depending on the grade of hemorrhoids, and the correlation between age and volume of sclerosant, were statistically analyzed. RESULTS: Patients had a male predominance with a ratio of 2.5:1 (grade 2:6 patients, grade 3:8 patients). Four children had underlying conditions including portal hypertension and Klippel-Trenaunay syndrome. Of the 14 patients, 43% had constipation requiring medication or enema. Only one minor complication, a perianal ulceration, was found to be associated with sclerotherapy. Patients with grade 3 hemorrhoids required a significantly larger amount of polidocanol than those with grade 2 hemorrhoids. Two patients with grade 3 hemorrhoids required a second session of treatment for recurrence. The success rate of sclerotherapy with polidocanol was 86%. CONCLUSIONS: Sclerotherapy with polidocanol is a safe, effective, and less invasive treatment option for internal hemorrhoids in children. Further studies are needed to investigate this treatment approach. | Polidocanol |
INTRODUCTION: The recent viral pneumonia caused by the COVID-19 has gained the attention of the people all over the world. We aim to investigate the effects of respiratory rehabilitation therapy on patients infected with the novel coronavirus by conducting a systematic review and meta-analysis. METHODS AND ANALYSIS: This systematic review and meta-analysis have been registered in the International Prospective Register of Systematic Reviews (PROSPERO). The PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data and Viper information databases will be searched from inception time to date without restricting research types to find relevant studies. We will also look into reference lists of relevant trials and reviews, and manually search grey literature, such as trial registries. Two reviewers will independently extract data and perform quality assessment of included studies. Review Manager V.5.3 (Cochrane Collaboration) and Stata V.16.0 software will be used to conduct this meta-analysis. The mean difference or standardised mean difference with 95% CIs is used in the computation of continuous variables to synthesise data. ETHICS AND DISSEMINATION: Ethical approval is not required due to the nature of this meta-analysis, which is based on published papers. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal once we finish this study. PROSPERO REGISTRATION NUMBER: CRD42020180214. | Pneumonia, Viral |
The effects of phytochemicals occurred in fractions and extracts of fruits of Maqui-berry" (Aristotelia chilensis), on the expression of cyclooxygenase-2 (COX-2), inducible-nitric oxide synthases (iNOS) and the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-activated murine macrophage RAW-264 cells, as well as their antioxidant activities. The MeOH extract (A), acetone/methanol extract (B), fractions F3, F4, subfractions (SF4-SF6, SF7, SF8-SF10, SF11-SF15, SF16-SF20), quercetin, gallic acid, luteolin, myricetin, mixtures M1, M2 and M3 exhibited potent anti-inflammatory and antioxidant activities. The results indicated that anthocyanins, flavonoids and its mixtures suppressed the LPS induced production of nitric oxide (NO), through the down-regulation of iNOS and COX-2 protein expressions and showed a potent antioxidant activity against SOD, ABTS, TBARS, ORAC, FRAP and DCFH. The inhibition of enzymes and NO production by selected fractions and compounds was dose-dependent with significant effects seen at concentration as low as 1.0-50.0 (ppm) and 5.0-10.0 muM, for samples (extracts, fractions, subfractions and mixtures) and pure compounds, respectively. Thus, the phenolics (anthocyanins, flavonoids, and organic acids) as the fractions and mixtures may provide a potential therapeutic approach for inflammation associated disorders and therefore might be used as antagonizing agents to ameliorate the effects of oxidative stress." | Elaeocarpaceae |
Operating room (OR) to intensive care unit (ICU) handoffs are complex and known to be associated with adverse events and patient harm. The authors hypothesized that handoff quality diminishes during nights/weekends and that bedside handoff practices are similar between ICUs of the same health system. Bedside OR-to-ICU handoffs were directly observed in 2 surgical ICUs with different patient volumes. Handoff quality measures were compared within the ICUs on weekdays versus nights/weekends as well as between the high- and moderate-volume ICUs. In the high-volume ICU, transmitter delivery scores were significantly better during off hours, while other measures were not different. High-volume ICU scores were consistently better than those in the moderate-volume ICU. Bedside handoff practices are not worse during off hours and may be better in ICUs used to a higher patient volume. Specific handoff protocols merit evaluation and training to ensure consistent practices in different ICU models and at different times. | After-Hours Care |
Valproate is an antiepileptic commonly used in the treatment of psychiatric and neurologic diseases. Some of the most frequently seen side effects affect the gastrointestinal, neurological, and hematological systems. Its side effects on reproductive functions have not been sufficiently studied. The use of valproate by females with bipolar disorder and epilepsy may cause menstrual cycle abnormalities, polycystic ovary syndrome, and hyperandrogenism. The effects on male reproductive functions have been researched only in epileptic patients and animals, and the results have been conflicting, because reproductive function abnormalities may be independent of the use of valproate and may be due to epilepsy itself. In the first part of this review reproductive function abnormalities due to epilepsy will be discussed, independent of the use of valproate or any other antiepileptic. Then, the results of research on valproate's effects on male reproductive functions (hormonal levels and sperm parameters) will be presented, including the possible underlying mechanisms of these effects, the effect of the duration of valproate use, and whether or not the effects are reversible. In the second section we review the results of animal research, which could be beneficial in assessing the effects of valproate and epilepsy. | Antimanic Agents |
The gelatinases (type IV collagenases) are members of the matrix metalloproteinase family that not only have a high degree of structural homology but are known to be nearly identical in their digestion profile against macromolecular substrates. We have shown previously that the preferred cleavage sites in the hydrolysis of type I gelatin, catalyzed by gelatinase A (72 kDa type IV collagenase), are bracketed by hydroxyproline in the P5 and P5' positions. In this report, a kinetic investigation using a series of collagenous dodecylpeptides in which the P5 and P5' hydroxyprolines were systematically varied and used as substrates for recombinant human gelatinase A, we show that replacement with either proline or alanine always resulted in increased Km. In contrast, substitution of the hydroxylated amino acids tyrosine and serine at P5 and P5' reduced the Km significantly, indicating that the hydroxyl moiety of the hydroxyproline is the functional group responsible for favorable enzyme-substrate affinity. This was shown by the kcat/Km ratio, which was doubled by the substitution of serine in that site. Cleavage of the same series of dodecylpeptides by recombinant human gelatinase B (92 kDa type IV collagenase) showed a very different kinetic profile for which no patterns were discernible. In subsequent comparisons of the two enzymes, it was found that gelatinase B cleaved the thiopeptolide substrate AcProLeuGly-S-LeuGly-OC2H5 at double the velocity of gelatinase A. In contrast, gelatinase A digested type I gelatin about 2.5-times faster than gelatinase B. SDS-PAGE analysis of gelatin cleavage products showed different patterns of product peptides for each enzyme. Further comparisons of the proteinases using synthetic peptide substrates with variations in size and in substituents at the P2' site again showed marked kinetic differences. Although these two matrix metalloproteinases seem similar in that they are both gelatinolytic and can degrade a nearly identical battery of macromolecular matrix components including type IV collagen, it is clear from these results that they are very different enzymatically. Since the regulatory portions of gelatinases A and B differ markedly, it has been assumed that the enzymes serve the same function, but respond to different stimuli. The differences in substrate specificity described herein suggest that their proposed physiological roles may require reevaluation. | Metalloendopeptidases |
K(+) uptake rates were measured in the anterior (An) and posterior (Pos) LV walls of pig hearts before and after regional ischemia and reperfusion using Rb(+) as a K(+) congener and 3D (87)Rb NMR imaging and spectroscopy as detection methods. The hearts were perfused by the Langendorff method with Krebs-Henseleit (KH) buffer and loaded with Rb(+) (4.7 mM, Rb-KH) after 120-min ischemia and 60-min reperfusion. A second protocol involved Rb(+) loading prior to ischemia. Ischemia was produced by occlusion of the left anterior descending artery, which after 110 min of reperfusion resulted in infarction in the An wall (24 +/- 6% of the LV mass) determined by triphenyltetrazolium chloride staining. At the end of reperfusion pressure-rate product and oxygen consumption rate decreased to 58 +/- 10 and 74 +/- 4% of their preischemic values, respectively. Phosphocreatine, ATP, and intracellular pH (pHi), measured by (31)P NMR spectroscopy in the infarcted area, decreased to 59 +/- 17, 32 +/- 6%, and 6.7 +/- 0.36 (from 7.05 +/- 0.13), respectively. Serial (87)Rb images were acquired according to both protocols. Rate constants (k x 10(3), min(-1)), relative amount of intracellular Rb(+) (A, %) and relative fluxes (F = kA, %/min) for the An and Pos walls were determined from the images. Before ischemia, F and k were comparable in the Pos and An walls. Ischemia + reperfusion decreased F in the An wall (from 4.4 +/- 0.3 to 1.4 +/- 0.85) due to a decrease in A (20 vs. 73) and increased F in Pos wall (from 3.2 +/- 0.6 to 6.6 +/- 0.23) due to an increase in k (from 42 +/- 3 to 93 +/- 6). The intensities of the Rb images correlated with the Rb(+) content measured in tissue samples. Magn Reson Med 44:83-91, 2000. Published 2000 Wiley-Liss, Inc. | Rubidium Radioisotopes |
Here we identify and characterize a cytoskeletal myosin protein required for IRE1alpha oligomerization, activation, and signaling. Proteomic screening identified nonmuscle myosin heavy chain IIB (NMHCIIB), a subunit of nonmuscle myosin IIB (NMIIB), as an ER stress-dependent interacting protein specific to IRE1alpha. Loss of NMIIB compromises XBP1s and UPR target gene expression with no effect on the PERK pathway. Mechanistically, NMIIB is required for IRE1alpha aggregation and foci formation under ER stress. The NMIIB-mediated effect on IRE1alpha signaling is in part dependent on the phosphorylation of myosin regulatory light chain and the actomyosin contractility of NMIIB. Biologically, the function of NMIIB in ER stress response is conserved as both mammalian cells and C. elegans lacking NMIIB exhibit hypersensitivity to ER stress. Thus, optimal IRE1alpha activation and signaling require concerted coordination between the ER and cytoskeleton. | Nonmuscle Myosin Type IIB |
Corticosteroid-binding globulin (CBG), a non-inhibitory member of the serine proteinase inhibitor (serpin) super-family, is the high-affinity transport protein for glucocorticoids in vertebrate blood. Plasma CBG is a glycoprotein with 30% of its mass represented by N-linked oligosaccharide chains. Its well-characterized steroid-binding properties represent a bench-mark data set" used extensively for in silico studies of protein-ligand interactions and drug design. Recent crystal structure analyses of intact rat CBG and cleaved human CBG have revealed the precise topography of the steroid-binding site, and shown that cortisol-bound CBG displays a typical stressed (S) serpin conformation with the reactive center loop (RCL) fully exposed from the central beta-sheet A, while proteolytic cleavage of the RCL results in CBG adopting a relaxed (R) conformation with the cleaved RCL fully inserted within the protein core. These crystal structures have set the stage for mechanistic studies of CBG function which have so far shown that helix D plays a key role in coupling RCL movement and steroid-binding site integrity, and provided evidence for an allosteric mechanism that modulates steroid binding and release from CBG. These studies have also revealed how the irreversible release of steroids occurs after proteolysis and re-orientation of the RCL within the R conformation. This recent insight into the structure and function of CBG reveals how naturally occurring genetic CBG mutations affect steroid binding, and helps understand how proteolysis of CBG enhances the targeted delivery of biologically active steroids to their sites of action." | Thyroxine-Binding Globulin |
Clostridium acetobutylicum JB200 is a hyper butanol tolerant and producing strain obtained from asporogenic C. acetobutylicum ATCC 55025 through mutagenesis and adaptation in a fibrous bed bioreactor. The complete genomes of both strains were sequenced by the Illumina Hiseq2000 technology and assembled using SOAPdenovo approach. Compared to the genomic sequence of the type strain ATCC 824, 143 single nucleotide polymorphisms (SNPs) and 17 insertion/deletion variations (InDels) were identified in the genome of ATCC 55025. Twenty-nine mutations were in genes involved in sporulation, solventogenesis and stress response. Compared to ATCC 55025, there were seven additional point mutations in the chromosome of JB200. Among them, a single-base deletion in cac3319 encoding an orphan histidine kinase caused protein C-terminal truncation. Disruption of this gene in ATCC 55025 and ATCC 824 resulted in significantly elevated butanol tolerance and production. This study provides genome-level information for the better understanding of solventogenic C. acetobutylicum in several key aspects of cell physiology and metabolism, which could help further metabolic engineering of Clostridium for butanol production. | Clostridium acetobutylicum |
Great hornbills (Buceros bicornis) are a long-lived, monogamous species that forms strong pair-bonds, and mate compatibility is thought to be important for successful reproduction. Within AZA, great hornbills are listed as a red SSP. The population consists of a limited number of individuals that do not breed reliably, and improving reproduction is a top priority for the Coraciiformes TAG. To better understand mating behavior and evaluate mate compatibility, this study documented the behavior of pairs of great hornbills during and immediately after courtship. Using live observations, the study followed one female, an experienced and successful breeder, as she was paired with four successive males over 11 breeding seasons. Initially, males frequently vocalized, investigated the nest, and approached the female. As the female spent more time in the nest, these behaviors were replaced by regurgitation and food offering. The female was most often observed plastering and vocalizing. Behavioral differences between successful and unsuccessful pairs, possibly indicative of pair compatibility, included rates of approaching, billing, and biting. Numerous behaviors occurred more frequently during years that a chick hatched, including pseudoregurgitation, regurgitation, offering food items, and nest investigation. Males also spent more time in proximity to both the female and the nest during years that a chick hatched. Together, these results suggest that the amount of time pairs spend in proximity, the amount of time a male spends near the nest, and the frequency of certain behaviors may help evaluate compatibility and the likelihood of successful reproduction for pairs of great hornbills. | Nesting Behavior |
Phospholipase D (PLD) hydrolyzes the phosphodiester bond of the glycerolipid phosphatidylcholine, resulting in the production of phosphatidic acid and free choline. Phosphatidic acid is widely considered to be the intracellular lipid mediator of many of the biological functions attributed to PLD. However, phosphatidic acid is a tightly regulated lipid in cells and can be converted to other potentially bioactive lipids, including diacylglycerol and lysophosphatidic acid. PLD activities have been described in multiple organisms, including plants, mammals, bacteria and yeast. In mammalian systems, PLD activity regulates the actin cytoskeleton, vesicle trafficking for secretion and endocytosis, and receptor signaling. PLD is in turn regulated by phosphatidylinositol-4,5-bisphosphate, protein kinase C and ADP Ribosylation Factor and Rho family GTPases. This review focuses on the lipid precursors and products of mammalian PLD metabolism, especially phosphatidic acid and the roles this lipid performs in the mediation of the functions of PLD. | Phospholipases |
A procedure for the determination of the CNS-active muscle-relaxant mephenesin in plasma samples is described. The method involved a single-step extraction with diethyl ether followed by high-performance liquid chromatography separation and fluorimetric detection. Linearity of the detection response was observed between 1 ng/ml, which is the limit of determination, and 500 ng/ml. Inter-day assays, including quality-control samples, performed over a 4-month period, showed the method to be reproducible and precise, and suitable for routine analysis in pharmacokinetic studies. | Mephenesin |
In Europe, Culicoides chiopterus, Culicoides dewulfi, Culicoides obsoletus and Culicoides scoticus, which belongs to the subgenus Avaritia and Obsoletus group are the most proficient Bluetongue and Schmallenberg vectors. Within this group, correct identification based on morphological traits is difficult but essential to assess disease transmission risk. The development of new tools has revolutionized taxonomy (i.e. geometric morphometrics and molecular biology). Wing morphology is of primary importance to entomologists interested in systematics. Here, we report phenotypic differentiation patterns among the species above mentioned using a landmark-based geometric morphometric approach that efficiently identified C. chiopterus and C. dewulfi. Wing shape of the C. scoticus sample exhibited large specific variability. Based on landmarks and phylogenetic analyses (Maximum Parsimony), we suggest that Obsoletus group in Europe includes only C. obsoletus and C. scoticus. C. dewulfi and C. chiopterus are clearly excluded. Their shape seems closer to C. obsoletus that is why we suggest that only these two species should be grouped in the Obsoletus group. In addition, the concordance between phenetic clusters and phylogenies inferred from molecular data based on a fragment of the mtDNA COI gene and rDNA 28S suggests the existence of a strong signal in wing shape. These findings encourage us to use this powerful tool in taxonomic studies. | Ceratopogonidae |
AIM: Chemokines usually direct the movement of circulating leukocytes to sites of inflammation or injury. CXCL1/GRO-alpha has been shown to be upregulated in atherosclerotic lesions and various cancers. The aim of this study was to investigate the mechanisms underlying the TNF-alpha-induced release of CXCL1 from human vascular endothelial cells in vitro. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with different proinflam-matory mediators and growth factors. CXCL1 expression and secretion were determined using RT-PCR and ELISA, respectively. TNF-alpha-induced cell signaling was assayed with Western blotting. Cell viability/growth was determined using MTT assay. Monocyte migration was measured with transwell migration assay. RESULTS: Among the 17 mediators and growth factors tested, TNF-alpha, LPS and thrombin induced marked increase in CXCL1 release from HUVEC cells. TNF-alpha (2, 5 ng/mL) induced CXCL1 release and mRNA expression in the cells in concentration- and time-dependent manners. TNF-alpha (5 ng/mL) caused activation of JNK, p38 MAPK, PI3K and Akt, whereas pretreatment with JNK inhibitor (SP600125), p38 MAPK inhibitor (SB202190) or PI-3K inhibitor (LY294002) significantly suppressed TNF-alpha-induced CXCL1 release from the cells. But only SP600125 significantly reduced TNF-alpha-induced CXCL1 mRNA expression in the cells. Moreover, dexamethasone (up to 500 nmol/L) failed to affect TNF-alpha-induced CXCL1 release from the cells. In functional studies, recombinant CXCL1 enhanced HUVEC proliferation, and both recombinant CXCL1 and TNF-alpha-induced CXCL1 from HUVECs attracted human monocyte migration. CONCLUSION: TNF-alpha stimulates CXCL1 release from human ECs through JNK-mediated CXCL1 mRNA expression and p38 MAPK- and PI-3K-mediated CXCL1 secretory processes. | Chemokine CXCL1 |
BACKGROUND: Nasal vestibulitis (NV) and nasal vestibular furunculosis (NVF) are two infectious processes of the nasal vestibule, sharing common etiology, the same risk of complications, and similar treatment while remaining two different pathological entities. METHODS: We performed a comprehensive literature research on NV and NVF in PubMed, Cochrane, and Google Scholar databases, with the aim to review the evidence on these two conditions and discuss the therapeutic approaches. RESULTS: We identified a total of 248 records; according to our inclusion/exclusion criteria, 27 of them, published over a period of 59 years (1962-2021), were included in this review. CONCLUSION: NV and NVF are reported to be common conditions, with well-known etiological agents and risk factors. The diagnosis is clinical and topical antibiotics are the mainstay of treatment. Complications appear to be infrequent. Further studies are necessary to clarify the pathogenetic mechanisms and the exact prevalence of both conditions. | Furunculosis |
Infectious laryngotracheitis (ILT) is an economically crucial respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in the control of the disease outbreak. In an earlier study, we comprehensively characterized the circulating strains in Egypt and identified both CEO-like and recombinant strains are dominant. Herein, we investigated the pathogenicity of two virulent strains representing the CEO-like (Sharkia_2018) and recombinant strain (Qalubia_2018). Additionally, we evaluated the efficacy of different commercial vaccines (HVT-LT, CEO, and TCO) against the two isolates in terms of the histopathological lesion scores and the viral (gC) gene load. A total of 270 White Leghorn-specific pathogen-free male chicks were divided into nine groups of 30 birds, each housed in separate isolators. Birds were distributed as follows; one group was non-vaccinated, non-challenged, and served as a negative control. Two groups were non-vaccinated and infected with the two isolates of interest and served as a positive control to test the pathogenicity. Six groups were vaccinated and challenged; two groups were vaccinated with vector vaccine at one day old. The other four groups were vaccinated with either the CEO- or TCO- vaccine (two groups each) at four weeks of age. Three weeks after vaccination, birds were infected with the virulent ILTV isolates. The larynx, trachea, and harderian gland samples were taken at 1, 3, and 7 days post-infection for histopathological lesion score and molecular detection. Notably, The recombinant strain was more virulent and pathogenic than CEO-like ILTV strains. Moreover, the TCO vaccine was less immunogenic than the vector and CEO vaccines. | Iltovirus |
Inflammatory myofibroblastic tumours (IMT), also called inflammatory pseudotumours, nodular lymphoid hyperplasia, plasma-cell granuloma and fibrous xanthoma, are rare soft-tissue lesions characterised by inflammatory cells and a fibrous stroma. Clinically and radiologically, they may look like malignant tumours. They rarely affect the central nervous system and are very rare in the spinal cord. We report an IMT of the spinal cord in a 22-year-old woman presenting with spinal cord compression and a cauda equina syndrome. MRI showed a lesion at T9 with extramedullary and intramedullary components giving low signal on T2-weighted images and enhancing homogeneously. Pial lesions on the lumbar enlargement and thoracic spinal were present 11 months after surgery, when the lesion recurred. We present the radiological, operative and pathological findings and review the literature. | Granuloma, Plasma Cell |
BACKGROUND: Bleeding events in surgery are a problem and can lead to revision surgery and bleeding anaemia, which sometimes must be treated by blood transfusion. Tranexamic acid is an antifibrinolytic agent and is already known for its role in the prevention and treatment of perioperative bleeding in the fields of orthopaedics, cardiovascular surgery and gynaecology. In plastic surgery, the use of tranexamic acid is increasing in popularity and has already been described in individual studies. METHODS: A literature search was performed using the database MEDLINE from the United States National Library of Medicine (NLM). The keywords tranexamic acid in plastic surgery", "intravenous tranexamic acid in plastic surgery", "topical tranexamic acid in plastic surgery" and "subcutaneous tranexamic acid in plastic surgery" were used. The search was limited to the period from 2010 to 2023. The studies were analysed according to the level of evidence, validity and availability and divided into three groups for the topical, intravenous or subcutaneous application of tranexamic acid. Randomised controlled trials and non-randomised prospective and retrospective cohort studies were included in the systematic review. Studies from other disciplines, review articles, technical notes, experimental studies, letters to the editor, comments and case reports were excluded. RESULTS: The literature search resulted in a total of 135 papers. Of these, 56 papers were assessed as relevant to plastic surgery. After further analysis, 41 papers were excluded using the exclusion criteria described above. Fifteen studies were finally included in the present work and recommendations for possible applications such as intravenous, topical and subcutaneous application of tranexamic acid, including the indications, contraindications and dosage formulas were developed. DISCUSSION: Although the current study situation on the use of tranexamic acid is limited, the results show more advantages than disadvantages for perioperative use. Establishing the use of tranexamic acid in plastic surgery could facilitate the reduction of perioperative bleeding and lead to more precision in surgery, and it could enable a rapid removal of drains. However, following the analysis of benefit and risk factors, further randomised controlled trials are required for use in plastic surgery." | Antifibrinolytic Agents |
Prognostic factor research is important as it helps in refining diagnosis, taking clinical and therapeutic decisions, enhances the design and analysis of intervention trials and helps to identify targets for new interventions that aim to modify the course of a disease. Prognostic factor research in homeopathy can be done by applying Bayes' theorem. This paper considers Bayes' theorem; Likelihood Ratio, conditional probability and research in subpopulations of a condition with examples. We analysed the likelihood ratios for 11 homeopathic medicines for the symptom 'cough' and other upper respiratory tract symptoms, based on data from the IIPCOS2 study. This yielded useful information since several medicines, including Belladonna, had LR >1 for cough, indicating that cough is not an indication for this medicine. The implications for improving homeopathic prescribing are discussed. | Atropa |
In view of the demographic development the topic of Nursing of elderly relatives" is gaining more and more importance within nursing research. The object of the investigation described in this paper was to assess the measures of the Pflegeversicherung [Long Term Care Insurance] with regard to its effects on care-giving daughters. This publication assesses one of the questions of the study--what part professional services play in the support of care-giving daughters. The data was collected by individual biographic-narrative interviews in the private household of care-giving daughters. The data was then evaluated according to the method of biographical case reconstruction developed by Gabriele Rosenthal. This way we were able to gain a deeper insight into the situation of care-giving daughters and analyse the consequences of the Pflegeversicherungsgesetz [Long Term Care Insurance Law] from an "inner perspective". The results of the study point to both the positive effects of the Pflegeversicherungsgesetz and its limits. We were able to show that the expansion of out patient services leads to an enhanced nursing infrastructure. In view of the part that professional nursing services play, however, the biographical access also made it clear that the Pflegeversicherung will not lead to far-reaching changes in nursing arrangements. In spite of Pflegeversicherung caregiving relatives still suffer from personal and emotional strain. Also the legal requirements are too narrow and allow hardly enough space for the consideration of the family environment and the history of life of relationship between daughter and mother." | Insurance, Nursing Services |
OBJECTIVE: Olfactory and taste dysfunction (OTD) is a potential neurological manifestation of coronavirus-2019 (COVID-19). We aimed to investigate the diagnostic value of symptoms of anosmia and dysgeusia for COVID-19. METHODS: A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar from 1 June 2020 to 12 June 2020. All studies reporting symptoms of anosmia and dysgeusia in COVID-19-positive patients were included. A total of 23 studies were included in the systematic review. RESULTS: Symptoms of anosmia and dysgeusia were frequently reported by COVID-19-positive patients. Symptoms were more common in females and in younger patients. There was no direct association between the severity of COVID-19 and the presence of symptoms. However, some evidence was found for a longer duration of these symptoms and increased severity of COVID-19 infection in young patients. CONCLUSION: OTD is commonly reported by COVID-19 patients. Due to limited literature on the association between OTD and COVID-19, it is currently not possible to conclude that these symptoms alone can be used to diagnose COVID-19. However, the presence of OTD can potentially be used as a screening tool for COVID-19 especially in young and female patients. Further research is required to establish the true diagnostic value of these symptoms and efficacy as screening tools for COVID-19 patients. | Dysgeusia |
The dentist can be confronted with a vesiculobullous lesion of the oral mucosa are a symptoms of herpes infection (herpangina) of throat. Human enteroviruses (HEVs) are a major cause of herpangina. Herpangina is an acute viral infection caused by certain viruses Coxsackie, is spread by respiratory droplets. The infection is mainly encountered in young children. Oral lesions rarely more than 7 days; treatment is symptomatic. Viral throat infections may accompany various skin rashes, such as erythema multiforme (which can also occur without any connection with a viral infection). At work was presented a case of 3-year-old boy with herpes symptoms of sore throat and mild forms of erythema multiforme. | Herpangina |
Since the first metabolic labeling experiments with stable isotopes beginning of the last century, several approaches were pursued to monitor protein dynamics in living animals. Today, almost all model organisms from bacteria to rodents can be fully labeled with SILAC (stable isotope labeling of amino acids in cell culture) amino acids. The development of special media and diets containing the labeled amino acids provides an efficient way to metabolically label prokaryotic and eukaryotic organisms. Preferentially, the essential amino acid lysine ((13)C6-lysine) is used to label mice (Mus musculus) and after one generation the natural isotope is fully replaced by the stable (13)C6-lysine isotope. So far, the SILAC mouse approach has been used to analyze several transgenic and knockout mouse models. Spike-in of labeled proteins into non-labeled samples provides an accurate relative protein quantification method without any chemical modification. Here we describe how to establish a SILAC mouse colony and describe the analysis of skeletal muscle tissue with different metabolic and contractile profiles. | Muscle Proteins |
BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor that generally involves the retroperitoneum, pelvis, omentum and mesentery in younger patients. However, extra-abdominal DSRCT is very rare. CASE PRESENTATION: A 49-year-old Japanese man noticed a mass in the right parotid gland. Ultrasound examination revealed a solid tumor about 2 cm in diameter. Computed tomography (CT) of the whole body revealed no other tumors or lymph node swelling. Superficial parotidectomy was performed. Histologically, the tumor was composed of various-sized tumor cell nests in an abundant fibromyxoid and collagenous background. The tumor cells were small to medium-sized. Immunohistochemistry showed that the tumor cells were immunoreactive for epithelial markers and desmin. They also showed strong nuclear staining with a Wilms tumor 1 (WT1) antibody detecting the C-terminal region (C-WT1), but not the N-terminal region (N-WT1). We also performed 3'/5' expression imbalance assay based on reverse transcription polymerase chain reaction (RT-PCR) to determine whether aberrant WT1 gene expression was present. This tumor was found to lack 5'-regional expression of the WT1 gene, as well as immunoreactivity with the N-WT1 antibody. Finally, fluorescence in situ hybridization (FISH) and RT-PCR analyses revealed the presence of a gene showing fusion between exon 7 of EWSR1 and exon 8 of WT1. The tumor was diagnosed as a DSRCT of the right parotid gland. The patient has been followed for 3 years without recurrence or metastasis. CONCLUSIONS: Although DSRCT in the salivary gland is extremely rare, it should be included in the differential diagnosis of poorly differentiated salivary gland neoplasms, especially with a fibromyxoid background. Pathologists should bear in mind that DSRCT may occur in major salivary glands and should perform immunohistochemistry with appropriate antibodies, not only those against keratin and desmin, but also one detecting the C-terminal region of WT-1. Furthermore, molecular detection of EWSR1-WT1 fusion gene conclusively confirmed the diagnosis of DSRCT in this uncommon location." | Desmoplastic Small Round Cell Tumor |
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