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pubmed_638_9026 | OBJECTIVE
Atrial fibrillation is one of the most common complications after cardiac surgery. This study evaluates the risk factors of paroxysmal atrial fibrillation in patients who underwent aortic valve replacement.
METHODS
The study comprised 300 patients with aortic valve defects of either aortic stenosis (n = 150) or regurgitation (n = 150) who underwent aortic valve replacement. For each patient, 2-mode and Doppler echocardiographic examinations were performed in the preoperative period, early postoperative period, and long-term observation, and selected hemodynamic parameters were analyzed.
RESULTS
Factors significantly associated with atrial fibrillation in patients with aortic stenosis were heart failure (odds ratio = 5.5), age 70 years or more (4.5), low (3.9) and high body mass index (1.7), maximal transvalvular gradient (3.7), low left ventricular ejection fraction (5.1), end-systolic (2.9) and end-diastolic intraventricular septum thickness (1.5), and insignificant mitral regurgitation (1.9) in the preoperative period; and left ventricular ejection fraction (4.4) and end-systolic intraventricular septum thickness (1.8) in the early postoperative period. In the aortic regurgitation group, factors significantly associated with atrial fibrillation were age (1.8), left ventricular ejection fraction (3.7), left ventricular end-systolic diameter (1.7), end-diastolic intraventricular septum thickness (1.7), left atrium dimension (4.1) and insignificant mitral regurgitation (2.5) in the postoperative period; essential arterial hypertension (3.3), diabetes mellitus (2.6), and heart failure in the history (4.5) in the preoperative period; and left ventricular ejection fraction (1.9) and left atrium dimension (2.9) in the early postoperative period.
CONCLUSION
On the basis of the separated risk factors, all patients should be preoperatively classified to applicable groups of risk of postoperative atrial fibrillation appearance, and the prophylactic treatment should be administered in the group of patients with the highest risk. It may essentially decrease the rate of complications and deaths, and, consequently, the costs of postoperative medical care. | 10.1016/j.jtcvs.2007.08.032 |
pubmed_1109_8317 | BACKGROUND
[18 F]fluorodopa (FDOPA) positron emission tomography (PET) allows assessment of levodopa (LDOPA) metabolism and is widely used to study Parkinson's disease. We examined how [18 F]FDOPA PET-derived kinetic parameters relate the dopamine (DA) and DA metabolite content of extracellular fluid measured by microdialysis to aid in the interpretation of data from both techniques.
METHODS
[18 F]FDOPA PET imaging and microdialysis measurements were performed in unilaterally 6-hydroxydopamine-lesioned rats (n = 8) and normal control rats (n = 3). Microdialysis testing included baseline measurements and measurements following acute administration of LDOPA. PET imaging was also performed using [11C]dihydrotetrabenazine (DTBZ), which is a ligand for the vesicular monoamine transporter marker and allowed assessment of denervation severity.
RESULTS
The different methods provided highly correlated data. Lesioned rats had reduced DA metabolite concentrations ipsilateral to the lesion (p < 0.05 compared to controls), with the concentration being correlated with FDOPA's effective distribution volume ratio (EDVR; r = 0.86, p < 0.01) and DTBZ's binding potential (BPND; r = 0.89, p < 0.01). The DA metabolite concentration in the contralateral striatum of severely (>80%) lesioned rats was lower (p < 0.05) than that of less severely lesioned rats (<80%) and was correlated with the ipsilateral PET measures (r = 0.89, p < 0.01 for BPND) but not with the contralateral PET measures. EDVR and BPND in the contralateral striatum were not different from controls and were not correlated with the denervation severity.
CONCLUSIONS
The demonstrated strong correlations between the PET and microdialysis measures can aid in the interpretation of [18 F]FDOPA-derived kinetic parameters and help compare results from different studies. The contralateral striatum was affected by the lesioning and so cannot always serve as an unaffected control. | 10.1186/2191-219X-3-69 |
pubmed_58_11994 | OBJECTIVE
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is closely related to tumorigenesis. Suppressors of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT signaling pathway. MiR-340 expression is significantly upregulated in gastric cancer (GC) tissue. This study investigated the role of miR-340 in regulating SOCS3 expression and affecting GC cell proliferation, cycle, and apoptosis.
PATIENTS AND METHODS
Dual luciferase assay was used to verify the targeted relationship between miR-340 and SOCS3. GC tissue was collected from patients. Normal gastric mucosal tissue was selected as control. MiR-340, SOCS3, p-JAK, p-STAT3, and Survivin protein expressions were compared with GES-1 and MKN-28 cells. MKN-28 cells were cultured in vitro and divided into four groups, including miR-NC, anti-miR-340, pSicoR-Blank, and pSicoR-SOCS3 groups. Cell proliferation, cycle, and apoptosis were detected by flow cytometry.
RESULTS
Bioinformatics analysis revealed the targeted relationship between miR-340 and the 3'-UTR of SOCS3 mRNA. Dual luciferase assay demonstrated that miR-340 regulated SOCS3 expression. MiR-340 level was significantly elevated, while SOCS3 level was obviously declined in GC tissue compared with normal mucosal tissue. MiR-340, p-JAK, p-STAT3, and Survivin expressions were upregulated, whereas SOCS3 expression was reduced in MKN-28 cells compared with that in GES-1 cells. Anti-miR-340 or pSicoR-SOCS3 transfection markedly increased SOCS3 expression, reduced p-JAK, p-STAT3, and Survivin levels, attenuated cell proliferation, arrested cell cycle, and enhanced cell apoptosis in MKN-28 cells.
CONCLUSIONS
Downregulation of miR-340 inhibited GC cell proliferation, arrested cell cycle, and facilitated apoptosis through upregulating SOCS3 expression to suppress JAK-STAT3 signaling pathway. | 10.1080/08923973.2018.1455208 |
pubmed_688_9601 | We surveyed health in Nourivier, Namaqualand, to see whether poverty prevented people from obtaining the care they needed. We interviewed families at 65 of the 74 households, and obtained satisfactory health information from 37. Health in Nourivier is generally good; 93% of the children aged 0-5 years are fully immunized. However, 20 children in this age group (35%) were below the third percentile (weight for age, National Center for Health Statistics' standards), while the clinical condition of 4 (7%) gave cause for concern. The water supply and sanitation were satisfactory. Twenty-one individuals reported having been ill in the preceding 2 months. People treat themselves before resorting to the herbalist, the clinic nurse or the general practitioner (GP). Money for transport to the GP in Garies and antenatal care and hospital delivery has to be scraped up by the population, although the police in Kamieskroon will take people to hospital in an emergency. The mean monthly cash income in 35 households was R194 (range R0-1-035). People there would like a nurse in the village or a weekly visit by a doctor. Their tradition of self-care is a sound basis for a village-based primary health care service. | pubmed_688_9601 |
pubmed_380_6788 | New 1H,3H-oxazolo[3,4-albenzimidazoles (OBZs) were synthesized as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) to extend the structure-activity relationships observed for an early series of related 1H,3H-thiazolo[3,4-a]benzimidazole derivatives (TBZs). The new compounds showed inhibitory activity against the replication of various HIV-1 strains, including NNRTI-resistant strains. Testing of a representative OBZ derivative in an HPLC assay on biological fluids, indicated that the sulphur substitution appreciably improved the metabolic stability of the TBZ compound. In addition, molecular modelling studies demonstrated that OBZs, TBZs and other NNRTIs have similar structural properties, that is a butterfly-like conformation, which is a key structural requirement for reverse transcriptase inhibition. | 10.1177/095632020101200304 |
pubmed_994_23115 | To establish and characterize the gemcitabine-resistant cholangiocarcinoma (CCA) cell lines, CCA KKU‑M139 and KKU‑M214 cell lines were exposed stepwisely to increasing gemcitabine (GEM). The resultant drug-resistant cell lines, KKU‑M139/GEM and KKU‑M214/GEM, retained the resistant phenotype in drug-free medium at least for 2 months. Sulforhodamine B assay demonstrated that KKU‑M139/GEM and KKU‑M214/GEM were 25.88- and 62.31-fold more resistant to gemcitabine than their parental cells. Both gemcitabine-resistant cell lines were cross-resistant to 5-fluorouracil (5-FU), doxorubicin and paclitaxel indicating their multidrug-resistant nature. Using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and western blot analyses, gemcitabine-resistant cells showed upregulation of RRM1 and downregulation of hENT1 and dCK. In relation to multidrug resistance, these cell lines showed upregulation of multidrug resistance protein 1 (MRP1) leading to an increase of drug efflux. Using cell adhesion and Boyden chamber transwell assays, these cell lines also showed higher cell adhesion, migration and invasion capabilities via the activations of protein kinase C (PKC), focal adhesion kinase (FAK), extracellular signal-regulated kinase-1/2 (ERK1/2) and nuclear factor-κB (NF-κB). Higher activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) was also observed by a gelatin zymography assay and a casein-plasminogen zymography assay. Flow cytometry analysis indicated the G2/M arrest regulated by downregulation of cyclin B1 and cyclin-dependent kinase 1 (Cdk1) resulted in an extended population doubling time. Using Annexin V/propidium iodide staining, evasion of apoptosis via an intrinsic pathway was observed in both cell lines in association with upregulation of Bcl-2 and downregulation of Bax. Interestingly, Fas was additionally downregulated in KKU‑M214/GEM supporting the view of its higher GEM resistant characteristics. These findings indicate that long-term exposure of CCA cell lines to gemcitabine induce not only multidrug resistance but also enhance their invasiveness. | 10.3892/ijo.2015.3019 |
pubmed_808_20090 | Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, exactly how neuroinflammation leads to, or contributes to, these central disorders is unclear. The objective of the study was to examine and compare the expression of mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R) and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA expression only in non-neuronal cells throughout the brain, but significantly elevated IL-6R mRNA in neuronal populations, where observed, except the cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced neuroinflammation has substantial but variable effects on the regional and cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA expression. It is apparent that administration of LPS can affect non-neuronal and neuronal cells in the brain. Further research is required to determine how CNS inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn contribute to the development of CNS neurological disorders. | 10.1016/j.neuroscience.2017.04.028 |
pubmed_452_8513 | AIMS
Recently, we demonstrated that the hearts of neonatal pigs (2-day old) have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after postnatal day 3. However, it is unknown if corticosteroid, a broad anti-inflammatory agent, will abrogate the regenerative capacity in the hearts of neonatal pigs. The aim of the current study is to evaluate the effect Dexamethasone (Dex), a broad anti-inflammatory agent, on heart regeneration, structure, and function of the neonatal pigs' post-myocardial infarction (MI).
METHODS AND RESULTS
Dex (0.2 mg/kg/day) was injected intramuscularly into the neonatal pig (age: 2 days postnatal) during the first week post-MI. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance (CMR) imaging. Bromodeoxyuridine (BrdU) pulse-chase labeling, histology, immunohistochemistry, and flow cytometry were performed to determine inflammatory cell infiltration, CM cytokinesis, and myocardial fibrosis. Dex injection during the first-week suppressed acute inflammation post-MI in the pig hearts. It inhibited BrdU incorporation to pig CMs and CM cytokinesis via inhibiting aurora-B protein expression which was associated with mature scar formation and thinned walls at the infarct site. CMR imaging showed Dex caused left ventricular aneurysm and poor ejection fraction.
CONCLUSIONS
Dex inhibited CM cytokinesis and functional recovery and caused ventricular aneurysm in the hearts of 2-day old pigs post-MI. | 10.1016/j.yjmcc.2020.04.033 |
pubmed_365_3068 | BACKGROUND
The ideal progestin for combined hormone replacement therapy should be free of adverse effects on lipid metabolism. We therefore examined lipid profiles during continuous hormone replacement therapy (HRT) with an estradiol-gel combined with either a levonorgestrel-releasing intrauterine device (LNG-IUD) or oral/vaginal natural progesterone.
METHODS
Sixty menopausal women recruited in this open, non-randomised parallel three-group study received percutaneous gel containing 1.5 mg of estradiol daily. Progestin was administered to the women with an LNG-IUD (n = 20), as oral natural progesterone (n = 21) 100 mg daily on the 1-25 calendar days of the month or as vaginal progesterone (n = 19) 100-200 mg daily on the 1-25 calendar days of the month. Serum concentrations for total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and sex hormone binding globulin (SHBG) were measured at 0, 6 and 12 months. The median (and 95% confidence interval) of the serum SHBG, total, LDL-, HDL- cholesterol and triglycerides concentrations at baseline and after 6 and 12 months of the study and the ratio of 6 and 12 months values to baseline values were calculated.
RESULTS
Total cholesterol was significantly decreased (8%) in the vaginal progesterone group at the end of the trial. HDL-cholesterol did not change in either of the progesterone groups, while a slight but transient decrease (median 15%) was seen at 6 months in the LNG-IUD group. There were no significant changes in triglycerides or LDL-cholesterol concentrations in any group. SHBG did not change significantly in the LNG-IUD and vaginal progesterone groups, while a slight but transient increase was seen in oral P group at 6 months.
CONCLUSIONS
As the only significant harmful effect observed was a transient decrease in HDL-cholesterol in the LNG-IUD group at 6 months, each of these HRT-administration methods can be regarded as being safe in their effects on lipid metabolism. | 10.1007/s004040050222 |
pubmed_109_4290 | The development of the 81Rb-81mKr generator-delivery system has made available an ultrashort (13-sec) half-life radionuclide for continuous, constant-rate delivery as a gas, or as an isotonic, nonionic solution in 5% dextrose and water. This system has been evaluated and applied to the scintigraphic imaging of various organs and anatomic regions by intravenous and intraarterial infusion and by inhalation and deglutition. This diffusible, noble gas is inert chemically and biologically. When the gas is administered intraarterially, the volume of tissue being perfused may be defined with the scintillation camera. The 13-sec half-life is of a similar magnitude to the rate of capillary exchange, producing a heterogeneous image with steady-state administration in which the intensity of detectable radioactivity is proprotional to the time of diffusion into the tissue. This system appears capable of defining the rate of capillary exchange and the moment-to-moment changes brought about by vasoactive stimuli in specific organs. | 10.1016/s0001-2998(76)80003-7 |
pubmed_486_14213 | BACKGROUND
Helicobacter pylori is a pathogenic bacterium that causes various gastrointestinal diseases in the human stomach. H. pylori is well adapted to the human stomach but does not easily infect other animals. As a model animal, Mongolian gerbils are often used, however, the genome of the inoculated H. pylori may accumulate mutations to adapt to the new host. To investigate mutations occurring in H. pylori after infection in Mongolian gerbils, we compared the whole genome sequence of TN2 wild type strain (TN2wt) and next generation sequencing data of retrieved strains from the animals after different lengths of infection.
RESULTS
We identified mutations in 21 loci of 17 genes of the post-inoculation strains. Of the 17 genes, five were outer membrane proteins that potentially influence on the colonization and inflammation. Missense and nonsense mutations were observed in 15 and 6 loci, respectively. Multiple mutations were observed in three genes. Mutated genes included babA, tlpB, and gltS, which are known to be associated with adaptation to murine. Other mutations were involved with chemoreceptor, pH regulator, and outer membrane proteins, which also have potential to influence on the adaptation to the new host.
CONCLUSIONS
We confirmed mutations in genes previously reported to be associated with adaptation to Mongolian gerbils. We also listed up genes that mutated during the infection to the gerbils, though it needs experiments to prove the influence on adaptation. | 10.1186/s13099-019-0326-5 |
pubmed_218_23268 | AIM
To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4(+)CD25(nt/hi)CD127(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients.
METHODS
Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4(+) T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software.
RESULTS
In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%+/-0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%+/-2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%+/-2.23%) than newly HIV-1 infected patients (3.22%+/-1.01%, P<0.05) and patients in progression to AIDS(5.21%+/-1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4(+) T cell absolute counts but elevated plasma viral load.
CONCLUSION
Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients. | pubmed_218_23268 |
pubmed_217_2991 | The preparation of magnetic molecularly imprinted polymers (MMIPs) which can be used for the separation and purification of rutin from Chinese medicinal plants has been proposed. By applying the improved co-precipitation method, magnetic Fe(3)O(4) particles were easily prepared, followed by the modification of TEOS and functionalization with -CH=CH(2). Using functionalized Fe(3)O(4) particles as the magnetic cores, rutin as the template, and acrylamide as the functional monomer, MMIPs were synthesized by surface-imprinted polymerization under the protection of nitrogen gas and successive mechanical stirring at 60 °C for 24 h. Magnetic non-molecularly imprinted polymers (MNIPs) were also prepared with the same synthesis procedure as with MMIPs only without the presence of rutin. Magnetic particles were characterized by FT-IR, XRD, and TG analysis. And the selectivity of MMIPs was also investigated in detail. In addition, the performance of the MMIPs for the adsorption of rutin in the analysis of Chinese medicinal plants was assessed. The mean recoveries were 84.33% (RSD: 3.22%, n = 3) for Saururus chinensis (Lour.) Bail and 85.20% (RSD: 3.58%, n = 3) for Flos Sophorae, respectively, which showed that the prepared MMIPs with many advantages possess the value of practical application. | 10.1039/c2an35259a |
pubmed_565_7658 | In order to establish the involvement of particular neurochemical brain groups in the response to blood volume expansion, we analyzed Fos-labeling in combination with immunolabeling for serotonin, tyrosine hydroxylase, vasopressin and oxytocin, 90 min after a sham or i.v. isotonic blood volume expansion (BVE) in unanesthetized, unrestrained rats. We also examined the changes in concentration of oxytocin, atrial natriuretic peptide and vasopressin plasma, induced by blood volume load, to confirm our previous studies. The results demonstrate the participation of specific paraventricular and supraoptic nucleus groups of cells (oxytocinergic-vasopressinergic), serotoninergic dorsal raphe nucleus cells and catecholaminergic A1/A2/A6 groups (in the caudal ventrolateral medulla, nucleus of the solitary tract and locus coeruleus respectively), in the regulatory response to BVE. They provide detailed neuroanatomical evidence to support previous observations showing the contribution of these neurochemical systems in the neural, behavioral and endocrine response to isotonic BVE. | 10.1016/j.neuroscience.2005.02.035 |
pubmed_345_15113 | INTRODUCTION
E-cigarettes or electronic nicotine delivery systems (ENDS) have recently attracted considerable attention. Among some individuals there is strong debate and a polarisation of views about the public health benefits versus harms of ENDS. With little regulation, the ENDS market is evolving, and new products are introduced and marketed constantly. Rapid developments in manufacturing, marketing and consumer domains related to ENDS will warrant frequent re-evaluation, based on the state of the evolving science. The purpose of this article is to describe a protocol for an ongoing comprehensive review of the published scientific literature on ENDS.
METHODS AND ANALYSIS
We will undertake a systematic review of published empirical research literature on ENDS using the National Library of Medicine's PubMed electronic database to search for relevant articles. Data from included studies will be extracted into a standardised form, tables with study details and key outcomes for each article will be created, and studies will be synthesised qualitatively.
ETHICS AND DISSEMINATION
This review synthesises published literature and presents no primary data. Therefore, no ethical approval is required for this study. Subsequent papers will provide greater detail on results, within select categories, that represent gaps in the literature base. | 10.1136/bmjopen-2015-007688 |
pubmed_580_12851 | Improvements in diagnostic techniques and, above all, breast cancer screening campaigns - essential for early diagnosis - have enabled the objectives of conservative surgery to be pursued: disease control, no or low incidence of recurrences and an excellent esthetic result. However, to reach these objectives, it is essential to ensure a careful evaluation of the medical history of every patient, a detailed clinical examination and the correct interpretation of imaging. Particular attention should be paid to all factors influencing the choice of treatment and/or possible local recurrence: age, site, tumor volume, genetic predisposition, pregnancy, previous radiotherapy, pathological features, and surgical margins. The decision to undertake conservative treatment thus requires a multidisciplinary approach involving pathologists, surgeons and oncological radiologists, as well, of course, as the patient herself. | pubmed_580_12851 |
pubmed_908_4320 | This study investigated the impacts of four cultivation patterns including farmer practice, high yield and high efficiency practice, super high yield practice, and super high yield and high efficiency practice on yields, soil nitrate and nitrogen (N) balances in 3 winter wheat-summer maize rotations with straw returning in Hebei Province. Results showed that the super high yield practice was identified with greatest winter wheat and summer maize yields, followed by high yield and high efficiency practice, and super high yield and high efficiency practice, which were all greater than that of farmer practice. The N use efficiency of high yield and high efficiency practice was significantly greater than the other cultivation patterns. The total nitrate accumulation in 0-400 cm soil of these cultivation patterns reached 768.4-1133.3 kg·hm-2, where 80%-85% of the accumulated nitrate were in 90-400 cm soil. Meanwhile, the nitrate leaching was observed in all cultivation patterns and nitrate accumulation peaks at 120-150 cm and 270-330 cm were found. Soil nitrate content of high yield and high efficiency practice was less than 30 mg·kg-1 and generally lower than other cultivation patterns, which to some extent reduced the environmental risk. In addition, nitrate surplus in 0-90 cm soil during winter wheat season was lower than that during summer maize season, and the high yield and high efficiency practice had the lowest apparent nitrogen loss. Overall, the high yield and high efficiency practice was evaluated to be the best cultivation pattern in consi-deration of yield, nitrogen use efficiency and nitrate accumulation in soil, but there was still certain achievable improvement potential. | 10.13287/j.1001-9332.201606.036 |
pubmed_227_18728 | In a period of catastrophic flood in 1998 and 2001 yrs there was noted the enhancement of general quantity of patients with gastroduodenal ulcer disease as well as with complicated course, including gastroduodenal ulcer perforation. In the period of flood in Zakarpattya in 2001 the quantity of patients, who were admitted to hospital, to Tyachiv and Vinogradiv central district hospitals in particular, too late, was enhanced as twice. In conditions of extreme situation it is expedient to conduct prophylactic treatment of patients, who are staying under the dispensary observation for gastroduodenal ulcer disease. Improvement of the surgical treatment results in patients with gastroduodenal ulcer disease complications in the disaster zone may be achieved due to accurate organization and coordination on all the stages of medical care to population, application of modern endoscopic technologies. | pubmed_227_18728 |
pubmed_765_3575 | The applicant BASF SE submitted a request to the competent national authority in the Netherlands to evaluate the confirmatory data that were identified for bentazone in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, a new livestock feeding study and storage stability data for bentazone and 6-hydroxy bentazone in animal matrices were submitted. To address the data gap for potatoes, adjusted less critical good agricultural practices (GAPs) were reported and supporting residue data were provided. The data gap related to analytical methods in fat and herbal infusions were addressed in the framework of the peer review. The data gap for residue trials on leek has not been addressed. Further confirmation from the applicant/Member States are needed for the clarification of the GAP for herbal infusions. Based on the information submitted in support of the confirmatory data request, the existing EU MRLs for bentazone need to be modified for potato and leek, for swine fat and kidney and for bovine, equine, goat and sheep fat, liver and milk. The consumer risk assessment performed in the MRL review was updated, using new toxicological reference values derived by the peer review. No consumer intake concerns were identified. | 10.2903/j.efsa.2019.5704 |
pubmed_260_18921 | We introduce a methodology to analyze random molecular fragment populations and determine conditional probability relationships between fragments. Random fragment profiles are generated for an arbitrary set of molecules, and each observed fragment is assigned a frequency vector. An algorithm is designed to compare frequency vectors and derive dependencies of fragment occurrence. Using calculated dependency values, random fragment populations can be organized in graphs that capture their relationships and make it possible to map fragment pathways of biologically active molecules. For sets of molecules having similar activity, unique fragment signatures are identified. The analysis reveals that random fragment profiles contain compound class-specific information and provides evidence for the existence of activity-specific fragment hierarchies. | 10.1021/ci700108q |
pubmed_183_24389 | BACKGROUND
Simple interruption of splanchnic nerve can lead to incomplete transection of nerve fibers responsible for cancer-derived abdominal visceral because lots of neural communications exist.
METHODS
From December 1999 to June 2005, a total of 21 cancer patients underwent bilateral thoracoscopic segmental resection of splanchnic nerve with sympathectomy for intractable abdominal pain based on the anatomic observation of 26 embalmed Korean cadaveric specimens in Yonsei University Medical Center, Seoul, Korea. All patients were preoperatively asked to rate the extent of their current pain by using the numeric rating scale (NRS), where 0 indicated no pain and 10 indicated intractable pain. The effectiveness of this thoracoscopic procedure was assessed based on the NRS reevaluated after surgery.
RESULTS
NRS score was significantly reduced after thoracoscopic surgery (1.71 +/- 1.10 versus 8.52 +/- 1.08, paired t test, P < .0001). Sixteen patients (76.2%) could tolerate pain without or with reduced dose of analgesics. No mortality and morbidity were found in this study.
CONCLUSION
This bilateral thoracoscopic splanchnicectomy with sympathectomy is safe, easy, and effective method in managing cancer-derived visceral abdominal pain. | 10.1016/j.amjsurg.2006.11.018 |
pubmed_529_22938 | During the terminal phase, access to medicines is critical for people wishing to spend their last days of life at home. Yet, access to medicines can be problematic. The aim of this study was to report the perspectives of specialist and generalist health professionals (HPs) on the issues of community access to medicines for this vulnerable group. A qualitative descriptive study design investigated the views of HPs working in palliative care roles in South Australia. Nurses, doctors and pharmacists described their experiences of accessing medicines for management of terminal phase symptoms during semi-structured focus group discussions. Content analysis identified six themes including: 'Medication Supply', 'Education and Training', 'Caregiver Burden', 'Safety', 'Funding' and 'Clinical Governance'. Future projects should aim to address these themes when developing strategies for the management of people wishing to die at home. | 10.1071/PY16153 |
pubmed_54_17773 | A TiO2/CdS:Mn hybrid structure cosensitized with two different sizes of CdTe quantum dots (QDs) was designed to develop a novel and ultrasensitive photoelectrochemical DNA assay. In this protocol, TiO2/CdS:Mn hybrid structure was prepared by successive adsorption and reaction of Cd(2+)/Mn(2+) and S(2-) ions on the surface of TiO2 film and then was employed as matrix for immobilization of hairpin DNA probe, whereas large-sized CdTe-COOH QDs and small-sized CdTe-NH2 QDs as signal amplification elements were successively labeled on the terminal of hairpin DNA probe. The target DNA detection was based upon the photocurrent change originated from conformation change of the hairpin DNA probe after hybridization with target DNA. In the absence of target DNA, the immobilized DNA probe was in the hairpin form and the anchored different sizes of CdTe-COOH and CdTe-NH2 QDs were close to the TiO2/CdS:Mn electrode surface, which led to a very strong photocurrent intensity because of the formation of the cosensitized structure. However, in the presence of target DNA, the hairpin DNA probe hybridized with target DNA and changed into a more rigid, rodlike double helix, which forced the multianchored CdTe QDs away from the TiO2/CdS:Mn electrode surface, resulting in significantly decreased photocurrent intensity because of the vanished cosensitization effect. By using this cosensitization signal amplification strategy, the proposed DNA assay could offer an ultrasensitive and specific detection of DNA down to 27 aM, and it opened up a new promising platform to detect various DNA targets at ultralow levels for early diagnoses of different diseases. | 10.1021/ac503043w |
pubmed_530_4979 | Human growth hormone (GH), but also GH related growth factors like the insulin-like growth factor-1 (IGF-1) are known to be abused in sports. Although the scientific evidence supporting a distinct effect of GH on performance in healthy trained subjects is limited, it has been repeatedly found with athletes or trainers, and the recent introduction of a first test to detect GH doping has led to a number of positive cases. Currently, there is no test for the detection of IGF-1 introduced worldwide, but confiscation of the drug from sports teams can be taken as indirect evidence for its abuse. The major biochemical difficulty for the detection of GH is that the recombinant form is identical in physicochemical properties to the endogenous GH secreted by the pituitary gland. Furthermore, the very short half-life of GH in circulation inherently shortens the window of opportunity where the drug can be detected. Two strategies have been followed for more than a decade to develop a test to detect the application of recombinant GH: the marker approach, which is based on the elevation of GH-dependent markers above the level seen under physiological conditions evoked by administration of recombinant GH, and the isoform approach, which is based on a change in the pattern of GH isoforms in circulation following the injection of recombinant GH. | 10.1159/000341748 |
pubmed_463_6037 | The mitochondrial (mt) genome of the scallop Mimachlamys senatoria (17,383 bp), an economically and ecologically important bivalve, was newly sequenced and annotated. Comparative analyses between M. senatoria and its congeneric sister species M. nobilis revealed three new findings: (1) M. senatoria is more prone to use G-rich start/stop codon, and variation in start/stop codon usage is species-correlated rather than gene-correlated, and in some extent, bears useful phylogenetic information; (2) The A + T content is unexpectedly low (54.1%) in MNR and that is unexpectedly high (65.4%) in atp8 in both congeneric scallops, which may represent a novel evolutionary pattern of mt genomic nucleotide composition; and (3) The tRNA gene cluster "NGV" locating upstream of the nad1 in M. senatoria is replaced by "NTGV" in M. nobilis, and a parsimonious explanation for the existence of trnT in M. nobilis is that this gene was derived from a recently duplicated trnG gene via an alloacceptor tRNA gene recruitment process. | 10.3109/19401736.2013.823181 |
pubmed_1032_10493 | Fernandes-Da-Silva, J, Castagna, C, Teixeira, AS, Carminatti, LJ, Francini, L, Póvoas, SCA, and Antonacci Guglielmo, LG. Ecological and construct validity of a repeated sprint test in male youth soccer players. J Strength Cond Res 35(7): 2000-2009, 2021-This study aimed to examine the relationship between a repeated sprint ability (RSA) test (5 bouts of 30-m sprints interspersed by 30 seconds of recovery) and match-related physical performance in male youth soccer players. Although 60 outfield players were evaluated, only data from players who participated in the full matches (n = 39) were retained (8 central defenders, 7 external defenders, 8 central midfielders, 8 external midfielders, and 8 forwards). To verify the ecological validity of this RSA protocol, the association between the best (RSAbest) and mean (RSAmean) sprint time in the 5 × 30-m and physical match performance during friendly youth soccer games was examined. Physical match demands were assessed using global positioning system technology (10 Hz) considering distance covered in selected arbitrary speed categories. The absolute speed thresholds were the same for all the players. Players were categorized into 2 groups based on the 5 × 30-m performance: RSAmean times below (i.e., faster) and above (i.e., slower) the median value. Players with faster RSAmean times covered significantly more distance sprinting during friendly matches (606 ± 204 m, +47.0%; t = 4.953; effect size = 1.88, 1.24; 2.52, p ≤ 0.001) compared to their slower counterparts (322 ± 145 m). A large negative correlation (r = -0.63, -0.77; -0.44, p ≤ 0.001) was found between RSAbest time (4.59 ± 0.27 seconds) and match sprint distance (457 ± 229 m). Likewise, RSAmean time (4.76 ± 0.25 seconds) was also largely associated (r = -0.60, -0.75; -0.39; p ≤ 0.001) with in-game sprinting performance. The results of this study provided evidence to support the construct and ecological validity of the 5 × 30-m protocol in male youth soccer players. Furthermore, differences in 5 × 30-m performance explained the amount of sprinting activity performed during the match. | 10.1519/JSC.0000000000003047 |
pubmed_974_13194 | Methane, the major component of natural gas, has been in use in human civilization since ancient times as a source of fuel and light. Methanogens are responsible for synthesis of most of the methane found on Earth. The enzyme responsible for catalyzing the chemical step of methanogenesis is methyl-coenzyme M reductase (MCR), a nickel enzyme that contains a tetrapyrrole cofactor called coenzyme F430, which can traverse the Ni(I), (II), and (III) oxidation states. MCR and methanogens are also involved in anaerobic methane oxidation. This review describes structural, kinetic, and computational studies aimed at elucidating the mechanism of MCR. Such studies are expected to impact the many ramifications of methane in our society and environment, including energy production and greenhouse gas warming. | 10.1007/978-94-017-9269-1_6 |
pubmed_1132_9148 | The reasons for differences in adverse reaction reporting rates between countries are partly methodological, partly due to the ways in which drugs are used and partly due to factors affecting the populations within countries such as disease prevalence, age distribution, genetic differences amongst others. Whilst these factors make international comparisons difficult to interpret, there can be some advantages in the global approach since some of the differences (e.g. a drug used in a special way for a disease seen only in some countries) may provide situations where early signals of drug problems are accentuated. Also the systems used to detect ADR's in one country may have advantages over others though this has yet to be agreed. On the other hand methodological problems arising out of discrepancies in definitions and terminology can give rise to apparent differences between countries and should be obviated by international agreement. There is very little published information on international differences but a careful analysis of the data may give new insights into drug safety and lead to a general improvement in pharmacovigilance methodology. | 10.3233/JRS-1993-4105 |
pubmed_142_23114 | The surface modification of nanometer- and micrometer-sized particles and planar substrates with polyethylene glycol (PEG) ligands of varying length is a very common strategy to tune the hydrophilicity and biocompatibility of such materials, minimize unspecific interactions, improve biofunctionalization efficiencies, and enhance blood circulation times. Nevertheless, simple methods for the quantification of PEG ligands are comparatively rare. Here, we present a new concept for the quantification of PEG ligands for maleimide-functionalized PEG molecules and the determination of PEG coupling efficiencies, exploiting the quantitative reaction of maleimide with l-cysteine, and the subsequent determination of the unreacted thiol with the photometric Ellman's test. This is shown for heterobifunctional PEG spacers of varying length and amino-functionalized polystyrene nanoparticles (PS NP) without and with differently charged encoding dyes. The reaction of l-cysteine with the Ellman's reagent was monitored photometrically and with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) to derive the reaction mechanism and to obtain the stoichiometry factor for l-cysteine quantification. Mass balances and quantification of l-cysteine via its sulfur concentration using elemental analysis and inductively coupled plasma mass spectrometry (ICP-MS) confirmed the accuracy and reliability of this approach that can be extended to other surface groups and ligands. | 10.1021/acs.analchem.5b02173 |
pubmed_170_21957 | BACKGROUND AND AIMS
It has been considered that the functional decline of renal vasoconstriction during senescence is associated with an alteration in renal alpha1-adrenergic receptor (alpha1-AR) expression. While alterations in renal angiotensin II receptor (ATR) expression was considered to have an effect on renal structure and function, until now little information has been available concerning alpha1-AR and ATR expression variations over the entire aging continuum. The present study was undertaken to examine the expression levels of alpha1-AR and ATR subtypes in renal tissue during the spectrum running from young adulthood, to middle age, to the presenium, and to the senium.
METHODS
Semiquantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot were used to quantify the messenger RNA (mRNA) and protein levels of alpha1-AR and ATR subtypes in renal tissue in 3-month-old (young adult), 12-month-old (middle age), 18-month-old (presenium) and 24-month-old (senium) Wistar rats.
RESULTS
alpha1A-AR expression decreased gradually with aging: it was decreased during middle age, the presenium and the senium, compared, respectively, with young adult values (p<0.01), and there was a significant decline both in the presenium with respect to middle age and in the senium with respect to the presenium. alpha1B-AR and alpha1D-AR expression were unmodified during senescence. AT1R expression was unaffected by aging during young adulthood and middle age, but exhibited a remarkable downregulation in the presenium and senium periods (p<0.01). AT2R expression was markedly increased in the senium (p<0.01).
CONCLUSIONS
These results suggest that there are considerable variations in the expression levels of renal alpha1-AR and ATR subtypes during aging. alpha1A-AR expression downregulation may account for the reduced reactivity of renal alpha1-AR to vasoconstrictors and to renal function decline in the senium. Both the downregulation of AT1R and the upregulation of AT2R may be influential in maintaining normal physiological renal function during aging. | 10.1007/BF03324784 |
pubmed_1094_4341 | BACKGROUND
The chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the commonest chronic inflammatory diseases in adult men, for which acupuncture has been used to relieve related symptoms. The present study aimed to evaluate the therapeutic effect of the long-needle acupuncture on CP/CPPS.
METHODS
A randomized traditional acupuncture-controlled single blind study was conducted on 77 patients who were randomized into long-needle acupuncture (LA) and traditional acupuncture (TA) groups. The patients received six sessions of acupuncture for 2 weeks and a follow-up was scheduled at week 24. The primary outcome was measured by the total National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score at week 2. Four domains of the NIH-CPSI (urination, pain or discomfort, effects of symptoms, and quality of life) and the clinical efficacy score served as the secondary outcome.
RESULTS
The total NIH-CPSI score at week 2 and week 24 was significantly improved in the LA group compared with the TA group. LA significantly improved urination, pain or discomfort, the effects of symptoms, and the quality of life at week 2 and week 24 and patients undergoing LA treatment had a higher clinical efficacy score.
CONCLUSION
Needling at the BL30 and BL35 using LA benefits patients with CP/CPPS.
TRIAL REGISTRATION
The study was registered at the Chinese Clinical Trial Register ( ChiCTR-ICR-15006138 ). | 10.1186/s12906-017-1768-2 |
pubmed_524_18954 | PURPOSE
Emerging evidence has suggested that macular microcirculation and microstructural changes after rhegmatogenous retinal detachment (RRD) successful reattachment surgery are currently evaluated in detail by OCT-Angiography (OCT-A). New imaging technology has revealed the existence of microscopic macular changes, even in cases that retinal morphology appears to be normal in fundus biomicroscopy. The use of OCT-A for the examination of foveal characteristics has attracted significant attention in recent years as the technique offers a potential explanation of the suboptimal recovery of visual acuity and incomplete restoration of the macula despite anatomical repair. However, the available evidence that is needed to establish the OCT-A parameters as predicting factors in clinical practice is both limited and contradictory.
METHODS
A detailed review of the literature was conducted. The association of OCT-A characteristics with postoperative visual acuity after RRD surgery, including vitrectomy with gas tamponade and in some cases scleral buckle, was extensively analyzed.
RESULTS
A comprehensive update on microcirculation and microstructural changes of the macula using OCT-A after RRD repair may indicate potential factors of functional outcomes in clinical practice.
CONCLUSION
A review of the existing literature sheds light on the microvascular changes of the macular capillary plexus that may significantly affect functional outcomes after RRD surgery. The current article discusses important aspects of key publications on the topic, highlights the importance of long-term effectiveness of these possible prognostic factors and proposes the need for further future research. | 10.1007/s10792-021-01777-2 |
pubmed_1092_8416 | DNA quantification is an important step in the molecular genetic analysis of a forensic sample, hopefully providing reliable data on DNA content for a subsequent generation of reproducible STR profiles for identification. For several years, this quantification has usually been done by real-time PCR protocols and meanwhile a variety of assays are commercially available from different companies. The newest one is the PowerQuant(TM) assay by Promega Inc. which is advertised with the promise that a determined DNA concentration of 0 ng/μl in a forensic sample guarantees the impossibility to achieve true STR results, thus allowing to exclude such samples from STR analysis to save time and money. Thus, the goal of this study was to thoroughly verify the quantification step with regard to its suitability as a screening method. We have evaluated the precision and reliability of four different real-time PCR quantification assays by systematically testing DNA dilutions and forensic samples with various DNA contents. Subsequently, each sample was subjected to the Powerplex® ESX 17 fast kit to determine a reliable cutoff level for exclusion of definitely negative samples from STR analysis. An accurate quantification of different cell line DNA dilutions was not possible with any kit. However, at least the PowerQuant(TM) assay provided suitable data analyzing forensic samples, whereas in other systems up to 46 % of negative samples still displayed reliable STR analysis results. All in all, the PowerQuant(TM) assay represents a big step forward, but the evaluation of real-time PCR quantification results has still to be done with great care. | 10.1007/s00414-016-1352-1 |
pubmed_655_10738 | Pulmonary alveolar proteinosis (PAP) is a disease characterized by the filling of alveolar spaces with periodic acid-Schiff-positive proteinaceous material and by the hypertrophy of type II pneumocytes in the alveolar interstitium. To examine if KL-6, a mucinlike glycoprotein, is useful for the diagnosis of PAP and the estimation of its activity, serum KL-6 levels in patients with PAP were measured by an enzyme-linked immunosorbent assay and compared with those of patients with other lung diseases. Furthermore, to estimate the origin of KL-6 in some patients, measurements of KL-6 levels in bronchoalveolar lavage (BAL) fluid and immunohistochemical staining of the lung tissues with a monoclonal antibody to KL-6 antigen were performed. Serum KL-6 levels in patients with PAP were extremely high and were significantly higher than those in patients with interstitial lung diseases in which elevation of serum KL-6 has been recognized. BAL-fluid KL-6 levels in patients with PAP were higher than serum levels. Both serum and BAL-fluid KL-6 levels in patients with PAP correlated well with the disease activity. Immunohistochemically, positive staining was observed in proliferating type II pneumocytes. These results suggest the usefulness of KL-6 measurement in the diagnosis and estimation of disease activity of PAP. | 10.1164/ajrccm.158.4.9712003 |
pubmed_277_22017 | 1. To study the role of interleukin (IL)-4 in the onset of contact hypersensitivity (CH) in mice, the effect of IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment on dinitrofluorobenzene (DNFB)-induced CH was examined. Simultaneously, to clarify the effect of background gene, DNFB-induced CH in BALB/c and C57BL/6 mice was compared. 2. Five repeated topical applications of DNFB to the ears of mice resulted in CH of the ears in terms of increases in ear thickness and histopathological changes. The magnitude of ear thickness increase in BALB/c mice was almost three times greater than that in C57BL/6 mice. 3. The CH in BALB/c mice was significantly suppressed by IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment. In contrast, the symptoms of dermatitis in C57BL/6 mice were slightly affected by the same treatment. These changes corresponded well to the production of specific IgE antibody. 4. Total IgE antibody production and the expression of productive Cepsilon mRNA were dramatically suppressed by IL-4 gene-depletion and anti-IL-4 treatment in BALB/c and C57BL/6 mice. Neither total IgG nor IgM levels in either strain of mice was altered by depletion of IL-4. 5. The expression of IFN-gamma in the skin lesion was dramatically suppressed by IL-4 gene-depletion in BALB/c mice, but not in C57BL/6 mice. 6. These findings indicate that IL-4 plays an important role in the onset of DNFB-induced CH in BALB/c mice, but not in C57BL/6 mice. | 10.1038/sj.bjp.0703054 |
pubmed_490_7980 | A thermal desorption comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (TD-GC×GC-TOFMS) method has been developed for the analysis of mainstream tobacco smoke (MTS) vapour phase (VP). The selection process of the sample introduction approach involved comparing the results obtained from three different approaches: a) use of gas sampling bag followed by SPME (Tedlar®-SPME), b) gas sampling bag followed by TD (Tedlar®-TD), and c) sampling directly on TD sorbents (Direct-TD). Six different SPME fibers and six different TD sorbent beds were evaluated for the extraction capacities in terms of total number of peaks and related intensities or peak areas. The best results were obtained for the Direct-TD approach using Tenax TA/Carbograph1TD/Carboxen1003 sorbent tubes. The optimisation of TD tube desorption parameters was carried out using a face-centered central composite experimental design and resulted in the use of the Tenax TA/Carbograph 1TD/Carboxen 1003 sorbent with a 7.5min desorption time, a 60mL/min tube desorption flow, and a 250°C tube desorption temperature. The optimised method was applied to the separation of MTS-VP constituents, with 665 analytes detected. The method precision ranged from 1% to 15% for over 99% of identified peak areas and from 0% to 3% and 0% to 1% for both first (1tR) and second (2tR) dimension retention times, respectively. The method was applied to the analyses of two cigarette types differing in their filter construction. Principal component analysis (PCA) allowed a clear differentiation of the studied cigarette types (PC1 describing 94% of the explained variance). Supervised Fisher ratio analysis permitted the identification of compounds responsible for the chemical differences between the two sample types. A set of 91 most relevant compounds was selected by applying a Fisher ratio cut-off approach and most of them were selectively removed by one of the cigarette filter types. | 10.1016/j.chroma.2017.10.013 |
pubmed_688_655 | A case report of a true intratendinous ganglion of the extensor pollicis brevis is described. It was excised. | 10.1016/s0363-5023(85)80218-5 |
pubmed_1033_7084 | Low gene transfer rate is the most substantial hurdle in the practical application of gene therapy. One strategy to improve transfer efficiency is the use of a conditionally replicating adenovirus (CRAD) that can selectively replicate in tumor cells. We hypothesized that conventional E1-deleted adenoviruses (ad) can become replication-competent when cotransduced with a CRAD to selectively supply E1 in trans in tumors. The resulting selective production of large numbers of the E1-deleted ad within the tumor mass will increase the transduction efficiency. We used a CRAD (Delta24RGD) that produces a mutant E1 without the ability to bind retinoblastoma but retaining viral replication competence in cancer cells with a defective pRb/p16. Ad-lacZ, adenovirus-luciferase (ad-luc), and adenovirus insulin-like growth factor-1R/dominant-negative (ad-IGF-1R/dn; 482, 950) are E1-deleted replication-defective adenoviruses. The combination of CRAD and ad-lacZ increased the transduction efficiency of lacZ to 100% from 15% observed with ad-lacZ alone. Transfer of media of CRAD and ad-lacZ cotransduced cells induced the transfer of lacZ (media transferable bystander effect). Combination of CRAD and ad-IGF-1R/dn increased the production of truncated IGF-1R or soluble IGF-1R > 10 times compared with transduction with ad-IGF-1R/dn alone. Combined intratumoral injection of CRAD and ad-luc increased the luciferase expression about 70 times compared with ad-luc alone without substantial systemic spread. Combined intratumoral injection of CRAD and ad-IGF-1R/482 induced stronger growth suppression of established lung cancer xenografts than single injections. The combination of CRAD and E1-deleted ad induced tumor-specific replication of CRAD and E1-deleted ad and increased the transduction rate and therapeutic efficacy of these viruses in model tumors. | 10.1158/0008-5472.CAN-04-1200 |
pubmed_98_15231 | Anion channelrhodopsin from Guillardia theta (GtACR1) has Asp234 (3.2 Å) and Glu68 (5.3 Å) near the protonated Schiff base. Here, we investigate mutant GtACR1s (e.g., E68Q/D234N) expressed in HEK293 cells. The influence of the acidic residues on the absorption wavelengths was also analyzed using a quantum mechanical/molecular mechanical approach. The calculated protonation pattern indicates that Asp234 is deprotonated and Glu68 is protonated in the original crystal structures. The D234E mutation and the E68Q/D234N mutation shorten and lengthen the measured and calculated absorption wavelengths, respectively, which suggests that Asp234 is deprotonated in the wild-type GtACR1. Molecular dynamics simulations show that upon mutation of deprotonated Asp234 to asparagine, deprotonated Glu68 reorients toward the Schiff base and the calculated absorption wavelength remains unchanged. The formation of the proton transfer pathway via Asp234 toward Glu68 and the disconnection of the anion conducting channel are likely a basis of the gating mechanism. | pubmed_98_15231 |
pubmed_1085_5712 | The variable time considered in science is a measurement. The relation of time to other variables is expressed in rates, and the variable time is seldom explicitly included in equations describing chemical reactions or radioactive decays. Recalling that the Greek word atom is applicable to indivisible particles in both spatial and temporal worlds, the term chronon is proposed to designate elementary particles of time in parallel to the atom in space. Considerations of interactions of chronons with material and nonmaterial objects could promote understanding of several paradoxes in physical and biological sciences. | 10.1073/pnas.89.21.10222 |
pubmed_1041_21844 | During routine dissection of a 75-year-old male cadaver, we observed a communicating branch between the posterior femoral cutaneous nerve and the sciatic nerve. The connection was 11 cm below the infrapiriform foramen and was 3 cm long. Excluding this communicating branch, the origin, course and distribution of the posterior femoral cutaneous nerve showed no variation. The other branches of the sacral plexus were as usual. | pubmed_1041_21844 |
pubmed_23_6756 | Translesion replication is a mechanism that employs specialized DNA polymerases for promoting continued nascent strand extension at forks blocked by the presence of unrepaired DNA damage. In Saccharomyces cerevisiae at least, this process contributes only modestly to the ability of cells to tolerate DNA damage, but is a major source of DNA-damage-induced substitutions and frameshifts, and of spontaneous mutations. Translesion replication past many types of DNA damage in yeast depends on the activities of DNA polymerase zeta (pol zeta) and Rev1p. Pol zeta is found in most, but not all, eukaryotes investigated, whereas Rev1p appears to be universal. Genes encoding these enzymes are found in humans, and appear to perform functions similar to those in yeast. | 10.1042/0300-5127:0290187 |
pubmed_833_3105 | The purpose of this paper is to challenge the uncritical use of incremental cost-outcomes ratios as decision variables. A scenario is presented which describes conditions under which increasing costs per unit of outcome prevail. Marginal costs increase as the proportion of patients treated under a given therapy increases. If the health system's objective is to maximise health benefits then patients will be switched until the marginal benefits per dollar expended are equal between the 2 therapies. In an example where the costs of the new therapy are greater, for a given proportion of patients treated, patients are switched from the existing to the new therapy until an equilibrium is achieved in the allocation of therapies among the treating population. At this point, the overall costs of treatment are at a minimum. This outcome could only be predicted if the underlying cost-outcomes functions are known and the consequent patterns of therapy substitution and cost impacts assessed. The paper concludes by raising concerns as to the role of incremental cost-outcomes ratios as decision variables where increasing costs may be expected to prevail and there is failure to consider the implications of these increasing costs in formulary decision making. If increasing costs are present then conventional cost-outcomes and incremental cost-outcomes ratios are of limited utility as decision variables in the choice of therapy options. | 10.2165/00019053-199610010-00009 |
pubmed_584_5687 | The genome sequences of multiple species has enabled functional inferences from comparative genomics. A primary objective is to infer biological functions from the conservation of homologous DNA sequences between species. A second, more difficult, objective is to understand what functional DNA sequences have changed over time and are responsible for species' phenotypic differences. The neutral theory of molecular evolution provides a theoretical framework in which both objectives can be explicitly tested. Development of statistical tests within this framework has provided insight into the evolutionary forces that constrain and in some cases change DNA sequences and the resulting patterns that emerge. In this article, we review recent work on how functional constraint and changes in protein function are inferred from protein polymorphism and divergence data. We relate these studies to our understanding of the neutral theory and adaptive evolution. | 10.1146/annurev.genom.4.020303.162528 |
pubmed_664_8445 | The aim of this study was to evaluate prospectively the efficacy of different imaging methods in differentiating between chronic pancreatitis and cancer in focal pancreatic lesions and staging of adenocarcinoma. MATERIAL AND METHODS. Between June 2005 and October 2007, 156 consecutive patients were enrolled into the prospective clinical trial. The patients were randomized into two groups. Ultrasonoscopy and endoscopic ultrasound were performed in both the groups. Group A patients were additionally examined by computed tomography and tumor marker assay, while in the group B, intraoperative ultrasonoscopy with biopsy and urgent histological examination were done. Results of each imaging technique regarding differential diagnosis and cancer stage were compared with the findings of surgical and histological examination. RESULTS. Chronic pancreatitis and adenocarcinoma were documented in 58 (37.2%) and 78 (50%) patients, respectively. The size of the lesions and clinical presentation were similar in both the groups, but cancer patients were older than patients with pancreatitis (P<0.001). Preoperatively endosonoscopy had the highest accuracy in assessing differential diagnosis (92.1%) and adenocarcinoma (91.8%), whereas computed tomography had the highest accuracy in assessing tumor size (84.5%) and transabdominal ultrasonography in assessing lymph node involvement (78.9%) and distant metastases (88.6%). Intraoperative ultrasound was the most accurate imaging technique in the assessment of differential diagnosis (100%), adenocarcinoma (98.5%), extent of primary tumor (84.8%), lymph node involvement (87.9%), and distant metastases (100%). CONCLUSIONS. In the differential diagnosis between chronic pancreatitis and adenocarcinoma, preoperative ultrasonography and intraoperative ultrasound are the best imaging methods. When ultrasonography is nondiagnostic, computed tomography and endoscopic ultrasound are alternative techniques. | pubmed_664_8445 |
pubmed_778_6789 | BACKGROUND
Parental support for infant hearing loss is essential for a successful infant screening programme. However, in developing countries where unfavourable customs and beliefs towards childhood disabilities have been reported, parental support towards infant screening is uncertain and there is presently no published evidence on the subject.
OBJECTIVE
To elicit the views of mothers and would-be mothers in order to ascertain their knowledge on infant hearing loss and their attitudes towards infant hearing screening.
METHODS
A structured questionnaire consisting of 15 questions was administered to 101 mothers (mean age 31.6+/-7.3 years, range: 21-55 years) attending two community hospitals in Lagos, Nigeria. The responses were evaluated by descriptive statistics, factor analysis of the principal components and multiple regression analysis. The reliability of the two main domains (knowledge and attitude) was tested for internal consistency by Cronbach's alpha coefficient.
RESULTS
Maternal knowledge was highest for measles (73%; mean score 2.54) and ear discharge (73%; mean score 2.51) but low for birth asphyxia (37%; mean score 1.90), traditional medicine (42%; mean score 2.03) and jaundice (47%; mean score 2.09) as causes of hearing loss. Attitude towards neonatal screening was positive in majority of mothers (92%; mean score 2.84) and there was a high acceptance of hearing aids as an early intervention option (84%; mean score 2.70). Five factors (eigenvalue>1) were extracted after principal component analysis with the attitude variables loading highly and exclusively on one factor. Age was the only demographic variable that was associated with a domain (knowledge) after multiple regression analysis. The component scales for the two domains were highly internally consistent (alpha coefficients of 0.84 and 0.83).
CONCLUSIONS
Contrary to the concerns often expressed about parental support for infant hearing screening programmes in developing countries, this study suggests that current parental knowledge and attitude favour early detection and intervention of childhood hearing impairment. | 10.1016/j.ijporl.2005.08.004 |
pubmed_422_1164 | Pantoprazole is a proton pump inhibitor which has recently had its clinical license extended to include maintenance therapy for the treatment of reflux oesophagitis, Helicobacter pylori eradication and short-term intravenous administration. This article reviews the history of gastric acid secretion and examines the role of proton pump inhibitors, particularly pantoprazole, in the treatment of acid-related disorders. | 10.12968/hosp.1999.60.7.1743 |
pubmed_32_14174 | An endoglucanase-encoding clone (egl2) was isolated from the phytopathogenic soilborne deuteromycete fungus Macrophomina phaseolina (Mp). Clones were obtained from a cDNA library by functional expression in Escherichia coli. The egl2 clone hybridized to a 1.3-kb mRNA. Expression is induced by carboxymethylcellulose (CMC) and repressed by glucose. The deduced amino acid (aa) sequence revealed strong similarity to the egl3 from Trichoderma reesei (Tr) (72% for identical residues and 81% with conservative substitution over a span of 324 aa). The Mp egl2 lacks the cellulose-binding domain and linker region found in the Tr egl3. Different codon usage between the two fungi resulted in a much shorter span of nucleotide homology. The Egl2 protein cleaves cellodextrins with continguous beta, 1-4 linkages of four and larger, and shows activity against CMC and birchwood xylan. | 10.1016/0378-1119(95)00094-m |
pubmed_431_8197 | BACKGROUND
The natural history of scar maturation in humans has never been formally described from either a clinical or a histologic standpoint.
METHODS
The maturation of incisional scars was observed in 58 healthy male volunteers who each had 2 x 1-cm incisional wounds created on the inner aspect of both upper arms. The resulting scars were photographed digitally at monthly intervals for 12 months and excised for histologic analysis at specific time points. All histologic specimens were stained using Masson's trichrome and reviewed together with the corresponding digital clinical scar images to produce macroscopic and microscopic descriptions of the maturation process.
RESULTS
Three distinct groups, each displaying a different rate of longitudinal progression of scar maturation, were identified from within the study group. The majority of volunteers belonged to a "representative" subset but distinct "poor" and "excellent" subsets were also identified. The poor subset invariably contained volunteers younger than 30 years of age, whereas the majority of the excellent subset comprised subjects older than 55 years of age.
CONCLUSIONS
Scar maturation occurs as a series of defined macroscopic and microscopic stages over the course of 1 year. The rate of scar maturation varied within the study group, with older subjects (>55 years) displaying accelerated maturation, whereas a prolonged high turnover state and a retarded rate of maturation were observed in younger subjects (<30 years). | 10.1097/PRS.0b013e31816a9f6f |
pubmed_77_2522 | The metabolism of phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] in rat parotid acinar cells was investigated, particularly with regard to the effects of receptor-active agonists. Stimulation of cholinergic-muscarinic receptors with methacholine provoked a rapid disappearance of 40--50% of [32P]PtdIns(4,5)P2, but had no effect on PtdIns4P. Adrenaline, acting on alpha-adrenoceptors, and Substance P also stimulated net loss of PtdIns(4,5)P2. The beta-adrenoceptor agonist, isoprenaline, and the Ca2+ ionophore, ionomycin, failed to affect labelled PtdIns(4,5)P2 or PtdIns4P. By chelation of extracellular Ca2+ with excess EGTA, and by an experimental protocol that eliminates cellular Ca2+ release, it was demonstrated that the agonist-induced decrease in PtdIns(4,5)P2 is independent of both Ca2+ influx and Ca2+ release. These results may suggest that net PtdIns(4,5)P2 breakdown is an early event in the stimulus-response pathway of the parotid acinar cell and could be directly involved in the mechanism of agonist-induced Ca2+ release from the plasma membrane. | 10.1042/bj2060555 |
pubmed_536_9390 | BACKGROUND
Many older people believe sensory problems are inevitably, a part of growing old, and avoid assessment and help. Such problems are often also overlooked by health professionals. The aim of this study was to find the prevalence of hearing and vision impairment and their associations with loss of instrumental activities in daily living (IADL) and risk of falling in patients aged 75 years or older, admitted to a medical ward in an acute hospital in each of the five Nordic countries.
METHOD
The Minimum Data Set for Acute Care was used for data collection in 770 patients. Premorbid data, admission data and history of falls over 3 months were obtained on admission by interview and observation. Hearing impairment was present if the patient required a quiet setting to be able to hear normal speech. Vision impairment was defined as unable to read regular print in a newspaper.
RESULTS
Bivariate and logistic regression analyses were performed. Forty-eight per cent of the patients had a hearing impairment, 32.3% had vision impairment and 20.1% had both. Hearing impairment was associated with falling but not in the logistic regression model. Hearing and vision impairment were associated with loss of IADL but only combined impairment was independently.
CONCLUSION
Hearing and vision impairments were frequent among older patients in the medical wards. Falling was associated with hearing loss and IADL loss with hearing, vision and combined impairments. Sensory loss was also associated with fear of falling. It is recommended routinely to screen sensory functions in older patients in a medical setting. Intervention studies are needed to determine whether improvements in hearing and vision can prevent falls and further loss of function in this patient population. | 10.1111/j.1471-6712.2008.00654.x |
pubmed_1075_5212 | The finless porpoise (Neophocaena phocaenoides) is one of the smallest cetacean species. Research into the immune system of the finless porpoise is essential to the protection of this species, but, to date, no genes coding for proteins from the tumor necrosis factor family (TNF family) have yet been reported from finless porpoises. The TNF B cell activating factor (BAFF) is critical to B cell survival, proliferation, maturation, and immunoglobulin secretion and to T cell activation. It acts through its three receptors, BAFF-R, BCMA, and TACI. In the present study, the full-length cDNA of BAFF (designated NpBAFF) from the finless porpoise was cloned using RT-PCR and rapid amplification of cDNA ends (RACE) techniques, and its biological activities have been characterized. To our knowledge, this is the first report of any BAFF gene being cloned from an aquatic mammal. The full-length cDNA of NpBAFF consists of 1502 bases including an 852 bp open reading frame encoding 283 amino acids. This protein was found to contain a predicted transmembrane domain, a putative furin protease cleavage site, and a typical TNF homology domain corresponding to other, known BAFF homologues. Sequence comparison indicated that the amino acid sequence of NpBAFF was very similar to its bovine (87.68%), porcine (76.33%), hircine (87.68%) and canine (82.19%) counterparts. The predicted three-dimensional (3D) structure of the NpsBAFF monomer, analyzed by comparative protein modeling, revealed that it was very similar to its human counterpart. Phylogenetic analysis indicated that NpBAFF showed a notable homology with Artiodactyla BAFFs. The SUMO-NpsBAFF was efficiently expressed in Escherichia coli BL21 (DE3) and confirmed by SDS-PAGE and Western blot analysis. Laser scanning confocal microscopy analysis showed that NpsBAFF could bind to its receptors on B cells. In vitro, MTT assays indicated that SUMO-NpsBAFF could promote the survival or proliferation of mouse splenic B cells grown with anti-mouse IgM. These findings indicate that NpBAFF plays an important role in the survival or proliferation of B cells and has functional cross-reactivity among cetaceans and other mammals. The present findings may provide valuable information for research into the immune system of the finless porpoise. | 10.1016/j.gene.2012.05.001 |
pubmed_398_10339 | The pharmacokinetics and metabolism of cocaine (COC) were determined in late gestation maternal and fetal guinea pigs. After a single i.v. dose of 2-12 mg/kg, the average +/- SD total body clearance of COC was 59 +/- 16 ml/min/kg and was not dose dependent. However, volume of distribution was 2.1 and 3.9 l/kg, mean resident time (MRT) was 42 and 57 min, and elimination half-life was 34 and 49 min at the 2 and 4 mg/kg dose of COC, respectively. With the exception of an increased MRT, the pharmacokinetics were similar after s.c. COC administration. Benzoylecgonine (BE) and benzoylnorecgonine (BN) were major and persistent metabolites. Norcocaine (NOR) concentrations were low and transient. After chronic maternal administration of 6 mg/kg COC s.c., there was no difference between maternal and fetal plasma COC concentrations one hour after the last injection, but COC and BN accumulated in amniotic fluid. Examination of in vitro metabolism of COC in fetal and maternal guinea pig hepatic microsomes demonstrated minimal fetal N-demethylation and induction of maternal N-demethylation by chronic COC exposure. The minimal fetal N-demethylation suggest BN seen previously in vivo after chronic maternal COC administration resulted from maternal formation of NOR and subsequent maternal and/or fetal hydrolysis to BN. | pubmed_398_10339 |
pubmed_970_22362 | Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral- and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given. | 10.2147/IJN.S222419 |
pubmed_150_21796 | The site-selective spectra and decay curves at 20 K of Eu3+ ions doped KGd2F7 were measured to study the local environment of the Eu3+ sites. The experimental results show that Eu3+ ions occupy three types of sites in the KGd2F7 host. And Eu3+ ions in different types of sites exhibit quite distinct emission spectra and have remarkably different 5D0 level decay lifetimes. Based on the intensity ratio of 5D0--> 7F2,1 transitions of Eu3+ and the 5D0 decay lifetimes in different types of sites, the correlation between the luminescent properties and the site symmetry is discussed. | 10.1166/jnn.2016.11811 |
pubmed_459_7020 | Skin biopsy specimens and discolored fingernails from minocycline-treated patients were examined by light and electron microscopy, histochemistry, and energy-dispersive x-ray analysis. Both hyperpigmented and adjacent normally pigmented skin samples contained pigment-laden macrophages in the dermis, although these cells were more numerous in the hyperpigmented skin samples. Elemental analysis showed that both pigment deposits and stratum corneum of hyperpigmented skin samples contained iron and calcium. Discolored areas of fingernails from a minocycline-treated patient also contained iron and calcium. Both skin and nail discoloration were possibly due to the presence of an iron chelate of minocycline and/or quinoid derivatives of minocycline. The presence of iron-containing pigment in normal as well as hyperpigmented skin may have predisposed to formation of minocycline-associated pigment in these patients. | pubmed_459_7020 |
pubmed_837_17721 | The reactivity of CE 407, a monoclonal antibody (MAb) known to bind to the cells of invasive cervical squamous cell carcinoma, was tested by the immunoperoxidase technique in samples from precursor lesions with and without associated condylomatous atypia. Antibody CE 407 bound with a high frequency to cells from cases of cervical intraepithelial neoplasia (CIN) and to cells showing condylomatous changes. Antibody CE 407 gave a positive reaction in 16 (64%) of 25 patients with CIN only. When the morphologic characteristics of human papillomavirus infection were present along with CIN, there was a higher frequency of positivity, with 27 (93%) of 29 such cases positive for CE 407. Reactivity of this MAb with normal exfoliated cervical epithelial cells was not observed. | pubmed_837_17721 |
pubmed_442_13095 | Understanding microbial adaptation to environmental stressors is crucial for interpreting broader ecological patterns. In the most extreme hot and cold deserts, cryptic niche communities are thought to play key roles in ecosystem processes and represent excellent model systems for investigating microbial responses to environmental stressors. However, relatively little is known about the genetic diversity underlying such functional processes in climatically extreme desert systems. This study presents the first comparative metagenome analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert, Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria, Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic hypoliths. However, no significant differences between the two metagenomes were identified. The Antarctic hypolithic metagenome displayed a high number of sequences assigned to sigma factors, replication, recombination and repair, translation, ribosomal structure, and biogenesis. In contrast, the Namib Desert metagenome showed a high abundance of sequences assigned to carbohydrate transport and metabolism. Metagenome data analysis also revealed significant divergence in the genetic determinants of amino acid and nucleotide metabolism between these two metagenomes and those of soil from other polar deserts, hot deserts, and non-desert soils. Our results suggest extensive niche differentiation in hypolithic microbial communities from these two extreme environments and a high genetic capacity for survival under environmental extremes. | 10.1093/gbe/evw189 |
pubmed_330_9771 | Flavonoids are ubiquitous in the plant kingdom and have many diverse functions including defense, UV protection, auxin transport inhibition, allelopathy, and flower coloring. Interestingly, these compounds also have considerable biological activity in plant, animal and bacterial systems - such broad activity is accomplished by few compounds. Yet, for all the research over the last three decades, many of the cellular targets of these secondary metabolites are unknown. The many mutants available in model plant species such as Arabidopsis thaliana and Medicago truncatula are enabling the intricacies of the physiology of these compounds to be deduced. In the present review, we cover recent advances in flavonoid research, discuss deficiencies in our understanding of the physiological processes, and suggest approaches to identify the cellular targets of flavonoids. | 10.1111/j.1744-7909.2010.00905.x |
pubmed_1104_9926 | BACKGROUND
Mucin deposition is a common feature in autoimmune collagen diseases including dermatomyositis. Nevertheless, clinical manifestations of mucinosis are uncommon in patients with dermatomyositis. Two cases of mucinosis associated with dermatomyositis are reported.
PATIENTS
A 53-year-old woman presented with symmetrical plaques on the upper limbs formed by the coalescence of small, violaceous papules. In addition, she showed the typical cutaneous and muscle features of dermatomyositis. A 44-year-old woman with dermatomyositis of 5 years' evolution developed linear, flesh-colored papules across the flexural creases of her palms and fingers.
RESULTS
Skin biopsy of the upper limb lesions in the first patient showed epidermal changes compatible with dermatomyositis and dermal mucin deposition. Histopathologic examination of the palmar lesions of the second patient showed less intense epidermal changes of dermatomyositis and dermal mucin deposition.
CONCLUSIONS
Mucin deposition in patients with dermatomyositis may have an unusual clinical presentation, and it should be considered in the differential diagnosis of atypical cutaneous lesions in these patients. | 10.1046/j.1365-4362.2001.01060.x |
pubmed_1031_6186 | We performed in-plane magnetodrag measurements on dilute double layer two-dimensional hole systems, at in-plane magnetic fields that suppress the apparent metallic behavior, and to fields well above those required to fully spin polarize the system. When compared to the single layer magnetoresistance, the magnetodrag exhibits exactly the same qualitative behavior. In addition, we have found that the enhancement to the drag from the in-plane field exhibits a strong maximum when both layer densities are matched. | 10.1103/PhysRevLett.90.226801 |
pubmed_755_18407 | A school-based prevalence survey of trachoma was conducted in three rural municipalities in the state of Sao Paulo, Brazil, in 1989. A total of 950 children aged 4-11 years were examined. The prevalence of inflammatory trachoma was found to be 6.3%, peaking at 24.1% in the 4 year-old age group. The prevalence of trachomatous scarring was 2.7% and was more prevalent in older children. Risk factors included household sleeping arrangements and nasal discharge. | pubmed_755_18407 |
pubmed_449_13170 | The mechanism of reduced fibrinolysis in lungs of rats whose right hemithorax had been exposed to a single dose of 25 Gy of 60Co gamma rays was determined, and fibrinolytic changes were correlated with perfusion and morphologic alterations. Reduced fibrinolytic activity in the irradiated lung was evident after 1 month, and decreased further at 2 months. From 2 to 6 months postirradiation, right lung fibrinolytic activity reached a plateau at about half of the activity in the shielded left lung or in sham-irradiated control lungs. The reduced fibrinolytic activity was largely due to decreased plasminogen activator activity, rather than to increased inhibitor activity. Changes in fibrinolytic activity of the irradiated lung closely paralleled changes in arterial perfusion. Mild ultrastructural changes in the irradiated lung (endothelial blebbing and interstitial edema) preceded fibrinolytic and perfusion defects. In contrast, marked changes such as fibrin deposition in the alveolar space and interstitial hypercellularity and fibrosis occurred after pulmonary fibrinolytic activity and perfusion were reduced. | pubmed_449_13170 |
pubmed_1027_9193 | Bisphenols, in particular bisphenol-A (BP-A), are monomers of various plastics including polycarbonates and epoxy resins which are used in numerous consumer products. The release of BP-A from some of these materials has recently been reported. BP-A is a weak estrogen and structurally related to the aneuploidogenic stilbene estrogen diethylstilbestrol (DES). We have therefore studied BP-A and four other bisphenols for their aneuploidogenic potential by assaying their (i) interference with the cell-free assembly of microtubules (MT); (ii) disruption of the cytoplasmic MT complex in cultured Chinese hamster V79 cells; (iii) disruption of the mitotic spindle and induction of metaphase arrest in V79 cells; and (iv) induction of micronuclei (MN) in V79 cells. At concentrations without gross cytotoxicity, BP-A as well as its alkyl-fluorinated and ring-methylated analog were active at all endpoints tested, whereas the bisphenol without alkyl groups was completely inactive. 4,4'-Dihydroxybenzophenone was inactive against cell-free and cytoplasmic MT but disrupted the mitotic spindle and induced metaphase arrest and MN. The MN caused by the various bisphenols were analyzed for the presence of kinetochores by staining with CREST antibodies. All induced MN were CREST-positive, implying that they contain whole chromosomes/chromatids. The effects on MT and the induction of metaphase arrest and of CREST-positive MN suggest that the environmental estrogen BP-A and some of its analogs are potential aneuploidogens. | 10.1016/s0165-1218(96)00161-9 |
pubmed_768_18751 | The critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients in whom IgE neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total IgE levels or body mass. In this study, we sought to generate a novel high affinity anti-IgE antibody (MEDI4212) with potential to treat a broad severe asthma patient population. Analysis of body mass, total and allergen-specific IgE levels in a cohort of severe asthmatics was used to support the rationale for development of a high affinity IgE-targeted antibody therapeutic. Phage display technology was used to generate a human IgG1 lead antibody, MEDI4212, which was characterized in vitro using binding, signaling and functional assay systems. Protein crystallography was used to determine the details of the interaction between MEDI4212 and IgE. MEDI4212 bound human IgE with an affinity of 1.95 pM and was shown to target critical residues in the IgE Cε3 domain critical for interaction with FcεRI. MEDI4212 potently inhibited responses through FcεRI and also prevented the binding of IgE to CD23. When used ex vivo at identical concentration, MEDI4212 depleted free-IgE from human sera to levels ~1 log lower than omalizumab. Our results thus indicate that MEDI4212 is a novel, high affinity antibody that binds specifically to IgE and prevents IgE binding to its receptors. MEDI4212 effectively depleted free-IgE from human sera ex vivo to a level (1 IU/mL) anticipated to provide optimal IgE suppression in severe asthma patients. | 10.4161/mabs.28394 |
pubmed_346_2876 | This paper describes the construction of 18 cloned bacteriophage T7 late promoters with single point mutations. In vitro transcription experiments were used to characterize the properties of these promoters. Since the mutated promoters are cloned into identical backgrounds, differences seen in the transcription assays are directly attributable to the point mutations. All of the mutated promoters are less active than wildtype, but they can be divided into two types. Type A mutations map from -4 to +1 and reduce promoter activity when the template is linearized or when 60mM NaCl is added to the reaction buffer. Type B mutations map from -9 to -7 and reduce promoter activity under all conditions tested. At several sites all three possible point mutations are available. At these sites we observed hierarchies of base pair preference, as determined by promoter activity, that may indicate that T7 RNA polymerase interacts with groups in the major groove. | 10.1093/nar/15.13.5413 |
pubmed_722_11892 | A coplanar refractive-diffractive doublet array employing surface-relief diffractive phase elements embedded within poly(methyl methacrylate) microlenses is introduced as an optomechanical building block for optoelectronic integrated systems. The design method, fabrication technology, and results are described. Coplanarity of the quadratic- and linear-phase elements constituting the doublet can reduce optomechanical complexity in applications to unguided optical interconnects. | 10.1364/AO.34.003048 |
pubmed_167_3976 | Female and male life expectancies have converged in most industrialized societies in recent decades. To achieve coherent forecasts between females and males, this convergence needs to be considered when forecasting sex-specific mortality. We introduce a model forecasting a matrix of the age-specific death rates of sex ratio, decomposed into two age profiles and time indices-before and after age 45-using principal component analysis. Our model allows visualization of both age structure and general level over time of sex differences in mortality for these two age groups. Based on a prior forecast for females, we successfully forecast male mortality convergence with female mortality. The usefulness of the developed model is illustrated by its comparison with other coherent and independent models in an out-of-sample forecast evaluation for 18 countries. The results show that the new proposal outperformed the other models for most countries. | 10.1186/s41118-018-0044-8 |
pubmed_669_22860 | Osteoarthritis (OA) is a common chronic inflammatory disease associated with aging. Etomidate is an intravenous anesthetic with profound antioxidant and anti-inflammatory effects. We speculated that etomidate might exert a beneficial effect on OA. Herein, we explored the effects of etomidate on interleukin-1β (IL-1β)- induced chondrocytes. Our results prove that etomidate ameliorated the IL-1β-induced oxidative stress in C28/12 chondrocytes by decreasing and increasing the reactive oxygen species (ROS) and glutathione peroxidase (GPx) levels, respectively. Etomidate prevented the IL-1β-induced increase in the expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13) in C28/I2 chondrocytes at both mRNA and protein levels. It also caused a significant reduction in the percentage of senescence-associated-β-galactosidase (SA-β-Gal)-stained chondrocytes, while inducing elevated telomerase activity in IL-1β-treated C28/I2 chondrocytes. The expression levels of senescence regulators, plasminogen activator inhibitor-1 (PAI-1) and p16, were also inhibited by etomidate in IL-1β-treated C28/I2 chondrocytes. In addition, etomidate caused the activation of Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), along with upregulated expression levels of phosphorylated AMPKα and phosphorylated acetyl-Co A carboxylase (ACC). Moreover, blockage of AMPK using compound C abolished the protective effects of etomidate on IL-1β-challenged C28/I2 chondrocytes. Taken together, these results demonstrate that etomidate protected C28/I2 chondrocytes from IL-1β-induced oxidative stress, ECM degradation, and cellular senescence via activating AMPK signaling. | 10.1080/21655979.2021.2016085 |
pubmed_922_9899 | A high power microwave source based on energy storage switching pulse compression technology can produce a high power microwave pulse with good repeatability and frequency stability for a long time and has a good development prospect. In order to improve the power gain, this paper studies the working characteristics of the energy extraction structure of the X-band energy storage switching pulse compression device. The theoretical analysis results show that the impedance mismatch exists in the traditional energy extraction structure after the pulse compression is transferred to the energy extraction stage and the energy extraction efficiency is not high, which results in the power gain limitation. Therefore, through theoretical calculation and simulation, an improved scheme based on output inductance diaphragm is proposed in this paper. The scheme has high power capacity and can achieve impedance matching without changing the resonant frequency of the energy storage cavity, so as to improve the power gain of the pulse compression device. The high power experimental results show that the power gain of the pulse compression device can be increased from 6.24 times to 7.22 times and the energy extraction efficiency can be increased by 17.5% by placing 17 mm slot spacing inductance diaphragm at 45 mm of the H-T arm of the waveguide, which verifies the feasibility of the improved scheme. | 10.1063/1.5091956 |
pubmed_919_7409 | We demonstrate intense pulse guiding in efficient femtosecond end-pumped waveguides generated in clustered gases. This novel scheme provides a route to significantly lower on-axis plasma density (< 10(18) cm(-3)) more than is feasible in conventional hydrodynamic plasma waveguides. Self-focused propagation and strong absorption of intense femtosecond laser pulses are used to produce long centimeter scale channels in an argon cluster jet, and a subsequent pulse is guided with 3 x 10(17) W cm(-2) intensity and approximately 50% coupling efficiency. Preliminary results with hydrogen clusters also show guiding. | 10.1103/PhysRevLett.94.205004 |
pubmed_996_12552 | This study analyzed the effect of breast-feeding on the frequency of acute otitis media. The protocol was designed to examine each child at 2, 6 and 10 months of age. At each visit nasopharyngeal cultures were obtained, the feeding pattern was recorded and the acute otitis media (AOM) episodes were documented. The analysis was based on 400 children from whom complete information was obtained. They represented 83% of the newborns in the study areas. By 1 year of age 85 (21%) children had experienced 111 AOM episodes; 63 (16%) had 1 and 22 (6%) had 2 or more episodes. The AOM frequency was significantly lower in the breast-fed than in the non-breast-fed children in each age group (P < 0.05). The first AOM episode occurred significantly earlier in children who were weaned before 6 months of age than in the remaining groups. The frequency of nasopharyngeal cultures positive for Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was significantly higher in children with AOM. At 4 to 7 and 8 to 12 months of age, the AOM frequency was significantly higher in children with day-care contact and siblings (P < 0.05 and < 0.01, respectively). The frequency of upper respiratory tract infections was increased in children with AOM but significantly reduced in the breast-fed group. | 10.1097/00006454-199403000-00003 |
pubmed_711_11639 | Based on the theory that obstructive (OSA) and central (CSA) sleep apneas share common pathophysiologic mechanisms, we attempted to treat eight patients with predominantly CSA by continuous positive airway pressure (CPAP). All patients exhibited repetitive episodes of CSA and mixed sleep apneas (MSA) in the supine position with a mean duration of 23.7 +/- 0.7 s and 34.5 +/- 1.3 s, respectively. The pattern of apnea changed when the subject lay in the lateral position. Five patients were observed to develop OSA in the lateral position with a mean duration of 27.2 +/- 1.5 s, while the other three patients snored continuously. High levels of CPAP (range 9.0 to 16.5 cm H2O) prevented all CSA and MSA and resulted in quiet breathing in all eight patients. Intermediate levels of CPAP produced firstly MSA, then purely OSA and/or continuous snoring. Low levels of nasal CPAP also prevented OSA and snoring occurring in the lateral posture in all subjects (range 2.0 to 8.3 cm H2O). Three patients are currently on home CPAP therapy for a range of four to 36 months. We conclude that upper airway collapse in the supine posture has a key role in the induction of CSA. We suggest that a reflex inhibition of respiration through activation of supraglottic mucosal receptors during passive oropharyngeal airway closure caused CSA in these patients. | 10.1378/chest.90.2.165 |
pubmed_727_3585 | Proteoglycanes, glycoprotein, fibrous collagen and elastin proteins were isolated from normal human aortic intima and from sclerotic lipid and calcium plaques and examined by electron microscope and thermal analysis. Differences between the structure and compositon of normal human aortic wall and aortic lipid plaques are chiefly found in the proteoglycan containing fraction. The calcium plaque shows structural changes in the fibrillar protein components. | pubmed_727_3585 |
pubmed_115_12067 | Small-angle X-ray scattering (SAXS) studies are reported on the interaction of chlorpromazine (CPZ) with micelles of anionic surfactant sodium dodecyl sulfate (SDS). Isotropic solutions of SDS (40 and 100 mM) at pH 4.0, 7.0, and 9.0 in the absence and presence of CPZ (2-25 mM) were investigated at the National Laboratory of Synchrotron Light (LNLS, Campinas, Brazil). The data were analyzed through the modeling of the micellar form factor and interference function. The results evidence a micellar shape transformation from prolate ellipsoid to cylinder accompanied by micellar growth and surface charge screening as the molar ratio CPZ : SDS increases in the complex. Small ellipsoids with axial ratio nu=1.5+/-0.1 at 40 mM SDS grow and reassemble into cylinder-like aggregates upon 5 mM drug incorporation (1 CPZ : 8 SDS monomers) with a decrease of the micelle surface charge. At 10 mM CPZ : 40 mM SDS cylindrical micelles are totally screened with an axial ratio nu approximately 2.5. The data also indicate the presence of small prolate ellipsoids (nu=1.7+/-0.1) in solutions of 100 mM SDS (no drug) and micellar growth (nu approximately 2.0 and 4.0) when 10 and 25 mM CPZ are added to the system. In the latter case, the aggregate is also better represented by a cylinder-like form. Therefore, our results demonstrate that the axial ratio and shape evolution of the surfactant : phenothiazine complex are both SDS concentration and drug : SDS molar ratio dependent. The drug location close to the SDS polar headgroup region without disrupting in a significant way both the paraffinic hydrophobic core and the polar shell thickness is inferred. SAXS data made it possible to obtain the shapes and dimensions of CPZ/SDS aggregates. | 10.1006/jcis.2001.8164 |
pubmed_118_24125 | Solid pseudopapillary tumor (SPT) of the pancreas is a pathological entity rarely encountered in children. Despite its malignant characteristics, SPT has a favorable clinical prognosis. This tumor is more frequently observed in females and is commonly localized in the tail and body of the pancreas. This is the case report of a 9-year-old female patient who presented with severe abdominal pain of sudden onset and vomiting following blunt abdominal trauma. Upon physical examination, abdominal distension, tenderness and abdominal guarding were detected. Abdominal magnetic resonance imaging revealed a mass sized 8×9×12 cm in the pancreas, with hemorrhagic-necrotic areas, and abundant intra-abdominal fluid. Intra-abdominal exploration confirmed the presence of an abundant amount of intraperitoneal hemorrhagic fluid. A mass was identified, originating from the body and the tail of the pancreas, adherent to the mesentery of the colon and the hilum of the spleen, which had ruptured in its inferolateral side. The tumor was extirpated together with the spleen and the involved parts of the pancreas. Histopathological examination demonstrated a solid pseudopapillary tumor of pancreatic origin. The patient's postoperative course was uneventful, clinically as well as metabolically. | 10.3892/mco.2016.997 |
pubmed_713_11885 | The use of DNA-damaging agents such as radiotherapy and chemotherapy has been a mainstay treatment protocol for many cancers, including lung and prostate. Recently, FDA approval of inhibitors of DNA repair, and targeting innate immunity to enhance the efficacy of DNA-damaging agents have gained much attention. Yet, inherent or acquired resistance against DNA-damaging therapies persists as a fundamental drawback. While cancer eradication by causing cancer cell death through induction of apoptosis is the ultimate goal of anti-cancer treatments, autophagy and senescence are two major cellular responses induced by clinically tolerable doses of DNA-damaging therapies. Unlike apoptosis, autophagy and senescence can act as both pro-tumorigenic as well as tumor suppressive mechanisms. DNA damage-induced senescence is associated with a pro-inflammatory secretory phenotype, which contributes to reshaping the tumor- immune microenvironment. Moreover, PTEN (phosphatase and tensin homolog) is a tumor supressor deleted in many tumors, and has been implicated in both senescence and autophagy. This review presents an overview of the literature on the regulation and consequences of DNA damage- induced senescence in cancer cells, with a specific focus on autophagy and PTEN. Both autophagy and senescence occur concurrently in the same cells in response to DNA damaging agents. However, a deterministic relationship between these fundamental processes has been controversial. We present experimental evidence obtained with tumor cells, with a prime focus on two models of cancer, prostate and lung. A better understanding of mechanisms associated with DNA damage-induced cellular senescence is central to fully exploit the potential of DNA-damaging agents against cancer. | 10.1016/bs.acr.2021.01.006 |
pubmed_703_1635 | Compartment syndrome is a limb-threatening and life-threatening emergency resulting from elevated intracompartmental pressure. Prompt surgical intervention and treatment are necessary to prevent irreparable damage to muscle and nerve tissues. Leukemic infiltration of the muscle is an unusual cause of compartment syndrome and has been documented to occur secondary to hyperleukocytic leukemias, most commonly in acute myeloid leukemia. We present a rare case of multiple compartment syndrome in the buttock and thigh of an 11-year-old male patient with chronic myelomonocytic leukemia. The diagnosis of acute compartment syndrome was delayed, causing irreversible tissue damage. Physicians are generally unfamiliar with leukemia-induced complications and may not initially suspect leukemic compartment syndrome because of its rarity. Awareness of its clinical features is critical, because early diagnosis and prompt surgical debridement can prevent significant morbidity and even death. | 10.1097/BPO.0b013e318237c3e0 |
pubmed_1105_14614 | The cholera toxin A1 (CTA1)-DD/QuilA-containing, immune-stimulating complex (ISCOM) vector is a rationally designed mucosal adjuvant that greatly potentiates humoral and cellular immune responses. It was developed to incorporate the distinctive properties of either adjuvant alone in a combination that exerted additive enhancing effects on mucosal immune responses. In this study we demonstrate that CTA1-DD and an unrelated Ag can be incorporated together into the ISCOM, resulting in greatly augmented immunogenicity of the Ag. To demonstrate its relevance for protection against infectious diseases, we tested the vector incorporating PR8 Ag from the influenza virus. After intranasal immunization we found that the immunogenicity of the PR8 proteins were significantly augmented by a mechanism that was enzyme dependent, because the presence of the enzymatically inactive CTA1R7K-DD mutant largely failed to enhance the response over that seen with ISCOMs alone. The combined vector was a highly effective enhancer of a broad range of immune responses, including specific serum Abs and balanced Th1 and Th2 CD4(+) T cell priming as well as a strong mucosal IgA response. Unlike unmodified ISCOMs, Ag incorporated into the combined vector could be presented by B cells in vitro and in vivo as well as by dendritic cells; it also accumulated in B cell follicles of draining lymph nodes when given s.c. and stimulated much enhanced germinal center reactions. Strikingly, the enhanced adjuvant activity of the combined vector was absent in B cell-deficient mice, supporting the idea that B cells are important for the adjuvant effects of the combined CTA1-DD/ISCOM vector. | 10.4049/jimmunol.176.6.3697 |
pubmed_681_20768 | The nanophase anatase of different sizes (2-40 nm) were synthesized with chemical precipitation method. Nanophase anatase (2-40 nm), anatase (micron) and natural anatase were investigated by Raman spectrum. The spectra indicate: when the crystalline particles sizes decreased, obvious Raman shifts towards higher frequencies were observed and the intensity of Raman scattering decreased markedly. The shift towards higher frequencies reached max (10 cm-1) at 143 cm-1 comparing 2 nm anatase and natural anatase; when the crystalline particles sizes decreased; the shifts at 515 and 637 cm-1 towards higher frequencies reached max, but while the crystalline particles sizes became smaller, the shifts reached towards lower frequencies; There was no obvious shift at 396 cm-1 with the decreasing of the crystalline particle sizes. These reflect the complexity of nanophase materials structure, that may be caused by flexibility distortion of crystal. | pubmed_681_20768 |
pubmed_512_9984 | Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus. It is characterized by retinal microvascular changes caused by chronic exposure to hyperglycemia, leading to low tissue oxygenation and ultimately to neovascularization. Laser photocoagulation and vitrectomy are the most efficient treatments for DR, but display severe side effects such as the destruction of the healthy retina. Another clinical approach uses antiangiogenic agents to prevent and delay progression of neovascularization, but these require recurrent local administrations that increase the possibility of retinal detachment, vitreous hemorrhage, and cataract formation. Studies in human diabetic retinas have revealed an imbalance between proangiogenic factors such as the vascular endothelial growth factor (VEGF) and antiangiogenic factors, such as pigment epithelial-derived factor (PEDF). This imbalance favors pathological angiogenesis contributing to DR, and can constitute a therapeutic target. Gene therapy was recently shown to be an adequate intervention for long-term treatment of several retinal pathologies. We have previously shown the newly engineered episomal vector pEPito to be able of sustained gene expression in the mouse retina. We here show that pEPito was able to overexpress PEDF for up to three months, both in in vitro cultures of human retinal pigment epithelial cells and in the retina of diabetic mice after a single subretinal injection. In vivo, in parallel with the increase in PEDF we observed a decrease in VEGF levels in injected compared with noninjected eyes and a significant effect on two hallmarks of DR: reduction of glucose transport (by glucose transporter GLUT1), and reduction of inflammation by decreased reactivity of microglia. Jointly, these results point to a significant therapeutic potential of gene therapy with pEPito-PEDF for the treatment of DR. | 10.1089/hgtb.2015.169 |
pubmed_470_16470 | Results of surgical treatment of 168 patients with diabetes mellitus (DM) in the diabetic foot syndrome (DFS) were analyzed. Expediency of operative intervention was substantiated by pathogenic form of affection, its depth and diffusion, composition of microorganisms in purulent-necrotic focus. Performance of more extensive surgical treatment or distal amputation of foot with consequent closure of vast wound defect using full-layer subcutaneous-cutaneous flap with protracted selective intra-arterial anti-aggregate and antibacterial therapy was indicated in order to preserve the lower extremity supporting function and for prophylaxis of diffusion of purulent-necrotic affection. Application of improved tactics and surgical treatment in patients with DFS have allowed to reduce frequency of the lower extremity high amputation performance from 24 to 8.6%. | pubmed_470_16470 |
pubmed_414_12449 | Novel Biginelli dihydropyrimidines of biological interest were prepared using p-toluene sulphonic acid as an efficient catalyst. All the thirty-two synthesised dihydropyrimidines were evaluated for their in vitro antioxidant activity using DPPH method. Only, compounds 28 and 29 exhibited reasonably good antioxidant activity. Furthermore, the synthesised Biginelli compounds were subjected for their in vitro anticancer activity against MCF-7 human breast cancer cells. The title compounds were tested at the concentration of 10 microg. Compounds exhibited activity ranging from weak to moderate and, from moderate to high in terms of percentage cytotoxicity. Among them, compounds 10 and 11 exhibited significant anticancer activity. In order to elucidate the three-dimensional structure-activity relationships (3D QSAR) towards their anticancer activity, we subjected them for comparative molecular similarity indices analysis (CoMSIA). Illustration regarding their synthesis, analysis, antioxidant activity, anticancer activity and 3D QSAR study is described. | 10.1016/j.ejmech.2009.05.014 |
pubmed_328_19344 | Anaerobic fungi (phylum Neocallimastigomycota), an early branching family of fungi, are commonly encountered in the digestive tract of mammalian herbivores. To date, isolates from ten described genera have been reported, and several novel taxonomic groupings are detected using culture-independent molecular methods. Anaerobic fungi are recognized as playing key roles in the decomposition of lignocellulose (up to 50% of the ingested and untreated lignocellulose), with their physical penetration and extracellular enzymatical secretion of an unbiased diverse repertoire of cell-wall-degrading enzymes. The secreted cell-wall-degrading enzymes of anaerobic fungi include both free enzymes and extracellular multi-enzyme complexes called cellulosomes, both of which have potential as fiber degraders in industries. In addition, anaerobic fungi can provide large amounts of substrates such as hydrogen, formate, and acetate for their co-cultured methanogens. Consequently, large amounts of methane can be produced. And thus, it is promising to use the co-culture of anaerobic fungi and methanogens in the biogas process to intensify the biogas yield owing to the efficient and robust degradation of recalcitrant biomass by anaerobic fungi and improved methane production from co-cultures of anaerobic fungi and methanogens. | 10.1007/s11274-018-2539-z |
pubmed_795_14317 | INTRODUCTION
Intracranial lipomas are rare lesions of developmental origin. They are generally asymptomatic and localized in the midline. However, they may occasionally produce neurological symptoms such as seizures. Surgical treatment is rarely indicated.
CASE REPORT
We report a child with a lipoma that is located on the ventral side of the mamillary bodies. The diagnosis was made using computerized tomography (CT) and magnetic resonance imaging (MRI). There have been no previous reports of lipomas in this location. | 10.1007/s00381-002-0631-y |
pubmed_113_1334 | This study aimed to identify factors influencing the work engagement of employees working from home during the COVID-19 pandemic in Japan. Employees' work engagement was examined using the following survey questions: "Do you feel energized when you are at work? (yes or no)" and "Do you take pride in your work? (yes or no)" After adjusting for potential confounders, Poisson regression was used to examine prevalence ratio and 95% confidence intervals for employees' work engagement. We analyzed 15,670 individuals (11,894 of whom did not work from home and 3776 of whom worked from home). Their mean age was 45.6 ± 13.8 years, and 58.3% were men. Those who worked from home were younger than those who did not (43.9 ± 13.1 vs. 46.1 ± 13.9, p < 0.001). About 44% of all employees reported high work engagement. Among the employees who worked from home, an increase in sleep hours, effective interactions with supervisors, and working hours of ≤40 h/week were associated with engagement. Sensitivity analysis showed similar results. Close communication with superiors, refraining from working long hours, and obtaining adequate sleep may boost the work engagement of employees working from home. | 10.3390/ijerph181910495 |
pubmed_1011_16178 | The diagnosis of angiofibroma can be suspected in most cases by clinical examination, supplemented by routine x-rays and tomograms and is confirmed by angiography. Adjunctive therapy including embolization, estrogens, cryotherapy and arterial ligation is discussed. Surgical resection is the preferred treatment. Radiotherapy as the primary treatment modality is contraindicated except in select cases. | 10.1177/000348947808700505 |
pubmed_1066_6870 | BACKGROUND/AIMS
Previous studies have investigated the relationship between visceral obesity and the risk of colorectal tumors. Visceral obesity may affect the outcome of colorectal cancer (CRC), including survival and metastasis. We investigated the associations between visceral adipose tissue and oncologic outcomes in stage III CRC.
METHODS
Four hundred seventy-two patients with stage III CRC were identified. Subcutaneous and visceral adipose tissue areas were measured volumetrically via computed tomography for each patient at different levels of the lumbar spine. After adjusting for age, sex, and other clinical factors, the effects of visceral adipose tissue area on mortality and recurrence were assessed using Cox proportional hazard regression.
RESULTS
In univariate and multivariate analyses, a higher visceral adipose tissue to total adipose tissue (VT) ratio (hazard ratio [HR], 1.041; 95% CI, 1.008 to 1.075; p=0.015) and higher visceral adipose tissue to subcutaneous adipose tissue (VS) ratio (HR, 1.016; 95% CI, 1.005 to 1.028; p=0.006) were both associated with poor CRC-specific survival. Interestingly, in the evaluation of each site of recurrence, a higher VT ratio (HR, 1.069; 95% CI, 1.010 to 1.131; p=0.020) and higher VS ratio (HR, 1.024; 95% CI, 1.003 to 1.045; p=0.023) were both related to a higher risk of peritoneal seeding and tumor recurrence. The VT ratio at the L3-L4 level was significantly associated with a higher risk of peritoneal seeding and tumor recurrence (HR, 4.969; 95% CI, 1.303 to 18.949; p=0.019), while other levels showed no such relationship.
CONCLUSIONS
Visceral obesity is closely related to increased risks of CRC-specific mortality and peritoneal seeding metastasis in stage III CRC patients. | 10.5009/gnl20266 |
pubmed_192_6624 | Much effort has been directed at studying the orexigenic actions of administered ghrelin and the potential effects of the endogenous ghrelin system on food intake, food reward, body weight, adiposity, and energy expenditure. Although endogenous ghrelin's actions on some of these processes remain ambiguous, its glucoregulatory actions have emerged as well-recognized features during extreme metabolic conditions. The blood glucose-raising actions of ghrelin are beneficial during starvation-like conditions, defending against life-threatening falls in blood glucose, but they are seemingly detrimental in obese states and in certain monogenic forms of diabetes, contributing to hyperglycemia. Also of interest, blood glucose negatively regulates ghrelin secretion. This article reviews the literature suggesting the existence of a blood glucose-ghrelin axis and highlights the factors that mediate the glucoregulatory actions of ghrelin, especially during metabolic extremes such as starvation and diabetes. | 10.1210/en.2019-00074 |
pubmed_130_9358 | We report on a 79-year-old man diagnosed with localized Merkel cell carcinoma (MCC) who also had acetylcholine receptor antibody (Ach-R-Ab)-positive myasthenia gravis (MG) controlled on prednisolone, mycophenolate and intravenous immunoglobulin (IVIG). His MCC was initially treated with radiation, followed by chemotherapy on metastatic recurrence. Chemotherapy initially stabilized the disease, but he experienced significant fatigue and his disease progressed within 3 months. After careful consideration of the risk of a myasthenic crisis, he was commenced on avelumab. He had initial partial response, though he ultimately developed progressive disease which led to a decision for best supportive care at 10 months post starting immunotherapy. Importantly, as per spirometry, his MG remained stable throughout immunotherapy. We present the current case to demonstrate that MG should not be viewed as an absolute contraindication to immunotherapy in scenarios where there are limited alternate therapeutic options. | 10.1093/omcr/omac012 |
pubmed_509_19890 | We employ 4Pi-microscopy to study SC organization in mouse spermatocyte nuclei allowing for the three-dimensional reconstruction of the SC's backbone arrangement. Additionally, we model the SCs in the cell nucleus by confined, self-avoiding polymers, whose chain ends are attached to the envelope of the confining cavity and diffuse along it. This work helps to elucidate the role of entropy in shaping pachytene SC organization. The framework provided by the complex interplay between SC polymer rigidity, tethering and confinement is able to qualitatively explain features of SC organization, such as mean squared end-to-end distances, mean squared center-of-mass distances, or SC density distributions. However, it fails in correctly assessing SC entanglement within the nucleus. In fact, our analysis of the 4Pi-microscopy images reveals a higher ordering of SCs within the nuclear volume than what is expected by our numerical model. This suggests that while effects of entropy impact SC organization, the dedicated action of proteins or actin cables is required to fine-tune the spatial ordering of SCs within the cell nucleus. | 10.1371/journal.pone.0036282 |
pubmed_91_6343 | The discovery of pulmonary metastasis is not a contraindication to operation. In the light of 21 personal cases and a review of the literature, the authors give their arguments in favour of surgery. No pronostic criterion is certain except for two facts: 1) the course is capricious; 2) spontaneous remissions do not occur. The results of surgery alone do not seem to be influenced by radiotherapy nor chemotherapy. | pubmed_91_6343 |
pubmed_730_15358 | Adhesion formation after peritoneal surgery is a major source of postoperative complications and pain. Previous studies showed that intraperitoneal administration of the nonsteroidal anti-inflammatory drug tolmetin reduced adhesion formation after two types of peritoneal surgery. The effect of tolmetin combined with hyaluronic acid (HA), a high-molecular-weight glucosaminoglycan found in the extracellular matrix, on the formation of adhesions was examined. In this study, the effect of tolmetin in HA on adhesion formation was evaluated in a standardized rabbit model. The medicament was administered intraperitoneally at the end of surgery. One week after surgery, a second laparotomy was performed and the extent of adhesion formation was determined. A range of molecular weights (7.5 x 10(5)-2 x 10(6) Da) and viscosities (1000-25,000 centapoise) of HA in combination with tolmetin was effective in reducing adhesion formation. However, low viscosity HA solutions in combination with tolmetin, 0.5-2.0 mg/mL, were most efficacious in reducing adhesion formation. These data suggest that HA, in combination with tolmetin, acts as an effective carrier to reduce adhesion formation in the abdominal cavity after surgery. | 10.3109/08941939709099600 |
pubmed_921_11125 | Insulin-dependent diabetes mellitus is an autoimmune disease that is genetically linked to the HLA class II molecule DQ in humans and to MHC I-Ag7 in nonobese diabetic mice. The I-Ag7 beta-chain is unique and contains multiple polymorphisms, at least one of which is shared with DQ alleles linked to insulin-dependent diabetes mellitus. This polymorphism occurs at position 57 in the beta-chain, in which aspartic acid is mutated to a serine, a change that results in the loss of an interchain salt bridge between alphaArg76 and betaAsp57 at the periphery of the peptide binding groove. Using mAbs we have identified alternative conformations of I-Ag7 class II molecules. By using an invariant chain construct with various peptides engineered into the class II-associated invariant chain peptide (CLIP) region we have found that formation of these conformations is dependent on the peptide occupying the binding groove. Blocking studies with these Abs indicate that these conformations are present at the cell surface and are capable of interactions with TCRs that result in T cell activation. | 10.4049/jimmunol.165.4.2059 |
pubmed_218_14149 | Men have a higher incidence of cardiovascular disease (CVD) than women of similar age, and it has been suggested that testosterone may influence the development of CVD. Recently, we demonstrated that elderly men with low testosterone levels had lower plasma levels of free tissue factor pathway inhibitor (TFPI) Ag associated with shortened tissue factor (TF)-induced coagulation initiation in a population based case-control study. Our hypothesis was that one year of testosterone treatment to physiological levels in elderly men would increase the levels of free TFPI Ag in plasma and have a favorable effect on TF-induced coagulation. Twenty-six men with low testosterone levels (< or =11.0 nM) were randomly assigned to treatment with intramuscular testosterone depot injections (testosterone undecanoate 1,000 mg) or placebo in a double-blinded study. Each participant received a total of five injections, at baseline, 6, 16, 28 and 40 weeks, and TF-induced thrombin generation ex vivo and plasma free TFPI Ag were measured after one year. At the end of the study total and free testosterone levels were significantly higher in the testosterone treated group (14.9 +/- 4.5 nM vs. 8.1 +/- 2.4 nM; p < 0.001, and 363.3 +/- 106.6 pM vs. 187.3 +/- 63.2 pM; p < 0.001, respectively). Testosterone treatment for one year did neither cause significant changes in TF-induced thrombin generation ex vivo nor changes in plasma levels of free TFPI Ag. In conclusion, normalising testosterone levels by testosterone treatment for 12 months in elderly men did not affect TF-induced coagulation or plasma TFPI levels. The potential antithrombotic role of testosterone therapy remains to be elucidated. | 10.1160/TH09-02-0090 |
pubmed_515_10400 | Nanogold particles of size 15 nm were used to label goat anti-human ceruloplasmin (GCP) to obtain an immunonanogold probe (AuGCP) for ceruloplasmin (CP). In a pH 7.8 citric acid-Na(2)HPO(4) buffer solution and in the presence of polyethylene glycol (PEG), an immunoreaction between AuGCP and CP took place, and the released nanogold particles aggregated to bigger clusters, which caused the resonance scattering (RS) intensity at 552 nm (I(552nm)) to be enhanced greatly. The enhanced intensity DeltaI was proportional to the CP concentration (C(CP)) in the range from 0.0030 to 1.26 microg/mL, with a regress equation of DeltaI = 101.0C(CP) + 1.8, a correlation coefficient of 0.9970, and a detection limit of 1.1 ng/mL CP. This simple and sensitive RS immunoassay was applied to the determination of CP in human plasma, with satisfactory results. | 10.2116/analsci.25.463 |
pubmed_801_17654 | BACKGROUND
The Tic complex (Translocon at the inner envelope membrane of chloroplasts) mediates the translocation of nuclear encoded chloroplast proteins across the inner envelope membrane. Tic110 forms one prominent protein translocation channel. Additionally, Tic20, another subunit of the complex, was proposed to form a protein import channel - either together with or independent of Tic110. However, no experimental evidence for Tic20 channel activity has been provided so far.
RESULTS
We performed a comprehensive biochemical and electrophysiological study to characterize Tic20 in more detail and to gain a deeper insight into its potential role in protein import into chloroplasts. Firstly, we compared transcript and protein levels of Tic20 and Tic110 in both Pisum sativum and Arabidopsis thaliana. We found the Tic20 protein to be generally less abundant, which was particularly pronounced in Arabidopsis. Secondly, we demonstrated that Tic20 forms a complex larger than 700 kilodalton in the inner envelope membrane, which is clearly separate from Tic110, migrating as a dimer at about 250 kilodalton. Thirdly, we defined the topology of Tic20 in the inner envelope, and found its N- and C-termini to be oriented towards the stromal side. Finally, we successfully reconstituted overexpressed and purified full-length Tic20 into liposomes. Using these Tic20-proteoliposomes, we could demonstrate for the first time that Tic20 can independently form a cation selective channel in vitro.
CONCLUSIONS
The presented data provide first biochemical evidence to the notion that Tic20 can act as a channel protein within the chloroplast import translocon complex. However, the very low abundance of Tic20 in the inner envelope membranes indicates that it cannot form a major protein translocation channel. Furthermore, the independent complex formation of Tic20 and Tic110 argues against a joint channel formation. Thus, based on the observed channel activity of Tic20 in proteoliposomes, we speculate that the chloroplast inner envelope contains multiple (at least two) translocation channels: Tic110 as the general translocation pore, whereas Tic20 could be responsible for translocation of a special subset of proteins. | 10.1186/1471-2229-11-133 |
pubmed_642_10106 | Virulence of isolates of Puccinia coronata collected during 1992 to 1998 from Sonora, Chihua-hua, Nuevo Leon, and five states in Central Mexico were compared on a set of 27 differential oat (Avena sativa) lines with different genes for race-specific resistance. Frequencies of virulence and the presence of specific pathogenic races were compared among the four regions of Mexico and between Mexico and the adjoining states of California and Texas in the United States. The P. coronata populations in Mexico were highly diverse even though the sexual stage of the fungus is not known to occur there. Overall virulence frequencies were most similar between Chihuahua and Nuevo Leon, but there were more races in common between Central Mexico and Chihuahua than between any other pair of regions of Mexico. No races found in Sonora were found in other regions of Mexico. More races found in Texas also occurred in Nuevo Leon than in any other region of Mexico. Mean virulence complexity was lowest in isolates from central Mexico; greatest in Sonora, California, and Texas; and intermediate in Chihuahua and Nuevo Leon. Significant (P < 0.05) associations of virulences occurred for 24 pairs of virulence genes in at least three of the four regions of Mexico. Virulences to 19 of the 24 pairs were also significantly associated in Texas; virulences to 13 were also significantly associated in California. | 10.1094/PD-89-0941 |
pubmed_43_16067 | Lifestyle is one of the most powerful instruments shaping mankind; the lifestyle includes many aspects of interactions with the environment, from nourishment and education to physical activity and quality of sleep. All these factors taken in complex affect neuroplasticity and define brain performance and cognitive longevity. In particular, physical exercise, exposure to enriched environment and dieting act through complex modifications of microglial cells, which change their phenotype and modulate their functional activity thus translating lifestyle events into remodelling of brain homoeostasis and reshaping neural networks ultimately enhancing neuroprotection and cognitive longevity. | 10.1186/s13062-021-00297-4 |
pubmed_968_13018 | Introduction: Two-stage revision surgery is the most frequently performed procedure in patients with a chronic periprosthetic joint infection (PJI). The infection eradication rates in the current literature differ between 54 % and 100 %, which could be attributed to different treatment strategies. The aim of this study was to retrospectively evaluate the infection eradication rate in patients with chronic PJI treated with two-stage revision surgery of the hip or knee in primary and re-revision cases. Methods: All patients treated with a two-stage revision for chronic PJI between 2005 and 2011 were analysed. Patient and infection characteristics were retrieved. Primary outcome was successful infection eradication at last follow-up. Successful eradication is specified as no need for subsequent revision surgery or suppressive antibiotic treatment. Results: Forty-seven patients were treated with a two-stage revision. Infection eradication was achieved in 36 out of 47 cases. Thirty-eight patients had positive cultures: 35 monomicrobial infections and 3 polymicrobial infections. Nine cases of culture-negative infections were identified. Accompanying eradication rates were 26 out of 35 cases, 2 out of 3 cases, and 8 out of 9 cases respectively. Mean follow-up was 128 (27-186) months. For hip and knee revisions the eradication rates were 22 out of 31 cases and 14 out of 16 cases respectively. After primary arthroplasty the infection was eradicated in 29 out of 38 cases and after re-revision in 7 out of 9 cases. Conclusion: In this study, the infection eradication rate for two-stage revision surgery after PJI of the hip and knee in primary and re-revision cases was 77 %. No statistically significant patient, infection and micro-organism characteristics were found which influence the infection eradication rates at long-term follow-up of 128 (27-186) months. | 10.5194/jbji-6-379-2021 |
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