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pubmed_310_18927 | UNLABELLED
One of the most successful reality-based television shows is The Learning Channel's "Trauma-Life in the ER," in which patients are filmed prior to being consented and camera crews are intimately intertwined in resuscitations.
OBJECTIVE
To assess provider and patient attitudes regarding privacy and satisfaction during filming.
METHODS
This was a prospective survey of patients and providers working in an urban, county teaching emergency department (ED). Scores of visual analog scales (VASs) for satisfaction, privacy, and willingness to return to the ED were accessed.
RESULTS
Eighty patients, 39 physicians and 39 nurses, were interviewed. On a 10-cm VAS where 0 = no invasion of patient privacy and 10 = extreme privacy invasion, the mean (+/-SD) rating by physicians was 5.4 (+/-2.6), by nurses was 4.9 (+/-3.1), and by patients was 2.3 (+/-3.2). There was no significant difference between physician and nurse ratings (p = 0.69), but patients rated invasion of privacy significantly lower (p < 0.0001). Filmed patients rated significantly higher invasion of privacy (3.8 +/- 4.1) than patients not filmed or those unsure whether they had been filmed (1.6 +/- 2.5); p < 0.01). On a 10-cm VAS where -5 = extreme decrease in satisfaction and 5 = extreme increase in satisfaction, the mean rating by physicians was -0.25 (+/-1.6), by nurses was -0.32 (+/-1.3), and by patients was 0.02 (+/-1.4). There was no statistical difference between the satisfaction levels of providers and patients (p = 0.19).
CONCLUSIONS
Providers rated invasion of patient privacy higher than patients rated their own invasion of privacy. Patients who were filmed rated invasion of privacy higher than patients who were not filmed. Filming had no significant effect on the satisfaction of providers or patients. | 10.1111/j.1553-2712.2001.tb00195.x |
pubmed_893_8723 | Hard coatings used to protect engineering components from external loads and harsh environments should ideally be strong and tough. Here we study the fracture toughness, K IC, of Ti1-xAlxN upon annealing by employing micro-fracture experiments on freestanding films. We found that K IC increases by about 11% when annealing the samples at 900 °C, because the decomposition of the supersaturated matrix leads to the formation of nanometer-sized domains, precipitation of hexagonal-structured B4 AlN (with their significantly larger specific volume), formation of stacking faults, and nano-twins. In contrast, for TiN, where no decomposition processes and formation of nanometer-sized domains can be initiated by an annealing treatment, the fracture toughness K IC remains roughly constant when annealed above the film deposition temperature. As the increase in K IC found for Ti1-xAlxN upon annealing is within statistical errors, we carried out complementary cube corner nanoindentation experiments, which clearly show reduced (or even impeded) crack formation for annealed Ti1-xAlxN as compared with their as-deposited counterpart. The ability of Ti1-xAlxN to maintain and even increase the fracture toughness up to high temperatures in combination with the concomitant age hardening effects and excellent oxidation resistance contributes to the success of this type of coatings. | 10.1038/s41598-017-16751-1 |
pubmed_500_8019 | The etiology of keratoconus is still unclear. This study presents a new clinical sign, Thalasselis' syndrome, defined as: an association between keratoconus, magnesium deficiency, type-A behavior and allergy. Also, it introduces the hypothesis that magnesium deficiency could affect pathologically the osmotic mechanism of the cornea, specifically the Na-K and/or Ca-ATPase pumps; the collagen structure by alteration of the adenylate cyclase activity; and other mechanisms as well. Furthermore, we propose the Thalasselis' syndrome is compatible with previous theories on keratoconus. In addition to the other therapeutic measures, such as contact lenses and keratoplasty, this study suggests a clinical, nutritional, psychological, and immunological treatment for keratoconic patients. | pubmed_500_8019 |
pubmed_227_8884 | Connective tissue growth factor (CTGF) plays a critical role in keloid pathogenesis by promoting collagen synthesis and deposition. Previous work suggested epithelial-mesenchymal interactions as a plausible factor affecting the expression of various growth factors and cytokines by both the epithelial and dermal mesenchymal cells. The aim of this study is to explore the role of epithelial-mesenchymal interactions in modulating CTGF expression. Immunohistochemistry was employed to check CTGF localization in skin tissue. Western blot assay was performed on total protein extracts from skin tissue, cell lysates and conditioned media to detect the basal/expression levels of CTGF. Study groups were subjected to serum stimulation (fibroblast-single cell culture) and pharmacological inhibitors targeted against mTOR (Rapamycin), Sp1 (WP631 and Mitoxanthrone), Smad3 (SB431542), and PI3K (LY294002). Increased localization of CTGF in the basal layer of keloid epidermis and higher expression of CTGF was observed in the keloid tissue extract. Interestingly, lower basal levels of CTGF was observed in fibroblast cell lysates cocultured with keloid keratinocytes compared to normal keratinocytes, while the conditioned media from the former culture consistently demonstrated a higher expression of secreted CTGF as compared to the latter group. These results demonstrate an important role of epithelial-mesenchymal interactions in the regulation of CTGF expression. Fibroblasts treated with inhibitors against mTOR, Sp1, Smad3, and PI3K demonstrated a reduced expression of CTGF, suggesting these signaling pathways to be important in the regulation of CTGF expression. Thus, revealing the therapeutic potentials for inhibitors that are selective for these factors in controlling CTGF expression in fibrotic conditions. | 10.1002/jcp.20668 |
pubmed_440_24409 | Diet-induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. The serum bicarbonate level is an independent predictor of chronic kidney disease progression. We investigated whether proton accelerates aging by analyzing both coupling factor 6-overexpressing transgenic (TG) and high salt-fed mice which display sustained intracellular acidosis, due to enhanced proton import through ecto-F1 Fo complex and/or reduced proton export through Na+ -K+ ATPase inhibition. Both types of mice displayed shortened lifespan and early senescence-associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In chronic intracellular acidosis mice, autophagy was impaired by regression of Atg7, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. The increase in histone 3 trimethylation at lysine 4 (H3K4me3) and H4K20me3 and the decrease in H3K9me3 and H3K27me3 were observed in the heart and kidney obtained from both TG and high salt-fed mice. The decrease in lamin A/C, emerin, and heterochromatin protein 1α without changes in barrier-to-autointegration factor and high-mobility group box 1 was confirmed in TG and high salt-fed mice. Suppression of nuclear histone deacetylase 3-emerin system is attributable to epigenetic regression of Atg7 and H4K5 acetylation. These findings will shed light on novel aging and impaired autophagy mechanism, and provide implications in a target for antiaging therapy. | 10.1002/jcb.27302 |
pubmed_849_17443 | Perpetrators use rape supportive attitudes and sexual assault incident characteristics to justify forcing sex on their victims. Perpetrators who can justify their behaviors are at increased risk for future perpetration. This study examined the relationships between rape supportive attitudes, sexual assault incident characteristics, and the post-assault justifications of 183 men sampled from the community who self-reported committing at least one act of sexual aggression. Hierarchical multiple regression analyses indicated that rape supportive attitudes, expectations for having sex, misperceptions of sexual intent, victims' alcohol consumption, attempts to be alone with her, and the number of consensual sexual activities prior to the unwanted sex were significant predictors of perpetrators' post-assault use of justifications. Greater use of justifications was a significant predictor of sexual aggression over a 1-year follow-up interval. These findings demonstrate the need for further research exploring when and why perpetrators use post-assault justifications and whether they are amenable to change. | 10.1177/1077801215589380 |
pubmed_777_6227 | Neurological symptoms in Wilson's disease (WD) may include oculomotor abnormalities. However, to date, eye movements in WD patients were rarely investigated and the data concerning this issue are sparse. The purpose of this study was to evaluate reflexive and voluntary eye movements in WD patients. We examined horizontal saccadic and smooth pursuit eye movements using infra-red oculography in 50 WD patients, including 29 neurologically symptomatic (WDn) and 21 asymptomatic ones (WDa), and in 29 healthy controls. We found statistically significant increase in mean antisaccadic latency (378 ms) and in mean antisaccadic error rate (22.5) in the WDn group, when compared with WDa group (317 ms and 9.1, respectively) and controls (318 ms and 9.7, respectively). In contrast, there were no statistically significant differences in mean latency of prosaccades and in size of the gap effect. Patients with neurological manifestations had also abnormal smooth pursuit-increased number of saccadic intrusions (mean: 8.6) and decreased gain (mean: 0.69) comparing with WDa patients (4.1 and 0.83, respectively) and controls (2.2 and 0.91, respectively). The data suggest that WD is associated both with impairment of voluntary control of saccades and with disturbed smooth pursuit eye movements while reflexive saccades seem to be preserved. | 10.1002/mds.22276 |
pubmed_220_632 | We sequenced 2939 ESTs from fetal and adult sheep skin. Stages of gestation were picked to coincide with the major events in skin appendage (wool follicle) formation. Clustering analysis generated a nonredundant set of ESTs 2435 strong (83% nonredundant). Approximately 24% of these gave no hit to NCBI build 29 of the human genome, while 35% were tentatively classified by putative function based on BLASTX hits with a p(N) of <10(-4). In addition to bioinformatics analysis of our ESTs and gene mapping, we have generated a large EST spatial expression data set using in situ hybridization. One thousand one hundred forty-two ESTs have been used for in situ localization; about 31% are from adult sheep skin, 39% from late gestation fetal sheep skin, and 30% from midgestation fetal sheep skin. These probes have been used in over 3000 hybridization experiments. In this report, we summarize the results of in situs on adult sheep skin. | 10.1016/s0888-7543(03)00210-6 |
pubmed_587_1366 | The present study was conducted to establish a new mouse model of dry skin pruritus. The rostral back was treated daily with cutaneous application of acetone/ether (1:1) mixture (AE), water following AE (AEW), 1% sodium lauryl sulfate (SLS) or tape stripping (TS). On the day after 5-day treatment, although all four treatments significantly decreased stratum corneum (SC) hydration and increased transepidermal water loss (TEWL), only AEW treatment significantly increased spontaneous scratching. An increase in the frequency of TS produced the marked increase of TEWL, without significant effects on SC hydration and spontaneous scratching. In AEW-treated mice, changes in SC hydration and TEWL were marked in the initial 2-day period, while spontaneous scratching increased gradually from 3 days after starting the treatment. The degranulation of cutaneous mast cells was increased by SLS treatment but not by other treatments. There was no apparent difference in AEW-induced spontaneous scratching between mast cell-deficient mice (WBB6F1-W/Wv) and normal littermates (WBB6F1-+/+). Opioid antagonists, naloxone and naltrexone, (1 mg/kg, subcutaneously) significantly suppressed spontaneous scratching in AEW-treated mice. It is suggested that spontaneous scratching of AEW-treated mice is an itch-related response and a useful model for studying the mechanisms of dry skin pruritus. | 10.1254/jjp.88.285 |
pubmed_532_982 | BACKGROUND
The study objective was to determine differences in the proportion of supranormal pulmonary function tests (PFTs) between active duty (AD) military personnel and a similar non-active duty (non-AD) population. Given the emphasis on cardiovascular fitness in the military, it has been hypothesized that regular exercise in this cohort leads to an increased proportion of supranormal PFTs. We hypothesized that a comparison of PFTs would identify no differences in the ratio of supranormal to normal PFTs between the AD and non-AD populations.
METHODS
A retrospective chart review was conducted of all PFT studies at the Brooke Army Medical Center from 2006 to 2011. Studies were included with either an FVC or FEV1 > 110% of predicted, with both values > 100% of predicted. A comparative analysis was performed for patients between 18 and 50 years of age based on AD status. Further analysis was performed on all ages to determine the distribution of supranormal findings in the entire study population.
RESULTS
A total of 16,600 interpreted PFTs were queried. Of those, 4,303 (31.6%) were AD patients, and 9,306 (68.4%) were non-AD patients. From all of the PFTs reviewed, a total of 912 (6.7%) were identified as supranormal. When further analyzed, 381 (9.4%) of AD patients 18-50 years old were supranormal, 175 (12.4%) of non-AD patients 18-50 years old were supranormal, and 356 (4.7%) of non-AD patients older than 50 years were supranormal.
CONCLUSIONS
This study revealed no significant difference in the proportion of supranormal-to-normal PFTs in an AD versus non-AD duty population of the same age range. Based on these findings, no assumption should be made that supranormal PFTs are more common in military personnel. Interpretation of normal PFTs in AD personnel undergoing evaluation should not differ from that in any typical patient. | 10.4187/respcare.02112 |
pubmed_293_2563 | OBJECTIVES
Attitudes to aging have been linked with important health outcomes. It is unclear whether interventions to improve attitudes to aging are effective across cultural contexts. This study investigated the efficacy of an intervention among women of either Australian or Chinese backgrounds.
METHODS
Among 96 women who provided baseline measures, 86 attended a single, 90-min group session on either healthy aging or healthy diet. Measures of three domains of attitudes to aging were collected at baseline, then immediately and 8 weeks after the intervention.
RESULTS
The intervention improved attitudes in the psychological growth domain, but not the physical change or psychosocial loss domains. Cultural identification did not moderate intervention efficacy.
DISCUSSION
The findings suggest that brief, culturally inclusive interventions may be partially effective at improving attitudes to aging. Furthermore, research is needed to investigate if the intervention would be more effective when baseline attitudes to aging are less positive. | 10.1177/1745506519846747 |
pubmed_134_22601 | BACKGROUND
Polyoma BK virus (BKV) is associated with hemorrhagic cystitis during hematopoietic stem cell transplantation (HSCT). The objective of this study was to test whether standard-dose ciprofloxacin might suppress reactivation of BKV infection during HSCT.
METHODS
Sixty-eight patients received ciprofloxacin or a cephalosporin as antibiotic prophylaxis after undergoing allogeneic HSCT. Urine samples were collected weekly from day 7 before HSCT to day 50 after HSCT. Laboratory investigations included quantification of BKV load and urinary ciprofloxacin levels and in vitro drug sensitivity of BKV.
RESULTS
Twenty-two patients received ciprofloxacin, 21 received cephalosporins, 12 received concomitant corticosteroids and antibiotics (9 received ciprofloxacin, and 3 received cephalosporins), and 13 received interrupted ciprofloxacin therapy. Ciprofloxacin recipients developed a significantly lower peak BKV load, compared with cephalosporin recipients (median, 3x10(5) copies/mL vs. 2.6x10(9) copies/mL; P=.021), irrespective of concomitant receipt of corticosteroid therapy. Fewer ciprofloxacin recipients than cephalosporin recipients (P=.013) developed BKV viruria with a > or =3-log increase in BKV load during HSCT, which was associated with significantly more cases of hemorrhagic cystitis (8 of 29 patients with a peak increase of > or =3 log vs. 0 of 39 patients without a peak increase of this level; P<.001). Ciprofloxacin recipients excreted ciprofloxacin in urine at a mean 24-h rate of 71.7 microg/mL (range, 23.0-152.9 microg/mL), which was comparable with the in vitro inhibitory concentration of 125-250 microg/mL of ciprofloxacin found for 3 of 7 BKV isolates.
CONCLUSIONS
Ciprofloxacin decreased urinary BKV reactivation after HSCT. | 10.1086/427291 |
pubmed_166_7461 | According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N-alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K₂CO₃ system the reaction of methyl 4-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N-substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (¹Н and 13С) spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N-benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N-methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models. | 10.3390/scipharm85010002 |
pubmed_940_1205 | PURPOSE
Cytokeratins are constituents of the intermediate filaments of epithelial cells in which they are expressed in various combinations depending on epithelial type and degree of differentiation. Of the 20 known cytokeratins, cytokeratin 19 is expressed in normal urothelium cells, whereas the recently identified cytokeratin 20 (CK-20) is expressed in urothelial carcinoma but not normal urothelium cells. We examine whether CK-20 expression can be used as a bladder tumor marker for transitional cell carcinoma in cells isolated from urine.
MATERIALS AND METHODS
The reverse transcriptase polymerase chain reaction method was used to determine expression of CK-20 in cells separated from urine of patients with bladder carcinoma. Cells were obtained from urine of 192 patients stratified into 3 groups of 21 healthy young volunteers without a history of transitional cell carcinoma, 27 with a negative bladder biopsy for transitional cell carcinoma and 144 with bladder transitional cell carcinoma. The parameters were tumor stage and grade, tumor size, number of tumors, urinary cytology and CK-20.
RESULTS
CK-20 amplification band (370 base pairs) was obtained with messenger ribonucleic acid extracted from transitional cell carcinoma cells of bladder tumor. CK-20 in the urine samples of the control group was negative (no false-positive results, specificity 100%). Among the 27 patients with pTo disease CK-20 was negative in 20 (specificity 74.1%). In the 7 patients with positive CK-20 histology showed chronic inflammation in 2, atypical hyperplasia in 3 and metaplasia in 1. In 1 patient who had a known history of transitional cell carcinoma the urothelium was normal. Among 144 patients with bladder transitional cell carcinoma CK-20 was positive in 131. Sensitivity of the method was much higher than urinary cytology (91 versus 56.3%, p <0.0001). We demonstrated no correlation between CK-20 and tumor grade.
CONCLUSIONS
Our results indicate that CK-20 is a potential marker for bladder cancer. The noninvasive detection method assesses urothelial cells from the voided urine specimen using reverse transcriptase-polymerase chain reaction. The CK-20 marker was significantly more sensitive than urinary cytology. | pubmed_940_1205 |
pubmed_603_20388 | We report the case of a 68-year-old woman with severe mitral valve regurgitation and concomitant multiple systemic artery-to-pulmonary artery fistulas. Endovascular embolization of the fistulas was unable to control her heart failure, and mitral valve replacement was also performed. Steps were taken during mitral valve surgery to ensure an adequate operative field in the left atrium, despite the large volume of in-pouring blood from the pulmonary vein. | pubmed_603_20388 |
pubmed_877_6376 | CsxWO3/TiO2 composites with different contents of CsxWO3 were successfully synthesized in this study by a facile hydrothermal process. CsxWO3/TiO2 composites were characterized by XRD, Raman, UV-visible diffuse reflectance spectra (DRS), photoluminescence spectra (PL) and SEM. TiO2 nanoparticles were distributed uniformly on the surface of the CsxWO3 microsphere in the prepared CsxWO3/TiO2 composites, and they formed heterojunctions with CsxWO3. The effect of CsxWO3 on the photoactivities of composites was investigated via DRS and PL. All CsxWO3/TiO2 catalysts showed enhanced photocatalytic activity for degrading rhodamine B under visible light irradiation. The 50% CsxWO3/TiO2 sample showed the best photocatalytic activity and its kinetic constant was 20 times larger than that of TiO2. The possible photocatalytic mechanism is also discussed from the trapping experiments of active species. The improved photocatalytic activity for the CsxWO3/TiO2 catalyst may be attributed to the synergetic effect between CsxWO3 microspheres and TiO2 nanoparticles. This novel photocatalyst can be used to degrade environmental pollutants in the future. | 10.1166/jnn.2018.15438 |
pubmed_65_11393 | Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled. | 10.1006/nbdi.1999.0262 |
pubmed_245_14183 | The prodrug strategy has been frequently employed as a chemical approach for overcoming the disadvantages of existing parent drugs. In this report, we synthesized four monoester prodrugs of ganciclovir, an anticytomegalovirus drug, and demonstrated their potential advantages in protease-targeted activation and biopharmaceutical profiles over the parent compound. We demonstrated that these four prodrugs of ganciclovir, i.e., N-benzyloxycarbonyl-(L)-alanine-ganciclovir (CbzAlaGCV), N-benzyloxycarbonyl-(α,l)-aminobutyric acid-ganciclovir (CbzAbuGCV), N-acetyl-(l)-phenylalanine-(l)-alanine-ganciclovir (AcPheAlaGCV), and N-acetyl-(l)-phenylalanine-(α,l)-aminobutyric acid-ganciclovir (AcPheAbuGCV), are hydrolytically activated by the protease of human cytomegalovirus (hCMV), a serine protease that possesses intrinsic esterase activities. CbzAlaGCV and AcPheAlaGCV were found to be activated at a higher rate by the hCMV protease than CbzAbuGCV and AcPheAbuGCV. These ganciclovir prodrugs could potentially be targeted to selective activation by the hCMV protease which is only present at the viral infection sites, thereby achieving higher efficacy and lower systemic toxicity. The tissue stability, cellular uptake, and trans-epithelial transport of these ganciclovir prodrugs were also characterized. The N-acetylated dipeptide prodrugs of ganciclovir were found to be generally more stable than Cbz-amino acid prodrugs in various tissue matrices. Among the four prodrug candidates, AcPheAbuGCV was the most stable in human cell homogenates, plasma, and pooled liver microsomes. AcPheAbuGCV also possessed a superior cellular uptake profile and permeability across epithelial cell monolayers. Since the targeting and selective activation of a prodrug is determined by not only its rate of hydrolysis catalyzed by the hCMV protease target but also its biopharmaceutical properties, i.e., oral absorption and systemic availability, AcPheAbuGCV is considered the best overall candidate among the four ganciclovir prodrugs for further research and development for treatment of hCMV infection. | 10.1021/acs.molpharmaceut.7b00792 |
pubmed_708_8779 | The novel H+/K(+)-adenosine triphosphatase inhibitor (gastric proton pump inhibitor), BY 1023/SK&F 96022, was found to be more potent than omeprazole in some rat models and slightly less potent in a dog model. Overall, both compounds are of a similar potency and efficacy. BY 1023/SK&F 96022 exhibited a somewhat longer duration of the antisecretory action than omeprazole in the Ghosh-Schild rat. In the modified Shay rat, on the basis of equieffective doses in terms of the initial effect, both compounds had a comparable duration of action. However, the p.o./i.v. dose ratio upon acute administration was larger for omeprazole, possibly reflecting its lower stability in the acidic environment of the secreting stomach, compared to BY 1023/SK&F 96022. As in vivo, both compounds were equipotent to inhibit acid production in rabbit isolated fundic glands. However, omeprazole interacted with the 7-ethoxycoumarin dealkylase in vitro with high affinity (Ki = 38.5 mumol/l), in contrast to BY 1023/SK&F 96022 (Ki = 135 mumol/l). Compared to omeprazole, BY 1023/SK&F 96022 also showed less interaction with the cytochrome P450 enzyme hydroxylating ionazolac. Moreover, this difference between the two compounds was also found in the rat in vivo with respect to their interaction with diazepam. Thus, both compounds displayed a comparable antisecretory potency in vivo and in vitro but showed a different interference with cytochrome P450 in favor of less interaction by BY 1023/SK&F 96022. | pubmed_708_8779 |
pubmed_135_6414 | The purpose of this study was to perform a comparative biochemical analysis between conventional spectrophotometry and Raman spectroscopy, techniques used for diagnoses, on the urine of healthy (CT) and diabetic and hypertensive patients (DM&HBP). Urine from 40 subjects (20 in the CT group and 20 in the DM&HBP group) was examined in a dispersive Raman spectrometer (an 830 nm excitation and a 350 mW power). The mean Raman spectra between both groups showed a significant difference in peaks of glucose; exploratory analysis by principal component analysis (PCA) identified spectral differences between the groups, with higher peaks of glucose and proteins in the DM&HBP group. A partial least squares (PLS) regression model estimated by the Raman data indicated the concentrations of urea, creatinine, glucose, phosphate, and total protein; creatinine and glucose were the biomarkers that presented the best correlation coefficient (r) between the two techniques analyzed (r = 0.68 and r = 0.98, respectively), both with eight latent variables (LVs) and a root mean square error of cross-validation (RMSecv) of 3.6 and 5.1 mmol/L (41 and 92 mg/dL), respectively. Discriminant analysis (PLS-DA) using the entire Raman spectra was able to differentiate the samples of the groups in the study, with a higher accuracy (81.5%) compared to the linear discriminant analysis (LDA) models using the concentration values of the spectrometric analysis (60.0%) and the concentrations predicted by the PLS regression (69.8%). Results indicated that spectral models based on PLS applied to Raman spectra may be used to distinguish subjects with diabetes and blood hypertension from healthy ones in urinalysis aimed at population screening. | 10.3390/bioengineering9100500 |
pubmed_855_14120 | PURPOSE
To analyse possibilities of diagnosis and treatment of eye diseases by practitioner.
MATERIAL AND METHODS
The number and diagnosis profile of patients treated in average municipal out-patient ward was calculated and possibilities of their treatment by general practitioner were analysed.
RESULTS
In 87.4% of eye-patients general practitioner cannot diagnose and treat the disease and he has to send them to an eye-doctor.
CONCLUSION
The system that eye-patient cannot check-in directly to an eye-doctor is more costly because general practitioners can diagnose and treat only small number of these patients. Therefore nearly every patient has to be consulted be eye-specialist, which increases the costs of treatment because patient has to be seen by two doctors. | pubmed_855_14120 |
pubmed_924_15240 | To link clinical vocabulary of diseases to gene entries in Online Mendelian Inheritance in Man (OMIM), we comprehensively matched diseases from Unified Medical Language System (UMLS) Metathesaurus to the OMIM text in Allelic Variant fields that describe relations between the mutations or polymorphisms of the genes and the phenotypes. Out of 1,786 genes having the field, 1,445 genes (80.9%) had matches with 2,417 types of diseases or disorders. The links are accessible at http://www.genelexpo.jp/diseases/. | pubmed_924_15240 |
pubmed_433_19050 | ETHNOPHARMACOLOGICAL RELEVANCE
Borago L., (family Boraginaceae) is a small genus of annual or perennial herbs with branched flowers, which is commonly found in the Mediterranean region. Some species known as Gavzabȃn in Asian and some African countries are traditionally used instead of Borago. Aims of the review: The purpose of this study was to provide comprehensive scientific information on phytochemistry, traditional uses and pharmacological activities of Borago species to provide an insight into further research on the therapeutic potential of these plants. In many studies, it has been shown that different parts of Borago species, including leaves, flowers, seeds, roots and aerial parts possess numerous ethnobotanical values.
MATERIALS AND METHODS
All ethnobotanical, phytochemical, pharmacological, and clinical data were collected from online journals, magazines and books (all of which were published in English, Arabic, and Persian) from 1968 to 2018. Electronic databases such as Google, Google Scholar, PubMed, Science Direct, Researchgate, and other online collections were used.
RESULTS
The phytochemical studies on five species showed a wide range of phytochemicals belonging to different classes of secondary metabolites. From a pharmacological point of view, different extracts and fractions, essential oils, and pure compounds isolated from various Borago species have shown diverse activities in in vitro, in vivo, and clinical studies confirming various traditional uses of Borago genus.
CONCLUSION
Considering the reported activities of the Borago genus both in traditional and modern medicine, further studies on biological aspects and identification of the mechanism of action for drug discovery are highly required. | 10.2174/1381612825666191216152733 |
pubmed_681_1054 | BACKGROUND
Olanzapine, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines.
OBJECTIVES
To review the efficacy and tolerability of olanzapine in the treatment of mania
SEARCH STRATEGY
The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched.
SELECTION CRITERIA
Randomised trials comparing olanzapine with placebo or other drug in acute manic or mixed episodes.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data from trial reports
MAIN RESULTS
Six trials (1422 participants) were included in the review. There was a high rate of failure to complete treatment on all treatments which may have biased the estimates of relative efficacy. Olanzapine was superior to placebo at reducing manic symptoms as monotherapy (Young Mania Rating Scale (YMRS) - weighted mean difference (WMD): -5.94, 95% CI -9.09 to -2.80) and in combination with lithium/valproate (YMRS) (WMD -4.01, 95% confidence interval -6.06 to -1.96). Olanzapine monotherapy was superior at reducing psychotic symptoms (PANSS positive symptoms subscale WMD: -3.54, 95% CI -5.28 to -1.80). Olanzapine was superior to divalproex at reducing manic symptoms (standardised mean difference (SMD): -0.29, 95% CI -0.50 to -0.08). Olanzapine did not lead to a statistically higher rate of clinical response than haloperidol (RR: 1.03, 95% CI 0.77 to 1.38). Fewer patients discontinued treatment on olanzapine than placebo (RR: 0.62, 95% CI 0.48 to 0.80). Olanzapine caused greater weight gain than placebo (WMD 1.91Kg, 95% CI 1.29 to 2.53) and somnolence (RR: 2.13 95% CI 1.62 to 2.79) but not more depressive symptoms (RR: 0.95, 95% CI 0.65 to 1.40) or movement disorder (WMD: -0.33, 95% CI -0.74 to 0.09). Olanzapine caused more prolactin elevation than placebo (RR: 4.35 95%CI 1.77 to 10.70). Olanzapine caused greater weight gain (WMD: 1.54, 95% CI 1.02 to 2.05); somnolence (RR: 1.80 95% CI 1.32 to 2.46) and movement disorders (SAS - WMD: 0.72 95% CI 0.11 to 1.33) than divalproex but less nausea ( RR: 0.36 95% CI 0.20 to 0.65). Olanzapine caused more weight gain than haloperidol (RR: 3.59, 95% CI 1.49 to 8.64) but less movement disorder (EPS RR: 0.10, 95% CI 0.04 to 0.24).
REVIEWER'S CONCLUSIONS
Olanzapine is an effective treatment for mania and may be more efficacious than divalproex, though leads to more weight gain. Clinicians should consider both the relative efficacy and the different incidence of specific adverse effects of available drugs. | 10.1002/14651858.CD004040 |
pubmed_1123_20120 | The p110 Cut homeobox 1 (CUX1) transcription factor regulates genes involved in DNA replication and chromosome segregation. Using a genome-wide-approach, we now demonstrate that CUX1 also modulates the constitutive expression of DNA damage response genes, including ones encoding ATM and ATR, as well as proteins involved in DNA damage-induced activation of, and signaling through, these kinases. Consistently, RNAi knockdown or genetic inactivation of CUX1 reduced ATM/ATR expression and negatively impacted hallmark protective responses mediated by ATM and ATR following exposure to ionizing radiation (IR) and UV, respectively. Specifically, abrogation of CUX1 strongly reduced ATM autophosphorylation after IR, in turn causing substantial decreases in (i) levels of phospho-Chk2 and p53, (ii) γ-H2AX and Rad51 DNA damage foci and (iii) the efficiency of DNA strand break repair. Similarly remarkable reductions in ATR-dependent responses, including phosphorylation of Chk1 and H2AX, were observed post-UV. Finally, multiple cell cycle checkpoints and clonogenic survival were compromised in CUX1 knockdown cells. Our results indicate that CUX1 regulates a transcriptional program that is necessary to mount an efficient response to mutagenic insult. Thus, CUX1 ensures not only the proper duplication and segregation of the genetic material, but also the preservation of its integrity. | 10.1093/nar/gks041 |
pubmed_960_6458 | Prostate cancer remains a significant health concern for men throughout the world. Recently, there has developed an expanding multidisciplinary body of literature suggesting a link between chronic inflammation and prostate cancer. In support of this hypothesis, population studies have found an increased relative risk of prostate cancer in men with a prior history of certain sexually transmitted infections or prostatitis. Furthermore, genetic epidemiological data have implicated germline variants of several genes associated with the immunological aspects of inflammation in modulating prostate cancer risk. The molecular pathogenesis of prostate cancer has been characterized by somatic alterations of genes involved in defenses against inflammatory damage and in tissue recovery. A novel putative prostate cancer precursor lesion, proliferative inflammatory atrophy, which shares some molecular traits with prostate intraepithelial neoplasia and prostate cancer, has been characterized. Here, we review the evidence associating chronic inflammation and prostate cancer and consider a number of animal models of prostate inflammation that should allow the elucidation of the mechanisms by which prostatic inflammation could lead to the initiation and progression of prostate cancer. These emerging insights into chronic inflammation in the etiology of prostate carcinogenesis hold the promise of spawning new diagnostic and therapeutic modalities for men with prostate cancer. | 10.1093/carcin/bgh317 |
pubmed_872_7912 | Human immunodeficiency virus type 1 (HIV-1) exonic splicing silencers (ESSs) inhibit production of certain spliced viral RNAs by repressing alternative splicing of the viral precursor RNA. Several HIV-1 ESSs interfere with spliceosome assembly by binding cellular hnRNP A/B proteins. Here, we have further characterized the mechanism of splicing repression using a representative HIV-1 hnRNP A/B-dependent ESS, ESSV, which regulates splicing at the vpr 3' splice site. We show that hnRNP A/B proteins bound to ESSV are necessary to inhibit E complex assembly by competing with the binding of U2AF65 to the polypyrimidine tracts of repressed 3' splice sites. We further show evidence suggesting that U1 snRNP binds the 5' splice site despite an almost complete block of splicing by ESSV. Possible splicing-independent functions of U1 snRNP-5' splice site interactions during virus replication are discussed. | 10.1128/MCB.23.23.8762-8772.2003 |
pubmed_861_16671 | AIM
To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome (MFS) phenotype and an unusual bilateral macular degeneration.
METHODS
Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals.
RESULTS
In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation (c.3932A>G, p.Y1311C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls.
CONCLUSION
A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome. | 10.18240/ijo.2019.05.05 |
pubmed_1075_25291 | The loss of anterior teeth can be painful for patients, both psychologically and socially. In recent years, fiber-reinforced composite resins (FRCs) have gained increasing acceptance in mainstream prosthodontics as viable alternatives to alloy-based restorations. A combination of good esthetics and fracture toughness validates their use in a diverse range of clinical applications. In this study, a bridge was constructed with hybrid composite resin placed around a resin-impregnated, plasma-etched, polyalkene fiber bonded to the abutment tooth enamel using the acid-etch technique. This method of tooth replacement is viewed as a fast, simple, cost-effective means of replacing anterior teeth. The restoration remained intact, with no discoloration or deterioration at the recall visits. While definitive long-term data about their clinical performance is scarce, FRC prostheses appear to have a worthwhile role in the conservative treatment of short, edentulous spaces. | pubmed_1075_25291 |
pubmed_476_3175 | Some veterans experience symptoms of moral injury after being exposed to the ethical and moral challenges associated with military service. While it is well known that moral injury is associated with an increased risk for suicide as well as other mental health concerns, few tools exist to systematically screen for moral injury in chaplaincy settings. This preliminary study examines the psychometric properties as well as feasibility of applying two new moral injury screening tools that could be used with routine spiritual assessments, purposefully designed to assess for moral injury in chaplaincy settings at Department of Veterans Affairs (VA) Medical Centers. The results provide preliminary psychometric evidence to support the reliability and validity of these two new screening tools, which were shown to be feasible for use in VA chaplaincy settings. | 10.1080/08854726.2022.2032980 |
pubmed_137_23393 | Purpose: Increasing knowledge suggests that nutrition and lifestyle factors affect multiple sclerosis. This study explores how people with multiple sclerosis experience daily multiple sclerosis disease activity and the influence of nutrition and lifestyle factors (e.g., stress, sleep, and environmental temperature).Methods: Four phases mix qualitative and quantitative elements in an exploratory study. The initial two phases consisted of an exploratory study with 14 participants followed by 15 semi-structured interviews. Results from the two first phases were substantiated in a survey completed by 425 respondents (response rate: 42.5%). Finally, findings and inconsistencies were elaborated in three focus group interviews.Results: In the initial exploratory study, several of the participants linked nutrition and lifestyle factors to disease activity. Results from the semi-structured interviews showed that particularly stress, meat, fatty foods, and processed sugar were perceived to have a negative impact on disease activity, and some participants had experienced immediate effects of these factors on their disease activity. The survey supported these findings that were further elaborated in focus groups.Conclusion: People with multiple sclerosis perceive nutrition and lifestyle to affect daily disease activity. Individuals who have experienced links between their multiple sclerosis, and nutrition and lifestyle attribute some of these changes to e.g., stress, and the consumption of sugar, meat, and fatty food.Implications for rehabilitationA majority of the participants in this study perceived nutrition and lifestyle factors to have an effect on their multiple sclerosis, particularly stress, meat, fatty foods, and processed sugar.Some participants with multiple sclerosis experienced that nutrition, stress, environmental temperature, and physical activity had a direct effect on the severity of daily symptom manifestations.Nutrition and lifestyle factors that potentially influence multiple sclerosis disease activity should be considered when organizing rehabilitation and care to better meet the needs of the individual with multiple sclerosis. | 10.1080/09638288.2019.1602675 |
pubmed_694_2072 | This paper examines variations in suicide within the Republic of Ireland in order to determine if the services, as currently available, require redistribution. The rates of suicide and undetermined death in the four provinces, 26 counties and five cities of Ireland are examined for the years 1976 to 1994, with the age and gender distributions of local populations taken into consideration. Marked variations between areas are noted with a threefold difference between the counties with the highest and lowest rates. Counties tend to be similarly ranked for men and women but the male suicide rate, overall, was almost three times that for women. The male:female ratio was 2.3:1 for the first half of the study, but this increased to 3.4:1 for the second half; a reflection of increasing numbers of male suicides. Surprisingly, the male suicide rate in Dublin city has stayed steady at 12 per 100,000 over the entire study period, while the national male rate has more than doubled reaching approximately 18 per 100,000 in recent years. There is a need for improved services in rural Ireland. If the various available services are to help reduce the suicide rate, then a mechanism must be found to deliver these in areas of low population density where the need could well be greatest. | pubmed_694_2072 |
pubmed_784_9149 | The effect of xylazine on the arrhythmogenic dose of epinephrine (ADE) was studied in 9 horses. Anesthesia was induced by administration of guaifenesin (50 mg/kg of body weight, IV) followed by thiamylal (4 to 6 mg/kg, IV) and was maintained at 1 minimal alveolar concentration (MAC) of halothane (0.89%). Base apex ECG and facial artery pressure were recorded. Epinephrine was infused in a sequence of arithmetically spaced increasing rates (initial rate 0.25 micrograms/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 micrograms/kg/min at which at least 4 premature ventricular depolarizations occurred in a 15-second period. Xylazine (1.1 mg/kg, IV) was administered after the control ADE was determined. Xylazine did not significantly alter the ADE (control, 1.12 +/- 0.38 micrograms/kg/min; xylazine, 1.21 +/- 0.46 micrograms/kg/min). Blood pressure increased transiently for 8 minutes after xylazine administration. Baseline systolic and diastolic arterial pressures and heart rate were not significantly different from control baseline pressures and heart rate 15 minutes after xylazine administration. Blood pressure and heart rate increased significantly during control and xylazine ADE determinations. Significant differences in pH, PaO2, PaCO2, or base excess were not observed between baseline and ADE in the control or xylazine groups. One horse developed atrial fibrillation, and 2 horses developed ventricular fibrillation during ADE determinations. | pubmed_784_9149 |
pubmed_972_12522 | Malaria remains one of the world's most important infectious diseases and is responsible for enormous mortality and morbidity. Resistance to antimalarial drugs is a challenging problem in malaria control. Clinical malaria is associated with the proliferation and development of Plasmodium parasites in human erythrocytes. Especially, the development into the mature forms (trophozoite and schizont) of Plasmodium falciparum (P. falciparum) causes severe malaria symptoms due to a distinctive property, sequestration which is not shared by any other human malaria. Ca(2+) is well known to be a highly versatile intracellular messenger that regulates many different cellular processes. Cytosolic Ca(2+) increases evoked by extracellular stimuli are often observed in the form of oscillating Ca(2+) spikes (Ca(2+) oscillation) in eukaryotic cells. However, in lower eukaryotic and plant cells the physiological roles and the molecular mechanisms of Ca(2+) oscillation are poorly understood. Here, we showed the observation of the inositol 1,4,5-trisphospate (IP(3))-dependent spontaneous Ca(2+) oscillation in P. falciparum without any exogenous extracellular stimulation by using live cell fluorescence Ca(2+) imaging. Intraerythrocytic P. falciparum exhibited stage-specific Ca(2+) oscillations in ring form and trophozoite stages which were blocked by IP(3) receptor inhibitor, 2-aminoethyl diphenylborinate (2-APB). Analyses of parasitaemia and parasite size and electron micrograph of 2-APB-treated P. falciparum revealed that 2-APB severely obstructed the intraerythrocytic maturation, resulting in cell death of the parasites. Furthermore, we confirmed the similar lethal effect of 2-APB on the chloroquine-resistant strain of P. falciparum. To our best knowledge, we for the first time showed the existence of the spontaneous Ca(2+) oscillation in Plasmodium species and clearly demonstrated that IP(3)-dependent spontaneous Ca(2+) oscillation in P. falciparum is critical for the development of the blood stage of the parasites. Our results provide a novel concept that IP(3)/Ca(2+) signaling pathway in the intraerythrocytic malaria parasites is a promising target for antimalarial drug development. | 10.1371/journal.pone.0039499 |
pubmed_417_12810 | 3,5,3'-Triiodo-L-thyronine (T3) regulation of beta-MHC expression was studied in rat fetal heart cells using deletion mutants of both the rat and human promoter regions fused to a CAT expression vector. T3 inhibited the expression of human and rat beta-MHC constructs with an IC50 of about 1nM, which was similar to the EC50 for beta MHC-mRNA observed in cardiomyocytes. Deletion analysis of beta MHC promoter constructs suggested that a T3 response element (TRE) is located near the start of transcription. Possibly, T3-receptor binding at this site interferes with formation of the transcriptional initiation complex. | 10.1006/bbrc.1994.1398 |
pubmed_200_12640 | β-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin oligosaccharides that are produced by the activity of chitinases on chitin in insects. Using bioinformatic methods based on genome and transcriptome databases, 11 β-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were identified and characterized. Phylogenetic analysis revealed a six-grouped tree topology. The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes NlHex11, which harbours a catalytic domain that differs from that of the other 10 NlHexs. Observations of the expression of NlHexs during different developmental stages revealed that NlHex4 is expressed with periodicity during moulting. Although the tissue-specific expression patterns of most NlHexs were nonspecific, NlHex4 was found to be expressed mainly in the female reproductive system as well as in the integument. RNA interference (RNAi) demonstrated failure to shed the old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting NlHex4, and these nymphs eventually died; no observable morphological abnormalities were found in insects treated with dsRNAs targeting the other 10 NlHexs. Based on this study and our previous analyses, a '5 + 1 + 3' pattern of chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three chitin deacetylases are required for moulting in N. lugens. A better understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would be achieved by considering three chitinolytic enzyme families: chitinase, chitin deacetylase and β-N-acetylhexosaminidase. | 10.1111/imb.12187 |
pubmed_335_7394 | Copper complexes with distorted tetrahedral structure in solution catalyze regioselectively the cyclization of 1,2-bisketenes with alcohols to give 5-alkoxy-2,3-dihydrofuran-2-ones in very high yields (shown on the right). It seems remarkable that these new compounds could remain undiscovered despite having structural similarities with a great number of well-investigated and biologically active butenolides. | 10.1002/(SICI)1521-3773(19980619)37:11<1540::AID-ANIE1540>3.0.CO;2-X |
pubmed_974_19226 | To compare the differences of the active ingredient contents and the sulfur dioxide residue in Astragali Radix before and after sulfur fumigation and provide a basis for establishing an alternative processing method. Astragali Radix, harvested at the same time in Longxi Gansu, were processed with different methods. high performance liquid chromatography (HPLC) was used to determine the contents of the active ingredients in Astragali Radix and the revised method of the pharmacopoeia of China in 2011 was applied to determine the sulfur dioxide residue. The results show that the three-fold sulfur-fumigation group has the highest level of astragaloside IV and the dried sulfur-fumigation group with 10% water has the lowest level; the content of calycosin-7-O-β-D-glucoside is the highest in naturally dried group and the lowest in the group of sulfur fumigating for 3 times; the sulfur dioxide residue of all sulfur-fumigation groups exceeds certain limit significantly and the group of sulfur fumigating for 3 times reaches the highest level. | pubmed_974_19226 |
pubmed_27_13234 | Several lines of evidence suggest that members of the 90-kDa family of heat shock proteins (hsp90) may support the folding of various homologues of the src kinase family. In this work, we utilized pulse-chase analyses in rabbit reticulocyte lysate to demonstrate that hsp90-bound intermediates existed for the majority of newly synthesized p56lck molecules. The hsp90-binding drug geldanamycin disrupted the association of p56lck with hsp90, prevented the kinase from demonstrating a protease-resistant conformation, and caused decreases in kinase specific activity. Requirements for geldanamycin-inhibitable hsp90 function and physical interactions between hsp90 and p56lck persisted during chase periods. Consistent with the effects observed in rabbit reticulocyte lysate, application of geldanamycin to fibroblasts caused specific reversion of lck-mediated transformation concomitant with loss of p56lck activity and protein. However, geldanamycin had no direct effect on purified p56lck. Also consistent with functional linkages between hsp90 and p56lck, physical interactions between these proteins were detected in cytoplasmic, but not membrane, fractions of LSTRA cells. Although hsp90 functions in both the initial de novo folding and the reiterative support of p56lck structure in rabbit reticulocyte lysate, the specific occurrence of complexes between hsp90 and p56lck in the cytoplasm of T cells suggests that hsp90 primarily folds nascent molecules of p56lck in vivo. | 10.1021/bi961332c |
pubmed_365_5674 | BACKGROUND
To assess the relationship between systemic blood pressure, metabolic variables and adipose tissue blood flow, we studied 55 subjects before and 36 subjects after an oral glucose load (100 g).
METHODS
The subjects were divided into four different groups: (a) young lean control subjects [age 31 +/- 1 years, mean +/- SE, BMI (body mass index) 22.7 +/- 0.4 kg m-2]; (b) young obese subjects (age 29 +/- 2 years, BMI 37.8 +/- 1.8 kg m-2); (c) middle-aged obese subjects (age 50 +/- 2 years, BMI 30.2 +/- 0.9 kg m-2); and (d) middle-aged obese non-insulin-dependent diabetic (NIDDM) subjects (age 54 +/- 2 years, BMI 30.0 +/- 0.7 kg m-2).
RESULTS
Groups 2-4 demonstrated a low fasting adipose tissue blood flow (ATBF) and the increase in ATBF after oral glucose was impaired. A further impairment was present in NIDDM subjects. Systolic and diastolic blood pressure were also increased in groups 2-4 and further so in group 4. Fasting glucose, lactate and free fatty acid (FFA) levels correlated positively with the systolic blood pressure, whereas ATBF correlated negatively with the diastolic blood pressure. Furthermore, in the NIDDM subjects fasting lactate correlated closely with both the systolic (r = 0.649, P = 0.01) and diastolic (r = 0.626, P = 0.013) blood pressure.
CONCLUSION
These data suggest a close relationship between insulin resistance and regulation of adipose tissue blood flow as well as blood pressure. | 10.1046/j.1365-2362.1998.00360.x |
pubmed_608_257 | This article was designed to report the results of the comprehensive clinical and morphological analysis of the cases of death from the complications of burn disease based on the available medical documentation, the results of autopsies, and the data obtained in the histological and biochemical investigations. The study made it possible to reveal and identify the most typical, reliable, and stable intravital clinical and laboratory features of sepsis developing in burned individuals as well as postmortem pathomorphological and biochemical changes characterizing this condition supposed to be the immediate cause of death. The results of the study may be used to enhance the objectiveness and the level of evidence of expert conclusions concerning the cause of death of the patients presenting with burn disease and developing complications during its late period. | 10.17116/sudmed2018610618 |
pubmed_1034_2208 | Perceived control is a key component of successful aging and may serve as a protective factor against age-related declines in central domains of functioning. However, it is a largely open question whether and how perceived control changes from midadulthood to very old age and how such change is shaped by health and social contexts. To examine these questions, we apply growth models to up to 15-year 4-wave longitudinal data from the German Ageing Survey (DEAS; N = 10,081; aged 40-85 years at baseline; 49% women). Results revealed that perceived control is relatively stable in midlife, but starts to decline after midlife. Starting at 70, perceived control declines an average of a quarter of a SD per 10 years. Suffering from comorbidity and functional limitations were each associated with considerably lower perceived control. Volunteering and less loneliness were each uniquely associated with higher perceived control, over and above the other social factors as well as sociodemographic and health variables. Surprisingly, less social support was associated with stronger perceived control. We also found significant interaction effects suggesting that the combination of functional limitations with older age and loneliness with lower education were each associated with particularly compromised perceived control. Overall we found little evidence for correlates of change in perceived control, with only the loneliness-control association becoming slightly weaker over time. We take our findings to suggest that various different facets of social integration later in life are uniquely relevant for perceived control and suggest routes for further inquiry. (PsycINFO Database Record | 10.1037/pag0000143 |
pubmed_441_7124 | One of the hypotheses to account for the increase in the drive to ventilation in exercise mediated by the peripheral chemoreceptors is that there is an improved linkage between breathing rate and lung to carotid body circulation time, such that peaks of arterial carbon dioxide arrive during a subsequent inspiration thereby stimulating ventilation. This study was designed to examine the mechanisms which may underlie the improved linkage. Auto- and cross-correlations of breathing and heart rhythms in volunteers at rest and during exercise showed an increased regularity of the rhythms but not entrainment between the rhythms. Although the increased regularity of the cardiac rhythm should promote a decrease in the variability of the lung to carotid body circulation time, the lack of entrainment shows that if there is an improved linkage of breathing and lung to carotid body circulation time, it is not by a coupling of heart rhythm to breathing rhythm. | 10.1139/y81-014 |
pubmed_1073_15800 | BACKGROUND/AIMS
Autophagy plays a fundamental role in cell survival under stress conditions such as nutrient deprivation. Decreased nitric oxide (NO) production, which may contribute to vascular dysfunction, is one of the consequences of autophagy in endothelial cells. The antimalarial drug chloroquine (CLQ) inhibits autophagy by blocking autophagosome formation and has been proposed as adjuvant chemotherapy in other diseases.
METHODS
Autophagy was induced by serum deprivation in Human Umbilical Vascular Endothelial Cells (HUVEC) as demonstrated by formation of Acidic Vesicular Organelles (AVOs), conversion of Microtubule-associated protein 1 light chain (LC3), and Sequestosome-1 (SQTM1/p62) degradation. Using endothelium-dependent vasorelaxation assays, intracellular NO production in an ex vivo rat aortic ring model pre-constricted with phenylephrine was estimated along with DAF-2 DA cell membrane-permeable NO sensitive fluorescent dye.
RESULTS
The inhibition of autophagy by CLQ restored NO levels, protected against superoxide generation and preserved morphology as well as proliferation of HUVEC under serum deprivation. Interestingly, the incubation of rat aortic rings with CLQ resulted in endothelium-dependent relaxation mediated by the increase of NO.
CONCLUSION
These findings emphasize the importance of autophagy in endothelial function and demonstrate the potential use of autophagy inhibitors to protect vascular function during nutrient deprivation. | 10.1159/000430240 |
pubmed_190_6047 | In a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as 'outcome-adaptive randomization.' In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior. While the design merits of outcome-adaptive trials have been debated, little attention has been paid to significant ethical concerns that arise in the conduct of such studies. These include loss of equipoise, lack of processes for adequate informed consent, and inequalities inherent in the research design which could lead to perceptions of injustice that may have negative implications for patients and the research enterprise. This article examines the ethical difficulties inherent in outcome-adaptive trials. | 10.1111/bioe.12084 |
pubmed_412_10897 | During the period between 1946 and 1996, 59 patients of intrinsic duodenal obstruction and 67 of intrinsic jejunoileal obstruction were treated in our institute. Analysis of data obtained from the patients revealed that the duodenal obstruction was the most successfully treated by diamond-shaped duodenoduodenostomy, jejunal obstruction by resection of the dilated oral blind end, tapering jejunoplasty and ileal obstruction by resection of the dilated blind end and anastomosis or ileostomy in case with peritonitis. Associated anomalies in duodenal obstruction, anastomotic malfunction and postoperative short bowel syndrome in jejunal obstruction and complicated peritonitis in ileal obstruction were the most effective as prognostic factors. | pubmed_412_10897 |
pubmed_861_17629 | A cyclic (amino)metal-substituted dicoordinated silylene derivative has been synthesized and fully characterized. Of particular interest is that the N-hetero-RhI -metallacyclic silylene exhibits a distorted tetrahedral geometry around the rhodium atom and a considerably shortened Si-Rh bond (2.138 Å) compared to classical Si-Rh single bonds (ca. 2.30-2.35 Å). A theoretical investigation reveals that the geometrical deviation around the rhodium center from the classical square-planar to a tetrahedral geometry increases the π-donating and σ-accepting character of the rhodium atom, thereby efficiently stabilizing the silylene moiety. | 10.1002/anie.201904594 |
pubmed_594_2669 | What has been responsible for the increase in Chinstrap penguin populations during the past 40 years in maritime Antarctica? One view ascribes it to an increase in availability of their prey brought on by the decrease in baleen whale stocks. The contrary opinion, attributes it to environmental warming. This causes a gradual decrease in the frequency of cold years with extensive winter sea ice cover. A number of penguin monitoring programs are in progress and are expected to provide some answers to these questions. Unfortunately, it is not easy to distinguish natural variability from anthropogenic change since penguins are easily accessible predators of krill and the feeding range of the penguins has almost overlapped with the krill fishery in time and space in the last four decades. Therefore it is important to reconstruct the change of ancient penguin abundance and distribution in the absence of human activity. Many efforts have focused on surveying the abandoned penguin rookeries, but this method has not been able to give a continuous historical record of penguin populations. In several recent studies, ancient penguin excreta was scooped from the penguin relics in the sediments of the lake on penguin rookery, Ardley Island, maritime Antarctica. In these studies, penguin droppings or guano soil deposited in the lake and changes in sediment geochemistry have been used to calculate penguin population changes based upon the geochemical composition of the sediment core. The results suggest that climate change has a significant impact on penguin populations. | 10.3184/003685001783239078 |
pubmed_1044_15191 | INTRODUCTION
In health professions education (HPE), focus is placed on developing clinically competent practitioners who can function within their professional scope in a broad range of health care contexts. In this study, the authors investigated diagnostic radiography lecturers' understanding of how students become socially responsive. The concept of 'critical consciousness' was explored as an intervention of being a transformer in the local environment. This places focus on learning and teaching that aims to develop radiography graduates who are critically conscious, such that they can take up the challenges of healthcare in their environment, in addition to being clinically competent in their field. The study under discussion therefore sought to find out how radiography lecturers understand a socially responsive curriculum at a University of Technology in the South African context.
METHOD
A qualitative, exploratory design was used where curriculum documents were reviewed and from which stimulus points were identified for a semi-structured focus group interview with radiography lecturers followed by five individual interviews. All interviews were audio-recorded, transcribed, coded and analysed through a process of thematic analysis.
RESULTS
Four dominant themes emerged from the analysis, namely i) diverse understandings of critical consciousness, ii) becoming a reflective practitioner, iii) a need for curriculum transformation and iv) emerging pedagogies.
CONCLUSION
Critical reflection by both the radiography students and lecturers is key to developing social awareness and critical consciousness which could drive critical motivation and critical action to effect social change. It is recommended that the current curriculum should be reviewed and transformed to include constructive reflective practice.
IMPLICATIONS FOR PRACTICE
Dedicated time should be scheduled, in the curriculum, to allow students and lecturers to engage in meaningful constructive reflection to enhance socially responsive practice. | 10.1016/j.radi.2022.06.001 |
pubmed_11_14199 | OBJECTIVE
National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated.
METHODS
A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests.
RESULTS
The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079-0.115%) (one of 1027 patients).
CONCLUSIONS
Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome. | 10.1111/1742-6723.12222 |
pubmed_598_8479 | Coracoid fractures are rare injuries, which may occur in isolation or in association with other shoulder pathology. The mechanism of trauma consists of a strong contraction of the conjoint tendon as a result of direct trauma. The diagnosis is usually difficult and many times overlooked, thereby requiring a high level of suspicion. In many cases, standard trauma series shoulder radiographs are unable to provide a definitive and reliable diagnosis. Therefore, other imaging modalities may be necessary to confirm the diagnosis. Although uncommon, if left untreated, a coracoid fracture will result in chronic pain and shoulder disability. Both conservative and surgical techniques have been previously reported and shown positive outcomes. In regard to the surgical technique, most reports describe the use of screw fixation, which has been associated with full recovery and high patient satisfaction. Nevertheless, the purpose of this Technical Note is to describe our preferred method to treat an isolated type II displaced coracoid process fracture through suture anchor fixation. | 10.1016/j.eats.2017.06.042 |
pubmed_282_21022 | AIM
To compare the therapeutic effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist (GnRHa) in the treatment of stage III-IV endometriosis after laparoscopic surgery.
METHODS
Fifty patients with stage III-IV endometriosis diagnosed on laparoscopy were randomized into two groups according to GnRHa dose. Sex hormone level, symptoms of estrogen deficiency and lumbar vertebrae bone density were compared and analyzed between the two groups.
RESULTS
Bone density was decreased in both groups at 20 weeks after treatment, and the degree of bone density loss in the full-dose group (5.6%) was higher than in the half-dose group (1.2%; P < 0.05). Surgery combined with the 3.75-mg GnRHa or with the 1.88-mg GnRHa relieved the degree of dysmenorrhea, although one case of light dysmenorrhea occurred in each group, but there was no significant difference (P > 0.05) after resumption of menstruation. Both groups had symptoms of perimenopause at 8 weeks after treatment (P > 0.05), but change in Kupperman score with time differed between the groups. At 16, 20 weeks after treatment, the symptoms of perimenopause in the half-dose group were improved, and Kupperman score was lower than at 8 weeks after treatment. In the full-dose group, however, Kupperman score was higher than at 8 weeks after treatment and higher than in the half-dose group (P < 0.05). After treatment, follicle-stimulating hormone and luteinizing hormone both decreased in both groups (P < 0.05), but there was no difference between the two groups (P > 0.05). Estradiol (E2) in the full-dose group was significantly lower than in the half-dose group (P < 0.05).
CONCLUSION
The 1.88-mg GnRHa treatment can be used in III-IV endometriosis patients after laparoscopic surgery, to reduce perimenopausal symptoms, significantly improve bone loss, and achieve a good clinical effect. | 10.1111/jog.13420 |
pubmed_26_6400 | INTRODUCTION
Hiccups are well-known to most people. In most cases, hiccups are limited to a short period of time, but in some cases, they persist for days, weeks, months and even years. Many interventions have been proposed and tested, but the most effective is probably long periods of apnoea. The aim of this article was to determine the effect of 10-minute apnoea on hiccups.
MATERIAL AND METHODS
PubMed, the Cochrane Library databases and Web of Science were searched for randomised controlled trials examining the effect of apnoea on hiccups. The main outcome measure was total absence of hiccups for at least two days after intervention.
RESULTS
We found no randomised controlled trials testing extensive apnoea as an intervention against hiccups.
CONCLUSIONS
In spite of massive positive empirical experience with the effect of long apnoea periods on hiccups, there is no solid scientific evidence confirming this effect. To determine the clinical effect, it is necessary to perform large double-blinded, randomised, placebo-controlled crossover trials. | pubmed_26_6400 |
pubmed_895_23875 | PURPOSE
To verify the utility and preliminary safety of a 20-gauge silicone cannula for use with 20-gauge horizontal scissors delamination during microincision vitrectomy surgery (MIVS).
METHODS
Thirty-eight eyes in 35 consecutive patients with diabetic tractional retinal detachment, who underwent MIVS between April 2010 and March 2012 and were followed for 3-24 months, were retrospectively assessed using a chart review. Twenty-gauge scissors delamination through a silicone cannula, with an additional 20-gauge port as a hybrid, was primarily selected when treating thick and rigid fibrovascular membranes, including fluctuating vessels over the detached retina near the macula. The main outcome measures included the proportion of patients treated with this hybrid method, the postoperative visual acuity, and the incidence of complications.
RESULTS
Compared with the 26 eyes treated with MIVS only, 12 eyes (32%) required a hybrid technique with the use of 20-gauge instruments through a silicone cannula in addition to MIVS. Two patients underwent additional surgery. Temporary silicone oil tamponade was performed in one case of retinotomy and one case of schizophrenia. The mean visual acuity (logarithm of the minimum angle of resolution [logMAR]) improved from 1.43 ± 0.85 to 0.72 ± 0.47 at the last follow-up visit. No patients exhibited worsening of their visual acuity postoperatively. No sclerotomy-related complications were recorded during the intraoperative or postoperative periods.
CONCLUSION
Hybrid MIVS combined with a 20-gauge silicone cannula for use with 20-gauge horizontal scissors in diabetic tractional retinal detachment eyes is useful and safe due to the reduced risk of sclerotomy-related retinal breaks. This procedure is a reasonable option when performing complex surgery for diabetic vitrectomy. | 10.2147/OPTH.S46486 |
pubmed_230_8606 | The purpose of this study was to test a diathesis-stress model of well-being for siblings who have a brother or sister with an autism spectrum disorder (ASD). Data were collected from 57 adolescents and their mothers. Sisters reported higher levels of depressive and anxiety symptoms than brothers. Having a family history of ASDs was associated with depressive, but not anxiety, symptoms. A high level of maternal depression was also associated with more depressive and anxiety symptoms. A diathesis-stress model was partially supported, primarily through the findings that sibling sub-threshold autism characteristics were associated with depressive and anxiety symptoms in siblings, but only in the presence of a high number of stressful life events. | 10.1007/s10803-009-0722-7 |
pubmed_125_10871 | Range verification in proton therapy is a critical quality assurance task. We studied the feasibility of online range verification based on proton-induced acoustic signals, using a bidirectional long-short-term-memory recurrent neural network and various signal processing techniques. Dose distribution of 1D pencil proton beams inside a CT image-based phantom was analytically calculated. The propagation of acoustic signal inside the phantom was modeled using the k-Wave toolbox. For signal processing, five methods were investigated: down-sampling (DS), DS + HT (Hilbert transform), Wavelet decomposition (Wavedec db1, db4 and db20). The performances were quantitatively evaluated in terms of mean absolute error, mean relative error (MRE) and the Bragg peak localization error ([Formula: see text]). In addition, the study analyzed the impact of noise levels, the number of sensors, as well as the location of sensors. For the noiseless case (32 sensors), the Wavedec db1 method demonstrates the best performance: [Formula: see text] is less than one pixel and the dose accuracy over the region adjacent to the Bragg peak (MRE50) is ∼3.04%. With the presence of noise, the Wavedec db1 method demonstrates the best noise immunity, achieving [Formula: see text] less than 1 mm and an MRE50 of ∼12%. The proposed machine learning framework may become a useful tool allowing for online range verification in proton therapy. | 10.1088/1361-6560/abaa5e |
pubmed_604_2431 | We report two cases of Grave's disease (GD) caracterized by the succession of hypothyroid and hyperthyroid states. Case 1: A 32 years old woman, has presented initially a typical GD with hyperthyroidism. Grave's ophtalmopathy and homogenous goiter. Four months later, she presented a spontaneous hypothyroidism necessiting treatment with thyroxine and a severe myasthenia gravis. More later (6 months), she experienced symptoms of hyperthyroidism after thymectomy. The level of anti-thyrotropin-receptor antibodies (TSab) was very high (141 UI/I, NV < 10). Case 2: A 29 years old woman has been treated by thyroxine (150 microg/day) for a primary hypothyroidism. Ten months later, she presented symptoms of hyperthyroidism even after stoppage of thyroxine. TSH value was decreased (TSH < 0.05 microU/ml) and FT4 level was raised (FT4 = 25.5 pmol/l). The thyroid antibodies were positive. We discuss, after review of the litterature, the physiopathological mecanisms of these changes in the thyroid state, particularly the role of the blocking and stimulating anti-thyrotropin-receptor antibodies. | pubmed_604_2431 |
pubmed_586_1421 | The paper describes sanitary-hygienic and technological investigations aimed at development of the sorption method of water reclamation for personal hygiene needs of cosmonauts from wash water. Catamine-AB was used as a detergent with bactericidal properties. Manned experiments helped to identify the conditions that provided an adequate cleaning of skin and simultaneous sterilization of wash water. The technology of wash water purification was developed, proper sorbents were selected and recommended values of their use were established. | pubmed_586_1421 |
pubmed_1051_21112 | Arginine-vasopressin (AVP) is a neurohypophyseal peptide that plays a critical role in the regulation of social behavior in mammals. Neuronal AVP regulates male-specific social signaling processes, such as exocrine urinary scent deposition and marking behavior in mice. In the periphery, AVP is transported to the portal bloodstream and acts as an antidiuretic hormone. These AVP dynamics imply that the central role of AVP in the stimulation of urinary marking is dissociated with the peripheral role of AVP in the retention of osmotic conditions. Using male BALB/c mice as subjects, peripheral injection of AVP decreased urinary marking and urination. In contrast, a central infusion of AVP facilitated urinary marking with no effect on urination, while an antagonist of the AVP 1a receptor inhibited marking. Centrally AVP-injected mice also exhibited typical behaviors, such as hiccough/sneeze-like reactions and flash scratching, particularly when confronted with a stimulus mouse through a wire mesh screen. Significant expression of these typical reactions in these mice resulted in the disruption of marking deposition. Further analysis of AVP synthesis illustrated that AVP levels increased in the midbrain but not in the circulation immediately after the test, particularly when confronted with a stimulus mouse. The central AVP regulates urinary marking and other typical behaviors in a dose- and situation-dependent manner. The sequential process implies that centrally synthesized AVP may be secreted into the circulation following immediate neuronal processes, and then peripheral AVP acts as an antidiuretic hormone on urinary marking behavior. | 10.1016/j.yhbeh.2022.105128 |
pubmed_910_11232 | In an attempt to identify the cell-associated protein(s) through which SMOC (Secreted Modular Calcium binding protein) induces mitogen-activated protein kinase (MAPK) signaling, the epidermal growth factor receptor (EGFR) became a candidate. However, although in 32D/EGFR cells, the EGFR was phosphorylated in the presence of a commercially available human SMOC-1 (hSMOC-1), only minimal phosphorylation was observed in the presence of Xenopus SMOC-1 (XSMOC-1) or human SMOC-2. Analysis of the commercial hSMOC-1 product demonstrated the presence of pro-EGF as an impurity. When the pro-EGF was removed, only minimal EGFR activation was observed, indicating that SMOC does not signal primarily through EGFR and its receptor remains unidentified. Investigation of SMOC/pro-EGF binding affinity revealed a strong interaction that does not require the C-terminal extracellular calcium-binding (EC) domain of SMOC or the EGF domain of pro-EGF. SMOC does not appear to potentiate or inhibit MAPK signaling in response to pro-EGF, but the interaction could provide a mechanism for retaining soluble pro-EGF at the cell surface. | 10.1371/journal.pone.0154294 |
pubmed_842_24682 | The abnormal synchronisation of neural networks may underlie some of the deficits observed in schizophrenia. Abnormal synchronisation can be induced in animal models. We investigated whether acute clozapine treatment might function therapeutically by ameliorating the deficit in theta frequency coherence between the prefrontal cortex and the hippocampus that is induced in rats exposed to maternal immune activation (MIA)--a risk-factor for schizophrenia. Clozapine treatment increased synchrony levels to that of control animals in a dose-dependent manner. Clozapine's effect on synchrony may in part be mediated through increases in local synchrony that occurred in prefrontal cortex but not hippocampus. | 10.1016/j.schres.2011.12.016 |
pubmed_134_17444 | BACKGROUND
Recently reported prevalences of myopia in primary school children vary greatly in different regions of the world. This study aimed to estimate the prevalence of refractive errors in an unselected urban population of young primary school children in eastern Sydney, Australia, between 1998 and 2004, for comparison with our previously published data gathered using the same protocols and other Australian studies over the last 30 years.
METHODS
Right eye refractive data from non-cycloplegic retinoscopy was analysed for 1,936 children aged 4 to 12 years who underwent a full eye examination whilst on a vision science excursion to the Vision Education Centre Clinic at the University of New South Wales. Myopia was defined as spherical equivalents equal to or less than -0.50 D, and hyperopia as spherical equivalents greater than +0.50 D.
RESULTS
The mean spherical equivalent decreased significantly (p < 0.0001) with age from +0.73 +/- 0.1D (SE) at age 4 to +0.21 +/- 0.11D at age 12 years. The proportion of children across all ages with myopia of -0.50D or more was 8.4%, ranging from 2.3% of 4 year olds to 14.7% of 12 year olds. Hyperopia greater than +0.50D was present in 38.4%. A 3-way ANOVA for cohort, age and gender of both the current and our previous data showed a significant main effect for age (p < 0.0001) but not for cohort (p = 0.134) or gender (p = 0.61).
CONCLUSIONS
Comparison of our new data with our early 1990s data and that from studies of over 8,000 Australian non-clinical rural and urban children in the 1970's and 1980's provided no evidence for the rapidly increasing prevalence of myopia described elsewhere in the world. In fact, the prevalence of myopia in Australian children continues to be significantly lower than that reported in Asia and North America despite changing demographics. This raises the issue of whether these results are a reflection of Australia's stable educational system and lifestyle over the last 30 years. | 10.1186/1471-2415-5-1 |
pubmed_1132_17273 | Ferguson et al. (2013) use applied physics to quantitate the fitness of HIV-1 Gag based on sequence variability across the protein. This enables a new approach to vaccine design that focuses CD8+ T cell responses on fitness-constrained parts of Gag. | pubmed_1132_17273 |
pubmed_379_2516 | This study assessed the inhibitory effect of nitroglycerin and sodium nitroprusside on platelet aggregation in a model of platelet activation across coronary circulation. Platelet aggregation is believed to contribute to the precipitation of acute ischemic syndromes. We previously showed that rapid atrial pacing in patients with stable coronary artery disease (CAD) causes platelet hyperaggregability during blood passage in coronary circulation. Because nitroglycerin and sodium nitroprusside have been shown to inhibit platelet aggregation, we examined the effect of these drugs on this model of platelet activation. During catheterization of 19 patients with CAD (> 50% diameter narrowing of epicardial coronary arteries), we measured platelet aggregation (using whole blood platelet aggregometry) on blood samples obtained simultaneously from the coronary sinus and aorta at rest, and 2 minutes after onset of rapid atrial pacing. This procedure was repeated during an intravenous infusion of either nitroglycerin (n = 9) or sodium nitroprusside (n = 10). There was no arteriovenous difference in platelet aggregation under resting conditions. Atrial pacing caused an increase in platelet aggregation in coronary sinus blood (+64 +/- 9%; p < 0.01), but not in arterial blood (15 +/- 12% decrease; p = NS). This increase was transient and returned toward baseline 10 minutes after termination of pacing. Although resting platelet aggregation was not affected by nitroglycerin or sodium nitroprusside, activation of platelets with atrial pacing across the coronary bed was stopped by pretreatment with therapeutic doses of nitroglycerin or sodium nitroprusside. When coronary blood flow increases in patients with CAD, platelets are activated and aggregate more easily. This activation can be blunted by pretreatment with nitroglycerin or sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1016/s0002-9149(99)80578-5 |
pubmed_31_8553 | Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progression. Sialylation is essential for early embryonic development and the deletion of UDP-GlcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision. | 10.1007/s13238-018-0597-5 |
pubmed_18_18309 | The hairy cell leukemia is a rare, low grade mature B-cell disease, a subtype of a Non Hodgkin-Lymphoma. The following article gives a short survey about the disease and the therapeutic options. | pubmed_18_18309 |
pubmed_550_16998 | The target of bone systemic factors and therapeutics has been assumed to be primarily osteoblasts and/or osteoclasts and their precursors. All the action with regard to bone modeling or remodeling has been assumed to take place on the bone surface. In this scenario, cells below the bone surface, that is, osteocyte, are considered to be inactive placeholders in the bone matrix. New data show osteocytes are involved. In addition to the function of osteocytes translating mechanical strain into biochemical signals between osteocytes and cells on the bone surface to affect (re)modeling, new functions are emerging. Osteocytes are exquisitely sensitive to mechanical strain in the form of shear stress compared to osteoblasts or osteoclasts and communicate with each other, with cells on the bone surface, and with marrow cells. Osteocytes are able to move their cell body and their dendritic processes and appear to be able to modify their local microenvironment. A novel function now attributed to osteocytes includes regulation of phosphate metabolism. Therefore, in addition to osteoblasts and osteoclasts, osteocytes are also important for bone health. | 10.1196/annals.1402.018 |
pubmed_636_3267 | BACKGROUND
Repetitive checking in obsessive-compulsive disorder (OCD) would serve to relieve obsession-related anxiety and/or to compensate memory deficit, but experimental literature on this subject is inconsistent. The main objective is to test the influence of obsession-related anxiety and memory on repetitive checking in OCD.
METHODS
Twenty-three OCD checkers, 17 OCD non-checkers and 41 controls performed a delayed-matching-to-sample task with an unrestricted checking option. Some stimuli were obsession-related in order to measure the influence of anxiety on checking. A version of the task without checking possibility was used to assess memory abilities.
RESULTS
OCD checkers had similar memory performances but checked more than the other groups when presented with non-anxiogenic stimuli. Level of anxiety associated to the stimulus did not influence the number of checks.
CONCLUSIONS
Increased checking in OCD checkers, being independent of memory abilities and primary obsession-related anxiety, would, therefore, be closer to an automated behaviour than a coping strategy. | pubmed_636_3267 |
pubmed_970_16045 | Plant hormones have various functions in plants and play crucial roles in all developmental and differentiation stages. Auxins constitute one of the most important groups with the major representative indole-3-acetic acid (IAA). A halogenated derivate of IAA, 4-chloro-indole-3-acetic acid (4-Cl-IAA), has previously been identified in Pisum sativum and other legumes. While the enzymes responsible for the halogenation of compounds in bacteria and fungi are well studied, the metabolic pathways leading to the production of 4-Cl-IAA in plants, especially the halogenating reaction, are still unknown. Therefore, bacterial flavin-dependent tryptophan-halogenase genes were transformed into the model organism Arabidopsis thaliana. The type of chlorinated indole derivatives that could be expected was determined by incubating wild type A. thaliana with different Cl-tryptophan derivatives. We showed that, in addition to chlorinated IAA, chlorinated IAA conjugates were synthesized. Concomitantly, we found that an auxin conjugate synthetase (GH3.3 protein) from A. thaliana was able to convert chlorinated IAAs to amino acid conjugates in vitro. In addition, we showed that the production of halogenated tryptophan (Trp), indole-3-acetonitrile (IAN) and IAA is possible in transgenic A. thaliana in planta with the help of the bacterial halogenating enzymes. Furthermore, it was investigated if there is an effect (i) of exogenously applied Cl-IAA and Cl-Trp and (ii) of endogenously chlorinated substances on the growth phenotype of the plants. | 10.3390/ijms21072567 |
pubmed_821_2873 | The ability to manipulate the mouse genome has made the mouse the primary mammalian genetic model organism. It has been possible to model human cancer in the mouse by overexpressing oncogenes or inactivating tumor suppressor genes, and these experiments have provided much of our in vivo understanding of cancer. However, these transgenic approaches do not always completely and accurately model human carcinogenesis. Recent developments in transgenic and knockout approaches have improved the accuracy of modeling somatic cancer in the mouse and analyzing the genomic instability that occurs in murine tumors. It is possible to use retroviral gene delivery, chromosome engineering and inducible transgenes to selectively manipulate the genome in a more precise spatial and temporal pattern. In addition, the development of powerful cytogenetic tools such as spectral karyotyping, fluorescence in situ hybridization and comparative genome hybridization have improved our ability to detect chromosomal rearrangements. Finally, global patterns of gene expression can be determined by microarray analysis to decipher complex gene patterns which occur in cancers. Several of these advances in mouse modeling of human cancer are discussed in this review. | 10.1093/hmg/10.7.669 |
pubmed_361_1826 | To evaluate the clinical significance of TBII and TSAb activities in euthyroid and hyperthyroid Graves' disease, these two activities were measured in 8 patients with euthyroid Graves' disease and 29 patients with hyperthyroid Graves' disease during treatment with antithyroid drugs. In 8 patients with euthyroid Graves' disease, TBII activity was detectable only in one patient and TSAb activity detected in 3 patients, these detectabilities being much lower than those in hyperthyroid Graves' disease. However, 2 of 4 patients who had either TSAb or TBII came to have both activities, and one of them became overt hyperthyroid. In patients with hyperthyroid Graves' disease, detectabilities of these activities became lower as they became euthyroid with antithyroid drug treatment, but TSAb tended to be higher than TBII when they remained euthyroid for more than 4 months. Although the majority of the patients who had TSAb and/or TBII activities were T3 non-suppressible, patients with no TSAb and TBII activities did not necessarily show remission of the disease. The present results suggest that patients with euthyroid Graves' disease with both TBII and TSAb may be apt to become hyperthyroid, and that TSAb and TBII activities and T3 suppressibility may not be a definite criteria for the remission of Graves' disease. | 10.1507/endocrine1927.64.3_206 |
pubmed_579_6824 | PURPOSE
The study aimed to investigate (a) if women's perceptions of their work environment changed during a 16-week rehabilitation period and at a 12-month follow-up; (b) whether such changes were related to outcomes in terms of return to work, well-being and valued occupations.
METHODS
Eighty-four gainfully employed women on sick-leave due to stress-related disorders responded to instruments assessing perceptions of the work environment, well-being (self-esteem, self-mastery, quality of life, perceived stress, self-rated health) and perceived occupational value. Data about return to work were collected from registers. Non-parametric statistics were used.
RESULTS
The increase in the women's ratings of their work environment was non-significant between baseline and completed rehabilitation but was statistically significant between baseline and the 12-month follow-up. No relationships were found between changes in perceptions of the work environment and outcomes after the rehabilitation. At the follow-up, however, there were associations between perceived work environment changes in a positive direction and return to work; improved self-esteem, self-mastery, quality of life, perceived occupational value and self-rated health; and reduced stress.
CONCLUSION
It seems important to consider the work environment in rehabilitation for stress-related problems, and a follow-up appears warranted to detect changes and associations not visible immediately after rehabilitation.
IMPLICATIONS FOR REHABILITATION
Work environment Perceptions of the work environment seem important for return to work, although other factors are likely to contribute as well. Perceptions of the work environment are associated with several aspects of well-being. When developing rehabilitation interventions a focus on the clients' perceptions of their work environment seems vital. | 10.3109/09638288.2015.1046567 |
pubmed_160_12979 | BACKGROUND
Pairwise sequence alignment methods are widely used in biological research. The increasing number of sequences is perceived as one of the upcoming challenges for sequence alignment methods in the nearest future. To overcome this challenge several GPU (Graphics Processing Unit) computing approaches have been proposed lately. These solutions show a great potential of a GPU platform but in most cases address the problem of sequence database scanning and computing only the alignment score whereas the alignment itself is omitted. Thus, the need arose to implement the global and semiglobal Needleman-Wunsch, and Smith-Waterman algorithms with a backtracking procedure which is needed to construct the alignment.
RESULTS
In this paper we present the solution that performs the alignment of every given sequence pair, which is a required step for progressive multiple sequence alignment methods, as well as for DNA recognition at the DNA assembly stage. Performed tests show that the implementation, with performance up to 6.3 GCUPS on a single GPU for affine gap penalties, is very efficient in comparison to other CPU and GPU-based solutions. Moreover, multiple GPUs support with load balancing makes the application very scalable.
CONCLUSIONS
The article shows that the backtracking procedure of the sequence alignment algorithms may be designed to fit in with the GPU architecture. Therefore, our algorithm, apart from scores, is able to compute pairwise alignments. This opens a wide range of new possibilities, allowing other methods from the area of molecular biology to take advantage of the new computational architecture. Performed tests show that the efficiency of the implementation is excellent. Moreover, the speed of our GPU-based algorithms can be almost linearly increased when using more than one graphics card. | 10.1186/1471-2105-12-181 |
pubmed_659_1858 | The inhibition of the Human Immunodeficiency Virus Type 1 Protease (HIV-1 PR) can prevent the synthesis of new viruses. Computer-aided drug design (CADD) would enhance the discovery of new therapies, through which the estimation of ligand-binding affinity is critical to predict the most efficient inhibitor. A time-consuming binding free energy method would reduce the usefulness of CADD. The modified linear interaction energy (LIE) approach emerges as an appropriate protocol that performs this task. In particular, the polar interaction free energy, which is obtained via numerically resolving the linear Poisson-Boltzmann equation, plays as an important role in driving the binding mechanism of the HIV-1 PR + inhibitor complex. The electrostatic interaction energy contributes to the attraction between two molecules, but the vdW interaction acts as a repulsive factor between the ligand and the HIV-1 PR. Moreover, the ligands were found to adopt a very strong hydrophobic interaction with the HIV-1 PR. Furthermore, the results obtained corroborate the high accuracy and precision of computational studies with a large correlation coefficient value R = 0.83 and a small RMSE δ RMSE = 1.25 kcal mol-1. This method is less time-consuming than the other end-point methods, such as the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) and free energy perturbation (FEP) approaches. Overall, the modified LIE approach would provide ligand-binding affinity with HIV-1 PR accurately, precisely, and rapidly, resulting in a more efficient design of new inhibitors. | 10.1039/c9ra09583g |
pubmed_143_7076 | A UHPLC-photodiode array-MS method was developed and validated for the quantification of one chromone and six anthraquinone type of compounds from Bulbine natalensis plant samples and dietary supplements. Metabolites 1: - 7: were identified based on their retention times and electrospray ionization-MS spectra compared with a mix of previously isolated compounds. The quantification of 1: - 7: was based on photodiode array detection. The optimized separation was achieved using a CORTECS C18 column with a gradient of water/acetonitrile as the mobile phase. Seven compounds were separated within 15 minutes with detection limits of 50 pg on the column. The analytical method was validated for linearity, repeatability, accuracy, limits of detection, and limits of quantification. The relative standard deviations for intra- and inter-day experiments were less than 5% and the recovery efficiency was 98 - 101%. Nine dietary supplements labeled as containing B. natalensis were examined. Anthraquinone-type compounds were detected in only five out of nine dietary supplements, with the total amount ranging from 11.3 to 90.4 mg per daily dose. The analytical method is simple, economic, rapid, and can be applied for quality assessment of B. natalensis and dietary supplements. Electrospray ionization-MS was used for the identification of these compounds in plant samples and dietary products. | 10.1055/a-1037-4051 |
pubmed_431_7449 | In this study, the impact of 17alpha-ethynylestradiol (EE2) on reproduction in zebrafish (Danio rerio) was evaluated using vitellogenin (Vtg) induction, mortality rate, growth, sex ratio, gonad histology, fecundity, and sperm parameters as endpoints. Two days post-hatch (2dph) zebrafish were exposed to solvent control or EE2 at 0.4, 2, and 10ng/l for 3 months. At 21dph, Vtg mRNA expression was detected only in fish exposed to 10ng/l EE2. At 90dph, increased mortality rate and sex ratio (female:male) were observed in fish exposed to 2 and 10ng/l EE2. A dose-dependent increase in gonads with underdeveloped gametes was observed in fish exposed to EE2. At 180dph, malformation of the sperm duct and reduced number of spermatozoa were found in fish exposed to 2ng/l and 10ng/l EE2. Reduced fecundity and 12hpf egg viability were found in EE2-exposed males and females. The number of fish with no expressible milt was elevated dose dependently in EE2-exposed males, although no difference in sperm density was found. After a 3-month recovery period, growth and sex ratio were partially recovered. Our findings suggest that EE2 can adversely affect the fecundity, sex differentiation, gametes development, and other reproductive functions of both male and female zebrafish, and some of the toxic effects persist. | 10.1016/j.aquatox.2008.01.020 |
pubmed_943_3475 | BACKGROUND
Macrophage accumulation is a prominent feature in many forms of glomerulonephritis. Local proliferation of macrophages within the kidney has been described in human and experimental glomerulonephritis and may have an important role in augmenting the inflammatory response. The current study examined the relationship between local macrophage proliferation and renal expression of macrophage colony-stimulating factor (M-CSF).
METHODS
A total of 118 renal biopsies of patients with a wide range of glomerulonephridities were examined for M-CSF protein and macrophage proliferation (KP1+PCNA+cells) by single and double immunohistochemistry staining, respectively.
RESULTS
Biopsies of thin membrane disease (TMD) with histologically normal kidney showed M-CSF protein expression by 33% of cortical tubules, while glomerular M-CSF expression was limited to resident macrophages and some podocytes. Glomerular M-CSF expression increased significantly in proliferative forms of glomerulonephritis, with M-CSF staining of infiltrating macrophages, podocytes and some mesangial cells. Segmental areas of strong M-CSF expression, particularly in crescents, co-localized with KP1+PCNA+ proliferating macrophages. There was also an increase in tubular M-CSF expression in most types of glomerulonephritis. Tubular M-CSF staining was strongest in areas of tubular damage and co-localized with KP1+ macrophages, including KP1+PCNA+ proliferating macrophages. Many interstitial macrophages and alpha-smooth muscle actin-positive myofibroblasts showed strong M-CSF staining. Statistical analysis showed a highly significant correlation between M-CSF expression and local macrophage proliferation in both the glomerulus and tubulointerstitium. Glomerular and tubular M-CSF expression gave a significant correlation with renal dysfunction.
CONCLUSIONS
Glomerular and tubulointerstitial M-CSF expression is up-regulated in human glomerulonephritis, being most prominent in proliferative forms of disease. This correlated with local macrophage proliferation, suggesting that increased renal M-CSF production plays an important role in regulating local macrophage proliferation in human glomerulonephritis. | 10.1093/ndt/16.8.1638 |
pubmed_69_24314 | BACKGROUND
Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease.
METHODS
In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices.
RESULTS
From the derivation cohort (n = 95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n = 11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%.
CONCLUSIONS
The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV. | 10.1371/journal.pone.0050965 |
pubmed_74_26048 | With an ever-increasing usage of electronic structure programs by the microwave spectroscopy community, there is a growing need to assess the performance of commonly used, low-cost quantum chemical methods, particularly with respect to rotational constants because these quantities are central in guiding experiments. Here, we systematically benchmark the predictive power afforded by several low-level ab initio and density functionals combined with a variety of basis sets that are commonly employed in the rotational spectroscopy literature. The data set in our analysis consists of 6916 optimized geometries of 76 representative species where high-resolution experimental gas-phase rotational constants are available. We adopted a Bayesian approach for analyzing the performance of each method and basis set combination, employing Hamiltonian Monte Carlo sampling to determine the uncertainty in theoretical predictions of rotational constants and dipole moments. Our analysis establishes a hierarchy of accuracy and uncertainty, with commonly used methods in the rotational spectroscopy literature such as B3LYP and MP2 yielding lower accuracy and higher uncertainty than newer-generation functionals such as those from the Minnesota family, and ωB97X-D, which, when paired with a modestly sized 6-31+G(d) basis, provides optimal performance with respect to computational cost. Additionally, we provide statistical scaling factors that can be used to empirically correct for vibration-rotation effects, as a means to further improve the accuracy of rotational constants predicted from these relatively low-cost theoretical methods. As part of this, we demonstrate that the uncertainties can be used in simulations of rotational spectra to cross-correlate with broadband spectra, a methodology that could be used to quickly and efficiently survey experimental spectra for new molecules. | 10.1021/acs.jpca.9b09982 |
pubmed_840_10292 | A system of hydrodynamic equations in the presence of large-scale inhomogeneities for a high plasma beta solar wind is derived. The theory is derived under the assumption of low turbulent Mach number and is developed for the flows where the usual incompressible description is not satisfactory and a full compressible treatment is too complex for any analytical studies. When the effects of compressibility are incorporated only weakly, a new description, referred to as "nearly incompressible hydrodynamics," is obtained. The nearly incompressible theory, was originally applied to homogeneous flows. However, large-scale gradients in density, pressure, temperature, etc., are typical in the solar wind and it was unclear how inhomogeneities would affect the usual incompressible and nearly incompressible descriptions. In the homogeneous case, the lowest order expansion of the fully compressible equations leads to the usual incompressible equations, followed at higher orders by the nearly incompressible equations, as introduced by Zank and Matthaeus. With this work we show that the inclusion of large-scale inhomogeneities (in this case time-independent and radially symmetric background solar wind) modifies the leading-order incompressible description of solar wind flow. We find, for example, that the divergence of velocity fluctuations is nonsolenoidal and that density fluctuations can be described to leading order as a passive scalar. Locally (for small lengthscales), this system of equations converges to the usual incompressible equations and we therefore use the term "locally incompressible" to describe the equations. This term should be distinguished from the term "nearly incompressible," which is reserved for higher-order corrections. Furthermore, we find that density fluctuations scale with Mach number linearly, in contrast to the original homogeneous nearly incompressible theory, in which density fluctuations scale with the square of Mach number. Inhomogeneous nearly incompressible equations for higher order fluctuation components are derived and it is shown that they converge to the usual homogeneous nearly incompressible equations in the limit of no large-scale background. We use a time and length scale separation procedure to obtain wave equations for the acoustic pressure and velocity perturbations propagating on fast-time-short-wavelength scales. On these scales, the pseudosound relation, used to relate density and pressure fluctuations, is also obtained. In both cases, the speed of propagation (sound speed) depends on background variables and therefore varies spatially. For slow-time scales, a simple pseudosound relation cannot be obtained and density and pressure fluctuations are implicitly related through a relation which can be solved only numerically. Subject to some simplifications, a generalized inhomogeneous pseudosound relation is derived. With this paper, we extend the theory of nearly incompressible hydrodynamics to flows, including the solar wind, which include large-scale inhomogeneities (in this case radially symmetric and in equilibrium). | 10.1103/PhysRevE.74.026302 |
pubmed_425_9528 | INTRODUCTION
Following bariatric surgery, ongoing postoperative testing is required to measure nutritional deficiencies; the purpose of this study was to quantify the prevalence of these nutritional deficiencies based on two-year follow-up tests at recommended time points.
METHODS AND PROCEDURES
A retrospective data analysis was conducted of all laboratory tests for bariatric patients who underwent surgery between May 2016 and January 2018 with available lab data (n = 397). Results for nine different nutritional labs were categorized into six recommended postoperative time periods based on time elapsed since the procedure date. Binary variables were created for each laboratory result to calculate descriptive statistics of abnormalities for each lab test over time and used in the individual GEE logistic regression models. Grouped logistic regression examined the total nutritional deficiencies of the nine combined nutrients considering total available labs.
RESULTS
Multiple lab tests indicated a very low frequency of abnormalities (e.g., Vitamin A, Vitamin B12, Copper, and Folate). Many of the nine included nutritional labs had an average deficiency of less than 10% across all time points. The grouped logistic model found preoperative nutritional deficiency to be predictive of postoperative nutritional deficiency (OR 3.70, p < 0.001).
CONCLUSIONS
We found the vast majority of routine lab test results to be normal at multiple time points. Current practice can add up to significant lab expenses over time. The frequency of postoperative testing in this population may be redundant and of very little value. Unnecessary follow-up laboratory testing costs the patients and the health care system in both time and resources. Patients with preoperative deficiencies appear to be at higher risk for nutritional deficiencies when compared to bariatric surgery patients that did not have preoperative nutritional deficiencies. Future research should focus on defining cost effective postoperative lab testing guidelines for at risk bariatric patients. | 10.1007/s00464-019-07216-9 |
pubmed_995_17622 | Three experiments were conducted to investigate hemispheric asymmetry for the perception of emotional sounds. Pairs of human nonspeech sounds were presented dichotically in a forced choice recognition task. Under divided attention conditions (Experiments 1 and 2) an left ear advantage (LEA) emerged during the second block of trials. Performance accuracy for the left and right ears was equal during the first block of trials. Under selective attention conditions (Experiment 3) an LEA emerged during the first block of trials. The results suggest that attention influences the rate of development of the laterality effect but not the direction of the effect. | 10.1016/0278-2626(87)90122-9 |
pubmed_87_2468 | Stylonychia lemnae is a classical model single-celled eukaryote, and a quintessential ciliate typified by dimorphic nuclei: A small, germline micronucleus and a massive, vegetative macronucleus. The genome within Stylonychia's macronucleus has a very unusual architecture, comprised variably and highly amplified "nanochromosomes," each usually encoding a single gene with a minimal amount of surrounding noncoding DNA. As only a tiny fraction of the Stylonychia genes has been sequenced, and to promote research using this organism, we sequenced its macronuclear genome. We report the analysis of the 50.2-Mb draft S. lemnae macronuclear genome assembly, containing in excess of 16,000 complete nanochromosomes, assembled as less than 20,000 contigs. We found considerable conservation of fundamental genomic properties between S. lemnae and its close relative, Oxytricha trifallax, including nanochromosomal gene synteny, alternative fragmentation, and copy number. Protein domain searches in Stylonychia revealed two new telomere-binding protein homologs and the presence of linker histones. Among the diverse histone variants of S. lemnae and O. trifallax, we found divergent, coexpressed variants corresponding to four of the five core nucleosomal proteins (H1.2, H2A.6, H2B.4, and H3.7) suggesting that these ciliates may possess specialized nucleosomes involved in genome processing during nuclear differentiation. The assembly of the S. lemnae macronuclear genome demonstrates that largely complete, well-assembled highly fragmented genomes of similar size and complexity may be produced from one library and lane of Illumina HiSeq 2000 shotgun sequencing. The provision of the S. lemnae macronuclear genome sets the stage for future detailed experimental studies of chromatin-mediated, RNA-guided developmental genome rearrangements. | 10.1093/gbe/evu139 |
pubmed_1052_16716 | With rapidly changing technology, prediction of candidate genes has become an indispensable task in recent years mainly in the field of biological research. The empirical methods for candidate gene prioritization that succors to explore the potential pathway between genetic determinants and complex diseases are highly cumbersome and labor intensive. In such a scenario predicting potential targets for a disease state through in silico approaches are of researcher's interest. The prodigious availability of protein interaction data coupled with gene annotation renders an ease in the accurate determination of disease specific candidate genes. In our work we have prioritized the cervix related cancer candidate genes by employing Csaba Ortutay and his co-workers approach of identifying the candidate genes through graph theoretical centrality measures and gene ontology. With the advantage of the human protein interaction data, cervical cancer gene sets and the ontological terms, we were able to predict 15 novel candidates for cervical carcinogenesis. The disease relevance of the anticipated candidate genes was corroborated through a literature survey. Also the presence of the drugs for these candidates was detected through Therapeutic Target Database (TTD) and DrugMap Central (DMC) which affirms that they may be endowed as potential drug targets for cervical cancer. | 10.1039/c4mb00004h |
pubmed_403_21145 | Leiomyosarcoma is an aggressive soft-tissue malignancy derived from smooth muscle cells that rarely affects the oral cavity. We discuss the case of an 11-year-old boy with leiomyosarcoma that presented initially as a gingival swelling over his unerupted mandibular right permanent second molar. We highlight how appropriate imaging, prompt follow-up, and biopsy led to early diagnosis and ultimately a favorable clinical outcome. | pubmed_403_21145 |
pubmed_970_9381 | BACKGROUND
The search for new antimicrobial drugs is a never-ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to humankind.
OBJECTIVE
The present studies were aimed at synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones.
MATERIALS AND METHODS
FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against different bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict the toxicity profile of the compounds using FAFDrugs2 predictor.
RESULTS AND DISCUSSION
The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives.
CONCLUSION
Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process. | 10.2174/1570179417666200407130122 |
pubmed_534_4382 | Nuclear or radiological terrorism in the form of uncontrolled radioactive contamination presents a unique challenge in the field of nuclear decontamination. Potential targets require an immediate decontamination response, or mitigation plan to limit the social and economic impact. To date, experience with urban decontamination of building materials - specifically hard, porous, external surfaces - is limited to nuclear weapon fallout and nuclear reactor accidents. Methods are lacking for performing wide-area decontamination in an urban environment so that in all release scenarios the area may be re-occupied without evaluation and/or restriction. Also lacking is experience in developing mitigation strategies, that is, methods of mitigating contamination and its resultant radiation dose in key areas during the immediate aftermath of an event and after lifesaving operations. To date, the tremendous strategy development effort primarily by the European community has focused on the recovery phase, which extends years beyond the release event. In this review, we summarize the methods and data collected over the past 70 years in the field of hard, external surface decontamination of radionuclide contaminations, with emphasis on methods suitable for response to radiological dispersal devices and their potentially unique physico-chemical characteristics. This review concludes that although a tremendous amount of work has been completed primarily by the European Community (EU) and the United Kingdom (UK), the few studies existing on each technique permit only very preliminary estimates of decontamination factors for various building materials and methods and extrapolation of those values for use in environments outside the EU and UK. This data shortage prevents us from developing an effective and detailed mitigation response plan and remediation effort. Perhaps most importantly, while the data available does include valuable information on the practical aspects of performing the various remediation methods including costs, coverage rates, manpower, pitfalls, etc., it lacks the details on lessons learned, best practices, and standard procedures, for instance, that would be required to develop a mitigation strategy. While the urban decontamination problem is difficult and there is much more research to do, the existing literature provides a framework for a response plan. Using this framework, in conjunction with computer modeling and relevant data collection, can lead to development of appropriate plans and exercises that would permit development of a mitigation and remediation response. | 10.1016/j.jhazmat.2015.11.014 |
pubmed_972_5847 | BACKGROUND
Growing antibiotic resistance warrants studying nonantibiotic prophylaxis for recurrent urinary tract infections (UTIs). Use of lactobacilli appears to be promising.
METHODS
Between January 2005 and August 2007, we randomized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim-sulfamethoxazole, 480 mg, once daily or oral capsules containing 109 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. Primary end points were the mean number of symptomatic UTIs, proportion of participants with at least 1 UTI during 12 months, time to first UTI, and development of antibiotic resistance by Escherichia coli.
RESULTS
The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, after 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The between-treatment difference of 0.4 UTIs per year (95% CI, -0.4 to 1.5) was outside our noninferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the trimethoprim-sulfamethoxazole and lactobacilli participants, respectively; median times to the first UTI were 6 and 3 months, respectively. After 1 month of trimethoprim-sulfamethoxazole prophylaxis, resistance to trimethoprim-sulfamethoxazole, trimethoprim, and amoxicillin had increased from approximately 20% to 40% to approximately 80% to 95% in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI. During the 3 months after trimethoprim-sulfamethoxazole discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis.
CONCLUSIONS
In postmenopausal women with recurrent UTIs, L rhamnosus GR-1 and L reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with trimethoprim-sulfamethoxazole. However, unlike trimethoprim-sulfamethoxazole, lactobacilli do not increase antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094. | 10.1001/archinternmed.2012.777 |
pubmed_187_18765 | Arachidonic acid (AA) is known to inhibit intercellular conductance in normal and tumour cells. We showed that junctional conductance (Gj) in isolated murine hepatocytes was relatively tolerant to the uncoupling effect of AA. Extracellular application of 100 microM AA decreased Gj in less than 50% of hepatocytes, and the effect was much slower in other cells (10-15 min vs. 2-5 min, respectively). The uncoupling effect of AA did not depend on the intracellular [Ca2+] within the pCa(i) range 7.7-9.0. Similar results were obtained using the pipette-filling solutions with low (1 mM) and high (10 mM) concentrations of a Ca-chelating agent (EGTA). To verify whether the resistance of the hepatocyte Gj to AA may result from the "wash-out" of the intracellular intermediates during the intracellular dialysis, Gj was measured 10-45 min after the preincubation of hepatocytes with AA. After such a treatment, in 62% of cell pairs the Gj values recorded did not differ from the control. Extracellular or intracellular acidification (pHo 6.0 or pHi 5.0-6.0) did not markedly affect the AA action. However, in some cases AA induced the recovery of Gj blocked after intracellular acidification, the phenomenon suggesting the activation of the H+ transport in the presence of AA. Possible mechanisms of the observed resistance of junctional conductance of mouse hepatocytes in primary culture are discussed. | pubmed_187_18765 |
pubmed_656_18412 | The evolution of superconformal Cu electrodeposition in high aspect ratio through silicon vias (TSVs) is examined as a function of polymer suppressor concentration, applied potential and hydrodynamics. Electroanalytical measurements in a CuSO4-H2SO4-Cl electrolyte are used to explore and quantify the effect of such parameters on the metal deposition process. Hysteretic voltammetry due to suppressor breakdown reveals an S-shaped negative differential resistance that leads to non-linear spatial-temporal patterning during metal deposition. For the given hydrodynamic conditions, cyclic voltammetry reveals the potential regime over which positive-feedback gives rise to the superconformal feature filling dynamic. Breakdown of suppression is primarily related to polymer concentrations in the electrolyte while its reformation is dependent on its transport to the interface. Morphological evolution during the early stages of TSV filling reveals two distinct growth front geometries. For dilute polymer concentrations, an initial bifurcation into passive-active surfaces occurs on the side walls of the TSVs followed by bottom-up fill. The depth of the initial sidewall bifurcation within the via increases with polymer concentration. For higher polymer concentrations, i.e. ≥ 25 μmol/L, active metal deposition is rapidly confined to the bottom surface of the via followed by sustained bottom-up filling. | pubmed_656_18412 |
pubmed_770_3550 | We have investigated uptake of 125I-labeled chylomicron remnants into livers of rats in the presence of lactoferrin. This glycoprotein possesses a cluster of four arginines at the N-terminus similar to the arginine rich binding sequence of apoprotein E (apoE) to the LDL-receptor. We found that this protein inhibits uptake of 125I-chylomicron remnant radioactivity by 50% when measured as accumulation of radioactivity into the intact organ, and even more pronounced, over 75%, when measured as uptake into an endosomal fraction prepared therefrom. Provided that the arginine rich sequence is responsible for the inhibition, a similarity in the characteristics of binding of apoE to the LDL (low density lipoprotein)- and chylomicron remnant-receptor is likely. Second, transferrin having sequence homologies with lactoferrin, but lacking the arginine cluster does not interfere with chylomicron remnant uptake. Third, lactoferrin does not inhibit the uptake of chylomicron remnants by the spleen, which is most likely mediated through scavenger cells by a mechanism different from the chylomicron remnant uptake system of the liver. We hypothesize from this that lactoferrin specifically interferes with the physiologically relevant chylomicron remnant uptake system of the liver. Investigation of the mechanism of this inhibition will provide information about the physical characteristics of the remnant receptor system. | 10.1016/s0009-9120(88)80093-6 |
pubmed_578_12357 | OBJECTIVE
To determine the quality of the evidence for the uses of fluoroscopy in dentistry.
METHODS
A systematic review using Ovid and MEDLINE was conducted to identify papers showing the uses of fluoroscopy in dentistry published between 1953 and September 2009. Human, animal and phantom/skull/mannequin studies on fluoroscopy with regard to its diagnostic value, research performance, and clinical and safety applications in dentistry were included in this analysis. Studies that were not in English, as well as those that employed fluoroscopy in dentistry without the use of image intensification, were excluded. Articles were evaluated, classified and graded by levels of evidence.
RESULTS
Fifty-five out of 139 papers fulfilled the inclusion criteria. Amongst them, 19 were related to diagnosis, 15 to research, 12 to clinical and nine to safety applications. Fluoroscopy has contributed to nine different areas of dentistry. Also, it was used on 895 dental patients, 37 animals and 17 phantoms/skulls/mannequins. Two randomised controlled trials, two cohort studies, two case controls, 48 case reports and one expert opinion were found.
CONCLUSION
Fluoroscopy with image intensification has been a useful, but not consistently used tool in dentistry for over 50 years. Several lines of evidence have shown fluoroscopy's diagnostic potential, research use, and clinical and safety applications in dentistry. | pubmed_578_12357 |
pubmed_769_19899 | INTRODUCTION
Postoperative thoracogastric necrosis (TGN) associated with thoracogastric-tracheal fistula (TGTF) of an endoscopic McKeown-type resection of esophageal carcinoma is rare and has a poor prognosis and high mortality. Few cases have been reported and successful treatment is rare. Surgery is the major treatment option.
PATIENT CONCERNS
A 71-year-old man was hospitalized in a local hospital for more than 2 months due to dysphagia. The patient was previously healthy and had no underlying diseases.
DIAGNOSIS
TGN associated with TGTF of an endoscopic McKeown-type resection of esophageal carcinoma.
INTERVENTION
Two-stage surgeries were performed.
OUTCOME
The patient recovered well at the time of the follow-up examination on April 4, 2021 with an ECOG score of 0.
CONCLUSION
Staging surgery can be an alternative treatment for TGN associated with TGTF of an endoscopic McKeown-type resection of esophageal carcinoma. | 10.1097/MD.0000000000028755 |
pubmed_486_14781 | BACKGROUND
Endoscopic ultrasonography (EUS) and narrow band imaging-magnifying endoscopy (NBI-ME) are often used as diagnostic tools to estimate the depth of invasion in early colorectal cancer (CRC). The aim of this study was to compare NBI-ME with EUS in distinguishing between slight submucosal invasion (invasion depth < 1000 μm) and massive submucosal invasion in patients with early CRC, since slight submucosal invasion is currently considered as an indication for endoscopic resection.
METHODS
For this meta-analysis, relevant studies were identified from PubMed, Embase, Web of Science, Scopus and the Cochrane Library databases between January 1997 and September 2016. Data on the yield of tumors were extracted, pooled, and analyzed by stata12.0 software. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio in differentiating slight submucosal invasion from massive submucosal invasion were calculated for both diagnostic modalities.
RESULTS
Sixteen studies involving 2197 lesions were included: nine were studies on EUS and 7 were studies on NBI-ME. The pooled sensitivity of EUS was 0.902 (95% CI 0.863-0.930), the specificity was 0.877 (95% CI 0.810-0.922), the positive likelihood ratio was 7.314 (95% CI 4.551-11.755) and the negative likelihood ratio was 0.112 (95% CI 0.076-0.164). The pooled sensitivity and specificity of NBI-ME were 0.981 (95% CI 0.949-0.993) and 0.651 (95% CI 0.600-0.699), respectively, the positive likelihood ratio was 2.815 (95% CI 2.432-3.258) and the negative likelihood ratio was 0.029 (95% CI 0.010-0.080).
CONCLUSIONS
The sensitivity tended to be higher in ME-NBI than EUS for early CRC with slight submucosal invasion, whereas the specificity was significantly lower in NBI-ME than in EUS. | 10.1007/s10151-019-02076-w |
pubmed_9_9903 | Large unilamellar liposomes (d approximately 160 nm) composed of dioleoylphosphatidylethanolamine (DOPE) (80-90%), a negatively charged phospholipid stabilizer (10-20%), and a small amount (0.1-1%) of a haptenated lipid are unusually stable in divalent cation-free isotonic buffer at pH 7.4. The liposomes can be stored under this condition at 4 degrees C for at least 6 months without any detectable leakage of the entrapped fluorescent dye calcein. However, the liposomes undergo a rapid (1 h) aggregation and lysis reaction in the presence of free bivalent anti-hapten antibody. The liposome destabilization was immunospecific in that it did not occur with the normal IgG or in the presence of excess free hapten. Liposome lysis was always accompanied by liposome aggregation. Aggregation and lysis of the liposomes was completed in 5 min if the incubation temperature was raised to 70-80 degrees C. Replacing DOPE with dioleoylphosphatidylcholine in the liposomes did not abolish the liposome aggregation, but no liposome lysis was observed even at 80 degrees C. Since liposome aggregation appeared to be a necessary (but not sufficient) prerequisite for liposome lysis, we have named this new class of liposome "contact-sensitive liposomes." The immunodiagnostic potential of the contact-sensitive liposome was demonstrated with liposomes containing theophylline-DOPE. The aggregation and lysis of the liposomes induced by a monoclonal anti-theophylline antibody could be inhibited by free theophylline at concentrations of therapeutic significance. The observation could be the basis of a homogeneous assay for theophylline. | 10.1021/bc00021a003 |
pubmed_861_10967 | Hypercholesterolemia is common in captive Psittaciformes. A point-of-care cholesterol analyzer would be useful to monitor hypercholesterolemia in psittacine birds. We compare a point-of-care cholesterol analyzer (PTS-Diagnostics CardioChek) with a reference laboratory analyzer (Roche Cobas c501) and provide initial assessment of precision and accuracy. A prospective method comparison study was designed to compare the CardioChek and Cobas c501 by assessment of clinical and analytical agreement using Passing-Bablock regression analysis and difference plots. Initial accuracy was assessed by running cholesterol standards, and initial precision was assessed by calculating between-run coefficient of variation on samples from selected birds. A total of 42 psittacine birds were sampled. No significant constant bias was found between the Cobas and CardioChek. However, a significant negative proportional bias was evident, suggesting that the point-of-care analyzer tended to underestimate cholesterol values. Lipemia and hemolysis had strong effects on increasing bias. Hematocrit, glucose level, and genus had no significant impact on bias, controlling for lipemia and hemolysis. Accuracy of the CardioCheck was suboptimal to that of the Cobas, but precision was good. When defining hypercholesterolemia as >8 mmol/L (309 mg/dL), the CardioChek had a sensitivity of 57% and specificity of 96%. There was neither analytical nor clinical agreement between the CardioChek and Cobas c501. Values obtained from the CardioChek cannot be used to determine or monitor hypercholesterolemia in parrots in the absence of analyzer-specific reference intervals. | 10.1647/2017-291 |
pubmed_1034_12761 | Glycan-binding proteins, which include galectins, are involved at all stages of immunity and inflammation, from initiation through resolution. Galectin-9 (Gal-9) is highly expressed in the liver and has a wide variety of biological functions in innate and adaptive immunity that are instrumental in the maintenance of hepatic homeostasis. In the setting of viral hepatitis, increased expression of Gal-9 drives the expansion of regulatory T cells and contraction of effector T cells, thereby favoring viral persistence. The dichotomous nature of Gal-9 is evident in hepatocellular carcinoma, where loss of expression in hepatocytes promotes tumor growth and metastasis, whereas overexpression by Kupffer cells and endothelial cells inhibits the antitumor immune response. In nonalcoholic fatty liver disease, Gal-9 is involved indirectly in the expansion of protective natural killer T-cell populations. In ischemic liver injury, hepatocyte-derived Gal-9 is both diagnostic and cytoprotective. In drug-induced acute liver failure, plasma levels correlate with outcome. Here, we offer a synthesis of recent and emerging findings on Gal-9 in the regulation of hepatic inflammation. Ongoing studies are warranted to better elucidate the pathophysiology of hepatic immune-mediated diseases and to develop new therapeutic interventions using glycan-binding proteins. (Hepatology 2017;66:271-279). | 10.1002/hep.29106 |
pubmed_1050_21054 | TIA1, a protein critical for eukaryotic stress response and stress granule formation, is structurally characterized in full-length form. TIA1 contains three RNA recognition motifs (RRMs) and a C-terminal low-complexity domain, sometimes referred to as a "prion-related domain" or associated with amyloid formation. Under mild conditions, full-length (fl) mouse TIA1 spontaneously oligomerizes to form a metastable colloid-like suspension. RRM2 and RRM3, known to be critical for function, are folded similarly in excised domains and this oligomeric form of apo fl TIA1, based on NMR chemical shifts. By contrast, the termini were not detected by NMR and are unlikely to be amyloid-like. We were able to assign the NMR shifts with the aid of previously assigned solution-state shifts for the RRM2,3 isolated domains and homology modeling. We present a micellar model of fl TIA1 wherein RRM2 and RRM3 are colocalized, ordered, hydrated, and available for nucleotide binding. At the same time, the termini are disordered and phase separated, reminiscent of stress granule substructure or nanoscale liquid droplets. | 10.1073/pnas.2007423117 |
pubmed_1127_16333 | An extremely rare subset of patients infected with HIV-1 designated as "non-progressing elite controllers" appears to be able to maintain stable CD4(+) T-cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (<50-80 copies/ml of plasma) for >10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4(+), CD8(+)), immune activation markers (HLA-DR(+), CD38(+), Beta-2-microglobulin), and HIV-specific antibody responses were longitudinally examined in four non-progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV-1 presenting detectable viremia were also included. None of the non-progressing elite controllers displayed the high T-cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non-progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV-1-specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV-1. One non-progressing elite controller exhibited CD8(+) T-cell counts and beta2-M levels above normal ranges and developed a low but "mature" (high-avidity) HIV-1-specific antibody response. Thus, the non-progressing elite controllers are able to maintain normal T-cell activation levels, which may contribute to prevent, or greatly reduce, the damage of the immune system typically induced by the HIV-1 over time. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV-1-specific immunity. | 10.1002/jmv.21565 |
pubmed_217_14572 | Pyrolysin-like proteases from hyperthermophiles are characterized by large insertions and long C-terminal extensions (CTEs). However, little is known about the roles of these extra structural elements or the maturation of these enzymes. Here, the recombinant proform of Pyrococcus furiosus pyrolysin (Pls) and several N- and C-terminal deletion mutants were successfully expressed in Escherichia coli. Pls was converted to mature enzyme (mPls) at high temperatures via autoprocessing of both the N-terminal propeptide and the C-terminal portion of the long CTE, indicating that the long CTE actually consists of the C-terminal propeptide and the C-terminal extension (CTEm), which remains attached to the catalytic domain in the mature enzyme. Although the N-terminal propeptide deletion mutant PlsΔN displayed weak activity, this mutant was highly susceptible to autoproteolysis and/or thermogenic hydrolysis. The N-terminal propeptide acts as an intramolecular chaperone to assist the folding of pyrolysin into its thermostable conformation. In contrast, the C-terminal propeptide deletion mutant PlsΔC199 was converted to a mature form (mPlsΔC199), which is the same size as but less stable than mPls, suggesting that the C-terminal propeptide is not essential for folding but is important for pyrolysin hyperthermostability. Characterization of the full-length (mPls) and CTEm deletion (mPlsΔC740) mature forms demonstrated that CTEm not only confers additional stability to the enzyme but also improves its catalytic efficiency for both proteineous and small synthetic peptide substrates. Our results may provide important clues about the roles of propeptides and CTEs in the adaptation of hyperthermophilic proteases to hyperthermal environments. | 10.1128/AEM.00548-12 |
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