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pubmed_143_19488 | OBJECTIVES
No previous studies have assessed the role of the FRAIL scale in predicting long-term outcomes in older patients with acute coronary syndromes (ACS).
DESIGN, SETTING AND PARTICIPANTS
The multicenter observational LONGEVO-SCA registry included unselected patients ≥80 years of age with ACS from 44 centers. A comprehensive geriatric assessment was performed during hospitalization.
MEASURES
Frailty was measured by the FRAIL scale. For the purpose of this study, main outcome measured was mortality or readmission at 24 months.
RESULTS
A total of 498 patients were included. Mean age was 84.3 years. A total of 198 patients (33.1%) were prefrail and 135 (27.1%) frail. Patients who were prefrail and frail had a higher degree of comorbidities, and higher prevalence of disability, cognitive impairment, and nutritional risk. A total of 165 out of 498 patients (33.1%) died, and 331 patients (66.7%) died or were readmitted at 24 months. Both prefrailty and frailty were associated with a higher mortality compared with robust patients (P < .001). The incidence of mortality or readmission was also higher in patients who were prefrail or frail (P < .001). After adjusting for potential confounders, the association between frailty and mortality or readmission remained significant (hazard ratio 1.28 for prefrailty and hazard ratio 1.96 for frailty, P < .001). The FRAIL scale showed an optimal ability for predicting mortality or readmission (area under the receiver operating characteristics curve 0.86, 95% confidence interval 0.83‒0.89). The area under the receiver operating characteristics curve from the Global Registry of Acute Coronary Events risk score was 0.89. No significant differences were observed between both AUC values (P = .163).
CONCLUSIONS AND IMPLICATIONS
The FRAIL scale independently predicted long-term outcomes in older patients with ACS. The predictive ability of this scale was comparable to the strongly recommended Global Registry of Acute Coronary Events risk score. Frailty assessment is mandatory for improving risk prediction in these complex patients. | 10.1016/j.jamda.2019.10.007 |
pubmed_673_10461 | The concentration of mast cells was estimated, and their distribution noted, in 132 benign nerve sheath tumours. With few exceptions, neurofibromas were characterised by a high concentration of diffusely distributed mast cells. In neurilemmomas fewer mast cells were present and these were restricted to Antoni type-B tissue. Based on these observations, and on the behaviour of mast cells in injured nerves, it is postulated that neurilemmomas are true neoplasms of Schwann cells sometimes incorporating reactive endoneurial tissue (Antoni type-B tissue). Neurofibromas probably consist of reactive endoneurial tissue and may not be true neoplasms. The distinction between neurofibromas and neurilemmomas thus seems to be a real one based on a difference in histogenesis. | 10.1002/path.1711190402 |
pubmed_186_4342 | Interstitial pregnancy (IP) occurs within the intramural portion of the tube and accounts for 2% of ectopic pregnancies. Surgery is considered the most definitive treatment for IPs, although there is no clear consensus regarding the optimal approach. In this paper we describe the advantages of cornual resection performed using the Endoloop technique and present three patients who were successfully treated using this approach. IP diagnosis was confirmed at two and three-dimensional ultrasound and laparoscopy in all cases. Fertility sparing surgery with cornuectomy by Endoloop ligature technique demonstrated low mean operating time and blood loss, and allowed the quick recovery and discharge of all patients. Laparoscopy has become the gold standard surgical approach for IP. Cornual resection or excision is the most commonly performed procedure. In our case series, the Endoloop technique showed excellent treatment outcomes in terms of effectiveness, blood loss, operative time, recovery and post-procedure fertility. Because of these features, Endoloop appears to be a suitable option for the laparoscopic management of IPs, both in elective and emergency settings. | 10.1111/jog.13005 |
pubmed_273_2955 | In the arsenal of tools that a computational modeller can bring to bare on the study of cardiac arrhythmias, the most widely used and arguably the most successful is that of an excitable medium, a special case of a reaction-diffusion model. These are used to simulate the internal chemical reactions of a cardiac cell and the diffusion of their membrane voltages. Via a number of different methodologies it has previously been shown that reaction-diffusion systems are at multiple levels Turing complete. That is, they are capable of computation in the same manner as a universal Turing machine. However, all such computational systems are subject to a limitation known as the Halting problem. By constructing a universal logic gate using a cardiac cell model, we highlight how the Halting problem therefore could limit what it is possible to predict about cardiac tissue, arrhythmias and re-entry. All simulations for this work were carried out on the GPU of an XBox 360 development console, and we also highlight the great gains in computational power and efficiency produced by such general purpose processing on a GPU for cardiac simulations. | 10.1016/j.compbiolchem.2009.05.001 |
pubmed_1112_6745 | A total of 167 ticks collected from humans in Istanbul (Turkey) in 2006 were screened for Rickettsia species, and nested PCRs targeting gltA and ompA rickettsial fragment genes were carried out. Rickettsia monacensis (51), R. aeschlimannii (8), R. conorii subsp. conorii (3), R. helvetica (2), R. raoultii (1), R. africae (1), R. felis (1), and other Rickettsia spp. (2), were detected. To our knowledge, these Rickettsia species (except R. conorii) had never been reported in ticks removed from humans in Turkey. The presence of R. africae also had not been previously described, either in Hyalomma ticks or in any European tick species. In addition, R. aeschlimannii and R. felis had not been found associated with Rhipicephalus bursa specimens. The presence of human pathogenic Rickettsia in ticks removed from humans provides information about the risk of tick-borne rickettsioses in Turkey. | 10.1089/vbz.2012.0996 |
pubmed_98_15629 | INTRODUCTION
The COVID-19 pandemic has increased the magnitude of mental illnesses such as depression, not only in the general population, but also in health personnel. However, in Peru the prevalence is not known and the associated factors for developing depression in health personnel are not known.
OBJECTIVE
To determine the prevalence and identify the factors associated with depression in health personnel, in the context of the SARS-CoV-2 pandemic.
MATERIAL AND METHOD
An analytical cross-sectional study was carried out between the months of May-September in health establishments. A sample of 136 health workers were included and a survey was applied to collect the data. Depression as a dependent variable was measured using the Zung self-report scale. To identify the associated factors, the bivariate and multivariate analysis was performed by logistic regression with STATA v 14.
RESULTS
The prevalence of depression was 8.8% CI 95% (4.64-14.90), likewise, the antecedent of having a family member or friend died from COVID-19 with a p value of 0.017 and OR of 6.78 (CI: 1.39-32.90). On the other hand, the use of personal protective equipment (PPE) was found to be a protective factor against the development of depression with p value 0.003 and OR of 0.03 (CI: 0.004-0.32).
CONCLUSIONS
Approximately 1 in 10 among health professionals and technicians developed depression during the SARS-CoV-2 pandemic in this study. In addition, the history of having relatives or friends killed by COVID-19 was negatively associated with depression and the use of PPE was identified as a protective factor for depression. | 10.1016/j.rcp.2021.11.005 |
pubmed_572_23354 | Recently, amorphous InGaZnO ultraviolet photo thin-film transistors have exhibited great potential for application in future display technologies. Nevertheless, the transmittance of amorphous InGaZnO (~80%) is still not high enough, resulting in the relatively large sacrifice of aperture ratio for each sensor pixel. In this work, the ultraviolet photo thin-film transistor based on amorphous InGaMgO, which processes a larger bandgap and higher transmission compared to amorphous InGaZnO, was proposed and investigated. Furthermore, the effects of post-deposition annealing in oxygen on both the material and ultraviolet detection characteristics of amorphous InGaMgO were also comprehensively studied. It was found that oxygen post-deposition annealing can effectively reduce oxygen vacancies, leading to an optimized device performance, including lower dark current, higher sensitivity, and larger responsivity. We attributed it to the combined effect of the reduction in donor states and recombination centers, both of which are related to oxygen vacancies. As a result, the 240-min annealed device exhibited the lowest dark current of 1.7 × 10-10 A, the highest photosensitivity of 3.9 × 10⁶, and the largest responsivity of 1.5 × 10⁴ A/W. Therefore, our findings have revealed that amorphous InGaMgO photo thin-film transistors are a very promising alternative for UV detection, especially for application in touch-free interactive displays. | 10.3390/ma10020168 |
pubmed_486_24692 | PURPOSE
We aimed to examine the prevalence of obesity among adolescents living in a refugee camp in Jordan and analyze the factors influencing their weight perceptions.
DESIGN
Cross-sectional survey.
METHODS
We examined the body weight perception, and the influence of psychological, cultural, and social factors, among Palestinian refugee adolescents living in Jordan using a cross-sectional survey. Univariate, bivariate, and multiple logistic regression analyses were used to investigate the relationships between body weight status, weight perception, satisfaction with weight, screen time, and depression status of these adolescents.
RESULTS
A total of 620 adolescents participated in the study, of which 24% were either overweight or obese. Overweight or obese adolescents were more likely to underestimate their weight (p < .001), while those with depressive symptoms (Patient Health Questionnaire for Adolescents score > 14), were more likely to overestimate their body weight (p = .021). Having symptoms indicative of depression (adjusted odds ratio [AOR] = 1.70; 95% confidence interval [CI] = 1.16-2.50) and having a body mass index in the overweight/obese range (AOR = 4.16; 95% CI = 2.73-6.35) were predictors of discordant weight perception.
CONCLUSIONS
This study showed that excess body weight is a significant issue among Palestinian refugee adolescents living in a refugee camp in Jordan. Underlying depression is an important factor in excess weight and distorted weight perceptions especially among this vulnerable group.
CLINICAL RELEVANCE
The study highlights the importance of addressing discordant body weight perception and depression in weight management in nursing interventions for vulnerable adolescent groups. | 10.1111/jnu.12517 |
pubmed_132_22961 | The distribution of amylase in rat parotid glands and von Ebner's glands was examined using ion etching-immunoscanning electron microscopy, which enables both light and electron microscopic observations of identical semi-thin resin sections immunolabeled with anti-α-amylase and immunogold in association with silver enhancement. At the light microscopic level, most acinar secretory granules (SG) and striated duct secretions of parotid glands were strongly stained dark brown. In von Ebner's glands, acinar SG and duct secretions were weakly to strongly stained light to dark brown. At the electron microscopic level, labeling was observed as bright gold-silver particles. The labeling intensity of acinar SG of parotid glands was higher than that of von Ebner's glands. In parotid glands, weak labeling of SG in transitional cells between acini and intercalated ducts, very weak labeling of SG in intercalated ducts, and strong labeling of striated duct secretions were observed. In von Ebner's glands, the secretions and some SG of interlobular ducts were strongly labeled compared to those of intralobular ducts and SG of acini. Less amylase was synthesized in von Ebner's acini compared to parotid acini, whereas von Ebner's ducts may secrete significantly more amylase to modify saliva than parotid ducts. | 10.1267/ahc.10039 |
pubmed_882_2627 | Correction for rigid object motion in helical CT can be achieved by reconstructing from a modified source-detector orbit, determined by the object motion during the scan. This ensures that all projections are consistent, but it does not guarantee that the projections are complete in the sense of being sufficient for exact reconstruction. We have previously shown with phantom measurements that motion-corrected helical CT scans can suffer from data-insufficiency, in particular for severe motions and at high pitch. To study whether such data-insufficiency artefacts could also affect the motion-corrected CT images of patients undergoing head CT scans, we used an optical motion tracking system to record the head movements of 10 healthy volunteers while they executed each of the 4 different types of motion ('no', slight, moderate and severe) for 60 s. From these data we simulated 354 motion-affected CT scans of a voxelized human head phantom and reconstructed them with and without motion correction. For each simulation, motion-corrected (MC) images were compared with the motion-free reference, by visual inspection and with quantitative similarity metrics. Motion correction improved similarity metrics in all simulations. Of the 270 simulations performed with moderate or less motion, only 2 resulted in visible residual artefacts in the MC images. The maximum range of motion in these simulations would encompass that encountered in the vast majority of clinical scans. With severe motion, residual artefacts were observed in about 60% of the simulations. We also evaluated a new method of mapping local data sufficiency based on the degree to which Tuy's condition is locally satisfied, and observed that areas with high Tuy values corresponded to the locations of residual artefacts in the MC images. We conclude that our method can provide accurate and artefact-free MC images with most types of head motion likely to be encountered in CT imaging, provided that the motion can be accurately determined. | 10.1088/0031-9155/61/4/1416 |
pubmed_294_3468 | The stability of zymodemes in clonal cultures of Trypanosoma cruzi derived from strain Y was followed. Reversible changes in the isoenzyme electrophoretic mobility pattern from type A to types B and C were observed after subculturing of cloned cultures in medium of different composition or after passage in newborn mice. Type A zymodeme was observed in clones grown in blood-containing media, while types B and C were found in clones and subclones grown in media progressively less rich in nutrients (10 and 5% fetal calf serum, respectively) and containing no blood. The change in zymodeme from type A to type B or C was associated with loss of infectivity, which could be recovered by passages in newborn mice. Parasites infective for mice always showed zymodeme A. Simultaneously with zymodeme change from type A to types B and C there is a decrease in the specific activity of G6PD and 6PGD. | 10.1006/expr.1993.1081 |
pubmed_631_10051 | Cultivation under hypoxia has beneficial effects on adipose-derived stem cells (ASCs). Despite a history of extensive research on the responses of ASCs to hypoxia, investigations have focused on functional alterations of ASCs. Therefore, we provide novel insight in this review into the cellular and molecular changes that occur in ASCs under hypoxic conditions. Hypoxia increases the proliferation and migration of ASCs by the generation of reactive oxygen species (ROS) and downstream phosphorylation of platelet-derived growth factor receptor-beta, ERK1/2, and Akt. Chronically, activation of these signaling pathways upregulates miR-210 via phosphorylation of NF-κB and Elk1. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) is a direct miR-210 target, and downregulation of PTPN2 mediates the proliferation and migration of ASCs during hypoxia. In addition, the paracrine effect of ASCs is enhanced under hypoxic conditions, irrespective of whether ROS are generated. Hypoxic preconditioning stabilizes hypoxia inducible factor-1α under hypoxic conditions and increases secretion of vascular endothelial growth factor, thereby improving the regenerative potential of ASCs. Therefore, understanding the cellular and molecular changes that occur during hypoxia is highly relevant for the development of novel ASC therapies. | 10.1002/cbin.10246 |
pubmed_949_5011 | The cellular distribution of the mRNAs encoding for the two isoforms of glutamate decarboxylase, GAD67 and GAD65, was analyzed by in situ hybridization histochemistry in the caudate nucleus and putamen of control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian squirrel monkeys. On brain sections processed with a radioactive and a digoxigenin-labeled cRNA probe, the GAD67 and GAD65 mRNAs were colocalized in virtually all labeled neurons of the caudate nucleus and putamen, in both control and MPTP-treated monkeys. Furthermore, neurons labeled with the GAD cRNAs constituted at least 90% of all striatal neurons, as estimated on adjacent Nissl-stained sections. In the two groups of monkeys, double-labeling experiments using a combination of radioactive GAD67 or GAD65 and digoxigenin-labeled preproenkephalin (PPE) cRNA probes showed that roughly half of all neurons labeled with the GAD cRNAs were also labeled with the PPE cRNA probe. When compared to controls, GAD67 and GAD65 mRNA levels were higher in the putamen, and to a lesser extent in the caudate nucleus, of MPTP-treated monkeys. Further analysis of labeling at the cellular level in a dorsolateral sector of the putamen revealed that GAD67 and GAD65 mRNA levels in MPTP-treated monkeys were increased in PPE-labeled (presumed striato-pallidal) neurons but not in PPE-unlabeled (presumed striato-nigral) neurons. Our results demonstrate that most neurons in the caudate nucleus and putamen of squirrel monkeys contain the mRNAs encoding for the two GAD isoforms. In addition, the selective increase in GAD mRNA levels in PPE-labeled neurons provides further evidence that striato-pallidal GABAergic neurons are hyperactive in MPTP-treated parkinsonian monkeys. | 10.1002/(SICI)1098-2396(199710)27:2<122::AID-SYN3>3.0.CO;2-G |
pubmed_590_15048 | Macromolecules confined within a nanoporous matrix experience entropic trapping when their dimensions approach the average pore size, leading to emergence of anomalous transport behavior that can be beneficial in separation applications. But the ability to exploit these effects in practical settings (e.g., electrophoretic separation of DNA) has been hindered by additional dispersion introduced as a consequence of the uncorrelated process by which the embedded macromolecules discretely hop from pore to pore. Here, we show how both the source and solution to these difficulties are intimately linked to the inherent dynamics of the underlying activated transport mechanism. By modulating the applied electric field at a frequency tuned to the characteristic activation timescale, a resonance condition can be established that synergistically combines accelerated mobility and reduced diffusion. This resonance effect can be precisely manipulated by adjusting the magnitude and period of the driving electric field, enabling enhanced separation performance and bi-directional transport of different-sized species to be achieved. Notably, these phenomena are readily accessible in ordinary hydrogels (as opposed to idealized nanomachined topologies) suggesting broad potential to apply them in a host of useful settings. | 10.1002/elps.201300644 |
pubmed_1053_9291 | The strong non-covalent interactions between T lymphocyte surface CD4 or CD8 molecules and the intracellular membrane-associated protein tyrosine kinase lck are likely to mediate the role of CD4 and CD8 molecules in the immune response. The delineation of the structural nature of the CD4/lck and CD8/lck complexes is important for the understanding of the biochemical and functional significance of the interactions. Complementary charged regions in the C-terminal intracytoplasmic portions of CD4 or CD8, and in the N-terminal region of protein tyrosine kinase lck were noted. Peptides spanning these regions, residues 417 to 429 of CD4 and 10 to 22 of lck, were found to specifically dissociate these two molecules in CD4/lck complexes. A structural model of the interaction that accounts for its high stability is proposed. | 10.1002/eji.1830200235 |
pubmed_808_9939 | Sulfonylureas are widely used class of drugs for the treatment of type 2 diabetes (T2DM). Recent research has demonstrated that SLCO1B3 functions as a determinant of the insulinotropic effect of glibenclamide at the tissue level. However, whether this gene can influence the efficacy of glibenclamide in type 2 diabetic patients is not currently well-understood. All of our study subjects were enrolled from the Xiaoke Pills Clinical Trial. The subjects were treated with glibenclamide, and followed for 48 weeks. The rs4149117 genotype (T334G) in the SLCO1B3 gene was identified by direct sequencing. Relationships between genotype and efficacy and safety outcomes were evaluated by logistic or linear regression models as appropriate. A total of 374 subjects were enrolled in this study. The average age was 54.4±8.9 years, the percentage of males was 52.9%, and 91% of participants finished the genotype analysis successfully. Logistic regression analysis demonstrated that there was no significant difference between genotype and treatment failure of glibenclamide under an additive genetic model after adjusting for age, sex, renal function and diabetes duration (OR=1.009, 95% CI 0.692-1.473, P=0.961). The linear regression model demonstrated that the rs4149117 mutation in SLCO1B3 was significantly associated with a reduction in FPG after 48 weeks of treatment, independent of age, sex, renal function and diabetes duration (P=0.017, beta=0.130). In safety outcome analysis, we observed that rs4149117 had no association with hypoglycaemia. The rs4149117 mutation in the SLCO1B3 gene is not associated with sulfonylurea efficacy. | 10.1055/s-0043-103968 |
pubmed_471_9456 | OBJECTIVES
The Patient Health Questionnaire-9 Modified (PHQ-9M) is a self-report tool used to assess the presence and severity of depressive symptoms in teenagers. Despite widespread use in primary care clinics and psychiatric settings, the PHQ-9M has not been validated nor are its psychometric properties adequately understood for the adolescent population. This study sought to examine the psychometrics of the PHQ-9M in treatment-seeking, depressed adolescents at a psychiatric psychopharmacology clinic who were concurrently assessed with the Children's Depression Rating Scale Revised (CDRS-R) and Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR).
METHODS
Adolescents (N = 160) aged 13 through 18 years with a diagnosis of major depressive disorder, determined on the basis of a clinical interview and semi-structured interview using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, were assessed for severity of depressive symptoms with the PHQ-9M, CDRS-R (adolescent interview only), and QIDS-A17-SR assessments at baseline, 4, and 8 weeks. Classical test theory analysis was used to evaluate the internal consistency and dimensionality of the PHQ-9M. Convergent validity was evaluated via intraclass correlations of the PHQ-9M with the CDRS-R and QIDS-A17-SR. Sensitivity to treatment response was also evaluated.
RESULTS
The internal consistency (Cronbach's coefficient α) at baseline, 4, and 8 weeks was 0.879, 0.859, and 0.827 for the PHQ-9M; 0.739, 0.835, and 0.867 for CDRS-R; and 0.712, 0.777, and 0.804 for QIDS-A17-SR, respectively. The PHQ-9M had moderate convergent validity with the CDRS-R but good convergent validity with the QIDS-A17-SR. The PHQ-9M was less sensitive to changes in symptom severity than the CDRS-R and QIDS-A17-SR.
CONCLUSIONS
The PHQ-9M appears to be a valid and reliable assessment tool for the severity of depressive symptoms in a psychiatric clinic setting. However, its utility as a treatment outcome measure may be limited compared with other available rating scales. | 10.1089/cap.2018.0112 |
pubmed_309_272 | Conway, T. W. (The University of Texas, Austin), E. M. Lansford, Jr., and W. Shive. Influence of phenylalanine analogues upon bacterial accumulation and incorporation of phenylalanine. J. Bacteriol. 85:141-149. 1963.-Phenylalanine accumulation and its relation to phenylalanine incorporation into trichloroacetic acid-insoluble material in Escherichia coli 9723 were studied with a variety of structural analogues of phenylalanine. Inhibition of phenylalanine-C(14) incorporation was exerted by analogues only when their concentration was sufficient to prevent the formation of 85 to 90% of the accumulated intracellular phenylalanine "pool," indicating that less than about 15% of the "free amino acid pool" of phenylalanine is essential for maintaining a normal rate of incorporation of phenylalanine into protein. Although certain analogues having high activity in inhibiting accumulation of phenylalanine showed low activity in preventing incorporation, no analogue was found that solely prevented accumulation. | 10.1128/jb.85.1.141-149.1963 |
others_153_15207 | Computed tomography (CT) was performed on 36 dogs with nasal aspergillosis to assess whether this imaging technique can be used to predict the success of a noninvasive intranasal infusion of enilconazole. A CT score based on the severity of the disease was given to each dog, prior to treatment, by dividing the nasal cavities and frontal sinuses into 8 anatomical regions. After therapy, the dogs were classified into 2 response groups (success group: dogs cured after 1 treatment; failure group: dogs needing more than 1 treatment or with treatment failure). No significant relationship on the logistic scale was found between the CT score and the response to treatment. High sensitivity (treatment failures correctly predicted) and specificity (treatment successes correctly predicted) could not be obtained at the same time, whatever the cut-off value chosen. The results of this study suggest that CT cannot predict the therapeutic success of nasal aspergillosis in dogs treated with a 1-hour infusion of enilconazole. However, dogs with a low score seem to be good candidates to respond after 1 treatmen | others_153_15207 |
pubmed_656_6268 | The multiplayer stochastic noncooperative tracking game (NTG) with conflicting target strategy and cooperative tracking game (CTG) with a common target strategy of the mean-field stochastic jump-diffusion (MFSJD) system with external disturbance is investigated in this study. Due to the mean (collective) behavior in the system dynamic and cost function, the designs of the NTG strategy and CTG strategy for target tracking of the MFSJD system are more difficult than the conventional stochastic system. By the proposed indirect method, the NTG and CTG strategy design problems are transformed into linear matrix inequalities (LMIs)-constrained multiobjective optimization problem (MOP) and LMIs-constrained single-objective optimization problem (SOP), respectively. The LMIs-constrained MOP could be solved effectively for all Nash equilibrium solutions of NTG at the Pareto front by the proposed LMIs-constrained multiobjective evolutionary algorithm (MOEA). Two simulation examples, including the share market allocation and network security strategies in cyber-social systems, are given to illustrate the design procedure and validate the effectiveness of the proposed LMI-constrained MOEA for all Nash equilibrium solutions of NTG strategies of the MFSJD system. | 10.1109/TCYB.2020.3018318 |
pubmed_177_16307 | Alzheimer's disease (AD) is marked by several cellular and molecular damage. Therefore, the therapeutic interest of multi-target molecules is increasingly justified. Polyphenols presenting multiple pharmacological effects would be more efficient. In this study, beneficial effects of trans ε-viniferin, a natural polyphenol were thus evaluated. This study reported that this stilbenoid (1) induced the disaggregation of amyloid β (Aβ) peptide and (2) rescued inflammation in murine primary neuronal cultures. These both effects are higher than those of resveratrol, and so, trans ε-viniferin could be a good therapeutic multi-target candidate. | 10.1016/j.mcn.2017.12.003 |
pubmed_1031_11969 | The mre genes of Escherichia coli and Bacillus subtilis are cell shape determination genes. Mutants affected in mre function are spheres instead of the normal rods. Although the mre determinants are not required for viability in E. coli, the mreB determinant is an essential gene in B. subtilis. Conflicting results have been reported as to whether the two membrane-associated proteins MreC and MreD are essential proteins. Furthermore, although the MreB protein has been studied in some detail, the roles of the MreC and MreD proteins in cell shape determination are unknown. We constructed a strain of B. subtilis in which expression of the mreC determinant is dependent upon the addition of isopropyl-beta-D-thiogalactopyranoside to the culture medium. Utilizing this conditional strain, it was shown that mreC is an essential gene in B. subtilis. Furthermore, it was shown that cells lacking sufficient quantities of MreC undergo morphological changes, namely, swelling and twisting of the cells, which is followed by cell lysis. Electron microscopy was utilized to demonstrate that a polymeric material accumulated at one side of the division septum of the cells and that the presence of this material correlated with the bending of the cell. The best explanation for the results is that the MreC protein is involved in the control of septal versus long-axis peptidoglycan synthesis, that cells lacking MreC perform aberrant septal peptidoglycan synthesis, and that lysis results from a deficiency in long-axis peptidoglycan synthesis. | 10.1128/JB.185.15.4490-4498.2003 |
pubmed_912_2545 | Partial knowledge of patient health status and treatment response is a pervasive concern in medical decision making. Clinical practice guidelines (CPGs) make recommendations intended to optimize patient care, but optimization typically is infeasible with partial knowledge. Decision analysis shows that a clinician's objective, knowledge, and decision criterion should jointly determine the care he prescribes. To demonstrate, this paper studies a common scenario regarding diagnostic testing and treatment. A patient presents to a clinician, who obtains initial evidence on health status. The clinician can prescribe a treatment immediately or he can order a test yielding further evidence that may be useful in predicting treatment response. In the latter case, he prescribes a treatment after observation of the test result. I analyze this scenario in three steps. The first poses a welfare function and characterizes optimal care. The second describes partial knowledge of response to testing and treatment that might realistically be available. The third considers decision criteria. I conclude with reconsideration of clinical practice guidelines. | 10.1073/pnas.1221405110 |
pubmed_1038_20911 | The use of a transaxillary latissimus dorsi musculocutaneous flap is suitable whenever a large volume of tissue is required for head and neck reconstruction. Our series of 63 transaxillary latissimus dorsi musculocutaneous flap reconstructions included three cases of complete flap necrosis and ten cases of partial flap necrosis. When used in reconstructive head and neck surgery, the latissimus dorsi vascular pedicle is separate from the radiated field. The pedicled latissimus dorsi flap provides coverage of the orbitocranium, including the supraorbital region and central portion of the upper face. In the event that the pedicle muscle flap does not reach far enough cephalad, the nutrient vessels can be separated from the axillary artery and anastomosed to vessels in the neck. Combined defects of the esophagus, the mandibulofacial region, and the neck may be reconstructed with a single large latissimus dorsi flap. In our experience, aesthetic and functional deficits have been well tolerated by patients after latissimus dorsi reconstruction. Disadvantages of the latissimus dorsi flap include repositioning of the patient, increased blood loss, and longer operating time. Permanent brachial plexus injury can also occur. In general, the transaxillary latissimus dorsi musculocutaneous flap should not be used when defects can be reconstructed using simpler methods. | pubmed_1038_20911 |
pubmed_840_2900 | OBJECTIVE
To develop and assess a community-based model for medical coverage for a large multisport event.
DESIGN
The model included pre-event risk stratification, a concise training program for all medical volunteers, and detailed medical control guidelines. Prospective data collection was performed using standardized injury reporting forms.
SETTING
The 2005 World Masters Games in Edmonton, Alberta, Canada.
PATIENTS
Approximately 21,600 athletes between the ages of 25 and 97 who were participants in the World Masters Games.
INTERVENTIONS
A 4-category risk scale was developed and applied to each sport. Medical volunteers were provided intensive training and guided by concise medical control guidelines. Medical encounters were recorded using a standardized injury report form.
MAIN OUTCOME MEASURES
Incidence of injury by sport. Rate of ambulance transportation. Rate of medication use. Relevance of medical control guidelines.
RESULTS
Medical coverage for over 80 venues was provided by 243 volunteers. A total of 1767 medical encounters were documented, with an overall injury rate of 8.2% (95% CI, 7.9 to 8.5). The majority of injuries were of a minor nature. Only 35 (0.16%) athletes had injuries that required medication or ambulance transportation. Cardiopulmonary resuscitation and defibrillation was required in only 1 patient.
CONCLUSIONS
The risk of injury during the World Masters Games appears to be low, and the risk of severe injury is extremely low. The described community-based model for medical coverage for multi-sport events appears to be safe and practical. | 10.1097/01.jsm.0000244608.45231.e4 |
others_381_15647 | Purpose: To evaluate the relative importance and predictive ability of salivary immunoglobulin A (s-IgA) measures with regards to upper respiratory illness (URI) in youth athletes. Methods: Over a 38-week period, 22 youth athletes (age = 16.8 [0.5] y) provided daily symptoms of URI and 15 fortnightly passive drool saliva samples, from which s-IgA concentration and secretion rate were measured. Kernel-smoothed bootstrapping generated a balanced data set with simulated data points. The random forest algorithm was used to evaluate the relative importance (RI) and predictive ability of s-IgA concentration and secretion rate with regards to URI symptoms present on the day of saliva sampling (URIday), within 2 weeks of sampling (URI2wk), and within 4 weeks of sampling (URI4wk). Results: The percentage deviation from average healthy s-IgA concentration was the most important feature for URIday (median RI 1.74, interquartile range 1.41–2.07). The average healthy s-IgA secretion rate was the most important feature for URI4wk (median RI 0.94, interquartile range 0.79–1.13). No feature was clearly more important than any other when URI symptoms were identified within 2 weeks of sampling. The values for median area under the curve were 0.68, 0.63, and 0.65 for URIday, URI2wk, and URI4wk, respectively. Conclusions: The RI values suggest that the percentage deviation from average healthy s-IgA concentration may be used to evaluate the short-term risk of URI, while the average healthy s-IgA secretion rate may be used to evaluate the long-term risk. However, the results show that neither s-IgA concentration nor secretion rate can be used to accurately predict URI onset within a 4-week window in youth athletes. © 2021 Human Kinetics, I | 10.1123/IJSPP.2019-0804 |
pubmed_504_19617 | Mycosis fungoides with penile involvement is extremely rare. Previous reports have shown successful treatment with imiquimod or a combination of beam radiation and chemotherapy. We present a patient with mycosis fungoides and penile involvement. The penile lesions were initially treated with topical imiquimod; however, he developed worsening glandular lesions and discharge. Therefore the treatment was discontinued. Subsequent treatment with brentuximab (anti-CD30) targeted therapy resulted in complete resolution of the penile lesions. To our knowledge, this represents the first case of a complete penile mycosis fungoides response to brentuximab therapy. Brentuximab may be considered for refractory penile mycoses fungoides. | 10.1016/j.eucr.2020.101460 |
pubmed_841_12656 | BACKGROUND
Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms.
METHODS
To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing.
RESULTS
Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there.
CONCLUSIONS
International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions. | 10.1002/cncr.10317 |
pubmed_358_7700 | A series of GH secretagogues based on modifications in the C-terminal of NN703 is reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated hydrazides in order to decrease the volume of distribution and identify GH secretagogues with shorter duration of action. Most of the prepared compounds show high potency in a rat pituitary assay. Subsequent to an initial in vivo screening in dogs, four compounds were selected for further pharmacological and pharmacokinetic evaluation. The four compounds showed oral bioavailability around 35% and equipotency in vitro compared to NN703. The relationship between lipophilicity and volume of distribution is discussed and it is speculated whether the lower volume of distribution is attributed to the observed higher in vivo potency and shorter plasma elimination half-life. | 10.1016/s0223-5234(00)00146-x |
pubmed_76_16388 | Opaque and translucent morphotypes of a TnphoA-containing strain of Vibrio vulnificus were fed to oysters, which were subsequently stored at temperatures ranging from 0.5 to 22 degrees C for 10 days. Samples of oysters were homogenized and plated at intervals to determine the cell density of V. vulnificus and total aerobic population of bacteria present. At all temperatures, the numbers of V. vulnificus (both morphotypes) declined over the 10-day study period. The same observation was made with a lower inoculum of V. vulnificus. Identical experiments with shucked oysters showed a more rapid decrease in V. vulnificus. Identical experiments with shucked oysters showed a more rapid decrease in V. vulnificus to levels below limits of detection. Little change in the total bacterial counts was observed in shellstock oysters at any of the test temperatures, whereas incubation at the higher temperatures (17 and 22 degrees C) resulted in large increases in total counts in shucked oysters. These data suggest that temperature abuse of oysters may not be a factor in increasing the public health risk of V. vulnificus through raw oyster consumption. However, the data also suggest that even with proper storage, indigenous levels of V. vulnificus may remain sufficiently higher in shellstock oysters to produce infection in compromised hosts. | 10.1128/aem.58.9.2771-2775.1992 |
pubmed_150_22427 | The purpose of this study was to compare the recurrence rate (RR) of keratocystic odontogenic tumors (KOTs) in patients who underwent enucleation with or without adjuvant therapy, to patients who underwent decompression with or without residual cystectomy. An extensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to identify all relevant articles published without date and language restrictions from inception to December 2015. Relevant articles were selected based on the specific inclusion criteria. A weighted RR and odds ratio (OR) using a Mantel-Haenszel (M-H) test and random effect model with 95% confidence interval (CI) were performed. Meta-regression analysis was conducted to further identify the influence of the duration of follow-up periods on the overall OR. A total of 997 KOTs enrolled in 14 studies were included in this analysis. There was a significant advantage for the enucleation ± adjuvant therapy group in preventing recurrence for patients with KOTs (M-H, OR, 0.514; 95% CI, 0.302-0.875; p = 0.014). The overall pooled weighted RR for enucleation ± adjuvant therapy and decompression ± secondary cystectomy were 18.2% and 27.1%, respectively. The meta-regression analysis showed that duration of follow-up time did not significantly influence the OR of KOT recurrence (Q = 0.506, p = 0.646). In conclusion, initial cystectomy ± adjuvant therapy was associated with fewer recurrences than decompression ± secondary cystectomy. | pubmed_150_22427 |
pubmed_874_14791 | During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility, and cellular uptake of two promising candidate systems for oral antigen delivery, that is, calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres was expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, neither CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies. | 10.1021/bm5005367 |
pubmed_691_13092 | Selective high-performance liquid chromatographic methods for the determination of tiapamil and its two main metabolites in plasma and urine are described. Tiapamil together with its metabolites is extracted at alkaline pH into dichloromethane. Separation is carried out using normal-phase high-performance liquid chromatography with ultraviolet detection (278 nm). The unchanged drug and the desmethyl metabolite are analysed simultaneously. The second metabolite is analysed separately under more polar conditions. The sensitivity limits are 50 ng/ml for tiapamil, 100 ng/ml for the desmethyl metabolite and 75 ng/ml for the second metabolite, using 0.5 ml of plasma. The sensitivity limits in urine are 100 ng/ml for all three compounds using a 0.5 ml specimen. The method has been applied to the analysis of human plasma and urine after intravenous (70 mg) and oral (400 mg) administration of tiapamil. | 10.1016/0378-4347(84)80073-0 |
pubmed_581_13332 | Systemic acid-base balance and osmotic/ionic regulation in decapod crustaceans are in part maintained by a set of transport-related enzymes such as carbonic anhydrase (CA), Na+/K+-ATPase (NKA), H+-ATPase (HAT), Na+/K+/2Cl- cotransporter (NKCC), Na+/Cl-/HCO[Formula: see text] cotransporter (NBC), Na+/H+ exchanger (NHE), Arginine kinase (AK), Sarcoplasmic Ca+2-ATPase (SERCA) and Calreticulin (CRT). We carried out a comparative molecular analysis of these genes in three commercially important yet eco-physiologically distinct freshwater crayfish, Cherax quadricarinatus, C. destructor and C. cainii, with the aim to identify mutations in these genes and determine if observed patterns of mutations were consistent with the action of natural selection. We also conducted a tissue-specific expression analysis of these genes across seven different organs, including gills, hepatopancreas, heart, kidney, liver, nerve and testes using NGS transcriptome data. The molecular analysis of the candidate genes revealed a high level of sequence conservation across the three Cherax sp. Hyphy analysis revealed that all candidate genes showed patterns of molecular variation consistent with neutral evolution. The tissue-specific expression analysis showed that 46% of candidate genes were expressed in all tissue types examined, while approximately 10% of candidate genes were only expressed in a single tissue type. The largest number of genes was observed in nerve (84%) and gills (78%) and the lowest in testes (66%). The tissue-specific expression analysis also revealed that most of the master genes regulating pH and osmoregulation (CA, NKA, HAT, NKCC, NBC, NHE) were expressed in all tissue types indicating an important physiological role for these genes outside of osmoregulation in other tissue types. The high level of sequence conservation observed in the candidate genes may be explained by the important role of these genes as well as potentially having a number of other basic physiological functions in different tissue types. | 10.7717/peerj.3623 |
pubmed_110_14002 | Urodynamic investigations were performed on 24 patients undergoing anterior resection or abdominoperineal excision of the rectum for carcinoma or benign disease. Anterior resection did not cause any changes in bladder function, but 4 out of the 10 preoperatively potent males (40%) had ejaculatory or erectile dysfunction after surgery. Bladder decentralization was observed in 4 out of 9 patients (44%) after abdominoperineal excision. Pressure measurements from abdominal stomas can be irrelevant and should be avoided. Postoperative urodynamic findings are difficult to interpret without a knowledge of the preoperative state of lower urinary tract function. | pubmed_110_14002 |
pubmed_590_933 | To fully harness the enormous potential offered by interfaces between graphitic nanostructures and biomolecules, detailed connections between adsorbed conformations and adsorption behaviour are needed. To elucidate these links, a key approach, in partnership with experimental techniques, is molecular simulation. For this, a force-field (FF) that can appropriately capture the relevant physics and chemistry of these complex bio-interfaces, while allowing extensive conformational sampling, and also supporting inter-operability with known biological FFs, is a pivotal requirement. Here, we present and apply such a force-field, GRAPPA, designed to work with the CHARMM FF. GRAPPA is an efficiently implemented polarisable force-field, informed by extensive plane-wave DFT calculations using the revPBE-vdW-DF functional. GRAPPA adequately recovers the spatial and orientational structuring of the aqueous interface of graphene and carbon nanotubes, compared with more sophisticated approaches. We apply GRAPPA to determine the free energy of adsorption for a range of amino acids, identifying Trp, Tyr and Arg to have the strongest binding affinity and Asp to be a weak binder. The GRAPPA FF can be readily incorporated into mainstream simulation packages, and will enable large-scale polarisable biointerfacial simulations at graphitic interfaces, that will aid the development of biomolecule-mediated, solution-based graphene processing and self-assembly strategies. | 10.1039/c4nr00468j |
others_40_19026 | The monocot mannose-binding lectins are an extended superfamily of structurally and evolutionarily related proteins, which until now have been isolated from species of the Amaryllidaceae, Alliaceae, Araceae, Orchidaceae, and Liliaceae. To explain the obvious differences in biological activities, the structure-function relationships of the monocot mannose-binding lectins were studied by a combination of glycan-binding studies and molecular modeling using the deduced amino acid sequences of the currently known lectins. Molecular modeling indicated that the number of active mannose- binding sites per monomer varies between three and zero. Since the number of binding sites is fairly well correlated with the binding activity measured by surface plasmon resonance, and is also in good agreement with the results of previous studies of the biological activities of the mannose-binding lectins, molecular modeling is of great value for predicting which lectins are best suited for a particular applica | 10.1104/pp.112.4.1531 |
pubmed_898_15031 | BACKGROUND
Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2017-18, predominated by influenza B. WHO-recommended, trivalent vaccine components were lineage-mismatched for B. The I-MOVE hospital network measured 2017-18 seasonal influenza vaccine effectiveness (IVE) against influenza A(H3N2) and B among hospitalised patients (≥65 years) in Europe.
METHODS
Following the same generic protocol for test-negative design, hospital teams in nine countries swabbed patients ≥65 years with recent onset (≤7 days) severe acute respiratory infection (SARI), collecting information on demographics, vaccination status and underlying conditions. Cases were RT-PCR positive for influenza A(H3N2) or B; controls: negative for any influenza. "Vaccinated" patients had SARI onset >14 days after vaccination. We measured pooled IVE against influenza, adjusted for study site, age, sex, onset date and chronic conditions.
RESULTS
We included 3483 patients: 376 influenza A(H3N2) and 928 B cases, and 2028 controls. Most (>99%) vaccinated patients received the B lineage-mismatched trivalent vaccine. IVE against influenza A(H3N2) was 24% (95% CI: 2 to 40); 35% (95% CI: 6 to 55) in 65- to 79-year-olds and 14% (95% CI: -22 to 39) in ≥80-year-olds. Against influenza B, IVE was 30% (95% CI: 16 to 41); 37% (95% CI: 19 to 51) in 65- to 79-year-olds and 19% (95% CI: -7 to 38) in ≥80-year-olds.
CONCLUSIONS
IVE against influenza B was similar to A(H3N2) in hospitalised older adults, despite trivalent vaccine and circulating B lineage mismatch, suggesting some cross-protection. IVE was lower in those ≥80 than 65-79 years. We reinforce the importance of influenza vaccination in older adults as, even with a poorly matched vaccine, it still protects one in three to four of this population from severe influenza. | 10.1111/irv.12714 |
pubmed_300_8074 | Understanding the structural organisation and mode of action of the initiating complex of the classical pathway of complement activation (C1) has been a central goal in complement biology since its isolation almost 50 years ago. Nevertheless, knowledge is still incomplete, especially with regard to the interactions between its subcomponents C1q, C1r and C1s that trigger activation upon binding to a microbial target. Recent studies have provided new insights into these interactions, and have revealed unexpected parallels with initiating complexes of the lectin pathway of complement: MBL-MASP and ficolin-MASP. Here, we develop and expand these concepts and delineate their implications towards the key aspects of complement activation via the classical and lectin pathways. | 10.1016/j.imbio.2009.08.006 |
pubmed_288_1148 | We studied the relationship between the decline in sensitivity that occurs with eccentricity for stimuli of different spatial scale defined by either luminance (LM) or contrast (CM) modulation. We show that the detectability of CM stimuli declines with eccentricity in a spatial frequency-dependent manner, and that the rate of sensitivity decline for CM stimuli is roughly that expected from their 1st order carriers, except, possibly, at finer scales. Using an equivalent noise paradigm, we investigated the possible reasons for why the foveal sensitivity for detecting LM and CM stimuli differs as well as the reason why the detectability of 1st order stimuli declines with eccentricity. We show the former can be modeled by an increase in internal noise whereas the latter involves both an increase in internal noise and a loss of efficiency. To encompass both the threshold and suprathreshold transfer properties of peripheral vision, we propose a model in terms of the contrast gain of the underlying mechanisms. | 10.1167/8.1.19 |
pubmed_674_22177 | The electrocatalytic activities of Mn₃O₄/C composites are studied in lithium-oxygen (Li-O₂) batteries as cathode catalysts. The Mn₃O₄/C composites are fabricated using ultrasonic spray pyrolysis (USP) with organic surfactants as the carbon sources. The physical and electrochemical performance of the composites is characterized by X-ray diffraction, scanning electron microscopy, particle size analysis, Brunauer-Emmett-Teller (BET) measurements, elemental analysis, galvanostatic charge-discharge methods and rotating ring-disk electrode (RRDE) measurements. The electrochemical tests demonstrate that the Mn₃O₄/C composite that is prepared using Trition X-114 (TX114) surfactant has higher activity as a bi-functional catalyst and delivers better oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic performance in Li-O₂ batteries because there is a larger surface area and particles are homogeneous with a meso/macro porous structure. The rate constant (k) for the production of superoxide radical (O₂•-) and the propylene carbonate (PC)-electrolyte decomposition rate constant (k) for M₃O₄/C and Super P electrodes are measured using RRDE experiments and analysis in the 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF₆)/PC electrolyte. The results show that TX114 has higher electrocatalytic activity for the first step of ORR to generate O₂•- and produces a faster PC-electrolyte decomposition rate. | 10.3390/nano6110203 |
pubmed_201_18628 | Macrophages are the key cells in metabolic syndrome and are also a risk factor for metabolic disease. Macrophages have different functions and transcriptional profiles, but all are required for maintaining homeostasis. It is well known that macrophages play a key role in inflammation and early atherogenesis, and are present in two phenotypes: pro-inflammatory (M1) and anti-inflammatory (M2). Osteoclast stimulatory transmembrane protein (oc-stamp) is a multiple-pass transmembrane protein; however, its function remains unclear. In this study, we explored the role of oc-stamp in macrophages physiology. The results showed that oc-stamp was notably decreased under LPS and IFN-γ stimulation, while it was increased with IL-4 treatment. Furthermore, oc-stamp induced a phenotypic switch in macrophage polarization, suppressing the M1 pro-inflammatory state in the overexpression group, and promoting the M1 pro-inflammatory state in the knockdown group. Further study revealed that oc-stamp regulated macrophage polarization possibly via STAT6. Taken together, our results are the first to demonstrate that oc-stamp may play an important role in macrophage polarization and inhibit the M1 pro-inflammatory state. | 10.1093/abbs/gmx092 |
pubmed_186_15990 | Accuracy of diagnosis defines the quality of treatment in patients with traumatic damage to eyelet walls. In this area, complex functional and anatomical breaches are typical and require full characterization of pathological changes in bone and soft tissue structures. A new plastic material with a high degree level of demineralization called "Perfoost" can be used to treat defects in the bones of the face of children and adults. In the present study, 79 patients with fractured eyelet walls were treated between 1999 and 2006 by grafting the defect wall with demineralized bone allografts. Grafts were applied from 2 days to 18 months after trauma. Magnetic resonance computer CT was used to check the realignment of allografts every 6 months after the reconstructive operation. The post-operative period of the observation was from 6 months to 7 years after the operation. Good or satisfactory results were obtained for 97.47 % of patients. | 10.1007/s10561-016-9561-x |
pubmed_738_13841 | Gallbladder cancer (GBC) is one of the most lethal malignancies worldwide, with extremely poor prognosis. Recently, forkhead box k1 (FOXK1), a member of the FOX transcription factor family, has been reported to be correlated with tumor progression in multiple malignancies. However, the role of FOXK1 in GBC has not been elucidated. In this study, we demonstrated that the expression level of FOXK1 was elevated in human GBC tissues and associated with increased liver metastasis, poor histological differentiation, advanced TNM stage, and shorter overall survival. Knockdown of FOXK1 expression inhibited GBC cells proliferation and metastasis. Consistently, overexpression of FOXK1 promoted GBC cells progression. Mechanical investigations verified that knockdown of FOXK1 could lead to G1/S cell cycle arrest through downregulating CDK4, CDK6, cyclin D1, and cyclin E1. And FOXK1 could regulate the expression of epithelial-mesenchymal transition (EMT) related proteins E-cad, N-cad, and Vimentin. Moreover, we found that FOXK1 could regulate the activation of Akt/mTOR signaling pathway. In addition, AKT special inhibitor MK-2206 could abolish the proliferation and metastasis discrepancy between FOXK1 overexpression GBC cells and control cells, which suggested the tumorpromoting effect of FOXK1 may be partially related with the activations of Akt/mTOR signaling pathway. Collectively, our results suggested that FOXK1 promotes GBC cells progression and represent a novel prognostic biomarker and potential therapeutic target in GBC. | 10.3389/fonc.2020.00545 |
pubmed_531_20922 | Sanatorium treatment results were evaluated for 31 patients suffering from dyscirculatory encephalopathy following atherosclerosis, arterial hypertension or both of them. Combined treatment involving chlorine-sodium baths, electrophoresis of 1% nicotinic acid according to the oculo-occipital technique, physical exercise, massage of the head, diet produced a marked positive effect on general brain symptoms, cerebral hemodynamics, lipid metabolism and coagulation. A subjective response was recorded in 90.3% of the patients. | pubmed_531_20922 |
pubmed_914_23834 | Statokinetic dissociation (SKD) refers to a greater reduction in sensitivity to stationary visual stimuli relative to similar targets in motion. We evaluated SKD perimetrically in nine optic neuritis (ON) patients and in nine normals by measuring the difference between static and 4 degrees /s kinetic thresholds for a size I target (0.11 degrees ) along the four oblique meridians. To assess temporal response characteristics, we used flicker perimetry to measure the sensitivity to 2-, 8-, and 20-Hz sinusoidal flicker at 5 degrees intervals along the oblique meridians. The ON patients' sensitivity to all three flicker frequencies was reduced at all eccentricities. In a number of cases, flicker sensitivity was unmeasurable to one or more frequencies within the region where kinetic targets were detectable. This was particularly marked at 20-25 degrees , where in half the cases there was no measurable sensitivity to a flickering target although a moving target could be seen. These results indicate that SKD in these patients may not be due to a selective loss of mechanisms sensitive to low frequency temporal modulation with a relative sparing of mechanisms sensitive to high-frequency temporal modulation as has been previously suggested [A. Safran and J. Glaser, "Statokinetic Dissociation in Lesions of Anterior Visual Pathways," Arch. Ophthalmol. 98, 291-295 (1980)]. We hypothesize that SKD may be due in part to differences in spatial summation in these patients, making a moving target, which has a greater spatial extent, more detectable than a stationary target. Thus ON patients exhibiting SKD should show great improvement in static perimetry thresholds as the target size is increased. We compared the results of standard 30-2 Humphrey perimetry for size III (0.43 degrees ) and size V (1.72 degrees ) targets for normals and ON patients and found that the patients showed a larger sensitivity difference between size III and size V targets than normals. | 10.1364/AO.30.002136 |
pubmed_129_3741 | CD 1 female mice were treated with Doxorubicin (5 mg/Kg i.v.) once a week for 8 weeks or with Isoproterenol (20 mg/Kg s.c.) once a week for 5 weeks. Other mice were treated with the chelating agent ICRF-187 (100 mg/Kg i.p.) 30 min. before Doxorubicin or Isoproterenol administration. The animals were sacrificed 4 weeks after the last administration and their cardiac morphology was evaluated by means of light microscopy. ICRF-187 significantly lessened the extent and the severity of the cardiac lesions by Doxorubicin (-68%, P less than 0.01 in left atrium; -69%, P less than 0.01 in ventricles) and the extent of those induced by Isoproterenol (-56%, P less than 0.05). These data confirm that ICRF-187 has good activity on Doxorubicin-induced myocardiopathy and provide new information about the "in vivo" effects of the compound on the cardiotoxicity caused by Isoproterenol. Moreover, they seem to confirm that a common event, probably the involvement of metal ions, plays a role in the morphologically different myocardiopathies induced by Doxorubicin or Isoproterenol. | pubmed_129_3741 |
pubmed_1071_9442 | OBJECTIVE
The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 A/G, and -318 C/T polymorphisms confer susceptibility to multiple sclerosis (MS).
METHODS
A meta-analysis of the associations between the CTLA-4 +49 A/G and -318 C/T polymorphisms and MS.
RESULTS
A total of 23 separate comparisons from 19 studies of the CTLA-4 +49 A/G polymorphism and 10 comparisons (8 studies) of the CTLA-4 -318 C/T polymorphism were considered. Meta-analysis showed no association between MS and the CTLA-4 +49G allele in the analysis of all study subjects (OR = 1.026, 95% CI = 0.967-1.089, p = 0.395). Stratification by ethnicity indicated no association between the CTLA-4 +49G allele and MS in Caucasians, Asians, or Arabs. Meta-analysis showed no association between RA and the CTLA-4 -318C allele in all study subjects (OR = 0.909, 95% CI = 0.704-1.175, p = 0.467). In addition, meta-analysis stratified by ethnicity revealed no association between MS and the CTLA-4 -318 C/T polymorphism in Caucasian, Asian, or Arab populations.
CONCLUSIONS
This meta-analysis of published studies did not find an association between the CTLA-4 +49 A/G and -318 C/T polymorphisms and susceptibility to MS in Caucasian, Asian, and Arab populations. | 10.3109/08820139.2013.803114 |
others_382_4074 | Soil microbial activity drives carbon and nutrient cycling in terrestrial ecosystems. Soil microbial biomass is commonly limited by environmental factors and soil carbon availability. We employed plant litter removal, root trenching and stem-girdling treatments to examine the effects of environmental factors, above- and belowground carbon inputs on soil microbial C in a subtropical monsoon forest in southwest China. During the experimental period from July 2006 through April 2007, 2 years after initiation of the treatments, microbial biomass C in the humus layer did not vary with seasonal changes in soil temperature or water content. Mineral soil microbial C decreased throughout the experimental period and varied with soil temperature and water content. Litter removal reduced mineral soil microbial C by 19.0% in the ungirdled plots, but only 4.0% in girdled plots. Root trenching, stem girdling and their interactions influenced microbial C in humus layer. Neither root trenching nor girdling significantly influenced mineral soil microbial C. Mineral soil microbial C correlated with following-month plant litterfall in control plots, but these correlations were not observed in root-trenching plots or girdling plots. Our results suggest that belowground carbon retranslocated from shoots and present in soil organic matter, rather than aboveground fresh plant litter inputs, determines seasonal fluctuation of mineral soil microbial biomass. © 2008 Elsevier Ltd. All rights reser | 10.1016/j.soilbio.2008.10.002 |
pubmed_58_15636 | Individual and small clusters of cancer cells may detach from the edges of a main tumor and invade vessels, which can act as the origin of metastasis; however, the mechanism for this phenomenon is not well understood. Using cancer tissue-originated spheroids, we studied whether disturbing the 3D architecture of cancer spheroids can provoke the reformation process and progression of malignancy. We developed a mechanical disruption method to achieve homogenous disruption of the spheroids while maintaining cell-cell contact. After the disruption, 9 spheroid lines from 9 patient samples reformed within a few hours, and 3 of the 9 lines exhibited accelerated spheroid growth. Marker expression, spheroid forming capacity, and tumorigenesis indicated that stemness increased after spheroid disruption. In addition, the spheroid forming capacity increased in 6 of 11 spheroid lines. The disruption signature determined by gene expression profiling supported the incidence of remodeling and predicted the prognosis of patients with colorectal cancer. Furthermore, WNT and HER3 signaling were increased in the reformed spheroids, and suppression of these signaling pathways attenuated the increased proliferation and stemness after the disruption. Overall, the disruption and subsequent reformation of cancer spheroids promoted malignancy-related phenotypes through the activation of the WNT and ERBB pathways. | 10.18632/oncotarget.24641 |
pubmed_323_3396 | This review is a partially personal account of the discovery of virus structure and its implication for virus function. Although I have endeavored to cover all aspects of structural virology and to acknowledge relevant individuals, I know that I have favored taking examples from my own experience in telling this story. I am anxious to apologize to all those who I might have unintentionally offended by omitting their work. The first knowledge of virus structure was a result of Stanley's studies of tobacco mosaic virus (TMV) and the subsequent X-ray fiber diffraction analysis by Bernal and Fankuchen in the 1930s. At about the same time it became apparent that crystals of small RNA plant and animal viruses could diffract X-rays, demonstrating that viruses must have distinct and unique structures. More advances were made in the 1950s with the realization by Watson and Crick that viruses might have icosahedral symmetry. With the improvement of experimental and computational techniques in the 1970s, it became possible to determine the three-dimensional, near-atomic resolution structures of some small icosahedral plant and animal RNA viruses. It was a great surprise that the protecting capsids of the first virus structures to be determined had the same architecture. The capsid proteins of these viruses all had a 'jelly-roll' fold and, furthermore, the organization of the capsid protein in the virus were similar, suggesting a common ancestral virus from which many of today's viruses have evolved. By this time a more detailed structure of TMV had also been established, but both the architecture and capsid protein fold were quite different to that of the icosahedral viruses. The small icosahedral RNA virus structures were also informative of how and where cellular receptors, anti-viral compounds, and neutralizing antibodies bound to these viruses. However, larger lipid membrane enveloped viruses did not form sufficiently ordered crystals to obtain good X-ray diffraction. Starting in the 1990s, these enveloped viruses were studied by combining cryo-electron microscopy of the whole virus with X-ray crystallography of their protein components. These structures gave information on virus assembly, virus neutralization by antibodies, and virus fusion with and entry into the host cell. The same techniques were also employed in the study of complex bacteriophages that were too large to crystallize. Nevertheless, there still remained many pleomorphic, highly pathogenic viruses that lacked the icosahedral symmetry and homogeneity that had made the earlier structural investigations possible. Currently some of these viruses are starting to be studied by combining X-ray crystallography with cryo-electron tomography. | 10.1017/S0033583513000012 |
pubmed_438_814 | OBJECTIVES
The role of estrogens in human bladder cancer still remains to be resolved. This study was undertaken to determine the estrogen receptor (ER) expression status and to elucidate the prognostic significance of ER in superficial transitional cell carcinoma (TCC) of the human bladder.
METHODS
Tumor tissue blocks which were obtained by transurethral resection (TUR) from 121 patients with superficial TCC and 30 control subjects were investigated. Median follow-up was 40 months. The expression of nuclear ER was evaluated by immunohistochemistry using avidin-biotin-peroxidase method and a monoclonal ER antibody. ER staining intensity in samples was assessed semi-quantitatively. Staining characteristics were compared with the clinico-pathological results.
RESULTS
ERs were detected in 12.4% of the superficial TCC patients and in 10% of the controls (P = 0.73). No association was found between ER immuno-reactive score and patients' age, sex, tumor multiplicity or tumor size. An association between the ER staining intensity and higher tumor grade was observed (P = 0.01). Grades I, II and III tumors showed 10.6, 8.7 and 44.4% staining, respectively. Survival was not affected by ER expression. In multivariate analysis ER expression was not an independent prognostic factor.
CONCLUSION
Superficial TCC of the bladder shows low ER expression and it appears that ERs do not have any direct role on the prognosis of patients with superficial TCC. | 10.1016/s0302-2838(02)00038-6 |
pubmed_532_11604 | OBJECTIVE
The purpose of this article is to determine whether the relationship between a renal cell carcinoma and the renal sinus fat on contrast-enhanced CT could predict muscular venous branch invasion and the type of surgery needed.
MATERIALS AND METHODS
A total of 115 consecutive patients underwent pre-operative contrast-enhanced CT between August 2011 and December 2011. Without access to histopathologic information, on nephrographic phase contrast-enhanced CT images, two radiologists independently determined whether the renal tumor was in contact with the renal sinus fat or separated from the renal sinus fat. Interreader agreements and performance characteristics of imaging tests were calculated, and histopathologic analysis served as the standard of reference.
RESULTS
Histopathologic analysis identified 115 renal tumors, 90% (103/115) of which were renal cell carcinomas. Thirty-nine percent (31/80) of renal cell carcinomas that abutted the renal sinus fat on CT displayed muscular venous branch invasion on histopathologic analysis. Patients with renal cell carcinomas separated from the renal sinus fat were more likely to undergo partial nephrectomies (96% [22/23]; p = 0.013). Sensitivity and specificity for the identification of muscular venous branch invasion on CT were 94% (95% CI, 80-99%) and 30% (20-42%), respectively. Interreader agreement of visual assessment was excellent (κ = 0.87; 95% CI, 0.81-0.92).
CONCLUSION
If a renal cell carcinoma was separated from the renal sinus fat on CT, the likelihood of muscular venous branch invasion being identified by histopathologic analysis was significantly decreased, and the patient was more likely to undergo a partial nephrectomy. | 10.2214/AJR.12.10496 |
pubmed_869_1945 | INTRODUCTION
High-frequency gastric electrical stimulation is a new therapeutic option to improve refractory nausea and vomiting, in gastroparetic patients. Its effects on gastric emptying are, however, inconstant and limited. Therefore, we have hypothesized that high-frequency gastric electrical stimulation could be also effective in patients suffering from refractory vomiting and nausea with normal gastric emptying, and we have compared the symptomatic efficacy of high-frequency gastric electrical stimulation between patients with delayed and normal gastric emptying.
PATIENTS AND METHODS
Fifteen patients with chronic, severe and medically resistant nausea and vomiting were included in the study. Gastric emptying was delayed in eight patients (Group 1) and normal in seven patients (Group 2). At inclusion and at 6 months after the start of the stimulation, symptoms (nausea and vomiting, bloating, regurgitations, abdominal pain and appetite) and quality of life were prospectively evaluated using the Gastrointestinal Quality of Life Index score whereas gastric emptying was assessed by scintigraphy and/or octanoic acid breath test.
RESULTS
Age, sex, symptoms and quality of life were not different at baseline between the two groups. At 6 months, Gastrointestinal Quality of Life Index and nausea/vomiting scores had significantly improved in both groups. Other symptoms (bloating, regurgitations, abdominal pain and appetite) had improved at 6 months in Group 1 but not in Group 2. Six months after the start of stimulation, gastric emptying was normal in 4/8 Group 1 patients and 5/7 Group 2 patients but was not significantly different from that calculated before the implantation of the stimulator.
CONCLUSION
Our results suggest that high-frequency gastric electrical stimulation could be an effective therapy for treating chronic, severe vomiting and nausea whether gastric emptying is delayed or not. | 10.1097/01.meg.0000250584.15490.b4 |
pubmed_98_18415 | Li-Fraumeni syndrome (LFS) is a cancer-prone, autosomal dominant syndrome caused by underlying germline gene mutations of TP53, a tumor-suppressor gene encoding the p53 protein with a major role in apoptosis, DNA repair and cell cycle regulation. Cumulative cancer incidence for LFS patients by the age of 70 years is 80-100%, mostly involving adrenocortical carcinoma, brain tumors, bone and soft tissue sarcomas, leukemia and female breast cancer from the age of 20 years. Dominant negative TP53 variant is correlated with an increased tumorigenesis risk in LFS. Sporadic TP53 mutations are related to almost half of global cancers since p53 in addition to p73 protein represent essential players in anticancer cellular protection. Epidemiological aspects concerning skin cancers, especially malignant melanoma (MM), in LFS are less clear. A low level of statistical evidence demonstrates LFS cases with pediatric MM, multiple MM, spitzoid MM, atypical presentations, mucosal and uveal MM. Retrospective cohorts indicate a higher cumulative risk than the general population by the age of 70 years for MM and basal cell carcinoma. Non-syndromic and syndromic TP53 mutations are a major pathway of metastasis, including MM. In LHS, an important level of awareness involves skin cancers despite not being a part of the typical malignancy-containing picture. Additional data are crucially needed. However, at least one dermatologic control is a step in the multidisciplinary panel of surveillance of these patients; but in cases with benign and pre-malign pigmentations, serial dermatoscopy and full body photography are recommended for early melanoma detection in order to improve the prognosis and to reduce the overall malignancy burden. | 10.3892/etm.2021.10998 |
pubmed_702_9152 | AIMS
Decomposition of solid waste is microbially mediated, yet little is known about the associated structure and temporal changes in prokaryotic communities. Bioreactors were used to simulate landfill conditions and archaeal and bacterial community development in leachate was examined over 8 months.
METHODS AND RESULTS
Municipal solid waste (MSW) was deposited in laboratory bioreactors with or without biosolids and combustion residues (ash). The near-neutral pH fell about half a log by day 25, but recovered to approximately 7.0 by day 50. Cell concentrations in bioreactors containing only MSW were significantly higher than those from co-disposal bioreactors. Archaeal and bacterial community structure was analysed by denaturing gradient gel electrophoresis targeting 16S rRNA genes, showing temporal population shifts for both domains. mcrA sequences retrieved from a co-disposal bioreactor were predominantly affiliated with the orders Methanosarcinales and Methanomicrobiales.
CONCLUSION
Regardless of waste composition, microbial communities in bioreactor leachates exhibited high diversity and distinct temporal trends. The solid waste filled bioreactors allowed simulation of solid waste decomposition in landfills while also reducing the variables.
SIGNIFICANCE AND IMPACT OF THE STUDY
This study advances the basic understanding of changes in microbial community structure during solid waste decomposition, which may ultimately improve the efficiency of solid waste management. | 10.1111/j.1365-2672.2009.04319.x |
pubmed_910_1728 | OBJECTIVE
The aim of this study was to explore the validity of self-rated health across different populations of older adults, when compared to the Short Physical Performance Battery.
DESIGN
Cross-sectional analysis of the International Mobility in Aging Study.
SETTING
Five locations: Saint-Hyacinthe and Kingston (Canada), Tirana (Albania), Manizales (Colombia), and Natal (Brazil).
PARTICIPANTS
Older adults between 65 and 74 years old (n = 1,995).
METHODS
The Short Physical Performance Battery (SPPB) was used to measure physical performance. Self-rated health was assessed with one single five-point question. Linear trends between SPPB scores and self-rated health were tested separately for men and women at each of the five international study sites. Poor physical performance (independent variable) (SPPB less than 8) was used in logistic regression models of self-rated health (dependent variable), adjusting for potential covariates. All analyses were stratified by gender and site of origin.
RESULTS
A significant linear association was found between the mean scores of the Short Physical Performance Battery and ordinal categories of self-rated health across research sites and gender groups. After extensive control for objective physical and mental health indicators and socio-demographic variables, these graded associations became non-significant in some research sites.
CONCLUSION
These findings further confirm the validity of SRH as a measure of overall health status in older adults. | 10.1371/journal.pone.0153855 |
pubmed_146_9285 | This study aimed to evaluate a small-molecule PAI-1 inhibitor (PAI-039; tiplaxtinin) in a rodent stenosis model of venous thrombosis in a two-phase experiment. Phase 1 determined the efficacy of tiplaxtinin against Lovenox (LOV), while phase 2 determined the dose-dependent efficacy. For both phases, drug treatment began 24 hours after surgically induced venous thrombosis and continued for four days. Phase 1 animals (n = 24) receiving low-dose (LD; 1 mg/kg oral gavage) PAI-1 inhibitor demonstrated a 52% decrease in thrombus weight (TW) versus controls (p < 0.05) with significant reductions in active plasma PAI-1, while the high-dose (HD; 10 mg/kg oral gavage) group demonstrated a 23% reduction in TW versus controls. Animals treated subcutaneously with LOV (3 mg/kg) showed a 39% decrease in TW versus controls (p < 0.05). Coagulation tests (aPTT and TCT) were significantly different in LOV compared to PAI-1 inhibitor groups. PAI-039 treatment was also associated with significantly increased return of inferior vena cava blood flow four days post-thrombosis versus controls (p < 0.05). In phase 2 (n = 30), TW was reduced from the 0.5 mg/kg to 5 mg/kg experimental groups, with the 10 mg/kg group demonstrating a paradoxical increase. The 5 mg/kg group showed statistically significant decreases in TW versus controls after four treatment days (p < 0.05). This is the first study to demonstrate dose related effects of PAI-039 on increasing thrombus resolution and inferior vena cava blood flow without adverse effects on anti-coagulation in a rat stenosis model of venous thrombosis. | 10.1160/TH07-11-0669 |
pubmed_886_17429 | We evaluated dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in canine brain tumors. Magnetic resonance data sets were collected on seven canine intracranial tumors with a 3 T magnet using a T1-weighted fast spin echo fluid attenuated inversion recovery sequence after an IV bolus injection (0.2 mmol/kg) of Gd-DTPA. The tumors were confirmed histopathologically as adenocarcinoma (n=1), ependymoma (n=1), meningioma (n=3), oligodendroglioma (n=1), and pituitary macroadenoma (n=1) The data were analyzed using a two-compartment pharmacokinetic model for estimation of three enhancement parameters, E(R) (rate of enhancement), Kel (rate of elimination), and Kep (rate constant), and a model-free phenomenologic parameter initial area under the Gd concentration curve (IAUGC) defined over the first 90s postenhancement. Pearson's correlations were calculated between parameters of the two methods. The IAUGC has a relatively strong association with the rate of enhancement E(R), with r ranges from 0.4 to 0.9, but it was weakly associated with Kep and Kel. To determine whether any two tumors differed significantly, the Kohnlmogorov-Smirnov test was used. The results showed that there were statistical differences (P < 0.05) between distributions of the enhancement pattern of each tumor. These kinetic parameters may characterize the perfusion and vascular permeability of the tumors and the IAUGC may reflect blood flow, vascular permeability, and the fraction of interstitial space. The kinetic parameters and the IAUGC derived from DCE-MRI present complementary information and they may be appropriate to noninvasively differentiate canine brain tumors although a larger prospective study is necessary. | 10.1111/j.1740-8261.2009.01635.x |
pubmed_80_16057 | Complex crystallization pathways are common in protein crystallization, tetrahedrally coordinated systems, and biomineralization, where single or multiple precursors temporarily appear before the formation of the crystal. The emergence of precursors is often explained by a unique property of the system, such as short-range attraction, directional bonding, or ion association. But, structural characteristics of the prenucleation phases found in multistep crystallization remain unclear, and models are needed for testing and expanding the understanding of fluid-to-solid ordering pathways. Here, we report 3 instances of 2-step crystallization of hard-particle fluids. Crystallization in these systems proceeds via a high-density precursor fluid phase with prenucleation motifs in the form of clusters, fibers and layers, and networks, respectively. The density and diffusivity change across the fluid-fluid phase transition increases with motif dimension. We observe crystal nucleation to be catalyzed by the interface between the 2 fluid phases. The crystals that form are complex, including, notably, a crystal with 432 particles in the cubic unit cell. Our results establish the existence of complex crystallization pathways in entropic systems and reveal prenucleation motifs of various dimensions. | 10.1073/pnas.1905929116 |
pubmed_435_15961 | INTRODUCTION
Bladder cancer (BCa) is one of the most common and aggressive cancers. It is the sixth most frequently occurring cancer in men and its rate of occurrence increases with age. The current method of BCa diagnosis includes a cystoscopy and biopsy. This process is expensive, unpleasant, and may have severe side effects. Recent growth in the power and accessibility of machine-learning software has allowed for the development of new, non-invasive diagnostic methods whose accuracy and sensitivity are uncompromising to function.
OBJECTIVES
The goal of this research was to elucidate the biomarkers including metabolites and corresponding genes for different stages of BCa, show their distinguishing and common features, and create a machine-learning model for classification of stages of BCa.
METHODS
Sets of metabolites for early and late stages, as well as common for both stages were analyzed using MetaboAnalyst and Ingenuity® Pathway Analysis (IPA®) software. Machine-learning methods were utilized in the development of a binary classifier for early- and late-stage metabolites of BCa. Metabolites were quantitatively characterized using EDragon 1.0 software. The two modeling methods used are Multilayer Perceptron (MLP) and Stochastic Gradient Descent (SGD) with a logistic regression loss function.
RESULTS
We explored metabolic pathways related to early-stage BCa (Galactose metabolism and Starch and sucrose metabolism) and to late-stage BCa (Glycine, serine, and threonine metabolism, Arginine and proline metabolism, Glycerophospholipid metabolism, and Galactose metabolism) as well as those common to both stages pathways. The central metabolite impacting the most cancerogenic genes (AKT, EGFR, MAPK3) in early stage is D-glucose, while late-stage BCa is characterized by significant fold changes in several metabolites: glycerol, choline, 13(S)-hydroxyoctadecadienoic acid, 2'-fucosyllactose. Insulin was also seen to play an important role in late stages of BCa. The best performing model was able to predict metabolite class with an accuracy of 82.54% and the area under precision-recall curve (PRC) of 0.84 on the training set. The same model was applied to three separate sets of metabolites obtained from public sources, one set of the late-stage metabolites and two sets of the early-stage metabolites. The model was better at predicting early-stage metabolites with accuracies of 72% (18/25) and 95% (19/20) on the early sets, and an accuracy of 65.45% (36/55) on the late-stage metabolite set.
CONCLUSION
By examining the biomarkers present in the urine samples of BCa patients as compared with normal patients, the biomarkers associated with this cancer can be pinpointed and lead to the elucidation of affected metabolic pathways that are specific to different stages of cancer. Development of machine-learning model including metabolites and their chemical descriptors made it possible to achieve considerable accuracy of prediction of stages of BCa. | 10.1007/s11306-019-1555-9 |
pubmed_866_1079 | N-Phenyl-N-(trifluoromethylsulfonyl)propiolamides react with triphenylphosphane in the presence of various active methylene compounds CH2XY in a 1:1:1 molar ratio to furnish 1-phosphonium-5-oxabetaines, Ph3P+-C(R)=CH-C(O-)=CXY. These betaines are formed preferentially, but not exclusively, as E-diastereoisomers with respect to the vinylic double bond. In some cases, separation of the two diastereoisomers was achieved by fractionating crystallization. Structure determination by X-ray diffraction analysis revealed marked conformational differences around the CH-C(O-) single bond of E and Z-isomers and extended charge delocalization in the anionic part. | 10.3762/bjoc.15.253 |
pubmed_256_6608 | This study compares the recanalization characteristics of intracoronary streptokinase (IC-SK) with those of intravenous tissue plasminogen activator (t-PA) in patients with acute myocardial infarction (AMI) treated in the first 6 hours after onset of symptoms. We studied 263 patients with AMI. Among these, 160 were treated with IC-SK; in 59 the drug was given within the first 3 hours and in 101 from 3 to 6 hours. Another 103 patients were treated with IV t-PA; in 64 the drug was given in the first 3 hours and in 39 within 3 to 6 hours. The recanalization rate in the IC-SK group at 0 to 3 hours was 73% and at 3 to 6 hours was 71%, with an overall recanalization rate of 72% from 0 to 6 hours. In the t-PA group, the recanalization rate at 0 to 3 hours was 72% and at 3 to 6 hours was 46%, with an overall recanalization rate of 62%. We conclude that during the first 6 hours of AMI, IC-SK treatment resulted in a rather steady thrombolysis rate, while t-PA treatment with the standard regimen produced a significant decline in recanalization when administered after 3 hours from the onset of AMI symptoms. | 10.1097/00007611-199509000-00012 |
pubmed_5_5227 | A series of indolylmethylamine derivatives were assayed toward MAO-A and MAO-B inhibition. The K(i) values of these compounds are in the range from 0.8 to >10(6) nM for MAO-A or from 0.75 to 476000 nM for MAO-B. The most selective MAO-A or MAO-B inhibitors elicit a ratio of K(i) in the order of 1500 or 1000, respectively. Comparison of MAO-A and MAO-B CoMFA models showed that both the steric and electrostatic properties at the 5 position of the indole ring are determinant for MAO selectivity. Computational simulations of the complex between this part of the ligand and Phe-208 of MAO-A or Ile-199 of MAO-B, experimentally identified as responsible for substrate selectivity, allowed us to further characterize the nature of these enzyme-inhibitor interactions. | 10.1021/jm991164x |
pubmed_681_1374 | To limit the morbidity of cardiopulmonary bypass (CPB), a new concept of integrating pumping, oxygenation, and air removal into a single unit has been developed (CardioVention Inc., Santa Clara, CA). The air filtration capacity of this system was tested. Three calves (73.2 +/- 2 kg) were connected to the integrated system by jugular and carotid cannulation. The integrated unit was challenged with injections of boluses of air of 5, 10, and 20 ml, three times each, and for a blood flow of 3 L/min and 5 L/min, respectively. The bubble count and size were recorded downstream of the unit with a Doppler ultrasound. At 3 L/min, bubbles were detected after injections of 20 ml only (n = 7 for the nine boluses). At 5 L/min, 1 bubble was detected with the nine injections of 5 ml, 14 bubbles were detected with nine injections of 10 ml, and 25 bubbles were detected with nine injections of 20 ml. No bubble exceeded 40 microm in diameter as determined by the Doppler ultrasound. The air filtering capacity of the CardioVention system is excellent both in terms of bubble count and of size after injection of large boluses of air. Its integrated concept offers a simplification of the circuit with fewer devices and connections, which further reduces the risk of accidental air introduction. | pubmed_681_1374 |
pubmed_466_16378 | The regulation of intracellular pH (pHi) was investigated in reticulospinal neurons of the lamprey using ion-selective microelectrodes. Steady-state pHi in 23 mM HCO-3-buffered Ringer was 7.44 +/- 0.03 with a membrane potential of 54 +/- 4 mV (mean +/- S.E.M., n = 6). In nominally HCO-3-free solutions, pHi recovery from acid loading was blocked by 10(-3)M amiloride. Recovery was stimulated by transition to HCO-3-containing solutions. Results suggest that pHi regulation in lamprey reticulospinal neurons is mediated by a Na+-H+ exchanger. The presence of a distinct, HCO-3-dependent pHi regulatory mechanism is postulated. | 10.1016/0006-8993(85)90330-0 |
pubmed_722_15726 | Pleomorphic carcinoma (PC) is a rare malignancy of the lung. We present 3 cases that were resected. Case 1: The patient was a 75-year-old asymptomatic man whose chest roentgenogram showed a cavity at the right apex. A right upper lobectomy was performed, and the pathological stage was IB (pT2N0M0). After 3 courses of adjuvant chemotherapy, he is alive without relapse 56 months after the operation. Case 2: The patient was a 60-year-old man with left high back pain whose chest roentgenogram showed a mass shadow in the left upper lung field. A left upper lobectomy with partial resection of S6 was performed after induction chemotherapy. The pathological stage was IIIA (pT2N2M0). He died of infection 4 months after the operation during adjuvant chemotherapy. Case 3: A 78-year-old man with hemoptysis underwent aortic arch replacement after a diagnosis of impending rupture of an aortic aneurysm. During the operation, a tumor in the left upper lung lobe was detected. A left upper division segmentectomy was performed one month later. The pathological stage was IIB (pT3N0M0). Despite adjuvant radiotherapy, the patient died of cancer 9 months after the segmentectomy. The final pathological diagnoses for all 3 cases were PC. More cases of PC should be reported to establish optimal management. | pubmed_722_15726 |
pubmed_978_2774 | A recently introduced method (dual-photon X-ray absorptiometry, DEXA) capable of measuring skeletal density in man (at present in the spine and hips, but ultimately for the whole body) has been evaluated in terms of its ability to perform long-term assessment of bone density changes. The method, which uses X rays rather than gamma rays as its photon source, represents a significant improvement over present systems both in image quality and precision (reproducibility) of results, which is better than 1% in vivo. Scanning time is approximately halved compared with present techniques and the radiation dose is reduced by 25%. First data on long-term drift of results and effects of changes in patient composition (i.e. thickness and fat content) are given and show the new method to be superior to present radionuclide systems. It is likely that this new method will become the standard for bone density measurements. | 10.1259/0007-1285-62-739-587 |
pubmed_1006_4847 | In reviewing the first 10 years experience of the Royal Women's Hospital Family Birth Centre (FBC), we examined the outcomes of pregnancy and labour in a group of women who requested alternative birthing care and who were identified antenatally as being a 'low-risk' population. This study is a retrospective analysis of 5,365 women booked with the birth centre between 1980 and 1989. Over 16% of women developed antenatal complications precluding further care there, while a further 16% developed complications in labour requiring transfer out to conventional labour wards. Thus 67% of those originally booked delivered in the FBC. The instrumental delivery rate was 11%, and the Caesarean section rate was 4%. Of the women who delivered in the FBC, 3.1% had a postpartum haemorrhage and 1.8% required manual removal of placenta. Approximately 4% of babies born in the FBC required some resuscitation, and 0.8% needed admission to the neonatal nursery. Two perinatal deaths occurred in women admitted in labour to the FBC with a live baby, whilst 2 other women presented in labour with a fetal death in utero (perinatal mortality 0.89 per 1,000). | 10.1111/j.1479-828x.1992.tb02836.x |
pubmed_729_12901 | Cytosolic and membrane-associated proteins prepared from rice cells were separated and compared by two different 2D-PAGE methods, isoelectric focusing (IEF)/SDS-PAGE and nonequilibrium pH gradient electrophoresis (NEPHGE)/SDS-PAGE. Although IEF/SDS-PAGE of the cytosolic proteins showed sufficient resolution, some mitochondrial and basic microsomal membrane-associated proteins were weakly or hardly detectable on the 2D gel. High-quality and -quantity separation of the organelle membrane-associated proteins was accomplished by NEPHGE/SDS-PAGE, the advantage of this method being more critical in tightly membrane-bound proteins that were unwashable with NaCl. These results indicate that NEPHGE/SDS-PAGE is a useful tool for the proteomic analysis of rice membrane-associated proteins. | 10.1271/bbb.66.1170 |
pubmed_943_21411 | The pendant bubble method is commonly used to measure the evolution of the surface tension of surfactant solutions. Initially, the bubble interface is free of adsorbed surfactant. As time progresses, surfactant diffuses to the interface, adsorbs, and reduces the surface tension. The surface tension is assumed to be in equilibrium with the instantaneous surface concentration. Therefore, surface tension data are analyzed in terms of interfacial thermodynamics and mass transfer models in order to infer the mechanisms which determine the surfactant transport. Diffusion from the bulk solution to the bubble can be approximated as diffusion to a spherical interface. Approximating this process as diffusion to a plane introduces significant errors into the data analysis. Mass transfer to a sphere differs from that to a plane; the equilibration of the spherical interface is more rapid simply because of geometry. The failure to account for this effect in the interpretation of pendant bubble data can lead to serious errors in the transport coefficients for the surfactants. In the diffusion-controlled limit, surfactant diffuses to the sublayer immediately adjacent to the interface and adsorbs in local equilibrium according to the adsorption isotherm. There is a closed-form solution for Fick's law describing adsorption to a sphere in an infinite solution which reduces to the Ward and Tordai solution when the bubble radius is large. This equation, along with the adsorption isotherm relating the surface concentration and the sublayer concentration, must be solved numerically in order to solve for the time evolution of the surface concentration. At early times, the adsorption isotherm can be expanded about the clean interface state. At long times, small departures from the equilibrium state can be assumed. In these limits, asymptotic expansions can be obtained. The short- and long-time expansions are found in this study for adsorption to a sphere and compared to those obtained previously for adsorption to a planar interface. In particular, the long-time asymptote for adsorption to a sphere is proportional to t(-3/2); this asymptote differs significantly from that for adsorption to a plane, which goes as t(-1/2). The full solution for adsorption to a sphere is compared to the Ward and Tordai solution for adsorption to a planar interface. From a comparison of the full solutions, it is established that curvature cannot be neglected unless the ratio of the adsorption depth to the bubble radius is negligible. This ratio can be calculated a priori from equilibrium isotherm parameters. Using constants which describe the surfactant C(12)E(8), for which curvature plays a strong role in the surfactant adsorption dynamics, the short- and long-time solutions for adsorption to the interface are compared to the full solutions and to dynamic surface tension data to infer the range of validity of the approximations. Copyright 2001 Academic Press. | 10.1006/jcis.2001.7737 |
pubmed_793_9233 | Sera from patients with Crohn's disease were tested for antibodies against organisms which are thought to cause inflammatory bowel disease in animals, or have been implicated in human Crohn's disease. Control sera were collected from healthy individuals and patients with ulcerative colitis. Sera from Crohn's disease and controls failed to agglutinate Clostridium colinum or Campylobacter sputorum subsp. mucosalis and two strains of Mycobacterium paratuberculosis (M26 and M27). Most of the sera agglutinated a Citrobacter freundii variant, Mycobacterium paratuberculosis (M28) and Mycobacterium avium (M41) but Crohn's disease sera did not differ from controls. A complement fixation test against Chlamydia gave more positive reactions in patients with Crohn's disease and colitis than in healthy controls. There was a clear difference between the sera from patients with Crohn's disease and other sera, including ulcerative colitis, in agglutination tests with the commensal coccoid rods of the genera Eubacterium and Peptostreptococcus; in these tests 54% of sera from Crohn's disease were positive compared with 11% in ulcerative colitis and none of the sera from healthy controls. All the results were essentially negative with the exception of those from Eubacterium and Peptostreptococcus and these bacteria merit investigation. | 10.1136/gut.21.5.376 |
others_158_10625 | Using a simple in vitro amyloidopathy CAD neuronal model, infrared (IR) 1068 nm light treatment (5 × 3 minutes) was investigated as a novel neuroprotection strategy. Synthetic human β-amyloid(1-42) peptide was subjected to aggregation in a test-tube, and shown to form fibrils of a range of sizes (individually ~10 μm), which compromised the cellular nuclear integrity of CAD cells in culture, and elicited a dose-dependent neurotoxicity (β-amyloid(1-42) peptide concentration range 0-25 μM) up to 73%, which was significantly suppressed (up to 24%; p < 0.001) by prior treatment with IR1068. © 2014 Duggett NA, et al | 10.4172/0974-8369.S1.003 |
pubmed_994_8917 | A novel one-pot laser-assisted approach is reported herein for the synthesis of ordered carbons with embedded cobalt nanoparticles. The process is based on a UV pulsed laser exposure of an ethanolic solution consisting of green carbon precursors, a structure directing agent and a cobalt salt. Very short irradiation times (5 to 30 min) are only required to polymerize and cross-link carbon precursors (i.e. phloroglucinol and glyoxylic acid) independent of a catalyst presence. The influence of three metallic salts (acetate, nitrate and chloride) on the phenolic resin and carbon characteristics (structure, texture and particle size/distribution) was systematically studied. When exposed to UV laser, the metallic salt exhibited a strong influence on the particle size and distribution in the carbon matrix rather than on the textural carbon properties. Using cobalt acetate, very small (3.5 nm) and uniformly dispersed particles were obtained by this simple, fast and green one-pot synthesis approach. An original combined (13)C CP-MAS and DP-DEC solid state NMR spectroscopy analysis allowed to determine the structure of phenolic resins as well as the location of the cobalt salt in the resin. Complementarily, the (1)H solid-state and relaxation NMR provided unique insights into the rigidity (cross-linking) of the phenolic resin and dispersion of the cobalt salt. The magnetic properties of cobalt nanoparticles were found to be size-dependent: large Co nanoparticles (∼50 nm) behave as bulk Co whereas small Co nanoparticles are superparamagnetic. | 10.1039/c5nr01687h |
pubmed_186_5191 | Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful. | 10.1080/03007995.2016.1181051 |
pubmed_409_4660 | Satellite cells are myogenic cells attributed with the role of postnatal growth and regeneration in skeletal muscle. Following proliferation and subsequent differentiation, these cells will fuse with one another or with the adjacent muscle fiber, thereby increasing myonuclei numbers for fiber growth and repair. The potential factors which could regulate this process are many, including exercise, trauma, passive stretch, innervation, and soluble growth factors. Three classes of growth factors in particular (fibroblast growth factor, insulin-like growth factor, and transforming growth factor-beta) have been studied extensively with respect to their effects on satellite cell proliferation and differentiation in culture. Fibroblast growth factor has been shown to stimulate proliferation but depress differentiation. Insulin-like growth factor stimulates both proliferation and differentiation, although the latter to a much greater degree. Transforming growth factor-beta slightly depresses proliferation but inhibits differentiation. When administered in combination, these factors can induce satellite cell activities in culture which mimic those typical of satellite cells found in vivo in growing, regenerating, or healthy mature muscle. Alterations in the concentrations of these growth factors in the muscle environment as well as alterations in the cell's sensitivity or responsiveness to these factors represent potential mechanisms for regulating satellite cell activity in situ. | 10.3181/00379727-194-43060 |
pubmed_311_9779 | Homojunctions comprised of transition-metal dichalcogenides (TMD) polymorphs are attractive building blocks for next-generation two-dimensional (2D) electronic circuitry. However, the synthesis of such homojunctions, which usually involves elaborate manipulation at the nanoscale, still remains a great challenge. Herein, we demonstrated a solution-processing strategy to successfully harvest lateral semiconductor-metal homojunctions with high yield. Specially, through precisely controlled lithiation process, precursors of polymorphic crystal arranged with 1T-2H domains were successfully achieved. A programmed exfoliation procedure was further employed to orderly laminate each phase in the polymorphic crystal, thus leading to 1T-2H TMD homojunction monolayers with sizes up to tens of micrometers. Moreover, the atomically sharp boundaries and superior band alignment improved the device on the basis of the semiconductor-metal homojunction with 50% decrease of electric field strength required in the derivation of state transition. We anticipate that solution processing based on programmed exfoliation would be a powerful tool to produce new configurations of 2D nanomaterials. | 10.1021/jacs.8b11656 |
pubmed_647_1386 | Although the rate of congenital syphilis is declining in developed countries, a significant increase has been observed in the underdeveloped countries. Unfortunately, little concern is raised about the increasing numbers of babies born with congenital syphilis. The procedure to prevent congenital syphilis through antenatal screening and treatment is well established. But implementation of effective programs has proved very difficult especially in resource--poor settings. Congenital syphilis, if not treated promptly and adequately, may result in significant physical and emotional squeal in children. A case of complicated late congenital syphilis is reported in order to emphasize that syphilis is still present nowadays, and re-emerging many countries even some of the industrialized ones. Most of the cases can not be prevented by routine antenatal screening. Thus it is essential to develop strategies to prevent sexually transmitted disease from being a hidden and neglected problem. | 10.1016/j.ijporl.2005.03.007 |
pubmed_1111_9545 | Most studies have focused on the role of the cellular prion protein (PrP(C)) in neurodegenerative diseases, whereas the function of this ubiquitous protein outside the nervous system remains elusive. Therefore, the anti-apoptotic property of PrP(C) in oral squamous cell carcinoma (HSC-2) and colon adenocarcinoma (LS 174T) was evaluated in this study, by stable shRNA knockdown and overexpression, respectively. PrP(C) confers resistance against oxidative stress-apoptosis as indicated by MTT assay, Annexin V-FITC/PI and DCFH-DA staining, but this property is abolished upon N-glycosylation inhibition by tunicamycin. Our results indicate that the inhibition of glycosylation in cancer cells overexpressing PrP(C) could represent a potential therapeutic target. | 10.1016/j.canlet.2011.02.040 |
pubmed_171_2216 | OBJECTIVES
To obtain a Spanish version of the CHIP-CE semantically and culturally equivalent to the original version.
METHOD
The methodology used was based on the forward-backward method. Two translations into Spanish were performed. After the first reconciled version, 44 cognitive interviews were carried out with children aged 6-11 years old, selected from two schools in Barcelona. The interviews were recorded and transcribed. A qualitative content analysis of the textual data was carried out. A panel of experts developed the second reconciled version taking into account the children's comments. A back-translation into English was carried out and was compared with the original version.
RESULTS
Of a total of 45 items induced in the first reconciled version, 21 were considered equivalent, 23 required changes and 1 was considered not equivalent. Comprehension of abstract concepts differed according to age. Older children differentiated among concepts and gave different examples of experiences related to these concepts, while younger children (6 to 7-year olds) provided similar examples for different concepts. The children's comments were used in the reformulation of the items. An illustrative figure reinforced understanding. Children aged 7 or more started to use an adequate recall period and used the response options correctly.
CONCLUSIONS
The Spanish version of the CHIP-CE seems appropriate for children aged 6-11 in Spain. The present study shows that children from the age of 6 years onwards are able to describe the health concepts included in the CHIP-CE. | 10.1016/s1695-4033(04)78321-6 |
pubmed_175_4444 | An indirect aptamer-based SERS assay for insulin-like growth factor 2 receptor (IGF-IIR) protein was developed. The gold substrate and silver nanoparticles (AgNPs) were employed simultaneously to achieve double enhancement for SERS signals. Firstly, the five commercial SERS substrates including Enspectr, Ocean-Au, Ocean-AG, Ocean-SP and Q-SERS substrates were evaluated using 4-mercaptobenzoic acid (4-MBA). The Q-SERS substrate was selected based on low relative standard deviation (RSD, 8.6%) and high enhancement factor (EF, 8.7*105), using a 785 nm laser. The aptamer for IGF-IIR protein was designed to include two sequences: one grafted on gold substrate to specifically capture the IGF-IIR protein and a second one forming a 3' sticky bridge to capture SERS nanotags. The SERS nanotag was composed by AgNPs (20 nm), 4-MBA and DNA probes that can hybridize with the aptamer. Due to the steric-hindrance effect, when the aptamer doesn't combine with IGF-IIR protein, it only can capture the SERS nanotags. Therefore, there was a negative correlation between the concentration of IGF-IIR protein and the intensity of 4-MBA at 1076 cm-1. The detection limit reached to 141.2 fM and linear range was from 10 pM to 1 μM. The SERS aptasensor also exhibits a high reproducibility with an average RSD of 4.5%. The interference test was conducted with other four proteins to verify the accuracy of measuring. The study provides an approach to quantitative determination of proteins based on specific recognition and nucleic acid hybridization of aptamers, to establish sandwich structure for SERS enhancement. Graphical abstractSchematic representation of surface-enhanced Raman scattering (SERS) assay on insulin-like growth factor 2 receptor (IGF-IIR) protein by combining the aptamer modified gold substrate and 4-mercaptobenzoic acid (4-MBA) and DNA probe modified silver nanoparticles. | 10.1007/s00604-020-4126-x |
pubmed_353_12720 | Antimycin A (AMA), an electron transport chain inhibitor in mitochondria can produce reactive oxygen species (ROS) in cells. It has been reported that ROS may have roles in cell cycle progression via regulating cell cycle-related proteins. In the present study, we investigated the changes of the cell cycle distribution in AMA-treated HeLa cells in relation to cell cycle-related proteins. DNA flow cytometric analysis indicated that treatment with AMA significantly induced an S phase arrest of the cell cycle at 72 h. AMA decreased the expression of cyclin-dependent kinase inhibitor (CDKI), p21 and p27, CDK4, and cdc2 proteins. The expression of CDK6, cyclin D1, cyclin E, cyclin A, and cyclin B proteins was increased by 0.5 microM AMA, but was decreased by 2 and 10 microM AMA. The phosphorylation of Rb on the Ser (780) residue was increased by 0.5 microM AMA. Furthermore, treatment with AMA caused the accumulation of cells expressing cyclin A, B, and D1 proteins at the S phase of the cell cycle. However, treatment with 100 microM AMA nonspecifically extended all phases of the cell cycle. In conclusion, treatment with AMA (2, 10 and 50 microM) induced an S phase arrest of the cell cycle. An S phase arrest was accompanied by the alteration of other cell cycle-regulated proteins as well as S phase-related proteins. | 10.1016/j.lfs.2008.06.023 |
pubmed_1098_24410 | Spontaneous material shape changes, such as swelling, growth or thermal expansion, can be used to trigger dramatic elastic instabilities in thin shells. These instabilities originate in geometric incompatibility between the preferred extrinsic and intrinsic curvature of the shell, which may be modified by active deformations through the thickness and in plane, respectively. Here, we solve the simplest possible model of such instabilities, which assumes the shells are shallow, thin enough to bend but not stretch, and subject to homogeneous preferred curvatures. We consider separately the cases of zero, positive and negative Gauss curvature. We identify two types of supercritical symmetry-breaking instability, in which the shell's principal curvature spontaneously breaks discrete up/down symmetry and continuous planar isotropy. These are then augmented by inversion instabilities, in which the shell jumps subcritically between up/down broken symmetry states and rotation instabilities, in which the curvatures rotate by 90° between states of broken isotropy without release of energy. Each instability has a thickness-independent threshold value for the preferred extrinsic curvature proportional to the square root of Gauss curvature. Finally, we show that the threshold for the isotropy-breaking instability is the same for deep spherical caps, in good agreement with recently published data. | 10.1098/rsos.220487 |
pubmed_1020_10772 | BACKGROUND AND OBJECTIVES
A quantitative evaluation of the PK of meropenem, a broad-spectrum β-lactam antibiotic, in plasma and interstitial space fluid (ISF) of subcutaneous adipose tissue of obese patients is lacking as of date. The objective of this study was the characterisation of meropenem population pharmacokinetics in plasma and ISF in obese and non-obese patients for identification of adequate dosing regimens via Monte-Carlo simulations.
METHODS
We obtained plasma and microdialysate concentrations after administration of meropenem 1000 mg to 15 obese and 15 non-obese surgery patients from a prospective clinical trial. After characterizing plasma- and microdialysis-derived ISF pharmacokinetics via population pharmacokinetic analysis, we simulated thrice-daily (TID) meropenem short-term (0.5 h), prolonged (3.0 h), and continuous infusions. Adequacy of therapy was assessed by the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) analysis based on time unbound concentrations exceeded minimum inhibitory concentrations (MIC) on treatment day 1 (%fT > MIC) and the sum of PTA weighted by relative frequency of MIC values for infections by pathogens commonly treated with meropenem. To avoid interstitial tissue fluid concentrations below MIC for the entire dosing interval during continuous infusions, a more conservative PK/PD index was selected (%fT > 4 × MIC).
RESULTS
Adjusted body weight (ABW) and calculated creatinine clearance (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.5-81.5 kg/m2) explained a considerable proportion of the between-patient pharmacokinetic variability (15.1-31.0% relative reduction). The ISF:plasma ratio of %fT > MIC was relatively similar for MIC ≤ 2 mg/L but decreased for MIC = 8 mg/L over ABW = 60-120 kg (0.50-0.20). Steady-state concentrations were 2.68 times (95% confidence interval [CI] = 2.11-3.37) higher in plasma than in ISF, supporting PK/PD targets related to four times the MIC during continuous infusions to avoid suspected ISF concentrations constantly below the MIC. A 3000 mg/24 h continuous infusion was sufficient at MIC = 2 mg/L for patients with CLCRCG_ABW ≤ 100 mL/min and ABW < 90 kg, whereas 2000 mg TID prolonged infusions were adequate for those with CLCRCG_ABW ≤ 100 mL/min and ABW > 90 kg. For MIC = 2 mg/L and %fT> MIC = 95, PTA was adequate in patients over the entire investigated range of body mass and renal function using a 6000 mg continuous infusion. A prolonged infusion of meropenem 2000 mg TID was sufficient for MIC ≤ 8 mg/L and all investigated ABW and CLCRCG_ABW when employing the PK/PD target %fT > MIC = 40. Short-term infusions of 1000 mg TID were sufficient for CLCRCG_ABW ≤ 130 mL/min and distributions of MIC values for Escherichia coli, Citrobacter freundii, and Klebsiella pneumoniae but not for Pseudomonas aeruginosa.
CONCLUSIONS
This analysis indicated a need for higher doses (≥ 2000 mg) and prolonged infusions (≥ 3 h) for obese and non-obese patients at MIC ≥ 2 mg/L. Higher PTA was achieved with prolonged infusions in obese patients and with continuous infusions in non-obese patients.
TRIAL REGISTRATION
EudraCT: 2012-004383-22. | 10.1007/s40262-021-01070-6 |
pubmed_256_12129 | The purpose of this study was to identify factors that affect the adjustment of women and their husbands to recurrent breast cancer and to examine the mutual effect that partners have on one another. An exploratory study was designed to determine the relationship between four predictor variables (support, uncertainty, symptom distress, hopelessness) and women's and husbands' adjustments. The sample consisted of 155 subjects; 81 women, who had a first recurrence of breast cancer, and 74 husbands. Multiple standardized instruments with established reliability and validity were used to measure the study variables. The independent variables were measured with the Social Support Questionnaire, the Mishel Uncertainty in Illness Scale, McCorkle Symptom Distress Scale and the Beck Hopelessness Scale. The dependent variable, psychosocial adjustment, was measured with the Brief Symptom Inventory and the Psychosocial Adjustment to Illness Scale. The results indicated that the independent variables accounted for 43% of the variance in women's distress and 32% of the variance in husbands' distress; they also explained 66% of the variance in women's role adjustment problems and 57% of the variance in husbands' role problems. Symptom distress and hopelessness accounted for the most variance in women's and husbands' levels of adjustment. A significant and positive relationship was found between women's and husbands' adjustment scores, indicating that partners have a mutual influence on one another. The findings suggest that there are multiple factors that influence couples' adjustment to recurrent breast cancer, and that these factors need to be taken into consideration when planning care for women and their partners. | 10.1016/0277-9536(94)00302-a |
pubmed_210_18450 | OBJECTIVES
The aim of this study was to investigate the impact of acute left ventricular unloading by percutaneous left ventricular assist device on pulmonary congestion and pneumonia in patients with cardiogenic shock (CS).
METHODS
In this retrospective study, we analysed patients with CS who received the Impella percutaneous left ventricular assist device (n=50) compared with those who received intra-aortic balloon pump (IABP) support (n=50). Pulmonary congestion was longitudinally assessed while on support by calculating characteristic findings on the chest X-ray using the Halperin score. The rate of pneumonia and early mortality were assessed as a secondary endpoint.
RESULTS
The groups (Impella vs IABP) did not differ in terms of age, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology, Chronic Health Evaluation (APACHE) II score or serum lactate levels. Pulmonary congestion decreased in patient treated with Impella at each time point postimplantation. No change in congestion status was observed in patients supported with IABP. Multivariate analysis indicated Impella support as an independent predictor for pulmonary decongestion (OR 4.06, 95% CI 1.15 to 14.35, p=0.030). The rate of early pneumonia was lower in the Impella group compared with the IABP group (54% vs 74%, p=0.037). Failure of pulmonary decongestion during mechanical circulatory support independently predicted early pneumonia (OR 0.28, 95% CI 0.12 to 0.70, p=0.006).
CONCLUSION
Pulmonary decongestion may facilitate treatment of pneumonia in patients with CS. Left ventricular unloading by Impella device might support pulmonary decongestion, although a larger prospective trial in this patient population is required. | 10.1136/openhrt-2020-001385 |
pubmed_161_2221 | Irradiation of nitric oxide myoglobin (NOMb) induces changes in the haem as well as protein moiety of NOMb, especially at doses of 400-800 krad. The changes in the protein include: Conformational changes, with apparent partial denaturation of globin alpha-helix as evidenced by circular dichroism. Preferential scission of the polypeptide chain and dimerization via covalent bond(s) as evidenced by SDS-polyacrylamide gel electrophoresis. Products with a spectrum of hydrodynamic volumes between those of the monomer and the dimer are also formed. The shift of NOMb pIs toward more acidic pHs (probably due to modification and/or destruction of basic amino acid residues by water radiolytic products) as evidenced by isoelectric focusing. | 10.1080/09553008314550931 |
pubmed_767_9273 | In this study, the dietary effects of probiotics with a liquid application system on meat quality and physicochemical characteristics of pigs were evaluated. A total of 80 Landrace×Yorkshire×Duroc (LYD) 3-way crossbred pigs (average age 175±5 d) were assigned to a conventional farm and a probiotics farm equipped with a liquid probiotics application system (40 pigs in each farm). The two treatments were: CON (diet without probiotics) and PRO (diet with probiotics). Dietary probiotics decreased shear force in the longissimus muscle compared to the control group (p<0.05). The treatment diet did not affect backfat thickness, carcass weight, meat color, cooking loss, water holding capacity (WHC), and drip loss. Dietary probiotics significantly reduced ash, salinity, and pH (at 5 and 15 d) (p<0.05). There was no significant effect on thiobarbituric acid reactive substance (TBARS) values. Polyunsaturated fatty acid (PUFA) and omega fatty acids (ω3 and ω6) were significantly (p<0.05) higher in the PRO group, whereas monounsaturated fatty acid (MUFA) was decreased. The free amino acid composition, serine, lysine, histidine, and arginine levels were significantly lower in the PRO than in the control group. The treatment group exhibited higher nucleotide compounds (hypoxanthine, inosine, GMP, IMP) than the controls. Also, levels of ascorbic acid and thiamin were significantly different (p<0.05), while minerals were not significantly different between the groups. In conclusion, feeding of probiotics had effects on shear force, ash, salinity, pH, PUFA, and some amino acids which related to taste and flavor without any negative effects on the pigs' carcass traits. | 10.5851/kosfa.2018.38.2.403 |
pubmed_1124_18998 | The core-lipid A region of the lipopolysaccharides from Proteus penneri strains 7, 8, 14, 15, and 21 was studied using NMR spectroscopy, ESI MS, and chemical analysis after alkaline deacylation, deamination, and mild-acid hydrolysis of the lipopolysaccharides. The following general structure of the major core oligosaccharides is proposed: [abstract: see text] where all sugars are in the pyranose form and have the D configuration unless otherwise stated, Hep and DDHep=L-glycero- and D-glycero-D-manno-heptose, respectively, K=H, and Q=H in strain 8 or alpha-Glc in strains 7, 14, 15, and 21. In addition, several minor structural variants are present, including those lacking Ara4N in strains 7 and 15 and having the alpha-GlcN residue N-acylated to a various degree with glycine in strains 7, 8, 14, and 21. In strain 14, there are also core oligosaccharides with K=amide of beta-D-GalpA with putrescine, spermidine, or 4-azaheptane-1,7-diamine; remarkably, these structural variants lack either the PEtN group or the alpha-Hep-(1-->2)-alpha-DDHep disaccharide fragment at alpha-D-GalpA. While structural features of the inner core part are shared by Proteus strains studied earlier, the outermost Q-(1-->4)-alpha-GalNAc-(1-->2)-alpha-DDHep-(1-->6)-alpha-GlcN oligosaccharide unit has not been hitherto reported. | 10.1016/s0008-6215(02)00024-1 |
pubmed_755_18185 | Cyclandelate and flunarizine, two vasoactive Ca2+ channel or Ca2+ overload blockers have been compared with respect to their in vivo action on field potentials recorded from the depths of the brain in freely moving rats. Whereas cyclandelate showed a dose dependent rapid onset of action in the range of 15 to 120 mg/kg i.p., flunarizine only induced weak effects very slowly, not reaching statistical relevance before the fourth hour after the injection (0.1 to 1.6 mg/kg). Even then no clear dose dependence could be recognized for flunarizine. With respect to the frequency content of the recorded signals a rather close similarity between both drugs could be seen. Comparison of the drug effects to our reference data base of more than 80 compounds revealed a close relationship to memantine, an antiparkinson drug, suspected to act on the NMDA (N-methyl-d-aspartate) receptor-ionophor complex controlling Ca2+ fluxes. There is some indication that cyclandelate might also act in a similar way at the molecular level. | 10.1016/s1043-6618(05)80078-7 |
pubmed_457_7163 | OBJECTIVE
The majority of age-dependent skin changes happen in the dermis layer inducing changes in skin collagen and in the proteoglycans. The main aim of this work is to study the efficacy of a Proteum serum, containing soybean-fragmented proteoglycans, against skin aging.
MATERIALS AND METHODS
In vitro tests were performed to evaluate the Proteum serum ability on activating the production of collagen and proteoglycans. An in vivo long-term study was performed to determine the efficacy of the Proteum serum when applied on skin. Protection of healthy skin against detergent-induced dermatitis and the antioxidant properties of the applied Proteum serum were also studied.
RESULTS AND DISCUSSION
The in vitro tests demonstrated that the Proteum serum was able to elevate the production of molecules which are essential for supporting the dermal extracellular matrix organization. These results were correlated by the in vivo measurements where a clear trend on improving the measured skin parameters due to the Proteum serum application was found.
CONCLUSIONS
A beneficial effect of the Proteum serum was demonstrated with an improvement in the skin roughness and a reinforcement of the skin barrier function. Moreover, a significant protector effect on human stratum corneum against lipids peroxides (LPO) was demonstrated. | 10.1080/14764172.2017.1288259 |
others_256_261 | Autosegregation for color types of aboveground and underground parts of plants (root flesh, petioles, and leaf nerves) in agamospermous progenies of sugar beet was analyzed. The ratio of dominant and recessive phenotypes in agamospermous progenies conformed to the model suggesting tight linkage (r = 0.08) between the genes Y/y and R/r controlling biosynthesis of the main pigments, betaxanthins and betacyanins, and the epistatic gene P/p controlling the amount and distribution of pigments in plant tissues. It was shown that color type is inherited independently both of monoanthousness-synanthousness and gene-cytoplasmic sterility-fertility of pollen. The degree of linkage between genes for color type, synanthousness-monoanthousness, and sterility-fertility of pollen estimated by gametic genetics completely coincided with values obtained earlier by methods of zygotic genetics | others_256_261 |
pubmed_1007_19837 | The inappropriate and over-prescribing of medication is an area of nursing fraught with legal and ethical considerations. It can lead to people being chemically restrained and must only be used in exceptional situations. Therapeutic alternatives should take precedent. This article reviews studies on chemical restraint that show high levels of neuroleptic drug prescribing, including pro re nata or 'when required' medication, in care settings for older people. Studies also demonstrate that chemical restraint tends to be used in busy and under-resourced settings. Reviews and audits of neuroleptic medication should be undertaken regularly to alert nurses to local trends and patterns. | 10.7748/nop2008.04.20.3.33.c6497 |
pubmed_809_15029 | Amyloid aggregates of the amyloid-beta (Abeta) peptide are implicated in the pathology of Alzheimer's disease. Anti-Abeta monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-Abeta mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize Abeta monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the Abeta(1-8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to Abeta(1-8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target Abeta with improved specificity and higher affinity. | 10.1073/pnas.0705888104 |
pubmed_800_9506 | Thrombotic microangiopathy (TM) is a serious complication of bone marrow transplantation (BMT) that resembles thrombotic thrombocytopenic purpura (TTP). In attempting to achieve hematopoietic cell chimerism in the pig-to-baboon model, we have observed TM following infusion of high doses (>10(10) cells/kg) of porcine peripheral blood mobilized progenitor cells (PBPC) into baboons. We performed investigations to analyze the pathobiology of this TM and to test therapeutic interventions to ameliorate it. PBPC were obtained by leukapheresis of cytokine-stimulated swine. The initial observations were made in two baboons that underwent a non-myeloablative regimen (NMR) prior to PBPC transplantation (TX) (group 1). We then studied three experimental groups. Group 2 (n = 2) received NMR without PBPC TX. Group 3 (n = 2) received PBPC TX alone. Group 4 (n = 6) received NMR + PBPC TX combined with prostacyclin, low-dose heparin, methylprednisolone, and cyclosporine was replaced by anti-CD40L mAb in five cases. Baboons in groups 1 and 3 developed severe thrombocytopenia (<10,000/mm3), intravascular hemolysis with schistocytosis (>10/high powered field (hpf)), increase in plasma lactate dehydrogenase (LDH) (2500-9000 U/l), transient neurologic changes, renal insufficiency, and purpura. Autopsy on two baboons confirmed extensive platelet thrombi in the microcirculation, and, similar to clinical BMT-associated TM/TTP, no unusually large vWF multimers or changes in vWF protease activity were observed in the plasma of baboons with TM. In group 2, self-limited thrombocytopenia occurred for 10-15 days following NMR. Group 4 baboons developed thrombocytopenia (<20,000/mm3) rarely requiring platelet transfusion, minimal schistocytosis (<3/hpf), minor increase in LDH (<1000 U/l), with no clinical sequelae. We conclude that high-dose porcine PBPC infusion into baboons induces a microangiopathic state with vWF biochemical parameters resembling clinical BMT-associated TM/TTP and that administration of antithrombotic and anti-inflammatory agents can ameliorate this complication. | 10.1038/sj.bmt.1703067 |
pubmed_616_13358 | Cardiac hypertrophy is determined by an increase of cell size in cardiomyocytes (CMCs). Among the cellular processes regulating the growth of cell size, the increase of protein synthesis rate represents a critical event. Most of translational factors promoting protein synthesis stimulate cardiac hypertrophy. In contrast, activity of translational repressor factors, in cardiac hypertrophy, is not fully determined yet. Here we report the effect of a translational modulator, eIF6/p27BBP in the hypertrophy of neonatal rat CMCs. The increase of eIF6 levels surprisingly prevent the growth of cell size induced by phenylephrine, through a block of protein synthesis without affecting skeletal rearrangement and ANF mRNA expression. Thus, this work uncovers a new translational cardiac regulator independent by other well-known factors such as mTOR signalling or eIF2β. | 10.1016/j.bbrc.2017.11.046 |
pubmed_618_6887 | Stress-inducible protein 1 (Stip1) is one of the well-studied co-chaperones, although limited researches have been conducted in testis and epididymis. Here we found that Stip1 was ubiquitously expressed in various human tissues, including the testis and epididymis. In human testis and epididymis, Stip1 was localized in the cytoplasm of diverse cell types. Stip1 showed a developmentally-regulated manner and it was up-regulated after heat shock in rat testis and epididymis. However, the expression of Stip1 was significantly down-regulated in the testis, with tremendous histomorphological changes under oxidative stress. This study will lay the foundation for revealing the mechanism of Stip1 in the male reproductive system. | pubmed_618_6887 |
pubmed_382_19055 | AIM
The study of effective and regulatory functions of neutrophilic granulocytes in patients with pollenosis exacerbation, correction of the impaired neutrophil function with standard treatment and specific immunotherapy (SIT).
MATERIALS AND METHODS
The study included 103 healthy donors (controls) and 122 patients with pollenosis aggravation. 69 of the latter received symptomatic treatment. 53 patients received preseasonal SIT with water-salt extracts of the pollen allergens.
RESULTS
The untreated pollenosis patients had hyperproduction of interleukin-1 (IL-1) by nonstimulated blood neutrophils associated with elevation of NBT-reduction and lowering of phagocytic activity in decreasing count of Fc- and Ca-receptors. Effective SIT produced recovery of phagocytic activity, the number of Fc- and Ca-receptors, IL-1-activity of cell supernatants.
CONCLUSION
One of the SIT targets in pollenosis patients is neutrophilic granulocytes. | pubmed_382_19055 |
pubmed_373_1594 | Galparan is a 27-amino acid long chimeric peptide, GWTLNSAGYLLGP-INLKALAALAKKIL amide, consisting of galanin-(1-13) linked to mastoparan amide via a peptide bond to provide the mastoparan and galanin effector parts of the molecules. Galparan (10 microM) powerfully stimulates insulin secretion from isolated rat pancreatic islets in a reversible and dose-dependent manner; the stimulation is 26-fold at 3.3 mM glucose and 6-fold at 16.7 mM glucose. Galparan also enhances insulin secretion to a similar extent from islets of diabetic GK rats. The stimulatory effect of galparan on insulin release is not directly dependent on extracellular Ca2+, nor can it be explained only by changes in free cytosolic Ca2+ concentrations. Furthermore, galparan is effective in evoking insulin release in B cells depolarized by 25 mM KCl when ATP-sensitive K+ channels are kept open by diazoxide. Thus, galparan, like mastoparan, stimulates exocytosis of insulin at a distal site in the stimulus-secretion coupling of the B cell. This distal site is not identical to that used by mastoparan, as pertussis toxin pretreatment does not influence the insulinogenic effect of galparan. In conclusion, galparan evokes a large and reversible insulin secretion, acting at a yet unknown distal site and also promoting exocytosis in depolarized B cells from normal rats as well as diabetic GK rats. | 10.1210/endo.138.8.5307 |
pubmed_135_6546 | In the present review, which is aimed at researchers, teachers and students in life sciences, we try to show how the physicochemical properties of the elements and molecules define the concept of redox balance. Living organism are open systems traversed by fluxes of energy and matter. During catabolic oxidative metabolism, matter-mostly hydrogenated organic molecules-is oxidized and ultimately released as CO2. Electrons are passed over to coupling molecules, such as NAD+ and FAD, whose reduced forms serve as electrons donors in anabolic reactions. Early photosynthetic activity led to the accumulation of O2 and the transformation of the reduction to an oxidizing atmosphere, favoring the development of oxidative metabolism in living organisms. We focus on the specific properties of O2 that provide the chemical energy for the combustion reactions occurring in living cells. We explain the concepts of redox potential and redox balance in complex systems such as living cells, we present the main redox couples involved in cellular redox balance and we discuss the chemical properties underlying their cellular roles and, in particular, their antioxidant properties in the defense against reactive oxygen species (ROS). Finally, we try to provide an integrative view emphasizing the interplay between metabolism, oxidative stress and metabolic compartmentation in mammalian cells. | 10.3390/antiox11101877 |
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