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pubmed_40_16639 | BACKGROUND
Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis.
METHODS
We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site.
RESULTS
By different assays in isogenic HCT116p53+/+ and HCT116 p53-/- cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53+/+ but not in HCT116 p53-/- xenografts in vivo. In addition, R2 sensitized HCT116p53+/+ cells to doxorubicin and 5-fluorouracil.
CONCLUSIONS
Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches. | 10.1186/1471-2407-13-342 |
pubmed_1117_1018 | Many functions of the brain and the sympathetic adrenal system are influenced by those amino acids that exert precursor control over neurotransmitter synthesis. One of the functions affected is regulation of blood pressure. Therefore, the purpose of this review is to describe how food proteins and amino acids affect the synthesis of neurotransmitters and their regulation of blood pressure. | 10.1139/y86-149 |
pubmed_921_18214 | The paper deals with psychophysiological monitoring on an automatic [symbol: see text] phi K-01 psychophysiological diagnosis unit made in Russia. The unit is intended to detect latent and initial manifestations of stress reactions in healthy individuals and to evaluate the efficiency of psychopharmacological therapy and psychotherapy. | pubmed_921_18214 |
pubmed_403_14629 | This paper investigates the nexus between the legal provisions for the certification of insanity and the introduction of psychological medicine into British medical education. Considering legal and published sources, it shows that the 1853 Lunatic Asylums Act proved fundamental for the promotion of medical psychology as part of medical training. By giving doctors the authority to report "facts of insanity", this law created the need for "psychological physicians" capable of certifying lunacy. I explore this connection in three sections. First, I introduce the emergence of medical certificates in the context of asylum committal. Second, I focus on the certification procedure introduced in 1853 which required "facts of insanity personally observed". Third, I consider how British asylum doctors advocated for the diffusion of psychological medicine as an essential university subject for certifying practitioners. This paper emphasizes the relevance of confinement legislation in the development of psychiatry as a medical specialty. | 10.1016/j.ijlp.2020.101667 |
pubmed_310_6373 | This paper studies the cytotoxic effect induced by the topoisomerase I inhibitor camptothecin in human osteosarcoma Saos-2 cells, which lack p53 and contain a non-functional form of the product of the retinoblastoma gene, pRb. Cytotoxicity induced by camptothecin was dose- and time-dependent; the treatment with 100 nM camptothecin reduced cell viability by 50% at 32 h and by 75% at 72 h of exposure. The cytotoxic effect was caused by apoptosis, as ascertained by morphological evidence, acridine orange-ethidium bromide staining and flow cytometric analysis. Apoptosis was accompanied by both the activation of caspase-3 and the fragmentation of poly(ADP-ribose) polymerase. Treatment with camptothecin caused a threefold increase in the activity of c-Jun N-terminal kinase (JNK) and an eightfold increase in the level of phosphorylated c-Jun. The introduction of the RB gene into Saos-2 cells reduced the rate of cell growth. Moreover, stable clones of transfected cells were resistant to camptothecin. Exposure to 100 nM camptothecin for 72 h reduced the viability of transfected cells by only 10%; moreover, very modest effects were observed on the activity of JNK as well as on the level of phosphorylated c-Jun. The results reported in this paper support the conclusion that the expression of wild-type pRb in Saos-2 cells exerts an anti-apoptotic influence through the control of JNK activity. | 10.1016/s0014-5793(01)02553-4 |
pubmed_665_2070 | Quantification of cerebral arterial blood volume (CBVa) is important for understanding vascular regulation. To enable measurement of CBVa with diffusion-weighted (DW) arterial spin labeling (ASL), a theoretical framework was developed using the effects of intravoxel incoherent motion (IVIM). The pseudo-diffusion coefficient (D*) in the IVIM model was evaluated at 9.4 T in DW-ASL of rat brain under isoflurane anesthesia by variations of both post-labeling delay (w) and magnetization transfer ratio (MTR). D* and its volume fraction decreased at values of w>or=0.3 s, and the normalized apparent diffusion coefficient (ADC) increased with MTR, suggesting that D* is closely correlated with CBVa. Thus, the difference between ASL measurements with and without DW gradients is related to CBVa. The CBVa values measured by this approach were compared with values obtained using the modulation of tissue and vessel (MOTIVE) technique with ASL, which varies MT levels without changing spin labeling efficiency. CBVa values from both methods were highly correlated. The measured CBVa values were linearly correlated with cerebral blood flow (CBF) for a PaCO2 range of 25-50 mmHg; DeltaCBVa (ml/100 g)=0.007 (min-1)xDeltaCBF (ml/100 g/min). The DW-ASL approach is simple and easy to implement for human and animal CBVa studies. | 10.1002/mrm.20867 |
pubmed_512_24443 | BACKGROUND AND OBJECTIVES
Describing emotional experiences using distinct terms, or affect differentiation, has been associated with emotion regulation and adaptive behavior under stress. There is little data, however, examining the association between differentiation and dispositional factors underlying psychopathology. The current study examines the association between differentiation and trait anxiety (TA) given prior evidence of cognitive biases in TA relevant to higher order processing of emotional experiences.
DESIGN
We examined cross-sectionally, via lab-based repeated assessment, the association between differentiation of negative and positive experiences and TA.
METHODS
Two hundred twenty-two adults completed an emotion reactivity task including repeated assessments of affect. We hypothesized that individuals higher in trait anxiety (HTA) would have greater difficulty differentiating their experiences.
RESULTS
HTA individuals exhibited lower levels of negative affect (NA) differentiation even when controlling for depression. Although negative emotion intensity was consistently associated with lower differentiation, this did not account for the influence of HTA on differentiation.
CONCLUSIONS
These data suggest that HTA individuals have greater difficulty differentiating negative emotions, regardless of negative emotion intensity and depression. As HTA is common to many emotional disorders; this evidence suggests that poor differentiation may also be an important transdiagnostic consideration in models of risk and of affective disease. | 10.1080/10615806.2016.1163544 |
pubmed_1028_1309 | Adrenocortical response to exogenous acetylcholine (Ach) was investigated, under anesthetized conditions, in intact, hypophysectomized and head X-irradiated dogs. Intravenous injection of Ach (1 mg/kg b.w.) to intact dogs resulted in marked increases in the secretion of 17-hydroxycorticosteroids (17-OHCS) by the adrenal gland. The maximum response was seen at 10 min after the injection and a return to preinjection levels tended to occur by 60 min. This effect was abolished completely by hypophysectomy. In dogs whose heads had been irradiated with 200 and 1,000 R of X-rays 1 day previously, a considerably lower response to Ach was found; 17-OHCS output at the time when the secretion had been maximum was 44--53% less than that in non-irradiated dogs. | 10.1159/000122799 |
pubmed_763_5811 | Refractory orthostatic hypotension (OH) has been described following surgery for posterior fossa tumors. We present the case of a patient with refractory OH following attempted surgical resection. We also reviewed the available literature to describe pathophysiologic mechanisms for this rare entity. A 58-year-old female was found to have a hemangioblastoma at the cervicomedullary junction following workup for dysphagia and coordination difficulties. She underwent successful suboccipital craniotomy and gross total resection. However, the patient's symptoms returned several years later and a magnetic resonance imaging (MRI) showed tumor recurrence. A surgical resection was attempted but could not be performed due to significant scarring. Following discharge, she returned to our care with severe syncopal episodes, refractory OH, and an inability to ambulate. Aggressive medical therapy resulted in a gradual improvement in her ability to ambulate and a reduction in her orthostatic episodes. Unfortunately she died due to sepsis from aspiration pneumonia several months later. A survey of the literature yielded a total of 10 reports (14 patients) with refractory OH as a result of tumors in the cervicomedullary region. Five of fourteen patients died from complications related to OH and brainstem compression while the remainder had some improvement and were discharged. Refractory OH can rarely be a presenting sign of a tumor in the cervicomedullary junction or can manifest following surgical resection of tumors in this region. Recognition of OH and the institution of medical therapy (sodium and fluid replacement) and pharmacotherapy may curb the significant morbidity associated with this condition. | 10.7759/cureus.540 |
pubmed_48_570 | PURPOSE
The purpose of this study was to evaluate the clinical efficacy of enhancing deficient interdental papilla with hyaluronic acid gel injection by assessing the radiographic anatomical factors affecting the reconstruction of the interdental papilla.
METHODS
Fifty-seven treated sites from 13 patients (6 males and 7 females) were included. Patients had papillary deficiency in the upper anterior area. Prior to treatment, photographic and periapical radiographic standardization devices were designed for each patient. A 30-gauge needle was used with an injection-assistance device to inject a hyaluronic acid gel to the involved papilla. This treatment was repeated up to 5 times every 3 weeks. Patients were followed up for 6 months after the initial gel application. Clinical photographic measurements of the black triangle area (BTA), height (BTH), and width (BTW) and periapical radiographic measurements of the contact point and the bone crest (CP-BC) and the interproximal distance between roots (IDR) were undertaken using computer software. The interdental papilla reconstruction rate (IPRR) was calculated to determine the percentage change of BTA between the initial and final examination and the association between radiographic factors and the reconstruction of the interdental papilla by means of injectable hyaluronic acid gel were evaluated.
RESULTS
All sites showed improvement between treatment examinations. Thirty-six sites had complete interdental papilla reconstruction and 21 sites showed improvement ranging from 19% to 96%. The CP-BC correlated with the IPRR. More specifically, when the CP-BC reached 6 mm, virtually complete interdental papilla reconstruction via injectable hyaluronic acid gel was achieved.
CONCLUSIONS
These results suggest that the CP-BC is closely related to the efficacy of hyaluronic acid gel injection for interdental papilla reconstruction. | 10.5051/jpis.2016.46.4.277 |
pubmed_138_182 | To determine if there are admission criteria that predict success in graduate nursing education, an investigation was conducted of 193 graduates who had successfully completed the masters nursing program at a private eastern university. Admission criteria and other variables chosen were nursing, nonnursing, and cumulative undergraduate grade point averages (GPAs); verbal, quantitative, and combined Graduate Record Examination (GRE) scores; age at entrance; number of years intervening between attainment of the bachelors and completion of the masters degree; and, number of years intervening between the basic nursing education and the completion of the masters degree. Each variable was correlated with masters GPA for degree of association. Pearson's coefficient of correlation was used to analyze the data. Subgroups were analyzed in relation to the chosen area of clinical concentration: community health, psychiatric, medical-surgical, and maternal-child nursing; basic nursing education: diploma or generic baccalaureate; and, marital status: single or married. Nursing, nonnursing, and cumulative undergraduate GPAs were found to be weakly associated with the masters GPA except for the psychiatric subgroup which showed a moderate correlation between the cumulative under-graduate and the masters GPAs. Weak associations were found between verbal, quantitative, and total GRE scores and the masters GPA, with two exceptions: for psychiatric and community health subgroups there were moderate degrees of association between verbal GRE scores and the masters GPA. Age was not an effective criterion for predicting degree of success in the program. Both measures of intervening years were found to be weakly associated with the masters GPA. | pubmed_138_182 |
pubmed_363_13858 | Theoretical mass transfer rates and concentration distributions were determined for transient diffusion of free nitric oxide (NO) generated in vivo from vascular endothelial cells. Our analytical framework is typical of the bronchial circulation in the human pulmonary system but is applicable to the microvascular circulation in general. We characterized mass transfer rates in terms of the fractional mass flux across a boundary relative to the total endothelial NO production rate. NO concentration in the tissue surrounding blood vessels was expressed in terms of fractional soluble guanylate cyclase (sGC) activity. Our results suggest that endothelium-derived free NO is capable of vascular smooth muscle dilation despite its rapid consumption by hemoglobin in blood. An optimal blood vessel radius of 20 microm was estimated for NO signaling. We hypothesize intermittent generation of endothelial NO as a possible mechanism for sGC activation in vascular smooth muscle. This mechanism enhances the efficacy of NO-modulated vascular smooth muscle dilation while minimizing NO losses to blood and surrounding tissue. | 10.1152/ajpheart.00003.2002 |
pubmed_875_396 | To date germanene has only been synthesized on metallic substrates. A metallic substrate is usually detrimental for the two-dimensional Dirac nature of germanene because the important electronic states near the Fermi level of germanene can hybridize with the electronic states of the metallic substrate. Here we report the successful synthesis of germanene on molybdenum disulfide (MoS_{2}), a band gap material. Preexisting defects in the MoS_{2} surface act as preferential nucleation sites for the germanene islands. The lattice constant of the germanene layer (3.8±0.2 Å) is about 20% larger than the lattice constant of the MoS_{2} substrate (3.16 Å). Scanning tunneling spectroscopy measurements and density functional theory calculations reveal that there are, besides the linearly dispersing bands at the K points, two parabolic bands that cross the Fermi level at the Γ point. | 10.1103/PhysRevLett.116.256804 |
pubmed_410_8027 | Giant cell myocarditis is a rare cause of cardiogenic shock requiring a high index of suspicion, rapid immunosuppressive therapy, and mechanical circulatory support. We present the case of a patient with giant cell myocarditis who underwent a successful bridge with four different types of mechanical circulatory support devices to heart transplantation. (Level of Difficulty: Advanced.). | 10.1016/j.jaccas.2021.11.013 |
pubmed_664_4622 | A novel supporting material containing polythiophene (PTh) and multiwalled carbon nanotubes (MWCNTs) (PTh-CNTs) is prepared by in situ polymerization of thiophene on carbon nanotubes using FeCl(3) as oxidizing agent under sonication. The prepared polythiophene/CNT composites are further decorated with Pt and Pt-Ru nanoparticles by chemical reduction of the corresponding metal salts using HCHO as reducing agent at pH = 11 (Pt/PTh-CNT and Pt-Ru/PTh-CNT). The fabricated composite films decorated with nanoparticles were investigated towards the electrochemical oxidation of ethylene glycol (EG). The presence of carbon nanotubes in conjugation with a conducting polymer produces a good catalytic effect, which might be due to the higher electrochemically accessible surface areas, electronic conductivity and easier charge-transfer at polymer/electrolyte interfaces, which allows higher dispersion of Pt and Pt-Ru nanoparticles. Such nanoparticle modified PTh-CNT electrodes exhibit better catalytic behavior towards ethylene glycol oxidation. Results show that Pt/PTh-CNT and Pt-Ru/PTh-CNT modified electrodes show enhanced electrocatalytic activity and stability towards the electro-oxidation of ethylene glycol than the Pt/PTh electrodes, which shows that the composite film is more promising for applications in fuel cells. | 10.1088/0957-4484/19/04/045504 |
pubmed_257_14084 | Histopathological alterations in the liver and kidneys were examined in adult female rats and in their offspring form two matings after oral exposure to 7500 ppm lead (acetate) in drinking water. The length of exposure was up to 20 weeks. To estimate the reversibility of the effects in a number of exposed females lead administration was discontinued five weeks before their second breeding with unexposed males (the recovered group). In the group of exposed adult females histopathological changes in parenchymal organs were analogous to those seen in their pups from the first (shorter exposure), and second offspring (longer exposure to lead). Fatty and/or hydropic degenerative changes in the liver and kidneys and haemosiderosis of the liver were observed in both adult females and their young. In the liver of exposed pups the presence of numerous large foci of extramedullary erythropoiesis was also detected. In the kidneys of exposed adult females non-specific chronic inflammatory changes were seen. In the group of recovered females, after discontinuation of oral exposure to lead, histopathological findings indicated the reversibility of morphological changes. In their "recovered" pups the findings were also almost normal. It may be concluded that young rats are more susceptible to adverse action of lead than their mothers.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_257_14084 |
pubmed_80_869 | As one important electrode reaction in electrocatalytic and photoelectrochemical cells for renewable energy circulation, oxygen catalysis has attracted considerable research in developing efficient and cost-effective catalysts. Due to the inevitable formation of oxygenic intermediates on surface sites during the complex reaction steps, the surface structure dynamically evolves toward reaction-preferred active species. To date, transition metal compounds, here defined as TM-Xides, where "X" refers to typical nonmetal elements from group IIIA to VIA, including hydroxide as well, are reported as high-performance oxygen evolution reaction (OER) electrocatalysts. However, more studies observe at least exterior oxidation or amorphization of materials. Thus, whether the TM-Xides can be defined as OER catalysts deserves further discussion. This Review pays attention to recent progress on the surface reconstruction of TM-Xide OER electrocatalysts with an emphasis on the identification of the true active species for OER, and aims at disseminating the real contributors of OER performance, especially under long-duration electrocatalysis. | 10.1002/smll.201901980 |
pubmed_892_20822 | The pathophysiology of left-ventricular hypertrophy is characterized by structural remodeling with increasing content of collagen and development of ventricular dilatation ('Gefügedilatation'). According to recent clinical view points, three stages may be distinguished: first stage, compensation, second stage, diastolic dysfunction with delayed relaxation and decrease of the passive-elastic properties, third stage, systolic and diastolic dysfunction with decreasing pump function and signs of left-ventricular failure. Diastolic dysfunction is linked to delayed rotation during isovolumetric relaxation (delayed 'untwisting') which leads to decreased ventricular filling. These changes of the myocardial adaptation process may be prevented and the vicious circle interrupted by appropriate therapeutic strategies. | pubmed_892_20822 |
pubmed_855_20511 | The purpose of the study was to investigate the effects of Opuntia megacantha leaf extracts on blood glucose concentrations and kidney function in normal and streptozotocin (STZ)-diabetic rats. STZ-diabetic and non-diabetic rats were orally administered extracts of O. megacantha leaves (20 mg/100 g body weight) daily for 5 weeks and respective control rats were administered normal saline (0.1 ml/100 mg body weight). Urine volume, urinary outputs of Na+, K+ and creatinine were monitored daily over the 5-week period. Plasma concentrations of Na+, K+, urea and creatinine and the glomerular filtration rate (GFR) as assessed by creatinine clearance were determined after 5 weeks. Plasma glucose concentrations in STZ-diabetic and non-diabetic rats were reduced by the administration of leaf extracts of O. megacantha. However, leaf extracts increased urinary Na+ output in STZ-diabetic and non-diabetic rats, concomitantly with a reduction in plasma concentration of the ion. O. megacantha leaf extracts significantly increased plasma creatinine and urea concentrations in non-diabetic and STZ-diabetic rats. Administration of the leaf extract was also associated with an increased GFR in STZ-diabetic rats (from 1.8 +/- 0.3 ml/min to 2.8 +/- 0.3 ml/min, n = 8) although the rate was unaltered in non-diabetic rats. The results suggest that leaf extracts of O. megacantha not only reduce blood glucose levels, but may be toxic to the kidney as shown by the elevation in plasma urea and creatinine concentrations and the reduction of plasma Na+ concentration. | 10.1016/s0378-8741(99)00123-3 |
pubmed_417_17922 | Gene transfer techniques have now achieved clinical realization in the wake of recent advances in recombinant DNA technology, together with increased understanding of the molecular biology and immunology of cancer. These novel treatments, and their applications and limitations merit intensive study. | 10.1002/bjs.1800800507 |
pubmed_686_12775 | A general strategy for synthesizing Fe(III) complexes of ligands containing carboxamido-N and thiolato-S donors has been described. Reaction of the doubly deprotonated ligand PyPepS2- (where PyPepSH2=N-2-mercaptophenyl-2'-pyridinecarboxamide) with Fe(III) salts in DMF had previously afforded the Fe(III) complex (Et4N)[Fe(PyPepS)2] without any problem(s) associated with autoredox reactions of the thiolate functionality. In the present work, similar reactions with the doubly deprotonated ligand PiPepS2- (where PiPepSH2=2-mercapto-N-pyridin-2-yl-methylbenzamide) with Fe(III) salts, however, fail to afford any Fe(III) complex because of autoredox reactions. The break in the conjugation in the PiPepSH2 ligand frame is the key reason for this difference in behavior between these two very similar ligands. This is demonstrated by the fact that the same reaction with AqPepS2- (where AqPepSH2=2-mercapto-N-quinolin-8-yl-benzamide), another ligand with extended conjugation, affords the Fe(III) complex (Et4N)[Fe(AqPepS)2] without any synthetic complication. It is therefore evident that ligands in which the carboxamide and thiolate functionalities are kept in conjugation could be used to isolate Fe(III) complexes with carboxamido-N and thiolato-S coordination. This finding will be very helpful in future research work in the area of modeling the active site of Fe-containing nitrile hydratase. | 10.1021/ic051183z |
pubmed_1138_16509 | The authors report the results of two clinical studies on postoperative pain relief with PCA. In the first clinical study 44 patients, undergoing gynecologic surgery, were assigned at random to two groups. The first was treated by PCA (infusor Baxter) with morphine i.v. (basal bolus 0.05 mg/kg, loading doses 1 mg every 6-15'), the second with 10 mg morphine i.m. at the end of surgery and then on demand with a lock-out of 6h at least. In the 2nd clinical study, 40 elder patients submitted to orthopedic surgery, were assigned at random to two groups treated with PCA (morphine i.v., basal bolus 0.07 mg/kg, bolus PCA 0.007 mg/kg lock-out 15') and with continuous infusion (i.c.) (basal bolus 0.07 mg/kg, i.c. 0.02 mg/kg/h). Our data were analyzed with Student's "t" unpaired test and showed lower doses of the drug in the groups PCA (1st study PCA 25.98 mg/48h, i.m. 45.45 mg/48h, 2nd study PCA 0.155 mg/kg/12h, i.c. 0.311 mg/kg/12h) and lower rate of side effects in the same groups. Side effects were well controlled using symptomatic drugs. We proposed to our patients, at the end of observation, a questionnaire about general conditions, sleep, pain evaluation using a descriptive scale and retrospective evaluation. Patients and nurses agree PCA. Nursing staff expressed a positive opinion and patients said they benefitted from PCA. As reported, PCA appears from our results, valid and safe in postoperative pain relief. | pubmed_1138_16509 |
pubmed_421_18486 | Antimicrobial resistance (AMR) is one of the most important global health concerns; therefore, the identification of AMR reservoirs and vectors is essential. Attention should be paid to the recognition of potential hazards associated with wildlife as this field still seems to be incompletely explored. In this context, the role of free-living birds as AMR carriers is noteworthy. Therefore, we applied methods used in AMR monitoring, supplemented by colistin resistance screening, to investigate the AMR status of Escherichia coli from free-living birds coming from natural habitats and rescue centers. Whole-genome sequencing (WGS) of strains enabled to determine resistance mechanisms and investigate their epidemiological relationships and virulence potential. As far as we know, this study is one of the few that applied WGS of that number (n = 71) of strains coming from a wild avian reservoir. The primary concerns arising from our study relate to resistance and its determinants toward antimicrobial classes of the highest priority for the treatment of critical infections in people, e.g., cephalosporins, quinolones, polymyxins, and aminoglycosides, as well as fosfomycin. Among the numerous determinants, bla CTX-M-15, bla CMY-2, bla SHV-12, bla TEM-1B, qnrS1, qnrB19, mcr-1, fosA7, aac(3)-IIa, ant(3")-Ia, and aph(6)-Id and chromosomal gyrA, parC, and parE mutations were identified. Fifty-two sequence types (STs) noted among 71 E. coli included the global lineages ST131, ST10, and ST224 as well as the three novel STs 11104, 11105, and 11194. Numerous virulence factors were noted with the prevailing terC, gad, ompT, iss, traT, lpfA, and sitA. Single E. coli was Shiga toxin-producing. Our study shows that the clonal spread of E. coli lineages of public and animal health relevance is a serious avian-associated hazard. | 10.3389/fmicb.2021.656223 |
pubmed_213_11814 | A common finding in acute renal failure, particularly if it is caused by septic shock, consists of fibrin deposits in the intrarenal blood vessels. In a study of fibrinolytic parameters in 82 patients with severe bacterial infections, a significant negative correlation between plasminogen plasma concentration and serum creatinine was found. On admission the plasminogen levels were lower than the alpha 2-antiplasmin concentrations, which means a reduction of the fibrinolytic capacity due to a preponderance of the inhibitor. Preliminary experience with a replacement therapy is here reported. In 9 patients with an acute renal failure due to septicaemia or other serious diseases with shock, a substitution with fresh frozen plasma and antithrombin III concentrate was carried out in order to stop disseminated coagulation. A considerable increase of urine excretion was observed in 5 of these patients in close connection with the additional administration of a plasminogen concentrate. | pubmed_213_11814 |
pubmed_869_4481 | OBJECTIVE
To describe the characteristics of self-described 'occasional' and 'social' Australian smokers.
DESIGN
Analysis of a national cross-sectional survey of smoking patterns, conducted in Australia in 2004.
SETTING AND PARTICIPANTS
Australian adults in 2004 who responded to a survey question about self-described smoking status.
MAIN OUTCOME MEASURES
Demographic characteristics, patterns of alcohol and tobacco use, smoking cessation attempts in the past year, and interest in cessation.
RESULTS
Smokers who described themselves as 'occasional' and 'social' smokers comprised 29% of all smokers. A significant proportion of occasional and social smokers had been daily smokers, but the majority either believed that they had 'already quit' or had no intention of quitting smoking.
CONCLUSIONS
Self-ascribed occasional and social smokers potentially represent an important target group for cessation. These types of smokers may be more resistant to public health messages regarding cessation because they do not view their smoking behaviour as presenting a high risk. | 10.1111/j.1467-842x.2006.tb00784.x |
pubmed_628_4404 | The kinetics of cyclization of the 2-methyl-6,6-diphenyl-5-hexeniminyl radical (3) were measured by laser flash photolysis methods from 0 to 50 degrees C, and the kinetics of trapping of radical 3 by thiophenol and p-chlorothiophenol were determined between 4 and 83 degrees C by indirect methods using the unimolecular rate constants as the basis values. Radical 3 cyclizes with a rate constant of 2.2 x 10(6) s(-)(1) at 25 degrees C and reacts with thiophenol and p-chlorothiophenol at this temperature with rate constants of 0.6 and 1.4 x 10(7) M(-)(1) s(-)(1), respectively. Bu(3)SnH reacted with 3 too slowly to prevent nearly complete cyclization, but a crude rate constant for the trapping reaction was estimated. The cyclization and trapping reactions of iminyl radical 3 are slower than the corresponding reactions of alkyl radicals. | 10.1021/jo961530+ |
pubmed_787_5022 | A physical organic chemist wants to understand the detailed sequence of bond makings and bond breakings by which new or well-known reactions take place, i.e., the reaction mechanism, and to identify any metastable intermediates involved. The ultimate goal of such studies is to predict, and hope to control, chemical reactivity by determining how molecular structure and the immediate local environment affect a reaction of probative interest. Physical organic chemistry, in turn, provides structural insight, upon which others significantly depend for making new materials and for predicting and understanding new chemical and biochemical processes. I was fortunate in my own research to be able to study photocatalysis and photoinduced electron transfer as unifying themes that underlined our most significant work. | 10.1021/jo901731t |
pubmed_901_1619 | Thirty-four patients with metastatic breast cancer and no prior chemotherapy were treated with an induction regimen of four courses of adriamycin-cyclophosphamide followed by a fixed sequence of three courses of methotrexate-5-fluorouracil alternating with each course of adriamycin-cyclophosphamide. In this protocol, adriamycin can be administered for a minimum of 18 months before the dose of 550 mg/m2 is reached. The objective response rate was 56% (19 of 34 patients) with three complete responses and 16 partial responses. The median duration of response is 219 days and six of 19 patients remain in remission. The median survival of responders is 469 days while the nonresponders and progressors have a median survival of 273 days. The chemotherapy was administered in the outpatient department and was well tolerated. The scheduling of drugs in this study does not appear to result in significantly different response rates, duration of responses, or survival compared to those protocols in which these drugs are administered simultaneously. | pubmed_901_1619 |
pubmed_832_25086 | OBJECTIVES
Nipple-sparing mastectomy (NSM) has become more frequently utilized due to superior psychological and cosmetic outcomes. The aim of this study was to evaluate the accuracy and utility of intraoperative frozen section evaluation of the retroareolar margin (RAM) in NSM. The management of atypical epithelial proliferative lesions at the RAM was also reviewed and discussed.
METHODS
A single institution, retrospective analysis was performed on all therapeutic NSM patients with intraoperative evaluation of the RAM from 2014 to 2018. Patient demographics, tumor characteristics, pathologic assessment of the RAM, surgical management, and clinical follow-up were reviewed.
RESULTS
Seventy-four nipple-sparing mastectomies with intraoperative evaluation of RAMs were identified. Concordance was 95% between frozen and permanent section diagnoses with 4 cases representing false negatives and no false positives. There were no instances of nipple-areolar complex (NAC) recurrence in all cases with preserved NACs (mean follow up: 750 days). In the 9 cases where NACs were excised based on intraoperative RAM evaluation, the findings in the excised NACs were negative in 6 and ductal carcinoma in situ in 3 cases. Postoperative measurement of the tumor to nipple distance was the only statistically significant variable associated with a positive RAM by multivariable logistic regression (OR 0.475; 95% CI 0.238-0.946).
CONCLUSIONS
Intraoperative RAM evaluation demonstrated high concordance with permanent histology. Negative RAM, including atypical epithelial proliferative lesions, led to NAC preservation without recurrence. Positive RAM alone did not predict NAC involvement, although pagetoid spread of ductal carcinoma in situ along nipple ducts may predict NAC positivity. | 10.1016/j.anndiagpath.2020.151697 |
pubmed_753_15760 | Silver-Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face, asymmetry and feeding difficulties. As many of these features are non-specific, clinical diagnosis of SRS remains difficult. Hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 and maternal uniparental disomy (mUPD) for chromosome 7 are found in up to 60% and around 5-10% of patients with SRS, respectively. Patients with ICR1 hypomethylation are more likely to have classical features of SRS, including asymmetry; patients with mUPD7 are more likely to have learning difficulties, particularly speech problems, although these are usually mild. As features vary widely in severity, clinicians should have a low threshold for genetic investigation of patients with features suggestive of SRS. | 10.1136/adc.2010.190165 |
pubmed_671_13750 | Venous drainage patterns at the craniocervical junction and skull base have been thoroughly described in the radiographic literature. The facial veins and their important anastomoses with the intracranial venous system are less well appreciated. This study of 54 consecutive normal cerebral angiograms demonstrates that visualization of the pterygoid plexus as well as the anterior facial, lingual, submental, and ophthalmic veins can be normal on common carotid angiograms. In contrast to previous reports, opacification of ophthalmic or orbital veins occurs in most normal internal carotid arteriograms. Visualization of the anterior facial vein at internal carotid angiography can also be normal if the extraocular branches of the ophthalmic artery are prominent and nasal vascularity is marked. | 10.2214/ajr.136.1.139 |
pubmed_599_1763 | We describe a method for observing real time replication of individual DNA molecules mediated by proteins of the bacteriophage replication system. Linearized lambda DNA is modified to have a biotin on the end of one strand, and a digoxigenin moiety on the other end of the same strand. The biotinylated end is attached to a functionalized glass coverslip and the digoxigeninated end to a small bead. The assembly of these DNA-bead tethers on the surface of a flow cell allows a laminar flow to be applied to exert a drag force on the bead. As a result, the DNA is stretched close to and parallel to the surface of the coverslip at a force that is determined by the flow rate (Figure 1). The length of the DNA is measured by monitoring the position of the bead. Length differences between single- and double-stranded DNA are utilized to obtain real-time information on the activity of the replication proteins at the fork. Measuring the position of the bead allows precise determination of the rates and processivities of DNA unwinding and polymerization (Figure 2). | pubmed_599_1763 |
pubmed_317_24131 | Zoos potential to facilitate visitor conservation behavior is commonly articulated. Few studies, however, have quantified whether zoos' conservation messages result in visitors implementing the behavior. To test if zoo conservation messages are adopted at home, I implemented a persuasive communication campaign which advocated keeping cats indoor at night, a behavior that is a potential solution to cats depredating native wildlife. Furthermore, I tested if a public commitment (signing a pledge card) strengthened the relationship between on-site intention to engage in the behavior and actual implementation of the behavior at home. The conservation behavior was included in the twice-daily animal presentations in the amphitheater. A sample of 691 visitors completed a survey as they exited the amphitheater that measured their recall of the conservation behavior and intention to engage in the behavior at home. The last 311 visitors to complete the survey were asked to sign a pledge card which was publicly displayed in the amphitheater. Six weeks after their zoo trip, visitors were contacted and asked if they had implemented the behavior. Recall of the conservation behavior was high (91% for control, 100% for pledge group) and the entire pledge group had implemented the behavior whereas just half (51%) of the control group did. Furthermore, signing the pledge card strengthened the relationship between onsite intention and at home behavior (r = 1.0 of for the pledge group and r = 0.21 for the control group). Overall, the zoo's conservation message was recalled and behavior implemented at home. | 10.1002/zoo.21197 |
pubmed_809_19468 | Midodrine, a prodrug, is converted after oral administration into its active drug, desglymidodrine, which acts as an alpha(1)-adrenoceptor stimulant. Midodrine is prescribed for the treatment of neurogenic orthostatic hypotension in patients with spinal cord injury. By virtue of its alpha(1)-adrenergic effects, midodrine causes an increase in the tone of the vesical sphincter, which may silently lead to progressive retention of urine, particularly in patients with spinal cord injury who void urine spontaneously. Further, midodrine may aggravate detrusor-sphincter dyssynergia, which can lead to hydroureteronephrosis. A 68-year-old man with C-4 tetraplegia was voiding urine satisfactorily through reflex detrusor contractions. He was prescribed midodrine (5 mg at 8:00 AM, 5 mg at 1:00 PM, and 2.5 mg at 10:00 PM) for postural hypotension. During the next 7 wk, this patient experienced severe leg spasms while passing urine, and the flow of urine became very slow. Intravenous urography showed bilateral hydroureteronephrosis, although an earlier study had revealed normal kidneys. Midodrine therapy was stopped, and intermittent catheterization 4 times a day, along with oral oxybutynin, was started. After midodrine was discontinued, the leg spasms during passage of urine and slowing of the urine stream coincident with the spasms disappeared completely. The patient was able to pursue activities of daily living without taking midodrine. A 40-year-old man with C-7 tetraplegia was passing urine spontaneously with no problem. For postural hypotension, he was prescribed midodrine (5 mg in the morning and 2.5 mg at lunchtime), fludrocortisone (100 microg daily), and ephedrine (15 mg by mouth, taken 10 min before getting up in the morning). Three months later, the patient presented with sweating. During the day, he would pass only small amounts of urine, but from evening onward, he would void large volumes of urine, and the sweating would diminish. Intravenous urography showed vesical diverticula; a postmicturition film revealed moderate residual urine. This patient was able to stop taking the second dose of midodrine, but he required midodrine and ephedrine in the morning to enable him to get up without feeling dizzy. After the noon midodrine dose was stopped, the patient's sweating diminished by late afternoon. During the morning hours, however, he continued to sweat and had difficulty passing urine. Intermittent catheterization was not possible in the community setting, and the patient remains under close follow-up. These cases illustrate that patients with cervical spinal cord injury who void spontaneously may develop insidious urologic adverse effects after taking midodrine for postural hypotension. When patients with spinal cord injury develop urologic adverse effects while taking midodrine, the drug should be stopped, and other pharmacologic agents (eg, fludrocortisone) and nonpharmacologic methods should be prescribed for management of orthostatic hypotension. If a patient continues to require midodrine to control postural hypotension, intermittent catheterization combined with antimuscarinic therapy (eg, oxybutynin) should be recommended instead of spontaneous voiding. | 10.1007/BF02849965 |
pubmed_348_21733 | Solar exposure, vitamin D, and their possible beneficial effect on cancer risk and cancer prognosis are a topic for research. Despite the distinct nature of sunlight, it has proved difficult to assess the exposure quantitatively in epidemiological studies. Skin cancers, latitude, and sunny climate have been used as proxy indicators of solar exposure above a reference level. The interpretation of such data may still be hampered by incomplete cancer registration, difference in protection against sunbeams, selection mechanisms, and absence of information on potential confounders. A recently published paper -- on second primary cancer following the diagnosis of a skin cancer -- is discussed to illustrate the difficulties. Further epidemiological studies of potentially protective effects from carcinogenic ultraviolet rays should include individual information on solar exposure and vitamin D levels, as well as on other recognised and relevant risk factors. | 10.1016/j.ejca.2007.10.019 |
pubmed_1017_8751 | Tyrosine kinase activity of the asymmetric EGFR homodimer is negatively regulated via ERK-mediated phosphorylation of Thr-669 in the juxtamembrane domain. In the present study, we investigated in human breast cancer cells whether a similar mechanism plays a role in the feedback regulation of the ErbB2/ErbB3 heterodimer, the most potent ErbB receptor dimer. Constitutive tyrosine phosphorylation of ErbB2 and ErbB3 was significantly decreased in phorbol ester- and growth factor-treated BT-474 and MDA-MB-453 cells. In contrast to the decreased tyrosine phosphorylation, Phos-tag Western blot analysis revealed that TPA induced phosphorylation of ErbB2 in an ERK-dependent manner. The target threonine residue corresponding to EGFR Thr-669 and the surrounding residues are highly conserved in ErbB2, but not in ErbB3. Therefore, we demonstrated ERK-mediated phosphorylation of ErbB2 at Thr-677 by generating phospho-specific monoclonal antibodies. Moreover, treatment with trametinib and SCH772984, inhibitors of the MEK-ERK pathway, and substitution of Thr-677 to alanine impaired the feedback inhibition of ErbB2 and ErbB3. These results demonstrated that ERK-mediated phosphorylation of the conserved threonine is a common mechanism for the negative feedback control of active ErbB receptor dimers. | 10.1038/srep31502 |
pubmed_1104_978 | Like insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-5 was recently shown to form ternary complexes with insulin-like growth factor (IGF) and the acid-labile subunit (ALS). Previous studies using IGFBP-5/IGFBP-6 chimeric proteins have identified major and minor ALS binding sites in the carboxyl-terminal and central regions, respectively of IGFBP-5. We now report that ALS binds to IGFBP-3 (K(a) = 1.1 +/- 0.1 liters/nmol) and IGFBP-5 (K(a) = 1.8 +/- 0.5 liters/nmol) with similar binding affinities. Using site-specific mutants, we have identified residues K(211)/R(214)/K(217)/R(218) within the carboxyl-terminal region of IGFBP-5 as being essential for ALS binding. Mutation of K(134)R(136) or K(138)K(139) in the central region of IGFBP-5 resulted in a small decrease in ALS binding. | 10.1210/endo.142.5.8284 |
pubmed_559_9237 | Recent experiments suggest that Xenopus Neurotrophin Receptor Homolog 1 (NRH1) proteins act through the planar cell polarity pathway to regulate convergent extension movements during gastrulation and neurulation. We show in this paper that NRH1 proteins are also required for the proper expression of mesodermally expressed genes such as Xbra and Chordin, and to a lesser extent, of Xwnt11. Loss of NRH1 function is followed, during gastrula and neurula stages, by a dramatic increase in apoptosis. Apoptosis is delayed by injection of Xbra RNA, suggesting that cell death is a consequence, at least in part, of the down-regulation of this gene, and it is also delayed by expression of activated forms of Rho, Rac and Cdc42. These small GTPases have previously been implicated in the planar cell polarity pathway in Xenopus and, in other systems, in the regulation of apoptosis. We conclude that the effects of NRH1 proteins include the regulation of mesodermal gene expression and that the disruption of gastrulation that is caused by their loss of function is a consequence of the down-regulation of Xbra and other genes, in addition to direct interference with the planar cell polarity pathway. The apoptosis observed in embryos lacking NRH1 function is not an indirect consequence of the disruption of gastrulation, and indeed it may contribute to the observed morphological defects. | 10.1016/j.ydbio.2006.09.038 |
pubmed_1076_3551 | The polymorphism of 15 STR loci has been studied in a population sample of 193 healthy unrelated individuals from the population of Duzce, a city in the northwestern Turkey. The most valuable loci, from forensic point of view according to their power of discrimination values, were D2S1338, D18S51, FGA, and D19S433 where CSF1PO appeared to be the least powerful one. From paternity point of view, FGA, D21S11 were found to be the loci with highest exclusion value whereas D3S1358 and TPOX were the locus with the lowest exclusion. | 10.1016/j.forsciint.2007.02.005 |
pubmed_669_10291 | Despite significant progress made in the past two decades, silver nanoparticles (AgNPs) have not yet made it to the clinical trials. In addition, they showed both positive and negative effects in their toxicity from unicellular organism to well-developed multi-organ system, for example, rat. Although it is generally accepted that capped (bio)molecules have synergistic bioactivities and diminish the toxicity of metallic Ag core, convincing evidence is completely lacking. Therefore, in this review, we first highlight the recent in vivo toxicity studies of chemically manufactured AgNPs, biologically synthesized AgNPs and reference AgNPs of European Commission. Then, their toxic effects are compared with each other and the overlooked factors leading to the potential conflict of obtained toxicity results are discussed. Finally, suggestions are given to better design and conduct the future toxicity studies and to fast-track the successful clinical translation of AgNPs as well. | 10.1016/j.chemosphere.2021.133397 |
pubmed_1123_18304 | Ergonomic sleep studies benefit from long-term monitoring in the home environment to cope with daily variations and habituation effects. Polysomnography allows to asses sleep accurately, but is costly, time-consuming and possibly disturbing for the sleeper. Actigraphy is cheap and user friendly, but for many studies lacks accuracy and detailed information. This proof-of-concept study investigates Least-Squares Support Vector Machines as a tool for automatic sleep stage classification (Wake-N1-Rem to N2-N3 separation), using automatic trainingset-specific filtered features as derived from three easy to register signals, namely heart rate, breathing rate and movement. The algorithms are trained and validated using 20 nights out of a 600 night database from over 100 different healthy persons. Different training and test set strategies were analyzed leading to different results. The more person-specific the training nights to the test nights, the better the classification accuracy as validated against the hypnograms scored by experts from the full polysomnograms. In the limit of complete person-specific training, the accuracy of the algorithm on the test set reached 94%. This means that this algorithm could serve its use in long-term monitoring sleep studies in the home environment, especially when prior person-specific polysomnographic training is performed. | 10.3233/WOR-2012-0419-1985 |
pubmed_418_24361 | OBJECTIVES
This study aimed to evaluate pulse pressure fluctuation on dental local anesthetic administration in diabetic patients with and without coronary heart disease undergoing tooth extraction.
MATERIALS AND METHODS
This retrospective study in diabetic patients undergoing tooth extraction included 33 patients with coronary heart disease (mean age 79.3 ± 7.4, 64% male) and 49 patients without coronary heart disease (mean age 78.6 ± 6.5, 29% male). The increase in pulse pressure before and after administration of local anesthetics was compared between diabetic patients with and without coronary heart disease.
RESULTS
Pulse pressure was increased in male diabetic patients with coronary heart disease compared with those without coronary heart disease following administration of 3% prilocaine hydrochloride with felypressin 0.03 IU/mL (prilocaine) (15.6 ± 15.4 mmHg in those with coronary heart disease (n = 11) versus 4.3 ± 10.9 mmHg in those without coronary heart disease (n = 13), p = 0.03).
CONCLUSIONS
Prilocaine administration increased pulse pressure in male diabetic patients with coronary heart disease compared with those without coronary heart disease. Further study is needed to reveal the mechanisms involved in the increase in pulse pressure.
CLINICAL RELEVANCE
This is the first study of pulse pressure fluctuation in diabetic patients with and without coronary heart disease following administration of local anesthetics. Our findings can help guide the choice of local anesthetics and serve as a predictor of coronary vascular condition in diabetic patients during dental treatment. | 10.1007/s00784-019-02924-x |
pubmed_315_11764 | Little is known of the molecular mechanisms whereby spermatogonia, mitotic germ cells of the testis, self-renew and differentiate into sperm. Here we show that Zfp145, encoding the transcriptional repressor Plzf, has a crucial role in spermatogenesis. Zfp145 expression was restricted to gonocytes and undifferentiated spermatogonia and was absent in tubules of W/W(v) mutants that lack these cells. Mice lacking Zfp145 underwent a progressive loss of spermatogonia with age, associated with increases in apoptosis and subsequent loss of tubule structure but without overt differentiation defects or loss of the supporting Sertoli cells. Spermatogonial transplantation experiments revealed a depletion of spermatogonial stem cells in the adult. Microarray analysis of isolated spermatogonia from Zfp145-null mice before testis degeneration showed alterations in the expression profile of genes associated with spermatogenesis. These results identify Plzf as a spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool. | 10.1038/ng1367 |
pubmed_805_6509 | Receptors for estrogen and for androgen in the nucleus and cytosol (ERn, ERc, ARn, and ARc, respectively) were studied on two newly established human esophageal carcinoma cell lines, ES-25C and ES-8C. ES-25C was ERn+ (the binding content 4.0 fmol/mg protein, Kd 0.09 nM), ERc-, ARn-, and ARc-. No receptors were found in ES-8C. Various doses of 17 beta-estradiol (E2) were added in vitro to investigate its effect on the growth of these cell lines. No effect of E2 was observed on ER--ES-8C cell line. The growth of ES-25C cell was significantly inhibited at the doses of 10(-10) and 10(-12) mol/l E2 compared with the control. The doubling time of 10(-12) mol/l E2-treated cells was 32 hours whereas that of control was 20 hours. This slower growth was reflected in the deduction of cells in S-phase utilizing 5-bromo 2'-deoxyuridine (BrdU) labeling. The current results strongly suggest that the growth inhibition of ER+ esophageal cancer cell by E2 is mediated by signal transduction induced by the estrogen-estrogen receptor system. | 10.1002/1097-0142(19910501)67:9<2284::aid-cncr2820670913>3.0.co;2-2 |
pubmed_943_21061 | In estuarine ecosystems, large spatial and seasonal variations in delta13C values of primary producers can occur, and knowledge of these variations may be crucial when interpreting stable isotope data of higher trophic levels. Obtaining clean phytoplankton samples for isotope analysis is usually impossible in such systems, and analysis of total suspended matter is not a simple proxy for phytoplankton delta13C variations. Based on a few simple assumptions regarding the C and N content of the two end-members (terrestrial detritus and phytoplankton) and the delta13C of the terrestrial component, we here present a simple model to estimate the phytoplankton delta13C variations using an existing dataset on the delta13C and elemental (C:N) composition of suspended organic matter from an estuarine mangrove ecosystem in southeast India. These variations are related to the monthly rainfall pattern during the sampling period. It is stressed that this method estimates approximate phytoplankton delta13C values, which should not be used in e.g., mixing models. However, we propose that in cases where sufficiently large datasets are available, the described procedure could provide a valuable method to semi-quantitatively estimate the seasonal or spatial variations of the phytoplankton delta13C signal. | 10.1080/10256010008036387 |
pubmed_22_13914 | Increase in the level of reactive oxygen species (ROS) is a common response to stress factors, including exposure to metals. ROS over-production is associated with oxidation of lipids, proteins, and nucleic acids. It is suggested that the products of oxidation are not solely the markers of oxidative stress but also signaling elements. For instance, it has been shown in animal models that mRNA oxidation is a selective process engaged in post-transcriptional regulation of genes expression and that it is associated with the development of symptoms of several neurodegenerative disorders. In the present study, we examined the impact of short-term cadmium (Cd) stress on the level of two RNA oxidation markers: 8-hydroxyguanosine (8-OHG) and apurinic/apyrimidinic sites (AP-sites, abasic sites). In the case of 8-OHG, a significant increase was observed after 3 h of exposure to moderate Cd concentration (10 mg/l). In turn, high level of AP-sites, accompanied by strong ROS accumulation and lipid peroxidation, was noted only after 24 h of treatment with higher Cd concentration (25 mg/l). This is the first report showing induction of RNA oxidations in plants response to stress factors. The possible signaling and gene regulatory role of oxidatively modified transcripts is discussed. | 10.3389/fpls.2017.02219 |
pubmed_773_3476 | A case is presented of progressive acro-osteolysis of the hands combined with progressive mandibular ramus osteolysis and multiple cortical defects. The features of acro-osteolysis are reviewed and classified. | 10.1148/121.1.63 |
pubmed_730_7143 | Several quantitative traits associated with the asthma phenotype have been linked to markers on chromosome 11q13, although the gene responsible has yet to be well established. The gene for Clara cell secretory protein (CC16) is an ideal candidate for involvement in an inherited predisposition to asthma because of its chromosomal location, the role of the CC16 protein in controlling airway inflammation, and differences in levels of the protein between asthmatics and healthy controls. All three CC16 exons were screened in an unselected population of 266 subjects from 76 families and a cohort of 52 severely asthmatic children. A combination of single strand conformational polymorphism (SSCP) analysis, heteroduplex analysis, DNA sequencing, and restriction digestion was used. Mutation detection methods identified an adenine to guanine substitution in the CC16 gene at position 38 (A38G) downstream from the transcription initiation site within the non-coding region of exon 1. In the unselected population, 43.6% were homozygous for the polymorphic sequence (38GG) and 46.2% were heterozygous (38AG). All the asthmatic and unaffected children from both populations were selected for an unmatched case control analysis consisting of 67 asthmatic and 46 unaffected subjects. Those homozygous for the published sequence (38AA) had a 6.9-fold increased risk of developing asthma (p=0.049) and heterozygotes (38AG) a 4.2-fold increased risk (p=0.028). Modelling of genotype as a continuous covariate indicated evidence of a significant linear trend across the three genotypes (odds ratio=2.84 per unit increase in genotype code, p=0.018). These associations were independent of age, gender, and tobacco smoke exposure. These data and the known anti-inflammatory role of CC16 in the respiratory tract suggest that alteration to the gene at position 38 may contribute to asthma. | 10.1136/jmg.35.6.463 |
pubmed_490_19138 | PURPOSE
Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear.
MATERIALS AND METHODS
This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates.
RESULTS
A low dose of kaempferol (20 μmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells.
CONCLUSION
The low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway. | 10.2147/OTT.S140886 |
pubmed_292_23054 | RATIONALE, AIMS AND OBJECTIVES
To assess (feasibility) of adherence to treatment guidelines among outpatients with common mental disorders in a routine Dutch clinical outpatient setting for common mental disorders using administrative data.
METHODS
In a retrospective cohort study, we analysed routinely collected administrative data of 5346 patients, treated for mood, anxiety or somatoform disorders with pharmacotherapy, psychotherapy or a combination of both. Available administrative data allowed assessment of guideline adherence with a disorder-independent set of five quality indicators, assessing psychotherapy, pharmacotherapy, a combination of both and routine outcome measurements (ROM) during diagnostic and therapeutic phases. Associations between the socio-demographic variables age, gender, clinical diagnosis and treatment type on the one hand and non-adherence to guidelines were tested using logistic regression analysis.
RESULTS
Patients were aged 39.5 years (SD 13.0) on average. The majority of patients were treated with a combination of pharmacotherapy and psychotherapy (50.1%), followed by psychotherapy (44.2%) and pharmacotherapy (5.6%). The majority of patients were suffering from a mood disorder (50.0%), followed by anxiety (43.9%) and somatoform disorders (6.1%). A diagnosis of anxiety or somatoform disorder was associated with higher odds of suboptimal duration [odds ratio (OR): 1.55 and 1.82[ and suboptimal frequency of psychotherapeutic treatment (OR of 0.89 and 0.63), and absence of ROM in the diagnostic phase (ORs 1.31 and 1.36, respectively) compared with depressive disorders. No ROM in the diagnostic phase was also predicted for by increasing age (ORs for the age categories of 56 and older of 1.48).
CONCLUSIONS
In this proof of principal study, we were able to assess some key indicators assessing adherence to clinical guidelines by using administrative data. Also, we could identify predictors of adherence with simple parameters available in every administrative data. Administrative data could help to monitor and aid guideline adherence in routine care, although quality may vary between settings. | 10.1111/jep.12414 |
pubmed_1123_18836 | In Sweden there is a joint focus on injury prevention in agriculture and this is coordinated through the Swedish Committee on Working Environment (LAMK). LAMK is a network working for a good, healthy and safe working environment in Swedish agriculture from the view of the enterprise with the humans in focus. It is a committee consisting of representatives of authorities, institutions, companies, research & education institutions and organisations referring to the green sector. Examples of on-going initiatives & partners are presented which are included in this mission against injuries in agriculture. It involves the Swedish Work Environment Authority,, the Federation of Swedish Farmers (LRF), the Swedish Institute of Agricultural and Environmental Engineering, Swedish University of Agricultural Sciences (SLU, the Federation of Swedish Forestry and Agricultural Employers (SLA) and the Swedish Municipal Worker's Union. | 10.3233/WOR-2012-0048-5304 |
pubmed_392_15193 | BACKGROUND
Cryoglobulins are immunoglobulins that precipitate at low temperature. Strict preanalytical and analytical conditions are critical for the detection of cryoglobulins.
CONTENT
This review will focus on practical recommendations for detection and characterization of cryoglobulins and the technical problems that may be encountered. A laboratory report format is proposed for presentation of these results that includes the parameters necessary for an optimal interpretation by clinicians. The first step of detection of cryoglobulins can be performed in any laboratory that has a 37 °C incubator and temperature-controlled centrifuge. The second step is the characterization of cryoglobulins, and this often must be performed in more specialized laboratories. Characterization includes immunoglobulin typing, for the classification of cryoglobulins and potential underlying disease(s); quantification of immunoglobulins and rheumatoid factor in the cryoprecipitate to define the pathogenicity; and quantification of serum complement, which is useful for diagnosis.
SUMMARY
These practical recommendations will be useful for the accurate detection of cryoglobulins, an essential step for the diagnosis of cryoglobulinemic vasculitis, a rare but severe clinical manifestation of cryoglobulins. | 10.1093/clinchem/hvab195 |
pubmed_642_14890 | The 26S proteasome is the ATP-dependent protease responsible for regulating the proteome of eukaryotic cells through degradation of mainly ubiquitin-tagged substrates. In order to understand how proteasome responds to ubiquitin signal, we resolved an ensemble of cryo-EM structures of proteasome in the presence of K48-Ub4, with three of them resolved at near-atomic resolution. We identified a conformation with stabilized ubiquitin receptors and a previously unreported orientation of the lid, assigned as a Ub-accepted state C1-b. We determined another structure C3-b with localized K48-Ub4 to the toroid region of Rpn1, assigned as a substrate-processing state. Our structures indicate that tetraUb induced conformational changes in proteasome could initiate substrate degradation. We also propose a CP gate-opening mechanism involving the propagation of the motion of the lid to the gate through the Rpn6-α2 interaction. Our results enabled us to put forward a model of a functional cycle for proteasomes induced by tetraUb and nucleotide. | 10.1016/j.molcel.2019.01.018 |
pubmed_748_12968 | Traumatic lesions of the subcutaneous fatty tissue provide important clues for forensic reconstruction. The interpretation of these patterns requires a precise description and recording of the position and extent of each lesion. During conventional autopsy, this evaluation is performed by dissecting the skin and subcutaneous tissues in successive layers. In this way, depending on the force and type of impact (right angle or tangent), several morphologically distinct stages of fatty tissue damage can be differentiated: perilobular hemorrhage (I), contusion (II), or disintegration (III) of the fat lobuli, and disintegration with development of a subcutaneous cavity (IV). In examples of virtopsy cases showing blunt trauma to the skin and fatty tissue, we analyzed whether these lesions can also be recorded and classified using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). MSCT has proven to be a valuable screening method to detect the lesions, but MRI is necessary in order to properly differentiate and classify the grade of damage. These noninvasive radiological diagnostic tools can be further developed to play an important role in forensic examinations, in particular when it comes to evaluating living trauma victims. | pubmed_748_12968 |
pubmed_347_24883 | Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50±6.90 vs. 27.10±19.50 MN) and significantly decreased the CBPI (1.52±0.20 vs. 1.38±0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined. | 10.1620/tjem.229.115 |
pubmed_751_8323 | The in vivo quantitative structure-activity relationships (QSARs) for several polychlorinated biphenyls (PCBs) were determined in the immature male Wistar rat. The ED25 and ED50 values for hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction as well as for body weight loss and for thymic atrophy were determined for nine PCB congeners and 4'-bromo-2,3,4,5-tetrachlorobiphenyl. The most active compounds were the coplanar PCB congeners, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl; for example, their ED50 values for body weight loss were 3.25 and 15.1 mumol/kg, respectively. The in vivo toxicity of the coplanar PCB, 3,3',4,4'-tetrachlorobiphenyl, was significantly lower (ED50 for body weight loss = 730 mumol/kg) than the values observed for the more highly chlorinated homologs, and this was consistent with the more rapid metabolism of the lower chlorinated congener. The dose-response biologic and toxic effects of several mono-ortho-chloro-substituted analogs of the coplanar PCBs, including 2,3,4,4'5-, 2,3,3',4,4'-, 2',3,4,4',5- and 2,3',4,4',5-penta-, 2,3,3',4,4',5- and 2,3,3',4,4',5'-hexachlorobiphenyl were also determined, and members of this group of compounds were all less toxic than 3,3',4,4',5-penta and 3,3',4,4',5,5'-hexachlorobiphenyl. There was a good rank order correlation between the in vivo QSAR data and the in vitro QSARs for PCBs that were developed from their relative receptor binding affinities and potencies as inducers of AHH and EROD in rat hepatoma H-4-II E cells in culture. These results are consistent with the proposed receptor-mediated mechanism of action for PCBs. In addition, for this series of halogenated biphenyls there was a linear correlation between their in vivo toxicity in rats and their in vitro monooxygenase enzyme induction results. Assuming that the in vivo toxic responses in the rat are representative toxic responses to PCBs, then these results support the predictive utility of the in vitro bioassay with rat hepatoma H-4-II E cells as a short-term test system for the potential toxicity of this class of halogenated aryl hydrocarbons. | 10.1080/15287398509530748 |
pubmed_1094_10905 | BACKGROUND
Cold-induced thermogenesis is known to improve insulin sensitivity, which may become increasingly relevant in the face of global warming. The aim of this study was to examine the relation between outdoor air temperature and the risk of gestational diabetes mellitus.
METHODS
We identified all births in the Greater Toronto Area from 2002 to 2014 using administrative health databases. Generalized estimating equations were used to examine the relation between the mean 30-day outdoor air temperature before the time of gestational diabetes mellitus screening and the likelihood of diagnosis of gestational diabetes mellitus based on a validated algorithm using hospital records and physician service claims.
RESULTS
Over the 12-year period, there were 555 911 births among 396 828 women. Prevalence of gestational diabetes mellitus was 4.6% among women exposed to extremely cold mean outdoor air temperatures (≤ -10°C) in the 30-day period before screening and increased to 7.7% among those exposed to hot mean 30-day temperatures (≥ 24°C). Each 10°C increase in mean 30-day temperature was associated with a 1.06 (95% confidence interval [CI] 1.04-1.07) times higher odds of gestational diabetes mellitus, after adjusting for maternal age, parity, neighbourhood income quintile, world region and year. A similar effect was seen for each 10°C rise in outdoor air temperature difference between 2 consecutive pregnancies for the same woman (adjusted odds ratio 1.06, 95% CI 1.03-1.08).
INTERPRETATION
In our setting, there was a direct relation between outdoor air temperature and the likelihood of gestational diabetes mellitus. Future climate patterns may substantially affect global variations in the prevalence of diabetes, which also has important implications for the prevention and treatment of gestational diabetes mellitus. | 10.1503/cmaj.160839 |
pubmed_979_12110 | According to the author, a successful leadership change should not be left to chance. Such a transition must be planned and carefully managed. | 10.1108/eb039383 |
pubmed_254_5607 | Purpose: To describe and compare the clinical characteristics and laboratory analysis results of aqueous humor (AH) in fuchs uveitis syndrome (FUS) patients caused by rubella virus (RV) and cytomegalovirus (CMV). Methods: A retrospective and observation-based study was performed on 32 patients with FUS. Etiologies, clinical characteristics, ocular complications, visual prognoses, inflammatory cytokines, and virus-specific antibodies in AH were compared. Results: Among all the cases involved, 24 had RV FUS and 8 had CMV FUS. The mean age at diagnosis of FUS in the CMV group was older than that of the RV group (P = 0.031). The mean LogMAR best corrected visual acuity (BCVA) at initial presentation and at the final visit were both significantly higher in the CMV FUS group than those in the RV FUS group (P = 0.004, 0.047). The highest intraocular pressure (IOP) was significantly higher in the CMV group (P = 0.040). Consistent with elevated IOP, the CMV FUS patients were significantly more prone to developing glaucoma eventually than the RV FUS patients (P = 0.039). Vitreous opacity was found in 66.7% of the RV patients and 25.0% of the CMV patients (P = 0.038). The gender ratio, initial symptoms, presence and types of keratic precipitates, severity of anterior segment inflammation, iris lesions, and incidence of complicated cataract were similar between the two groups. There was no detectable difference of inflammatory cytokines in AH between RV FUS and CMV FUS. Conclusion: The clinical manifestations and disease prognosis vary between CMV FUS and RV FUS. However, clinical differences are always not obvious enough for differential diagnosis. The laboratory AH analysis is necessary to identify the etiology, determine the therapeutic strategies, and assess the disease prognosis. | 10.3389/fmed.2020.610341 |
pubmed_484_640 | PURPOSE
To investigate the changes of taste buds following injury to lingual nerve and the regeneration of the fungiform papillae and taste buds following microsurgical epineurial anastomosis of transecting injured lingual nerves in rats.
METHODS
We observed the numbers and shapes of the fungiform papillae and taste buds with stereomicroscope, light microscope, and scanning electron microscope at 20 and 100 days after the clamp injury to lingual nerve, or the transecting injury to lingual nerve with/without immediate microsurgical epineurial anastomosis of the injured lingual nerve in rats.
RESULTS
The fungiform papillae and taste buds degenerated, atrophied and their numbers diminished obviously at 20 days following either the clamp injury or transecting injury to the lingual nerve. The fungiform papillae and taste buds didn't regenerate spontaneously at 100 days following transection of the lingual nerve without microsurgery. The degenerated fungiform papillae and taste buds regenerated and recovered completely at 100 days following both clamp injury to the lingual nerve and transection of the lingual nerve with immediate microsurgical epineurial anastomosis.
CONCLUSION
The degenerated fungiform papillae and taste buds have good ability to regenerate spontaneously following clamp injury to the lingual nerve; the degenerated fungiform papillae and taste buds can regenerate completely with immediate microsurgical epineurial anastomosis of the transected lingual nerve. The quantity and morphology of fungiform papillae and taste buds can be used as objective indicators in the function rehabilitation of injured lingual nerve. | pubmed_484_640 |
pubmed_530_1601 | To investigate the lag effects and seasonal differences of urban air quality change on human health, we carried out a time-series analysis of daily general practitioner consultations for allergic rhinitis (AR) in Beijing, China. In earlier publications we had assessed the relative risks of air pollutants on AR in Beijing during the period 2009-2010. This article analyzes for the same time period the lag effects of air pollutants and the seasonal effects on daily number of outpatient with allergic rhinitis; differences among age groups and gender groups were also taken into consideration. The results show that, the largest effect RRs of PM(10) were at lag01, lag0, lag01, lag01, and lag01 for the total population, male, female, young/middle aged people (20-60 years age group), and old people (more than 60 years age group), respectively. The largest associations of SO(2) were observed at lag3, lag1, lag3, lag0 and lag0 for the total population, male, female, young people/middle aged people (20-60 years age group), and old people (more than 60 years age group), respectively. The strongest effects of NO(2) were found at lag03 for the total population, female and the young/middle aged people; at lag0 for male and lag03 for elder people. RRs of the three pollutants for AR have shown a decreasing relevance from NO(2) to PM(10) to SO(2). The seasonal effect models show that PM(10), SO(2), and NO(2) had higher risk for AR in the warm season than in the cold season. | pubmed_530_1601 |
pubmed_488_4408 | The author thinks that psychiatric examination (asked by the judge) can be a therapeutic act: the first. The expert should not think he is a therapeutic man, nor should he say he is, but he must create by his intervention the circumstances that are necessary for a therapy. | pubmed_488_4408 |
pubmed_240_19265 | Formulation development of protein therapeutics using polymeric nanoparticles has found very little success in recent years. Major formulation challenges include rapid denaturation, susceptibility to lose bioactivity in presence of organic solvents and poor encapsulation in polymeric matrix. In the present study, we have prepared hydrophobic ion pairing (HIP) complex of lysozyme, a model protein, using dextran sulfate (DS) as a complexing polymer. We have optimized the process of formation and dissociation of HIP complex between lysozyme and DS. The effect of HIP complexation on enzymatic activity of lysozyme was also studied. Nanoparticles were prepared and characterized using spontaneous emulsion solvent diffusion method. Furthermore, we have also investigated release of lysozyme from nanoparticles along with its enzymatic activity. Results of this study indicate that nanoparticles can sustain the release of lysozyme without compromising its enzymatic activity. HIP complexation using a polymer may also be employed to formulate sustained release dosage forms of other macromolecules with enhanced encapsulation efficiency. | 10.3109/10837450.2012.737806 |
pubmed_167_20233 | Enterobacter strains 090008T and 090028T were recovered from the blood of two different patients at West China Hospital, Chengdu, PR China in 2017. Phylogenetic analysis based on the 16S rRNA gene and multi-locus sequence analysis of the rpoB, gyrB, infB and atpD housekeeping genes revealed that the two strains were distinct from any previously known species of the genus Enterobacter. Both average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strains 090008T, 090028T and type strains of all known Enterobacter species were lower than the cut-off (≥95-96 % for ANI and ≥70 % for isDDH) to define a bacterial species. The major cellular fatty acids of strains 090008T and 090028T are C16 : 0, C17 : 0cyclo and C18 : 1ω7c, which are similar to other Enterobacter species, and the genomic DNA G+C content was 55.73 and 55.68 mol%, respectively. Strain 090008T can be differentiated from other Enterobacter species by its ability to ferment sucrose, melibiose and d-arabitol, but with a negative methyl α-d-mannopyranoside reaction. Strain 090028T can ferment potassium gluconate, but is negative for l-fucose, mdecarboxylase, deaminase aelibiose and d-sorbitol, which distinguishes it from all other Enterobacter species. Genotypic and phenotypic characteristics indicate that strains 090008T and 090028T represent two novel species of the genus Enterobacter, for which the names Enterobacter huaxiensissp. nov. and Enterobacter chuandaensis sp. nov. are proposed, respectively. The type strain of Enterobacter huaxiensissp. nov. is 090008T (=GDMCC1.1426T=CCTCC AB 2018174T=CNCTC 7648T) and the type strain of Enterobacter chuandaensissp. nov. is 090028T (=GDMCC1.1427T=CCTCC AB 2018173T=CNCTC 7649T). | 10.1099/ijsem.0.003207 |
pubmed_718_20116 | The presence of a genome-linked protein (VPg) at the RNA 5'-end of the genome is a characteristic of different groups of animal and plant positive-sense single-stranded RNA viruses. These viruses express their structural and functional proteins from polyproteins that are sequentially processed by at least one viral proteinase. The grapevine fanleaf nepovirus 24K chymotrypsin-like cysteine proteinase, located between the VPg and the RNA polymerase in the RNA-1 encoded polyprotein P1, is active in its free form and in various precursors forms. The VPg proteinase precursor (VPg-Pro) constitutes a stable protein and its maturation in the reticulocyte lysate system occurs at a very low rate. Differences on cleavage activity were observed between the proteinase and its VPg-Pro precursor forms, depending upon the cleavage site considered. The proteinase alone has a greater cleavage efficiency than VPg-Pro at the Arg605/Gly606 and Cys257/Ala258 sites of polyprotein P2. On the other hand, the presumed Cys415/Ala416 site, present at the amino terminus of polyprotein P1, was preferentially cleaved by the VPg-Pro precursor. During their in vitro maturation, proteins containing the VPg proteinase-polymerase coding region or the proteinase-polymerase region were similar in their ability to cleave in cis between the proteinase and the RNA polymerase. | 10.1006/viro.1994.1165 |
pubmed_63_12057 | alpha1-Antitrypsin is the prototypical member of the serine proteinase inhibitor or serpin superfamily of proteins. The family includes alpha1-antichymotrypsin, C1 inhibitor, antithrombin and neuroserpin, which are all linked by a common molecular structure and the same suicidal mechanism for inhibiting their target enzymes. Point mutations result in an aberrant conformational transition and the formation of polymers that are retained within the cell of synthesis. The intracellular accumulation of polymers of mutant alpha1-antitrypsin and neuroserpin results in a toxic gain-of-function phenotype associated with cirrhosis and dementia respectively. The lack of important inhibitors results in overactivity of proteolytic cascades and diseases such as COPD (chronic obstructive pulmonary disease) (alpha1-antitrypsin and alpha1-antichymotrypsin), thrombosis (antithrombin) and angio-oedema (C1 inhibitor). We have grouped these conditions that share the same underlying disease mechanism together as the serpinopathies. In the present review, the molecular and pathophysiological basis of alpha1-antitrypsin deficiency and other serpinopathies are considered, and we show how understanding this unusual mechanism of disease has resulted in the development of novel therapeutic strategies. | 10.1042/CS20080484 |
pubmed_984_990 | We performed preoperative chemotherapy with combined docetaxel, cisplatin and S-1 (DCS therapy) for treatment of advanced gastric cancer with para-aortic lymph node metastases. The aim of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities. Furthermore, we evaluated the feasibility of DCS therapy in a preoperative setting, and also examined the pathological response. Fifteen patients received intravenous docetaxel and cisplatin (30, 35 or 40 mg/m2, each dose escalation was reciprocal) on days 1 and 15 and oral S-1 (40 mg/m2 twice daily) on days 1-14 every 4 weeks. After one cycle of chemotherapy, toxicities were evaluated and after two cycles of chemotherapy, patients who were judged to be candidates for curative resection underwent gastrectomy with D2 lymphadenectomy plus para-aortic lymph node dissection. The MTD of this combination was presumed to be at dose level 3 (docetaxel 40 mg/m2 and cisplatin 35 mg/m2). The dose-limiting toxicities were grade 4 neutropenia in one patient, grade 3 febrile neutropenia in two patients and grade 3 diarrhoea in two patients. Thirteen of the 15 patients received complete resection and there was no operation-related death. Good pathological responses were observed in 12 cases with lesions in the lymph nodes (complete response, n = 4; partial response, n = 8) and 11 patients with primary stomach lesions (complete response, n = 2; partial response, n = 9). This preoperative DCS therapy was considered feasible and provided a high pathological response rate in gastric cancer patients with para-aortic lymph node metastases. | 10.1097/CAD.0b013e32832ec02b |
pubmed_962_8870 | In two experiments, we examined when and why ease of retrieval of information from memory affects behavioral frequency and attitudinal judgments. Overall, the results suggest that when the subjective experience of ease of retrieval is consistent with the expected ease of retrieval, the content of the information retrieved is used to make judgments. However, when there is a discrepancy between experienced and expected ease of retrieval, the subjective experience of ease of retrieval is used to make judgments. Ease of retrieval is more informative when the discrepancy between experienced and expected ease of retrieval cannot be attributed to task contingencies; when it can, ease of retrieval ceases to be informative. | 10.3758/bf03193077 |
pubmed_826_14344 | AIM
To investigate the effect of DT-13 on gastric cancer cell migration, and to explore the possible mechanisms underlying the anti-metastasis activity of DT-13.
METHODS
Growth inhibition of DT-13 was analyzed by the MTT assay. Cell migration was measured by the scratch-wound assay and transwell double chamber assay. To investigate the possible mechanisms underlying the anti-metastasis activity of DT-13, chemokine receptors that are involved in cancer metastasis (CCR2, CCR5, CCR7, CXCR4, and CXCR6) were detected by conventional PCR. The effect of DT-13 on CCR5 and CXCR4 expression was further evaluated by quantitative PCR and Western blot, respectively. The secretion of CCL5 (ligand of CCR5) and SDF-1 (ligand of CXCR4) were detected by enzyme-linked immunosorbent assay (ELISA).
RESULTS
DT-13 inhibited BGC-823 and HGC-27 cell growth in a dose dependent manner, and the estimated IC50 value for 24 h treatment was 23.5 ± 5.1 μmol·L(-1) for BGC-823 cells and 35.6 ± 7.6 μmol·L(-1) for HGC-27 cells. DT-13 also significantly decreased gastric cancer cell migration. DT-13 significantly decreased the gene expression of CCR5 in both BGC-823 and HGC-27 gastric cancer cells, and moderately reduced the expression of CXCR4. Similar to the results of gene expression, significant down-regulation of CCR5 protein was observed, but CXCR4 protein levels were much less affected. CCL5 secretion, but not SDF-1 production, was inhibited by DT-13.
CONCLUSION
DT-13 inhibited gastric cancer cell migration by down-regulation of the CCR5-CCL5 axis. | pubmed_826_14344 |
pubmed_28_8994 | We quantify the causal impact of human mobility restrictions, particularly the lockdown of Wuhan on January 23, 2020, on the containment and delay of the spread of the Novel Coronavirus (2019-nCoV). We employ difference-in-differences (DID) estimations to disentangle the lockdown effect on human mobility reductions from other confounding effects including panic effect, virus effect, and the Spring Festival effect. The lockdown of Wuhan reduced inflows to Wuhan by 76.98%, outflows from Wuhan by 56.31%, and within-Wuhan movements by 55.91%. We also estimate the dynamic effects of up to 22 lagged population inflows from Wuhan and other Hubei cities - the epicenter of the 2019-nCoV outbreak - on the destination cities' new infection cases. We also provide evidence that the enhanced social distancing policies in the 98 Chinese cities outside Hubei province were effective in reducing the impact of the population inflows from the epicenter cities in Hubei province on the spread of 2019-nCoV in the destination cities. We find that in the counterfactual world in which Wuhan were not locked down on January 23, 2020, the COVID-19 cases would be 105.27% higher in the 347 Chinese cities outside Hubei province. Our findings are relevant in the global efforts in pandemic containment. | 10.1016/j.jpubeco.2020.104272 |
pubmed_638_2466 | BACKGROUND
Small-bowel obstruction (SBO) is a common cause of hospital admission. Our objectives were to determine outcomes of laparoscopic adhesiolysis and outline clinical parameters for its utilization.
METHODS
We reviewed medical records of patients with SBO undergoing initial laparoscopic treatment by the authors between July 1997 and March 2006. Data obtained included demographics, clinical and radiologic presentation, intraoperative outcomes, and postoperative course.
RESULTS
Forty-two patients were included for analysis. The mean age was 54.3 years, whereas the mean body mass index was 29.5 (range 20.2-46.1). Laparoscopy diagnosed the site of obstruction in all patients. Thirty-five patients (83.3%) were successfully treated laparoscopically without conversion to laparotomy. The median procedural time was lower in patients completed laparoscopically (96.3 vs 207.3 minutes, P = .006). The median postoperative stay was 6.5 days (range 1-19) in patients who were completed laparoscopically.
CONCLUSIONS
Laparoscopy is safe and feasible in the management of acute SBO in selected patients. It is an excellent diagnostic tool and therapeutic in most cases. | 10.1016/j.amjsurg.2007.08.025 |
pubmed_895_2688 | Snake venoms can show biochemical and toxicological variability even in specimens from the same specie. The geographical localization of the snakes is one of the factors that can influence those variations. By these reasons the venom from specimens of Bothrops (Rhinocerophis) alternatus ("crucera", "yararágrande"), one of the snakes of highest medical importance in Argentina, from three different regions of Córdoba was studied. Lehtal potency, hemorrhagic, coagulant on plasma and thrombin like activities as well as the electrophoretic patterns of venom from snakes of Calamuchita, Traslasierras and the East of the province were determined. The venom from the snakes of the three regions showed the characteristic activities of the venom of the majority of Bothrops, causing hemorrhage, hemostatic disturbances acting on plasma or directly on fibrinogen with a "thrombin like activity". The different samples were very similar regarding their biochemical characteristics and toxic potencies at difference of previous observations on venoms from the same specie in different regions of other provinces fro Argentina. Bivalent antivenom, the one used by the Provincial Ministry of Health to treat the bothropic accidents, neutralized in all the cases the toxic activities of the venom in very similar range of neutralizing potency. | pubmed_895_2688 |
pubmed_887_2997 | The effects of medicinal plants on the mutagenicity of benzo[a]pyrene were studied with Salmonella typhimurium tester strains. The chosen medicinal plants are very frequently used as Chinese herbal medicines. Each medicinal plant was extracted with hot water, which is similar to the method used in Chinese medicinal treatment. Cinnamomi cortex, Rhei rhizoma, Scutellariae radix and Rehmanniae radix were found to decrease the mutagenic activity of benzo[a]pyrene. Atractylodis rhizoma also reduced the mutagenicity of benzo[a]pyrene, but this was not certain, because it showed a killing effect on the cell survival test. Bupleuri radix and Aurantii nobilis pericarpium had an enhancing effect, but then neither of these extracts is itself mutagenic. Each medicinal plant extract showed a different effect on the mutagenicity of benzo[a]pyrene. These effects were classified into 5 types: (I) decreasing effect, (II) killing effect, (III) enhancing effect, (IV) enhancing and decreasing effect and (V) inactive. | 10.1016/0165-1218(88)90118-8 |
pubmed_558_10318 | The aim of this work was to prepare and evaluate an oral dosage form intended for time-dependent colon delivery of insulin along with a selected protease inhibitor (camostat mesilate) and absorption enhancer (sodium glycocholate). A previously described release platform, which had proven potentially suitable for the protein delivery, was exploited. Insulin compatibility with the above-mentioned adjuvants was preliminarily evaluated. For this purpose, the drug and its main degradation products were assayed by HPLC in insulin powder mixtures with camostat mesilate and/or sodium glycocholate stored 12 months at 4 degrees C. No significant decrease in protein content or increase in degradation product percentages beyond Eur. Ph. 6th Ed. limits was highlighted. Moreover, calorimetric studies performed on physical and compacted binary insulin mixtures with camostat mesilate and sodium glycocholate showed that the thermal behavior of both adjuvants was unchanged. Subsequently, tablet cores with differing compositions were prepared and spray-coated with an aqueous HPMC solution in order to obtain pulsatile delivery systems. The coated units were demonstrated to concurrently release the drug and the adjuvants in a prompt and quantitative mode after consistent lag times. Based on these results, the device was proven a potential candidate for colon delivery of insulin and the selected adjuvants. | 10.1002/jps.21761 |
pubmed_258_25038 | The need to reduce carbon emission to cope with climate change has gradually become a global consensus, which also poses a great challenge to cold-chain logistics companies. It forces them to implement green distribution strategies. To help the distribution companies reduce carbon emission, this paper studies two aspects-carbon tax value and investing in the freshness-keeping cost-and proposes corresponding solutions. A new green vehicle-routing model for fresh agricultural products with the goal of minimizing the total cost is proposed. To solve the model proposed, an improved ant-colony optimization (IACO) is designed specifically. On one hand, the experimental results show that the increase in carbon tax will restrict the carbon emission behaviors of the distribution companies, but it will also reduce their economic benefits to a certain extent, at the same time. On the other hand, investing in the freshness-keeping cost can help actively achieve the carbon emission reduction target, reduce the loss of fresh agricultural products in the distribution process, improve the company's economic benefits and satisfy customers. The comparison results of different algorithms prove that the IACO proposed in this paper is more effective in solving the model, which can help increase the economic benefits of the companies and reduce carbon emission. This study provides a new solution for cold-chain logistics distribution companies to reduce carbon emission in the distribution process, and also provides a reference for government departments to formulate carbon tax policies. | 10.3390/ijerph19148675 |
pubmed_578_17206 | Some commonly encountered hand disorders such as trigger finger, carpal tunnel syndrome and Dupuytren's contracture occur up to 4 times more frequently in diabetic patients, affecting their activity and decreasing the quality of their life. The natural history of these disorders in diabetic patients and the outcome of treatment may not be the same as in the general population. Furthermore, some patients develop hand problems due to limited joint mobility. In this article, the authors review epidemiologic aspects as well as therapeutic considerations and outcomes of these hand disorders in diabetics. | pubmed_578_17206 |
pubmed_882_3140 | BACKGROUND
Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.
METHODS AND FINDINGS
Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications.
CONCLUSIONS
Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease. | 10.1371/journal.pntd.0004302 |
pubmed_792_10722 | Hypotaurine, concentrated under reduced pressure in HCl solution, partially (30-40%) degrades into taurine (about 30%), 2-aminoethyl-2-aminoethanethiolsulfonate (about 10%) and ethanolamine. The degradation products were identified using LC/APCI-MS, NMR, amino acid analysis and various chromatographies. The identities were confirmed by comparing the HPLS, MS and NMR characteristics of authentic compounds. One of the degradation processes during concentration of HCl solution of hypotaurine is therefore a disproportionation reaction which can interfere with the experimental results, when studying hypotaurine in biological systems. | 10.1007/BF01320900 |
others_201_7923 | (1) Background: Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECC causes non-physiological damage to blood components, its pathophysiology has not been fully elucidated. In our previous study, we constructed a rat ECC system and observed a systemic inflammatory response during and after blood tests assessing ECC, while the damage per organ localization caused by ECC was not examined. In this study, we used a rat model to assess the gene expression of inflammatory cytokines in major organs during ECC. (2) Methods: The ECC system consisted of a membranous oxygenator, tubing line, and a small roller pump. Rats were divided into a SHAM (which received surgical preparation only, without ECC) group and an ECC group. Proinflammatory cytokines were measured using real-time PCR in major organs after ECC to evaluate local inflammatory responses in the organs. (3) Results: Interleukin (IL)-6 levels were significantly elevated in the ECC group compared to the SHAM group, especially in the heart and lungs. (4) Conclusions: This study suggests that ECC promotes organ damage and the inflammatory response, but the degree of gene expression of proinflammatory cytokines varies from organ to organ, suggesting that it does not uniformly cause organ damage. © 2023 by the authors | 10.3390/jcm12082813 |
pubmed_524_16893 | In a cohort of 257 infants with congenital heart disease admitted to the pediatric intensive care unit, 22 infants had positive cultures for extended-spectrum beta-lactamase or AmpC Gram-negative bacteria. These infants had longer exposure to broad-spectrum antibiotics, greater support with invasive devices and longer intensive care and hospital lengths of stay. | 10.1097/INF.0000000000003129 |
pubmed_974_4101 | We report the first case of a neonate with concurrent Chiari II malformation and achondroplasia. Although rare, both these conditions contribute to several deleterious anatomical changes at the cervicomedullary junction and thus predispose to acute hydrocephalus. Although our patient was initially asymptomatic, hydrocephalus ensued several weeks after birth and required cerebral spinal fluid diversion. We discuss the potential links between the two conditions, the pathophysiology, and the important clinical implications for the management of the increased risk of hydrocephalus. | 10.12998/wjcc.v2.i11.711 |
pubmed_310_3894 | The codons, 64 in number, are distributed over the coding parts of DNA sequences. The distribution function is the plot of frequency versus rank of the codons. These distributions are characterized by parameters that are almost universal, i.e., gene independent. There is but a small part that depends on the gene. We present the theory to calculate the universal (gene-independent) part. The part that is gene-specific, however, has undetermined overlaps and fluctuations. | 10.1103/PhysRevE.63.051908 |
pubmed_60_19088 | Two experiments were designed to compare the effects of two pig dehairing techniques. In the first experiment, 120 pigs were slaughtered in the same abattoir in five weekly sereis. One half of each series was dehaired by singeing (the usual technique in this abattoir), while the other half was dehaired in a scalding-dehairing combination. In the second experiment, 48 pigs were slaughtered in two series, one-half of each series in an abattoir practising singeing, the other half in an abattoir practising scalding. Temperature and pH were measured 30 min after slaughter in the longissimus lumborum. Meat quality was assessed the day after slaughter in various muscles. One ham was cured and cooked, while the other one was processed by dry-curing. In both experiments, carcass weights and yields were noticeably higher after singeing. Hams were heavier in singed carcasses, but their proportions in the carcasses were little or not at all affected by the dehairing technique. Proportions of loins, shoulders and bellies were similar with both dehairing techniques. The dehairing technique affected neither temperature nor rate of post-mortem pH fall. Meat quality as assessed on fresh meat was slightly better in singed carcasses. Weights of cooked ham and dry ham per side were higher in singed carcasses, due to the higher initial ham weight, but processing yields were not affected by the dehairing technique. | 10.1016/0309-1740(94)p1825-g |
pubmed_392_12313 | BACKGROUND
Lesbian, Gay, Bisexual, Transgender, Queer, and Asexual (LGBTQA+) youth have a greater chance of experiencing stressful life events when compared to cisgender heterosexual peers, which can lead to mental health problems. We aimed to estimate the prevalence of mental disorders among LGBTQA+ youths from two large cities in Brazil.
METHODS
Participants were 13-22 years old youths from the 3rd wave of the Brazilian High-Risk Cohort for Psychiatric Disorders (n = 1475). Mental disorders were assessed using the Development and Well-Being Behavior Assessment. Sexual orientation and gender identity were assessed using a self-report confidential questionnaire. Data were analyzed through logistic regressions (adjusting for sociodemographic) using sampling weights to account for attrition and our oversampling high-risk design.
RESULTS
15.18% of the sample described themselves as LGBTQA+. The LGBTQA+ group presented higher rates of anxiety disorders (30.14% vs. 13.37%; OR = 3.37; 95%CI:2.51-4.50), depressive disorders (27.75% vs. 15.34%; OR = 2.17; 95%CI:1.60-2.93) and post-traumatic stress disorder (4.98% vs. 2.25%; OR = 4.20; 95%CI:2.24-7.82), if compared with the cisgender heterosexual group. No difference was found for conduct disorders (2.97% vs. 5.21%; OR = 0.82; 95%CI:0.35-1.65) or attention deficit hyperactivity disorder (5.92% vs. 3.28%; OR = 1.56; 95%CI:0.83-2.79).
LIMITATIONS
Although recruitment was performed at 57 schools in the two cities, sampling was non-probabilistic and included only urban areas, which might bias prevalence estimates and group comparisons.
CONCLUSIONS
Our results elucidate the mental health disparities between LGBTQA+ people and cisgender heterosexuals in Brazil. It highlights the need to promote the inclusion of this population in policy formulation and support actions to mitigate the suffering related to sexual orientation and gender identity. | 10.1016/j.jad.2021.10.108 |
pubmed_889_1028 | Motivation
The Cancer Genome Atlas (TCGA) has greatly advanced cancer research by generating, curating and publicly releasing deeply measured molecular data from thousands of tumor samples. In particular, gene expression measures, both within and across cancer types, have been used to determine the genes and proteins that are active in tumor cells.
Results
To more thoroughly investigate the behavior of gene expression in TCGA tumor samples, we introduce a statistical framework for partitioning the variation in gene expression due to a variety of molecular variables including somatic mutations, transcription factors (TFs), microRNAs, copy number alternations, methylation and germ-line genetic variation. As proof-of-principle, we identify and validate specific TFs that influence the expression of PTPN14 in breast cancer cells.
Availability and implementation
We provide a freely available, user-friendly, browseable interactive web-based application for exploring the results of our transcriptome-wide analyses across 17 different cancers in TCGA at http://ls-shiny-prod.uwm.edu/edge_in_tcga. All TCGA Open Access tier data are available at the Broad Institute GDAC Firehose and were downloaded using the TCGA2STAT R package. TCGA Controlled Access tier data are available via controlled access through the Genomic Data Commons (GDC). R scripts used to download, format and analyze the data and produce the interactive R/Shiny web app have been made available on GitHub at https://github.com/andreamrau/EDGE-in-TCGA. | 10.1093/bioinformatics/bty551 |
pubmed_638_4702 | Doctor Billings discusses in this paper some of the subjects which must always be taken into consideration in controlling the communicable disease situation in any community-among these are the following: Registration, Recognition, Termination, Hospitalization, School Exclusion, Disinfection-and the Education and Instruction of Profession and Public. | 10.2105/ajph.5.12.1204 |
pubmed_365_9050 | Xylanase activity assays were used to screen a Streptomyces coelicolor genomic library in Escherichia coli, and a xylanase gene that is 99% identical to the xylanase B gene (xlnB) of S. lividans (GenBank accession no. M64552) was identified. The promoter region of this gene was identified by using a transcriptional fusion between the upstream region of the S. coelicolor xlnB gene and the xylE reporter gene. Transcription from the xlnB promoter was found to be induced by xylan and repressed by glucose. A single apparent transcription start site was identified by both primer extension analysis and in vitro run off transcription assays. Analysis of deletions of the promoter identified a region required for glucose repression. By using the transcriptional and protein localization signals of the Streptomyces xlnB gene, an in-frame translational fusion between the end of the xlnB signal sequence and the ATG of the Thermotoga maritima xynA gene was constructed. The xynA gene encodes a thermostable xylanase that has been demonstrated to be useful in the bleaching of Kraft pulp. The xlnB-xynA gene fusion was expressed in Streptomyces, and the activity of the protein produced was thermostable and was localized to the supernatant fraction of harvested cells. | 10.1128/AEM.64.11.4217-4225.1998 |
pubmed_489_796 | We describe a method of determining the conformational fluctuations of RNA based on the incorporation of nuclear magnetic resonance (NMR) residual dipolar couplings (RDCs) as replica-averaged structural restraints in molecular dynamics simulations. In this approach, the alignment tensor required to calculate the RDCs corresponding to a given conformation is estimated from its shape, and multiple replicas of the RNA molecule are simulated simultaneously to reproduce in silico the ensemble-averaging procedure performed in the NMR measurements. We provide initial evidence that with this approach it is possible to determine accurately structural ensembles representing the conformational fluctuations of RNA by applying the reference ensemble test to the trans-activation response element of the human immunodeficiency virus type 1. | 10.1063/1.4804301 |
pubmed_207_14282 | The purpose of this study is to determine the characteristics of spirometric performance in a group of smokers and to carry out a prospective study of the changes in ventilatory lung function after smoking withdrawal. The ventilatory lung function was studied in 90 smokers and 30 non-smokers. Afterwards the smokers were included in smoking withdrawal program. One year later, the ventilatory function tests were repeated in those individuals who were able to stop smoking. Respiratory function tests were likewise repeated in 10 subjects chosen randomly among those who were not able to stop smoking. The initial study of the ventilatory lung function showed that smokers had significantly lower values of FVC (p < 0.001), FEV1 (p < 0.001), FEVC1/FVC (p < 0.001), FEF25-75 (p < 0.01 and PEF (p < 0.01) compared to non-smokers. Likewise smokers also had a statistically significant higher prevalence rate of obstructive pulmonary disease (p < 0.001). Ventilatory function studies performed one year after smoking withdrawal on those who were able to stop smoking showed a significant improvement of respiratory function parameters compared to studies done one year before. There was also a significant decrease in the prevalence and severity of obstructive pulmonary disease. No differences were observed in the ventilatory function tests performed on the ten subjects who did not stop smoking. From these data we suggest that tobacco consumption produces obstruction of the airways that can be reverted, at least in part, after smoking withdrawal. | pubmed_207_14282 |
pubmed_304_20637 | A systematic study of anion partitioning and ion pairing was performed for an extraction of individual cesium salts into 1,2-dichloroethane (1,2-DCE) using 4,5' '-bis(tert-octylbenzo)dibenzo-24-crown-8 as the cesium receptor. Equilibrium constants corresponding to the extraction of ion pairs and dissociated ions, formation of the 1:1 cesium/crown complex (confirmed by electrospray mass spectrometry), and dissociation of the ion pairs in water-saturated 1,2-DCE at 25 degrees C were obtained from equilibrium modeling using the SXLSQI program. The standard Gibbs energy of partitioning between water and water-saturated 1,2-DCE was determined for picrate, permanganate, trifluoromethanesulfonate, methanesulfonate, trifluoroacetate, and acetate anions. The dissociation of the organic-phase complex ion pair [Cs(4,4' '-bis(tert-octylbenzo)dibenzo-24-crown-8]+NO3- observed in the extraction experiments was shown to be consistent with the dissociation constant determined independently by conductance measurements. As attributed to the large effective radius of the complex cation, the evident anion discrimination due to ion pairing in the 1,2-DCE phase was relatively small, by comparison only a tenth of the discrimination exhibited by the anion partitioning. Only chloride and picrate exhibit evidence for significantly greater-than-expected ion-pairing tendency. These results provide insight into the inclusion properties of the clefts formed by opposing arene rings of the crown ether upon encapsulation of the Cs+ ion, whose weak anion recognition likely reflects the preferential inclusion of 1,2-DCE molecules in the clefts. Observed anion extraction selectivity in this system, which may be ascribed predominantly to solvent-induced Hofmeister bias selectivity toward large charge-diffuse anions, was nearly the same whether cesium salts were extracted as dissociated ions or ion pairs. | 10.1021/ic061605k |
pubmed_167_20442 | Background
Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes.
Objective
The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes.
Design
We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine.
Results
When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16).
Conclusion
Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254. | 10.1093/ajcn/nqy234 |
pubmed_665_2562 | Neurons sensitive to optic flow patterns have been recorded in the the olivo-vestibulocerebellar pathway and extrastriate visual cortical areas in vertebrates, and in the visual neuropile of invertebrates. The complex spike activity (CSA) of Purkinje cells in the vestibulocerebellum (VbC) responds best to patterns of optic flow that result from either self-rotation or self-translation. Previous studies have suggested that these neurons have a receptive-field (RF) structure that "approximates" the preferred optic flowfield with a "bipartite" organization. Contrasting this, studies in invertebrate species indicate that optic flow sensitive neurons are precisely tuned to their preferred flowfield, such that the local motion sensitivities and local preferred directions within their RFs precisely match the local motion in that region of the preferred flowfield. In this study, CSA in the VbC of pigeons was recorded in response to a set of complex computer-generated optic flow stimuli, similar to those used in previous studies of optic flow neurons in primate extrastriate visual cortex, to test whether the receptive field was of a precise or bipartite organization. We found that these RFs were not precisely tuned to optic flow patterns. Rather, we conclude that these neurons have a bipartite RF structure that approximates the preferred optic flowfield by pooling motion subunits of only a few different direction preferences. | 10.1017/S0952523806231109 |
pubmed_953_8826 | Epidemiological studies have shown positive preventive action of flavonoids on cardiovascular and neurodegenerative events. Among the six groups in which flavonoids are classified, the flavones and flavonols, based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) are the most commonly encountered within the families and genera of the higher plants. Numerous studies support a neuroprotective activity of flavones such as luteolin and flavonols such as kaempherol and quercetin in experimental focal ischemia and models of neurodegeneration. Antioxidation, modulation of signaling cascades and gene expression as well as anti-inflammation appear as the main protective mechanisms and mitochondria are a likely main target mediating the preventive actions against oxidative stress. Flavones and flavonols re-establish the redox regulation of proteins, transcription factors and signaling cascades that are otherwise inhibited by elevated oxidative stress. The final survival or death of the neuron depends on flavone and flavonol concentrations, time of exposure and, mainly, metabolic and oxidative neuronal circumstances. Neuroprotection appears to be linked to specific structural motifs, beyond those involved in antioxidation. By themselves or as templates for synthetic compounds, flavone and flavonol molecules show potential as multi-targeted therapeutic tools for protecting the brain. Nonetheless, more research needs to be done on the correlation of potential beneficial effects of flavones and flavonols and their mechanisms of action. | 10.2174/1871524911313010005 |
pubmed_354_14145 | In this work, a modification procedure for the functionalization of silicon nanowire (SiNW) is applied in biological field effect transistor (BioFET) system. The proposed method precedes the silanization reaction in a manner that the only SiNW and not its SiO2 substrate is functionalized by (3-Aminopropyl) triethoxysilane (APTES) initiators. This method has an effective role in increasing the sensitivity of BioFET sensors and can be applied in commercial ones. Furthermore, we introduce an efficient computational technique to estimate unknown senor parameters. To that end, Bayesian inversion is used to determine the number of PSA target molecules bound to the receptors in both selective and nonselective SiNWs. The approach is coupled with the Poisson-Boltzmann-drift-diffusion (PBDD) equations to provide a comprehensive system to model all biosensor interactions. | 10.1016/j.bios.2019.111527 |
pubmed_943_21040 | Streptococcus thermophilus CNRZ368 is an anaerobic aerotolerant bacteria and its ability to survive under aerobic growth conditions raises the question of the existence of a putative defence system against oxidative stress. Thus, survival of CNRZ368 in the presence of increasing concentrations of hydrogen peroxide was studied. Moreover, the influence of the physiologic state of the cells, as well as that of a preexposition with sublethal doses of hydrogen peroxide, upon S. thermophilus CNRZ368 survival were determined. The results suggest that S. thermophilus displays a defence system against oxidative stress and that this system is inducible. | 10.1016/s0923-2508(01)01234-7 |
pubmed_1025_18975 | Regulation of alternative mRNA processing by ELAV (embryonic lethal abnormal visual system)/Hu proteins is mediated by binding to AU-rich elements of low complexity. Since such sequences diverge very rapidly during evolution, it has not been clear if ELAV regulation is maintained over extended phylogenetic distances. The transcription factor Erect wing (Ewg) is a major target of ELAV in Drosophila melanogaster and coordinates metabolic gene expression with regulation of synaptic plasticity. Here, we demonstrate evolutionary conservation of ELAV regulation of ewg despite massive degeneration of its binding site and of associated elements in the regulated intronic 3'-end processing site in distantly related Drosophila virilis. In this species, the RNA-binding part of ELAV protein is identical to D. melanogaster. ELAV expression as well as expression and regulation of ewg are also conserved. Using in vitro binding assays and in vivo transgene analysis, we demonstrate, however, that the ELAV-binding site of D. virilis is fully functional in regulating alternative splicing of ewg intron 6 in D. melanogaster. Known features of the ELAV-binding site, such as the requirement of multiple poly(U) motifs spread over an extended binding site of ∼150 nt and a higher affinity to the 3' part of the binding site, are conserved. We further show that the 135-bp ELAV-binding site from D. melanogaster is sufficient for ELAV recruitment in vivo. Hence, our data suggest that ELAV/Hu protein-regulated alternative RNA processing is more conserved than anticipated from the alignment of degenerate low-complexity sequences. | 10.1534/genetics.111.131383 |
pubmed_1081_15034 | Topological metals/semimetals (TMs) have emerged as a new frontier in the field of quantum materials. A few two-dimensional (2D) boron sheets have been suggested as Dirac materials, however, to date TMs made of three-dimensional (3D) boron structures have not been found. Herein, by means of systematic first principles computations, we discovered that a rather stable 3D boron allotrope, namely 3D-α' boron, is a nodal-chain semimetal. In momentum space, six nodal lines and rings contact each other and form a novel spindle nodal chain. This 3D-α' boron can be formed by stacking 2D wiggle α' boron sheets, which are also nodal-ring semimetals. In addition, our chemical bond analysis revealed that the topological properties of the 3D and 2D boron structures are related to the π bonds between boron atoms, however, the bonding characteristics are different from those in the 2D and 3D carbon structures. | 10.1039/c8cp03874k |
pubmed_1046_7556 | BACKGROUND
Initiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa.
METHODS
From September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras.
FINDINGS
We tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6-25) in eras 1 and 2 to 2 days (1-8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1-2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5-10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8-24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23).
INTERPRETATION
HIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities.
FUNDING
Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme. | 10.1016/S2352-3018(18)30251-0 |
pubmed_239_23257 | Cellular protrusion formation capacity is a key feature of developing neurons and many eukaryotic cells. However, the mechanisms underlying membrane growth in protrusion formation are largely unclear. In this study, photo-reactive unnatural amino acid 3-(3-methyl-3H-diazirin-3-yl)-propamino-carbonyl-Nε-l-lysine was incorporated by a genetic code expansion strategy into protrudin, a protein localized in acidic endosomes and in the endoplasmic reticulum, that induces cellular protrusion and neurite formation. The modified protrudin was used for covalent trapping of protrudin-interacting proteins in living cells. Fatty acid synthase (FASN), which synthesizes free fatty acids, was identified to transiently interact with protrudin. Further characterization revealed a unique cooperation mechanism in which protrudin cooperates with FASN to facilitate cellular protrusion formation. This work reveals a novel mechanism involved in protrusion formation that is dependent on transient interaction between FASN and protrudin, and establishes a creative strategy to investigate transient protein-protein interactions in mammalian cells. | 10.1038/srep46569 |
pubmed_1006_13656 | Ehlers-Danlos (ED) syndrome type VII is characterized by the accumulation of collagen precursors in connective tissues. ED VII A and B are caused by mutations in the genes of alpha 1 and alpha 2 collagen I which result in the disruption of the cleavage site of procollagen I N-proteinase. The existence of ED VII C in humans has been hypothesized on the basis of a disorder in cattle and sheep related to the absence of the enzyme. We now present evidence for the existence of this disease in humans, characterized by skin fragility, altered polymers seen as hieroglyphic pictures with electron microscopy, accumulation of p-N-alpha 1 and p-N-alpha 2 collagen type I in the dermis and absence of processing of the p-N-I polypeptides in fibroblast cultures. | 10.1038/ng0692-214 |
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