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pubmed_458_5185 | Mechanosensitive channels are a class of ubiquitous membrane proteins gated by mechanical strain in the cellular membrane. MscS, the mechanosensitive channel of small conductance, is found in the inner membrane of Escherichia coli and its crystallographic structure in an open form has been recently solved. By means of molecular dynamics simulations we studied the stability of the channel conformation suggested by crystallography in a fully solvated lipid (POPC) bilayer, the combined system encompassing 224,340 atoms. When restraining the backbone of the protein, the channel remained in the open form and the simulation revealed intermittent permeation of water molecules through the channel. Abolishing the restraints under constant pressure conditions led to spontaneous closure of the transmembrane channel, whereas abolishing the restraints when surface tension (20 dyn/cm) was applied led to channel widening. The large balloon-shaped cytoplasmic domain of MscS exhibited spontaneous diffusion of ions through its side openings. Interaction between the transmembrane domain and the cytoplasmic domain of MscS was observed and involved formation of salt bridges between residues Asp62 and Arg128; this interaction may be essential for the gating of MscS. K+ and Cl- ions showed distinctively different distributions in and around the channel. | 10.1529/biophysj.104.046045 |
pubmed_1085_29 | A panel of seven monoclonal antibodies (MAbs) directed against the bovine herpesvirus-1 (BHV-1) glycoprotein E (gE) was obtained. For that purpose, mice were either tolerized to BHV-1 gE-negative virus and then immunized with wild type BHV-1 or immunized with plasmid DNA expressing the gE and gI glycoproteins. The MAbs were characterized by their reactivity with the gE protein or the gE/gI complex and by competition experiments. Results showed that the MAbs were directed against three antigenic domains, two located on the gE glycoprotein and one on the gE/gI complex. Blocking experiments were performed with sera from experimentally vaccinated and infected cattle. A competition was observed between gE-positive bovine sera and six of the seven MAbs. The bovine sera thus recognized two of the three antigenic sites. Field sera were then tested in blocking enzyme-linked immunosorbent assay using one horseradish peroxidase-conjugated MAb. A specificity of 98.2% and a sensitivity of 98.2% compared to the commercially available test were observed. | 10.1016/s0378-1135(01)00430-8 |
others_250_5135 | To investigate whether tick-borne encephalitis viruses (TBEVs) are present in South Korea, Korean ixodid ticks were tested for TBEV RNA. Ticks (n = 2460) were collected from wild and domestic animals or by flagging at forest and grassland in 12 regions of five provinces in 2005-06. Four species in two genera were identified, yielding 197 sample pools (1-20 ticks per pool); from these, 12 envelope protein gene fragments of TBEV were amplified by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). Ten of the 2104 adult ticks (0.4%) and two of the 356 nymph ticks (0.2%) were positive for the envelope (E) gene of TBEV. Twelve TBEV RNA-positive samples were detected in Gyeonggi and Gangwon provinces. Phylogenetic analysis showed that the E genes of the TBEV isolates were clustered with the Western European subtype (98% identity). This study suggests that TBEVs may exist in Korea. © 2009 The Royal Entomological Society | 10.1111/j.1365-2915.2008.00755.x |
pubmed_284_8882 | Performic-acid-oxidized isoinhibitor K of snails (Helix pomatia) was subjected to arginine-directed tryptic proteolysis. Six peptide fragments including one overlap peptide from limited cleavage of the Arg-3-Pro-4 bond were purified to homogeneity. Four arginine peptides and the C-terminal peptide were sequenced by automatic Edman degradation using a special peptide program. The phenylthiohydantoins were all identified by chemical ionization mass spectrometry, except four cysteic acid residues that were identified on an amino acid analyzer after acid hydrolysis. Quantitative evaluation of the phenylthiohydantoins by chemical ionization mass spectrometry using total molecular-ion beam integration greatly facilitated sequencing. The mass spectrum of the dipeptide less than Glu-Gly revealed that the N-terminus was blocked by pyroglutamic acid. The complete amino acid sequence of isoinhibitor K was determined. An almost 50% homology between the sequences of the snail inhibitor and the bovine trypsin-kallikrein inhibitor (Kunitz) became obvious. A comparison of all homologous sequences of this particular class of proteins known to date is presented. | 10.1111/j.1432-1033.1975.tb02391.x |
pubmed_798_2344 | Changes in goal orientations and self-concept in Greek language and physical education classes during the first months of junior high school in Greece were studied. Participants, 572 students in their first year of junior high school, responded to questionnaires assessing (a) goal orientations and satisfaction in physical education and Greek language classes, (b) multidimensional self-concept, (c) attitudes toward school and teachers, and (d) life satisfaction. The measures were collected in three sessions: at the beginning of the school year, 6 wk. later, and 14 wk. later. The third measurement followed the students' grades for the first term. Students showed significant decreases in mastery and social-approval goal orientations in both physical education and Greek language classes. They also showed negative attitudes toward teachers, perceptions of physical ability, and relationships with parents. Most differences emerged between Weeks 6 and 14. The learning environment and the assessment system in Greek junior high school seem to play an important role in the decrease of students' motivation and perceived competence. | 10.2466/pr0.103.3.745-763 |
pubmed_914_21672 | BCR-ABL1 is a fusion tyrosine kinase, which causes multiple types of leukemia. We used an integrated proteomic approach that includes label-free quantitative protein complex and phosphorylation profiling by mass spectrometry to systematically characterize the proximal signaling network of this oncogenic kinase. The proximal BCR-ABL1 signaling network shows a modular and layered organization with an inner core of three leukemia transformation-relevant adaptor protein complexes (Grb2/Gab2/Shc1 complex, CrkI complex and Dok1/Dok2 complex). We introduced an 'interaction directionality' analysis, which annotates static protein networks with information on the directionality of phosphorylation-dependent interactions. In this analysis, the observed network structure was consistent with a step-wise phosphorylation-dependent assembly of the Grb2/Gab2/Shc1 and the Dok1/Dok2 complexes on the BCR-ABL1 core. The CrkI complex demonstrated a different directionality, which supports a candidate assembly on the Nedd9 (Hef1, CasL) scaffold. As adaptor protein family members can compensate for each other in leukemic transformation, we compared members of the Dok and Crk protein families and found both overlapping and differential binding patterns. We identified an additional level of regulation for the CrkII protein via binding to 14-3-3 proteins, which was independent from its inhibitory phosphorylation. We also identified novel components of the inner core complexes, including the kinases Pragmin (Sgk223) and Lrrk1 (Lrrk2 paralog). Pragmin was found as a component of the CrkI complex and is a potential link between BCR-ABL1/CrkI and RhoA signaling. Lrrk1 is an unusual kinase with a GTPase domain. We detected Lrrk1 as a component of the Grb2/Gab2/Shc1 complex and found that it functionally interacts with the regulator of small GTPases Arap1 (Centd2) and possibly participates in the mitogen-activated protein kinase response to cellular stresses. This modular and phosphorylation-driven interaction network provides a framework for the integration of pleiotropic signaling effects of BCR-ABL1 toward leukemic transformation. | 10.1038/onc.2010.331 |
pubmed_180_9972 | Emulsification/internal gelation has been suggested as an alternative to extrusion/external gelation in the encapsulation of several compounds including non-steroidal anti-inflammatory drugs such as diclofenac sodium. The objective of the present study was a trial to formulate diclofenac sodium as controlled release microparticles that might be administered once or twice daily. This could be achieved via emulsification/internal gelation technique applying Box-Behnken design to choose these formulae. Box-Behnken design determined fifteen formulae containing specified amounts of the independent variables, which included stirring speed in rpm (X1), drug:polymer ratio (X2) and the surfactant span 80% (X3). The dependent variables studied were cumulative percent release after two hours (Y1), four hours (Y2) and eight hours (Y3). The prepared microparticles were characterized for their production yield, sizes, shapes and morphology, entrapment efficiency and Diclofenac sodium in vitro release as well. The results showed that the production yield of the prepared diclofenac sodium microparticles was found to be between 79.55% and 97.41%. The formulated microparticles exhibited acceptable drug content values that lie in the range 66.20-96.36%. Also, the data obtained revealed that increasing the mixing speed (X1) generally resulted in decreased microparticle size. In addition, scanning electron microscope images of the microparticles illustrated that the formula contains lower span concentration (1%) in combination with lower stirring speed (200 rpm) which showed wrinkled, but smooth surfaces. However, by increasing surfactant concentration, microspheres' surfaces become smoother and slightly porous. Kinetic treatment of the in vitro release from drug-loaded microparticles indicated that the zero order is the drug release mechanism for the most formulae. | 10.1016/j.jsps.2011.08.004 |
pubmed_1140_11178 | BACKGROUND
Linear programming is an analytic method that can be used to develop models for health care that optimize distribution of resources through mathematical means.
STUDY DESIGN
The linear programming model contained objective, decision, and constraint elements. The objective was to optimize financial outcomes for both the hospital and physicians in the Department of Surgery. The decision concerns procedure mix or the number of each type of surgical procedure. Constraints apply to resources that are consumed during the course of the patient's surgical encounter.
RESULTS
The optimal solution produced an increase in professional payments of 3.6% and an increase in hospital total margin of 16.1%. This solution favored surgical procedures that require inpatient care; these patients had greater comorbidity, reflected in a higher case-mix index of 3.74 compared to 2.97. Substantial differences were noted in use of general care and ICU days, and in consumption of preoperative, intraoperative, and recovery room time.
CONCLUSIONS
Aligning quality surgical care with optimal financial performance may be assisted by mathematical models such as linear programming. | 10.1016/j.jamcollsurg.2005.01.001 |
others_22_2853 | 18F-FDG is the most widely used PET tracer worldwide. Before the examination, recommendations are given to patients to avoid muscular activities, with the goal to limit 18F-FDG uptake in muscles. Here, we report the case of a 36-year-old man with Hodgkin disease referred to our department to perform an 18F-FDG PET/CT for immunotherapy assessment. The PET images showed a homogeneous, symmetric, and very intense uptake of the masticatory muscles. The medical examination exhibited a trismus, and the patient revealed to have been using cocaine 15 minutes before injection of 18F-FDG. © Wolters Kluwer Health, Inc. All rights reser | 10.1097/RLU.0000000000003288 |
pubmed_976_17629 | Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain. | 10.1016/s0306-4522(03)00040-x |
pubmed_375_1529 | Isoprinosine (NPT-10381) was given orally to a group of 22 volunteers at a daily dose of 6 g for 7 days; a control group of 23 volunteers received placebo. Volunteers were inoculated intranasally with both rhinovirus type 9 and rhinovirus type 31, and the clinical picture, extent of virus shedding, and serological responses were assessed. There was no evidence that the compound had useful antiviral activity under the conditions of this trial. | 10.1128/AAC.3.3.332 |
pubmed_507_669 | Urine bladder diverticula are usually asymptomatic, therefore they are incidentally diagnosed during examinations for other purposes. A Chinese patient, with a history of pulmonary adenocarcinoma first underwent a technetium-99m methylene diphosphonate whole-body bone scan. In addition to multiple skeletal metastases, abnormal shape of the urine bladder was also noted, which overlapped the superior ramus of the right pubic bone. In order to: a) better delineate the shape and structure of the urine bladder; b) visualize the pubic bone and c) detect the exact location and structural changes of skeletal lesions in the lumbosacral region, single photon emission tomography/computerized tomography (SPET/CT) scan of this region was performed immediately, and demonstrated: a) a big urine bladder diverticulum in the right hemipelvis; b) structural changes of skeletal metastases while metastases in the pubic bone were ruled out. An overview of the etiology, histopathology, complications, management and imaging of urine bladder diverticulum is also presented. We consider our case the first to be diagnosed by SPET/CT and differentiated from metastases of the overlapping bone in a 69 years old female. | pubmed_507_669 |
pubmed_487_21794 | Chronic myelogenous leukemia is characterized by the reciprocal chromosomal translocation (9;22), which generates a novel fusion gene, BCR-ABL. Bcr-Abl-expressing leukemia cells are highly resistant to apoptosis. Imatinib an Abl kinase inhibitor, is a highly effective agent for patients with CML. However, a small percentage of these patients and most advanced-phase patients relapse on imatinib therapy. It is poorly understood whether the Abl kinase inhibitors are able to eradicate CML progenitor or stem cells. In this study, we investigated the role of HOXA10 in CML cell lines and the hematopoietic progenitor cells derived from CML patients, and whether the regulation of HOXA10 eradicates Bcr-Abl(+) hematopoietic stem/progenitor cells. The Abl kinase inhibitors and PI3K inhibitor, LY294002, induced the expression of HOXA10, and it enhanced apoptosis in CML cells. Moreover, the reduction of HOXA10 expression by siRNA in CML cells inhibited apoptosis by treatment with the Abl kinase inhibitors and LY294002. These results revealed that HOXA10 had an important role in induction of apoptosis by the Abl kinase inhibitors in CML cells. Finally, we showed that the inhibition of HOXA10 expression by siRNA increased the numbers of CFU-GEMM, BFU-E, and CFU-GM when the cells were treated with the combination of BMS354825 and LY294002 compared to control cells, and HOXA10 played a critical role in the committed colony-formation in CML. This study shows for the first time that the Abl kinase inhibitor and LY294002 induced HOXA10, and HOXA10 had an important role in apoptosis or cell growth inhibition in CML cells in vitro. | 10.1016/j.leukres.2007.11.034 |
pubmed_262_15085 | Endosomes are emerging as specialized signaling compartments that endow receptors with distinct signaling properties. The diversity of endosomal signaling pathways and their contribution to various biological responses is still unclear. CD158d, which is also known as the killer cell immunoglobulin-like receptor (KIR) 2DL4 (KIR2DL4), is an endosome-resident receptor in natural killer (NK) cells that stimulates the release of a unique set of proinflammatory and proangiogenic mediators in response to soluble human leukocyte antigen G (HLA-G). Here, we identified the CD158d signaling cascade. In response to soluble agonist antibody or soluble HLA-G, signaling by CD158d was dependent on the activation of nuclear factor kappaB (NF-kappaB) and the serine-threonine kinase Akt. CD158d associated with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), promoted the recruitment of Akt to endosomes, and stimulated the DNA-PKcs-dependent phosphorylation of Akt. The sequential requirement for DNA-PKcs, Akt, and NF-kappaB in signaling by CD158d delineates a previously uncharacterized endosomal signaling pathway for a proinflammatory response in NK cells. | 10.1126/scisignal.2000467 |
pubmed_882_6757 | OBJECTIVE
To evaluate the effectiveness and safety of Ligation of the Intersphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-plug) in the treatment of chronic anal fistula.
METHODS
A total of 239 patients (199 males, 40 females) with chronic anal fistula were recruited from 5 hospitals between March 2011 and April 2013. These patients were randomly assigned to the experimental group (n=119) treated with LIFT-plug or the control group (n=120) treated with LIFT. The follow-up period was 180 days. The collected data included healing rate, the median healing time, the recurrence rate, the Visual Analogue Scale (VAS), the incontinence rate, and the safety indicators associated with the anal fistula plug.
RESULTS
The healing rate of the experimental group was better than the control group (96.5% vs 83.7%, P<0.05). The median healing time of the experimental group was 22 days and the latter was 30 days (P<0.05). By the end of the follow-up period, there was no recurrence found in the two groups. The VAS and the incontinence rate had no statistically significant difference between the two groups. There were no adverse events associated with the anal fistula plug in the experimental group.
CONCLUSION
LIFT-plug is simple, less invasive, and with shorter healing time and more satisfactory healing rate in treating chronic anal fistula compared with LIFT. | pubmed_882_6757 |
pubmed_1135_9078 | BACKGROUND
Ugandan law prohibits abortion under all circumstances except where there is a risk for the woman's life. However, it has been estimated that over 250 000 illegal abortions are being performed in the country yearly. Many of these abortions are carried out under unsafe conditions, being one of the most common reasons behind the nearly 5000 maternal deaths per year in Uganda. Little research has been conducted in relation to societal views on abortion within the Ugandan society. This study aims to analyze the discourse on abortion as expressed in the two main daily Ugandan newspapers.
METHOD
The conceptual content of 59 articles on abortion between years 2006-2012, from the two main daily English-speaking newspapers in Uganda, was studied using principles from critical discourse analysis.
RESULTS
A religious discourse and a human rights discourse, together with medical and legal sub discourses frame the subject of abortion in Uganda, with consequences for who is portrayed as a victim and who is to blame for abortions taking place. It shows the strong presence of the Catholic Church within the medial debate on abortion. The results also demonstrate the absence of medial statements related to abortion made by political stakeholders.
CONCLUSIONS
The Catholic Church has a strong position within the Ugandan society and their stance on abortion tends to have great influence on the way other actors and their activities are presented within the media, as well as how stakeholders choose to convey their message, or choose not to publicly debate the issue in question at all. To decrease the number of maternal deaths, we highlight the need for a more inclusive and varied debate that problematizes the current situation, especially from a gender perspective. | 10.1186/s12978-015-0049-0 |
pubmed_51_21056 | OBJECTIVE
Symptomatic osteoarthritis (OA) is a common painful disease with limited treatment options. A rising number of patients with OA have been treated with intraarticular injections of hyaluronic acid, including the high-molecular-weight hylan G-F 20, which is injected following arthrocentesis. We investigated the effectiveness of hylan G-F 20 to lower coefficient of friction (COF) and prevent chondrocyte apoptosis in vitro.
METHODS
A disc-on-disc bovine cartilage bearing was used to measure the static and kinetic COF when lubricated with hylan G-F 20, human synovial fluid (HSF), and phosphate buffered saline (PBS). Following friction testing, we stained paraffin-embedded sections of these cartilage bearings for activated caspase-3, a marker of apoptosis.
RESULTS
Bearings lubricated with hylan G-F 20 had kinetic COF values that were similar to bearings lubricated with PBS, but significantly higher than those lubricated with HSF. There were no significant differences in static COF values in bearings lubricated with hylan G-F 20 as compared to PBS or HSF. However, bearings lubricated with HSF had significantly lower static COF values compared to bearings lubricated with PBS. The mean percentage of caspase-3-positive chondrocytes in the superficial and upper intermediate zones of bearings lubricated with hylan G-F 20 was significantly higher compared to that of bearings lubricated with HSF or unloaded controls, but significantly lower than in those lubricated with PBS.
CONCLUSION
These findings indicate that joint lubrication may prevent chondrocyte apoptosis by lowering the COF. Further, removal of synovial fluid prior to hylan G-F 20 injection may be detrimental to cartilage health. | 10.3899/jrheum.111427 |
pubmed_285_3533 | Modification of the previously disclosed (S)-N-(2-(aminomethyl)-5-chlorobenzyl)-1-((R)-2-hydroxy-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamide 2 by optimization of the P3 group afforded novel, low molecular weight thrombin inhibitors. Heterocycle replacement of the hydroxyl functional group helped maintain thrombin in vitro potency while improving the chemical stability and pharmacokinetic profile. These modifications led to the identification of compound 10, which showed excellent selectivity over related serine proteases as well as in vivo efficacy in the rat arteriovenous shunt. Compound 10 exhibited significantly improved chemical stability and pharmacokinetic properties over 2 and may be utilized as a structurally differentiated preclinical tool comparator to dabigatran etexilate (Pro-1) to interrogate the on- and off-target effects of oral direct thrombin inhibitors. | 10.1021/acsmedchemlett.5b00047 |
pubmed_385_13432 | In mammalian cells, apoptosis is often mediated via organelles. While apoptotic-like cell death occurs in plants, the mechanistic details are unresolved. Transgenic tobacco plants have been generated that harbour selected animal anti-apoptotic genes. Subcellular fractionation followed by western blot analysis indicated that chloroplasts serve as a location for these animal anti-apoptotic proteins in addition to the established mitochondrial location. To explore the functional significance of this observation, tobacco plants were treated with three chloroplast-directed herbicides. Wild-type plants died and exhibited features associated with apoptosis. Transgenic plants survived and did not show any apoptotic-like characteristics. Moreover, the herbicide-induced apoptotic-like cell death was light requiring. It was concluded that chloroplasts may be involved in mediating certain types of plant programmed cell death. | 10.1093/jxb/erh275 |
pubmed_524_17504 | ELOVL fatty acid elongase 6 (ELOVL6) is a long-chain fatty acid elongase, and the hepatic expression of the Elovl6 gene and accumulation of triglycerides (TG) are enhanced by long-term high-fructose intake. Fatty acid synthesis genes, including Elovl6, are regulated by lipogenic transcription factors, sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP). In addition, carbohydrate signals induce the expression of fatty acid synthase not only via these transcription factors but also via histone acetylation. Since a major lipotrope, myo-inositol (MI), can repress short-term high-fructose-induced fatty liver and the expression of fatty acid synthesis genes, we hypothesized that MI might influence SREBP-1c, ChREBP, and histone acetylation of Elovl6 in fatty liver induced by even short-term high-fructose intake. This study aimed to investigate whether dietary supplementation with MI affects Elovl6 expression, SREBP-1 and ChREBP binding, and acetylation of histones H3 and H4 at the Elovl6 promoter in short-term high-fructose diet-induced fatty liver in rats. Rats were fed a control diet, high-fructose diet, or high-fructose diet supplemented with 0.5% MI for 10 days. This study showed that MI supplementation reduced short-term high-fructose diet-induced hepatic expression of the Elovl6 gene, ChREBP binding, but not SREBP-1 binding, and acetylation of histones H3 and H4 at the Elovl6 promoter. | 10.1016/j.nutres.2020.12.022 |
pubmed_785_19395 | Preconceptional care is a set of interventions, aimed to identify and modify medical, behavioral, and social risks to a woman's health and her pregnancy outcome, prior to conception. Diagnosing and treating some of the common noncommunicable diseases (NCDs) may have an impact on pregnancy outcome. Ample time should be allowed to properly intervene in some of the following situations: hypertension, diabetes, obesity, systemic lupus erythematosus, thyroid disease, anemia, epilepsy, asthma, and cardiac disease. Diabetes mellitus and obesity are common NCDs, with proven efficacy for preconceptional care, for both maternal and perinatal outcome. These primary components of the metabolic syndrome, if properly treated prior to pregnancy, will prevent long-term hazards for the mother, her children, and the next generations, by providing in utero primary prevention of NCDs. | pubmed_785_19395 |
pubmed_830_11146 | Lily (Lilium) is used as an important edible and medical plant species with a vague taxonomic classification and a long history in China. Bulbs of six Lilium species (L. regale, L. concolor, L. pumilum, L. leucanthum, L. davidii var. unicolor and L. lancifolium) native to China were investigated with a view to their exploitation as a potential source of natural antioxidants due to their phenolic composition and dietary antioxidant potential. The results showed that all bulb extracts exhibited strong antioxidant activities, which generally correlated positively with the total phenolic contents (r = 0.68 to 0.94), total flavonoid contents (r = 0.51 to 0.89) and total flavanol contents (r = 0.54 to 0.95). High-performance liquid chromatography (HPLC) analysis revealed that rutin and kaempferol were the major phenolic components in the extracts. Hierarchical cluster analysis showed that L. regale belonged to the group with high phenolic content and strong antioxidant power. L. concolor and L. pumilum were arranged in one group characterized by moderate phenolic content and antioxidant capacity, while L. leucanthum, L. davidii var. unicolor and L. lancifolium were clustered in the third group with low phenolic content and weak antioxidant activity. These strongly suggest that lily bulbs may serve as a potential source of natural antioxidant for food and pharmaceutical applications. | 10.3390/molecules17089361 |
pubmed_235_22492 | BACKGROUND
Tumor mutation burden (TMB) predicts immunotherapy efficacy in solid tumors. However, the biomarker role of TMB is still conflicting in resected tumors. We aimed to examine the association of TMB with prognosis and postoperative chemotherapy (CT) or radiochemotherapy (RCT) efficacy in resected gastric cancer (GC).
METHODS
Whole-exome sequencing (WES) was performed in 73 resected GC specimens. Validation cohorts included 352 patients from The Cancer Genome Atlas (TCGA) and 222 patients from the Asian Cancer Research Group (ACRG). Immune infiltration and hypoxia were evaluated by transcriptome data and immunohistochemistry assay.
RESULTS
TMB-high GC had favorable overall survival (OS) and disease-free survival (DFS), but the OS and DFS benefits with postoperative CT/RCT were more pronounced in TMB-low GC. These findings were consistent among all three cohorts and were maintained in the pooled cohort. Stratified by stages in the pooled cohort, stage III GC benefited from postoperative CT/RCT regardless of TMB level while stage Ib/II GC benefited from postoperative CT/RCT in TMB-low but not in TMB-high subgroup. TMB positively correlated with immune infiltration which was characterized by NK cell rather than CD8 + T cell enrichment. TMB-high GC was more hypoxic than TMB-low GC, and TMB-high stage Ib/II GC was the most hypoxic.
CONCLUSIONS
High TMB may predict favorable prognosis in resected GC but poor response to postoperative CT/RCT in stage Ib/II subgroup, which may be determined by TMB-associated immune infiltration and hypoxia, respectively. | 10.1007/s10120-021-01175-8 |
pubmed_343_13312 | In spite of improvements in expected survival, neurodevelopmental outcome, and quality of life, decision-making in neonatal dialysis remains controversial in high-resource countries. In part, this may be based upon the significant burdens experienced by the child, and also those experienced by the parents as caregivers. Emerging research offers a clearer description of the burdens experienced by dialysis caregivers worldwide. Caregiver burden represents an important area for nephrologists to advocate for patients and their families; however, nephrologists must also recognize the realities caregivers currently experience. Incorporation of caregiver burden into medical decision-making for children with end-stage kidney disease is necessary, but raises several ethical concerns. | 10.1007/s00467-019-04332-5 |
pubmed_345_21091 | BACKGROUND
Although renal colic in children in the United States remains relatively uncommon compared to in adults, its incidence has nearly doubled from 1999 to 2008. Noncontrast computed tomography (CT) is the current standard for the evaluation of suspected renal colic, given its high sensitivity and specificity. However, the greater lifetime risk of radiation-induced cancer from CT in pediatric patients has led to efforts to minimize radiation exposure. Additionally, pediatric renal colic is often recurrent, which might require multiple imaging studies during their lifetime. Point-of-care ultrasound (POCUS) by emergency physicians avoids radiation, has a low marginal cost, can be performed concurrently with other management, and allows for earlier diagnosis and more rapid treatment of renal colic. Adult randomized controlled trial evidence supports using POCUS as the initial approach to imaging and management of suspected renal colic. However, there remain limited data on POCUS in children for renal colic.
CASE REPORT
This is a case series where the sonographic findings of hydronephrosis, ureteral jets, "twinkling artifact," and the identification of urinary tract stones were used to evaluate adolescent and pediatric patients with renal colic. We report five cases of renal colic in adolescent and pediatric patients where urolithiasis was confirmed by using POCUS and irradiation by CT was avoided in all 5 patients. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: POCUS can provide information about the presence or absence of urinary tract stones as well as obstruction of the collecting system without the cost and radiation exposure of CT. | pubmed_345_21091 |
others_237_6716 | Introduction: Difficulty in measuring sensitive behaviors in 12-15- year-old adolescents is a barrier to research. This study determined whether early adolescents reported substance use and sexual activity similarly in assisted paper-and-pencil versus touch-tone telephone responses. Methods: Adolescents 12-15 years old completed confidential, interviewer-assisted questionnaires first in a physician office by paper-and-pencil and then at home by touch-tone approximately 3 months later. Adolescents were from a high-risk urban area, 71% were minority, and all had parent consent to participate. Results: The follow-up participation rate was 94% (follow-up n = 207). Test-retest stability was generally poor for low-frequency behaviors such as injection drug use, anal intercourse, and sexual behaviors in 12-13- year-olds. Test-retest stability was fair to good for common substance use items. Test-retest stability was generally good among females and 14-15- year-old adolescents, and poor to fair among males and 12-13-year-olds, for common sexual experiences in the last 3 months. Test-retest stability was generally good to excellent for all lifetime sexual experiences except among 12-13-year-olds in which it was generally poor. Internal consistency of the self-esteem scale was high using both response technologies. Both response technologies reproduced correlations between substance use and lifetime sexual experience. Conclusion: A high participation rate and reliable data capture were achieved when assessing sensitive behaviors of 14-15-year-olds using touch-tone telephone response. Sexual behaviors were more reliably captured using a 'lifetime' versus 'last 3-month' reference period. Low prevalence contributed to poor reliability in 12-13-year-olds | 10.1016/S0749-3797(97)00061-5 |
pubmed_975_7867 | Spinal cord stimulation (SCS) affects peripheral, coronary and cerebral blood flow (CBF) in humans. In 1986 Meglio et al. [Appl Neurophysiol 1986;49:139-146] advocated a functional reversible sympathectomy as one of the mechanisms of SCS in man. An experimental animal model was developed to study SCS effects on CBF and to investigate the possible mechanisms. Twenty-one white New Zealand rabbits were anesthetized with Fluothane; spontaneous ventilation was permitted. A steady hemodynamic and metabolic state was maintained. A small cervical laminectomy was performed and an electrode (Medtronic Sigma 3483) was placed in the epidural space over the posterior spinal cord. Both common carotid arteries were exposed and external carotid arteries were ligated. In 3 animals, the cervical symapthetic trunk (CST) was exposed and wrapped with bipolar hook-stimulating electrodes. SCS was performed for 20 min with electrical square waves of 210 microseconds duration, 80 cycles/s, at 2/3 motor threshold intensity. CST stimulation was delivered for 1 min with the following parameters: 10 V, 10 cycles/s, 0.5 ms duration. CBF velocities of both internal carotid arteries were measured by using a CW Doppler (in all the animals) and electromagnetic flowmeter (in 2 animals), at rest, during sympathetic trunk stimulation, during SCS, during simultaneous SCS and CST stimulation. During SCS, an increase of CBF was detected in 11 rabbits (52.4%); a decrease was observed in two cases (9.5%). No change was detected in the remaining 8 animals (38%). CST stimulation induced a decrease of CBF in all animals. Electromagnetic flowmetry confirmed velocitometric findings in the 2 cases studied.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1159/000098616 |
pubmed_103_18709 | BACKGROUND/AIMS
Optimized regimen has not yet been established for failures of multiple Helicobacter pylori (H. pylori) eradication. Hence, we aimed to evaluate the efficacy of rifabutin-based rescue therapy, at least after three eradication failures.
METHODS
Twelve patients, who failed in the treatment for H. pylori eradication at least three times, were consecutively enrolled between 2007 and 2015 at Seoul National University Bundang Hospital. The rifabutin-based rescue regimen was consisted of proton pump inhibitor (PPI), rifabutin (150 mg b.i.d.), and amoxicillin (1 g b.i.d.), given for 7 or 14 days. MIC concentration test by the agar dilution method was performed on six patients prior to rifabutin-based rescue therapy.
RESULTS
One patient did not take this regimen, and per-protocol (PP) analysis was performed in 11 patients. The overall eradication rate by intention-to-treat and PP analysis with rifabutin-based rescue therapy was 50.0% (6/12 patients) and 54.5% (6/11 patients), respectively. There was no difference of the eradication rate depending on the underlying disease, smoking, alcohol, number of previous eradication failures, and CYP2C19 genotype. All of the six patients were susceptible to rifabutin, but only three of them succeeded in eradicating with H. pylori. Side effects occurred in two patients (18.2%), and compliance was 90.9%.
CONCLUSIONS
Even the eradication rate of rifabutin-based rescue therapy was not very good. Rifabutin-based rescue therapy could be considered as a rescue therapy, perhaps as the fourth or the fifth-line treatment option. No correlation of rifabutin sensitivity with eradication success rate of H. pylori suggests that frequent administration of high dose PPI and amoxicillin might be important. | 10.4166/kjg.2017.69.2.109 |
pubmed_919_7327 | The evaluation of the valvular opening due to a pulse flow, as is the case of cardiac valves, requires the knowledge of the leaflets material properties and the coupled solution of the fluid and solid equations. This approach is not commonly feasible. A different approach is introduced here to describe the opening behavior of valvular leaflets by a functional kinematic relationship. The asymptotic analysis, in the limit of leaflet opening without vortex shedding, is presented for a two-dimensional rigid leaflet model under the irrotational scheme. The approach is then verified by numerical solution of the Navier-Stokes equation in asymptotic and nonasymptotic conditions. | 10.1103/PhysRevLett.94.194502 |
pubmed_245_21371 | l-Amino acid oxidases (l-AAO) catalyze the oxidative deamination of l-amino acids to the corresponding α-keto acids. The non-covalently bound cofactor FAD is reoxidized by oxygen under formation of hydrogen peroxide. We expressed an active l-AAO from the fungus Rhizoctonia solani as a fusion protein in E. coli. Treatment with small amounts of the detergent sodium dodecyl sulfate (SDS) stimulated the activity of the enzyme strongly. Here, we investigated whether other detergents and amphiphilic molecules activate 9His-rsLAAO1. We found that 9His-rsLAAO1 was also activated by sodium tetradecyl sulfate. Other detergents and fatty acids were not effective. Moreover, effects of SDS on the oligomerization state and the protein structure were analyzed. Native and SDS-activated 9His-rsLAAO1 behaved as dimers by size-exclusion chromatography. SDS treatment induced an increase in hydrodynamic radius as observed by size-exclusion chromatography and dynamic light scattering. The activated enzyme showed accelerated thermal inactivation and an exposure of additional protease sites. Changes in tryptophan fluorescence point to a more hydrophilic environment. Moreover, FAD fluorescence increased and a lower concentration of sulfites was sufficient to form adducts with FAD. Taken together, these data point towards a more open conformation of SDS-activated l-amino acid oxidase facilitating access to the active site. | 10.3390/molecules22122272 |
pubmed_959_18491 | Posterior rhabdosphincter reconstruction (PRR) has been proposed to improve early urinary continence (UC) recovery after radical prostatectomy (RP). In order to generate level 1b evidence, we designed a double-blind randomised controlled trial powered to detect a 20% increase in early UC recovery after robot-assisted RP (RARP). A group of 153 patients with cT1c-3a N0M0 prostate cancer were randomised (73 to control arm and 80 to PRR arm) and 152 completed 12-mo follow-up. For UC defined as no pad use, the recovery hazard ratio at 1-mo follow-up was 2.312 (95% confidence interval [CI] 1.081-4.937; p = 0.030). UC recovery was observed in 33.8% of patients in the PRR arm and 18.1% of patients in the control arm (p = 0.022). At 3-mo follow-up the corresponding rates were 58.8% and 43.1% (p = 0.038). The median time to UC recovery was 106 d (95% CI 73-139) in the control arm and 64 d (95% CI 39-89) in PRR arm (p = 0.897). No differences in pathological outcomes or early and late surgical complications were observed between the arms. We conclude that PRR is safe and increases early UC recovery after RARP. PATIENT SUMMARY: We investigated reconstruction of a muscular ring that controls the flow of urine, called the rhabdosphincter, after removal of the prostate in robot-assisted surgery. The procedure is safe and increases early recovery of urinary continence. This trial is registered at ClinicalTrials.gov as NCT03302169. | 10.1016/j.euo.2021.02.005 |
pubmed_321_20097 | Organic greenhouse (OGH) production is characterized by different systems and agricultural practices with diverse environmental impact. Soil arthropods are widely used as bioindicators of ecological sustainability in open field studies, while there is a lack of research on organic production for protected systems. This study assessed the soil arthropod abundance and diversity over a 2-year crop rotation in three systems of OGH production in the Mediterranean. The systems under assessment differed in soil fertility management: SUBST - a simplified system of organic production, based on an input substitution approach (use of guano and organic liquid fertilizers), AGROCOM - soil fertility mainly based on compost application and agroecological services crops (ASC) cultivation (tailored use of cover crops) as part of crop rotation, and AGROMAN - animal manure and ASC cultivation as part of crop rotation. Monitoring of soil fauna was performed by using pitfall traps and seven taxa were considered: Carabidae, Staphylinidae, Araneae, Opiliones, Isopoda, Myriapoda, and Collembola. Results demonstrated high potential of ASC cultivation as a technique for beneficial soil arthropod conservation in OGH conditions. SUBST system was dominated by Collembola in all crops, while AGROMAN and AGROCOM had more balanced relative abundance of Isopoda, Staphylinidae, and Aranea. Opiliones and Myriapoda were more affected by season, while Carabidae were poorly represented in the whole monitoring period. Despite the fact that all three production systems are in accordance with the European Union regulation on organic farming, findings of this study displayed significant differences among them and confirmed the suitability of soil arthropods as bioindicators in protected systems of organic farming. | 10.1017/S0007485317001158 |
pubmed_341_18588 | OBJECTIVE
The usual seminal profile has been customarily used for diagnosing male infertility based on an examination of semen samples. However, sperm DNA fragmentation has also been causally linked to reproductive failure, suggesting that it should be evaluated as part of male infertility assessments. To compare the ability of the five most widely utilized methodologies of measuring DNA fragmentation to predict male infertility and reactive oxygen species by Oxisperm kit assay.
METHODS
In this case-control study, which received ethical committee approval, the participants were divided into fertile and infertile groups (50 patients in each group).
RESULTS
The alkaline comet test showed the best ability to predict male infertility, followed by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, the sperm chromatin dispersion (SCD) test, and the sperm chromatin structure assay (SCSA), while the neutral comet test had no predictive power. For our patient population, the projected cut-off point for the DNA fragmentation index was 22.08% using the TUNEL assay, 19.90% using SCSA, 24.74% using the SCD test, 48.47% using the alkaline comet test, and 36.37% using the neutral comet test. Significant correlations were found between the results of the SCD test and those obtained using SCSA and TUNEL (r =0.70 and r =0.68, respectively; p<0.001), and a statistically significant correlation was also found between the results of SCSA and the TUNEL assay (r =0.77, p<0.001). Likewise, the results of the alkaline comet test showed significant correlations with those of the SCD, SCSA, and TUNEL tests (r =0.59, r =0.57, and r =0.72, respectively; p<0.001).
CONCLUSION
The TUNEL assay, SCSA, SCD, and the alkaline comet test were effective for distinguishing between fertile and infertile patients, and the alkaline comet test was the best predictor of male infertility. | 10.5653/cerm.2019.46.1.14 |
pubmed_1026_3036 | Interacting dynamical systems abound in nature, with examples ranging from biology and population dynamics, through physics and chemistry, to communications and climate. Often their states, parameters and functions are time-varying, because such systems interact with other systems and the environment, exchanging information and matter. A common problem when analysing time-series data from dynamical systems is how to determine the length of the time window for the analysis. When one needs to follow the time-variability of the dynamics, or the dynamical parameters and functions, the time window needs to be resolved first. We tackled this problem by introducing a method for adaptive determination of the time window for interacting oscillators, as modeled and scaled for the cardiorespiratory interaction. By investigating a system of coupled phase oscillators and utilizing the Dynamical Bayesian Inference method, we propose a procedure to determine the time window and the propagation parameter of the covariance matrix. The optimal values are determined so that the inferred parameters follow the dynamics of the actual ones and at the same time the error of the inference represented by the covariance matrix is minimal. The effectiveness of the methodology is presented on a system of coupled limit-cycle oscillators and on the cardiorespiratory interaction. Three cases of cardiorespiratory interaction were considered-measurement with spontaneous free breathing, one with periodic sine breathing and one with a-periodic time-varying breathing. The results showed that the cardiorespiratory coupling strength and similarity of form of coupling functions have greater values for slower breathing, and this variability follows continuously the change of the breathing frequency. The method can be applied effectively to other time-varying oscillatory interactions and carries important implications for analysis of general dynamical systems. | 10.3389/fphys.2020.00341 |
pubmed_48_8264 | OBJECTIVES
The purpose of this study is to identify the safety and feasibility of laparoscopic caudate lobectomy.
BACKGROUND
Caudate lobectomy has been considered as technically difficult because of the deep location of the caudate lobe and its proximity to great vessels. Due to the technical difficulty, laparoscopic caudate lobectomy was not feasible in patients with malignancy in the caudate lobe.
METHODS
Six consecutive patients with caudate hepatic malignancy received laparoscopic caudate lobectomy at Samsung Medical Center from September 2007 to May 2014. Demographic data, intraoperative parameters, and postoperative outcomes were assessed.
RESULTS
All procedures for these 6 patients with caudate malignancy were completed with totally laparoscopic technique. Only 1 patient who had hepatocellular carcinoma in the Spiegel lobe underwent partial caudate lobectomy, and others underwent complete caudate lobectomy. The mean tumor size was 2.65 cm (range 0.9-5.1 cm). The mean operative time was 382 minutes (range 168-615 minutes) and none required transfusion. The mean duration of hospital stay was 8 days (range 6-13 days). There was no perioperative complication and patient mortality in this series. The resected margins of the specimens were tumor free (R0 resections, range 0.1-1.2 cm). The mean follow-up period was 56 months (range 12.9-93.7 months). No patient died during the follow-up period.
CONCLUSIONS
Our experience demonstrated that laparoscopic caudate lobectomy is safe and feasible in selected patients with malignancy in the caudate lobe. | 10.1089/lap.2016.0161 |
pubmed_806_21259 | [Pt2(μ-P2O5H2)4](4-) (Pt(pop)) and its perfluoroborated derivative [Pt2(μ-P2O5(BF2)2)4](4-) (Pt(pop-BF2)) are d(8)-d(8) complexes whose electronic excited states can drive reductions and oxidations of relatively inert substrates. We performed spin-orbit (SO) TDDFT calculations on these complexes that account for their absorption spectra across the entire UV-vis spectral region. The complexes exhibit both fluorescence and phosphorescence attributable, respectively, to singlet and triplet excited states of dσ*pσ origin. These features are energetically isolated from each other (∼7000 cm(-1) for (Pt(pop-BF2)) as well as from higher-lying states (5800 cm(-1)). The lowest (3)dσ*pσ state is split into three SO states by interactions with higher-lying singlet states with dπpσ and, to a lesser extent, pπpσ contributions. The spectroscopically allowed dσ*pσ SO state has ∼96% singlet character with small admixtures of higher triplets of partial dπpσ and pπpσ characters that also mix with (3)dσ*pσ, resulting in a second-order (1)dσ*pσ-(3)dσ*pσ SO interaction that facilitates intersystem crossing (ISC). All SO interactions involving the dσ*pσ states are weak because of large energy gaps to higher interacting states. The spectroscopically allowed dσ*pσ SO state is followed by a dense manifold of ligand-to-metal-metal charge transfer states, some with pπpσ (at lower energies) or dπpσ contributions (at higher energies). Spectroscopically active higher states are strongly spin-mixed. The electronic structure, state ordering, and relative energies are minimally perturbed when the calculation is performed at the optimized geometries of the (1)dσ*pσ and (3)dσ*pσ excited states (rather than the ground state). Results obtained for Pt(pop) are very similar, showing slightly smaller energy gaps and, possibly, an additional (1)dσ*pσ - (3)dσ*pσ second order SO interaction involving higher (1)dπpσ* states that could account in part for the much faster ISC. It also appears that (1)dσ*pσ → (3)dσ*pσ ISC requires a structural distortion that has a lower barrier for Pt(pop) than for the more rigid Pt(pop-BF2). | 10.1021/acs.inorgchem.5b00063 |
pubmed_1089_13351 | UNLABELLED
Approximately 10%-20% of all systemic lymphomas have central nervous system (CNS) involvement, which has been correlated to a worsened prognosis. It is well known that secondary involvement of the adrenal glands may occur in up to 25% of patients during the course of diffuse lymphoma. Primary adrenal lymphoma (PAL), however, is a different entity, and it is defined as the presence of adrenal lymphoma without evidence of either nodal involvement or leukemia. It has been shown that this occurrence is rarely accompanied by extranodal involvement, such as in the CNS. PAL exhibits a tendency for CNS relapse and this possibility should be examined even before symptoms are present. Herein we present a patient with PAL and secondary CNS involvement.
CONFLICT OF INTEREST
None declared. | 10.4274/Tjh.2012.0172 |
pubmed_950_2281 | 3D imaging is becoming more and more popular, as it allows us to identify interactions between structures in organs. Furthermore, it gives the possibility to quantify and size these structures. To allow 3D imaging, the tissue sample has to be transparent. This is usually achieved by using optical tissue clearing protocols. Although using optical tissue clearing often results in perfect 3D images, these protocols have some pitfalls, like long duration of sample preparation (up to several weeks), use of toxic substances, damage to antibody staining, fluorescent proteins or dyes, high refractive indices, and high costs of sample processing.Recently we described [Huang et al., Scientific Reports 9(1): 521 (2019)] a fast, safe, and inexpensive ethyl cinnamate (ECi) based optical tissue clearing protocol. Here, we present extensions of our protocol with respect to the deparaffinization of old paraffin-embedded samples allowing 3D imaging of the blocks. In addition, we learned to remove ECi from the samples allowing the use of routine immunolabeling protocols. Furthermore, we demonstrate new pictures of lungs after expansion microscopy and adaptation of already existing protocols. The aim of our work is, in summary, to describe the advances in these methodologies, focusing on the morphological imaging of kidneys and lungs. | 10.1002/ar.24463 |
pubmed_617_18533 | BACKGROUND
Decision analysis was used to clarify differences in survival and complication rates comparing surgery alone versus surgery plus chemotherapy for Stage I, favorable histology Wilms tumor patients.
PROCEDURE
A state transition model was used to simulate treatment with nephrectomy-only, nephrectomy with adjuvant vincristine (VCR) or with vincristine plus dactinomcyin (NWTS Regimen EE4A). Rates of relapse and complications of therapy were obtained from the literature. In sensitivity analysis, the model was probed for the value(s) at which the treatment of choice changes.
RESULTS
The overall survival (OS) is essentially the same for patients treated with any of the three strategies (OS(Nephrectomy) = 98.8%; OS(EE4A) = 98.8%; OS(VCR) = 98.6%). Rates of serious long-term complications in the surviving population are also similar across treatment strategies (nephrectomy = 1.4%; VCR = 1.2%; EE4A = 0.3%). Both the progression and salvage rates after nephrectomy-only would have to be much worse than expected for nephrectomy-only to be an unacceptable strategy.
CONCLUSIONS
The differences in overall survival and rates of long-term complications between the three different initial strategies were negligible in the model. Based on this analysis, it was decided by the Children's Oncology Group that it was acceptable to continue to include nephrectomy without adjuvant chemotherapy as an experimental arm of the low risk Wilms tumor protocol with stringent eligibility criteria and close follow-up. Decision analysis can have a role in clinical trial design by making the tradeoffs between strategies more explicit. The robustness of these conclusions can be tested by widely varying the underlying assumptions. | 10.1002/pbc.22396 |
pubmed_591_9508 | BACKGROUND
Use of Haemophilus influenzae type b conjugate vaccine is effective in reducing the disease burden, but its coverage in China is unclear. The aim of this meta-analysis is to assess the coverage of Hib conjugate vaccines in children in Mainland China.
METHODS
We systematically searched Pubmed, Web of Science, Medline, CNKI and Wanfang to identify studies assessing the coverage of Hib vaccine in Chinese children. Random-effects models were used to obtain pooled estimates for Hib vaccine coverage and analyzed heterogeneity with meta-regression and subgroup analyses.
RESULTS
Thirty-three studies that included 7,227,480 subjects in 12 provinces met our inclusion criteria. The pooled overall coverage of Hib conjugate vaccine was 54.9% [95% confidence interval (CI): 52.9-57.0]. The pooled coverage for the nonlocal population (54.3%; 95% CI: 52.4-56.3) was lower than that for the local residents (62.0%; 95% CI: 58.4-65.6). The region-pooled coverage was higher in the east of China (59.7%; 95% CI: 57.3-62.1) than in the central and west parts of the country (48.5%; 95% CI: 40.6-56.4). Overall, 26.7% (95% CI: 20.1-33.2) had 1 dose only, 14.8% (95% CI: 10.0-19.6%) had 2 doses, 13.5% (95% CI: 9.1-17.8) had 3 doses and 14.3% (95% CI: 9.7-18.9) had 4 doses.
CONCLUSIONS
We found a low coverage of Hib conjugate vaccine, particularly for the nonlocal children and those living in the central and west parts of China. Including Hib vaccine into the national immunization program is recommended to reduce disparities in vaccination coverage. | 10.1097/INF.0000000000002132 |
pubmed_1021_11741 | The synthesis of 16 metabolites of S-1452, an orally active thromboxane A2 (TXA2) receptor antagonist, is described. Regioselective hydroxylation at C-5 or C-6 of the bicyclo[2.2.1]heptane skeleton of the optically active intermediate 16 was attempted by using 9-borabicyclo[3.3.1]nonane followed by H2O2 or m-chloroperbenzoic acid (m-CPBA) and then LiA1H4, to obtain the hydroxylated product 17a or 17b, respectively. Modification of the C-2 substituent of 17a and 17b afforded eight metabolites of S-1452. Eight non-hydroxylated metabolites were synthesized by using a similar reaction sequence. | 10.1248/cpb.39.2842 |
pubmed_1007_12225 | Previous research on the evaluation of the Challenge Project, a community treatment program for sex offenders in southeast London, identified the potential role of key developmental variables as enhancing actuarial risk measures to identify individuals at highest risk for community failure. The aim of the current study was to assess the relationship between developmental variables and later personality dysfunction in adult-hood, and the contribution of these factors to assessing risk for sexual recidivism, in a wider group of sex offenders managed in the community by the probation service. Over an 8-month period, 241 participants were assessed, including 162 child molesters and 79 rapists. A wide range of background data were collected, including the administration of several psychometric measures. A strong relationship was found between key developmental variables and adult mental health and personality difficulties, as well as a range of risk measures. The implications of the findings for further research are discussed. | 10.1177/1079063208317464 |
pubmed_74_8872 | BACKGROUND
The optimal revascularization technique in diabetic patients with complex coronary artery disease (CAD), including left main CAD and multivessel coronary disease (MVD), remains controversial. The current study aimed to compare adverse clinical endpoints of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM).
METHODS
Relevant studies were found from MEDLINE, OVID, Science Direct, Embase and the Cochrane Central database from January 2010 to April 2019. Risk ratio (RR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables. Outcomes evaluated were all-cause mortality, major adverse cardiac/cerebrovascular events (MACCE), cardiac death, myocardial infarction, stroke, and repeat revascularization.
RESULTS
Sixteen studies were included (18,224 patients). PCI was associated with the increase risk for MACCE (RR 1.59, 95% CI 1.38-1.85), cardiac death (RR 1.76, 95% CI 1.11-2.80), MI (RR 1.98, 95% CI 1.53-2.57), repeat revascularization (RR 2.61, 95% CI 2.08-3.29). The risks for all-cause mortality (RR 1.23, 95% CI 1.00-1.52) and stroke (RR 0.71, 95% CI 0.48-1.03) were similar between two strategies. Stratified analysis based on studies design and duration of follow-up showed largely similar findings with the overall analyses, except for a significant increased risk of all-cause mortality (RR 1.32, 95% CI 1.04-1.67) in long-term group, and CABG was associated with a higher stroke rate compared to PCI, which are results that were found in RCTs (RR 0.47, 95% CI 0.28-0.79) and mid-term groups (RR 0.39, 95% CI 0.23-0.66).
CONCLUSIONS
CABG was superior to PCI for diabetic patients with complex CAD (including left main CAD and/or MVD), but might be associated with a higher risk of stroke mid-term follow-up.Number of Protocol registration PROSPERO CRD 42019138505. | 10.1186/s13098-019-0506-y |
pubmed_522_20379 | BACKGROUND
Binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein (GP) Ib-IX-V complex initiates a cascade of events leading to alphaIIbbeta3 activation and platelet aggregation. The roles of ADP and thromboxane A2 (TXA2) in agglutination-induced GPIbalpha-mediated platelet activation have not been fully described.
METHODS
Botrocetin and human VWF were used to stimulate washed mouse platelets. Platelets deficient in TXA2 receptors, Galphaq, or alphaIIbbeta3, and inhibitors and chelating agents were used to investigate the roles of TXA2, ADP, alphaIIbbeta3 and Ca2+ in botrocetin/VWF-induced signaling.
RESULTS
Our data demonstrate that botrocetin/VWF/GPIbalpha-mediated agglutination results in calcium-independent protein kinase C (PKC) and phospholipase A2 (PLA2) activities required for GPIbalpha-elicited TXA2 production that in turn causes dense granule secretion. Aggregation of washed platelets requires TXA2-induced alphaIIbbeta3 activation and ADP signaling. TXA2 or ADP can activate alphaIIbbeta3, but both are required for alpha-granule secretion and aggregation. Botrocetin/VWF-induced dense granule secretion is Galphaq-dependent. alpha-Granule secretion requires initial ADP signaling through P2Y1 and subsequent signaling through P2Y12. Signaling initiated by agglutination is propagated and amplified in an alphaIIbbeta3-dependent manner.
CONCLUSIONS
In contrast to adhesion or shear stress-induced GPIb-elicited signaling, agglutination-elicited GPIb signaling that activates alphaIIbbeta3 requires TXA2. Agglutination-elicited TXA2 production is independent of Ca2+ influx and mobilization of internal Ca2+ stores. Therefore, our results demonstrate that agglutination-elicited GPIb signaling causes alphaIIbbeta3 activation by a mechanism that is distinct from those used by adhesion, or shear stress-induced GPIb signaling. | 10.1111/j.1538-7836.2004.01023.x |
pubmed_869_12079 | BACKGROUND
The high-density silicone oil (Densiron 68), a mixture of F6H8 with silicone oil, seems to be a therapeutic option, at least in selected patients with complex inferior retinal re-detachment, where standard procedures have already failed. In an interventional case series we used Densiron as a primary endotamponade.
METHODS
Twelve eyes of 12 patients aged 31 years to 85 years with inferior complex rhegmatogenous retinal detachment with secondary proliferative vitreoretinopathy (PVR) grades CP2 to CA8 were included. Surgical techniques (pars plana vitrectomy, membrane peeling, retinotomy, retinectomy, endophotocoagulation, cryocoagulation, endotamponade) did not include a scleral buckling procedure (except one eye). Mean duration of the Densiron endotamponade was 78.3 +/- 29.74 days, with a mean follow up after removal of 400.6 +/- 85.4 days.
RESULTS
After Densiron removal, four patients (33.3%) showed a stable reattached retina without further interventions, while, in six patients (50%), recurrent retinal re-detachment appeared during endotamponade, generally within 2 months. One patient (8.3%) developed re-detachment 5 months after Densiron removal. One eye (8.3%) lost light perception due to severe intraretinal fibrosis with chronic hypotonia, despite complete retinal re-attachment. Visual acuity improved from mean logarithm of the minimum angle of resolution (logMAR) of 2.95 +/- 1.21 to 1.87 +/- 1.32 (statistically significant, P = 0.022). Side effects included temporary inflammatory reaction/fibrin accumulation (n = 2/2), moderate-to-severe intraretinal fibrosis (n = 3), elevated intraocular pressure (IOP) (n = 3), emulsification (n = 2), sterile hypopyon (n = 1), vitreous haemorrhage (n = 1) and chronic hypotony (n = 1).
CONCLUSION
Primary anatomical success rate of 33.3% was less encouraging than as expected. Especially, re-detachments within the posterior staphyloma in highly myopic patients were common during Densiron endotamponade. However, the surgical success increased to 75% after reintervention, even without the use of an additional encircling band. The observed adverse effects and the functional outcomes do not contraindicate the use of Densiron as an internal tamponade for a period of 3 months. | 10.1007/s00417-006-0496-y |
pubmed_78_22449 | Satellite cells represent a cellular source of regeneration in adult skeletal muscle. It remains unclear why a large pool of stem myoblasts in denervated muscle does not compensate for the loss of muscle mass during post-denervation atrophy. In this study, we present evidence that satellite cells in long-term denervated rat muscle are able to activate synthesis of contractile proteins after single fusions in situ. This process of early differentiation leads to formation of abnormally diminutive myotubes. The localization of such dwarf myotubes beneath the intact basal lamina on the surface of differentiated muscle fibers shows that they form by fusion of neighboring satellites or by the progeny of a single satellite cell following one or two mitotic divisions. We demonstrated single fusions of myoblasts using electron microscopy, immunocytochemical labeling and high resolution confocal digital imaging. Sequestration of nascent myotubes by the rapidly forming basal laminae creates a barrier that limits further fusions. The recruitment of satellite cells in the formation of new muscle fibers results in a progressive decrease in their local densities, spatial separation and ultimate exhaustion of the myogenic cell pool. To determine whether the accumulation of aberrant dwarf myotubes is explained by the intrinsic decline of myogenic properties of satellite cells, or depends on their spatial separation and the environment in the tissue, we studied the fusion of myoblasts isolated from normal and denervated muscle in cell culture. The experiments with a culture system demonstrated that the capacity of myoblasts to synthesize contractile proteins without serial fusions depended on cell density and the availability of partners for fusion. Satellite cells isolated from denervated muscle and plated at fusion-permissive densities progressed through the myogenic program and actively formed myotubes, which shows that their myogenic potential is not considerably impaired. The results of this study suggest that under conditions of denervation, progressive spatial separation and confinement of many satellite cells within the endomysial tubes of atrophic muscle fibers and progressive interstitial fibrosis are the important factors that prevent their normal differentiation. Our findings also provide an explanation of why denervated muscle partially and temporarily is able to restore its functional capacity following injury and regeneration: the release of satellite cells from their sublaminal location provides the necessary space for a more active regenerative process. | 10.1007/s00418-005-0012-1 |
pubmed_526_6808 | The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue because it has major implications for the prevention of pathological vascular conditions. Using microRNA array screen, we found the expression levels of 200 unique miRNAs in hyperplasic tissues. Among them, miR-200c expression substantially was down-regulated. The objective of this work was to assess the function of miR-200c and SUMOylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in both cultured cells and animal models of balloon injury. Under basal conditions, we found that miR-200c inhibited the expression of KLF4 and the SUMO-conjugating enzyme Ubc9. Upon PDGF-BB treatment, Ubc9 interacted with and promoted the SUMOylation of KLF4, which allowed the recruitment of transcriptional corepressors (e.g., nuclear receptor corepressor (NCoR) and HDAC2) to the miR-200c promoter. The reduction in miR-200c levels led to increased target gene expression (e.g., Ubc9 and KLF4), which further repressed miR-200c levels and accelerated VSMC proliferation. These results demonstrate that induction of a miR-200c-SUMOylated KLF4 feedback loop is a significant aspect of the PDGF-BB proliferative response in VSMCs and that targeting Ubc9 represents a novel approach for the prevention of restenosis. | pubmed_526_6808 |
pubmed_207_6764 | To assess the potential health risks associated with exposure to low levels of ozone, it is essential to know if the ozone-induced responses are dependent on cumulative exposures or on the peak concentrations. To answer this question female F344/N rats, 11-13 weeks of age, were exposed to a matrix of equal concentration x time values that included exposures to 0, 0.12, 0.24, and 0.48 ppm ozone for 3, 6, 12, or 24 hr. the response of the nasal epithelium was measured as induced DNA synthesis determined by the uptake of bromodeoxyuridine (a thymidine analog) into epithelial cells lining the nasal anterior maxilloturbinates. No increased DNA synthesis was observed in rats exposed to 0.12 ppm ozone for any of the time periods. For exposures higher than 0.12 ppm ozone, the response of the nasal epithelium was similar for equal cumulative exposures. The responses, however, were not linearly related to the cumulative (concentration x time) exposures. It appeared that some mitigating factor was present which decreased the responses at the higher cumulative exposures. No frank toxicity or cellular necrosis was observed, indicating that sublethal cell damage was sufficient to induce DNA synthesis. A simple mathematical model was developed to describe the relationship between ozone exposure and the induction of DNA synthesis in the nasal epithelium. The model predicted that the threshold concentration of ozone for inducing DNA synthesis in the nasal epithelium was 0.1 +/- 0.1 ppm. For one measure of ozone toxicity (induced DNA synthesis) at a sensitive site in the respiratory tract (maxilloturbinates), the effects of ozone were dependent on cumulative exposures at concentrations > 0.12 ppm and within the time and concentration ranges used in this study. | 10.1006/taap.1993.1044 |
pubmed_65_10592 | The internal auditory canal (IAC) and its extended areas of 27 normal human temporal bone specimens were investigated histologically for the distribution of psammoma bodies. A total of 145 +/- 25 (mean +/- SE) psammoma bodies were counted in series of every tenth 30-microm-thick section. Psammoma bodies were observed in the IAC and around the labyrinthine portion of the facial nerve (FN), the geniculate ganglion of the FN, and the posterior ampullary nerve in the singular canal. The number of psammoma bodies increases with age. We believe that psammoma bodies are a normal finding of aging in the IAC. The compression of the FN by psammoma bodies in the labyrinthine portion of the facial canal and the distribution of numerous psammoma bodies surrounding the posterior ampullary nerve in the narrow singular canal raise the questions of the involvement of psammoma bodies in the FN and in vestibular dysfunction and the presence of psammoma bodies in the subarachnoid space. | 10.1177/000348949910801007 |
pubmed_1114_14595 | OBJECTIVES
The hypothesis was that a reminder about recommended primary care physician (PCP) follow-up, sent via e-mail to patients discharged from the emergency department (ED), would increase the proportion of patients who followed up with their PCPs within the recommended time frame. Patient receptiveness to e-mail follow-up reminders was also assessed.
METHODS
This was a mixed methods clinical intervention study with subjects randomized either to receive the usual care discharge instructions only or to also receive a reminder e-mail message the day after the ED visit. The reminder e-mail contained the subject's PCP's name and address and the recommended PCP follow-up time interval. A blinded review of outpatient PCP medical records was conducted to determine whether and when follow-up occurred. Researchers attempted to contact patients with a telephone survey 2 weeks after their ED visits. The primary outcomes between groups were compared using chi-square tests and relative risks (RRs) with 95% confidence intervals (CIs).
RESULTS
Thirty-three percent of the intervention group and 32% of the control group followed-up as recommended (RR = 1.04, 95% CI = 0.81 to 1.33); 52% of the intervention group and 48% of the control group followed-up within 10 days of the recommended time (RR = 1.08, 95% CI = 0.91 to 1.29). The 334 patients (57%) successfully contacted via telephone demonstrated a high interest in receiving future e-mail reminders (75%), with the group that received e-mail reminders more likely to want one in the future than those who did not receive e-mail reminders (82.5% vs. 69.76%; p = 0.04).
CONCLUSIONS
E-mail reminders sent after ED visits did not improve patients' adherence to the recommended timing of primary care follow-up contained in discharge instructions. Subjects in both the control and the intervention groups favorably viewed the concept of e-mail reminders, suggesting that the value of e-mail reminders after ED discharge may be in areas such as patient satisfaction that were not specifically targeted for measurement in this study. | 10.1111/acem.12564 |
pubmed_520_4597 | BACKGROUND
The recent COVID-19 pandemic has highlighted the weaknesses of health care systems around the world. In the effort to improve the monitoring of cases admitted to emergency departments, it has become increasingly necessary to adopt new innovative technological solutions in clinical practice. Currently, the continuous monitoring of vital signs is only performed in patients admitted to the intensive care unit.
OBJECTIVE
The study aimed to develop a smart system that will dynamically prioritize patients through the continuous monitoring of vital signs using a wearable biosensor device and recording of meaningful clinical records and estimate the likelihood of deterioration of each case using artificial intelligence models.
METHODS
The data for the study were collected from the emergency department and COVID-19 inpatient unit of the Hippokration General Hospital of Thessaloniki. The study was carried out in the framework of the COVID-X H2020 project, which was funded by the European Union. For the training of the neural network, data collection was performed from COVID-19 cases hospitalized in the respective unit. A wearable biosensor device was placed on the wrist of each patient, which recorded the primary characteristics of the visual signal related to breathing assessment.
RESULTS
A total of 157 adult patients diagnosed with COVID-19 were recruited. Lasso penalty function was used for selecting 18 out of 48 predictors and 2 random forest-based models were implemented for comparison. The high overall performance was maintained, if not improved, by feature selection, with random forest achieving accuracies of 80.9% and 82.1% when trained using all predictors and a subset of them, respectively. Preliminary results, although affected by pandemic limitations and restrictions, were promising regarding breathing pattern recognition.
CONCLUSIONS
This study represents a novel approach that involves the use of machine learning methods and Edge artificial intelligence to assist the prioritization and continuous monitoring procedures of patients with COVID-19 in health departments. Although initial results appear to be promising, further studies are required to examine its actual effectiveness. | 10.2196/36933 |
pubmed_51_15490 | INTRODUCTION
Over a half a century ago, radiolabeled antibodies were shown to localize selectively in tissues based on the expression of unique antigens. Antibodies have since become the de facto targeting agent, even inspiring the development of non-antibody compounds for targeting purposes.
AREAS COVERED
In this article, we review various aspects of how antibodies are transforming the way cancer is being detected and treated, with the growing demand for unconjugated and many new antibody conjugates. While unconjugated antibodies continue to garner most of the attention, interest in new antibody drug conjugates and immunotoxins has expanded over the past few years. However, there continues to be active research with new radioimmunoconjugates for imaging and therapy, particularly with α-emitters, as well as antibody-targeted cytokines and other biological response modifiers.
EXPERT OPINION
The increasing number of new agents being developed and tested clinically suggests that antibody-targeted compounds will have an expanding role in the future. | 10.1517/14712598.2012.693472 |
pubmed_51_18950 | Cardiac cushion formation is crucial for both valvular and septal development. Disruption in this process can lead to valvular and septal malformations, which constitute the largest part of congenital heart defects. One of the signaling pathways that is important for cushion formation is the TGFβ superfamily. The involvement of TGFβ and BMP signaling pathways in cardiac cushion formation has been intensively studied using chicken in vitro explant assays and in genetically modified mice. In this review, we will summarize and discuss the role of TGFβ and BMP signaling components in cardiac cushion formation. | 10.1016/j.diff.2012.04.003 |
pubmed_561_7028 | OBJECTIVE
To study the effect of carbon disulfide (CS(2)) on pyrogallol-luminol auto-oxidation chemiluminescence (PA-L) system and production of superoxide anion.
METHODS
Luminescence dynamic curve of CS(2) and inhibition effect of superoxide dismutase (SOD) on intensity of chemiluminescence induced by CS(2) were studied with PA-L chemiluminescence system.
RESULTS
Different concentrations of CS(2) (10, 40, 80 mg/ml) could enhance the emission intensity of chemiluminescence of PA-L system and delayed its peak time, with a significant dose-effect relationship, as compared with that of solvent ethanol. Peak of chemiluminescence induced by 80 mg/ml of CS(2) was higher than its background value without solvent ethanol. Chemiluminescence induced by CS(2) could be inhibited by SOD.
CONCLUSION
CS(2) can generate superoxide anion in PA-L system and delay the peak time of chemiluminescence emission dynamic curve. | pubmed_561_7028 |
pubmed_1076_5255 | Vibrational spectroscopy [both Raman and INS (inelastic neutron scattering)], coupled to quantum mechanical calculations, was used in order to perform a thorough structural analysis of linear polyamines and polynuclear polyamine metal chelates [e.g. with Pt(II) and Pd(II)] with potential anticancer activity. The complementarity of the Raman and INS spectroscopies was exploited in order to gain a better knowledge of the conformational behaviour of these systems. Moreover, the conjugation of the experimental spectroscopic data to the theoretical results allows us to obtain valuable information on the structural preferences of this kind of system, which may lead to the establishment of SARs (structure-activity relationships) ruling their biological activity. Some of the most significant results obtained by the 'Molecular Physical-Chemistry' Research Group of the University of Coimbra (Portugal) are reviewed here. | 10.1042/BST0350374 |
pubmed_1012_19855 | The purpose of this study was an assessment average daily intake of calcium and phosphorus by prepubertal adolescents (aged 11 and 12) during monitoring their diets in last 10 years. In 1989-1999 years, it was investigated 767 randomly selected girls and 817 boys, aged 11 and 12 in Warsaw. Information on dietary intake was obtained by 24-hour recall method, always spring, having representation of weekdays and weekends. Among environmental factors, nutrition, and particularly calcium intake is assumed to influence whether the genetically determined maximal peak bone mass is reached. However, near half of examined prepubertal adolescents have intake less than 600 mg calcium per day. It was also observed low calcium to phosphorus ratio in diets and stated Ca:P < 0.25 among 10% diet in different groups of girls and boys. Consequently, due to consider the activity educational efforts directed to prepubertal adolescent with reference to means realization of calcium RDA in daily diet through increase milk and dairy products consumption. | pubmed_1012_19855 |
pubmed_424_23607 | The authors has list different surgical emergencies in an hospital in a rural area in Central African Republic, by a retrospective and prospective study. There were 213 cases, distributed among: 88 cases of trauma (41.3%), 78 cases of abdominal emergencies (21.5%), 46 cases of gynaecologic and obstetrical emergencies (21.5%), one case of urologic emergency (0.4%). Those pathologies have been studied through the age and sex of the patients, the different aetiologies and the body areas injured ( for the traumatims). Then they compared their results with those of the others and concluded that an effort must be done in those areas, mainly about the traffic accidents which number are growing. | pubmed_424_23607 |
pubmed_772_2987 | OBJECTIVE
The objective was to determine the importance of the "sagittal shoulder sign" on magnetic resonance (MR) images for the diagnosis of conjoined lumbosacral nerve roots (CLNR) that are compromised by herniated disks.
MATERIALS AND METHODS
Magnetic resonance images of 11 patients (6 men and 5 women; age range, 25-71 years; average age, 48.7 years) with surgically proven CLNR, which was compromised by herniated disks, were retrospectively evaluated by two musculoskeletal radiologists. MR images were evaluated for the presence or absence of the sagittal shoulder sign-a vertical structure connecting two consecutive nerve roots and overlying disk on the sagittal MR images. The radiologists noted the type of accompanying disk herniation and bony spinal canal changes, as well as other characteristic MR features of CLNR, the common passage of two consecutive nerve roots through the neural foramen on axial MR images.
RESULTS
The sagittal shoulder sign was identified with a mean frequency of 90.9% by the two observers (in 10 of 11 patients). The common passage of two consecutive nerve roots through the neural foramen on axial MR images was identified with a mean frequency of 59.1% (in 7 and 6 out of 11 patients, by observers 1 and 2, respectively). Good interobserver agreement for the sagittal shoulder sign was present (k = 0.621, p < 0.05).
CONCLUSION
Observation of the sagittal shoulder sign may prove helpful for diagnosing CLNR in patients with disk herniation. In particular, this sign appears to be useful when there is no evidence of CLNR on axial MR images. | 10.1007/s00256-007-0421-4 |
pubmed_163_5612 | A small non-coding, evolutionarily conserved regulatory RNA molecule known as microRNA (miRNA) regulates various cellular activities and pathways. MicroRNAs remain evolutionarily conserved in different species of same taxa. They are present in all organisms including viruses. Viral miRNAs are small, less conserved and less stable and have higher negative minimal folding free energy than miRNAs of different organisms. The size of viral precursor miRNA is approximately 60-119 nucleotides in length. The structure of the mature miRNA sequences is predicted by using higher negative MFE (ΔG) value. Rous sarcoma Virus (RSV), named after its inventor Peyton Rous, has been known for causing tumors in the chicken for which it is known as an oncogenic retrovirus. Using specific criteria we have predicted 5 potential miRNAs in RSV which targeted 8 tumor suppressor genes in Gallus gallus. This study aims to predict the potential miRNAs, secondary structures and their targets for better understanding of the regulatory network of Rous sarcoma virus miRNA in forming sarcoma. | 10.1016/j.meegid.2021.105139 |
pubmed_559_15829 | Cystinosis is a rare metabolic disorder characterized by lysosomal cystine accumulation leading to multi-organ damage, with kidneys being clinically first affected. Longer survival of cystinosis patients due to successful renal replacement therapy, revealed previously unknown extra-renal symptoms of cystinosis, generally appearing after the first decade. Respiratory insufficiency caused by overall respiratory muscle myopathy is a severely invalidating and sometimes a life-threatening complication of cystinosis. We report a successful treatment of hypoventilation, due to diaphragm myopathy in a cystinosis patient, by nocturnal non-invasive positive pressure ventilation (NIPPV). After initiation of NIPPV the clinical condition of the patient improved and blood-gasses normalized, indicating that this treatment modality should be considered in cystinosis patients with severe respiratory insufficiency. | 10.5414/cnp66306 |
pubmed_285_10926 | Gap junction-mediated communication helps synchronize interconnected Sertoli cell activities. Besides, coordination of germ cell and Sertoli cell activities depends on gap junction-mediated Sertoli cell-germ cell communication. This report assesses mechanisms underlying the regulation of connexin 46 (Cx46) and Cx50 in mouse testis and those accompanying a "natural" seasonal and a pathological arrest of spermatogenesis, resulting from autoimmune orchitis (AIO) in mink. Furthermore, the impact of deleting Cx46 or Cx50 on the expression, phosphorylation of junction proteins, and spermatogenesis is evaluated. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. During the mink active spermatogenic phase, Cx50 became phosphorylated and localized to the site of the blood-testis barrier. By contrast, Cx46 was dephosphorylated and associated with annular junctions, suggesting phosphorylation/dephosphorylation of Cx46 and Cx50 involvement in the barrier dynamics. Cx46-positive annular junctions in contact with lipid droplets were found. Cx46 and Cx50 expression and localization were altered in mink with AIO. The deletion of Cx46 or Cx50 impacted on other connexin expression and phosphorylation and differently affected tight and adhering junction protein expression. The level of apoptosis, determined by ELISA, and a number of Apostain-labeled spermatocytes and spermatids/tubules were higher in mice lacking Cx46 (Cx46-/-) than wild-type and Cx50-/- mice, arguing for life-sustaining Cx46 gap junction-mediated exchanges in late-stage germ cells secluded from the blood by the barrier. The data show that expression and phosphorylation of Cx46 and Cx50 are complementary in seminiferous tubules. | 10.1152/ajpregu.00152.2015 |
pubmed_511_21923 | BACKGROUND
Stromal vascular fraction (SVF) is a mixture of adipose-derived stem cells/mesenchymal stem cells, endothelial/progenitors, pericytes, fibroblasts, and other cells obtained from fat tissue. A small sample of fat or adipose tissue can be obtained under local anesthesia using a cannula. After an enzymatic digestion and centrifugation, the adipocytes (fat cells) are removed to obtain an SVF. Here, we describe the rationale and, to our knowledge, the first clinical implementation of SVF intravenously in a patient with severe psoriasis.
METHODS
Adipose tissue (60 mL) was collected under local anesthesia via a mini-lipoaspirate procedure. The SVF was separated from the adipocytes via centrifugation after an enzymatic digestion. The cells were resuspended in normal saline and injected via bolus push intravenous. The subject was monitored over a period of 12 months for safety (adverse events), medication changes, and quality of life parameters.
RESULTS
The patient did not report any safety concerns and did not experience any severe adverse events. The patient demonstrated a significant decrease in symptoms with a noticeable difference in skin quality appearance. Psoriasis area and severity index score went from 50.4 at baseline to 0.3 at 1 month follow-up.
CONCLUSION
Overall, the patient reported improved quality of life and willingness to continue treatments. This successful initial case study demonstrates that this may be a feasible treatment plan for patients suffering from psoriasis. | 10.2147/IMCRJ.S163612 |
pubmed_1089_17710 | A series of porous metal-organic frameworks having flexible carboxylic acid pendants in their pores (UiO-66-ADn: n=4, 6, 8, and 10, where n denotes the number of carbons in a pendant) has been synthesized by post-synthetic ligand exchange of terephthalate in UiO-66 with a series of alkanedioic acids (HO2 C(CH2 )n-2 CO2 H). NMR, IR, PXRD, TEM, and mass spectral data have suggested that a terephthalate linker in UiO-66 was substituted by two alkanedioate moieties, resulting in free carboxyl pendants in the pores. When post-synthetically modified UiO-66 was partially digested by adjusting the amount of added HF/sample, NMR spectra indicated that the ratio of alkanedioic acid/terephthalic acid was increased with smaller amounts of acid, implying that the ligand substitution proceeded from the outer layer of the particles. Gas sorption studies indicated that the surface areas and the pore volumes of all UiO-66-ADns were decreased compared to those of UiO-66, and that the CO2 adsorption capacities of UiO-66-ADn (n=4, 8) were similar to that of UiO-66. In the case of UiO-66-AD6, the CO2 uptake capacity was 34 % higher at 298 K and 58 % higher at 323 K compared to those of UiO-66. It was elucidated by thermodynamic calculations that the introduction of flexible carboxyl pendants of appropriate length has two effects: 1) it increases the interaction enthalpy between the host framework and CO2 molecules, and 2) it mitigates the entropy loss upon CO2 adsorption due to the formation of multiple configurations for the interactions between carboxyl groups and CO2 molecules. The ideal adsorption solution theory (IAST) selectivity for CO2 adsorption over that of CH4 was enhanced for all of the UiO-66-ADns compared to that of UiO-66 at 298 K. In particular, UiO-66-AD6 showed the most strongly enhanced CO2 uptake capacity and significantly increased selectivity for CO2 adsorption over that of CH4 at ambient temperature, suggesting that it is a promising material for sequestering CO2 from landfill gas. | 10.1002/chem.201303801 |
pubmed_118_15576 | This is a review of the 63rd British Association of Pediatric Surgeons (BAPS) annual conference which was held in July 2016 in Amsterdam in the Netherlands. This congress issue contains papers presented during the open sessions and transcripts based on invited lectures. | 10.1016/j.jpedsurg.2016.11.007 |
pubmed_112_16891 | Balanced continuous flow resection has been offered as the best form of irrigation in uroendoscopy. Although it will keep the bladder pressure low, using flow visualization techniques it has been demonstrated that it does not fulfil the requirements of an irrigating fluid when used in a confined environment such as the prostatic urethra. The outflowing irrigating fluid has been shown to be taken directly from the inflowing jet ('steal effect') thereby reducing the effectiveness of the irrigating jet on the working area of the resectoscope. | 10.1159/000474806 |
pubmed_248_17861 | Interferon-gamma (IFN-gamma) induces the enzyme indoleamine dioxygenase (IDO) in a variety of human cell types. Furthermore, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) synergistically increase IFN-induced IDO activity. Inasmuch as cytokines can upregulate cytokine receptor expression, one mechanism of cytokine synergy may be at the level of receptor expression. To test the hypothesis that this mechanism of IDO regulation is active in epithelial cells, HeLa cells were treated with IFN-gamma, TNF-alpha, or IL-1beta to determine optimal cytokine concentrations and time for maximal cytokine receptor expression. Flow cytometric analysis with antibodies to receptors for IFN-gamma, TNF-alpha, or IL-1beta indicated that each cytokine upregulated expression of the other cytokine receptors by 4 h, with maximal expression observed between 16 and 20 h after cytokine treatment. Furthermore, increases in IFN-gamma receptors (IFNGR) induced by IL-1beta were found to be dependent on NF-kappaB transactivation. To determine if increases in IFNGR expression alone contributes to synergistic IDO induction, cells were stimulated with IL-1beta to upregulate receptor expression, and the NF-kappaB concentration was allowed to return to basal levels. When treated with IFN-gamma, enhanced Stat1 signaling and IDO induction were still observed, indicating that increased cytokine receptor expression contributes to synergistic increases in IDO activity. | 10.1089/jir.2006.26.53 |
others_257_14493 | This experiment carried out in a southwestern Korea on a commerce silt loam soil at paddy field. Pungsannamulmong (PSNK), a yellow seed color type, was a relatively high-yielding late maturing cultivar and Nogchaekong (NCK), green seed color type, was a relatively low-yielding early maturing cultivar. Two seeds per hill were sowed with the planting density of 70 × 10 cm on May 20 and June 20, 2007. Fertilizer was applied prior to planting at a rate of 3.0-3.0-3.4 g (N-P-K) per m2 by all basal fertilizations. Experimental design was a randomized complete block with three replications. The days from planting to flowering date (R1) and maturing date were longer in PSNK than in NCK on two planting dates. Each seed yield of PSNK planted on May 20 or June 20, which was 282 or 248 g m-2, was higher than that of NCK, which was 244 and 213 g m-2, respectively. Also, the number of pod, number of seed and seed per pod were higher in PSNK than in NCK. The leaf area and top dry matter were higher in PSNK than in NCK, especially, at 60 and 70 days after emergence, respectively. Photosynthetic rate (PN) at flowering stage (R1), there was no significant difference between cultivars in the uppermost leaf but there was a significant difference in PN of the 7th leaf on seed development stage (R5) | 10.5109/12846 |
pubmed_851_2174 | BACKGROUND
Women and their relatives can play an important role in early detection and help seeking for acute perinatal events. Recent UK reports indicate that patient-professional partnership in 'working for safety' can be difficult to achieve in practice, sometimes with catastrophic consequences. This research explored the experiences of women and relatives who had experienced early warning signs about their condition and sought help in escalating care.
METHODS
Secondary analysis of case study data which included qualitative interviews with 22 women purposively sampled on account of experiencing a step up in care and 4 of their relatives from two NHS Trusts in England during 2010. Analysis focused on the type of safety work participants engaged in, and the opportunities and challenges reported by women and family members when negotiating safety at home and in hospital.
RESULTS
Women and relatives took on a dual responsibility for self-diagnosis, self-care and seeking triage, whilst trying to avoid overburdening stretched services. Being informed, however, did not necessarily enable engagement from staff and services. The women's narratives highlighted the work that they engaged in to build a case for clinical attention, the negotiations that took place with health care professionals and the strategies women and partners drew on (such as objective signs and symptoms, use of verbal insistence and repetition) to secure clinical help. For some women, the events left them with a lasting feeling that their concerns had been disregarded. Some described a sense of betrayal and loss of trust in an institution they believed had failed to care for them.
CONCLUSION
The notion of 'safety partnerships' which suggests a sense of equality and reciprocity was not borne out by our data, especially with regards to the experiences of teenage women. To enable women and families to secure a rapid response in clinical emergencies, strategies need to move beyond the provision of patient information about warning signs. Effective partnerships for safety may be supported by system level change such as improved triage, continuity of care, self-referral pathways and staff training to address asymmetries of power that persist within the health system. | 10.1186/s12884-017-1401-x |
pubmed_392_22870 | The time course of the neuronal activity in the brain network, the neurodynamics, reflects the structure and functionality of the generating neuronal pools. Here, using the intracranial stereo-electroencephalographic (sEEG) recordings of the public Montreal Neurological Institute (MNI) atlas, we investigated the neurodynamics of primary motor (M1), somatosensory (S1) and auditory (A1) cortices measuring power spectral densities (PSD) and Higuchi fractal dimension (HFD) in the same subject (M1 vs. S1 in 16 subjects, M1 vs. A1 in 9, S1 vs. A1 in 6). We observed specific spectral features in M1, which prevailed above beta band, S1 in the alpha band, and A1 in the delta band. M1 HFD was higher than S1, both higher than A1. A clear distinction of neurodynamics properties of specific primary cortices supports the efforts in cortical parceling based on this expression of the local cytoarchitecture and connectivity. In this perspective, we selected within the MNI intracortical database a first set of primary motor, somatosensory and auditory cortices' representatives to query in recognizing ongoing patterns of neuronal communication. Potential clinical impact stands primarily in exploiting such exchange patterns to enhance the efficacy of neuromodulation intervention to cure symptoms secondary to neuronal activity unbalances. | 10.1093/cercor/bhab389 |
pubmed_757_21961 | Natural products have been known for their antimicrobial factors since time immemorial. Infectious diseases are a worldwide burden that have been deteriorating because of the improvement of species impervious to various anti-infection agents. Hence, the distinguishing proof of antimicrobial specialists with high-power dynamic against MDR microorganisms is central to conquer this issue. Successful treatment of infection involves the improvement of new drugs or some common source of novel medications. Numerous naturally occurring antimicrobial agents can be of plant origin, animal origin, microbial origin, etc. Many plant and animal products have antimicrobial activities due to various active principles, secondary metabolites, or phytochemicals like alkaloids, tannins, terpenoids, essential oils, flavonoids, lectins, phagocytic cells, and many other organic constituents. Phytocomplexes' antimicrobial movement frequently results from a few particles acting in cooperative energy, and the clinical impacts might be because of the direct effects against microorganisms. The restorative plants that may furnish novel medication lead the antimicrobial movement. The purpose of this study is to investigate the antimicrobial properties of the phytocomplexes and natural extracts of the plants that are ordinarily being utilized as conventional medications and then recommended the chance of utilizing them in drugs for the treatment of multiple drug-resistant disease. | 10.3390/antibiotics10091076 |
pubmed_536_25070 | The aims of this study were to analyse the stress distribution developing around an orthodontic miniscrew (OM) inserted into the maxilla and to determine the stress field changes for different screw lengths and for different levels of osseointegration occurring at the bone/screw interface. An integrated experimental/numerical approach was adopted. Using the photoelastic technique, the stress field arising in the bone after screw insertion and the application of the initial orthodontic load was assessed. The finite element (FE) method was used to determine the stress acting in the bony tissue after a given time following screw application, when, for the viscoelastic relaxation effects, the only stress field remaining was that due to the application of the orthodontic load. Different levels of osseointegration were hypothesized. Photoelastic analyses showed that stress distribution does not change significantly for moderate initial orthodontic loads. From the FE simulations, it was found that critical conditions occur for screws 14 mm long with an orthodontic load of 2 N. The optimal screw length seems to be 9 mm. For such a dimension, small stress values were found as well as low risk of lesion to the anatomical structures. | 10.1093/ejo/cjn066 |
pubmed_733_18256 | CONTEXT
The dimethylbenz(alpha)anthracene (DMBA) breast cancer model induced in the rat is used for the study of mammary carcinogenesis because it closely mimics human breast disease.
OBJECTIVE
To analyze the histopathologic features of mammary carcinomas induced in the DMBA experimental model, in a manner similar to that used in human pathology, to allow a comparative analysis between both systems.
DESIGN
Three experimental series of 20 animals were used. At 53 days of age, a single dose of 5 mg of DMBA per rat was given. Mammary tumors were collected when the rats were killed. Several histopathologic parameters were studied. For grading, the parameters described in the modified Scarff-Bloom-Richardson scheme were used, adapted to rat mammary tumors.
RESULTS
More than 50% of the carcinomas presented a pattern grade I, a nuclear grade I or II, and fewer than 10 mitoses/10 high-power fields (P <.05). Although the tumors were generally well differentiated, they showed a range of differentiation. More than 85% of carcinomas did not display tumoral necrosis (P <.05). This feature was observed mostly in high-grade carcinomas. There was no or scanty lymphoplasmacytic infiltration in more than 70% of carcinomas (P <.05). The degree of infiltration increased with the histologic grade. Microcalcifications were found rarely (P <.05). The carcinomas exhibited a mixed structural pattern, most with a predominant cribriform pattern (P <.05). No or light (+) stromal response was seen in most cases (P <.05). Some carcinomas, especially when poorly differentiated, presented a desmoplastic reaction. Most carcinomas presented scanty mast cell infiltration (P <.05), no features of secretion (P <.05), and absence of microcribriform pattern (P <.05). These features were seen more often in low-grade carcinomas.
CONCLUSIONS
Despite the presence of some structural differences, rat mammary adenocarcinomas and the most common human breast carcinomas share several morphologic similarities. Moreover, some features could be related to the aggressive behavior of the tumor. The analysis carried out in this study, similar to that done in human pathology, allows a more extensive understanding of mammary tumors in rats, as well as a more accurate use of this animal model, and has made it possible to develop an innovative classification of rat mammary lesions. | 10.5858/2002-126-0915-HCOMNL |
pubmed_1015_13022 | The use of elongated prophase and prometaphase chromosome preparations has allowed detection of an insertion of a small segment of 3q into 11q in a kindred with 4 balanced carriers and 8 unbalanced offspring. Those with partial 3q deletion have a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome with an appearance suggestive of the Schwartz-Jampel syndrome. | 10.1002/ajmg.1320090204 |
pubmed_115_20377 | OBJECTIVES
Resistance to antidepressant medication is the commonest stated indication for electroconvulsive therapy (ECT) by psychiatrists, but what this means in practice has not been described. Our aims were to survey what antidepressant drug treatment had been prescribed to patients before they underwent ECT and to what extent this treatment would satisfy operational criteria for adequate antidepressant drug treatment used in ECT research.
METHODS
The survey was conducted prospectively among 37 depressed patients referred for a new course of bilateral ECT and where antidepressant medication resistant was identified as the indication for ECT.
RESULTS
Only half the sample had been prescribed more than one antidepressant drug, and only 38% had been prescribed any augmentation compound. Although the majority of patients were resistant to medication when rated by the older operational criteria, only half the sample met contemporary criteria for medication resistance.
CONCLUSIONS
The findings suggest a lack of agreement between clinicians and researchers in what constitutes medication resistance as a possible indication for ECT. It will take some time to establish if the revised UK Royal College of Psychiatrists ECT Handbook will encourage more intensive medical treatment of depressive illness before the use of ECT. | 10.1097/01.yct.0000179006.36132.a3 |
others_91_1013 | Models of feeding regulation postulate that chemosensory information from available food both initiates and maintains feeding. However, we find that removing antennae and maxillae (AM) from Manduca sexta and Diacrisia virginica larvae has little effect on amounts eaten, patterns of feeding, and the microstructure (each bite and pause) of feeding, as quickly as two days after the operation. However, there was a small change in the microstructure of feeding of AM D. virginica. Bite frequency of AM D. virginica was significantly lower than for controls when larvae began meals without exploring the food first. Exploring was also followed by longer chewing bouts. Acute effects of the ablution were tested using only Manduca. Six hours after the operation larvae ate less than most controls by eating fewer meals and by biting more slowly. Unilateral ablates also ate less 6 h post-operatively, by eating fewer meals; their bite frequency was not low. These observations suggest that chemosensory input affects bite frequency but not other aspects of feeding. As quickly as 24 h post-operatively other sensory input to the CNS of AM larvae may compensate for the reduction in chemosensory information, but overall, chemosensory input appears relatively unimportant in non-choice situations | 10.1016/S0022-1910(97)00065-6 |
pubmed_491_7914 | PURPOSE
To determine the prognostic value of pretreatment anemia, pretreatment elevated C-reactive protein (CRP) levels, and 6-month posttreatment anemia in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone (R-CHOP).
PATIENTS AND METHODS
A total of 104 patients with newly diagnosed DLBCL were retrospectively included. Pretreatment hemoglobin and CRP levels and 6-month posttreatment hemoglobin levels were measured. Cox regression analyses were used to determine the associations of laboratory assessments and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) risk groups with progression-free survival (PFS) and overall survival (OS).
RESULTS
Pretreatment anemia, elevated pretreatment CRP levels, and higher risk NCCN-IPI groups were significantly associated with reduced PFS and OS (P = .001 and P = .003 for pretreatment anemia, P = .035 and P = .029 for elevated CRP, and P < .001 and P < .001 for higher risk NCCN-IPI groups). On multivariate Cox regression analysis, only the NCCN-IPI risk group remained as an independent significant predictor for PFS (P < .001) and OS (P < .001). In the subgroup of patients in complete remission 6 months after chemotherapy (n = 80), 6-month posttreatment anemia was significantly associated with reduced PFS (P = .046) but not OS (P = .062), and higher risk NCCN-IPI groups were significantly associated with both reduced PFS (P = .008) and OS (P = .017). On multivariate Cox regression analysis, only the NCCN-IPI group remained an independent significant predictor for PFS (P = .008) and OS (P = .017).
CONCLUSION
Pretreatment anemia, pretreatment CRP levels, and 6-month posttreatment anemia are significantly associated with poor outcome, but were not proven to be of additional prognostic value to the current risk stratification index for DLBCL. | pubmed_491_7914 |
pubmed_923_4961 | Receptors for hypoglycemic sulfonylureas, such as glibenclamide, are commonly linked to the activity of ATP-sensitive K+ channels (K-ATP). High and low affinity binding sites for glibenclamide were described previously in numerous tissues. High affinity binding sites have been thought to be responsible of the modulation of K-ATP, but new evidences suggest that low affinity ones could also regulate these channels. In order to clarify the properties of the two binding sites, with respect to their interaction with K-ATP, we characterized biochemically and pharmacologically [3H]glibenclamide binding in the rat brain cortex. Competitive inhibition plots with [3H]glibenclamide performed on membranes of adult and neonatal rat brain cortex exhibited a biphasic pattern with similar binding parameters, indicating the presence of two similar binding sites in adult as well as in neonatal animals. Membranes of adult rat cortex treated with thiol groups modifying agents, N-ethylmaleimide or 1,4-dithiothreitol, increased the inhibition constant of glibenclamide for the low affinity binding sites (K(i)L) by about 4-fold. The divalent cations Mg++ and Ca++ also increased K(i)L by 3- to 6-fold and enhanced the low affinity binding capacity (BmaxL) by 55 and 103%, respectively, both cations increasing BmaxL by 144%. Among the numerous nucleotides studied, adenine and guanidine triphosphate nucleotides were the most potent to affect the low affinity binding sites. ATP, ADP, GTP and respective nonhydrolysable nucleotides increased K(i)L by 7- to 12-fold and decreased BmaxL by 10 to 30%. The effects of nucleotides were not Mg++ dependent.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_923_4961 |
pubmed_160_16831 | Spectroscopic properties of 1:n complexes (n = 1, 2, and 3) formed between an oxirane molecule and water clusters have been evaluated using experimental techniques (FTIR spectroscopy using a new supersonic jet experiment coupled to the infrared AILES beamline of synchrotron SOLEIL and also cryogenic neon matrix device) and theoretical approaches (SAPT, ab initio, DFT, and topological analyses). From a systematic comparison between the theoretical results (obtained with both wave function based methods and several newly hydrogen bonded adapted functionals) with the available experimental results on the studied compounds, it was concluded that only the wave function based methods (particularly coupled clusters ones) are able to well describe these compounds, while the newly hydrogen bonded adapted functionals (long-range and/or dispersion-corrected ones and also double hybrids) cannot adequately describe all the spectroscopic properties in a systematic way. The MP2 method, although more expensive than DFT, still offers a reliable method to study both isolated molecules and hydrogen bonded complexes provided the contribution of the dispersion energy in total energy is properly taken into account. The nature of interaction between oxirane and water molecules has been analyzed using the symmetry adapted perturbation theory (SAPT) method. It was evidenced that the water-oxirane interaction corresponds to the hydrogen-bonded systems with a large contribution of the dispersion energy. The nature of the oxirane-water bonding has been studied using two topological methods: atoms in molecules and electron-localization function (ELF). Geometrical structures of the titled complexes were rationalized from the spatial arrangement of ELF attractors. Secondary interaction was also accounted for the bond critical points found at H(oxirane)···O(water) bond paths. | 10.1021/jp202867t |
pubmed_611_630 | A method is described in which proteins that match PROSITE patterns are filtered by the root-mean-square deviation of the local 3D structures of the probe and target over the pattern components. This was found to increase the discrimination between true and false members of the protein family but was dependent on how unique the structural features in the pattern were compared to equivalent fragments extracted from the structure databank (for example; if the pattern fell in an alpha-helix, then discrimination was poor.) We then generalised the sequence patterns (by widening the range of amino acid residues allowed at each position) and monitored how well the structural information helped retain specificity. While the discrimination of the pure sequence pattern had generally disappeared at information content values less than ten bits, the discrimination of the combined sequence structure probe remained high at this point before following a similar decay. The displacement between these curves indicates that the structural component is, on average, equivalent to about ten bits. The sequence patterns were also filtered using the structure comparison program SAP, giving a global, rather than local "view" of the proteins. This allowed the information content of the sequence patterns to become even less specific but raised problems of whether some proteins encountered with the same fold but no PROSITE pattern should constitute family members. | 10.1006/jmbi.2000.4211 |
others_247_17840 | Peronospora sparsa Berkeley was identified on cherry laurel (Prunus laurocerasus) which was being propagated in four nurseries across England and Wales in 1987. This is the first record of a downy mildew on Prunus laurocerasus. Copyright © 1992, Wiley Blackwell. All rights reser | 10.1111/j.1365-3059.1992.tb02341.x |
pubmed_809_22256 | Premature infants are routinely exposed to invasive medical procedures during neonatal intensive care treatment that are largely performed in the absence of anesthetics or analgesics. Data collected to date suggest that exposure to early insult during this time of increased plasticity alters the development of the CNS and influences future pain responses. As previous studies examining the impact of neonatal injury on nociception have been conducted primarily in males, the potential adverse effects on females are not known. Therefore, the present studies were conducted to determine whether neonatal injury differentially impacts male and female sensory thresholds in adulthood. A short lasting inflammatory response was evoked in male and female rats on the day of birth with an injection of carrageenan (CGN; 1% or 2%) into the right hindpaw. Nociceptive thresholds were assessed using a noxious thermal stimulus at both adolescence (P40) and adulthood (P60). A more persistent inflammation was subsequently evoked in adult rats with an intraplantar injection of Complete Freund's adjuvant (CFA). Neonatally injured females exhibited significantly greater hypoalgesia at P60, and displayed enhanced inflammatory hyperalgesia following re-injury in adulthood compared to neonatally injured males and controls. These results demonstrate that the long-term adverse effects of neonatal injury are exacerbated in females, and may contribute to the higher prevalence, severity and duration of pain syndromes noted in women compared to men. | 10.1016/j.pain.2007.08.010 |
pubmed_1133_9000 | OBJECTIVES
Biomass subpopulations in mammalian cell culture processes cause impurities and influence productivity, which requires this critical process parameter to be monitored in real-time.
RESULTS
For this reason, a novel soft sensor concept for estimating viable, dead and lysed cell concentration was developed, based on the robust and cheap in situ measurements of permittivity and turbidity in combination with a simple model. It could be shown that the turbidity measurements contain information about all investigated biomass subpopulations. The novelty of the developed soft sensor is the real-time estimation of lysed cell concentration, which is directly correlated to process-related impurities such as DNA and host cell protein in the supernatant. Based on data generated by two fed-batch processes the developed soft sensor is described and discussed.
CONCLUSIONS
The presented soft sensor concept provides a tool for viable, dead and lysed cell concentration estimation in real-time with adequate accuracy and enables further applications with respect to process optimization and control. | 10.1007/s10529-017-2408-0 |
pubmed_174_72 | This study was done to correlate mitochondrial behaviour with nuclear behaviour and cell division as well as with the germ tube formation in the dimorphic yeast Candida albicans. Three-dimensional reconstruction of electron micrographs of serially sectioned cells of the three strains was used to determined the morphological and quantitative relationships between the structures. The results suggested that at the time of entry into the bud a few mitochondria fused into a single giant one, which fragmented during mitosis and resumed a single giant form before cytokinesis, and was then partitioned into two parts. This tendency was also shown during germ tube formation. Quantitative analysis has established that growth of organelles such as the nucleus and mitochondria closely followed total cell growth, the ratio of organelle volume to total cell volume being held relatively constant. | 10.1242/jcs.73.1.207 |
pubmed_901_9206 | Computer-generated prescription drug purchase records for ambulatory patients receiving oral anticoagulants (OAC) were studied for concomitant use of other drugs which have been reported to induce clinically significant interactions. One third of 479 patients taking OAC were exposed to a potentially interacting drug at some time during this 6-month period. The percentage of patients with drug interaction exposure correlated directly with total drug use (p less than 0.0005). There were no significant differences when interaction exposure rates were compared in the cases of single : multiple pharmacy and single : multiple physician-patient groups. Warfarin was the most common anticoagulant (greater than 95%) and barbiturates the most common interacting drug. | 10.1002/cpt1978246644 |
pubmed_94_14806 | Crimean-Congo hemorrhagic fever virus (CCHFV) is a tri-segmented, tick-borne nairovirus that causes disease of ranging severity in humans. The CCHFV M segment encodes a complex glycoprotein precursor (GPC) that undergoes extensive endoproteolytic cleavage, giving rise to two structural proteins (Gn and Gc) required for virus attachment and entry, and to multiple non-structural proteins (NSm, GP160, GP85, and GP38). The functions of these non-structural proteins remain largely unclear. Here, we investigate the role of NSm during infection by generating a recombinant CCHFV lacking the complete NSm domain (10200∆NSm) and observing CCHFV ∆NSm replication in cell lines and pathogenicity in Ifnar-/- mice. Our data demonstrate that the NSm domain is dispensable for viral replication in vitro, and, despite the delayed onset of clinical signs, CCHFV lacking this domain caused severe or lethal disease in infected mice. | 10.3390/microorganisms8050775 |
pubmed_93_2210 | In the present theoretical note we examine how different learning constraints, thought to be involved in optimizing the mapping of print to meaning during reading acquisition, might shape the nature of the orthographic code involved in skilled reading. On the one hand, optimization is hypothesized to involve selecting combinations of letters that are the most informative with respect to word identity (diagnosticity constraint), and on the other hand to involve the detection of letter combinations that correspond to pre-existing sublexical phonological and morphological representations (chunking constraint). These two constraints give rise to two different kinds of prelexical orthographic code, a coarse-grained and a fine-grained code, associated with the two routes of a dual-route architecture. Processing along the coarse-grained route optimizes fast access to semantics by using minimal subsets of letters that maximize information with respect to word identity, while coding for approximate within-word letter position independently of letter contiguity. Processing along the fined-grained route, on the other hand, is sensitive to the precise ordering of letters, as well as to position with respect to word beginnings and endings. This enables the chunking of frequently co-occurring contiguous letter combinations that form relevant units for morpho-orthographic processing (prefixes and suffixes) and for the sublexical translation of print to sound (multi-letter graphemes). | 10.3389/fpsyg.2011.00054 |
pubmed_181_10069 | PURPOSE
To evaluate a single eye bank's measurement of endothelial cell density (ECD) of Descemet membrane endothelial keratoplasty (DMEK) grafts before and after preparation using 2 separate counting methods.
METHODS
A series of 60 donor tissues were prepared for DMEK surgery. One to 4 specular images of the central endothelium were taken both before and after preparation, and ECDs were evaluated for a total of 345 unique images. Images were then masked and provided to the Cornea Image Analysis Reading Center (CIARC) for independent analysis.
RESULTS
Before preparation, average eye bank-determined ECD with the center method was 2678 ± 259 cells/mm and was 2599 ± 280 cells/mm CIARC-determined by the variable frame method (P < 0.001, n = 176). After preparation, eye bank-determined ECD was 2719 ± 265 cells/mm and CIARC-determined ECD was 2615 ± 344 cells/mm (P < 0.001, n = 169). The difference in ECD before and after DMEK preparation was not found to be statistically significant when evaluated using either analysis method (P = 0.19; P = 0.64) before and after preparation, respectively.
CONCLUSIONS
Although the absolute ECD value may differ by the analysis method statistically, pre- and post-DMEK preparation ECDs did not significantly change by either analysis method. Other methods such as vital staining to assess tissue damage after preparation in conjunction with specular microscopy are suggested. | 10.1097/ICO.0000000000001044 |
pubmed_567_8227 | The effects of ascorbic acid (AsA) on membrane phospholipids (PLs) and tocopherols (Tocs) of human erythrocyte during peroxidation by soybean lipoxygenase (LOX) were investigated. After extraction of the membrane lipids, alpha-tocopherol (alpha-Toc), gamma-tocopherol (gamma-Toc) and cholesterol were simultaneously measured by high-performance liquid chromatography (HPLC), and the changes of Tocs were expressed on the basis of cholesterol. The phospholipid classes and corresponding hydroperoxides (PL-OOHs) were detected simultaneously by HPLC, and the changes were calculated on the basis of sphingomyelin. These methods are sensitive to the changes of membrane Tocs and PLs by peroxidation. Control incubation without LOX and AsA was done for 45 min at 30 degrees C. After the incubation with LOX, alpha- and gamma-Tocs were exhausted, PLs decreased, and PL-OOHs and malondialdehyde (MDA) increased. Incubation with both AsA and LOX further increased MDA significantly, but it preserved about 30% of alpha-Toc and 45% of gamma-Toc of the control levels and did not decrease PLs or PL-OOHs from the levels after the incubation with LOX. Subsequent incubation with AsA for 45 min after the incubation with LOX (after Tocs were exhausted) showed a 240% increase in MDA, but it decreased PLs by only about 15% of the preincubation values and recovered gamma-Toc to about 13% of the control. The subsequent incubation with AsA after the control incubation increased PLs to higher than that of the control reaction. These results show that AsA protects and regenerates the membrane Tocs against enzymatic peroxidation. The results also indicate that repair of the membrane PLs is promoted in the presence of AsA. | 10.3177/jnsv.45.687 |
pubmed_370_5398 | The extent of plasma protein binding of diazepam (DZ) and its major metabolite, desmethyldiazepam (DMDZ), was determined by equilibrium dialysis in plasma samples drawn from 62 nonfasting unheparinized volunteers aged 20 to 85 years. The free fraction for diazepam averaged 1.48 per cent (range 0.85 to 2.30 per cent) and increased with age (r = 0.33). Desmethyldiazepam also was extensively bound. The mean free fraction was 2.97 per cent (range 1.78 to 5.28 per cent) and increased with age (r = 0.27). Free fractions for both diazepam and desmethyldiazepam were negatively correlated with plasma albumin concentration (r = --0.17 and --0.39). However, age, sex, and albumin explained only a small proportion of variability in free fraction for either compound. Free fraction for desmethyldiazepam always exceeded that for diazepam, and the two were correlated (r = 0.32). Thus, at any given total plasma concentration, the unbound concentration of desmethyldiazepam will exceed that of diazepam. | 10.1002/j.1552-4604.1981.tb02551.x |
pubmed_1032_6210 | Under the seeming disorder of "junk" sequences the last decade has seen developments in our understanding of non-coding RNA's (ncRNAs). It's a complex revised order and nowhere is this more relevant than in the developing heart whereby old rules have been set aside to make room for new ones. The development of the mammalian heart has been studied at the genetic and cellular level for several decades because these areas were considered ideal control points. As such, detailed mechanisms governing cell lineages are well described. Emerging evidence suggests a complex new order regulated by epigenetic mechanisms mark cardiac cell lineage. Indeed, molecular cardiologists are in the process of shedding light on the roles played by ncRNAs, nucleic acid methylation and histone/chromatin modifications in specific pathologies of the heart. The aim of this article is to discuss some of the recent advances in the field of cardiovascular epigenetics that are related to direct cell reprogramming and repair. As such, we explore ncRNAs as nodes regulating signaling networks and attempt to make sense of regulatory disorder by reinforcing the importance of epigenetic components in the developmental program. | 10.1016/j.yjmcc.2019.01.019 |
pubmed_1131_14144 | This phase 1, open-label study evaluated the pharmacokinetic effects of coadministration of the antifungal agent, isavuconazole (administered as its water-soluble prodrug isavuconazonium sulfate), with the antiretroviral agent lopinavir/ritonavir in healthy adults. In part 1, 13 subjects were randomized to 2 arms to receive multiple doses of oral isavuconazole 100 mg either alone or with lopinavir/ritonavir 400/100 mg. In part 2, a different group of 55 subjects were randomized to 3 arms to receive multiple doses of oral isavuconazole 200 mg, either alone or with lopinavir/ritonavir 400/100 mg, or to receive oral lopinavir/ritonavir 400/100 mg alone. Mean area under the concentration-time curve (AUC) following the last dose (AUCτ ) and Cmax of isavuconazole increased by 113% and 96% in part 1 and by 96% and 74% in part 2 in the presence vs absence of lopinavir/ritonavir, respectively. Mean AUCτ and Cmax of lopinavir were 27% and 23% lower, and mean AUCτ and Cmax of ritonavir were 31% and 33% lower in the presence vs absence of isavuconazole, respectively. Mild to moderate gastrointestinal disorders were the most common adverse events experienced. These findings indicate that coadministration of lopinavir/ritonavir with isavuconazole can decrease the exposure of lopinavir/ritonavir and increase the exposure of isavuconazole. Patients should be monitored for reduced antiviral efficacy if these agents are coadministered. | 10.1002/cpdd.282 |
pubmed_567_388 | The 11 beta-hydroxysteroid dehydrogenase type 2 (11 PHSD2) enzyme inactivates 11 betahydroxy steroids in sodium-transporting epithelia such as the kidney, thus protecting the non-selective mineralocorticoid receptor (MR) from occupation by cortisol in humans. Inhibition by xenobiotics such as liquorice or mutations in the HSD11 B2 gene, as occur in the rare monogenic hypertensive syndrome of apparent mineralocorticoid excess (AME), result in a compromised 11 betaHSD2 enzyme activity, which in turn leads to overstimulation of the MR by cortisol, sodium retention, hypokalaemia, low plasma renin and aldosterone concentrations, and hypertension. Whereas the first patients described with AME had a severe form of hypertension and metabolic derangements, with an increased urinary ratio of cortisol (THF+5alphaTHF) to cortisone (THE) metabolites, more subtle effects of mild 11 beta HSD2 deficiency on blood pressure have recently been observed. Hypertension with no other characteristic signs of AME was found in the heterozygous father of a child with AME, and we described a girl with a homozygous gene mutation resulting in only a slightly reduced 11 beta HSD2 activity causing 'essential' hypertension. Thus, depending on the degree of loss of enzyme activity, 11 beta HSD2 mutations can cause a spectrum of phenotypes ranging from severe, life-threatening hypertension in infancy to a milder form of the disease in adults. Patients with essential hypertension usually do not have overt signs of mineralocorticoid excess, but nevertheless show a positive correlation between blood pressure and serum sodium levels, or a negative correlation with potassium concentrations, suggesting a mineralocorticoid influence. Recent studies revealed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites in some patients with essential hypertension. These abnormalities may be genetically determined. A genetic association of a HSD11 B2 flanking microsatellite and hypertension in black patients with end-stage renal disease has been reported. A recent analysis of a CA-repeat allele polymorphism in unselected patients with essential hypertension did not find a correlation between this marker and blood pressure. Since steroid hormones with mineralocorticoid action modulate renal sodium retention, one might hypothesize that genetic impairment of 11 beta HSD2 activity would be more prevalent in salt-sensitive as compared with salt-resistant subjects. Accordingly, we found a significant association between the polymorphic CA-microsatellite marker and salt-sensitivity. Moreover, the mean ratio of urinary cortisol to cortisone metabolites, as a measure for 11betaHSD2 activity, was markedly elevated in salt-sensitive subjects. These findings suggest that variants of the HSD11 B2 gene may contribute to the enhanced blood pressure response to salt in some humans. | 10.1097/00004872-200018030-00001 |
pubmed_238_27837 | We have used NMR experiments to explore the binding of selected glycans and glycomimetics to the SARS CoV-2 spike glycoprotein (S-protein) and to its receptor binding domain (RBD). STD NMR experiments confirm the binding of sialoglycans to the S-protein of the prototypic Wuhan strain virus and yield dissociation constants in the millimolar range. The absence of STD effects for sialoglycans in the presence of the Omicron/BA.1 S-protein reflects a loss of binding as a result of S-protein evolution. Likewise, no STD effects are observed for the deletion mutant Δ143-145 of the Wuhan S-protein, thus supporting localization of the binding site in the N-terminal domain (NTD). The glycomimetics Oseltamivir and Zanamivir bind weakly to the S-protein of both virus strains. Binding of blood group antigens to the Wuhan S-protein cannot be confirmed by STD NMR. Using 1 H,15 N TROSY HSQC-based chemical shift perturbation (CSP) experiments, we excluded binding of any of the ligands studied to the RBD of the Wuhan S-protein. Our results put reported data on glycan binding into perspective and shed new light on the potential role of glycan-binding to the S-protein. | 10.1002/chem.202202614 |
pubmed_1003_5968 | Angiogenesis has a causal role in many diseases, including neovascular age-related macular degeneration (AMD). Identification of key regulators of angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor 2, pigment epithelium-derived growth factor, angiopoietins and extracellular matrix molecules, has facilitated the development of novel therapeutic agents that target the underlying pathological angiogenic process. Among these, VEGF serves as a "master switch" for many ocular neovascular conditions through its promotion of endothelial cell proliferation and survival, vascular permeability and ocular inflammation. Two anti-VEGF agents are now clinically available: bevacizumab, an antibody for metastatic colorectal cancer, and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible for pathological ocular neovascularization and thus an ideal target for treatment of AMD. Although other therapies targeting angiogenesis in AMD are in clinical development, to date, pegaptanib is the only therapy approved by the Food and Drug Administration of the United States for the treatment of all neovascular AMD and represents a valuable addition to the hitherto limited options available for patients. | 10.1016/S0008-4182(05)80078-X |
pubmed_989_984 | Microplastics (MPs) are new persistent organic pollutants derived from the degradation of plastics. They can accumulate along the food chain and enter the human body through oral administration, inhalation and dermal exposure. To identify the impact of Polystyrene (PS) MPs on the cardiovascular system and the underlying toxicological mechanism, 32 male Wister rats were divided into control group and three model groups, which were exposed to 0.5 μm PS MPs at 0.5, 5 and 50 mg/L for 90 days. Our results suggested that PS MPs exposure increased Troponin I and creatine kinase-MB (CK-MB) levels in serum, resulted in structure damage and apoptosis of myocardium, and led to collagen proliferation of heart. Moreover, PS MPs could induce oxidative stress and thus activate fibrosis-related Wnt/β-catenin signaling pathway. These results suggested that PS MPs could lead to cardiovascular toxicity by inducing cardiac fibrosis via activating Wnt/β-catenin pathway and myocardium apoptosis triggered by oxidative stress. The present study provided some novelty evidence to elucidate the potential mechanism of cardiovascular toxicity induced by PS MPs. | 10.1016/j.envpol.2020.115025 |
pubmed_812_17703 | BACKGROUND AND PURPOSE
Endothelial progenitor cells (EPCs) are associated with endothelial repair after ischemia in cardiac or peripheral circulation. There are no reports of EPCs with cerebrovascular disease. We present our experience with EPCs in patients with cerebrovascular disease.
SUMMARY OF REPORT
EPC counts differed significantly (P<0.001) between stroke patients (acute stroke: median 4.75 and range 0 to 33; stable stroke: median 7.25 and range 0 to 43) and control subjects (median 15.5 and range 4.3 to 50), independent of age. The level of EPCs was significantly correlated with the Framingham coronary risk score (FCRS) (rho=-0.349; P=0.002).
CONCLUSIONS
Similar to cardiac experience, the low EPC levels may play a role in the pathophysiology of cerebrovascular disease. | 10.1161/01.STR.0000149944.15406.16 |
pubmed_157_1699 | The individual monitoring service at the Helmholtz Zentrum München has adopted the recommendations of the ISO 4037 and 6980 standards series as base of its dosimetric systems for X-ray, gamma and beta dosimetry. These standards define technical requirements for radiation spectra and measurement processes, but leave flexibility in the implementation of irradiations as well as in the resulting uncertainty in dose or dose rate. This article provides an example for their practical implementation in the Munich IAEA/WHO secondary standard dosimetry laboratory. It focusses on two aspects: automation issues and uncertainties in calibration. | 10.1093/rpd/ncv537 |
pubmed_585_4435 | Chemical investigation of the Dongsha Atoll soft coral Lobophytum crassum has afforded four new cembranoids, crassumols A-C (1-3) and 13-acetoxysarcophytoxide (4). The structures of these isolated compounds were elucidated by extensive NMR and HRESIMS experiments. The cytotoxicity and anti-HCMV (Human cytomegalovirus) activities of 1-4 were evaluated in vitro. Compound 4 exhibited cytotoxicity against A-549 (human lung carcinoma) cell line with an ED(50) of 3.6 μg/mL. | 10.3390/md9122705 |
pubmed_242_4351 | Blood product transfusion is one of the most common invasive procedures performed in the health care setting. In contrast to pharmaceuticals, blood is actually a liquid transplant. Transfusion complications consequently encompass complex biological processes and infectious possibilities. Changes in vital signs are regularly seen during transfusion. Knowledge of common transfusion reaction signs and symptoms enables the clinical team to differentiate a normal patient response from a life-threatening reaction. Direct care nurses responsible for this procedure play a vital role in its success. Understanding the possible complications of transfusion and how to quickly recognize reactions at the bedside helps ensure the best patient outcomes. | 10.1097/NAN.0000000000000097 |
pubmed_926_14308 | We present first evidence showing that some electrophoretically homogeneous IgGs from the sera of patients with schizophrenia (36.4%) and their Fab and F(ab)2 fragments as well as from healthy donors (33.3%) possess catalase activity. The relative catalase activity of IgGs from the sera of individual schizophrenia patients (and healthy donors) significantly varied from patient to patient, but the activity of IgGs from healthy donors is on average 15.8-fold lower than that for schizophrenia patients. After extensive dialysis of purified IgGs against EDTA chelating metal ions, the relative catalase activity of IgGs decreases on average approximately 2.5-3.7-fold; all IgGs possess metal-dependent and independent catalase activity. The addition of external Me2+ ions to dialyzed and non-dialyzed IgGs leads to a significant increase in their activity. The best activator of dialyzed and non-dialyzed IgGs is Co2+, the activation by Cu2+, Mn2+, and Ni2+ ions were rare and always lower than by Co2+. Every IgG preparation demonstrates several individual sets of very well expressed pH optima in the pH range from 4.0 to 9.5. These data speak for the individual repertoire of catalase IgGs in every person and an extreme diversity of abzymes in their pH optima and activation by different metal ions. It is known that antioxidant enzymes such as superoxide dismutases, catalases, and glutathione peroxidases represent critical defense mechanisms preventing oxidative modifications of DNA, proteins, and lipids. Catalase activity of human IgGs could probably also play a major role in the protection of organisms from oxidative stress and toxic compounds. | 10.1371/journal.pone.0183867 |
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