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pubmed_1041_10847 | The ferrocene-imidazopyrene dyad, bearing the imidazole ring as the only receptor site, acts as a redox and optical molecular sensor for ion pairs, exhibiting an easily detectable signal change in the redox potential of the ferrocene/ferrocinium redox couple and in the emission spectrum. Perturbation of the emission spectrum follows the order Pb(2+) > Hg(2+) > Zn(2+) for cations and H(2)PO(4)(-) > AcO(-) for anions. | 10.1021/ol2004935 |
pubmed_220_11375 | Abnormally low concentrations of brain gamma-aminobutyric acid (GABA) have been reported in unipolar depression. Almost all of the brain GABA is synthesized by glutamate decarboxylase (GAD) enzymes (GAD67 and GAD65). These enzymes, therefore, play a central role in brain GABA homeostasis. We screened all the 17 exons of the GAD67 gene for mutations using single strand conformation polymorphism (SSCP) or denaturing high pressure liquid chromatography (dHPLC) in a sample of 43 individuals diagnosed with major unipolar depression or other disorders with putative GABAergic dysfunction. We identified eight novel variants (five synonymous base substitutions, two insertion/deletions and one tandem repeat). Three relatively common (minor allele frequency >20%) single nucleotide polymorphisms (SNPs), located in the 5' non-coding region (exon 0), intron 8, and the 3' non-coding region (exon 16) of the gene, were genotyped in 103 European-American (EA) subjects with depression and 125 EA psychiatrically screened controls. Linkage disequilibrium (LD) and haplotype frequencies were estimated using the 3LOCUS program. Significant LD was observed between the intron 8 SNP and the exon 16 SNP and between the exon 0 SNP and the exon 16 SNP. Three common GAD67 haplotypes were observed in this population, which accounted for >90% of the possible GAD67 three-locus haplotypes. Comparison of SNP and haplotype frequencies between individuals with depression and controls revealed no differences. These results demonstrate a significant within-gene LD for GAD67 in the EA population and begin to establish a haplotype map for this gene. Furthermore, these results suggest that common genetic variation within the GAD67 gene does not play a major role in the predisposition to unipolar depression. | 10.1002/ajmg.b.20055 |
pubmed_622_22623 | PURPOSE
Although succinylcholine (SCh) is often used as a muscle relaxant in electroconvulsive therapy, its influence on airway reactivity has not been fully investigated. We examined the effects of SCh on acetylcholine (ACh)-, carbachol (CCh)-, and electrical field stimulation (EFS)-induced contractions, and on the ACh-induced phosphatidylinositol (PI) response of rat trachea.
METHODS
Thirty-two male Wistar rats weighing 250-350 g were used. The trachea was rapidly isolated and cut into 3-mm-wide rings. The resting tension was adjusted periodically to 1.0 g during the equilibration period. ACh, 1 microM; carbachol (CCh), 0.05 microM; or neither of them, was added, and SCh was then added at 1-300 microM final concentrations, and ring tension was examined. Contractions were elicited by EFS in the presence or absence of 100 microM SCh. Tracheal slices were incubated with [3H] myo-inositol, 1 microM ACh, and various concentrations of SCh. The accumulation of [3H] inositol monophosphate (IP1) was measured.
RESULTS
SCh did not affect the tension by itself without ACh, or with CCh, but SCh potentiated the ACh-induced contraction of rat trachea at concentrations of 10 microM or more (50% effective concentration [EC50]; 43.6 microM). SCh produced a significant increase in the amplitude and duration of EFS-induced contractions. SCh, at concentrations of 10 microM and 100 microM, potentiated ACh-induced IP1 accumulation.
CONCLUSION
SCh potentiated ACh-induced, but not CCh-induced, contractile and PI responses, and enhanced EFS-induced contraction of rat trachea, suggesting that competition for butyrylcholinesterase (BChE) in airway smooth muscle could be involved in the potentiation by SCh of ACh-induced airway smooth muscle contraction. | 10.1007/s00540-006-0478-6 |
pubmed_300_10409 | Current strategies for marine pollution monitoring are based on the integration of chemical and biological techniques. The sea urchin embryo-larval bioassays are among the biological methods most widely used worldwide. Cryopreservation of early embryos of sea urchins could provide a useful tool to overcome one of the main limitations of such bioassays, the availability of high quality biological material all year round. The present study aimed to determine the suitability of several permeant (dimethyl sulfoxide, Me(2)SO; propylene glycol, PG; and ethylene glycol, EG) and non-permeant (trehalose, TRE; polyvinylpyrrolidone, PVP) cryoprotectant agents (CPAs) and their combination, for the cryopreservation of eggs and embryos of the sea urchin Paracentrotus lividus. On the basis of the CPAs toxicity, PG and EG, in combination with PVP, seem to be most suitable for the cryopreservation of P. lividus eggs and embryos. Several freezing procedures were also assayed. The most successful freezing regime consisted on cooling from 4 to -12 degrees C at 1 degrees C/min, holding for 2 min for seeding, cooling to -20 degrees C at 0.5 degrees C/min, and then cooling to -35 degrees C at 1 degrees C/min. Maximum normal larvae percentages of 41.5% and 68.5%, and maximum larval growth values of 42.9% and 60.5%, were obtained for frozen fertilized eggs and frozen blastulae, respectively. | 10.1016/j.cryobiol.2009.09.010 |
pubmed_146_18575 | In the last 30 years, major improvements have been made in understanding the pathogenesis, diagnosis and treatment of infective endocarditis. Nevertheless, mortality still remains high, close to 30-40% at 1 year, and its reduction remains the main challenge. Moreover, important epidemiological changes have been recorded. Social changes in Western countries have led to an increase in the mean length of life, and thus in degenerative valvular diseases, whereas rheumatic heart disease has almost disappeared. Increasing medicalization has led to a rise in complications and diseases related to longer hospital stay, surgical therapies and other invasive interventions. At the same time, there is an increase in immunosuppressive therapies, diseases such as cancer, diabetes mellitus and renal insufficiency that may enhance the disease. Further knowledge is needed for specific subgroups to improve both treatment and prognosis. Nevertheless, randomized trials are lacking to guide the management of the disease, and the role and indications of antibiotic prophylaxis are still the subject of debate. International multicenter studies are providing new important findings based on the experience of tertiary centers; these results may reflect referral biases. The proposal of an Italian national registry on infective endocarditis (RIEI) will overcome these limitations and provide a wide picture of the national presentation of the disease. The aim of the registry is to improve the management of infective endocarditis, through a better understanding of demographic, clinical, therapeutic and prognostic features of the disease in the real world. The background, rationale, aims and expected results of the registry are reviewed. | 10.2459/JCM.0b013e3282f20ae6 |
pubmed_596_2039 | OBJECTIVE
To make recommendations concerning cochlear implantation during humanitarian medical trips by exploring the attitudes of US cochlear implant surgeons.
STUDY DESIGN
Cross-sectional survey.
SETTING
Academic.
SUBJECTS AND METHODS
Questionnaires were sent to 405 members of the William House Cochlear Implant Study Group. The 198 respondents (49%), all active cochlear implant surgeons, were divided into 3 groups depending on their level of experience working in a developing country.
RESULTS
Eighty-nine percent of respondents supported cochlear implants in these environments, although 42% of these cochlear implant surgeons stated that they would modify their criteria for implantation considering the challenges in developing countries. There was strong support for cochlear implants in postlingual deafened patients and prelingual deafened patients under the age of 3 years, although nearly half of respondents (48%) would not implant prelingual deafened patients after they reached the age of 3 years. Three-quarters of respondents (74%) believed that developing countries should have the same access to current multichannel devices used in developed countries, as opposed to simpler, possibly lower cost devices. A local audiologist was deemed the most important personnel requirement (83%), and limited audiology and rehabilitative resources were the greatest postoperative concern rather than lack of postoperative care or infection.
CONCLUSION
. This survey strongly supports the practice of performing cochlear implants during humanitarian trips to developing countries and makes best-practice recommendations to make outcomes successful. | 10.1177/0194599811401343 |
pubmed_256_7324 | The use of autotransfusion devices is an established method of reducing the need for homologous transfusions in surgery [3, 11, 13], but technical factors still contraindicate the washing and concentration of blood volumes smaller than 300 ml. Therefore, haemoconcentration of small volumes of salvaged blood, as usually found in paediatric surgery, is considered to be a complicated and questionable practice [5]. Whereas these amounts of blood loss are easily tolerated by adults, they may necessitate homologous transfusions in paediatric surgery. In a prospective study, we investigated whether a simple technical modification in the processing of salvaged blood could facilitate the use of autotransfusion devices, especially in children. PATIENTS AND METHODS. Intraoperative blood salvage was performed in children 6 months to 10 years old undergoing surgery for hip dysplasia. Autotransfusion (Dideco STAT) was started when the blood loss was estimated to be more than 20% of the total blood volume (TBV). As a reference, we used a formula based on body weight [10]: for children up to the age of 6 years 80 ml/kg blood volume and for children up to 10 years 75 ml/kg. The total volume of salvaged fluid including blood, anticoagulant solution, and surgical irrigation was collected in a reservoir and transferred to the autotransfusion set, after which the reservoir was rinsed with 500 ml 0.9% saline solution in order to save the remaining blood. After processing, the blood was stored in the retransfusion bag. By adding the same volume of plasma expander (6% hydroxyethyl starch [HES], molecular weight 450,000), spontaneous sedimentation of the washed autologous erythrocytes (RBCs) for 10-15 min led to a concentrate of RBCs. After 10 mu filtration, the RBC suspension was retransfused (Figs. 1-3). RESULTS. Within 12 months, autotransfusion was performed during 6 out of 15 surgical procedures according to the method described above. The calculated blood loss averaged 25.6% of TBV, of which 21.4% (= 272 ml) could be processed by the autotransfusion device (Table 3). The mean values of 2.6 g/dl haemoglobin (Hb) and 6.8% haematocrit (HCt) in the salvaged blood increased to 9.4 g/dl and 27.3% in the processed RBC concentrates. After adding 6% HES solution, spontaneous sedimentation of the RBCs led to values of Hb 22.1 g/dl and HCt 59.8%. An average of 59.5 ml (22-99 ml) sedimented RBCs was retransfused to the patients, including 11.6 ml 6% HES solution (Table 4). In this manner, the need for homologous transfusions could be avoided in these patients both during and after surgery. CONCLUSIONS. This study shows that the use of blood salvaging in paediatric surgery is indicated under certain conditions. With the aid of the simple modification described above, we solved the main problem in paediatric autotransfusion by concentrating RBC suspensions with low Hb and Hct values after using the autotransfusion device. | 10.1007/s001010050183 |
pubmed_192_538 | Leishmaniasis is an infectious disease caused by a protozoan belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and patient's health condition. The outcomes can range from single cutaneous lesions to lethal visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and, in some cases, the second-line drug, amphotericin B, is used. Beside the toxicity of both classes of drugs, in some areas of the world, parasites are resistant to antimonial. These detrimental features make fundamental the discovery and characterization of new drugs or plant extracts with leishmanicidal effects. Brazil is a well-known country for its biodiversity. Additionally, the common knowledge inherited for generations in small villages makes Brazil a source of new information and resources for the discovery and development of new drugs. Based on ethnopharmacology, elderlies were interviewed about plants they commonly used for skin diseases and infections. Five native plants from Atlantic forest were indicated; EtOH and n-hexane extracts were prepared with the vegetative organs of the plants and assayed against promastigote and amastigote forms of L. (L.) amazonensis. The major molecules of each extract were detected using qualitative nuclear magnetic resonance. Among all tested extracts, the n-hexane extract from the leave of Eugenia uniflora (Myrtaceae), enriched in myricitrin and quercitrin flavonoids, was the most effective against L. (L.) amazonensis amastigotes. This data supports the ethnopharmacology approach as a successful tool for the discovery of new drugs with leishmanicidal effects. | 10.1155/2019/8780914 |
pubmed_486_15723 | BACKGROUND Colorectal cancer (CRC) has become a heavy health burden around the world, accounting for about 10% of newly diagnosed cancer cases. In the present study, we aimed to establish the miRNA-based prediction signature to assess the prognosis of CRC patients. MATERIAL AND METHODS A total of 451 CRC patients' expression profiles and clinical information were download from the TCGA database. LASSO Cox regression was conducted to construct the overall survival (OS)- and recurrence-free survival (RFS)-associated prediction signatures, by which CRC patients were divided into low- and high-risk groups. Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curves were used to explore the discriminatory ability and stability of the signatures. Functional enrichment analyses were performed to identify the probable mechanisms. RESULTS miRNA-216a, miRNA-887, miRNA-376b, and miRNA-891a were used to build the prediction formula associated with OS, while miR-1343, miR-149, miR-181a-1, miR-217, miR-3130-1, miR-378a, miR-542, miR-6716, miR-7-3, miR-7702, miR-677, and miR-891a were obtained to construct the formula related to RFS. K-M curve and ROC curve revealed the good discrimination and efficiency of OS in the training (P<0.001, AUC=0.712) and validation cohorts (P=0.019, AUC=0.657), as well as the results of RFS in the training (P<0.001, AUC=0.714) and validation cohorts (P=0.042, AUC=0.651). The function annotations for the targeted genes of these miRNAs show the potential mechanisms of CRC. CONCLUSIONS We established 2 novel miRNA-based prediction signatures of OS and RFS, which are reliable tools to assess the prognosis of CRC patients. | 10.12659/MSM.916948 |
pubmed_1061_23463 | Microemulsion represents an important class of the colloidal system, though the development of stimuli-responsive microemulsion is still in its infancy. Here, we demonstrated the temperature responsiveness of a conventional surfactant-free microemulsion composed of n-octanol as nonpolar phase, ethanol as amphi-solvent, and water as polar phase for the first time. In the single-phase region of the phase diagram, the pre-ouzo zone was confirmed by dynamic light scattering (DLS), and the type of microemulsion was confirmed via the conductivity and polarity probe methods. The effects of temperature on the phase behavior and droplet size of the n-octanol-water-ethanol microemulsion system were systemically evaluated by the ternary phase diagram and DLS techniques. The results showed that the area of single-phase increases upon increasing temperature, but the area of pre-ouzo zone decreases accompanied by a decrease in the droplet size. Moreover, the critical point gradually draws close to the n-octanol corner with increasing temperature. When one formulation is far away from the demixing border, the droplet size can be reversibly and precisely regulated by changing temperature. When one formulation is located on the vicinity of the boundary, a minor variation in temperature can lead to a prominent phase transition between Winsor IV (high temperature) and Winsor II (low temperature). Such a temperature-responsive microemulsion can be used as a microreactor for Knoevenagel condensation. The reaction was carried out at 35 °C, and the product was collected from the water phase by simple filtration at 25 °C. | 10.1021/acs.langmuir.9b02842 |
pubmed_520_13791 | OBJECTIVES
Endovascular treatment (EVT) of basilar tip aneurysms (BTAs) is arduous because of the lesions' angioarchitecture and the relatively high recanalization rate after EVT. In this study, we aimed to report the clinical characteristics of BTAs and evaluate the incidence of and risk factors for recanalization.
METHODS
One hundred twenty-five patients with BTAs (11 ruptured, 114 unruptured) treated with EVT between 2009 and 2019 at one institution were retrospectively reviewed. Among them, 113 patients were included in statistical analyses. The anatomical parameters of the aneurysms and clinical data were analyzed. Univariate (chi-square test and t-test) and multivariate (multiple logistic regression) analyses were performed to identify risk factors for recanalization.
RESULTS
Recanalization of the BTA occurred in 15 patients (13.3%). One patient (0.9%) was retreated endovascularly. The mean follow-up duration was 49.8 months. Neck size, posterior cerebral artery (PCA) angle, maximum diameter, and the rupture rate differed significantly between the recanalization and non-recanalization groups (P=.007, P<.001, P=.006, and P=.048, respectively). The maximum diameter (odds ratio, 1.483 per mm; 95% confidence interval, 1.145-1.919; P=.003) and PCA angle (odds ratio, 1.020 per degree; 95% confidence interval, 1.001-1.039; P=.036) were independently associated with recanalization.
CONCLUSIONS
Of all investigated BTAs, 96.8% were wide-neck aneurysms. The recanalization rate of BTAs after EVT was 13.3%. The PCA angle and maximal aneurysmal diameter were independently associated with recanalization; no associations were observed regarding vertebral artery dominance or modality of treatment. As such, BTA patients with wide PCA angles should be carefully monitored over time. | 10.1080/01616412.2022.2132459 |
pubmed_486_4005 | The spatial and temporal availability of cytokines, and the microenvironments this creates, is critical to tissue development and homeostasis. Creating concentration gradients in vitro using soluble proteins is challenging as they do not provide a self-sustainable source. To mimic the sustained cytokine secretion seen in vivo from the extracellular matrix (ECM), we encapsulated a cargo protein into insect virus-derived proteins to form nanoparticle co-crystals and studied the release of this cargo protein mediated by matrix metalloproteinase-2 (MMP-2) and MMP-8. Specifically, when nerve growth factor (NGF), a neurotrophin, was encapsulated into nanoparticles, its release was promoted by MMPs secreted by a PC12 neuronal cell line. When these NGF nanoparticles were spotted onto a cover slip to create a uniform circular field, movement and alignment of PC12 cells via their extended axons along the periphery of the NGF nanoparticle field was observed. Neural cell differentiation was confirmed by the expression of specific markers of tau, neurofilament, and GAP-43. Connections between the extended axons and the growth cones were also observed, and expression of connexin 43 was consistent with the formation of gap junctions. Extensions and connection of very fine filopodia occurred between growth cones. Our studies indicate that crystalline protein nanoparticles can be utilized to generate a highly stable cytokine gradient microenvironment that regulates the alignment and differentiation of nerve cells. This technique greatly simplifies the creation of protein concentration gradients and may lead to therapies for neuronal injuries and disease. | 10.3390/biom9100510 |
pubmed_491_13085 | We demonstrate the use of an all-fiberized, mode-locked 1.94 μm laser with a saturable absorption device based on a tungsten disulfide (WS2)-deposited side-polished fiber. The WS2 particles were prepared via liquid phase exfoliation (LPE) without centrifugation. A series of measurements including Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) revealed that the prepared particles had thick nanostructures of more than 5 layers. The prepared saturable absorption device used the evanescent field interaction mechanism between the oscillating beam and WS2 particles and its modulation depth was measured to be ~10.9% at a wavelength of 1925 nm. Incorporating the WS2-based saturable absorption device into a thulium-holmium co-doped fiber ring cavity, stable mode-locked pulses with a temporal width of ~1.3 ps at a repetition rate of 34.8 MHz were readily obtained at a wavelength of 1941 nm. The results of this experiment confirm that WS2 can be used as an effective broadband saturable absorption material that is suitable to passively generate pulses at 2 μm wavelengths. | 10.1364/OE.23.019996 |
pubmed_159_13073 | PURPOSE
To assess the prevalence of epiphora in the general adult population based on PubMed search citations.
METHODS
1) Electronic PubMed MEDLINE database search (September 13, 2019) with the terms (Medical Subject Headings or MeSH) "prevalence" and "epiphora", 2) "epiphora" and "dry eye", and 3) "prevalence", "epiphora", and "dry eye". Review of all citations from these searches containing the term "epiphora" either in their abstract or title.
RESULTS
1) PubMed search retrieved 2 617 137 citations for "prevalence", 26 135 for "epiphora", and 2554 for "prevalence" AND "epiphora". Within the latter 2554 citations, the word "epiphora" appeared in the abstract or title of only 109 citations (< 5%). None of these 109 citations assessed the prevalence of epiphora in the adult general population as the primary end point. Only one abstract mentioned that out of 125 patients, 7.2% indicated, retrospectively, that they had already had epiphora before cataract surgery. Two large population-based studies addressed the incidence of epiphora, not in adults, but in infants (20%) and children (7.7%). 2) The PubMed search showed 22 487 citations for "dry eye", 30 211 for "epiphora" OR "dry eye", and up to 18 414 joint citations for the terms "epiphora" AND "dry eye". These 18 414 citations were 70 and 82% of the number of MeSH citations for "epiphora" and "dry eye" alone, respectively. Of these 18 414 citations, the word "epiphora" only appeared in 131 citations (< 1%), one of them being an extra report mentioning a 32% incidence of epiphora among postmenopausal women. 3) The search found 2206 citations for "prevalence" AND "epiphora" AND "dry eye", with only 10 of them (< 1%) containing the word "epiphora".
CONCLUSIONS
Despite a large number of citations retrieved by PubMed searches, there seems to be a lack of studies on the prevalence of epiphora in the adult general population. There is apparently also a large number of overlapping PubMed citations retrieved for searches with the terms "epiphora" AND "dry eye", although more than 99% of them did not even display the word "epiphora". Although epiphora is considered a common complain, its prevalence in the adult general population deserves to be further assessed. | 10.1055/a-1112-7335 |
pubmed_135_6623 | N6-methyladenosine (m6A) is the most abundant internal modification that widely participates in various immune and inflammatory responses; however, its regulatory mechanisms in the inflammation of liver induced by lipopolysaccharide in piglets remain largely unknown. In the present study, piglets were intraperitoneally injected with 80 μg/kg LPS or an equal dose of sterile saline. Results indicated that LPS administration increased activities of serum alanine aminotransferase (ALT), induced M1 macrophage polarization and promoted secretion of inflammatory cytokines, and finally led to hepatic lesions in piglets. The NOD1/NF-κB signaling pathway was activated in the livers of the LPS group. Moreover, the total m6A level was significantly elevated after LPS treatment. MeRIP-seq showed that 1166 and 1344 transcripts contained m6A methylation in control and LPS groups, respectively. The m6A methylation sites of these transcripts mainly distributes in the 5' untranslated region (5'UTR), the coding sequence (CDS), and the 3' untranslated region (3'UTR). Interestingly, these genes were mostly enriched in the NF-κB signaling pathway, and LPS treatment significantly changed the m6A modification in NOD1, RIPK2, NFKBIA, NFKBIB, and TNFAIP3 mRNAs. In addition, knockdown of METTL3 or overexpression of FTO both changed gene levels in the NOD1/NF-κB pathway, suggesting that activation of this pathway was regulated by m6A RNA methylation. Moreover, the alteration of m6A RNA methylation profile may be associated with the increase of reactive oxygen species (ROS), HIF-1α, and MAT2A. In conclusion, LPS activated the NOD1/NF-κB pathway at post-transcriptional regulation through changing m6A RNA methylation, and then promoted the overproduction of proinflammatory cytokines, ultimately resulting in liver inflammation and damage. | 10.3390/antiox11101954 |
pubmed_581_24116 | BACKGROUND
Hemoconcentration has been proposed as surrogate for changes in volume status among patients hospitalized with acute heart failure (AHF) and is associated with a favorable outcome. However, there is a dearth of research assessing the clinical outcomes of hospitalized patients with hemoconcentration, hemodilution and unchanged volume status.
METHODS
We enrolled 510 consecutive patients hospitalized for AHF from April 2011 to July 2015. Hematocrit (HCT) levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients were stratified by delta HCT tertitles into hemodilution (ΔHCT ≤ - 1.6%), no change (NC, -1.6% < ΔHCT ≤1.5%) and hemoconcentration (ΔHCT >1.5%) groups. The endpoint was all-cause death, with a median follow-up duration of 18.9 months.
RESULTS
Hemoconcentration was associated with lower left ventricle ejection fraction, as compared with NC and hemodilution groups, while renal function at entry, New York Heart Association class IV, and in-hospital worsening renal function (WRF) were not significantly different across the three groups. After multivariable adjustment, hemoconcentration had a lower risk of mortality as compared with hemodilution [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.24-0.63, P < 0.001], or NC (HR 0.54, 95% CI 0.33-0.88, P = 0.015], while hemodilution and NC did not have significantly differ in mortality (HR 0.72, 95% CI 0.48-1.10, P = 0.130).
CONCLUSIONS
In patients hospitalized with AHF, an increased HCT during hospitalization is associated with a lower risk of all-cause mortality than a decreased or unchanged HCT. Furthermore, all-cause mortality does not differ significantly between patients with unchanged and decreased HCT values. | 10.1186/s12872-017-0669-0 |
pubmed_1058_11870 | Two years after the October 1995 pill scare that received worldwide attention, this synthesis of evidence goes back to the earliest research on risks of first generation oral contraceptives (OCs). It also covers epidemiological data published since, emphasising the 1995-1996 findings. Late breaking data are also examined. The key issue: are there differences in the risk profiles of second and third generation OCs. The ultimate question is: did any epidemics of venous thromboembolism (VTE) occur? This synthesis of evidence leads to the following conclusions and observations: (i) all OCs on the market are becoming progressively safer; (ii) relative risks of about 2 for VTE, even if real, are clinically unimportant and of no public health significance; (iii) the weak odds ratios contrasting third and second generation OCs, ranging from 1.5 to 2.3 in the 1995-1996 studies are more likely explained by bias than by a causal relationship; (iv) incidences of VTE among users of any OC have been declining over the past three decades; (v) absolute rates of VTE for third generation OC users reported in 1995-1996 are lower than those for users of second generation OCs in 1988 and 1991; (vi) there is no difference in risk of VTE between first starters on second generation OCs versus first starters on third generation OCs; (vii) users of third generation OCs are at much lower risk of acute myocardial infarction than users of second generation OCs; (viii) among users of any OC, the occurrence rates of stroke are low, they are declining, and no differences between second and third generation OCs are apparent; (ix) 2 years after the pill scare there are no epidemics of VTE; (x) there have been excessive rates of therapeutic abortions in some countries; and (xi) the benefit-risk ratio is favourable for users of any OC. | 10.1093/humrep/12.11.2347 |
pubmed_702_12293 | Long-term potentiation (LTP) is a well-characterized form of synaptic plasticity that fulfills many of the criteria for the neural correlate of memory. LTP reversal (or depotentiation, DP) is thought to correlate with prevention or elimination of memory storage. LTP during and immediately after induction can be easily reversed by afferent stimulation, when applied within the optimal time window. The aim of the present study was to determine whether later-phase LTP (L-LTP) could be reversed by special patterned stimulation applied at 2 h after LTP induction, as well as to characterize the receptor mechanisms underlying this reversal. Field excitatory postsynaptic potentials evoked by Schaffer collateral stimulation were recorded from the CA1 subfield of adult rat hippocampal slices. Results demonstrated that stable LTP, which was induced by six theta-burst stimulations, was mediated by NR2A-containing N-methyl-d-aspartate receptors (NMDARs). This L-LTP was partially reversed by high-intensity paired-pulse low-frequency stimulation (HI-PP-LFS) and was inhibited by Zn(2+) (30 nm), a voltage-independent NR2A-NMDAR antagonist. However, NR2B-NMDAR antagonists (Ro 25-6981, 1 mum) displayed no effect on L-LTP reversal. L-LTP partial reversal was also induced by HI-PP-LFS, when the protein synthesis inhibitors anisomycin (25 microm) and cycloheximide (60 microm) were applied following LTP induction. These results suggested that NR2A-containing NMDARs are required for L-LTP induction and DP in the hippocampal CA1 area of adult rats. Moreover, HI-PP-LFS was an effective stimulation pattern to induce DP. | 10.1111/j.1460-9568.2009.06783.x |
pubmed_866_15753 | Context
Vancomycin-intermediate Staphylococcus aureus remains one of the most prevalent multidrug-resistant pathogens causing healthcare infections that are difficult to treat.
Aims
This study uses a comprehensive computational analysis to systematically investigate various gene expression profiles of resistant and sensitive S. aureus strains on exposure to antibiotics.
Settings and Design
The transcriptional changes leading to the development of multiple antibiotic resistance were examined by an integrative analysis of nine differential expression experiments under selected conditions of vancomycin-intermediate and -sensitive strains for four different antibiotics using publicly available RNA-Seq datasets.
Materials and Methods
For each antibiotic, three experimental conditions for expression analysis were selected to identify those genes that are particularly involved in the development of resistance. The results were further scrutinised to generate a resistome that can be analysed for their role in the development or adaptation to antibiotic resistance.
Results
The 99 genes in the resistome are then compiled to create a multiple drug resistome of 25 known and novel genes identified to play a part in antibiotic resistance. The inclusion of agr genes and associated virulence factors in the identified resistome supports the role of agr quorum sensing system in multiple drug resistance. In addition, enrichment analysis also identified the kyoto encyclopedia of genes and genomes (KEGG) pathways - quorum sensing and two-component system pathways - in the resistome gene set.
Conclusion
Further studies on understanding the role of the identified molecular targets such as SAA6008_00181, SAA6008_01127, agrA, agrC and coa in adapting to the pressure of antibiotics at sub-inhibitory concentrations can help in learning the molecular mechanisms causing resistance to the pathogens as well as finding other potential therapeutics. | 10.4103/ijmm.IJMM_18_311 |
pubmed_573_4802 | Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease with a poor prognosis and targeted therapies have failed in the clinic so far. Several evidences point to the phosphatidylinositol 3-kinase (PI3K)-mTOR pathway as a promising signaling node for targeted therapeutic intervention. Markers, which predict responsiveness of PDAC cells towards PI3K inhibitors are unknown. However, such markers are needed and critical to better stratify patients in clinical trials. We used a large murine Kras(G12D)- and PI3K (p110α(H1047R))-driven PDAC cell line platform to unbiased define modulators of responsiveness towards the dual PI3K-mTOR inhibitor Bez235. In contrast to other tumor models, we show that Kras(G12D)- and PI3K (p110α(H1047R))-driven PDAC cell lines are equally sensitive towards Bez235. In an unbiased approach we found that the extracellular matrix protein Efemp1 controls sensitivity of murine PDAC cells towards Bez235. We show that Efemp1 expression is connected to the cyclin-dependent kinase inhibitor p27(Kip1). In a murine Kras(G12D)-driven PDAC model, p27(Kip1) haploinsufficiency accelerates cancer development in vivo. Furthermore, p27(Kip1) controls Bez235 sensitivity in a gene dose-dependent fashion in murine PDAC cells and lowering of p27(Kip1) decreases Bez235 responsiveness in murine PDAC models. Together, we define the Efemp1-p27(Kip1) axis as a potential marker module of PDAC cell sensitivity towards dual PI3K-mTOR inhibitors, which might help to better stratify patients in clinical trials. | 10.18632/oncotarget.859 |
pubmed_896_1795 | BACKGROUND
Lack of biomarkers and in vitro models has contributed to inadequate understanding of the mechanisms underlying the inferior clinical response to immune checkpoint inhibitors (ICIs) in patients with oncogene-driven non-small cell lung cancer (NSCLC).
METHODS
The effect of small molecule tyrosine kinase inhibitors (TKIs) on peripheral blood mononuclear cells (PBMCs) in 34 patients with oncogene-driven NSCLC (cohort A) was compared with those from 35 NSCLC patients without oncogene-driven mutations received ICI (cohort B) or from 22 treatment-naïve NSCLC patients (cohort C). Data for each blood biomarker were summarized by mean and standard deviation and compared by Wilcoxon rank sum tests or Kruskal-Wallis tests with significance at 2-sided p value < 0.05. Co-culture of PBMCs and pleural effusion-derived tumor cells from individual patients with oncogene-driven NSCLC was used to determine the in vitro cytotoxicity of TKI and ICI.
RESULTS
Except for low CD3% in cohort A, there were no significant differences in other 12 blood biomarkers among the 3 cohorts at baseline. TKI treatment in cohort A was associated with significant increase in CD3% and decrease in total and absolute neutrophils (p < 0.05). In cohort B, patients with good clinical response to ICI treatment (N = 18) had significant increases in absolute lymphocyte counts (ALCs), CD4 and/or CD8 cell counts. Conversely, those patients with poor clinical response to ICI (N = 17) had significant decreases in these cell counts. Of the 27 patients with pre- and post-treatment blood samples in cohort A, 11 had poor clinical response to TKIs and decreased lymphocyte counts. Of the remaining 16 patients who had good clinical response to TKI therapy, 10 (62.5%) patients had decreased, and 6 (37.5%) patients had increased lymphocyte counts. Multicolor immunophenotyping of PBMCs revealed ICI treatment activated additional immune cell types that need further validation. We confirmed that TKI treatment could either antagonize or enhance the effect of ICIs in the co-culture assay using patient's tumor cells and PBMCs.
CONCLUSIONS
To the best of our knowledge, this is the first study showing that TKIs can have various effects on blood immune cells, which may affect their response to ICIs. Further validation of the blood biomarker and in vitro assay is warranted. | 10.1186/s40364-021-00324-6 |
pubmed_498_26079 | Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, and these had higher proliferative potential, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γ-H2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability. | 10.1016/j.yexcr.2021.112740 |
pubmed_705_4841 | Hamsters infected with Leishmania donovani develop a disease similar to human kala-azar. They present hypergammaglobulinemia, and their T cells do not respond to parasite antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) from L. donovani-infected hamsters produce high levels of the inhibitory cytokine transforming growth factor beta (TGF-beta). Immunohistochemical studies with an anti-TGF-beta monoclonal antibody (MAb) showed that this cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of TGF-beta are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite antigen or lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens of L. donovani-infected hamsters caused profound inhibition of the in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inhibition was totally abrogated by the anti-TGF-beta MAb. These results suggest that the immunosuppression observed in visceral leishmaniasis is, at least in part, due to the abundant production of TGF-beta during the course of the infection. | 10.1128/IAI.66.3.1233-1236.1998 |
pubmed_987_19872 | A fast and precise analysis of complex biological samples is one of the most important challenges in clinical- and life-sciences. In this field, the paper spray ionization (PSI) becomes a more and more successful ambient ionization technique for mass spectrometry. The PSI is based on the electrospray mechanism and is limited to polar target analytes. In this work, a transition from the paper spray ionization to a corona discharge under standard PSI conditions is observed and evaluated by using a complex liver sample. This evaluation leads to an advancement of the PSI by adding a flexible microtube plasma (FμTP) that is more efficient in respect to non- and low polar molecules. The combination of the PSI and the FμTP in a sequential way allows the determination of polar lipids as well as non-polar compounds like cholesterol and possible lung cancer biomarkers. As add-on for PSI, this approach enhances the number of detectable species in one single measurement and seems to be a powerful tool for the rapid analysis of complex biological samples in clinical- and life-sciences. | 10.1016/j.aca.2022.339619 |
pubmed_153_11054 | Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD. | 10.1017/S1461145714000716 |
pubmed_465_1177 | Most chemical compounds and physical agents recognized as human carcinogens were first identified in the occupational environment by epidemiological studies. Some 2%-8% of all cancers have been attributed to occupational exposures, but the limitations of such estimates should be recognized. The use of existing medical information systems on occupational cancer for hypothesis generation may be improved by comparing the results emerging from different countries. An initiative in this direction is recommended. Clues emerging from such general systems should be submitted to further studies to test specific hypotheses concerning risk factors. Record linkage is necessary for the epidemiological study of occupational cancer. Efforts must be made towards the storage of identifiable records with information on occupation and cancer occurrence. | 10.1007/BF00390455 |
pubmed_586_335 | The responsiveness of the medullary chemoreceptors, measured by the ventilatory response to hypercapnia given in an hyperoxic gas mixture in intact anesthetized dogs has been evaluated during normothermia and at two levels of hypothermia. The response was studied in: 1) 20 dogs during normothermia, 2) 10 of these dogs at a blood temperature of 32-33 degrees C, and 3) in the other 10 dogs during deeper hypothermia (28-29 degrees C). The ventilatory response to CO2 decreased while blood temperature was lowered until the response became absent during deep hypothermia. For normothermia and both levels of hypothermia a similar oxygen drive of ventilation was found which was equivalent to approximately one fourth of the spontaneous ventilation. It is suggested, that in the deeply hypothermic animal the normal respiratory drive is apparently of peripheral (arterial) chemoreceptor origin and when this drive is nullified or significantly decreased, gentle shivering could be responsible for stimulating the respiratory center. | 10.1007/BF00583923 |
pubmed_76_5801 | Twelve ergolines (O-acylated lysergol and dihydrolysergol-I derivatives) were synthesized to study their antagonism of 5-HT responses in comparison with methylsergide and LY 53857 [6-methyl-1-(1-methylethyl)-8 beta-ergoline carboxylic acid 2-hydroxy-1-methylpropyl-ester hydrogen maleate] in cylindrical segments of the isolated rat tail artery. With regard to (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate, the most potent new ergoline derivative, we examined the phenomenon of insurmountable antagonism to 5-HT by methylsergide. O-Acylated lysergol and dihydrolysergol-I derivatives competitively antagonized 5-HT-induced contractions with calculated pA2 values of 7.30 +/- 0.42 for the weakest and 8.42 +/- 0.35 for the most potent ergoline derivative in this series. N1-isopropyl substitution did not generally enhance 5-HT2 receptor affinities but lowered affinities for alpha 1 adrenoceptors in rat aorta. Methysergide and LY 53857 were insurmountable antagonists of 5-HT in rat tail artery. Preincubation with (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l) partially prevented the depression of 5-HT-induced contractions caused by methysergide (1-10 nmol/l). Methysergide (100 nmol/l) abolished the protective effect of (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate. (9.10-Didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l), concomitantly incubated with methysergide (30 nmol/l), partially restored the maximum response to 5-HT that had been depressed by methysergide (30 nmol/l). Partial restoration could not be mimicked by washout of methysergide.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1007/BF00176616 |
pubmed_686_20818 | OBJECTIVE
Lactase gene Lac isolated from BALB/c mice was sequenced, in order to clarify the characteristics of its encoding product and prepare the cDNA probe for further researches on Latose Intolerance by in situ experiment.
METHODS
A total RNA was isolated by Trizol kit from the small intestine of 4wk old BALB/c mice, then its cDNA was obtained by RT-PCR, etc. After sequencing, the cDNA sequence was submitted to NCBI GenBank. Then a prediction of the characteristics of its deduced protein was made by bioinformatics. The The cDNA coding preparation of the cDNA probe was carried out by the method of random primer.
RESULTS
The cDNA coding sequence was possessed of 912 bp, encoding 303 amino acids residues. In the secondary structure of its deduced product, there existed a motif of glycosyl-hydro-F1-1 located between the amino acid residues 121-129, and there was a transmembrane helicers at the C-terminal.
CONCLUSION
The Lac gene thus obtained is lactase gene authentically; its deduced protein product is lactase. | pubmed_686_20818 |
pubmed_713_19972 | Background: The current study is conducted with the aim to the fill the gap of information regarding treatment outcomes and variables associated with unsuccessful outcome among XDR-TB patients from Pakistan. Methods: A total of 404 culture confirmed XDR-TB patients who received treatment between 1st May 2010 and June 30, 2017 at 27 treatment centers all over Pakistan were retrospectively followed until their treatment outcomes were reported. A p-value <0.05 reflected a statistical significant association. Results: The patients had a mean age 32.9 ± 14.1 years. The overall treatment success rate was 40.6% (95% confidence interval [CI]:35.80-45.60%). A total of 155 (38.4%) patients were declared cured, 9 (2.2%) completed treatment, 149 (36.9%) died, 60 (14.9%) failed treatment and 31 (7.7%) were lost to follow up (LTFU). The results of the multivariate binary logistic regression analysis revealed that the patients' age of >60 years (OR = 4.69, 95%CI:1.57-15.57) and receiving high dose isoniazid (OR = 2.36, 95%CI:1.14-4.85) had statistically significant positive association with death, whereas baseline body weight >40 kg (OR = 0.43, 95%CI:0.25-0.73) and sputum culture conversion in the initial two months of treatment (OR = 0.33, 95%CI:0.19-0.58) had statistically significant negative association with death. Moreover, male gender had statistically significant positive association (OR = 1.92, 95%CI:1.04-3.54) with LTFU. Conclusion: The treatment success rate (40.6%) of XDR-TB patients in Pakistan was poor. Providing special attention and enhanced clinical management to patients with identified risk factors for death and LTFU in the current cohort may improve the treatment outcomes. | 10.3389/fphar.2021.640555 |
pubmed_497_17179 | In the cuttlefish Sepia officinalis, the successive steps of egg laying are controlled by multiple neuropeptides. Recent experiments led us to suppose that there was possible involvement of a second regulation pathway by the release of ovarian regulatory peptides in the genital tract. Using HPLC fractionation and an in vitro biological test, a C-terminal amidated peptide modulating the motility of the Sepia officinalis oviduct was isolated from an extract of vitellogenic ovarian follicles. The mass of this peptide as determined by MALDI-TOF (1501.8 Da) and analysis by Edman degradation led to the following sequence: Pro-Lys-Asp-Ser-Met-Leu-Leu-Leu-Gln-Val-Pro-Val-Tyr-amide. The peptide mapping performed by LC/MS revealed a distribution restricted to the follicles, the full grown oocytes and the eggs. This new peptide, called SepOvotropin, modulated contractions of the whole genital tract in physiological conditions from a threshold concentration between 10(-20) and 10(-19) M, demonstrating for the first time the occurrence of a specific peptidergic control of egg-laying in cephalopods. | 10.1006/bbrc.2000.3595 |
pubmed_320_5538 | Decision to select unprotected left main (ULM) stenting versus coronary artery bypass grafting surgery (CABG) depends on a multiplicity of factors, one of the most critical of which is myocardial viability. Delayed enhancement cardiac magnetic resonance (CMR) imaging has emerged as a useful means of comprehensively evaluating viable myocardium in postmyocardial infarct patients who require further revascularization. We present a patient with ULM stenosis in whom CMR imaging assisted in the decision to perform percutaneous coronary intervention over CABG. | 10.1016/j.carrev.2007.03.172 |
pubmed_822_5312 | Pain is a clinical challenge to health care providers who care for hand disorders. Pathologic pain that prevents recovery leads to dissatisfaction for both patients and providers. Despite pain being common, the root cause is often difficult to diagnose. This article reviews the examination and diagnostic tools that are helpful in identifying pathologic and neuropathic pain. This article provides tools to speed recognition of these processes to allow earlier intervention and better patient outcomes. | pubmed_822_5312 |
pubmed_820_23995 | Tracking secular trends in the pubertal development of a country's children is important for social and public health reasons. Although comparable studies are largely lacking for US children over the last half century, existing data on girls, particularly that for menarche, indicate that the trend for earlier sexual maturatin has continued and that racial differences are significant, with African-American girls developing earlier than white girls. Data on boys, though less reliable, suggest that they may be beginning maturation earlier as well. More studies on boys with reliable methodologies are needed. Earlier development may not be healthy and may indicate environmental problems that need to be further researched and addressed. | 10.1111/j.1365-2605.2005.00575.x |
pubmed_147_17115 | The Middle Eastern site in the INTERGROWTH-21(st) Project was Muscat, the capital city of Oman, with approximately 10,500 births per year. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two hospitals covering 96% of the region's births. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from four primary health facilities serving Khoula Hospital, using the eligibility criteria in the INTERGROWTH-21(st) protocol. Special activities to encourage participation in this population included local advocacy campaigns to encourage early antenatal booking and ultrasound dating in the population. The major challenges at the site were the recruitment of sufficient numbers of women at an early gestational age, and the timely measurement of all newborns within 12 hours of birth. Many individuals and institutions collaborated effectively over a period of several years on these studies, which required careful planning and close monitoring for their successful implementation. | 10.1111/1471-0528.12043 |
pubmed_51_4696 | Some plants are known as indoor air purifiers. A large number of studies report kinetic purification results for an extensive panel of plants, i.e. the pollutant concentration (volatile organic compounds, as known as VOC, most of the time) is continuously monitored by gas chromatography. However, only a few papers describe the mechanisms involved in such processes. This study deals with the use of secondary ion mass spectrometry imaging as an efficient tool to locate atmospheric pollutant as bromotoluene within the Hedera helix plant (leaf, roots) and the substrate on which it was previously grown. Hedera helix plants have been placed in a pollution chamber with control of the exposure parameters. Plant and soil samples excised were transferred into a fixative solution of glutaraldehyde and paraformaldehyde for a few days, were dehydrated using ethanol and were embedded with resin. Cross sections were made from the pale brown solids obtained. Then, a device using a cathodic pulverization device capable of depositing a few nanometers of gold atoms over the sample was used to make the surface electronically conductive for the NanoSIMS. Hence, polluted and unpolluted samples of Hedera helix and substrates were obtained following a careful procedure that allowed for the discrimination between polluted and nonpolluted ones. Nanoscale spatial resolution was an invaluable tool (NanoSIMS) to achieve this, and proved that VOCs, such as bromotoluene, were actually trapped by plants such as Hedera helix. | 10.1016/j.chemosphere.2012.04.058 |
pubmed_1005_17684 | A new neuroimaging dimension is currently being adopted. The structural connectome reveals macroscale white matter connectivity of the human brain, providing insights into brain networks organization. Connectomics (analysis of the connectome) has potential for elucidating aberrant networks (eg, in congenital brain malformations, especially axonal pathfinding disorders). Connectomics provides a powerful set of network measures, which can serve as noninvasive biomarkers for the diagnosis, prognostication, and treatment response of children. We discuss the principles of connectome reconstruction and visualization of the pediatric structural connectome using current state-of-the-art neuroimaging and postprocessing techniques, and we describe potential connectomics applications to study brain malformations. | 10.1016/j.nic.2019.03.005 |
pubmed_648_25878 | Although the available proteomic studies have made it possible to identify and characterize Trichinella stage-specific proteins reacting with infected host-specific antibodies, the vast majority of these studies do not provide any information about changes in the global proteomic serum profile of Trichinella-infested individuals. In view of the above, the present study aimed to examine the protein expression profile of serum obtained at 13 and 60 days postinfection (d.p.i.) from three groups of pigs experimentally infected with Trichinella spiralis, Trichinella britovi, and Trichinella pseudospiralis and from uninfected, control pigs by two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The comparative proteomic analysis of the T. spiralis group vs the control group revealed 5 differently expressed spots at both 13 and 60 d.p.i. Experimental infection with T. britovi induced significant expression changes in 3 protein spots at 13 d.p.i. and in 6 protein spots at 60 d.p.i. in comparison with the control group. Paired analyses between the group infected with T. pseudospiralis and the uninfected control group revealed 6 differently changed spots at 13 d.p.i. and 2 differently changed spots at 60 d.p.i. Among these 27 spots, 15 were successfully identified. Depending on the Trichinella species triggering the infection and the time point of serum collection, they were IgM heavy-chain constant region, antithrombin III-precursor, immunoglobulin gamma-chain, clusterin, homeobox protein Mohawk, apolipoprotein E precursor, serum amyloid P-component precursor, Ig lambda chains, complement C3 isoform X1, and apolipoprotein A-I. Our results demonstrate that various Trichinella species and different phases of the invasion produce a distinct, characteristic proteomic pattern in the serum of experimentally infected pigs. | 10.3390/pathogens9010055 |
pubmed_1027_21363 | Earlier work indicates that the major DNA repair phosphodiesterase (PDE) in yeast cells is the well-characterized Apn1 protein. Apn1 demonstrates both Mg2+-independent PDE activity and Mg2+-independent class II apurinic/apyrimidinic (AP) endonuclease activity and represents greater than 90% of the activity detected in crude extracts from wild-type yeast cells. Apn1 is related to Echerichia coli endonuclease IV, both in its enzymatic properties and its amino acid sequence. In this work, we report the partial purification of a novel yeast protein, Pde1, present in Apn1-deficient cells. Pde1 is purified by sequential BioRex-70, PBE118, and MonoS chromatography steps using a sensitive and highly specific 3'-phosphoglycolate-terminated oligonucleotide-based assay as a measure of PDE activity. Mg2+-stimulated PDE and Mg2+-stimulated class II AP endonuclease copurify during this procedure. These results indicate that yeast, like many other organisms studied to date, has enzymatic redundancy for the repair of 3'-blocking groups and abasic sites. | 10.1021/bi970048y |
pubmed_659_15183 | PURPOSE
MEDI0680 is a humanized anti-programmed cell death-1 (PD-1) antibody, and durvalumab is an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity and safety of MEDI0680 plus durvalumab versus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal cell carcinoma who received at least one prior line of antiangiogenic therapy.
PATIENTS AND METHODS
Patients received either MEDI0680 (20 mg/kg) with durvalumab (750 mg) or nivolumab (240 mg), all intravenous, every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included best overall response, progression-free survival (PFS), safety, overall survival (OS), and immunogenicity. Exploratory endpoints included changes in circulating tumor DNA (ctDNA), baseline tumor mutational burden, and tumor-infiltrated immune cell profiles.
RESULTS
Sixty-three patients were randomized (combination, n = 42; nivolumab, n = 21). ORR was 16.7% [7/42; 95% confidence interval (CI), 7.0-31.4] with combination treatment and 23.8% (5/21; 95% CI, 8.2-47.2) with nivolumab. Median PFS was 3.6 months in both arms; median OS was not reached in either arm. Because of adverse events, 23.8% of patients discontinued MEDI0680 and durvalumab and 14.3% of patients discontinued nivolumab. In the combination arm, reduction in ctDNA fraction was associated with longer PFS. ctDNA mutational analysis did not demonstrate an association with response in either arm. Tumor-infiltrated immune profiles showed an association between immune cell activation and response in the combination arm.
CONCLUSIONS
MEDI0680 combined with durvalumab was safe and tolerable; however, it did not improve efficacy versus nivolumab monotherapy. | 10.1158/1078-0432.CCR-21-4115 |
pubmed_647_14378 | The glutamate transporter GLT-1 from Rattus norvegicus was expressed at high level in BHK cells using the Semliki Forest virus expression system. BHK cells infected with viral particles carrying the GLT-1 gene exhibited 30-fold increased aspartate uptake compared to control cells. The expression level of GLT-1 as determined by binding of labelled substrate to membrane preparations was about 3.5 x 10(6) functional transporters per cell, or 61 pmol GLT-1 per milligram of membrane protein. Purification of the His-tagged protein by Ni2+-NTA affinity chromatography enabled the routine production and purification of milligram quantities of fully functional transporter. Transport activity required reducing conditions and the addition of extra lipid throughout the purification. The apparent molecular mass of the recombinant transporter was 73 kDa or 55 kDa, corresponding to the glycosylated and non-glycosylated form, respectively. Both forms were active upon separation on a lectin column and reconstitution into liposomes. Glycosylated and non-glycosylated GLT-1 were transported to the plasma membrane with equal efficiency. Our results show that N-glycosylation does not affect the trafficking or the transport activity of GLT-1. The low-resolution structure of GLT-1 was determined by electron microscopy and single particle reconstruction. | 10.1016/j.jmb.2005.06.036 |
pubmed_703_22805 | Obtaining random homozygous mutants in mammalian cells for forward genetic studies has always been problematic due to the diploid genome. With one mutation per cell, only one allele of an autosomal gene can be disrupted, and the resulting heterozygous mutant is unlikely to display a phenotype. In cells with a genetic background deficient for the Bloom's syndrome helicase, such heterozygous mutants segregate homozygous daughter cells at a low frequency due to an elevated rate of crossover following mitotic recombination between homologous chromosomes. We constructed DNA vectors that are selectable based on their copy number and used these to isolate these rare homozygous mutant cells independent of their phenotype. We use the piggyBac transposon to limit the initial mutagenesis to one copy per cell, and select for cells that have increased the transposon copy number to two or more. This yields homozygous mutants with two allelic mutations, but also cells that have duplicated the mutant chromosome and become aneuploid during culture. On average, 26% of the copy number gain events occur by the mitotic recombination pathway. We obtained homozygous cells from 40% of the heterozygous mutants tested. This method can provide homozygous mammalian loss-of-function mutants for forward genetic applications. | 10.1093/nar/gkr908 |
pubmed_419_15244 | The mechanical behavior of carbonaceous mudstone deteriorates greatly when exposed to wet environments, and the precise evaluation of its slope stability has been a difficulty. This study aims to establish a numerical analysis method for the instability problems of its slopes; this method considers the effects of weathering and water-softening by establishing their mathematical expressions. The weathering and water-softening effects are reflected by variations in the mechanical properties (e.g., elastic modulus, angle of internal friction, and cohesion) of carbonaceous mudstone, with the depth following a logistic function and the shear strength parameters varying with wetting duration and degree of saturation. Their weathering and water-softening effects are reproduced with the use of the ABAQUS finite-element software and MATLAB programming. The proposed numerical method is applied to analyze the seepage field and stability of a highway cut slope with and without protection structures; the application results show that the proposed numerical method is reliable in analyzing the slope's instability problem. The use of the herringbone skeleton structures can reduce the water-softening effects and thus increase the safety factor of the slope. The findings of this study could provide guidance to the design and construction of highway cut slopes in mountain areas that are rich in carbonaceous mudstone. | 10.3390/ijerph192114308 |
pubmed_1114_10584 | PURPOSE
The implementation of the Patient Protection and Affordable Care Act has facilitated the development of an innovative and integrated delivery care system, Accountable Care Organizations (ACOs). It is timely, to identify how health care managers in rural health clinics are responding to the ACO model. This research examines RHC managers' perceived benefits and barriers for implementing ACOs from an organizational ecology perspective.
METHODOLOGY/APPROACH
A survey was conducted in Spring of 2012 covering the present RHC network working infrastructures - 1) Organizational social network; 2) organizational care delivery structure; 3) ACO knowledge, perceived benefits, and perceived barriers; 4) quality and disease management programs; and 5) health information technology (HIT) infrastructure. One thousand one hundred sixty clinics were surveyed in the United States. They cover eight southeastern states (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee) and California. A total of ninety-one responses were received.
FINDINGS
RHC managers' personal perceptions on ACO's benefits and knowledge level explained the most variance in their willingness to join ACOs. Individual perceptions appear to be more influential than organizational and context factors in the predictive analysis.
RESEARCH LIMITATIONS/IMPLICATIONS
The study is primarily focused in the Southeastern region of the U.S. The generalizability is limited to this region. The predictors of rural health clinics' participation in ACOs are germane to guide the development of organizational strategies for enhancing the general knowledge about the innovativeness of delivering coordinated care and containing health care costs inspired by the Affordable Care Act.
ORIGINALITY/VALUE OF PAPER
Rural health clinics are lagged behind the growth curve of ACO adoption. The diffusion of new knowledge about pros and cons of ACO is essential to reinforce the health care reform in the United States. | 10.1108/S0275-495920140000032023 |
pubmed_946_2975 | Proteoglycan biosynthesis by human osteochondrophytic spurs (osteophytes) obtained from osteoarthritic femoral heads at the time of surgical joint replacement was studied under defined culture conditions in vitro. Osteophytes were primarily present in two anatomic locations, marginal and epi-articular. Minced tissue slices were incubated in the presence of [(35)S]sulphate or [(14)C]glucosamine. Osteophytes incorporated both labelled precursors into proteoglycan, which was subsequently characterized by CsCl-isopycnic-density-gradient ultracentrifugation and chromatography on Sepharose CL-2B. The material extracted with 0.5m-guanidinium chloride showed 78.1% of [(35)S]sulphate in the A1 fraction after centrifugation. Only 23.0% of the [(35)S]sulphate in this A1 fraction was eluted in the void volume of Sepharose CL-2B under associative conditions. About 60-80% of the [(35)S]sulphate in the tissue 4m-guanidinium chloride extract was associated with monomeric proteoglycan (fraction D1). The average partition coefficient (K(av.)) of the proteoglycan monomer on Sepharose CL-2B was 0.28-0.33. Approx. 12.4% of this monomer formed stable aggregates with high-molecular-weight hyaluronic acid in vitro. Sepharose CL-2B chromatography of fractions with lower buoyant densities (fractions D2-D4) demonstrated elution profiles on Sepharose CL-2B substantially different than that of fraction D1, indicative of the polydisperse nature of the newly synthesized proteoglycan. Analysis of the composition and chain size of the glycosaminoglycans showed the following: (1) preferential elution of both [(35)S]sulphate and [(14)C]glucosamine in the 0.5m-LiCl fraction on DEAE-cellulose; (2) the predominant sulphated glycosaminoglycan was chondroitin 6-sulphate (60-70%), with 9-11% keratan sulphate in the monomer proteoglycan; (3) K(av.) values of 0.38 on Sephadex G-200 and 0.48 on Sepharose CL-6B were obtained with papain-digested and NaBH(4)-treated D1 monomer respectively. A comparison of the synthetic with endogenous glycosaminoglycans indicated similar types. These studies indicated that human osteophytes synthesized in vitro sulphated proteoglycans with some characteristics similar to those of mature human articular cartilage, notably in the size of their proteoglycan monomer and predominance of chondroitin 6-sulphate. They differed from articular cartilage primarily in the lack of substantial quantities of keratan sulphate and aggregation properties associated with monomer interaction with hyaluronic acid. | 10.1042/bj2060329 |
pubmed_890_23542 | OBJECTIVES
Surgical trauma produces metabolic and hormonal responses, which are characterized by insulin resistance. Due to extension of the preoperative fasting period, which increases the magnitude of postoperative insulin resistance, preoperative oral carbohydrates (POC) have been developed.
PATIENTS AND METHODS
This prospective, randomized, controlled study was performed on 43 ASA I-II patients undergoing elective microsurgical lumbar discectomy. The intervention group received oral carbohydrate solution 800mL the night before and 400mL 2h prior to operation. The other group fasted for 8h prior to operation. Blood samples were obtained the day before the operation, before induction of anesthesia, after skin incision, 1h, 2h, 6h and 24h following skin incision. Blood glucose, plasma insulin, cortisol and interleukin-6 (IL-6) levels were determined. The primary endpoint was to assess the effect of POC treatment on insulin resistance and surgical stress response following lumbar disc surgery. The secondary endpoint was to assess POC's effects on postoperative nausea and vomiting.
RESULTS
The serum insulin levels were higher before induction of anesthesia in the study group and returned to fasted group levels by 2h after skin incision. The plasma IL-6 levels were higher in the intervention group at 6h after the skin incision. There were no differences between the two groups with respect to blood glucose, plasma cortisol levels and the incidence of nausea and vomiting.
CONCLUSION
This study suggests that use of POC treatment does not attenuate development of insulin resistance in patients undergoing lumbar disc surgery. | 10.1016/j.clineuro.2016.12.016 |
pubmed_664_11443 | Magnetic Heusler alloys which undergo a martensitic transition display interesting functional properties. In the present review, we survey the magnetocaloric effects of Ni-Mn-based Heusler alloys and discuss their relation with the magnetic shape-memory and magnetic superelasticity reported in these materials. We show that all these effects are a consequence of a strong coupling between structure and magnetism which enables a magnetic field to rearrange martensitic variants as well as to provide the possibility to induce the martensitic transition. These two features are respectively controlled by the magnetic anisotropy of the martensitic phase and by the difference in magnetic moments between the structural phases. The relevance of each of these contributions to the magnetocaloric properties is analysed. | 10.1088/0953-8984/21/23/233201 |
pubmed_300_8771 | Effects of hypoxic solution (O(2) tension, 161 +/- 11 mmHg) on electrical responses of the membrane (slow waves), intracellular Ca(2+)-responses measured by Fura-2 fluorescence (Ca-transients) and isometric mechanical responses (phasic contraction) were observed in circular smooth muscles isolated from the guinea-pig stomach antrum. In normoxic solution (O(2) tension, 362 +/- 28 mmHg), muscle cells generated slow waves spontaneously, and switching to hypoxic solution caused an increase in frequency and decrease in duration of slow waves, with no significant change in the resting membrane potential. Hypoxia also reduced the amplitude and duration and increased the frequency of Ca-transients. The increase in frequency of slow waves by hypoxia was prevented by cyclopiazonic acid (CPA) but not by carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), potassium cyanide (KCN) or low-Ca solution. The reduction by hypoxia of the duration of slow waves was prevented by CCCP or KCN but not by CPA or low-Ca solution. Hypoxia resulted in an increase in frequency and decrease in amplitude of phasic contractions, and the changes were prevented by CPA but not by CCCP. These results suggested that in antrum smooth muscle tissues, the increase in frequency of spontaneous activity by hypoxia is related to the enhanced function of the CPA-sensitive internal Ca-stores in pacemaker cells, while the inhibition in amplitude of phasic contractions by hypoxia may be mainly related to the decrease in Ca(2+) release from the CPA-sensitive internal stores in smooth muscle cells. It is concluded that in hypoxic solution, the function of internal Ca(2+) stores is enhanced in ICC-MY and is inhibited in smooth muscle cells in the guinea-pig stomach antrum. | 10.1540/jsmr.45.149 |
pubmed_1094_5205 | Recombinase polymerase amplification (RPA) is a rapid, isothermal amplification method with high specificity and sensitivity. In this study, an assay was developed and evaluated for the detection of banana bunchy top virus (BBTV) in infected banana plants. Three oligonucleotide primer pairs were designed from the replicase initiator protein gene sequences of BBTV to function both in RPA as well as in polymerase chain reaction (PCR). A total of 133 symptomatic as well as asymptomatic banana leaf samples from various cultivars were collected from the different regions of India and evaluated for BBTV infection using the RPA assay. BBTV was efficiently detected using crude leaf sap in RPA and the results obtained were consistent with PCR-based detection using purified DNA as template. To our knowledge, this is the first report of reliable diagnosis of BBTV infection by RPA using crude leaf sap as a template. | 10.1007/s00705-017-3399-9 |
pubmed_286_10144 | Enasidenib (Idhifa®) is an oral isocitrate dehydrogenase-2 (IDH2) inhibitor developed by Celgene Corporation under a global, exclusive license from Agios Pharmaceuticals. Enasidenib has been approved in the USA for the treatment of adults with relapsed or refractory acute myeloid leukaemia (AML) and an IDH2 mutation as detected by an FDA-approved test. It is at various stages of development in other countries for AML, myelodysplastic syndromes and solid tumours. This article summarizes the milestones in the development of enasidenib leading to this first global approval in the USA for the treatment of adults with relapsed or refractory IDH2-mutated AML. | 10.1007/s40265-017-0813-2 |
pubmed_385_3317 | The potential benefit of the simultaneous integrated boost (SIB) concept in proton therapy was investigated in a planning study. The proposed fractionation strategy consisted of a SIB treatment following a first phase of conventional fractionation to the elective volume (named SEQ/SIB). The novel method was compared to a conventional sequential fractionation and to a full SIB approach. Treatment plans were designed for five patients on the proton planning system developed for spot scanning at the Paul Scherrer Institute of Villigen (CH). Three to five beams were applied for all plans and fractionations. All effective dose distributions were corrected using biological models to take into account repopulation and time at repopulation onset. Corrected and uncorrected plans were compared on the basis of dosimetry criteria and dose-volume histograms. The results showed a dosimetric advantage for the SEQ/SIB approach in terms of target coverage, without significant disadvantages for risk structures and healthy tissue. Considering the high logistic impact and the limited availability of radiation facilities, the clinical exploitation of accelerated SIB treatment with protons appears promising. | 10.1078/0939-3889-00218 |
pubmed_670_5826 | Twelve normal subjects (aged 22-80 yr, mean 47 yr) performed three blocks of 20 saccades made to LED targets stepped back and forth. The first and last blocks were performed at a (slow) rate of 0.18 Hz, while the middle block was performed at the faster rate of 1.15 Hz. Mean saccadic amplitude was unaffected by saccade rate, but latency and duration became shorter at the higher frequency. Most interestingly, the peak velocity increased by approx. 6% when saccades were performed at the higher rate. This increase was statistically significant, even after normalization for saccade amplitude. That saccadic frequency may affect saccadic peak velocity must be considered as a potential variable when analysing saccades. | 10.1016/0042-6989(91)90062-a |
pubmed_235_15522 | This study aimed to test the association between personality traits and affect among boxers and to figure out whether loneliness mediated this relationship. This study used The Big Five Personality Traits Scale, The UCLA Loneliness Scale, and The Positive and Negative Affect Scale (PANAS) which were administered to N = 231 boxers (age: M = 20.28; SD = 2.60), of which 62% were male (n = 144) and 38% were female (n = 87). The results showed that (1) conscientiousness, extraversion, and agreeableness were negatively related with negative affect, neuroticism was positively associated with negative affect, and openness showed no relationship with negative affect; (2) conscientiousness, extraversion, and agreeableness were all positively correlated with positive affect, neuroticism was negatively associated with positive affect, and openness showed no relationship with positive affect; (3) conscientiousness, extraversion, openness, and agreeableness were negatively related with loneliness and neuroticism was positively associated with loneliness; and (4) loneliness was positively associated with negative affect; loneliness was negatively associated with positive affect; and loneliness had mediating effect on the relationship between the personality traits and affect. Furthermore, these findings suggest that loneliness might be one mechanism explaining how boxer's personality traits influence their athletic performance. Therefore, in the future, we should start by helping them reduce their loneliness to reduce their negative affect and improve their positive affect and also, in some degree, to enhance boxers' athletic ability and mental quality health. | 10.3389/fpsyg.2021.609153 |
pubmed_713_10146 | BACKGROUND
Although migraine is widespread and disabling, stigmatisation and poor awareness of the condition still represent barriers to effective care; furthermore, research on migraine individual and social impact must be enhanced to unveil neglected issues, such as caregiving burden. The project investigated the migraine illness experience through Narrative Medicine (NM) to understand daily life, needs and personal resources of migraneurs, their caregivers and clinicians, and to provide insights for clinical practice.
METHODS
The project involved 13 Italian headache centres and targeted migraneurs, their caregivers and migraine specialists at these centres. Written narratives, composed by a sociodemographic survey and illness plot or parallel chart, were collected through the project's webpage. Illness plots and parallel charts employed open words to encourage participants' expression. Narratives were analysed through Nvivo software, interpretive coding and NM classifications.
RESULTS
One hundred and seven narratives were collected from patients and 26 from caregivers, as well as 45 parallel charts from clinicians. The analysis revealed migraine perception in social, domestic and work life within the care pathway evolution and a bond between chaos narratives and day loss due to migraine; furthermore, narratives suggested the extent of the caregiving burden and a risk of underestimation of migraine burden in patients' and caregivers' life.
CONCLUSION
The project represents the first investigation on migraine illness experience through NM simultaneously considering migraneurs', caregivers' and clinicians' perspectives. Comparing narratives and parallel charts allowed to obtain suggestions for clinical practice, while NM emerged as able to foster the pursuing of migraine knowledge and awareness. | 10.1007/s10072-021-05227-w |
pubmed_575_6581 | BACKGROUND
The association of bronchiectasis (BE) in patients with severe eosinophilic asthma (SEA) is quite frequent. Mepolizumab is a well-recognized treatment for SEA; we aim to evaluate its effectiveness in SEA patients with and without BE in real-life.
METHODS
We performed a single-center retrospective pilot study, including patients with SEA treated with mepolizumab for one year. Asthma control test (ACT), lung function, annual exacerbations rate, oral corticosteroid dosage, FeNO, chronic mucous secretions, blood and sputum eosinophils were recorded at baseline and after 6 and 12 months.
RESULTS
we included 32 patients (mean age: 52.3 ± 10, 59% female). 50% showed co-presence of bronchiectasis, (SEA + BE). Significant improvements were found in ACT [(13.8 ± 4.6 to 20.7 ± 4.1, p = 0.0009) and (13 ± 4.8 to 20.7 ± 4.6, p = 0.0003)], annual exacerbations rate [from 7 (4-12) to 0 (0.00-0.75) and from 8 (4-12) to 0 (0-1), p < 0.0001], and blood eosinophils count [748 cells/μL (400-1250) vs. 84 cells/μL (52.5-100), and from 691 cells/μL (405-798) vs. 60 cells/μL (41-105), p < 0.0001] in SEA and SEA + BE group respectively, already after 6 months of treatment. A reduction in daily oral corticosteroids intake at 12 months was shown [from 15 mg (0-25) to 0 mg (0-0), p = 0.003 and from 8.8 mg (0-25) to 0 mg (0-0) (p = 0.01)] in both SEA and SEA + BE, respectively. Similar results were found, comparing SEA + BE patients based on the severity of bronchiectasis.
CONCLUSIONS
Mepolizumab effectively improves asthma symptoms control, reducing annual exacerbations and corticosteroid intake in all patients with SEA, even in the subgroup with coexisting bronchiectasis, independently of their severity. | 10.1016/j.rmed.2021.106491 |
pubmed_703_4175 | In studies focusing on the factors that impact solid waste generation habits and rates, the potential spatial dependency in solid waste generation data is not considered in relating the waste generation rates to its determinants. In this study, spatial dependency is taken into account in determination of the significant socio-economic and climatic factors that may be of importance for the municipal solid waste (MSW) generation rates in different provinces of Turkey. Simultaneous spatial autoregression (SAR) and geographically weighted regression (GWR) models are used for the spatial data analyses. Similar to ordinary least squares regression (OLSR), regression coefficients are global in SAR model. In other words, the effect of a given independent variable on a dependent variable is valid for the whole country. Unlike OLSR or SAR, GWR reveals the local impact of a given factor (or independent variable) on the waste generation rates of different provinces. Results show that provinces within closer neighborhoods have similar MSW generation rates. On the other hand, this spatial autocorrelation is not very high for the exploratory variables considered in the study. OLSR and SAR models have similar regression coefficients. GWR is useful to indicate the local determinants of MSW generation rates. GWR model can be utilized to plan waste management activities at local scale including waste minimization, collection, treatment, and disposal. At global scale, the MSW generation rates in Turkey are significantly related to unemployment rate and asphalt-paved roads ratio. Yet, significances of these variables may diminish at local scale for some provinces. At local scale, different factors may be important in affecting MSW generation rates. | 10.1016/j.wasman.2011.10.017 |
pubmed_51_6742 | The pituitary transcription factor POU1F1 is required for the differentiation of lactotrope, thyrotrope, and somatotrope cells. Its expression is maintained in the adult and is crucial for the expression of prolactin, GH, and TSHβ-subunit. Different studies indicated that POU1F1 could also have other functions in these cells. The identification of new targets of this factor could be useful to obtain a better understanding of these functions. To address this question we combined data obtained from expression microarrays and from chromatin immunoprecipitation (ChIP)-chips. Gene expression microarray assays were used to detect genes that have their expression modified in somatolactotrope GH4C1 cells by the expression of a dominant-negative form of POU1F1, POU1F1(R271W), and led to the identification of 1346 such genes. ChIP-chip experiments were performed from mouse pituitaries and identified 1671 POU1F1-binding sites in gene-promoter regions. Intersecting the gene expression and the ChIP-chip data yielded 121 potential new direct targets. The initial set of 1346 genes identified using the microarrays, as well as the 121 potential new direct targets, were analyzed with DAVID bioinformatics resource for gene ontology term enrichment and cluster. This analysis revealed enrichment in different terms related to protein synthesis and transport, to apoptosis, and to cell division. The present study represents an integrative genome-wide approach to identify new target genes of POU1F1 and downstream networks controlled by this factor. | 10.1210/me.2011-1308 |
pubmed_402_10279 | As the interest in weak-affinity antibodies has been widened by their introduction to various analytical techniques such as HPLC, capillary electrophoresis and biosensors, there has been a need for new screening/monitoring methods. In this study, weak-affinity chromatography was adopted to screen/monitor directly for monoclonal antibodies in ascites. Monoclonal antibodies against a carbohydrate antigen (maltohexaose) were used to evaluate this approach. In short, malthohexaose was immobilized on an HPLC support in such a configuration to allow, during HPLC, retardation of weak monoclonal antibodies. Based on the retention, the affinity or the avidity, as determined by the presence of multiple binding of the monoclonal antibody towards antigen, can be estimated. In this way it is possible to select clones of hybridomas that produce desired weak monoclonal antibodies. Adjustments in temperature (10-20 degrees C) were used to moderate the retention and hence affinity of the weak monoclonal antibodies during chromatography. | 10.1002/(SICI)1099-1352(199812)11:1/6<114::AID-JMR403>3.0.CO;2-# |
pubmed_438_4026 | Despite the large number of persons affected by cognitive impairment, very little is known about how they and their families make choices and decisions about everyday living and long-term care. Moreover few studies have examined the concept of consumer direction, particularly the ability ofcognitively impaired persons to delegate decision-making to other persons. This study explored decision-making through personal interviews with 51 respondent pairs, or dyads (i.e., the cognitively impaired person and the family caregiver). Results suggest that persons with mild to moderate cognitive impairment are able to answer questions about their preferences for daily care and to choose a person, usually a spouse or adult child, to make a variety of decisions on their behalf by recognizing both voices-those of the care receiver and the family caregiver--we can enhance future research and practice, foster the development of consumer direction in long-term care, and advance public policy to support caregiving families. | 10.1177/153331750201700406 |
pubmed_708_9616 | Exposure of 3T3-L1 adipocytes to 100 ng/ml of cholera toxin or 1 mM dibutyryl cyclic AMP caused a marked stimulation of deoxyglucose transport. A maximal increase of 10- to 15-fold was observed after 12-24 h of exposure, while 100 nM insulin elicited an increase of similar magnitude within 30 min. A short term exposure (4 h) of cells to cholera toxin or dibutyryl cyclic AMP resulted in a 3- to 4-fold increase in deoxyglucose transport which was associated with significant redistribution of both the HepG2/erythrocyte (GLUT1) and muscle/adipocyte (GLUT4) glucose transporters from low density microsomes to the plasma membrane fraction. Total cellular amounts of both transporter proteins remained constant. In contrast, cells exposed to cholera toxin or dibutyryl cyclic AMP for 12 h exhibited elevations in total cellular contents of GLUT1 (but not GLUT4) protein to about 1.5- and 2.5-fold above controls, respectively. Although such treatments of cells with cholera toxin (12 h) versus insulin (30 min) caused similar 10-fold enhancements of deoxyglucose transport, a striking discrepancy was observed with respect to the content of glucose transporter proteins in the plasma membrane fraction. While insulin elicited a 2.6-fold increase in the levels of GLUT4 protein in the plasma membrane fraction, cholera toxin increased the amount of this transporter by only 30%. Insulin or cholera toxin increased the levels of GLUT1 protein in the plasma membrane fraction equally (1.6-fold). Thus, a greater number of glucose transporters in the plasma membrane fraction is associated with transport stimulation by insulin compared to cholera toxin. We conclude that: 1) at early times (4 h) after the addition of cholera toxin or dibutyryl cyclic AMP to 3T3-L1 adipocytes, redistribution of glucose transporters to the plasma membrane appears to contribute to elevated deoxyglucose uptake rates, and 2) the stimulation of hexose uptake after prolonged treatment (12-18 h) of cells with cholera toxin may involve an additional increase in the intrinsic activity of one or both glucose transporter isoforms. | pubmed_708_9616 |
pubmed_432_4511 | A mouse monoclonal anti human filaggrin antibody was found to bind keratohyaline granules of normal epidermis as well as of premalignant and malignant lesions in formalin-fixed tissue sections. In addition, an unexpected binding of this antibody with cells containing glycogen and other PAS positive substances was found, which could be abolished by adsorption of the anti-filaggrin antibody with glycogen or pretreatment of the sections with diastase. | 10.1007/BF00492476 |
pubmed_795_12611 | BACKGROUND
Rabeprazole has been demonstrated to be a potent antisecretory agent and has been shown to be clinically effective in the treatment of acid-related diseases.
AIMS
It was to determine the efficacy of rabeprazole at 20 and 40 mg in addition to amoxicillin and clarithromycin in the treatment of active Helicobacter pylori-positive duodenal ulcers compared with omeprazole 40 mg.
PATIENTS AND METHODS
One hundred and twenty-seven patients were randomised into three treatment groups: 40 patients were treated with rabeprazole 40 mg daily, 42 patients with rabeprazole 20 mg daily and 45 patients with omeprazole 40 mg daily for 10 days. All patients received amoxicillin 1 g twice a day and clarithromycin 500 mg twice a day for 5 days. All patients were re-assessed at least 4 weeks after the end of the treatment.
RESULTS
According to the intention-to-treat (ITT) protocol, ulcer healing was observed in 90% of patients in the rabeprazole 40 group, in 85.7% in the rabeprazole 20 group and in 93.3% in the omeprazole 40 group. We observed H. pylori eradication in 90% ITT in the rabeprazole 40 group, in 80.9% ITT in the rabeprazole 20 group and in 88.8% ITT in the omeprazole 40 group. Statistical analysis did not show significant differences among the three groups.
CONCLUSIONS
A 10-day rabeprazole 20 mg regimen represents an efficacious and safe regimen for H. pylori eradication and ulcer healing. | 10.1159/000066756 |
pubmed_1004_20553 | BACKGROUND
Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option.
METHODS
This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India.
RESULTS
Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%).
CONCLUSION
Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections. | 10.1089/sur.2007.013 |
pubmed_622_122 | The temperature threshold for protection by brief postischemic cooling was evaluated in a model of transient focal ischemia in the Spontaneously Hypertensive Rat, using an array of epidural probes to monitor regional brain temperatures. Rats were subjected to 90 mins tandem occlusion of the right middle cerebral artery (MCA) and common carotid artery. Systemic cooling to 32 degrees C was initiated 5 mins before recirculation, with simultaneous brain cooling to temperatures ranging from 28 degrees C to 32 degrees C within the MCA territory by means of a temperature-controlled saline drip. Rewarming was initiated at 2 h recirculation and was complete within 30 mins. Tissue damage and edema volume showed clear temperature-dependent reductions when evaluated at 3 days survival, with no protection evident in the group at 32 degrees C but progressive effects on both parameters after deeper cooling. A particularly striking effect was the essentially complete elimination of edema progression between 1 and 3 days. Temperature at distal sites within the MCA territory better predicted reductions in lesion volume, indicating that protection required effective cooling of the penumbral regions destined to be spared. These results show that even brief cooling can be highly protective when initiated at the time of recirculation after focal ischemia, but indicate a substantially lower temperature threshold for hypothermic protection than has been reported for other strains, occlusion methods, and cooling durations. | 10.1038/sj.jcbfm.9600492 |
pubmed_372_18339 | Diabetes increases fracture and falls risks. We evaluated the performance of the Garvan fracture risk calculator (FRC) in individuals with versus without diabetes. Using the population-based Manitoba bone mineral density (BMD) registry, we identified individuals aged 50-95 years undergoing baseline BMD assessment from 1 September 2012, onwards with diabetes and self-reported falls in the prior 12 months. Five-year Garvan FRC predictions were generated from clinical risk factors, with and without femoral neck BMD. We identified non-traumatic osteoporotic fractures (OF) and hip fractures (HF) from population-based data to 31 March 2018. Fracture risk stratification was assessed from area under the receiver operating characteristic curves (AUROC). Cox regression analysis was performed to examine the effect of diabetes on fractures, adjusted for Garvan FRC predictions. The study population consisted of 2618 women with and 14,064 without diabetes, and 636 and 2201 men with and without the same, respectively. The Garvan FRC provided significant OF and HF risk stratification in women with diabetes, similar to those without diabetes. Analyses of OF in men were limited by smaller numbers; no significant difference was evident by diabetes status. Cox regression showed that OF risk was 23% greater in women with diabetes adjusted for Garvan FRC including BMD (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.01-1.49), suggesting it slightly underestimated risk; a non-significant increase in diabetes-related HF risk was noted (HR 1.37, 95% CI 0.88-2.15). Garvan FRC shows similar fracture risk stratification in individuals with versus without diabetes, but may underestimate this risk. | 10.1007/s00223-021-00941-1 |
pubmed_929_7057 | PURPOSE
To introduced our experience with progressive extra-axial hematoma (EAH) in the original frontotemporoparietal (FTP) site after contralateral decompressive surgery (CDS) in traumatic brain injury patients and discuss the risk factors associated with this dangerous situation.
METHODS
This retrospective study was conducted on 941 patients with moderate or severe TBI treated in Daping Hospital, Army Medical University, Chongqing, China in a period over 5 years (2013-2017). Only patients with bilateral lesion, the contralateral side being the dominant lesion, and decompressive surgery on the contralateral side conducted firstly were included. Patients were exclude if (1) they underwent bilateral decompression or neurosurgery at the original location firstly; (2) although surgery was performed first on the contralateral side, surgery was done again at the contralateral side due to re-bleeding or complications; (3) patients younger than 18 years or older than 80 years; and (4) patients with other significant organ injury or severe disorder or those with abnormal coagulation profiles. Clinical and radiographic variables reviewed were demographic data, trauma mechanisms, neurological condition assessed by Glasgow coma scale (GCS) score at admission, pupil size and reactivity, use of mannitol, time interval from trauma to surgery, Rotterdam CT classification, type and volume of EAH, presence of a skull fracture overlying the EAH, status of basal cistern, size of midline shift, associated brain lesions and types, etc. Patients were followed-up for at least 6 months and the outcome was graded by Glasgow outcome scale (GOS) score as favorable (scores of 4-5) and unfavorable (scores of 1-3). Student's t-test was adopted for quantitative variables while Pearson Chi-squared test or Fisher's exact test for categorical variables. Multivariate logistic regression analysis was also applied to estimate the significance of risk factors.
RESULTS
Initially 186 patients (19.8%) with original impact locations at the FTP site and underwent surgery were selected. Among them, 66 met the inclusion and exclusion criteria. But only 50 patients were included because the data of the other 16 patients were incomplete. Progressive EAH developed at the original FTP site in 11 patients after the treatment of, with an incidence of 22%. Therefore the other 39 patients were classified as the control group. Multivariate logistic regression analysis showed that both the volume of the original hematoma and the absence of an apparent midline shift were significant predictors of hematoma progression after decompressive surgery. Patients with fracture at the original impact site had a higher incidence of progressive EAH after CDS, however this factor was not an important predictor in the multivariate model. We also found that patients with progressive EAH had a similar favorable outcome with control group.
CONCLUSION
Progressive EAH is correlated with several variables, such as hematoma volumes ≥10 mL at the original impact location and the absence of an apparent midline shift (<5 mm). Although progressive EAH is devastating, timely diagnosis with computed tomography scans and immediate evacuation of the progressive hematoma can yield a favorable result. | 10.1016/j.cjtee.2019.10.005 |
pubmed_236_274 | Our theme centers on the complex processes that constitute and regulate the function of the gastric mucosa. Although some investigators promote the critical importance of a given element, such as acid, blood flow, or mucus, it is clear that both gastric secretory function and mucosal defense and repair mechanisms are multifactorial and are regulated by redundant control circuits. While it is true that critical studies can be performed in vivo with intact mucosa, at the same time it is frequently difficult, using these methods, to define the specific cellular elements involved in the regulation of secretion, defense, and repair. We now recognize that ulcer disease does not occur simply when this balance is thrown off. To the contrary, ulcer disease commonly occurs when the normal mucosal mechanisms are perturbed by Helicobacter pylori-associated gastro-duodenitis or nonsteroidal anti-inflammatory drugs. In the absence of such perturbation, the redundancy of the regulatory mechanisms underlying gastric secretion and the multiple lines of defense and healing would render ulcer disease rare indeed. | pubmed_236_274 |
pubmed_953_17157 | The intershell spacing in different regions of a multi-walled carbon nanotube (MWCNT) was determined by analysis of high resolution transmission electron (HR-TEM) micrographs. Three general effects can be pointed out, (1) the regular intershell spacing of a CNT is bigger than that in a graphitic carbon because the curvature generates geometrical and electronic deformations which increase repulsion forces between the graphene sheets, (2) when an extra curvature appears, e.g. at the tip of a closed CNT or in a bamboo-like structure, the intershell spacing is expanded due to the extra repulsion caused by the combination of pentagonal and heptagonal rings imbibed in the hexagonal lattice, and (3) when a metal particle interacts with a CNT, the intershell spacing is compressed due to strong metal-CNT interactions. | pubmed_953_17157 |
pubmed_497_918 | The procedural standard for DNA profiling developed by the U.S. advisory board on DNA quality assurance methods mandates annual confirmation of forensic DNA measurement systems against an appropriate reference material supplied by or traceable to the National Institute of Standards and Technology (NIST). NIST Standard Reference Material (SRM) 2390 is a suitable and appropriate standard for HaeIII restriction enzyme-based restriction fragment length polymorphism (RFLP) profiling systems. Originally issued in 1992, an among-laboratory SRM 2390 recertification study was initiated in 1997. Using data provided by the 20 state, local, or commercial forensic laboratory participants, quantitative band sizes values (expected mean values and associated bivariate tolerance intervals) are established for two different-source DNAs (female cell line K562 and healthy male "TAW") for genetic loci D1S7, D2S44, D4S139, D5S110, D1OS28, and D17S79. Methods for validating an RFLP measurement system, validating a control material or other secondary standard, and for tracing a particular set of RFLP measurements to NIST SRM 2390 are described in detail. | pubmed_497_918 |
pubmed_214_3359 | Reliable sensory discrimination must arise from high-fidelity neural representations and communication between brain areas. However, how neocortical sensory processing overcomes the substantial variability of neuronal sensory responses remains undetermined1-6. Here we imaged neuronal activity in eight neocortical areas concurrently and over five days in mice performing a visual discrimination task, yielding longitudinal recordings of more than 21,000 neurons. Analyses revealed a sequence of events across the neocortex starting from a resting state, to early stages of perception, and through the formation of a task response. At rest, the neocortex had one pattern of functional connections, identified through sets of areas that shared activity cofluctuations7,8. Within about 200 ms after the onset of the sensory stimulus, such connections rearranged, with different areas sharing cofluctuations and task-related information. During this short-lived state (approximately 300 ms duration), both inter-area sensory data transmission and the redundancy of sensory encoding peaked, reflecting a transient increase in correlated fluctuations among task-related neurons. By around 0.5 s after stimulus onset, the visual representation reached a more stable form, the structure of which was robust to the prominent, day-to-day variations in the responses of individual cells. About 1 s into stimulus presentation, a global fluctuation mode conveyed the upcoming response of the mouse to every area examined and was orthogonal to modes carrying sensory data. Overall, the neocortex supports sensory performance through brief elevations in sensory coding redundancy near the start of perception, neural population codes that are robust to cellular variability, and widespread inter-area fluctuation modes that transmit sensory data and task responses in non-interfering channels. | 10.1038/s41586-022-04724-y |
pubmed_126_20141 | The structural features of protein binding sites for volatile anesthetics are being explored using a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Earlier work has demonstrated that a prototype hydrophobic core is capable of binding the volatile anesthetic halothane. Exploratory work on the design of an improved affinity anesthetic binding site is presented, based upon the introduction of a simple cavity into a prototype (alpha 2)2 four-alpha-helix bundle by replacing six core leucines with smaller alanines. The presence of such a cavity increases the affinity (Kd = 0.71 +/- 0.04 mM) of volatile anesthetic binding to the designed bundle core by a factor of 4.4 as compared to an analogous bundle core lacking such a cavity (Kd = 3.1 +/- 0.4 mM). This suggests that such packing defects present on natural proteins are likely to be occupied by volatile general anesthetics in vivo. Replacing six hydrophobic core leucine residues with alanines results in a destabilization of the folded bundle by 1.7-2.7 kcal/mol alanine, although the alanine-substituted bundle still exhibits a high degree of thermodynamic stability with an overall folded conformational delta GH2O = 14.3 +/- 0.8 kcal/mol. Covalent attachment of the spin label MTSSL to cysteine residues in the alanine-substituted four-alpha-helix bundle indicates that the di-alpha-helical peptides dimerize in an anti orientation. The rotational correlation time of the four-alpha-helix bundle is 8.1 +/- 0.5 ns, in line with earlier work on similar peptides. Fluorescence, far-UV circular dichroism, and Fourier transform infrared spectroscopies verified the hydrophobic core location of the tryptophan and cysteine residues, showing good agreement between experiment and design. These small synthetic proteins may prove useful for the study of the structural features of small molecule binding sites. | 10.1021/bi9721290 |
pubmed_98_20782 | PURPOSE
The study aimed to estimate the prevalence of subnormal stereoacuity in school children and to assess the factors associated with it.
METHODS
In this prospective cross-sectional study, a total of 2,376 school children without amblyopia and manifest squint were screened by the titmus fly test, Snellen chart, tests for heterophoria, anterior segment examination, and fundoscopy. Children with a manifest squint, amblyopia (best-corrected visual acuity [BCVA] <6/18), and history of ocular trauma or surgery, and one-eyed children were excluded. Cycloplegic refraction was done in children with uncorrected or undercorrected refractive errors, and stereoacuity was assessed again with spectacle correction.
RESULTS
The prevalence of normal stereoacuity by titmus fly test was 93.18% with correction of refractive errors. Girls had slightly better stereopsis compared with boys. The subnormal stereoacuity was significantly associated with refractive error (P < 0.00001, significant at P < 0.05), unilateral refractive error (P < 0.00001, significant at P < 0.05), bilateral refractive error (P < 0.00001, significant at P < 0.05), anisometropia (P < 0.00001, significant at P < 0.05), ametropia (P < 0.00001, significant at P < 0.05), lower BCVA (P < 0.00001, significant at P < 0.05), hyperopia (P < 0.05, significant at P < 0.05), and heterophoria (P = 0.014, significant at P < 0.05). The subnormal stereoacuity was positively correlated with the magnitude of refractive error of the eyes.
CONCLUSION
This study underlines the significant impact of identification and correction of refractive errors and squints in school children. The measurement of stereoacuity will be of immense importance and must be included in the screening programs for children. | 10.4103/ijo.IJO_1572_21 |
pubmed_1048_23016 | Sexuality is inseparable from sexual health and can refer to sex, gender identities, orientation, pleasure, intimacy, expression, and reproduction. While each element of human sexuality is important, all of these components interconnect to make us complete sexual beings. Educators and other human service providers thus require professional preparation to ensure they can meet the needs of their learners, effectively manage programming, and successfully implement strategies that allow individuals to embrace or manage their sexual existence. An inclusive approach to sexual health is best to meet the sexual health needs of all women, while ensuring their agency and control of their own bodies. | 10.18043/ncm.77.6.430 |
pubmed_1124_1948 | The performance of ten deaf-blind and ten sighted-hearing participants on four tactile memory tasks was investigated. Recognition and recall memory tasks and a matching pairs game were used. It was hypothesized that deaf-blind participants would be superior on each task. Performance was measured in terms of the time taken, and the number of items correctly recalled. In Experiments 1 and 2, which measured recognition memory in terms of the time taken to remember target items, the hypothesis was supported, but not by the length of time taken to recognize the target items, or for the number of target items correctly identified. The hypothesis was supported by Experiment 3, which measured recall memory, with regard to time taken to complete some of the tasks but not for the number of correctly recalled positions. Experiment 4, which used the matching pairs game, supported the hypothesis in terms of both time taken and the number of moves required. It is concluded that the deaf-blind people's tactile encoding is more efficient than that of sighted-hearing people, and that it is probable that their storage and retrieval are normal. | 10.1111/1467-9450.00270 |
pubmed_887_8563 | A 70 year old patient with malignant hypertension due to bilateral renal artery disease developed acute renal failure within 36 hrs of starting an angiotensin converting enzyme (ACE) inhibitor. Review of the consecutive series of 14 patients with bilateral renal artery disease who had also been given ACE inhibitors showed that functional renal sufficiency was common but not invariable under these circumstances. Although renal function returned towards pretreatment levels in most cases when ACE inhibitors were withdrawn, the speed with which acute renal failure may occasionally develop suggests that renal artery disease should be excluded before prescribing ACE inhibitors for hypertensive patients with undiagnosed renal impairment. | pubmed_887_8563 |
pubmed_632_11004 | Shrimp, as invertebrates, have an open vasculature that allows circulating hemocytes to infiltrate the tissues, where they are referred to as sessile hemocytes. Sessile hemocytes are known to express immune-related genes, but it is not known whether their functions differ from those of circulating hemocytes. To answer this question, we enriched them from suspensions of different tissues using discontinuous density gradient centrifugation and analyzed their transcripts by RNA-seq. The results suggest that circulating hemocytes and sessile hemocytes of the gills are in a state that could react quickly to pathogens, immune-related genes expression of sessile hemocytes differ from circulating hemocytes, and the gills, heart and lymphoid organs have cells that express immune-related genes that are different from hemocytes. | 10.1016/j.fsi.2018.04.036 |
pubmed_438_12534 | Seven patients underwent release of the piriformis from the femur. Patients with residual symptoms after conservative treatment had dramatic relief of sciatica and 70% resumed customary work after surgery. Minimum follow-up was 31 months (average: 51 months). Early diagnosis can avoid prolonging ineffective empiric treatment and disability with satisfactory results achieved in most patients by conservative treatment and relief of sciatica in selected surgical cases. | 10.3928/0147-7447-20020801-12 |
pubmed_389_18037 | Laparoscopic ovariectomy was performed in two Asiatic black bears ( Ursus thibetanus ). Bears were placed in a 20° Trendelenburg position on a surgical table. A three-portal technique was used. A camera port was established 10 cm caudal to the umbilicus with a 5-mm cannula. Two instrument ports were made 1 cm caudal to the umbilicus with a 5-mm cannula and 8 cm caudal to the camera port with a 12-mm cannula, respectively. The suspensory ligament, ovarian vasculature, and uterine horn tip were progressively dissected following coagulation with the Sonicision™ cordless ultrasonic dissection device. The resected ovary was exteriorized through the 12-mm instrument portal site but enlarged to a 2-cm incision length. The abdominal musculature, subcutaneous tissue, and skin of the portal sites were closed separately. Total surgical time was 113 min (Bear A) and 49 min (Bear B), and no postoperative complications were encountered. This is the first report of laparoscopic ovariectomy in the Asiatic black bear. | 10.1638/2015-0082.1 |
pubmed_1140_16675 | Three fowl adenovirus 4 (FAV4) isolates from chicken and one from quail, all from Tamil Nadu, India were analyzed. The L1 loop variable region of hexon gene of these isolates was amplified by PCR and sequenced. The nucleotide sequences (442 bp) and deduced amino acid sequences of the four isolates were compared with those of other isolates of FAV4. The nucleotide sequences of the four isolates had a 98% homology with other Indian isolates and a 96% homology with Belgian and Russian isolates. The amino acid sequences of the four Indian isolates had a more than 98% homology with other Indian isolates and a more than 92% homology with Belgian and Russian isolates. Hence, the variable of L1 loop region of hexon gene was found to be highly homologous in all the FAV4 isolates tested both at nucleotide and amino acid level. | pubmed_1140_16675 |
pubmed_321_1206 | The quality of kiwifruit became worse as a result of the abuse of plant growth regulators (PGRs). The safety of the fruits treated with PGRs also worried consumers. Therefore, the present study analyzed the structure of thidiazuron [TDZ, (1-phenyl-3-(1,2,3-thidiazol-5-yl)-urea)] (1) and its metabolites of biotransformation in kiwifruits using liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS). Standard compounds were also synthesized and used for structural identification of those metabolites. In addition, cytotoxicity of TDZ and its metabolites was tested through sulforhodamine B assays against normal Chinese hamster ovary (CHO) cells. Four metabolites were identified. They were 4-hydroxy-thidiazuron (2), 3-hydroxy-thidiazuron (3), thidiazuron-4-O-β-d-glucoside (4), and thidiazuron-3-O-β-d-glucoside (5). Values of IC50 of compounds 1, 2, and 3 to CHO cells were 18.3 ± 1.8, 37.56 ± 1.5, and 23.36 ± 1.59 μM, respectively. Compounds 4 and 5 had no effect on CHO cells. | 10.1021/acs.jafc.7b03522 |
pubmed_926_2300 | The vast majority of streptococci colonizing the human upper respiratory tract are commensals, only sporadically implicated in disease. Of these, the most pathogenic is Mitis group member, Streptococcus pneumoniae Phenotypic and genetic similarities between streptococci can cause difficulties in species identification. Using ribosomal S2-gene sequences extracted from whole-genome sequences published from 501 streptococci, we developed a method to identify streptococcal species. We validated this method on non-pneumococcal isolates cultured from cases of severe streptococcal disease (n = 101) and from carriage (n = 103), and on non-typeable pneumococci from asymptomatic individuals (n = 17) and on whole-genome sequences of 1157 pneumococcal isolates from meningitis in the Netherlands. Following this, we tested 221 streptococcal isolates in molecular assays originally assumed specific for S. pneumoniae, targeting cpsA, lytA, piaB, ply, Spn9802, zmpC and capsule-type-specific genes. Cluster analysis of S2-sequences showed grouping according to species in line with published phylogenies of streptococcal core genomes. S2-typing convincingly distinguished pneumococci from non-pneumococcal species (99.2% sensitivity, 100% specificity). Molecular assays targeting regions of lytA and piaB were 100% specific for S. pneumoniae, whereas assays targeting cpsA, ply, Spn9802, zmpC and selected serotype-specific assays (but not capsular sequence typing) showed a lack of specificity. False positive results were over-represented in species associated with carriage, although no particular confounding signal was unique for carriage isolates. | 10.1098/rsob.170074 |
pubmed_1038_12629 | A survey of the collective experience reveals that between 1976 and 1990, a sutureless intraluminal prosthesis was used to replace the ascending thoracic aorta, arch, and descending thoracic aorta in 122, 14, and 81 patients, respectively. During these 217 operations, at least 364 of the 434 anastomoses were performed by sutureless fixation. The underlying disease processes consisted of acute and chronic dissections; atherosclerotic, Marfan's, and mycotic aneurysms; and intraoperative disruptions of the ascending aorta. The data in the literature suggest that sutureless fixation shortens aortic cross-clamp time and reduces blood loss. Early graft-related complications were few and probably can be further reduced by improving surgical techniques. The incidence of paraplegia and renal failure after descending aortic grafting was identical at 2.5%. The operative mortality rate for ascending aortic, arch, and descending aortic replacement was 13.1%, 42.9%, and 14.8%, respectively. Long-term follow-up of 143 patients revealed satisfactory graft function with three possible device-related deaths and no other known complications attributable to the prosthesis. There are, however, anecdotal references to late complications from the intraluminal prosthesis. Most of these relate to faulty implantation techniques, but some could be due to flaws inherent in the concept of sutureless grafting. The collective experience suggests that grafting of the thoracic aorta is less hazardous with the sutureless than with the conventional sutured anastomosis technique. The implications of the anecdotal accounts about late complications remain to be determined. | 10.1016/0003-4975(92)91475-o |
pubmed_637_13313 | In the present study, microwave assisted extraction (MAE) was applied as an efficient, green and rapid approach to prepare the aqueous extract of Suaeda aegyptiaca (SA) plant. The obtained aqueous extracts at two different irradiation power (90 and 270W; 15min) in MAE process as well as maceration method (24h) were used in a green and eco-friendly approach for the synthesis of zinc oxide nanoparticles (ZnO NPs). The synthesized ZnO NPs have been characterized via different techniques including UV-Vis absorption; fluorescence and Fourier transform infrared (FT-IR) spectroscopices, scanning electron microscopy (SEM), and X-ray diffraction (XRD). According to the results, the average size of the prepared ZnO particles was estimated around 60nm. A broad absorption band around 382nm in UV-Vis absorption spectrum and a maximum emission at wavelength of 458nm in fluorescence spectrum clarified the successful biosynthesis of ZnO NPs. Moreover, the biological properties of the extracts and biosynthesized ZnO NPs were investigated by antimicrobial tests (i.e. Well-diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) tests), antifungal and antioxidant tests (total phenolic and flovonoid content, antioxidant activity against dipheny-picrylhydrazyl (DPPH), and ethylbenzothiazolin-6sulphonic acid (ABTS+)). Finally, DNA cleavage potential of the samples was studied, too. | 10.1016/j.msec.2017.03.090 |
pubmed_827_5607 | RATIONALE
A growing number of studies suggest that gamma-aminobutyric acid type-B (GABA(B)) receptor agonists reduce alcohol use and craving.
OBJECTIVES
This study was designed to further clarify behavioral mechanism(s) by which GABA(B) agonists may decrease alcohol reinforcement.
METHODS
Male C57BL/6 J mice were trained to lever press on a concurrent schedule of ethanol (10% v/v) and water reinforcement during 16-h overnight sessions. Effects of the GABA(B) agonist baclofen (0-17 mg/kg, IP) or SKF 97541 (0-1 mg/kg, IP) were examined on parameters of self-administration. Subsequently, potential motor inhibition and interaction with ethanol-induced sedation by GABA(B) agonists was examined in ethanol naive and self-administering mice.
RESULTS
Baclofen (10 mg/kg) and SKF 97541 (0.3 mg/kg) reduced ethanol-reinforced responding. In a locomotor activity test, these doses of the GABA(B) agonists inhibited locomotion in the ethanol-experienced mice and in a group of ethanol-inexperienced mice; locomotor suppression was greater in the ethanol-inexperienced mice. These doses of the GABA(B) agonists also potentiated the sedative effects of ethanol (4 g/kg) and converted a nonsedative dose of ethanol (2 g/kg) into a fully sedative dose. GABA(B) agonist enhancement of the sedative effects of ethanol was less pronounced in ethanol self-administering mice, suggesting cross-tolerance at the low dose of ethanol.
CONCLUSIONS
GABA(B) agonists decrease the reinforcing effects of ethanol at doses that inhibit locomotor activity and potentiate the sedative hypnotic effects of ethanol. These nonspecific effects of GABA(B) agonists were reduced in alcohol experienced mice, suggesting cross-tolerance to the inhibitory properties of GABA(B) positive modulation. These data question the safety of prescribing GABA(B) agonists to alcoholics since these drugs may potentiate ethanol's sedative/hypnotic effects during relapse. | 10.1007/s00213-003-1769-3 |
pubmed_922_11048 | Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and mortality of individual patients based on the degree of lung function impairment, nor does the degree of airflow limitation allow guidance regarding therapies. Over the last decades, understanding of the factors contributing to the heterogeneity of disease trajectories, clinical presentation, and response to existing therapies has greatly advanced. Indeed, diagnostic assessment and treatment algorithms for COPD have become more personalized. In addition to the pulmonary abnormalities and inhaler therapies, extra-pulmonary features and comorbidities have been studied and are considered essential components of comprehensive disease management, including lifestyle interventions. Despite these advances, predicting and/or modifying the course of the disease remains currently impossible, and selection of patients with a beneficial response to specific interventions is unsatisfactory. Consequently, non-response to pharmacologic and non-pharmacologic treatments is common, and many patients have refractory symptoms. Thus, there is an ongoing urgency for a more targeted and holistic management of the disease, incorporating the basic principles of P4 medicine (predictive, preventive, personalized, and participatory). This review describes the current status and unmet needs regarding personalized medicine for patients with COPD. Also, it proposes a systems medicine approach, integrating genetic, environmental, (micro)biological, and clinical factors in experimental and computational models in order to decipher the multilevel complexity of COPD. Ultimately, the acquired insights will enable the development of clinical decision support systems and advance personalized medicine for patients with COPD. | 10.2147/COPD.S175706 |
pubmed_399_3000 | Clinical effect of Estracyt was investigated in prostatic cancer patients. Twenty seven patients had been previously treated and 20 had not received prior treatment. Improvement rate of subjective symptoms was 85% in the previously untreated patients and that of objective findings was 85%, while those rates were 44% and 50% in the previously treated patients, respectively. Most of the adverse reactions were changes in mamma and mammary papilla which were considered to be due to the estrogenic activity. | pubmed_399_3000 |
pubmed_585_13009 | While neighborhood deprivation is associated with prevalence of chronic diseases, it is not well understood whether neighborhood deprivation is also associated with cardiometabolic risk factors among adults with chronic disease. Subjects (n = 19,804) from the Diabetes Study of Northern California (DISTANCE) cohort study, an ethnically-stratified, random sample of members of Kaiser Permanente Northern California (KPNC), an integrated managed care consortium, with type 2 diabetes who completed a survey between 2005 and 2007 and who lived in a 19 county study area were included in the analyses. We estimated the association between a validated neighborhood deprivation index (NDI) and four cardiometabolic risk factors: body mass index (BMI = kg/m2), glycosylated hemoglobin (A1c), low density lipoproteins (LDL) and systolic blood pressure (SBP) using multi-level models. Outcomes were modeled in their continuous form and as binary indicators of poor control (severe obesity: BMI ≥35, poor glycemic control: A1c ≥9%, hypercholesterolemia: LDL ≥130 mg/dL, and hypertension: SBP ≥140 mmHg). BMI, A1c and SBP increased monotonically across quartiles of NDI (p < 0.001 in each case); however, LDL was significantly associated with NDI only when comparing the most to the least deprived quartile. NDI remained significantly associated with BMI and A1c after adjusting for individual level factors including income and education. A linear trend (p < 0.001) was observed in the relative risk ratios for dichotomous indicators of severe obesity, poor glycemic control, and 2 or more poorly controlled cardiometabolic risk factors across NDI quartile. In adjusted models, higher levels of neighborhood deprivation were positively associated with indicators of cardiometabolic risk among adults with diabetes, suggesting that neighborhood level deprivation may influence individual outcomes. However, longitudinal data are needed to test the causal direction of these relationships. | 10.1016/j.socscimed.2011.11.036 |
pubmed_647_6064 | OBJECTIVE
To explore the metabolic transformation and the absorbed metabolites of ophiopognin saponin D' (OD') given orally in rats.
METHOD
The contents of both original OD' and its metabolites were detected by means of HPLC-ELSD and the metabolites of OD' in blood and urine were measured by use of TLC and HPLC-MS in vivo.
RESULT
OD' could be metabolized by intestinal bacteria in rats. The content of diosgenin, one of the metabolites, increased gradually as the time passed.
CONCLUSION
OD' can be metabolized in intestine of rat and its metabolite, diosgenin, was absorbed in blood of rat. | pubmed_647_6064 |
pubmed_1123_16133 | The extreme cold and aridity of the Antarctic McMurdo Dry Valleys have led to the longstanding belief that metabolic rates of soil microbiota are negligible, and that ecosystem changes take place over millennia. Here we report the first direct experimental evidence that soil microbial communities undergo rapid and lasting changes in response to contemporary environmental conditions. Mummified seals, curious natural artifacts found scattered throughout Dry Valleys, alter their underlying soil environment by stabilizing temperatures, elevating relative humidity and reducing ultraviolet exposure. In a unique, multi-year mummified seal transplantation experiment, we found that endemic Dry Valley microbial communities responded to these changes within 3 years, resulting in a sevenfold increase in CO(2) flux and a significant reduction in biodiversity. These findings challenge prevailing ideas about Antarctic Dry Valley ecosystems and indicate that current and future environmental conditions may strongly influence the ecology of the dominant biota in the Dry Valleys. | 10.1038/ncomms1645 |
pubmed_203_1738 | ENTROPY index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.5 and 19.0 microg.ml(-1) plasma drug concentrations of propofol. Spectral entropy from the frequency band 0.8-32 Hz was calculated and cerebral blood flow assessed using positron emission tomography and [(15)O]-labelled water at baseline and at each anaesthesia level. Both drugs induced significant reductions in spectral entropy and cortical and global cerebral blood flow. Midfrontal-central spectral entropy was associated with individual frontal and whole brain blood flow values across all conditions, suggesting that this novel measure of anaesthetic depth can depict global changes in neuronal activity induced by the drugs. The cortical areas of the most significant associations were remarkably similar for both drugs. | 10.1111/j.1365-2044.2005.04289.x |
pubmed_703_10525 | The question, 'Does religion (or spirituality) cause physical health benefits?' may be given at least four diverging interpretations in terms of causal path diagrams. In common usage, the question may be interpreted to indicate that religion causally influences health by: (1) any mechanism, including well-established factors such as social support and improved health behaviors; (2) additional mechanisms, such as enhanced positive psychological states (e.g. faith, hope, inner peace) acting through psychoneuroimmunologic or psychoneuroendocrinologic pathways; (3) offering psychological strength for acquiring or maintaining positive health behaviors; or (4) causally influencing health by distant healing or intercessory prayer. We review historical confusion between these interpretations, arguing that disentangling them is important for collaborative health care, promotion and research. | 10.1177/1359105302007004326 |
pubmed_573_23425 | In a webchat on leg ulcer management issues, hosted by Nursing Times, participants raised three key areas of care: the role of healthcare assistants in compression bandaging; reporting and investigating damage caused by compression therapy; and recommendations for dressings to be used under compression. This article discusses each of these in turn. | pubmed_573_23425 |
pubmed_452_4949 | Nanoarchaeum equitans is a species of hyperthermophilic archaea with the smallest genome size. Its alanyl-tRNA synthetase genes are split into AlaRS-α and AlaRS-β, encoding the respective subunits. In the current report, we surveyed N. equitans AlaRS-dependent alanylation of RNA minihelices, composed only of the acceptor stem and the T-arm of tRNAAla. Combination of AlaRS-α and AlaRS-β showed a strong alanylation activity specific to a single G3:U70 base pair, known to mark a specific tRNA for charging with alanine. However, AlaRS-α alone had a weak but appreciable alanylation activity that was independent of the G3:U70 base pair. The shorter 16-mer RNA tetraloop substrate mimicking only the first four base pairs of the acceptor stem of tRNAAla, but with C3:G70 base pair, was also successfully aminoacylated by AlaRS-α. The end of the acceptor stem, including CCA-3' terminus and the discriminator A73, was able to function as a minimal structure for the recognition by the enzyme. Our findings imply that aminoacylation by N. equitans AlaRS-α may represent a vestige of a primitive aminoacylation system, before the appearance of the G3:U70 pair as an identity element for alanine. | 10.1007/s00239-020-09945-1 |
pubmed_566_310 | Polynoxylin and noxythiolin (Anaflex and Noxyflex) have been recommended for the treatment of certain bacterial infections. Both compounds were shown to release formaldehyde. Detailed studies with noxythiolin showed that it decomposed in solution to liberate most of its formaldehyde, and that solutions of formaldehyde of the appropriate strength gave zones of inhibition on seeded plates comparable in size with those given by noxythiolin. It is suggested that the effects observed with these compounds are caused by the formaldehyde released. | 10.1136/jcp.18.5.666 |
pubmed_453_16476 | This article reviews MRI techniques and results in the assessment of bone marrow in patients with lymphoma. MRI is more sensitive than blind biopsy (BB) in detecting bone marrow invasion. False-negative results have been reported in low-grade non Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia. Bone marrow imaging is particularly indicated in patients with Hodgkin's disease, high grade NHL or myelocytic leukemia, with a negative BB and abnormal clinical (stage B, bone pains) or biochemical data (elevated alkaline phosphatase) and who have relapsed. During treatment. MR imaging is a valuable tool for the evaluation of response and the diagnosis of benign bone marrow complications. Knowledge of post-therapeutic patterns is essential to avoid misinterpretations. The main drawback with this technique is its inability to differentiate residual lesions from fibrosis and needle guided-biopsy is mandatory if treatment decision-making relies on the MR result, alone. | 10.3109/10428199709042496 |
pubmed_638_11391 | Problems stemming from quantitative phase imaging from intensity measurements play a key role in many fields of physics. Techniques based on the transport of intensity equation require an estimate of the axial derivative of the intensity to invert the problem. Derivation formulas in two adjacent planes are commonly used to experimentally compute the derivative of the irradiance. Here we propose a formula that improves the estimate of the derivative by using a higher number of planes and taking the noisy nature of the measurements into account. We also establish an upper and lower limit for the estimate error and provide the distance between planes that optimizes the estimate of the derivative. | 10.1364/ao.46.007978 |
pubmed_1091_12652 | OBJECTIVE
Heart failure (HF) is a complex medical condition with a multitude of genetic and other factors being involved in the pathogenesis. Emerging evidence points to an involvement of inflammatory mechanisms at least in subgroups of patients. The same is true for depression and depressive symptoms, which have a high prevalence in HF patients and are risk factors for the development and outcomes of cardiovascular disease.
METHODS
In 936 patients of the Interdisciplinary Network Heart Failure (INH) program, CRP and IL-6 protein blood levels were measured and genetic variants (single nucleotide polymorphisms) of the CRP and IL6 gene analyzed regarding their influence on mortality.
RESULTS
Less common recessive genotypes of two single nucleotide polymorphisms in the CRP gene (rs1800947 and rs11265263) were associated with significantly higher mortality risk (p < 0.006), higher CRP levels (p = 0.029, p = 0.006) and increased depressive symptoms in the PHQ-9 (p = 0.005, p = 0.003). Variants in the IL-6 gene were not associated with mortality.
CONCLUSION
Our results hint towards an association of less common CRP genetic variants with increased mortality risk, depressive symptoms and peripheral CRP levels in this population of HF patients thereby suggesting a possible role of the inflammatory system as link between poor prognosis in HF and depressive symptoms. | 10.1016/j.bbi.2018.04.002 |
pubmed_648_141 | The United States' criminal justice system has seen exponential growth in costs related to the incarceration of persons with mental illness. Jails, prisons, and state hospitals' resources are insufficient to adequately treat the sheer number of individuals cycling through their system. Reversing the cycle of criminalization of mental illness is a complicated process, but mental health diversion programs across the nation are uniquely positioned to do just that. Not only are these programs providing humane treatment to individuals within the community and breaking the cycle of recidivism, the potential fiscal savings are over 1 billion dollars. | 10.1017/S1092852919001792 |
pubmed_453_11361 | The search for the good life is used as a framework for understanding the meaning of geriatric practice to occupational therapists. Data consisted of a subset of phenomenological interviews drawn from a nationwide study of 148 occupational therapists in all areas of practice. Narratives of satisfying and dissatisfying experiences with older clients were analyzed to understand the uniqueness of therapists' lived experiences in geriatrics. The realities of practice with older clients--the settings, the meanings and symbols of continuity in old age, and the older client's uncertain future--merge to create an uncertain ideology in geriatric occupational therapy. We suggest that a fundamental task of occupational therapists in geriatrics, as they seek the good life for themselves and their older clients, is to reconcile the realities of practice with traditional rehabilitation ideologies by redefining themselves and their roles in practice. | 10.5014/ajot.51.2.132 |
pubmed_371_16037 | Xenopus lamin A and a lamin A mutant lacking the complete 280 amino acid long carboxy-terminal tail were expressed in bacteria and purified from inclusion bodies. Electron microscopic analysis of lamin A dimers revealed that the carboxy-terminal 280 amino acids correspond to the globular domain seen in rotary-shadowed wild-type lamin and that the rodlike domain consists of the short non-helical amino terminus and the alpha-helical region. During reconstitution lamin A dimers first formed polar head to tail aggregates which then associated laterally resulting in paracrystals with periodic repeats of 25 nm. In the mutant, the longitudinal and lateral association of dimers had not been influenced, however, periodic repeats were absent in the filament bundles formed. Thus our data clearly demonstrate that carboxy-terminal tails are localized in light-stained regions of negatively stained paracrystals and that they are responsible for the alternating light dark staining of paracrystals. Fibrils, 2 to 3 nm thick, were a common structural element of paracrystals and filament bundles. | pubmed_371_16037 |
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