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pubmed_1029_16522 | The enzymes catalyzing the NAD-dependent oxidation of malonic dialdehyde (MDA) were isolated from rat liver extracts. Upon 5'-AMP-Sepharose chromatography MDA dehydrogenase was separated into two isoforms, I and II. Isoform I was eluted from the affinity carrier with a 0.1 M phosphate buffer pH 8.0. This isoform had a broad substrate specificity towards aliphatic and aromatic aldehydes. Kinetic studies showed that short- and medium-chain aliphatic aldehydes (C2-C6) were characterized by the lowest Km values and the highest Vmax values. The Km' values for MDA and acetaldehyde were 2.8 microM and 0.69 microM, respectively. Isoform II was eluted with a 0.1 M phosphate buffer pH 8.0 containing 0.5 mM NAD, was the most active with medium- and long-chain aliphatic aldehydes (C6-C11) and had Km values for MDA and acetaldehyde equal to 37 microM and 52 microM, respectively. Isoform I was much more sensitive towards disulfiram inhibition than isoform II. Both isoforms had an identical molecular mass (93 kD) upon gel filtration. It is concluded that MDA dehydrogenase isoform I is identical to mitochondrial aldehyde dehydrogenase having a low Km for acetaldehyde, whereas isoform II may be localized in liver cytosol. The role of aldehyde dehydrogenases in the metabolism of aldehydes derived from lipid peroxidation is discussed. | pubmed_1029_16522 |
others_14_2113 | Mycobacterium paratuberculosis (MPT) is the etiologic agent of paratuberculosis. The disease is prevalent in cattle worldwide, and exacts a heavy financial toll. Effective control requires the development of acellular vaccines offering a better protection than the current available vaccines without side effects and allowing the discrimination between infected and vaccinated animals. We studied the immune response of mice to the MPT superoxide dismutase (SOD) alone or adjuvanted by Ribi. We cloned, overexpressed and purified this antigen in Escherichia coli. Spleen cells from immunized mice, after exposure to recombinant MPT SOD (MPT rSOD), produced significant levels of IFNγ, TNFα and IL-6. IFNγ and TNFα production was increased by the addition of Ribi. In contrast, low levels of NO, IL-4 and IL-10 were secreted by spleen cells culture from immunized mice. The immunoglobulin isotype distribution analysis showed that Ribi adjuvant clearly induced a significantly higher anti-MPT rSOD antibody production of all classes tested and decreased the IgG1/IgG2a ratio thus improving the Th1 response. Delayed-type hypersensitivity responses in mice footpads were observed only in mice immunized with MPT rSOD emulsified in Ribi. Vaccination of MPT rSOD emulsified with Ribi induced both a Th2 and Th1 type of immune response with the later slightly more pronounced. The results presented here on the immunogenicity of MPT SOD suggest that this antigen should be further tested as a candidate antigen for a future acellular vaccine against paratuberculosis. © 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reser | 10.1016/S0928-8244(02)00339-5 |
pubmed_1111_22706 | This study examined the cell response to a TiO2 nanotubular surface (Ti-NT) for future biomedical applications. The level of cell attachment and spreading at 20 min and 60 min was evaluated by SEM. IL-6 and PGE2 secretion was evaluated by ELISA. In SEM analysis, the Ti-NT surface had more fully spread cells compared to the machined titanium surface (Ti-S). ELISA revealed that the level of IL-6 and PGE2 production was higher on the Ti-NT than on the Ti-S. These results suggest that a surface treatment with a nanotubular TiO2 surface enhances the early osteoblast responses, such as cell spreading and cytokine release, which are important for subsequent cell functions and bone healing in vivo. | 10.1166/jnn.2011.3413 |
pubmed_661_11559 | In preparation for an efficacy study, the effect of the low molecular weight heparinoid Org 10172 on postoperative blood loss was assessed in a randomized double-blind, placebo controlled study in patients undergoing transurethral resection of the prostate (TURP). Org 10172 and placebo were given twice daily as i.v. injection for three postoperative days starting one hour preoperatively. Three doses of Org 10172 (800, 1600, and 2400 anti-Xa units b.d.) were evaluated against placebo in three consecutive patient blocks respectively. Each block consisted of 20 patients, 15 receiving Org 10172 and 5 patients placebo. The study was discontinued after 9 patients of the third block had completed the protocol because of excessive urinary blood loss. Data analysis showed a dose-dependent increase in postoperative haemoglobin loss, this was not significant for the 800 anti-Xa units b.d. dosage but was significant in those patients treated with 1600 (p less than 0.05) and 2400 anti-Xa units b.d. (p less than 0.01). It was concluded that the heparinoid Org 10172 caused a dose dependent increase in urinary blood loss following TURP. | pubmed_661_11559 |
pubmed_286_11024 | Previous data have demonstrated that mesenchymal stem cells (MSCs) can exert immunomodulatory activity in vitro, in which of the process nearly all kinds of immune cell subsets are involved. However, there is still a paucity of information about whether and why MSCs inhibit the ongoing immune responses in vivo. Working in a murine splenocyte transfusion model across the major histocompatibility barrier (C57BL/6 → BALB/c, H2b → H2d), we have found that MSC coinfusion prolongs the mean survival time (MST) of the recipient mice in a dose-dependent manner and reduces graft-versus-host-associated histopathology in comparison to the allosplenocyte transfusion controls. In vivo eGFP tracing with polymerase chain reaction analysis revealed that grafted MSCs could migrate and settle into the lungs, spleen, liver, intestine, and skin shortly after administration. Further investigations into the functional characteristics of intrasplenic lymphocytes showed that their proliferation and cytotoxic activity against P815 cells (H2d) were significantly restrained by MSC cotransfer. FACS analysis demonstrated that MSC infusion not only increased the proportion of CD4+ subset but also decreased that of CD8+ cells at the belated observation points, resulting in the increase of the ratio of CD4+/CD8+ cells. Also, in contrast to the slight increase of the proportion of CD4+CD25+ T regulatory cells (Tregs) in MSC cotransfer mice, the ratio of Tregs/CD8+ cells was dramatically elevated. Furthermore, RT-PCR analysis on the cytokine array of IL-2, IL-4, IL-12, TNF-α, and TGF-β in recipient splenocytes implied the Th1 to Th2 polarization. Therefore, it is deducible that alteration in the proportions of different T-lymphocyte subsets may be one of the main mechanisms by which grafted MSCs suppress the ongoing immune responses in vivo. The study here might provide some new clues for the design of therapeutic approaches for MSC transplantation. | 10.3727/000000007783464470 |
pubmed_326_3807 | In this paper the main aspects of characterization, handling and applications of liposomes are presented. In the last 25 years much attention has been focused to liposomal systems for optimization of the drug targeting. Several pathways to optimize the drug action of liposomes in various situations as cancer, microbial therapy, vaccines, oral therapy and diagnosis were tested. Certain applications of liposomes especially those implying the phagocytic cells sustain a real interest for industrial applications. | pubmed_326_3807 |
pubmed_72_9269 | Plant viruses depend on the host translational machinery to establish their infectious cycle. In a recent Nature publication, Zorzatto et al. (2015) highlight the suppression of the protein synthesis process as an antiviral defense mechanism in plants. | pubmed_72_9269 |
pubmed_390_13551 | beta-Phenylethylamine (PEA) is an endogenous constituent of human, rat and other mammalian brain tissue. It is rapidly metabolised by type B monoamine oxidase, and there is evidence for specific binding sites for PEA in rat brain. In the first experiment, the effects of systemically-administered PEA (3.125-50.0 mg/kg) on water consumption in water deprived male rats were investigated. PEA produced a depression of drinking within the first 15 min following its administration, with a strong linear relation between drug dose and the degree of depression. In the following 45 min, there was evidence of a dose-related recovery in the drinking. In the second experiment, the effects of PEA on activity in water-deprived rats were investigated. PEA at 12.5 m/kg produced behavioral stimulation, which was particularly evident in measures of total horizontal activity. At higher doses, 25.0 and 50.0 mg/kg, PEA induced a behavioral stereotypy syndrome, associated with a depression of horizontal and vertical activities. Relationships between the hypodipsic effect of PEA and its ability to produce psychomotor stimulation at a moderate dose level, and stereotypy at higher dose levels are considered. | 10.1016/0091-3057(84)90092-3 |
pubmed_189_9964 | BACKGROUND
Gallbladder carcinoma (GBC) is a relatively rare but highly aggressive cancer with late clinical detection and a poor prognosis. However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies.
METHODS
We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole-exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC-101 and CUDC-907, were evaluated in vitro and in vivo.
RESULTS
The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single-cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K/HDAC inhibitor CUDC-907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids.
CONCLUSIONS
Patient-derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs. | 10.1002/ctm2.678 |
pubmed_1090_15531 | Previous results from our laboratory have shown with intra-axonal recordings that hindfoot cutaneous primary afferents are subjected to rhythmic depolarizations during fictive locomotion (L-PAD) suggesting that cutaneous presynaptic mechanisms are activated by the central locomotor program. In this study, we examined the transmission in pathways responsible for primary afferent depolarizations (PAD) of cutaneous fibres during spontaneous fictive locomotion in decorticate cats and in spinal cats injected with nialamide and L-DOPA. PADs were evoked (E-PADs) by electrical stimulation of peripheral nerves and recorded intra-axonally with micropipettes in identified superficialis peroneal (SP; n = 7) and tibialis posterior (TP; n = 17) cutaneous primary afferents. Results showed that the amplitude of E-PADs, which were superimposed on the L-PAD, was deeply modulated throughout the locomotor cycle; decreasing to reach a minimum during the flexor phase and increasing to a maximum during the extensor phase. The results were not statistically different in fibres of the two nerves and in both types of preparation. The amplitude of E-PADs was always maximum during the extensor phase whether there was a large L-PAD or not during that phase. This suggests that the presynaptic mechanisms activated by central locomotor networks (L-PAD) and those activated by peripheral inputs (E-PAD) may in part be controlled differently. The results thus show that the transmission in PAD pathways activated by cutaneous inputs is phasically modulated by the central pattern generator for locomotion. This strongly suggests that the presynaptic inhibition in cutaneous fibres evoked by the movement-related feedback during real locomotion could be similarly modulated. | 10.1016/0006-8993(90)90334-8 |
pubmed_665_6390 | INTRODUCTION
Neuropsychiatry, which is the point where neurology and psychiatry meet, together with other neighbouring disciplines (psychology, anthropology, neurochemistry, neurophysiology, and so forth), are committed to unravelling both the psychopathological definition and the anatomical-physiological foundations of mental symptoms (signs).
DEVELOPMENT
This work attempts to review several moments in the history of the localisation of neurology and the difficulties involved in accomplishing a systematisation of mental symptoms.
CONCLUSIONS
Further knowledge of this delicate matter--the mind, or more specifically, the sick brain-mind complex--can only be gained by cooperation in a number of different areas (clinical, psychological, philosophical, biochemical, imaging, and so forth). | pubmed_665_6390 |
pubmed_573_13664 | Soil nematode community response to treatments of three, four-year crop rotations (spring wheat-pea-spring wheat-flax, spring wheat-green manure-spring wheat-flax, and spring wheat-alfalfa-alfalfa-flax) under conventional and organic management, and native tall grass restoration (restored prairie) were assessed in June 2003, and July and August 2004. The research site was the Glenlea Long-term Rotation and Crop Management Study, in the Red River Valley, Manitoba, established in 1992. The nematode community varied more with sample occasion than management and rotation. The restored prairie favored high colonizer-persister (c-p) value omnivores and carnivores, and fungivores but less bacterivores. The restored prairie soil food web was highly structured, mature and low-to-moderately enriched as indicated by structure (SI), maturity (MI) and enrichment (EI) index values, respectively. Higher abundance of fungivores and channel index (CI) values suggested fungal-dominated decomposition. Nematode diversity was low even after more than a decade of restoration. A longer time may be required to attain higher diversity for this restored fragmented prairie site distant from native prairies. No consistent differences were found between organic and conventional management for nematode trophic abundance, with the exception of enrichment opportunists of the c-p 1 group which were favored by conventional management. Although EI was lower and SI was higher for organic than conventional their absolute values suggested decomposition channels to be primarily bacterial, and fewer trophic links with both management scenarios. A high abundance of fungivores in the rotation including the green manure indicates greater fungal decomposition. | pubmed_573_13664 |
pubmed_558_16439 | The experimental system consisted of anoxic filter and aerobic suspended carrier biofilm reactor. The partial nitrification was achieved and maintained stably in the aerobic reactor under normal temperature (15-29 degrees C) and high DO (6-9 mg/L). The nitritation with 70%-80% nitrite accumulation efficiency was obtained when FA concentration was in the range of 1.0-10.3 mg/L by controlling influent ammonia loading rate (ALR), ratio of alkalinity and ammonia and HRT in the aerobic reactor. The effluent nitrite/ammonia ratio was about 1.25 when the average influent ammonia, influent ALR and influent ratio of alkalinity and ammonia were 315.80 mg/L, 0.43 kg/(m3 x d) and 5.25, respectively. So the effluent of partial nitrification process provided the influent substrate demand for the following ANAMMOX process. The integrative analysis indicated that the proper FA concentration was the main factor achieving the partial nitrification. The study developed a novel partial nitrification technology adapt to water characteristics of digested sludge liquor. | pubmed_558_16439 |
pubmed_712_4929 | The presumptive ventral blood islands were reciprocally transplanted between chromosomally labelled 72-hour-old leopard frog embryos. At 10 days of development, the differentiating epithelial thymus glands were surgically removed. Following metamorphosis, the spleen and bone marrow from juvenile frogs were analysed cytophotometrically. During normal ontogeny, the vast majority of peripheral lymphocytes are derived from the thymus, not the ventral blood islands. In the absence of the thymus, the ventral blood islands made the major lymphocyte contribution to the peripheral lymphoid organs. Thus, removal of the thymus appears to initiate an alternate pathway of lymphocyte differentiation in the leopard frog. | pubmed_712_4929 |
pubmed_186_9384 | It is often important to include prestress in computational models of biological tissues. The prestress can represent residual stresses (stresses that exist after the tissue is excised from the body) or in situ stresses (stresses that exist in vivo, in the absence of loading). A prestressed reference configuration may also be needed when modeling the reference geometry of biological tissues in vivo. This research developed a general framework for representing prestress in finite element models of biological materials. It is assumed that the material is elastic, allowing the prestress to be represented via a prestrain. For prestrain fields that are not compatible with the reference geometry, the computational framework provides an iterative algorithm for updating the prestrain until equilibrium is satisfied. The iterative framework allows for enforcement of two different constraints: elimination of distortion in order to address the incompatibility issue, and enforcing a specified in situ fiber strain field while allowing for distortion. The framework was implemented as a plugin in FEBio (www.febio.org), making it easy to maintain the software and to extend the framework if needed. Several examples illustrate the application and effectiveness of the approach, including the application of in situ strains to ligaments in the Open Knee model (simtk.org/home/openknee). A novel method for recovering the stress-free configuration from the prestrain deformation gradient is also presented. This general purpose theoretical and computational framework for applying prestrain will allow analysts to overcome the challenges in modeling this important aspect of biological tissue mechanics. | 10.1016/j.jmbbm.2016.04.012 |
pubmed_43_3377 | School closure and distance learning during the COVID-19 pandemic have posed several challenges to children. Drawing upon the social-ecological framework, in this preliminary study, we tested what factors may help to explain students' difficulties with distance learning during COVID-19 lockdown, by analyzing family, school, and individual variables. The final sample included 183 Italian middle-school students (97 girls and 86 boys; Mage = 11 years, 9 months; SDage = 8 months; range: 11-14 years), who completed online surveys before the pandemic (November 2019) and during lockdown (May 2020). Key findings indicate that students who showed fewer difficulties with distance learning reported a more positive family climate, a better relationship with their teachers, and were more able to regulate their emotions in stressful situations. The educational and policy implications of these findings are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved). | 10.1037/spq0000437 |
pubmed_200_18583 | BACKGROUND
Non-infectious uveitis represents one of the most common causes of blindness, even at pediatric age; in particular, idiopathic chronic uveitis can pose significant difficulties during treatment, due to a partial response to TNF-α antagonists. To date, very few case series exist describing the treatment of idiopathic uveitis not adequately controlled by TNF-α antagonists. The aim of our study is to describe the role of abatacept in achieving remission in patients with idiopathic uveitis previously treated with TNF-α antagonists, and to assess how long abatacept efficacy is maintained during follow-up. The treatment's safety profile and tolerability were also specifically investigated.
METHODS
Three patients affected with chronic idiopathic uveitis, who have been treated with abatacept due to loss of efficacy of TNF-α antagonists, were reviewed. Details of the demographic and clinical characteristics were recorded, and a summary of the medical history was obtained. Patients were regularly reviewed in the ophthalmology and rheumatology clinics. Assessment of their ocular condition was characterized according to the Standardization of Uveitis Nomenclature (SUN) group.
RESULTS
In our patients, abatacept was able to induce remission and to discontinue systemic corticosteroids after a mean of 30 weeks; the drug maintained its efficacy through a long follow-up period (42, 33, and 18 months respectively), with an excellent safety profile.
CONCLUSION
Our small case series seems to suggest abatacept to be a promising therapy in children affected with chronic idiopathic uveitis not adequately controlled by TNF-α antagonists. | 10.1007/s00417-015-3140-x |
pubmed_718_383 | Major advances have been made that make it necessary to revise our thinking about the mechanisms of neuronal control to regulate cardiac functions, and that have implications for our understanding of cardiac diseases and their treatment. These advances include: function-specific pathways, co-transmitters, neuromodulators, sensory-efferent functions, changes in expression of autonomic nerves, neuroeffector junctions, and subtypes of neurotransmitter receptors. Studies of the molecular structure of the superfamily of the cation amine receptors have revealed that there might be a common ancestral G-protein coupled receptor to be derived from. Although noradrenaline effectively stimulates alpha 1- and alpha 2-adrenoceptors, they are completely different as a beta-adrenoceptors subfamily. The possible subtypes of beta 1-adrenoceptors are discussed in relation with the treatment of cardiac failure. | pubmed_718_383 |
pubmed_997_2822 | The seedlings of purple leafed rice (SPLR) are characterized by high contents of anthocyanins and various polyphenols, whose total anthocyanin content can reach 15.16 mg g-1, indicating that SPLR may have many bioactivities. Therefore, in order to evaluate the anti-obesity potential value of SPLR, the nutrient components were first identified, and the anti-obesity effect of SPLR was evaluated with a high-fat diet (HFD) induced obese mouse model for 12 weeks. The results demonstrated that SPLR supplementation could alleviate HFD-induced obesity and suppress pro-inflammatory cytokine production and macrophage infiltration in epididymal white adipose tissue of HFD-induced obese mice. The findings indicated that supplementation with SPLR may contribute to preventing obesity and related complications. | 10.1039/d2fo02374a |
pubmed_1033_10367 | Serine/threonine/tyrosine (STY) protein kinase from peanut is developmentally regulated and is induced by abiotic stresses. In addition, STY protein kinase activity is regulated by tyrosine phosphorylation. Kinetic mechanism of plant dual specificity protein kinases is not studied so far. Recombinant STY protein kinase occurs as a monomer in solution as shown by gel filtration chromatography. The relative phosphorylation rate of kinase against increasing enzyme concentrations follows a first-order kinetics indicating an intramolecular phosphorylation mechanism. Moreover, the active recombinant STY protein kinase could not transphosphorylate a kinase-deficient mutant of STY protein kinase. Molecular docking studies revealed that the tyrosine kinase inhibitors bind the protein kinase at the same region as ATP. STY protein kinase activity was inhibited by the tyrosine kinase inhibitors, and the inhibitor potency series against the recombinant STY protein kinase was tyrphostin > genistein > staurosporine. The inhibition constant (K(i)), and the IC(50) value of STY protein kinase for tyrosine kinase inhibitors with ATP and histone are discussed. All the inhibitors competed with ATP. Genistein was an uncompetitive inhibitor with histone, whereas staurosporine and tyrphostin were linear mixed type noncompetitive inhibitors with histone. Molecular docking and kinetic analysis revealed that Y148F mutant of the "ATP-binding loop" and Y297F mutant of the "activation loop" showed a dramatic increase in K(i) values for genistein and tyrphostin with respect to wild-type STY protein kinase. Data presented here provide the direct evidence on the mechanism of inhibition of plant protein kinases by tyrosine kinase inhibitors. This study also suggests that tyrosine kinase inhibitors may be useful in unraveling the plant tyrosine phosphorylation signaling cascades. | 10.1021/bi0497042 |
pubmed_726_18359 | OBJECTIVES
To assess the association between mortality and the day of elective surgical procedure.
DESIGN
Retrospective analysis of national hospital administrative data.
SETTING
All acute and specialist English hospitals carrying out elective surgery over three financial years, from 2008-09 to 2010-11.
PARTICIPANTS
Patients undergoing elective surgery in English public hospitals.
MAIN OUTCOME MEASURE
Death in or out of hospital within 30 days of the procedure.
RESULTS
There were 27,582 deaths within 30 days after 4,133,346 inpatient admissions for elective operating room procedures (overall crude mortality rate 6.7 per 1000). The number of weekday and weekend procedures decreased over the three years (by 4.5% and 26.8%, respectively). The adjusted odds of death were 44% and 82% higher, respectively, if the procedures were carried out on Friday (odds ratio 1.44, 95% confidence interval 1.39 to 1.50) or a weekend (1.82, 1.71 to 1.94) compared with Monday.
CONCLUSIONS
The study suggests a higher risk of death for patients who have elective surgical procedures carried out later in the working week and at the weekend. | pubmed_726_18359 |
pubmed_1030_22966 | Nowadays, the bakery industry includes different bioactive ingredients to enrich the nutritional properties of its products, such as betalains from red beetroot (Beta vulgaris). However, cereal products are considered a major route of exposure to many mycotoxins, both individually and in combination, due to their daily consumption, if the cereals used contain these toxins. Only the fraction of the contaminant that is released from the food is bioaccessible and bioavailable to produce toxic effects. Foods with bioactive compounds vary widely in chemical structure and function, and some studies have demonstrated their protective effects against toxics. In this study the bioaccessibility and bioavailability of three legislated mycotoxins (AFB1, OTA and ZEN), individual and combined, in two breads, one with wheat flour and the other with wheat flour enriched with 20% Beta vulgaris, were evaluated. Bioaccessibility of these three mycotoxins from wheat bread and red beet bread enriched individually at 100 ng/g was similar between the breads: 16% and 14% for AFB1, 16% and 17% for OTA and 26% and 22% for ZEN, respectively. Whereas, when mycotoxins were co-present these values varied with a decreasing tendency: 9% and 15% for AFB1, 13% and 9% for OTA, 4% and 25% for ZEN in wheat bread and in red beet bread, respectively. These values reveal that the presence of other components and the co-presence of mycotoxins can affect the final bioavailability; however, it is necessary to assess this process with in vivo studies to complete the studies. | 10.3390/toxins14080540 |
pubmed_777_13497 | Long-term efficacy of acetyl-cholinesterase-inhibitor (ACHEI) treatment in mild-to-moderate Alzheimer's disease (AD) is of great relevance for clinical routine and has been investigated over a 21-month period of treatment in a "real word" population. We investigated cognitive (mini mental state examination=MMSE) and functional (instrumental activities of daily living=IADL; activities of daily living=ADL) outcomes in 427 AD patients throughout the above period. At the end of the study, first-time drug takers (naives) declined by 1.2 MMSE points, whereas non-naives by 3.8 points. Predictors of responsiveness for first-time drug takers were MMSE score at baseline and MMSE points gained at 3 months of treatment. Further investigations are needed to shed light on the characteristics of responsiveness to a tailored ACHEI treatment for dementia. | 10.1016/j.archger.2008.07.006 |
pubmed_72_21175 | BACKGROUND
Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known.
METHODS
Plasma ghrelin and PYY(3-36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clinical and laboratory parameters, including anthropometrics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed.
RESULTS
Plasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p=0.009), whereas PYY(3-36) levels did not differ significantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p=0.003), whereas fever change during the course of infection was significantly associated with change of ghrelin levels (p=0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC=0.728, p=0.005).
CONCLUSIONS
Circulating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflecting and/or participating in the inflammatory process. | pubmed_72_21175 |
others_294_3786 | The most serious problem in current gene therapy is that clinical applications have often led to unsatisfactory results. Here we show novel concepts and crucial factors that have been missing for successful cytokine gene therapy. A clinically-relevant mouse model of primary and micro-metastatic osteosarcoma was generated by subcutaneously and intravenously injecting murine osteosarcoma LM8 cells, in which adenoviral gene transduction efficiencies were extremely low; current therapies remain less effective for such disseminated micro-metastases. A single injection of adenoviral vector encoding interleukin-2 gene (Ad.IL-2) was given only into the established primary tumor. Notably, antitumoral immunity was successfully elicited by IL-2 secretion from connective tissues adjacent to the primary tumor, and this immunity not only suppressed primary tumor growth but also eradicated disseminated micro-metastases in distant organs. Most importantly, not only minimal side effects but also maximal therapeutic effects were exerted only in the case of injecting the optimal (i.e., not the highest) dose of Ad.IL-2, because spleen injuries caused by excessive levels of circulating IL-2 might diminish the therapeutic effect. Although the narrow range of the optimal therapeutic expression level of IL-2 may be crucial, it was feasibly determined by serum IL-2 levels. Thus, a crucial factor for successful cytokine gene therapy is not the high gene transduction efficiency in the tumor, which has been generally recommended, but the use of the optimal therapeutic expression level. In conclusion, just a single injection of Ad.IL-2 into a primary tumor lesion, which is feasible, not invasive and cost effective, is potently therapeutic for distant disseminated micro-metastases, as long as the optimal therapeutic level is monitored. These novel concepts, which contradict those of previous studies, warn researches about the possible problems with the ongoing clinical cytokine gene therapy | 10.3892/ijo.24.3.549 |
pubmed_807_24099 | We report a case of simultaneous reconstruction of a quadriceps tendon rupture after total knee arthroplasty (TKA) and neglected Achilles tendon rupture, which occurred before TKA with an ipsilateral hamstring autograft. A 64-year-old woman presented with persistent right knee pain. She also had right heel pain and had received multiple steroid injections at the knee joint and heel. On examination, she showed osteoarthritis in the medial and lateral compartments of the knee joint and an Achilles tendon rupture in the ipsilateral limb. There was skin dimpling and the proximal portion of tendon was migrated. We performed TKA, and the postoperative course was satisfactory. She returned 3 months postoperatively, however, with skin dimpling around the suprapatellar area and weakness of knee extension. Her ankle symptoms were also aggravated because she could not use the knee joint freely. We performed simultaneous reconstruction of the quadriceps tendon and the Achilles tendon using an ipsilateral hamstring autograft.Hamstring autograft offers a good alternative treatment option for rupture repair, particularly with concommitant ruptures of multiple sites when primary repair is not possible or the viability of repaired tissue is poor. | 10.3928/01477447-20100329-31 |
pubmed_213_11749 | A comparison was made between oil-contrast hysterosalpingogram (HSG) with 1-hour follow-up radiograph and the traditional 24-hour follow-up radiograph with respect to detection of tubal patency and pelvic adhesive disease. The results on either modality were assessed by subsequent laparoscopy. The 1-hour HSG was comparable to the 24-hour HSG in defining tubal patency. Even though it was inferior to the 24-hour HSG with respect to identifying pelvic adhesions, it may serve as an adequate substitute to the above since the sensitivity of the HSG in identifying adhesions is low and has little influence on the clinical decision process in the evaluation of infertility. | 10.1016/s0015-0282(16)61026-9 |
pubmed_671_901 | Two cases of traumatic rupture of the biliary tract in the liver hilum region are reported. Similar cases (27 patients) reported in the published literature are discussed and the physiopathological, pathological, and clinical characteristics described. Road accidents account for the majority of these cases of biliary tract injury, which are seen mainly in young males. Diagnosis is confirmed either during emergency laparotomy for haemoperitoneum, the presence of bile leading to cholangiography which establishes the diagnosis, or after several days from the presence of jaundice and signs of a peritoneal effusion, when urgent surgery was not required. Treatment is by direct suture or hepatojejunal anastomosis, choice being dictated by two parameters: the type of lesion and the time when it is repaired. | pubmed_671_901 |
pubmed_142_1962 | Higher dietary intakes of Mg and Ca, individually, have been associated with a decreased risk for the metabolic syndrome (MetSyn). Experimental studies suggest that a higher intra-cellular ratio of Ca:Mg, which may be induced by a diet high in Ca and low in Mg, may lead to hypertension and insulin resistance. However, no previous epidemiological studies have examined the effects of the combined intake of Mg and Ca on MetSyn. Thus, we evaluated the association between dietary intakes of Ca and Mg (using 24-h recalls), independently and in combination, and MetSyn in the National Health and Nutrition Examination Study 2001-2010 data, which included 9148 adults (4549 men and 4599 women), with complete information on relevant nutrient, demographic, anthropometric and biomarker variables. We found an inverse association between the highest (>355 mg/d) v. the lowest (<197 mg/d) quartile of Mg and MetSyn (OR 0.70; 95% CI 0.57, 0.86). Women who met the RDA for both Mg (310-320 mg/d) and Ca (1000-1200 mg/d) had the greatest reduced odds of MetSyn (OR 0.59; 95% CI 0.45, 0.76). In men, meeting the RDA for Mg (400-420 mg/d) and Ca (1000-1200 mg/d), individually or in combination, was not associated with MetSyn; however, men with intakes in the highest quartile for Mg (≥ 386 mg/d) and Ca (≥ 1224 mg/d) had a lower odds of MetSyn (OR 0.74; 95% CI 0.59, 0.93). Our results suggest that women who meet the RDA for Mg and Ca have a reduced odds of MetSyn but men may require Ca levels higher than the RDA to be protected against MetSyn. | 10.1017/S0007114515002482 |
pubmed_1122_3495 | BACKGROUND
To overcome problems of lack of conduit and to maximize the number of arterial anastomoses in coronary reoperations we reused previously placed arterial grafts.
METHODS
Sixteen patients were identified from February 1994 to July 1997. Mean age was 62.8 years (range, 44 to 75 years). Fifteen (94%) were in Canadian Cardiovascular Society angina class III or IV. The mean interval from primary to secondary operation was 8.5 years (range, 3 to 12 years). Eleven patients had a patent internal mammary artery graft used as the recipient for a proximal Y anastomosis. In 3 cases an arterial graft was reimplanted distally on the same coronary vessel and in 2 onto different coronary vessels. One patient had a combination of these techniques. Five patients required venous conduit.
RESULTS
There were no deaths. Mean length of intensive care stay was 69 hours (range, 24 to 144) and mean hospital stay was 14 days (range, 10 to 28 days). All patients were discharged home. Follow-up averages 13 months (range, 2 to 43 months). Twelve patients (75%) are now in Canadian Cardiovascular Society angina class I and 3 (19%) in class II.
CONCLUSIONS
Reusing arterial conduits during coronary reoperations is possible with minimal in-hospital morbidity and satisfactory results in terms of freedom from angina. Using these techniques can help overcome the problems of inadequate conduit and maximize the number of arterial anastomoses that can be made per patient. | 10.1016/s0003-4975(98)01252-1 |
pubmed_200_6736 | BACKGROUND
Traditionally, the female belt range extended to C5, but in current rock/pop Broadway productions, women are often required to belt up to an F5. This recent extension of the belt voice beyond C5 is a significant change, and female musical theater singers need effective strategies to produce these higher belt notes.
OBJECTIVE
The intent of this study was to gain a clear understanding of the strategies used to successfully teach and produce the higher range of the female musical theater belt voice.
METHODS
The study is a qualitative design composed of two data collection methods: interviews with four nationally recognized master musical theater voice teachers and 17 of their female belt students, and observations of the master teachers working with these students in their private studios.
RESULTS
There was much consensus among the teachers and singers on the strategies of producing the higher belt range, such as incorporating more head voice involvement with closed vowels and maintaining a speech-like quality. Singers report that they produce high belt notes with more of a mix vocal approach. Teachers suggest that female voice type may determine the extent of a singer's ability in this high belt range.
CONCLUSIONS
The high belt will be narrow, based on closed vowels, mixing in some degree of head voice function. Although this study has revealed some guidelines for the female musical theater high belt and similar strategies among master teachers, voice teachers should be aware of the variability of their female musical theater voice students. | pubmed_200_6736 |
pubmed_741_13340 | In the Bengali-speaking population of Calcutta (India) the genotype frequencies of the Hb beta-A/E/T system are given. The fitness of the genotypes has been calculated. It is found that this system is not in stable or semistable equilibrium in this population. | 10.1159/000153395 |
pubmed_779_18477 | BACKGROUND
Patients with inherited haemorrhagic disorders may bleed during surgery. No questionnaire on bleeding diathesis has been yet validated for the preoperative period and current guidelines provide conflicting recommendations.
AIM
We aimed to assess if preoperative assessment with ISTH-BAT (International Society on Thrombosis and Haemostasis Bleeding Assesment Tool) and laboratory screening tests is useful to identify mild previously undiagnosed bleeding disorders (BDs) and to predict bleeding complications in selected patients undergoing elective surgery.
METHODS
Consecutive patients undergoing elective surgery received ISTH-BAT evaluation and laboratory screening for platelet count, Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT). Subjects with an abnormal ISTH-BAT and/or laboratory results underwent further testing, and they were compared with a 1:1 random gender-, age- and type of surgery- matched control group.
RESULTS
Overall, 1502 consecutive surgical patients (1186 adults, 316 children) were enrolled. Of these, 83 (5.5%, 95% confidence interval 4.4-6.8) patients (37 adults and 46 children) had an abnormal ISTH-BAT, and/or prolonged PT and/or prolonged aPTT and/or low platelet count; of them, one subject had low von Willebrand factor level, three Factor XII deficiency and four anticardiolipin and/or antiB2GPI antibodies. No major bleeding was reported in these 83 patients and their controls.
CONCLUSION
ISTH-BAT and laboratory screening tests do not accurately detect mild BDs in selected patients undergoing elective surgery. | 10.1111/hae.14376 |
pubmed_997_173 | PURPOSE
Unilateral skipping is an asymmetrical gait only exceptionally used by humans, due to high energetic demands. In skipping, the cost of transport decreases as speed increases, and the spring-mass model coexists with the vaulting pendular one. However, the mechanisms of energy transfers and recovery between the vaulting and the bouncing steps are still unclear in this gait. The objective of this work is to study how spatiotemporal and spring-mass asymmetries impact on metabolic cost, lowering it despite speed augmentation.
METHODS
Kinematics and metabolic rates of healthy subjects were measured during running and skipping on a treadmill at controlled speeds.
RESULTS
Metabolic power in skipping and running increased with similar slope but different intercepts. This fact determined the different behaviour of the cost of transport: constant in running, decreasing in skipping. In skipping the step time asymmetry remained constant, while the step length asymmetry decreased with speed, almost disappearing at 2.5 m/s-1. Leg stiffness in trailing limb increased with higher slope than in leading limb and running; however, the relative leg stiffness asymmetry remained constant.
CONCLUSIONS
Slow skipping presents short bouncing steps, even shorter than the vaulting, impacting the stride mechanics and the metabolic cost. Faster speeds were achieved by taking longer bouncing steps and a stiffer trailing limb, allowing to improve the effectiveness of the spring-mass mechanism. The step asymmetries' trends with respect to speed in skipping open the possibility to use this gait as an experimental paradigm to study mechanisms of metabolic cost reduction in locomotion. | 10.1007/s00421-022-05088-x |
pubmed_504_22297 | Most chemical warfare agents partition rapidly into stratum corneum (SC) and subsequently slowly diffuse through - or are retained in the membrane. Since chemicals can interact with SC components during the process, skin decontamination poses a challenging yet important problem. To address these issues, we have developed a new method in combination with wet and dry decon technologies with new materials for emergency or delayed contamination scenarios. An in vitro human skin diffusion system was employed to model various dermal exposures of radiolabeled chemical warfare simulants, followed by surface decontamination with metal organic frameworks (MOFs), super-absorbent polymers (SAP), and/or dermal decontamination gel (DDGel). All samples measured for radioactive recovery and acetylcholinesterase activity to ascertain relative decon efficacy. Results demonstrated powerful water absorption of SAP, strong catalysis of UiO-66 MOF, and decon enhancement of pre-wetting surface contaminants. SAP had no interfering interactions with MOF yet provided additional benefits as porosity and reactivity that allowed for fast liquidized chemical transportation, absorption, and degeneration. We then designed a cotton-based SAP/MOF patch that worked cooperatively in decontamination and detoxification. Together with pre-wet, SAP/MOF wipe, and DDGel applications, maximum effect was observed in early and/or extended dermal exposure, and no "wash-in" effect occurred. | 10.1016/j.toxlet.2020.11.004 |
pubmed_436_14239 | To know the prognosis of a patient with cancer allows choosing the most appropriate therapeutic. The expression of the oncogen HER2/neu has been related to an unfavourable prognosis in patients with infiltrating breast carcinoma, for this reason, the purpose of this work was to analyze its predictive and prognostic value in patients with locally advanced breast cancer, treated in the Oncological Institute "Dr Miguel Perez Carreño". Information about personal data of 58 patients was compiled, as well as the received treatment, clinical response data of the biopsy report, histological grade, nuclear grade, node status and evolution of the patient. The determination of the HER2/neu expression was made by inmunohistochemistry, using the avidina-estreptavidin-peroxidasa technique. For the interpretation of the HER2/neu, an agreed score from 0 to 3+ was assigned, using the guidelines of interpretation of the Hercep-Test (DAKO). 37.9% of the cases displayed expression of the HER2/neu in the membrane of the tumour cells. The node state and the hormonal receptors state turned out to be significant to predict the disease-free interval. Patients with strong oncoprotein expression seem to have a quimioresistant tendency to the FAC (5-fluorouracil, doxorubicin and cyclophosphamide) regime. The expression of the HER2/neu receptor is related to a reduction of the disease-free interval and global survival in patients with infiltrating ductal breast carcinoma locally advanced, confirming, in this work, to be a good prognostic factor. | pubmed_436_14239 |
pubmed_550_5309 | The authors analysed laboratory samples testing positive for rabies virus collected between 2000 and 2005 from Santa Cruz de la Sierra, Bolivia, to assess the spatial and spatio-temporal distribution of the endemic of canine rabies. According to the results of the spatial analysis, canine rabies was not evenly distributed in the city. Significant spatio-temporal clustering of canine rabies cases showed a trend towards clusters with high incidence rates in two particular areas compared with surrounding areas in the city. Benefits obtained from each of the analytical techniques utilised are described and practical difficulties in conducting and interpreting the results are discussed. | 10.1016/j.actatropica.2007.06.003 |
pubmed_313_2860 | Objective: It has been reported by some prospective studies that C-reactive protein (CRP) is associated with cancer risk. However, the correlation between CRP and digestive system cancers has not been evaluated in Chinese females. We conducted a large population-based cohort study to investigate whether elevated level of CRP in serum is associated with an increased risk of digestive system cancers in Chinese women. Methods: From the Chinese Kailuan Female Cohort, 19, 437 women were enrolled in this study in July 2006, and all of the subjects were followed up through 2014. At the baseline investigation, the serum levels of high-sensitivity CRP (hsCRP) were tested for all subjects, and demographic information and risk factor data were collected. Multivariable Cox proportional hazards regression model was used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) for the baseline levels of hsCRP after adjusting for age, marital status, smoking, drinking, body mass index (BMI), diabetes and physical activity, and risk of digestive system tumors (including colorectal cancer, stomach cancer, pancreas cancer, liver and gallbladder cancer, and other cancers). Results: By Dec 31, 2014, a total of 100 incident cancer cases were observed, including 47 colorectal cancers, 17 stomach cancers, and altogether 29 pancreas, liver and gallbladder cancers. All the subjects investigated were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The 8-year cumulative incidence of digestive system cancers were 405/100 000, 520/100 000 and 787/100 000 in these 3 groups, respectively (Log rank test χ2 = 8.37, P=0.015). Compared to those with lower hsCRP levels (<1 mg/L), the women with higher hsCRP (>3 mg/L) had a significantly increased risk of pancreas, liver and gallbladder cancers (HR = 2.70, 95% CI = 1.06-6.91; Ptrend = 0.036). Conclusions: Elevated levels of hsCRP at baseline may be associated with increased risk of certain digestive system cancers. | 10.3760/cma.j.issn.0253-3766.2016.11.015 |
pubmed_929_11546 | OBJECTIVE
The objective of this study was to report the midterm outcomes of the brachial arterio-arterial prosthetic loop (AAPL) as an alternative permanent vascular access in strictly selected patients with end-stage renal disease.
METHODS
This single-center prospective observational study was conducted between January 2014 and June 2017 and included 89 brachial AAPL procedures. Primary, assisted primary, and secondary patency rates were calculated using Kaplan-Meier analysis.
RESULTS
Exhausted peripheral veins were the most common indication for brachial AAPL. Patients were followed up for a mean period of 28.7 ± 4.9 months. Nineteen grafts developed thrombosis, 13 grafts developed pseudoaneurysms, 9 grafts developed hematoma, and 6 grafts were abandoned because of infection. The primary, assisted primary, and secondary patency rates were 62% ± 5.2%, 71.2% ± 4.9%, and 89.6% ± 3.3% at 24 months, respectively.
CONCLUSIONS
Brachial AAPL can offer a simple, safe, and efficient alternative as a permanent hemodialysis access in a selected subset of end-stage renal disease patients, with acceptable durability and rate of complications. Because of its unique specifications, cooperation between vascular surgeons and dialysis staff is mandatory. | 10.1016/j.jvs.2019.10.081 |
pubmed_313_20404 | Interprofessional care is joint working between health care professionals by pooling their skills, knowledge and expertise, to make joint decisions and learn from each other for the benefits of service users and healthcare professionals. Service users involvement is considered as one of the important aspects of planning, management and decision making process in the delivery of health care to service users. Service users' involvement is not the same as public involvement and partnership arrangements in health care. The active involvement and engagement of service users in health care positively contributes to improve quality of care, to promote better health and to shape the future of health services. Service users are always at the centre of health care professionals' values, work ethics and roles. Moreover, service users centred interprofessional team collaboration is very important to deliver effective health services. | pubmed_313_20404 |
pubmed_435_8245 | OBJECTIVE
People with type 2 diabetes vary greatly in their use of high-cost health care resources. We examined the association of anxiety with high-cost use after accounting for depression and medical comorbidity.
RESEARCH DESIGN AND METHODS
Using electronic health record data, we assessed past anxiety diagnosis, health care use and costs, demographics, comorbidities, and diabetes control status and complications during 2008-2012 for 143,573 adult members of an integrated health care system with type 2 diabetes. Multivariable regression models estimated associations between anxiety and emergency department (ED) use, total hospitalization costs, and high-cost status (i.e., incurring total health care costs in the top 20% among all system members).
RESULTS
During 2008-2011, 12.9% of participants received a diagnosis of anxiety, of whom 52.9% also had received a depression diagnosis. After adjustment for covariates including depression, anxiety was positively related to the number of ED visits in 2012 (incidence rate ratio 1.27; 95% CI 1.21, 1.34), the likelihood of visiting the ED on a chronic, frequent basis during 2010-2012 (odds ratio 2.55; 95% CI 1.90, 3.44), and high-cost status in 2012 (odds ratio 1.29; 95% CI 1.23, 1.36), but anxiety was not related to total hospitalization costs in 2012 (relative cost ratio 1.06; 95% CI 0.94, 1.21; P = 0.33).
CONCLUSIONS
Anxiety is highly comorbid with depression among individuals with type 2 diabetes and is independently associated with high-cost resource use. Strategies to improve anxiety management among people with diabetes hold the potential to also reduce health care costs. | 10.2337/dc18-1553 |
pubmed_560_11204 | BACKGROUND
The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predicts the risk of diabetes and cardiovascular disease (CVD). Adipokines may contribute to the development of obesity and insulin resistance and may be a causal link between MS, diabetes and CVD. Hence, we studied the adipokines - adiponectin and plasminogen activator inhibitor-1 (PAI-1) - in subjects with MS.
MATERIALS AND METHODS
We studied 50 subjects with MS diagnosed by International Diabetes Federation (IDF) criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, highly sensitive C-reactive protein, insulin, adiponectin, and PAI-1 measurement.
RESULTS
Subjects with MS had lower adiponectin (4.01 ± 2.24 vs. 8.7 ± 1.77 μg/ml; P < 0.0001) and higher PAI-1 (53.85 ± 16.45 vs. 17.35 ± 4.45 ng/ml; P < 0.0001) levels than controls. Both were related with the number of metabolic abnormalities. Adiponectin was negatively and PAI-1 was positively associated with body mass index, waist hip ratio (WHR), body fat mass, percent body fat, and all the parameters of MS, except HDL where the pattern reversed. WHR and triglycerides were independent predictors of adipokines in multiple regression analysis. Receiver operating characteristic curve analysis showed that adiponectin (6.7 μg/ml) and PAI-1 (25.0 ng/ml) levels predicted the MS with high sensitivity, specificity and accuracy in Indian population.
CONCLUSIONS
Subjects with MS have lower adiponectin and higher PAI-1 levels compared to healthy controls. Lifestyle measures have been shown to improve the various components of MS, and hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD. | 10.4103/2230-8210.91206 |
pubmed_15_7583 | During the past few years, medical treatments of cancer have improved thanks to the discovery of targeted therapies. These therapies are today widely used in cancer treatment. The mechanism of action of targeted therapies and the adverse effects they induce are different from the classic chemotherapies, and require a specific management. Most of these drugs are taken at home and orally, and as a consequence, general practitioners should be able to manage these side effects. The most current toxicities in general medicine are fatigue, high blood pressure, dermatologic, gastrointestinal and metabolic side effects. These effects, often moderate are frequent and diverse, and can impact the patient's quality of life and reduce treatment compliance. Management of these toxicities should then be well known by general practitioners in order to optimize care and improve patient wellness. | pubmed_15_7583 |
pubmed_873_8892 | In the original publication of the article, the seventh author name "Giampaolo Tocci" has been misspelt. The correct name is given in this. | 10.1007/s10554-018-1409-y |
pubmed_472_15798 | Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor. | 10.1126/sciimmunol.aah4576 |
pubmed_83_3188 | Worldwide rates of Western-diet-induced obesity epidemics are growing dramatically. Being linked with numerous comorbidities and complications, including cardiovascular disease, type 2 diabetes, cancer, chronic inflammation, and osteoarthritis (OA), obesity represents one of the most threatening challenges for modern healthcare. Mouse models are an invaluable tool for investigating the effects of diets and their bioactive components against high fat diet (HFD)-induced obesity and its comorbidities. During recent years, very high fat diets (VHFDs), providing 58-60% kcal fat, have become a popular alternative to more traditional HFDs, providing 40-45% total kcal fat, due to the faster induction of obesity and stronger metabolic responses. This project aims to investigate if the 60% fat VHFD is suitable to evaluate the protective effects of curcumin in diet-induced obesity and osteoarthritis. B6 male mice, prone to diet-induced metabolic dysfunction, were supplemented with VHFD without or with curcumin for 13 weeks. Under these experimental conditions, feeding mice a VHFD for 13 weeks did not result in expected robust manifestations of the targeted pathophysiologic conditions. Supplementing the diet with curcumin, in turn, protected the animals against obesity without significant changes in white adipocyte size, glucose clearance, and knee cartilage integrity. Additional research is needed to optimize diet composition, curcumin dosage, and duration of dietary interventions to establish the VHFD-induced obesity for evaluating the effects of curcumin on metabolic dysfunctions related to obesity and osteoarthritis. | 10.3390/biom10101368 |
pubmed_445_5276 | Phenotypic sexual differentiation during embryogenesis is a complex process involving the action of at least 18 genes. These genes regulate gonadal differentiation, gonadal hormone formation, and in the male the cellular action of three necessary hormones, namely mullerian regression factor, testosterone, and dihydrotestosterone. Analysis of two of the mutations affecting sexual development is consistent with the thesis that the two androgens testosterone and dihydrotestosterone have separate and specific roles in virilization of the male urogenital tract, testosterone stimulating wolffian duct development and dihydrotestosterone mediating development of the urogenital sinus and external genitalia. In the disorder familial incomplete male pseudohermphroditism, type 2, deficient dihydrotestosterone formation is associated with a selective failure of virilization of the urogenital sinus and external genitalia, whereas the wolffian duct derivatives develop normally. On the other hand, in the testicular feminization syndrome there is a complete failure in the development of the male phenotype, indicating that the primary defect involves an abnormality in some biochemical step that is common to the action of both androgens. Evidence from studies in the submandibular gland of the mouse with testicular feminization suggest that the fundamental defect lies in the translocation and/or nuclear binding of the cytoplasmic androgen receptor. It remains to be proven whether these events in the postnatal, sexually dimorphic submandibular gland of the testicular feminization mouse reflect prenatal events occurring in the urogenital tissues during embryogenesis. | 10.1002/jcp.1040850405 |
pubmed_571_7962 | OBJECTIVES
To compare the risk-adjustment model empirically derived from the 'Italian CABG Outcome Project' with that of the additive and logistic EuroSCORE in terms of accuracy, predictive power and ability to rank hospital performances.
METHODS
The Italian CABG model, the logistic and additive EuroSCORE were applied to the Italian CABG population; the observed deaths/expected deaths (O/E) ratios, as obtained by the three models, were computed for each Italian cardiac surgery centre and for six classes of risk-stratified patients. The performance of the three models in predicting the 30-day mortality was formally assessed for calibration (Hosmer-Lemeshow test) and discrimination (ROC area). According to the three models, risk-adjusted mortality rates (RAMR = O/E x Italian CABG population mortality rate) were estimated for each centre; possible differences were detected in the identification of hospitals with mortality rates higher and lower than average.
RESULTS
The Italian CABG model uses fewer variables than the EuroSCORE system (14 vs 17) and exhibits the best performance in terms of discrimination and calibration. Contrary to the other tested models, the logistic EuroSCORE shows a significant Hosmer-Lemeshow test (chi(H-L)(2)=19.30, p<0.0001), indicating unsatisfactory calibration, and a clear predicted death overestimation in each of the considered risk classes (O/E = 0.4). When a proper recalibration procedure is applied, the logistic EuroSCORE performance parameters achieve acceptable levels. The Italian CABG model identified seven centres as having higher than average mortality, while the EuroSCORE identified the same seven centres plus one other. The Italian CABG model identified eight centres with lower than average mortality, five of which were identified by the additive EuroSCORE and four of which were identified by the logistic EuroSCORE. The additive EuroSCORE identified four more and the logistic EuroSCORE three more low mortality centres.
CONCLUSIONS
Although this analysis reveals a satisfactory concordance between results from the three models, a detailed comparison shows that the Italian CABG model uses fewer variables and performs better than the others. Nevertheless, when properly recalibrated, the EuroSCORE model can be exported to the Italian population and used to rank hospital performance and evaluate preoperative risk of patients undergoing open-heart surgery. | 10.1016/j.ejcts.2007.12.001 |
pubmed_158_11509 | A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(ethoxycarbonyl)-5-(arylamino)thiazoles and 5-(arylamino)-4-carbamoylthiazoles, respectively, is described. In vitro cytotoxicity of a large number of derivatives of these compounds has been tested against several cell lines. The highest activities observed are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]amino] substituent at C-2 and a fluorine atom at the C-7 position of the tricyclic planar heteroaromatic framework. Three structural features seem to be essential for antitumor activities: a positive charge density at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloquinoline skeleton with two basic nitrogens and a pKa value of 7.5-10 in the most basic center, and a conformational flexibility of this basic side chain. These structural requirements must be simultaneously satisfied in order to ensure a significant antitumor activity. | 10.1021/jm960556q |
pubmed_215_5959 | Endocytotic-active cells in the branchial heart complex of Sepia officinalis were studied by in situ injection of different types of xenobiotics and by in vitro perfusion of the organ complex with a bacterial suspension. The rhogocytes (ovoid cells) ingest particles of all tested sizes by endocytosis and phagocytosis. The hemocytes of the circulating blood and the adhesive hemocytes in the wall of the branchial heart incorporate all tested kinds of foreign materials, including bacterial cells due to phagocytosis achieved by the triangular mesenchymatic cells. The ultrastructural findings also give strong evidence that the triangular mesenchymatic cells are fixed hemocytes that have migrated into the branchial heart tissue. The ingestion and digestion of allogeneic substances and bacteria or their debris by rhogocytes and/or all (forms of) hemocytes suggests the involvement of these either fixed or mobile endocytotic-active cells in the defense and detoxification system of cephalopods. | 10.1016/s0040816602000708 |
pubmed_294_168 | Fourteen experienced nurses participated in an explorative study aimed at describing the experiential aspects of moral decision making in psychiatric nursing practice. In-depth interviews were conducted according to the grounded theory method. These were transcribed, coded and categorized in order to generate conceptual categories. The concept of benevolence was identified as a central motivating factor in the nurses' own accounts of situations in which decisions were made on behalf of the patient. This seems to conceptualize the nurses' expressed aim to do that which is 'good' for the patient in responding to his or her vulnerability. This study indicates the need for further research into the subjective, experiential aspect of ethical decision making from a contextual perspective. | 10.1046/j.1365-2648.1993.18071106.x |
pubmed_100_21266 | Confocal mosaicing microscopy enables rapid imaging of large areas of fresh tissue, without the processing that is necessary for conventional histology. Mosaicing may offer a means to perform rapid histology at the bedside. A possible barrier toward clinical acceptance is that the mosaics are based on a single mode of grayscale contrast and appear black and white, whereas histology is based on two stains (hematoxylin for nuclei, eosin for cellular cytoplasm and dermis) and appears purple and pink. Toward addressing this barrier, we report advances in digital staining: fluorescence mosaics that show only nuclei, are digitally stained purple and overlaid on reflectance mosaics, which show only cellular cytoplasm and dermis, and are digitally stained pink. With digital staining, the appearance of confocal mosaics mimics the appearance of histology. Using multispectral analysis and color matching functions, red, green, and blue (RGB) components of hematoxylin and eosin stains in tissue were determined. The resulting RGB components were then applied in a linear algorithm to transform fluorescence and reflectance contrast in confocal mosaics to the absorbance contrast seen in pathology. Optimization of staining with acridine orange showed improved quality of digitally stained mosaics, with good correlation to the corresponding histology. | 10.1117/1.3596742 |
pubmed_880_14561 | Photosynthesis-irradiance (P-E)-curves describe the photosynthetic performance of autotrophic organisms. From these P-E-curves the photosynthetic parameters α-slope, P(max), and E(k) can be deduced which are often used to characterize and to compare different organisms or organisms in acclimation to different environmental conditions. Particularly, for in situ-measurements of P-E curves of phytoplankton the analysis of variable chlorophyll fluorescence proved its potential as a sensitive and rapid method. By using Chlorella vulgaris (Trebouxiophyceae), Nannochloropsis salina (Eustigmatophyceae), Skeletonema costatum and Cyclotella meneghiniana (Bacillariophyceae), the present study investigated the influence of cellular bio-optical properties on the correlation of the photosynthetic parameters derived from fluorescence-based P-E-curves with photosynthetic parameters obtained from the measurement of oxygen evolution. It is demonstrated that small planktonic algae show a wide range of cellular absorptivity which was subject to species-specifity, growth stage and environmental conditions, e.g. nutrient limitation. This variability in bio-optical properties resulted in a great deviation of relative electron transport rates (rETRs) from oxygen-based photosynthesis rates. Thus, the photosynthetic parameters α-slope and P(max) derived from rETRs strongly depend on the specific cellular absorptivity and cannot be used to compare the photosynthetic performance of cells with different optical properties. However, it was shown that E(k) is independent of cellular absorptivity and could be used to compare samples with unknown optical properties. | 10.1016/j.plaphy.2011.04.010 |
pubmed_741_4903 | During 1981, 265 bovine abortions were investigated by serological and histological methods for evidence of leptospiral infection. Leptospires were demonstrated in the tissues of 10 foetuses by a Levaditi silver impregnation technique. Serological testing of maternal sera indicated that Leptospira interrogans serovar hardjo was associated with 5 of the abortions while the remaining 5 were due to L. interrogans serovar pomona infection. In cases of abortion associated with L. interrogans serovar hardjo leptospires were readily demonstrated in foetal liver, kidney, intestine and heart. They were demonstrated less often in lung and placenta and could not be found in foetal brain. Autolysis did not appear to interfere with the demonstration of leptospires by silver impregnation. No lesions attributable to leptospiral infection were seen in placentas but mild interstitial nephritis was found in some of the foetuses. Fourteen other cows had serological evidence of recent leptospiral infection but leptospires were not detected in foetal tissues. Histological examination of silver impregnated foetal tissues in combination with the microscopic agglutination test was shown to be an effective method for diagnosing abortion associated with L. interrogans serovar hardjo in cattle. | 10.1111/j.1751-0813.1983.tb09583.x |
pubmed_786_3552 | Hepatocellular carcinoma (HCC) ranks as the eighth most common cancer in the world. Although uncommon in North America, the incidence of HCC in the United States has increased by 70% since the 1980s (Yu, Yuan, Govindarajan, & Ross, 2000). The most frequent causes of malignant hepatic disease in the United States are metastases from melanoma and primary tumors of the gastrointestinal tract, breast, and lung. Surgical resection and systemic chemotherapy are the standard treatments for this disease. However, surgery is not an option for patients with advanced disease, and the response rate from systemic chemotherapy remains low. An alternative therapy for patients with HCC or cancers with liver metastases is hepatic arterial infusion of chemotherapy directly into the liver. This method allows a high total body clearance and hepatic extraction to generate high hepatic and low systemic exposures. Nursing care of patients receiving hepatic arterial infusion of chemotherapy includes patient education and monitoring for complications. | 10.1188/03.CJON.647-652 |
pubmed_215_22589 | OBJECTIVE
Efficiency of lithotripsy on ureteral stones treated in situ by EDAP-LT02.
MATERIAL AND METHOD
Between January 1992 and March 2001, 1,690 ureteric stones were treated in situ by extracorporeal shock-wave lithotripsy (ESWL) in 1,480 patients with 1 to 4 stones. This study compared two series: series 1998, comprising 1,013 stones in 859 patients treated between January 1992 and January 1998, and series 2001, comprising 677 stones in 621 patients treated between February 1998 and March 2001. This second series benefited from improvement of the equipment especially the ultrasound apparatus, which improved the mixed detection rate from 36% to 58%. The stone was situated in the lumbar ureter in 48.5% of cases, the iliac ureter in 7.5% of cases and the pelvic ureter in 44% of cases. Stone diameter ranged from 5 mm to 25 mm. Treatment consisted of 1 to 4 sessions. All sessions were performed on an outpatient basis without anaesthesia.
RESULTS
The results were better with mixed detection (p < 0.028). Comparison of the 2 series showed a significant improvement (p < 0.012): the mean number of sessions per patient decreased from 1.47 to 1.21, the mean duration of treatment decreased from 84 min to 74 min, the mean cumulative energy delivered decreased from 86 to 72. The overall success rate (elimination of all fragments) increased from 58% to 85% after the first session, from 83% to 95% after the second session and from 91% to 98% after the third session.
COMPLICATIONS
0.43% of treated patients developed acute pyelonephritis and 6.1% experienced renal colic. IVU, performed three months after ESWL in patients treated by several sessions, did not reveal any ureteric lesions.
CONCLUSION
ESWL by EDAP-LT02 is a noninvasive outpatient procedure and constitutes the treatment of choice for ureteric stones. It is more effective in combination with mixed detection. The results are improved by several treatment sessions without any adverse effects. | pubmed_215_22589 |
others_332_9733 | sed on document consulting, and taken Tianmu Mount National Nature Reserve, Qingliangfeng National Nature Reserve and Baishanzu National Nature Reserve as key investigation areas, floristic composition and feature, life-form and geographical composition type of wild Orchidaceae in Zhejiang Province were investigated and analyzed. The results show that there are 89 wild species (including varieties) belonging to 45 genera, 2 subfamilies of Orchidaceae in Zhejiang Province, in which 1 species belonging to 1 genus of Subfam. Cypripedioideae and 88 species belonging to 44 genera, 4 tribes of Subfam. Orchidoideae. The percentage of genera with single species and a few species is the largest with an accounting for 84. 4% of total genus number, and the number of Chinese endemic species is 22 with an accounting for 24.7% of total species number. The life-form includes edaphic, epiphytic and saprophytic types, each with 62, 24 and 3 species, respectively, in which edaphic type is the main one. Distribution type of genus of Orchidaceae flora in Zhejiang Province can be divided into ten types and two subtypes. The genus number belonging to Trop. Asia to Trop. Australia type and E. Asia type is the most with an accounting for 22.2% of total genus number. Tropical distribution composition has 22 genera 35 species accounting for 48.9% and 39.3% of total genus and species number, respectively, and temperate distribution composition has 19 genera 27 species accounting for 42.2% and 30.3% of total genus and species number, respectively. Orchidaceae flora in Zhejiang Province includes some relative primitive taxa of Cypripedium L., Cephalanthera L. C. Rich., Pogonia Juss., etc and Chinese endemic species are abundant and appears differentiation of local endemic species. The comprehensive analysis results indicate that the tropical affinity relationship of Orchidaceae flora in Zhejiang Province is stronger, its origin is more ancient and differentiation degree is higher with a certain significance in system and evolution researches | others_332_9733 |
pubmed_140_12904 | BACKGROUND
The combination of cisplatin, 5-fluorouracil (5-FU) and cetuximab (PFC) is the reference first-line treatment for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). We analysed whether treatment intensification by the addition of docetaxel to PFC improved efficacy in R/M SCCHN.
METHODS
A total of 180 patients with R/M SCCHN (1:1) were assigned to receive either cisplatin (40 mg/m2), docetaxel (40 mg/m2) and 5-FU (2000 mg/m2) at days 1 and 8 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (DPFC) or standard cisplatin (100 mg/m2) at day 1, 5-FU (1000 mg/m2) at days 1-4 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (PFC). Chemotherapy was repeated every 21 days and continued for a maximum of 6 cycles in absence of disease progression or limiting toxicity, followed by cetuximab maintenance (500 mg/m2 every 2 weeks). The primary end-point was progression-free survival (PFS).
RESULTS
A preplanned interim analysis for toxicity after 20 patients/arm revealed excessive grade 3 and 4 gastrointestinal (65%) and infectious toxicities (35%) in arm A, which led to dose reduction of cisplatin to 30 mg/m2 and 5-FU to 1000 mg/m2 for subsequent patients. With a median follow-up of 2 years, grade 4 toxicities were 21.3% vs. 30.8% for DPFC and PFC, respectively. More treatment-related deaths occurred with DPFC vs. PFC, with 11.2% and 6.6%, respectively. For DPFC and PFC, the median PFS was 6.3 vs. 6.4 months (hazard ratio [HR] = 0.97, p = 0.87), the median overall survival was 8.9 vs. 10.6 months (HR = 1.29 p = 0.1) and response rates were 38.2% vs. 31.9% (p = 0.9), respectively.
CONCLUSIONS
DPFC failed to improve efficacy in R/M SCCHN. On the contrary, a high toxicity and mortality rate was detected in both arms, which underscores the vulnerability of patients with R/M SCCHN, and research on the need for further optimisation of the front-line chemotherapy backbone is ongoing. | 10.1016/j.ejca.2019.08.018 |
pubmed_0_3045 | A microbial consortium with a high cellulolytic activity was enriched to degrade raw corn stover powder (RCSP). This consortium degraded more than 51% of non-sterilized RCSP or 81% of non-sterilized filter paper within 8 days at 40°C under facultative anoxic conditions. Cellulosome-like structures were observed in scanning electron micrographs (SEM) of RCSP degradation residue. The high cellulolytic activity was maintained during 40 subcultures in a medium containing cellulosic substrate. Small ribosomal gene sequence analyses showed the consortium contains uncultured and cultured bacteria with or without cellulolytic activities. Among these bacteria, some are anaerobic others aerobic. Analyses of the culture filtrate showed a typical anoxic polysaccharide fermentation during the culturing process. Reducing sugar concentration increased at early stage followed by various fermentation products that were consumed at the late stage. | 10.1016/j.biortech.2010.08.074 |
pubmed_1132_24043 | BACKGROUND
The adenovirus E4orf4 protein must bind protein phosphatase 2A (PP2A) for its functions.
RESULTS
The E4orf4 binding site in PP2A was mapped to the α1,α2 helices of the B55α subunit.
CONCLUSION
The E4orf4 binding site in PP2A-B55α lies above the substrate binding site and does not overlap it.
SIGNIFICANCE
A novel functional significance was assigned to the α1,α2 helices of the PP2A-B55α subunit. The adenovirus E4orf4 protein regulates the progression of viral infection and when expressed outside the context of the virus it induces nonclassical, cancer cell-specific apoptosis. All E4orf4 functions known to date require an interaction between E4orf4 and protein phosphatase 2A (PP2A), which is mediated through PP2A regulatory B subunits. Specifically, an interaction with the B55α subunit is required for induction of cell death by E4orf4. To gain a better insight into the E4orf4-PP2A interaction, mapping of the E4orf4 interaction site in PP2A-B55α has been undertaken. To this end we used a combination of bioinformatics analyses of PP2A-B55α and of E4orf4, which led to the prediction of E4orf4 binding sites on the surface of PP2A-B55α. Mutation analysis, immunoprecipitation, and GST pulldown assays based on the theoretical predictions revealed that the E4orf4 binding site included the α1 and α2 helices described in the B55α structure and involved at least three residues located in these helices facing each other. Loss of E4orf4 binding was accompanied by reduced contribution of the B55α mutants to E4orf4-induced cell death. The identified E4orf4 binding domain lies above the previously described substrate binding site and does not overlap it, although its location could be consistent with direct or indirect effects on substrate binding. This work assigns for the first time a functional significance to the α1,α2 helices of B55α, and we suggest that the binding site defined by these helices could also contribute to interactions between PP2A and some of its cellular regulators. | 10.1074/jbc.M112.343756 |
pubmed_172_39 | Reversible valproic acid-induced dementia was documented in a 21-year-old man with epilepsy who had a 3-year history of insidious progressive decline in global cognitive abilities documented by serial neuropsychological studies. Repeat neuropsychological testing 7 weeks after discontinuation of the drug revealed dramatic improvement in IQ, memory, naming, and other tasks commensurate with clinical recovery in his intellectual capacity. Possible pathophysiological mechanisms which may have been operative in this case include: a direct central nervous system (CNS) toxic effect of valproic acid; a paradoxical epileptogenic effect secondary to the drug; and an indirect CNS toxic effect mediated through valproic acid-induced hyperammonemia. | 10.1111/j.1528-1157.1986.tb03534.x |
pubmed_503_11588 | The ability to taste 6-n-propylthiouracil (PROP) is genetically determined. PROP tastes moderately bitter to 'medium tasters' (MT), intensely bitter to 'supertasters' (ST), and tasteless to 'nontasters' (NT). The psychophysical method used to characterize PROP status should capture the entire range of perception, while minimizing context, ceiling and other effects. Magnitude estimation successfully captures the variability in PROP perception, but requires normalization and may be difficult to conduct in industrial settings. Two labeled scales were tested as part of three separate studies (S1, S2 and S3) to measure perceived intensity of PROP and sweeteners. All studies included reportedly healthy volunteers aged 21-62 years recruited at Cultor Food Science in Groton, CT. In S1 [n = 163 (55 males, 108 females)], subjects rated perceived intensity of PROP-saturated paper and sucrose (1.0 M) on the Labeled Magnitude (Green) Scale (LMS) [labeled line with descriptors (no taste--strongest imaginable)]. In S2 [n = 152 (49 males, 103 females)], subjects rated perceived intensity of sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on the LMS. In S3 [n = 136 (48 males, 88 females)], subjects rated perceived intensity of sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on a 9-point category scale (1 = not at all; 9 = extremely). In all experiments, water rinses were included between each tastant and PROP was the final stimulus. Statistical analyses included descriptive statistics, regression analysis, and ANOVA. In S1 and S2, those with higher PROP perception perceived sucrose more intensely [(S1: r = 0.32; p < 0.001); (S2: r = 0.25; p < 0.01)]. A higher frequency of females were ST than males. Also, the PROP effect on sweet perception was most evident in female ST. This apparent sex difference may be the result of hormonal variation associated with menstruation. As well, in S1 and S2 subjects aged 20-40 years, females had significantly greater variance among sucrose intensity ratings than males (F = 3.66; p < 0.01), which may be due to hormonal changes with menses. The S3 results failed to show either the positive correlation between PROP and sucrose perception or the sex difference. Thus of the two labeled scales, the LMS appears to be better for assessing PROP perception, as it is continuous and also minimizes ceiling effects. Future research will extend these studies by including sucrose and high intensity sweetener concentration series. | 10.1111/j.1749-6632.1998.tb10666.x |
pubmed_401_2607 | The emergence and infusion of digital technologies bring greater chances for start-ups to conduct disruptive innovation through digital entrepreneurship. Despite the existed business practices, the happening mechanism of start-up's disruptive innovation in the digital economy context remains unclear. This study aims to understand the evolutionary mechanism and fulfillment path start-ups' disruptive innovation in the digital era. The longitudinal case study is conducted for a Chinese Internet start-up that successfully launched disruptive innovation under the digital economy background. Adopting a process perspective, this study analyzes the evolutionary phases of digital disruptive innovation. Moreover, this study identifies the digital technologies adoption, dynamic capabilities deployment, and business model innovation as the key pillars, and their interactions. Finally, this study induces and proposes its evolution mechanism and fulfillment path models. This study enriches the research scope of disruptive innovation and digital entrepreneurship. This study can offer theoretical guidance for the start-ups' disruptive innovation in the digital era, and practical implications for implementing a digital catching-up strategy. | 10.3389/fpsyg.2022.925277 |
pubmed_12_20492 | The North Carolina Seat Belt Law required an evaluation of the effectiveness of the act with a report of the findings to the Legislature three years after the law went into effect. This paper addresses changes in statewide belt usage and in occupant injury associated with that law. Observational data collected bimonthly from a probability sample of 72 sites stratified by geographic region, rural/urban location, road type, and time of day show that belt use rose from a baseline rate of 25% to a warning ticket phase rate of 45%. Belt use then reached 78% upon enforcement and is now nearly 64%. Time series analysis showed that statistically significant reductions in percentages of moderate and serious injuries occurred at the beginning of both the warning ticket and the enforcement phases. Forecasts of injuries and deaths were also developed from the time series models and were compared with observed totals. Warning tickets brought about a modest 5.4% reduction in serious injuries; fatalities among occupants covered by the law showed no change. In contrast, the subsequent enforcement phase saw a reduction of 11.6% in fatalities and 14.6% in serious or worse injuries. This represents an estimated annual savings of 131 lives and over 2,300 serious injuries in North Carolina during the 18 months following onset of enforcement. | 10.1016/0001-4575(90)90012-a |
pubmed_841_1217 | BACKGROUND
A mitochondrial protein, steroidogenic acute regulatory protein (StAR), plays an essential role in steroidogenesis by facilitating delivery of cholesterol across the mitochondrial membrane. Because ethanol (EtOH) causes suppressed estradiol (E2) secretion in prepubertal female rats and rhesus monkeys, we evaluated the effects of chronic EtOH administration on prepubertal ovarian StAR.
METHODS
Rats were implanted with a gastric cannula on day 24 and began receiving control or EtOH diets on day 28. At 0800 hr on day 33, the experimental groups were subdivided. Half of the EtOH-treated animals received a subcutaneous injection of pregnant mare serum gonadotropin (PMSG; 15 IU), and the other half received an injection of saline. The chow-fed and liquid-diet control groups were also subdivided, with half receiving the PMSG and the other half receiving saline. Eight hours after the respective injections, the animals were killed, and their ovaries and blood were collected.
RESULTS
The ovaries from EtOH-treated rats showed decreased basal expression of both the 3.8-kb (p < 0.05) and 1.7-kb (p < 0.01) StAR transcripts. PMSG-stimulated animals not exposed to EtOH showed a more than 2-fold increase (p < 0.01) in the ovarian levels of both transcripts. Western blot analysis revealed that EtOH exposure decreased (p < 0.001) the basal expression of StAR protein, which paralleled the decrease in basal StAR messenger RNA. PMSG induced an increase (p < 0.001) in the levels of StAR protein, and this effect was blunted (p < 0.01) by EtOH. These changes observed in ovarian StAR protein were paralleled by decreases in serum pregnenolone and E2.
CONCLUSIONS
These results demonstrate for the first time that ovarian StAR is a target for the chronic action of EtOH to alter prepubertal steroidogenesis, resulting in suppressed serum E2 secretion during a critical time of development. | pubmed_841_1217 |
pubmed_1023_6474 | Sixteen poultry workers with poultry house--related rhinitis and/or asthma underwent clinical and laboratory evaluation that included history and physical examination, skin tests with common inhalant and PAg, total- and specific-IgE levels, and pulmonary-function studies. Sixteen age- and sex-matched atopic subjects who were not occupationally exposed to poultry and 12 asymptomatic veterinarians with occupational exposure to poultry served as controls. Rhinitis and asthma developed only in symptomatic poultry workers after exposure to poultry; only in these individuals could immediate wheal-and-flare reactions to poultry antigens be detected (p less than 0.001). The elapsed time between the initial poultry exposure and the onset of poultry house--related symptoms averaged 10 yr. In the symptomatic poultry workers, immediate skin test reactivity and RAST reactions were most frequently associated with NFM. The association between respiratory symptoms temporally related to poultry house exposure and the demonstrable IgE antibody-mediated reaction suggests a relationship between the two. | 10.1016/s0091-6749(84)80019-6 |
pubmed_192_13392 | Aberrant activation of Ras is common in several human cancers, including cervical cancer. In this study, we show that Ras function can be inhibited by zoledronic acid (ZA) owing to its ability in inhibiting protein prenylation. Using in-vitro cell culture system and an in-vivo xenograft mouse model, the effects of ZA on cervical cancer cell growth and survival were determined. The molecular mechanisms of ZA's action were analyzed focusing on prenylation and its downstream signaling pathways. ZA inhibited proliferation and induced apoptosis of multiple cervical cancer cell lines regardless of their cellular origin and genetic profiling. The combination of ZA with paclitaxel or doxorubicin was superior to a single drug alone in cervical cancer in vitro and in vivo. Notably, complete inhibition of cervical cancer growth was observed in the combination groups. Mechanistically, ZA inhibited prenylation of oncoproteins. Ras activity was largely affected by ZA in a prenylation-dependent manner. Consistently, Ras-mediated signaling pathways such as Raf/ERK and AKt/mTOR were deactivated in cervical cancer cells exposed to ZA. Overexpression of constitutively active Ras reversed the inhibitory effects of ZA, confirming that Ras inhibition was required for the action of ZA in cervical cancer. Despite extensive efforts, there has been limited progress in the development of direct Ras inhibitors. Our findings suggest that ZA inhibits Ras activity. Our work provides fundamental evidence to repurpose ZA for the treatment of cervical cancer. | 10.1097/CAD.0000000000000779 |
pubmed_1095_2839 | Renal anemia is a well-recognized complication of chronic kidney disease (CKD), and the deficiency of erythropoietin (EPO) is the primary cause. Observational population-based studies continue to demonstrate the association of low hemoglobin with adverse outcomes, and renal failure, cardiac failure, and anemia all may interact to cause or worsen each other, the so-called cardio-renal anemia syndrome. Treatment of anemia can be successfully achieved with the use of erythropoiesis-stimulating agents (ESAs). From a mechanistic point of view, however, the therapeutic benefits of ESA could be far beyond the correction of anemia. ESA modulates a broad array of cellular processes that include progenitor stem cell development, cellular integrity, and angiogenesis. A pleiotropic effect of EPO has been shown in the central nervous system, the cardiovascular system, and the kidney. While recent results of randomized controlled trials have established that there is little support for normalizing hemoglobin in CKD patients, the results of these studies do not negate renoprotective effects of EPO. A large number of patients with CKD will benefit from early recognition and appropriate correction of anemia with ESA. | 10.1038/sj.ki.5002480 |
pubmed_565_980 | OBJECTIVE
To assess pre-operative behavioral and physiological characteristics of healthy dogs hospitalized for elective surgery.
STUDY DESIGN
Open clinical observational study.
ANIMALS
Forty-one bitches hospitalized for elective ovariohysterectomy.
METHODS
While undisturbed in a hospital cage, the behavior of the dog was recorded using a video camera and recorder. From the video recordings, various behavioral variables were registered. Simultaneous measurements were made on heart rates and heart rate variability (HRV) by use of an ambulatory electrocardiogram. In addition, the dog's response to human approach was noted.
RESULTS
Different behavioral patterns were found in the dogs studied. Thirteen individuals were regarded as highly active, and were seen to bark or howl, manipulate the environment or attempt to flee vigorously. In 13 dogs (passive dogs) none of these activities occurred. Panting and displacement behaviors, such as snout licking, were observed in nearly all the animals monitored. In general, heart rates were higher and HRV lower with the most active individuals; however, the presence of physiological arousal could not be excluded in two animals with passive behaviors. To some extent, the behavior of the dog while undisturbed in the cage was reflected in the responses to a person entering the cage.
CONCLUSIONS AND CLINICAL RELEVANCE
The different individual responses detected in this study raise an important question concerning their role and existence throughout the entire peri-operative period, especially during the post-anesthetic recovery phase when behavioral characteristics are commonly used to assess patient welfare. The results also emphasize the need for further investigations to explore the effects of pre-operative stressors on canine surgical patients, and the factors contributing to them. | 10.1111/j.1467-2995.2005.00188.x |
pubmed_65_13246 | This report describes a pilot study of a waiting-list group (preliminary process group [PPG]) that provided treatment for applicants to a university affiliated, urban mental health center. All individuals on the treatment waiting list were informed of the PPG. This semistructured group, meeting weekly, began with members presenting their problems, followed by free discussion, and ending with goal setting for the next week. Approximately one seventh (35 out of 262) of the clinic's applicants during a 4 1/2-month period chose to enter the PPG. They differed from those who chose not to participate (wait list) by being older and less educated. Approximately 80% of both wait-list and PPG participants subsequently entered therapy. Significantly more PPG patients than those on the wait list entered group treatment. The PPG served clinic needs by providing prompt service for self selected individuals and by supporting the group therapy program. | 10.1080/00207284.1999.11490962 |
pubmed_170_15005 | Each of the four canonical acid-base disorders expresses as a primary change in carbon dioxide tension or plasma bicarbonate concentration followed by a secondary response in the countervailing variable. Quantified empirically, these secondary responses are directional and proportional to the primary changes, run a variable time course, and tend to minimize the impact on body acidity engendered by the primary changes. Absence of an appropriate secondary response denotes the coexistence of an additional acid-base disorder. Here we address the expected magnitude of the secondary response to each cardinal acid-base disorder in humans and offer caveats for judging the appropriateness of each secondary response. | 10.1681/ASN.2009121211 |
pubmed_915_19162 | Neurodevelopmental disorders (NDDs) caused by aberrant brain growth and development are life-long, debilitating illnesses that markedly impair the quality of life. Animal models are a valuable tool for studying NDD pathobiology and therapies. Mounting evidence suggests the zebrafish (Danio rerio) as a useful model organism to study NDDs, possessing both high physiological homology to humans and sensitivity to pharmacological and genetic manipulations. Here, we summarize experimental models of NDDs in zebrafish and highlight the growing translational significance of zebrafish NDD-related phenotypes. We also emphasize the need in further development of zebrafish models of NDDs to improve our understanding of their pathogenesis and therapeutic treatments. | 10.1016/j.neuroscience.2019.08.034 |
pubmed_828_1180 | OBJECTIVE
To study the prevalence of dementia and its related risk factors in people aged 65 years and older in Gushan township.
METHODS
People aged 65 years or older in 22 villages of Gushan township were screened, from July 2007 to November 2007. Face to face interview with mini-mental state examination, and followed by clinical assessment. A series of neuropsychological examination was done on selected subjects based on the results of the screening tests. Clinical diagnosis on dementia was made according to the Diagnosis and Statistical Manual of Mental Disorder Fourth Edition.
RESULTS
Out of the 2913 people 2696 aged 65 years or older, were enrolled. Among the participants, 197 were confirmed of having dementia, accounting for the overall rate as 7.3%. The prevalence rate of dementia was 5.1% in males and 8.9% in females. Prevalence of dementia in the highly educated intellectuals was 9.2%, followed by 5.2%, 3.9% and 2.5% in those having received primary, junior high or senior high school education. Results from logistic regression analysis showed that the major risk factors which influencing the prevalence of dementia would include age, activies of daily living, marital status, monthly income, frequency in watching TV/movie/field show, poker player or tress and taking care of the family etc.
CONCLUSION
The prevalence rate of dementia went up along with age. Factors as watching TV/movie/field show or playing poker/chess more frequently, as well as taking good care on families tend to help reduce or postpone the development of dementia. | pubmed_828_1180 |
pubmed_906_18267 | Part 1 of these studies described poly(methyl methacrylate-r-polyoxyethylene methacrylate) P(MMA-r-POEM) comb polymers that present Arg-Gly-Asp (RGD) peptides at a surface in nanoscale clusters on a protein-resistant background for control of cell adhesion. Here in part 2, we examine surface segregation of these peptide-modified and unmodified comb polymers blended with polylactide (PLA) as a self-assembly approach suitable for surface modification of porous tissue engineering scaffolds. Multiple thermodynamic driving forces for surface enrichment of the comb polymer are exploited by annealing PLA/P(MMA-r-POEM) blends above the glass transition of the blend components but below the melting point of PLA, while in contact with water. Predictions of the interfacial composition profiles of annealed blends were made using a self-consistent field (SCF) lattice model. The calculations predict strong enrichment of the comb in the top approximately 50 A of blends, and organization of comb molecules in quasi-2D conformations at the interface, similar to the apparent structure of pure comb surfaces in contact with water described in part 1. Experimentally, PLA/comb blend surfaces were characterized by contact angle measurements, XPS, quantification of ligand-cluster surface density and stability by AFM and fluorescent nanosphere labeling, and cell attachment assays. These data were consistent with SCF predictions, showing significant enrichment of the comb at water-annealed surfaces and RGD cluster densities consistent with 2D conformations for comb molecules in the surface layer. Bulk miscibility of the blends was verified by dynamic rheometry, small-angle neutron scattering, DSC and X-ray diffraction studies. Surface segregation of combs provided tunable cell adhesion on PLA through surface-localized nanoclusters of RGD atop a cell-resistant background. | 10.1021/bm015510f |
pubmed_340_7312 | Bone homeostasis requires a delicate balance between the activities of bone-resorbing osteoclasts and bone-forming osteoblasts. Various molecules coordinate osteoclast function with that of osteoblasts; however, molecules that mediate osteoclast-osteoblast interactions by simultaneous signal transduction in both cell types have not yet been identified. Here we show that osteoclasts express the NFATc1 target gene Efnb2 (encoding ephrinB2), while osteoblasts express the receptor EphB4, along with other ephrin-Eph family members. Using gain- and loss-of-function experiments, we demonstrate that reverse signaling through ephrinB2 into osteoclast precursors suppresses osteoclast differentiation by inhibiting the osteoclastogenic c-Fos-NFATc1 cascade. In addition, forward signaling through EphB4 into osteoblasts enhances osteogenic differentiation, and overexpression of EphB4 in osteoblasts increases bone mass in transgenic mice. These data demonstrate that ephrin-Eph bidirectional signaling links two major molecular mechanisms for cell differentiation--one in osteoclasts and the other in osteoblasts--thereby maintaining bone homeostasis. | 10.1016/j.cmet.2006.05.012 |
pubmed_14_18550 | Osteoporosis is recognized as a disorder of both men and women. However, the World Health Organization's (WHO) definition of osteoporosis (a bone mineral density [BMD] T-score of -2.5 or less) was formulated for use with postmenopausal women only. In the absence of a BMD-based definition for male osteoporosis, the WHO definition is often applied to men as well. Several important questions exist when considering the use of T-scores in men. First, is the WHO definition appropriate for men? What is the impact of using a -2.5 criteria, in terms of the number of men that would be identified as osteoporotic? When calculating T-scores in men, should male or female young normal values be used? Can the same T-score criteria be used for all skeletal sites and technologies? To address these questions, osteoporosis prevalence estimates for men aged 50 yr and over were generated using WHO methods and manufacturer normative data from dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and ultrasound. Estimates were determined for several skeletal sites and technologies using both male and female young normal values. Prevalence estimates were compared to published fracture risk estimates. Mean T-scores declined with age at all measurement sites. Discrepancies were found between the different skeletal sites and techniques, similar to the previously reported differences in women. A -2.5 criterion (based on young normal males or females) appeared to underestimate the prevalence of osteoporosis, except for QCT, which seemed to overestimate risk. Depending on the technique used, 0 to 12.5 million US men 50 yr of age and older would be classified as osteoporotic using the WHO definition. T-Scores based on male norms were less discordant across skeletal sites than female-based T-scores. Male-based T-scores between -1.8 and -2.3 using DXA and ultrasound and -3.1 for QCT provided osteoporosis prevalence estimates that approximated the likelihood of common fractures in men 50 and over. We conclude that the use of single T-score-based criterion for the diagnosis of osteoporosis in men has many potential difficulties. BMD measurement techniques provide discrepant estimates of prevalence and may underestimate the size of the male population at risk for fracture. Based on available normative data, a -2.5 criterion underestimates osteoporosis prevalence in men, whether based on male or female norms. Prospective studies are needed to further refinement to the BMD definition of osteoporosis in men. | 10.1385/jcd:5:1:087 |
pubmed_1142_8860 | BACKGROUND
Within the ovary, the optimal growth of the follicle, oocyte maturation and ovulation are highly conditioned by the two-way cross talk and interactions between the oocyte and the immediate somatic cells, known as cumulus cells (CCs). This biological communication between cell lines triggered the interest in the study of CCs as a biomarker of oocyte competence.
CASE PRESENTATION
The findings of a 45,X mosaic pattern on CCs from a female patient with unremarkable medical history are reported in this study. The patient came to the Centre for Reproductive and Genetic Health, London on 14th August 2019 for her first visit and the follow up procedures were done for her to determine underlying genetic status. For this purpose, four sources of DNA including CCs, blood lymphocytes, buccal cells and immature oocytes were analyzed in the present report.
CONCLUSION
In the present case study, the hypothesis of the female patient being mosaic 45,X was confirmed although the degree of mosaicism and whether this was affecting the germinal line could not be determined. In the event of the discovery of a cell line with an apparently abnormal genetic makeup, genetic counselling is important in order to understand the implications from somatic to germinal cells for patients exploring fertility journeys. | 10.18502/jri.v22i2.5803 |
pubmed_854_6585 | As multiple sclerosis (MS) has a dynamic process, monitoring of the disability is important in the remission period. The main aim of the present study was to investigate the usefulness of MSFC instead of EDSS in the follow-up period of MS. In addition, evaluation of the effect of immunomodulatory therapy, and the difference among the type of MS in follow-up was purposed. One hundred and eighty-three patients with definite MS were enrolled in the present study. Patients were diagnosed as having relapsing-remitting (RR) MS (n=149) or secondary progressive (SP) MS (n=34). Fifty-eight out of 149 RRMS patients who had at least two relapses in the last 2 years have received any of the immunomodulator agents. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were performed at baseline and after 2 years to assess disability. Patients who were under disease modifying therapy were assessed before the treatment and 2 years after starting the treatment. Cross-sectional correlations between MSFC and EDSS score at baseline and follow-up were studied. Patients were divided into three subgroups: (1) RRMS patients who did not receive disease modifying therapy (DMT)--non-DMT group, (2) RRMS patients who received DMT--DMT group, (3) SPMS patients who did not receive DMT--SPMS group. EDSS and MSFC scores got worsened significantly at the end of the second year. Decreases in either EDSS or MSFC scores were more prominent in SPMS group. The most significant worsening was found in T25WT. The most prominent and significant decrease was in PASAT of SPMS group. Moderately strong cross-sectional correlations were found between MSFC and EDSS scores at baseline and follow-up. The most prominent correlation was between EDSS and T25WT scores with an excellent correlation. We concluded that the MSFC assesses aspects of neurological function not measured by the EDSS, suggesting that it is more sensitive to detect change over time and better able to demonstrate a therapeutic effect. The pattern of correlations among the MSFC, its components, and the EDSS supported the validity of MSFC. | 10.1016/j.jns.2005.01.008 |
pubmed_617_13997 | The accumulating failures in HIV vaccine development demonstrate that the immunization approaches used so far are insufficient to reproduce the naturally occurring immunity that controls the virus in long-term non-progressors, HIV controllers, and continuously exposed sex workers. They also underscore the desperate need for new approaches in the design of more effective vaccination protocols. Recent findings might have brought us closer to that goal by providing proof of concept for a novel preventative HIV vaccine by establishing CD8 effector memory T cells within the mucosal sites of transmission. | 10.3410/B1-89 |
pubmed_1044_13326 | Background
Distal intracranial aneurysms are often located deep in the lateral or longitudinal fissure pool or brain parenchyma, lacking a fixed anatomical location. Precise intraoperative localization of distal intracranial aneurysms is a problem that plagues neurosurgeons. Studies have shown that neuronavigation and Computed Tomography (CT) three-dimensional angiography can significantly improve the accuracy of intracranial aneurysm surgery. However, their values in the distal intracranial aneurysm surgery remain unknown. The objective of this study was to explore the application value of neuronavigation combined with CT three-dimensional angiography in distal intracranial aneurysm surgery.
Methods
112 patients admitted to our hospital for intracranial distal aneurysm surgery were retrospectively collected and divided into an observation group (n=51) and a control group (n=61) according to the surgical method received by the patients. The observation group underwent clipping treatment based on neuronavigation combined with CT three-dimensional angiography, and the control group received clipping treatment under the guidance of CT angiography. Both groups were observed for the accuracy of localization and approach design, duration of surgery, intraoperative bleeding volume, Glasgow Outcome Scale (GOS), National Institute of Health Stroke Scale (NIHSS), length of hospital stay, and complications.
Results
Compared with the control group, the localization accuracy of patients in the observation group was significantly increased (94.12% vs. 78.69%, P=0.020), and the accuracy of approach design was markedly improved (90.20% vs. 72.13%, P=0.017). Furthermore, the length of hospital stay in the observation group was notably reduced compared with the control group (8.12±2.12 vs. 8.99±1.87 d, P=0.023). There was no statistical difference in the NIHSS scores between the two groups before treatment and at 3 days after treatment (P>0.05). However, compared with the control group, the NIHSS score was significantly reduced in the observation group at 28 days after surgery (4.10±2.48 vs. 6.30±3.20, P=0.000). There were no statistically significant postoperative complications in either group (P>0.05).
Conclusions
Neuronavigation combined with CT three-dimensional angiography can enhance the accuracy of localization and approach design in intracranial distal aneurysm surgery, improve patient nerve function, and is worth promoting. | 10.21037/atm-22-1749 |
pubmed_704_24522 | OBJECTIVE
We sought to quantify the extent to which a depression screening instrument commonly used in primary care settings provides additional information regarding pain interference symptoms, anxiety, and substance use.
METHODS
Veterans Aging Cohort Study (VACS) data collected from 2003 through 2015 was used to calculate odds ratios (OR) for associations between positive depression screening result cutoffs and clustering conditions. We assessed the test performance characteristics (likelihood ratio value, positive predictive value, and the percentage of individuals correctly classified) of a positive Patient Health Questionnaire (PHQ-9 & PHQ-2) depression screen for the identification of pain interference symptoms, anxiety, and substance use.
RESULTS
A total 7731 participants were included in the analyses. The median age was 50 years. The PHQ-9 threshold of ≥20 was strongly associated with pain interference symptoms (OR 21.6, 95% CI 17.5-26.7) and anxiety (OR 72.1, 95% CI 52.8-99.0) and yielded likelihood ratio values of 7.5 for pain interference symptoms and 21.8 for anxiety and positive predictive values (PPV) of 84% and 95%, respectively. A PHQ-9 score of ≥10 still showed significant associations with pain interference symptoms (OR 6.1, 95% CI 5.4-6.9) and symptoms of anxiety (OR 11.3, 95% CI 9.7-13.1) and yet yielded lower likelihood ratio values (4.36 & 8.24, respectively). The PHQ-9 was less strongly associated with various forms of substance use.
CONCLUSION
Depression screening provides substantial additional information regarding the likelihood of pain interference symptoms and anxiety and should trigger diagnostic assessments for these other conditions. | 10.1177/2150132720949123 |
others_313_1854 | The patient presenting in an undifferentiated shock state can produce a diagnostic challenge for even the most seasoned clinician. Case Report We present an unusual case of an elderly woman in obstructive shock from a large atrial mass that was promptly diagnosed with point-of-care ultrasound. Why Should an Emergency Physician Be Aware of This? Ultrasound is a non-invasive tool that can help facilitate the early diagnosis of a patient in undifferentiated shock. © 2015 Elsevier I | 10.1016/j.jemermed.2015.06.033 |
pubmed_381_9910 | The production of onions bulbs (Allium cepa L.) requires a high amount of nitrogen. According to the demand of sustainable agriculture, the information-development and communication technologies allow for improving the efficiency of nitrogen fertilization. In the south of the province of Buenos Aires, Argentina, between 8000 and 10,000 hectares per year-1 are cultivated in the districts of Villarino and Patagones. This work aimed to analyze the relationship of biophysical variables: leaf area index (LAI), canopy chlorophyll content (CCC), and canopy cover factor (fCOVER), with the nitrogen fertilization of an intermediate cycle onion crop and its effects on yield. A field trial study with different doses of granulated urea and granulated urea was carried out, where biophysical characteristics were evaluated in the field and in Sentinel-2 satellite observations. Field data correlated well with satellite data, with an R2 of 0.91, 0.96, and 0.85 for LAI, fCOVER, and CCC, respectively. The application of nitrogen in all its doses produced significantly higher yields than the control. The LAI and CCC variables had a positive correlation with yield in the months of November and December. A significant difference was observed between U250 (62 Mg ha-1) and the other treatments. The U500 dose led to a yield increase of 27% compared to U250, while the difference between U750 and U500 was 6%. | 10.3390/agronomy12081884 |
pubmed_1030_21094 | Pembrolizumab is an immunotherapeutic agent used in various malignancies including metastatic melanoma. While immunotherapies are effective in treating several malignancies, they do come at the expense of inadvertent side effects. The numerous side effects of pembrolizumab, including, but not limited to, adrenal insufficiency, myocarditis, and pancreatitis, are well documented in clinical literature. In this case report, we describe a unique presentation of myocarditis and acute inflammatory demyelinating polyradiculoneuropathy secondary to pembrolizumab. While both side effects of pembrolizumab are well known, the delayed presentation of symptoms is of particular interest in our case report. We hope to inform the clinical community on the pharmacokinetics of pembrolizumab causing the delayed onset of symptoms. | 10.7759/cureus.27112 |
pubmed_377_2855 | Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that the adaptive immune response influences the course of human CRC. Specifically, high densities of TILs in the primary tumor are associated with good prognosis independent of other prognostic markers. However, the prognostic role of TILs in metastatic CRC lesions is unknown, as is their role in response or resistance to conventional chemotherapy. We analyzed the association of TIL densities at the invasive margin of CRC liver metastases with response to chemotherapy and progression-free survival in a set of 101 large section samples. High-resolution automated microscopy on complete tissue sections was used to objectively generate cell densities for CD3, CD8, granzyme B, or FOXP3 positive immune cells. A predictive scoring system using TIL densities was developed in a training set and tested successfully in an independent validation set. TIL densities at the invasive margin of liver metastases allowed the prediction of response to chemotherapy with a sensitivity of 79% and specificity of 100%. The association of high density values with longer progression-free survival under chemotherapy was statistically significant. Overall, these findings extend the impact of the local immune response on the clinical course from the primary tumor also to metastatic lesions. Because detailed quantification of TILs in metastatic lesions revealed a strong association with chemotherapy efficacy and prognosis, we suggest that the developed scoring system may be used as a predictive tool for response to chemotherapy in metastatic CRC. | 10.1158/0008-5472.CAN-11-0268 |
pubmed_36_16548 | In this report, we demonstrate a rapid, simple, and green method for synthesizing silver-gold (Ag-Au) bimetallic nanoparticles (BNPs). We used a novel modification to the galvanic replacement reaction by suspending maltose coated silver nanoparticles (NPs) in ≈ 2% aqueous solution of EO100PO65EO100 (Pluronic F127) prior to HAuCl4 addition. The Pluronic F127 stabilizes the BNPs, imparts biocompatibility, and mitigates the toxicity issues associated with other surfactant stabilizers. BNPs with higher Au:Ag ratios and, subsequently, different morphologies were successfully synthesized by increasing the concentration of gold salt added to the Ag NP seeds. These BNPs have enhanced catalytic activities than typically reported for monometallic Au or Ag NPs (∼ 2-10 fold) of comparable sizes in the sodium borohydride reduction of 4-nitrophenol. The 4-nitrophenol reduction rates were highest for partially hollow BNP morphologies. | 10.1039/C4RA07581A |
pubmed_183_7355 | BACKGROUND
Concordance tests are designed to assess the component of uncertainty of clinical reasoning. Scoring is based on a comparison of examinees' answers with those of a panel of reference, including their variability. This allows construction of tests that are close to real clinical life, with all its complexity and ambiguity.
AIM
This study was carried out to determine the effect of teaching functions of members composing the reference panels on students' scores and ranking.
METHODS
A group of 80 residents in family medicine from a French University (Bobigny) completed a 72-item concordance test. The answers of two panels, each made up of 29 family physicians (teaching function versus non-teaching function), were used to generate the correction keys.
RESULTS
Correlation between the sets of data obtained with the two panels is high (ICC = 0.98). Concordance scores obtained from the teaching-function panel are higher than scores obtained from the non-teaching-function panel (72.0 versus 76.3; p < 0.001). Ranking provided by the two panels was very similar.
CONCLUSIONS
This legitimizes the use of non-teaching physicians on panels. Panel composition influenced absolute score values: Residents showed more concordance with their academic trainers than with community-based physicians. | 10.1080/01421590601032427 |
pubmed_710_3867 | In studies around the world, medical students have been identified as being at high risk for poor mental wellbeing, burnout and mental ill health. This can lead on to poorer physical health, substance misuse and reduced academic performance. We surveyed Portuguese medical students to assess burnout (using the Oldenburg Burnout Inventory, OLBI), minor psychiatric illness (General Health Questionnaire 12, GHQ12) and alcohol misuse (CAGE questionnaire). A total of 622 medical students participated in the study. We found high levels of exhaustion (89%), disengagement (81%) and minor psychiatric illness (91%). The CAGE questionnaire was positive in 10% of students. Future research is required to confirm these results, assess and monitor local and global trends and investigate interventions at both local and national level to improve the mental wellbeing of medical students. | 10.1080/09540261.2019.1675283 |
pubmed_927_18374 | Short- and long-latency somatosensory evoked potentials (SEPs) were elicited by stimulation of the median nerve in 43 patients with neurological disorders. Abnormalities of short-latency peaks, P9, N13, and P14, were seen in patients with lesions of the peripheral nerve, cervical spinal cord, and brain stem, respectively. Subsequent component, N18, was affected in patients with thalamic or hemispheric disease. In some patients with parietal lobe lesions, however, abnormalities were limited to later components, N32 or N63. Analysis of SEPs is helpful in localizing a lesion along the somatosensory pathway, although differentiation between thalamic and other subcortical or cortical involvement may not be possible with the present SEP technique. Both short- and long-latency SEPs should be studied for maximal clinical information. The latter can be most reliably evaluated by simultaneous bilateral stimulation. | 10.1001/archneur.1983.04050040045007 |
pubmed_876_2543 | Self-assembly and aggregation of guanine rich sequences can provide useful insights into DNA nanotechnology and telomeric structure and function. In this paper, we designed a guanine rich sequence d(GGCGTTTTGCGG). We found that it can form stable structure in appropriate condition and it exhibits an anomalous CD spectra. This structures can be imaged in ambient environment with a Nanoscope III AFM (Digital Instruments). We found it forms branch structure and long multistrand DNA nanowire after incubation at 37 degrees C for 6-12 hours in 25 mM TE (pH=8.0) + 5 mM Mg2+ + 50 mM K+. The ability to self-assemble into branches and long wires not only clearly demonstrate its potential as scaffold structures for nanotechnology, but also give aids to understand telomeric structure further. We have proposed a model to explain how these structures formed. | 10.1080/07391102.2001.10506708 |
pubmed_262_12899 | BACKGROUND
Individuals living in poverty are more likely to smoke, and they suffer disproportionately from tobacco use. Strategies used to deliver tobacco-cessation interventions often fail to reach smokers living in poverty. Providing tobacco interventions to smokers when they present to community organizations is a potential strategy, but the acceptability and effectiveness of such interventions is unknown.
METHODS
In this 2007 pilot study, 295 smokers seeking emergency assistance from the Salvation Army in Wisconsin were randomly assigned to either a very brief (30-second) smoking intervention condition or to a control no-intervention condition. All participants completed a follow-up survey at the end of their visit assessing their satisfaction with the community agency, interest in quitting, and motivation to quit.
RESULTS
This brief intervention increased the likelihood that smokers would seek help when they decided to quit (61% vs 44%, p<0.05) but did not affect intention to quit in the next 6 months or perceived difficulty of quitting. The intervention was well received by both participants and Salvation Army staff.
CONCLUSIONS
Smokers in this pilot study found it acceptable to have their smoking addressed when seeking services from a community agency. Such interventions may need to be more intense than the one used in this study in order to achieve the goal of increased motivation to quit. Community agencies should consider including brief tobacco-dependence interventions as a secondary mission to improve their clients' health. | 10.1016/j.amepre.2009.11.015 |
pubmed_857_10461 | Retarded colonic transit and disturbed defecation are the most prominent pathophysiological mechanisms in constipation. Both may be influenced by bulking agents and by laxatives such as senna. Direct measurements of the influence of such substances on colonic transit are rare mainly because of technical problems. We measured gastric emptying, small and large intestinal transit in 24 healthy volunteers by a newly developed method employing a metal detector. Twelve persons taking a normal diet received loperamide in a dose sufficient to double the individual transit time. All subjects measured gastrointestinal transit time under normal conditions and with Sennatin containing purified sennosides 20 mg, Agiocur (30 g) as a fibre product containing 20 g Plantago ovata seeds/husks, or Agiolax (10 g) as a combination of 5.4 g P. ovata seeds/husks + 1.2 g senna pod with a sennoside content of 30 mg. Colonic transit was reduced by Sennatin and by Agiolax from 39 +/- 4 h to 17 +/- 3 h (p < 0.005). Agiocur did not influence colonic transit (39 +/- 3 h). Loperamide prolonged colonic transit from 27 +/- 0.7 to 72 +/- 12 h. This effect was abolished by Sennatin (30 +/- 5 h) and Agiolax (27 +/- 1 h) (p < 0.005), but not by Agiocur (64 +/- 13 h). The same effects were seen when right and left colonic transit were analyzed separately. Neither gastric emptying nor small intestinal transit were affected by either substance. All of the three study drugs increased stool weight significantly (p < 0.05). When stool frequency and consistency were compared, the effects were less clear.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1159/000139864 |
pubmed_365_17247 | The plethora of actions attributed to 1,25(OH)2D3 throughout the body have suggested potential therapeutic applications for the treatment of hyperproliferative diseases, immune dysfunction, endocrine disorders, and metabolic bone disease. However, the potent calcemic activity of the natural vitamin D hormone has precluded its use in most cases. New vitamin D analogues are under development that display greater specificity, in most cases, by retaining the therapeutic properties of 1,25(OH)2D3, but with lower calcemic activity. Two analogues have been approved for use in patients: calcipotriol (Dovonex from Leo Pharmaceuticals, Copenhagen, Denmark) for the treatment of psoriasis; and 19-nor-1,25(OH)2D2 (Zemplar from Abbott Laboratories, Abbott Park, IL) for secondary hyperparathyroidism. Many others analogues are currently being tested in preclinical and clinical trials for the treatment of various types of cancer and osteoporosis, and for immunosuppression. The selectivity of the analogues can be attributed to the combined interactions with four proteins: the vitamin D receptor (VDR), the serum vitamin D binding protein (DBP), the vitamin D-24-hydroxylase and to a newly described membrane receptor. Low DBP affinity has been shown to be responsible for the reduced calcemic actions of calcipotriol and 22-oxacalcitriol (OCT), which is being tested for secondary hyperparathyroidism. However, the low calcemic activity of other analogues, including 19-nor-1,25(OH)2D2, involves other, as yet undefined, mechanisms. Understanding of the molecular basis for the selectivity of the vitamin D analogues will allow the design of more effective and safer vitamin D compounds for the treatment of a wide range of clinical disorders. | 10.1053/ajkd.1998.v32.pm9808141 |
pubmed_130_25233 | Cancer is a severe health condition and considered one of the major healthcare issues and is in need of innovative strategy for a cure. The current study aimed to investigate the chemical profile of Trigonella hamosa L. and a potential molecular approach to explain its regulation in cancer progression through an inflammatory mediator (COX-2) in A549 non-small lung cancer cell lines via in silico, mechanistic and molecular aspects. T. hamosa was extracted and then subjected to a CCK-8 cell viability assay in different cancer cell lines including MDA-MB-231, A549 and HCT-116. Total extract was subjected to several chromatographic techniques to yield orientin (OT); the structure was elucidated by inspection of NMR spectroscopic data. To achieve anticancer effects of OT, a cell viability assay using a CCK-8 kit, immunoprecipitation by Western blot, cell migration using a wound healing assay, cell invasion using a Matrigel-Transwell assay, apoptosis by AO/EB dual staining, flow cytometric analysis and DAPI staining, a silenced COX-2 model to determine PGE-2 production and real-time PCR and Western blot of BCL-2, CYP-1A1, iNOS and COX-2 markers were carried out. The results demonstrated that OT decreased the cell proliferation and controlled cell migration and invasive properties. OT destabilized the COX-2 mRNA and downregulated its expression in A549 cell lines. Virtual binding showed interaction (binding energy -10.43) between OT and COX-2 protein compared to the selective COX-2 inhibitor celecoxib (CLX) (binding energy -9.4). The OT-CLX combination showed a superior anticancer effect. The synergistic effect of OT-CLX combination was noticed in controlling the migration and invasion of A549 cell lines. OT-CLX downregulated the expression of BCL-2, iNOS and COX-2 and activated the proapoptotic gene CYP-1A1. OT mitigated the COX-2 expression via upregulation of miR-26b and miR-146a. Interestingly, COX-2-silenced transfected A549 cells exhibited reduced expression of miR-26b and miR-146a. The findings confirmed the direct interaction of OT with COX-2 protein. PGE-2 expression was quantified in both naïve and COX-2-silenced A549 cells. OT downregulated the release of PGE-2 in both tested conditions. These results confirmed the regulatory effect of OT on A549 cell growth in a COX-2-dependent manner. OT activated apoptosis via activation of CYP-1A1 expression in an independent manner. These results revealed that the OT-CLX combination could serve as a potential synergistic treatment for effective inflammatory-mediated anticancer strategies. | 10.3390/ph15020154 |
pubmed_19_22910 | INTRODUCTION
Cycloxygenase-2 (COX-2) is an enzyme involved in prostaglandin E2 (PGE(2)) synthesis associated with higher renal cell carcinoma stage. COX-2 inhibition enhances interferon (IFN-α) anti-tumor immune effects in pre-clinical models. A phase II trial of celecoxib and IFN-α in a targeted population of metastatic renal cell carcinoma patients with maximal COX-2 expression was conducted.
METHODS
Cytokine-naive metastatic renal cell carcinoma patients with tumors expressing ≥10% maximal COX-2 staining by immunohistochemistry received IFN-α 5 million units daily and celecoxib 400 mg orally twice daily in an open-label, single-arm phase II trial.
RESULTS
There were 3 partial responses among 17 patients (objective response rate 18%; 95% confidence interval, 4-43%). Time to progression was 5.6 months. Increased tumor staining 3+ for COX-2 was associated with increased baseline peripheral blood PGE(2) levels, and these patients demonstrated less PGE(2) decrease with therapy. Patients with more 3+ COX-2 staining had significantly more CD3(+) (p = 0.004) and CD4(+) (p = 0.002) IFN-γ T cells at baseline and a significantly greater decrease in these cells with therapy.
DISCUSSION
Celecoxib plus IFN-α in renal cell carcinoma (RCC) patients with maximally staining COX-2 tumors does not significantly enhance overall response rates over IFN monotherapy.
CONCLUSION
COX-2-expressing RCC demonstrates inherent immunosuppression. COX-2 inhibition with IFN results in minimal immunomodulation and no augmented clinical activity in RCC. | 10.1007/s10875-011-9530-x |
pubmed_328_24948 | The current opioid epidemic is an urgent public health problem, with enormous individual, societal, and healthcare costs. Despite effective, evidence-based treatments, there is significant individual variability in treatment responses and relapse rates are high. In addition, the neurobiology of opioid-use disorder (OUD) and its treatment is not well understood. This review synthesizes published fMRI literature relevant to OUD, with an emphasis on findings related to opioid medications and treatment, and proposes areas for further research. We conducted a systematic literature review of Medline and Psychinfo to identify (i) fMRI studies comparing OUD and control participants; (ii) studies related to medication, treatment, abstinence or withdrawal effects in OUD; and (iii) studies involving manipulation of the opioid system in healthy individuals. Following application of exclusionary criteria (e.g., insufficient sample size), 45 studies were retained comprising data from ~1400 individuals. We found convergent evidence that individuals with OUD display widespread heightened neural activation to heroin cues. This pattern is potentiated by heroin, attenuated by medication-assisted treatments for opioids, predicts treatment response, and is reduced following extended abstinence. Nonetheless, there is a paucity of literature examining neural characteristics of OUD and its treatment. We discuss limitations of extant research and identify critical areas for future neuroimaging studies, including the urgent need for studies examining prescription opioid users, assessing sex differences and utilizing a wider range of clinically relevant task-based fMRI paradigms across different stages of addiction. | 10.1038/s41386-018-0232-4 |
pubmed_248_2807 | Normal pregnancy is characterized by attenuated vascular reactivity to a variety of contractile agonists and this, in part, has been attributed to increased circulating vasodilators and/or impaired Ca(2+)-influx through L-type Ca(2+)-channels. Our hypothesis in this study was that reduced Ca(2+)-dependent (influx) and Ca(2+)-independent (involving the RhoA/Rho-kinase pathway) mechanisms contributed to attenuated vasopressin-induced contraction of the pregnant rat aorta. AVP (10(-10) -3 x 10(-7) M) induced concentration-dependent contraction of aortic ring segments from nonpregnant and pregnant rats with no significant change in pD(2) values (8.53+/-0.11 and 8.33+/-0.18 in nonpregnant and pregnant rats, respectively). The maximum response was however significantly reduced in aorta segments from pregnant rats. Nifedipine (10(-6) M) significantly inhibited AVP-induced contraction in artery segments from nonpregnant but not pregnant rats indicating a reduced role for Ca(2+)-influx through L-type Ca(2+)-channels in AVP-induced contractions of the pregnant rat aorta. Western blot analysis revealed the expression of ROCK-1 and ROCK-II isoforms in aorta segments from both groups. There was a significant reduction in the expression of ROCK-1 and ROCK-II isoforms in aortic tissues from pregnant rats. This is consistent with the reduced potency of Y-27632 in inhibiting AVP (10(-7) M) induced contraction in aorta segments from pregnant rats. It was concluded that pregnancy-induced attenuated vascular response to AVP was due to decreased Ca(2+)-influx through L-type Ca(2+)-channels and decreased sensitization of the contractile myofilaments to Ca(2+). | 10.1016/j.vph.2005.11.003 |
pubmed_343_2842 | INTRODUCTION
The rapid ageing of populations around the world is accompanied by increasing prevalence of multimorbidity. This study is one of the first to present the prevalence of multimorbidity that includes HIV in the complex epidemiological setting of South Africa, thus filling a gap in the multimorbidity literature that is dominated by studies in high-income or low-HIV prevalence settings.
METHODS
Out of the full sample of 5059 people aged 40+, we analysed cross-sectional data on 10 conditions from 3889 people enrolled in the Health and Ageing in Africa: A longitudinal study of an INDEPTH Community in South Africa (HAALSI) Programme. Two definitions of multimorbidity were applied: the presence of more than one condition and the presence of conditions from more than one of the following categories: cardiometabolic conditions, mental disorders, HIV and anaemia. We conducted descriptive and regression analyses to assess the relationship between prevalence of multimorbidity and sociodemographic factors. We examined the frequencies of the most prevalent combinations of conditions and assessed relationships between multimorbidity and physical and psychological functioning.
RESULTS
69.4 per cent (95% CI 68.0 to 70.9) of the respondents had at least two conditions and 53.9% (52.4-55.5) of the sample had at least two categories of conditions. The most common condition groups and multimorbid profiles were combinations of cardiometabolic conditions, cardiometabolic conditions and depression, HIV and anaemia and combinations of mental disorders. The commonly observed positive relationships between multimorbidity and age and decreasing wealth were not observed in this population, namelydue to different epidemiological profiles in the subgroups, with higher prevalence of HIV and anaemia in the poorer and younger groups, and higher prevalence of cardiometabolic conditions in the richer and older groups. Both physical functioning and well-being negatively associated with multimorbidity.
DISCUSSION
More coordinated, long-term integrated care management across multiple chronic conditions should be provided in rural South Africa. | 10.1136/bmjgh-2018-001386 |
pubmed_653_21852 | Intact male Boer and Kiko goats (n=48) were harvested after 0, 4, 8, or 12 weeks on a 16% crude protein concentrate diet. Boneless goat carcass left sides were ground and formed into patties to evaluate cook loss, texture profile analysis, and descriptive sensory characteristics. Increasing feeding duration increased percent fat and decreased moisture in raw ground meat (P<0.05). Boer ground meat had more fat and less moisture than Kiko meat (P<0.05). Breed and feeding duration did not affect cook loss (P>0.05). Increased feeding duration increased aroma intensity and goaty, bloody, musty, and liver/organy aromas; salty, bitter, umami, grassy, goaty, fat, liver/organy, metallic, earthy, and chemical flavors; and juiciness and oiliness, while decreasing chewiness and crumbliness (P<0.05). Boer and Kiko patties had similar sensory properties after 0 and 4weeks on feed, but breeds were more distinguishable after 8 or 12 weeks on feed. | 10.1016/j.meatsci.2012.01.002 |
pubmed_875_8134 | BACKGROUND
Non-albicans Candida (NAC) spp. in immunocompromised patients are linked to invasive infections with narrow treatment choice. This study aimed at comparing the oral colonization of NAC spp. between HIV and non-HIV infected individuals in Mwanza, Tanzania.
METHOD
Oral rinse of 351 HIV-infected and 639 non-HIV infected individuals were collected between March and July 2015. Phenotypic identifications of Candida spp. was done using Candida Chromogenic agar and confirmed by MALDI-TOF MS.
RESULTS
NAC spp. were detected in 36/351 (10.3%) HIV-infected individuals compared to 28/639 (4.4%) of non-HIV infected individuals; P=0.0003. In HIV infected individuals, commonly isolated NAC spp. were Candida tropicalis, 10(2.8%), C. krusei (Issatschenki orientalis) 9(2.6%) and C. glabrata 8(2.3%). While for non-HIV infected individuals C. dubliniensis 8(1.3%) and C. tropicalis 5(0.9%) were commonly detected. As CD4 count/μl decreases by one unit the risk of being colonized by NAC spp. among HIV infected individuals increases by 1% (OR 1.01, 95% CI; 1.001-1.004, P=0.001).
CONCLUSION
The prevalence of NAC spp. is high among HIV-infected individuals with low CD4 count placing them at higher risk of invasive infections. Further studies to investigate the role of NAC spp. in causing invasive infections among immunocompromised patients are recommended. | pubmed_875_8134 |
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