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pubmed_687_11330
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Serial third trimester ultrasound examinations for fetal biometry are recommended for women with risk factors of fetal growth restriction (FGR). We conducted a retrospective cohort study on all singleton births in Victoria from 2009 to 2017 to assess how many women with major risk factors for FGR had serial third trimester biometry. Only 19.5% of women with at least one major risk factor for FGR had evidence of serial third trimester ultrasound assessments. The development and implementation of a state-wide or nationwide guideline for early pregnancy risk factor assessment in FGR may be beneficial.
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10.1111/ajo.13147
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pubmed_899_6306
|
BACKGROUND
Genetic material from large patient cohorts is increasingly central to translational genetic research. However, patient blood samples are a finite resource and their supply and storage are often dictated by clinical and not research protocols. Our experience supports difficulty in amplifying DNA from blood stored in herparin; a scenario that other researchers may have or will encounter. This technical note describes a number of simple steps that enable successful PCR amplification.
METHODS
DNA was extracted using the Illustra Nucleon Genomic DNA Extraction Kit. PCR amplification was attempted using a number of commercially available PCR mastermixes.
RESULTS
PCR DNA amplification failed using ReddyMix™ PCR Master Mix, Thermo-Start® (Thermo Scientific Inc. US) and ZymoTaq™ (Zymo research, US) PCR mastermixes, as demonstrated absence of products on gel electrophoresis. However, using the Invitrogen™ (Thermo Scientific Inc., US) Platinum® Taq DNA Polymerase, PCR products were identified on a 1% agarose gel for all samples. PCR products were cleaned with ExoSAP-IT® (Affymetrix Inc., US) and a sequencing reaction undertaken using a standard Big Dye protocol. Subsequent genotyping was successful for all samples for alleles at the CDH1 locus.
CONCLUSION
From our experience a standard phenol/chloroform purification and using the Invitrogen™ Platinum® Taq has enabled the amplification of whole blood samples taken into lithium heparin and stored frozen for up to a month. This simple method may enable investigators to utilise blood taken in lithium heparin for DNA extraction and amplification.
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10.1007/s13402-015-0250-8
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pubmed_418_20900
|
Prosthetic joint infections (PJIs) are rare but feared complications following joint replacement surgery. Cutibacterium acnes is a skin commensal that is best known for its role in acne vulgaris but can also cause invasive infections such as PJIs. Some phylotypes might be associated with specific diseases, and recently, a plasmid was detected that might harbour important virulence genes. In this study, we characterized C. acnes isolates from 63 patients with PJIs (n = 140 isolates) and from the skin of 56 healthy individuals (n = 56 isolates), using molecular methods to determine the phylotype and investigate the presence of the plasmid. Single-locus sequence typing and a polymerase chain reaction designed to detect the plasmid were performed on all 196 isolates. No statistically significant differences in sequence types were seen between the two study groups indicating that the C. acnes that causes PJIs originates from the patients own normal skin microbiota. Of the 27 patients with multiple tissue samples, 19 displayed the same sequence types among all their samples. Single-locus sequence typing identified different genotypes among consecutive C. acnes isolates from four patients with recurrent infections. The plasmid was found among 17 isolates distributed in both groups, indicating that it might not be a marker for virulence regarding PJIs. Patients presenting multiple sequence types in tissue samples may represent contamination or a true polyclonal infection due to C. acnes.
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10.1016/j.anaerobe.2019.04.011
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pubmed_149_16658
|
PURPOSE OF REVIEW
This article summarizes recent advances in the identification of genetic and environmental factors that affect the risk of developing multiple sclerosis (MS) and the pathogenic processes involved in acute relapses and relapse-independent disability progression.
RECENT FINDINGS
The number of single-nucleotide polymorphisms associated with increased risk of MS has increased to more than 200 variants. The evidence for the association of Epstein-Barr virus infection, vitamin D deficiency, obesity, and smoking with increased risk of MS has further accumulated, and, in cases of obesity and vitamin D deficiency, the evidence for causal association has strengthened. Interactions between genetic and environmental factors have been studied more extensively. Dietary factors and changes in the gut microbiota are emerging as possible modulators of the disease risk. Several processes important to MS pathogenesis have been newly investigated or investigated more comprehensively, including the role of B cells, innate immune cells, meningeal inflammation, cortical and gray matter demyelination, and early axonal and neuronal loss.
SUMMARY
MS is a complex disease in which the interaction between genetic and environmental factors causes a cascade of events, including activation of the adaptive and innate immune system, blood-brain barrier breakdown, central nervous system demyelination, and axonal and neuronal damage with variable degrees of repair. These events manifest as potentially reversible focal neurologic symptoms or progressive nonremitting physical and cognitive disability, or both. Advances in the understanding of the risk factors and pathogenic mechanisms of MS have resulted in improved therapeutic strategies. The results of ongoing or future studies are needed to successfully and fully translate these advances into clinical practice.
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10.1212/CON.0000000000000725
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pubmed_861_19458
|
Religions often operate as comprehensive worldviews, attempting to answer the deepest existential questions that human beings can ask: Who am I? Where do I come from? Where am I going after I die? How should I live? Often ethical systems are embedded and justified within these broader narratives. Inevitably, the clinical ethics consultant will encounter and engage with religiously based ethical systems. In this issue, the authors reflect seriously and deeply on the implications of such engagement.
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10.1007/s10730-019-09374-8
|
pubmed_108_5181
|
BACKGROUND
Primary headaches are the most common cause of absence from work and school and one of the most common reasons for referring to the neurologists.
OBJECTIVES
The present study was designed to investigate the relationship of cognitive processing style and mindfulness with pain intensity and the ultimate aim was to provide the role of pain-related cognitive processes and mindfulness in the prediction of headache intensity.
METHODS
The study was conducted descriptively by using the correlation method. The statistical population of this study was composed of 85 patients (56 females and 29 males) with one type of primary headache, which were selected through purposive sampling after the diagnosis of a headache by a neurologist at Imam Hossein Hospital in Tehran province. To measure the variables of the study, the numeric pain rating scale (NRS) and the pain-related cognitive processes questionnaire (PCPQ) were used. All data were analyzed using descriptive statistics (frequency and percentages). Bivariate correlation matrix and hierarchical stepwise linear regression statistics were used.
RESULTS
The results showed that there was a significant and negative association between pain intensity (NRS) and mindfulness (P < 0.01) and all pain-related cognitive processes, except pain focus (P < 0.01). The results of stepwise linear regression indicated that mindfulness only explains 39% of total score changes in pain intensity (P < 0.05 and ΔF (1 and 83) = 53.63, ΔR = 0.385). Adding cognitive processing styles to the model led to an 18% increase of the explained variance (R2 change = 0.179). In total, the present research model justifies 54% of the severity of headache variance (P < 0.01, ΔR = 0.54).
CONCLUSIONS
The results suggest that pain-related cognitive processes and mindfulness are effective on pain intensity prediction. In other words, this result can explain the role of mindfulness and adaptive cognitive processing in primary headache pain management.
|
10.5812/aapm.82470
|
pubmed_78_18429
|
A stacking approach based on pH junction and field amplification has been developed for determining amines by capillary electrophoresis (CE) with electrochemiluminescence (ECL) detection. A two-electrode configuration was employed with an indium/tin oxide-coated glass as a working electrode and a platinum wire as a pseudoreference electrode. The ECL system also contains a flow cell (poly(dimethylsiloxane)-aluminum oxide) that was made from a mixture of Sylgard 184 silicone elastomer, a curing agent, and aluminum oxide. In order to improve the sensitivity of the present CE-ECL system using tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)(3) (2+)), a stacking approach based on pH junctions and field amplification has been tested for the analysis of triethylamine (TEA), tripropylamine (TPA), and tributylamine (TBA). Once amines (cations) prepared in citric acid solution (pH < 4.0) migrate towards the background electrolyte (15 mM sodium borate at pH 8.0), they slow down and are stacked at the boundary as a result of deprotonation and decreases in the electric field. By applying hydrodynamic injection of the sample for 60 s, this method provides the concentration limits of detection (signal-to-noise ratio = 3) of 24, 20, and 32 nM for TEA, TPA, and TBA, respectively. The results indicate that the stacking CE-ECL system is better than CE-ECL systems using a two-electrode configuration and comparable to those using a three-electrode configuration. The potential applicability of the new and low-cost CE-ECL system has been demonstrated by the determination of 1.0 microM lidocaine, a local anesthetic drug, in urine without any tedious sample preparation.
|
10.1002/elps.200500009
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pubmed_647_13338
|
The olfactory bulb is the target of neural progenitor cells that are generated in the subventricular zone of the lateral ventricle in the adult brain. This permanent neurogenesis is likely influenced by olfactory input to the bulb since previous studies have shown that cell proliferation and/or apoptotic death are stimulated by naris closure or surgical transection of the olfactory nerve. Since the olfactory bulb is densely innervated by noradrenergic afferents originating in the locus coeruleus, we have studied the impact of pharmacologically activating this noradrenergic system on cell death and proliferation following unilateral olfactory axotomy in the adult mouse olfactory bulb. We found that noradrenaline release in the olfactory bulb was significantly increased by intraperitoneal injections of the selective alpha(2)-adrenoceptor antagonists, dexefaroxan (0.63 mg/kg) and 5-fluoro-methoxyidazoxan (F 14413; 0.16 mg/kg). A chronic treatment with either compound for 7 days following olfactory axotomy significantly reduced neuronal death, glial activation and cell proliferation in the deafferented olfactory bulb. These data (1) confirm that alpha(2)-adrenoceptor antagonists, presumably by facilitating central noradrenergic transmission, afford neuroprotection in vivo, as previously shown in models of cerebral ischemia, excitotoxicity and devascularization-induced neurodegeneration, and (2) support a role of the locus coeruleus noradrenergic system in promoting survival of neurons in areas of the brain where neurogenesis persists in the adult.
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10.1016/j.expneurol.2005.03.004
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pubmed_290_21273
|
Indigo, an emblematic violet dye used for thousands of years to colour fabric, is resistant to fading on exposure to sunlight. Prior work has indicated that indigo is reactive towards both hydroperoxyl radicals and superoxide anions in solution. In order to promote photobleaching of indigo, we have utilised a BOPHY-based (BOPHY = aryl fused symmetrical pyrrole-BF2 complex) chromophore known to form both superoxide ions and a stable alkyl hydroperoxide under illumination in aerated solution. Selective irradiation of the photocatalyst causes relatively fast fading of indigo, with the rate increasing gently with increasing concentration of indigo. Molecular oxygen and light are essential for effective bleaching. One molecule of photocatalyst can bleach more than 40 molecules of indigo. An active component of the photocatalyst is a butylated hydroxytoluene (BHT) residue which itself quenches the triplet excited state of indigo. This provides an ancillary mechanism for effecting photofading of indigo but, because the triplet is formed in very low yield, this route is less practical.
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10.1039/c9pp00355j
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pubmed_856_2908
|
The gilthead sea bream (Sparus aurata) is a marine fish of great importance for Mediterranean aquaculture. This species has long been considered resistant to Nervous Necrosis Virus (NNV), an RNA virus that causes massive mortalities in several farmed fish animals. However, the recent appearance of RGNNV/SJNNV reassortant strains started to pose a serious threat to sea bream hatcheries, as it is able to infect larvae and juveniles of this species. While host response to NNV has been extensively studied in adult fish, little attention has been devoted to early life history stages, which are generally the most sensitive ones. Here we report for the first time a time-course RNA-seq analysis on 21-day old fish gilthead sea bream larvae experimentally infected with a RGNNV/SJNNV strain. NNV-infected and mock-infected samples were collected at four time points (6 h, 12 h, 24 h, and 48 h post infection). Four biological replicates, each consisting of five pooled larvae, were analysed for each time point and group. A large set of genes were found to be significantly regulated, especially at early time points (6 h and 12 h), with several heat shock protein encoding transcripts being up-regulated (e.g. hspa5, dnaj4, hspa9, hsc70), while many immune genes were down-regulated (e.g. myd88 and irf5 at T06, pik3r1, stat3, jak1, il12b and il6st at T12). A gene set enrichment analysis (GSEA) identified several altered pathways/processes. For instance, the formation of peroxisomes, which are important anti-viral components as well as essential for nervous system homeostasis, and the autophagy pathway were down-regulated at 6 h and 24 h post infection (hpi). Finally, two custom "reactomes" (i.e. significant gene sets observed in other studies) were defined and used. The first reactome integrated the transcriptomic response to NNV in different fish species, while the second one included all genes found to be stimulated either by interferon (IFN) or by IFN and Chikungunya virus in zebrafish. Genes in both reactomes showed predominant up-regulation at 6hpi and 12hpi and a general down-regulation at 24hpi. Such evidence suggest a certain degree of similarity between the response of sea bream and that of other fish species to NNV, while the observed down-regulation of IFN- and viral-stimulated pathways argues for a possible interference of NNV against the host response.
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10.1016/j.fsi.2021.04.021
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pubmed_284_604
|
Tallis [1962] formulated and solved the problem of constructing a selection index whose use will produce changes in the means of genotypic values of various traits that are proportional to ultimately desired changes. Several meaningful variations of this problem are described, and their solutions are presented in a common framework.
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pubmed_284_604
|
pubmed_1034_19006
|
OBJECTIVES
The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease.
METHODS
We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls. Moreover, to detect sui generis language disturbances, we ran analysis of covariance tests using executive functions as covariate.
RESULTS
The two clinical groups showed impairments in all measures, most of which survived covariation with executive functions. However, the key finding concerned asymptomatic mutation carriers. While these subjects showed intact executive, semantic, and action-verb production skills, they evinced deficits in a syntactic test with minimal working memory load.
CONCLUSIONS
We propose that this sui generis disturbance may constitute a prodromal sign anticipating eventual development of PD. Moreover, our results suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. (JINS, 2017, 23, 150-158).
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10.1017/S1355617716000710
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pubmed_902_1637
|
In this work, the constrained equilibrium principle is introduced and applied to the derivations of the nonequilibrium solvation free energy and solvent reorganization energy in the process of removing the hydrated electron. Within the framework of the continuum model, a modified expression of the vertical detachment energy (VDE) of a hydrated electron in water is formulated. Making use of the approximation of spherical cavity and point charge, the variation tendency of VDE accompanying the size increase of the water cluster has been inspected. Discussions comparing the present form of the VDE and the traditional one and the influence of the cavity radius in either the fixed pattern or the varying pattern on the VDE have been made.
|
10.1021/jp908759s
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pubmed_491_22863
|
There is compelling evidence that the tumor microenvironment plays a major role in mediating aggressive features of cancer cells, including invasive capacity and resistance to conventional and novel therapies. Among the different cell populations that infiltrate cancer stroma, mast cells (MCs) can influence several aspects of tumor biology, including tumor development and progression, angiogenesis, lymphangiogenesis, and tissue remodelling. Thyroid cancer (TC), the most frequent neoplasia of the endocrine system, is characterized by a MC infiltrate, whose density correlates with extrathyroidal extension and invasiveness. Recent evidence suggests the occurrence of epithelial-to-mesenchymal transition (EMT) and stemness in human TC. The precise role of immune cells and their mediators responsible for these features in TC remains unknown. Here, we review the relevance of MC-derived mediators (e.g., the chemokines CXCL1/GRO-α, CXCL10/IP-10, and CXCL8/IL-8) in the context of TC. CXCL1/GRO-α and CXCL10/IP-10 appear to be involved in the stimulation of cell proliferation, while CXCL8/IL-8 participates in the acquisition of TC malignant traits through its ability to induce/enhance the EMT and stem-like features of TC cells. The inhibition of chemokine signaling may offer novel therapeutic approaches for the treatment of refractory forms of TC.
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10.1155/2015/705169
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pubmed_1123_7545
|
Osteoarthritis (OA) is one of the most debilitating diseases affecting mankind with severe financial and emotional consequences. The heterogeneity of the human population, lack of complete understanding of the OA disease process, and the slow progressive nature of the disease characterized by prolonged periods of nonsymptomatic, degenerative changes has hampered development of ideal diagnostic and prognostic portfolios. The difficulties associated with early OA diagnosis by exclusively radiographic techniques has propelled a need to identify specific biomarkers for rapid and effective early OA diagnosis, better patient prognosis, and for monitoring the efficacy of pharmacological interventions to the disease process. This review highlights some of the biochemical biomarkers in current use in OA, their applications and limitations. Investigation of single nucleotide polymorphisms as genetic biomarkers and the application of technologies such as lipidomics and metabolomics to OA are generating potentially additional biomarkers that could be helpful for detecting early OA phenomena in humans.
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10.1055/s-0031-1286192
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pubmed_291_5609
|
A few studies have reported the existence of depletion of synaptic vesicles, and changes in neurotransmitter release and in the content of exocytotic proteins in the hippocampus of diabetic rats. Recently, we found that diabetes alters the levels of synaptic proteins in hippocampal nerve terminals. Hyperglycemia is considered the main trigger of diabetic complications, although other factors, such as low insulin levels, also contribute to diabetes-induced changes. Thus, the aim of this work was to evaluate whether long-term elevated glucose per se, which mimics prolonged hyperglycemia, induces significant changes in the content and localization of synaptic proteins involved in exocytosis in hippocampal neurons. Hippocampal cell cultures were cultured for 14 days and were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose), for 7 days. Cell viability and nuclear morphology were evaluated by MTT and Hoechst assays, respectively. The protein levels of vesicle-associated membrane protein-2 (VAMP-2), synaptosomal-associated protein-25 (SNAP-25), syntaxin-1, synapsin-1, synaptophysin, synaptotagmin-1, rabphilin 3a, and also of vesicular glutamate and GABA transporters (VGluT-1 and VGAT), were evaluated by immunoblotting, and its localization was analyzed by immunocytochemistry. The majority of the proteins were not affected. However, elevated glucose decreased the content of SNAP-25 and increased the content of synaptotagmin-1 and VGluT-1. Moreover, there was an accumulation of syntaxin-1, synaptotagmin-1 and VGluT-1 in the cell body of some hippocampal neurons exposed to high glucose. No changes were detected in mannitol-treated cells. In conclusion, elevated glucose per se did not induce significant changes in the content of the majority of the synaptic proteins studied in hippocampal cultures, with the exception of SNAP-25, synaptotagmin-1 and VGluT-1. However, there was an accumulation of some proteins in cell bodies of hippocampal neurons exposed to elevated glucose, suggesting that the trafficking of these proteins to the synapse may be compromised. Moreover, these results also suggest that other factors, in addition to hyperglycemia, certainly contribute to alterations detected in synaptic proteins in diabetic animals.
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10.1016/j.neuroscience.2010.10.019
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pubmed_703_13730
|
The aim of this study was to investigate whether direct PCR (DP) gave similar results to culture prior to PCR (CPP) for detecting mycoplasmas in different types of pig tissues. A total of 724 samples obtained from lungs, tonsils, or synovial fluids from 270 slaughtered pigs were used. The history of clinical signs, lung score, and the presence of joint lesions were recorded during sample collection. The rates of detection of Mycoplasma hyopneumoniae, Mycoplasma hyosynoviae, and Mycoplasma hyorhinis using both procedures were evaluated. The overall prevalences of M. hyopneumoniae, M. hyosynoviae, and M. hyorhinis were 40.3%, 12.3%, and 64.6%, respectively, and the detection rate depended on the sample type and the procedure used. With lung tissue, DP gave a higher detection rate for M. hyopneumoniae (77.4%) than CPP (38.5%). M. hyorhinis was detected by CPP at 15.6% and 18.1% and by DP at 31.5% and 5.2%, respectively. The positive rate derived from tonsil from CPP was closed to that of DP. Using synovial fluid could not yield any positive M. hyorhinis from CPP whereas 37.2% was positive from DP. In contrast, using sample tissue from lung and tonsil by CPP could show much higher positive number than that of DP. There was a significant relationship between joint lesion and M. hyorhinis detection by DP (P < 0.05) but not for M. hyosynoviae and M. hyorhinis detected by CPP. We speculated that lung was a proper sample for M. hyopneumoniae and M. hyorhinis detection by DP and CPP, respectively. Tonsil was likely the community of persistent M. hyosynoviae and M. hyorhinis with highly detection by CPP. Synovial fluid was apparently unsuitable for mycoplasmal culture. The accuracy of mycoplasmal detection may depend upon the type of sample relevant to the detection procedure used.
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10.1007/s11250-011-0022-z
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pubmed_239_16954
|
In this work, we present a statistical mechanical analysis to elucidate the molecular-level factors responsible for the static and dynamic properties of polymer films. This analysis, which we term conformal sites theory, establishes that three dimensionless parameters play important roles in determining differences from bulk behavior for thin polymer films near to surfaces: a microscopic wetting parameter, αwx, defined as the ratio of polymer-substrate interaction to polymer-polymer interaction; a dimensionless film thickness, H*; and dimensionless temperature, T*. The parameter αwx introduced here provides a more fundamental measure of wetting than previous metrics, since it is defined in terms of intermolecular forces and the atomic structure of the substrate, and so is valid at the nanoscale for gas, liquid or solid films. To test this theoretical analysis, we also report atomic force microscopy measurements of the friction coefficient (μ), adhesion force (FA) and glass transition temperature (Tg) for thin films of two polymers, poly(methyl methacrylate) (PMMA) and polystyrene (PS), on two planar substrates, graphite and silica. Both the friction coefficient and the glass transition temperature are found to increase as the film thickness decreases, and this increase is more pronounced for the graphite than for the silica surface. The adhesion force is also greater for the graphite surface. The larger effects encountered for the graphite surface are attributed to the fact that the microscopic wetting parameter, αwx, is larger for graphite than for silica, indicating stronger attraction of polymer chains to the graphite surface.
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10.1039/c7sm00261k
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pubmed_391_10509
|
Platelet activating factor (PAF) is produced by the rat renal papilla from a neutral lipid, alkylacetylglycerol. Renal release of another neutral lipid, antihypertensive neutral renomedullary lipid, and PAF might account for normalization of blood pressure after unclipping in Goldblatt hypertensive rats. We studied the potential storage and release of hypotensive substances by the rat renal papilla in vitro. Rat kidneys were snap-frozen in liquid N2-cooled freon immediately after removal and the total lipids were extracted from pooled dissected papillae and partially separated by thin layer chromatography on silica gel with a hexane: ether: acetic acid (40:60:1) solvent system. Lipids eluted from four, contiguous silica gel zones were assayed in anesthetized spontaneously hypertensive rats. No hypotensive activity was found in the thin layer chromatography lipid fraction co-migrating with palmitylacetylglycerol or in any other neutral lipid fraction. In contrast, the Krebs medium obtained after 30-min incubation of freshly minced papillary tissue induced dose-related hypotension and bradycardia. The hypotensive activity was equivalent to 48 +/- 9 ng prostaglandin E2 (PGE2)/mg wet papilla. Bradycardia induced by the incubation medium was correlated with decrements in blood pressure. In the same assays, nitroprusside caused tachycardia which was correlated with hypotension, and the bradycardia associated with PGE2-induced hypotension was significantly less than that induced by the incubation medium. The dose-related effects of the incubation medium were dramatically attenuated by indomethacin treatment of the papilla, suggesting that the hypotensive activity is dependent upon papillary cyclooxygenase activity. However, PGI2 elicited hypotension concomitant with tachycardia rather than bradycardia and PGE2 did not mimic the incubation medium-induced bradycardia. Therefore, the effects of the papillary incubation medium may be mediated by other cyclooxygenase metabolites. Production/release of hypotensive material by indomethacin-treated papillary tissue was potentiated by co-incubation with non-hypotensive quantities of PGE2, suggesting a potential role for PGE2 in the renal antihypertensive function. Increasing pressure on the papilla from 6 to 20 mmHg during incubation did not increase release of non-prostanoid hypotensive substance(s). These results suggest that the formation and release of cyclooxygenase metabolites accounts primarily for the hypotensive activity released from rat renal papillae in vitro, and that prostaglandins might play a permissive role in the release of other renomedullary hypotensive substances.
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10.1097/00004872-199108000-00009
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pubmed_532_14401
|
Ion channels modulate ion flux across cell membranes, activate signal transduction pathways, and influence cellular transport-vital biological functions that are inexorably linked to cellular processes that go awry during carcinogenesis. Indeed, deregulation of ion channel function has been implicated in cancer-related phenomena such as unrestrained cell proliferation and apoptotic evasion. As the prototype for ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs) have been extensively studied in the context of neuronal cells but accumulating evidence also indicate a role for nAChRs in carcinogenesis. Recently, variants in the nAChR genes CHRNA3, CHRNA5, and CHRNB4 have been implicated in nicotine dependence and lung cancer susceptibility. Here, we silenced the expression of these three genes to investigate their function in lung cancer. We show that these genes are necessary for the viability of small cell lung carcinomas (SCLC), the most aggressive type of lung cancer. Furthermore, we show that nicotine promotes SCLC cell viability whereas an α3β4-selective antagonist, α-conotoxin AuIB, inhibits it. Our findings posit a mechanism whereby signaling via α3/α5/β4-containing nAChRs promotes lung carcinogenesis.
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10.3389/fphys.2013.00251
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pubmed_809_16237
|
The melanin-concentrating hormone receptor 1 (MCH-1R) has been recognized as a receptor which mediates effects of the endogenous melanin-concentrating hormone (MCH) on appetite and body weight gain in rodents. In the last several years, a number of hMCH analogs have been designed which were potent and selective ligands for hMCH-1R. These peptidic agonists and antagonists have served as research tools in animal studies that showed a key role of the MCH-1R in the development of obesity and proved that MCH-1R antagonism can produce anti-obesity effects in rodents.
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10.2174/156802607782194734
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pubmed_400_12300
|
OBJECTIVE
To compare the incidence and define the risk factors associated with liver toxicity in patients beginning treatment with nevirapine (NVP) and efavirenz (EFZ).
METHOD
This was a retrospective chart review of all HIV-infected patients starting any antiretroviral regimen containing at least two nucleoside analogues plus either NVP or EFZ between January 1998 and January 2000. Liver toxicity was defined as an increase in transaminase levels 5-fold above the upper limits of normal if they were normal at baseline or 3.5-fold above baseline levels if they were previously elevated.
RESULTS
Out of 298 patients included in the study, 162 received NVP and 136 EFZ. Overall, 75% were men, and 45% were coinfected with the hepatitis C virus (HCV). Median (interquartile range) time on follow-up was 10 (6-12) months. Liver toxicity was more frequently associated with NVP (12%) than with EFZ (4%) (p =.016). Overall, it was first recognized at a median time of 5.5 months (2.7-9.2) on therapy, with no differences between treatment arms. Both univariate and multivariate analyses identified the use of NVP, HCV coinfection, alcohol abuse, and female gender as independent risk factors for liver toxicity.
CONCLUSION
Liver damage is three times more common in patients receiving NVP than in those taking EFZ. In both groups of patients, it is recognized late, after an average of 5.5 months on therapy. Coinfection with HCV, alcohol abuse, and female gender increase the risk for developing liver toxicity with both drugs.
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10.1310/N4VT-3E9U-4BKN-CRPW
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pubmed_312_14605
|
Free radicals from the one-electron reduction of adrenochrome have been studied in aqueous solutions. These radicals have been detected and identified by electron spin resonance spectroscopy, using spin stabilization methods (complexation with diamagnetic metal ions) to enhance radical concentrations. It is shown that the radicals have a characteristic ESR spectrum enabling their identification in complex systems. The spin density distribution in the radicals has been studied as a function of complexing metal ions and solvent composition. In the presence of oxidants (e.g., oxygen) the spectrum of the radical is replaced by that derived from the one-electron exidation of adrenochrome.
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10.1016/0304-4165(85)90157-6
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pubmed_197_6399
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The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, peripheral T cells expressing a TCR with low avidity for self-antigens were strongly reduced, whereas an overall impairment of T-cell activation by weak antigenic stimulation was observed. Mechanistically, Nck deletion resulted in a significant decrease in calcium mobilization and ERK phosphorylation upon TCR engagement. Taken together, our findings unveil a crucial role for the Nck adaptors in shaping the T-cell repertoire to ensure maximal antigenic coverage and optimal T cell excitability.
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10.1073/pnas.1009743107
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pubmed_952_8966
|
Chlormethiazol in body-fluids and tissues is measured with a sensitive gaschromatographic method. The blood-concentration is a reference point for calculating the dosage and effect of chlormethiazol especially in medical questions of behaviour in traffic. The blood levels after a single and also long-term dosage were determined.
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10.1007/BF02332344
|
pubmed_924_17396
|
When space limitations are primary constraints, laminated barriers with metals can be an option to provide sufficient shielding for a radiotherapy treatment room. However, if a photon clinical beam with end point energy of 10 MeV or higher interacts with the metal inside the barriers neutrons are ejected and can result in an exposure problem inside and outside the vault. The empirical formulae existing in the literature to estimate neutron dose equivalents beyond laminated barriers do not take into account neutron production for spectra below 15 MV. In this work, the Monte Carlo code MCNP was used to simulate the production and transport of photoneutrons across primary barriers of 10 MV accelerator treatment rooms containing lead or steel, in order to obtain the ambient dose equivalents produced by these particles outside the room and in the patient plane. It was found that the neutron doses produced are insignificant when steel is present in the primary barriers of 10 MV medical accelerators. On the other hand, the results show that, in all cases where lead sheets are positioned in the primary barriers, the neutron ambient dose equivalents outside the room generally exceed the shielding design goal of 20 microSv/week for uncontrolled areas, even when the lead sheets are positioned inside the treatment room. Moreover, for laminated barriers, the photoneutrons produced in the metals are summed with the particles generated in the accelerator head shielding and can represent a significant component of additional dose to the patients. In this work, it was found that once lead sheets are positioned inside the room, the neutron ambient dose equivalents can reach the value of 75 microSv per Gray of photon absorbed dose at the isocenter. However, for all simulated cases, a tendency in the reduction of neutron doses with increasing lead thickness can be observed. This trend can imply in higher neutron ambient dose equivalents outside the room for thinner lead sheets. Therefore, when a medical accelerator treatment room is designed with laminated barriers to receive equipment with an end point energy equal to or higher than 10 MeV, not only the required shielding thickness for photon radiation attenuation should be considered, but also the dose due to photoneutrons produced in the metal, which may involve an increase of the lead thickness or even the use of neutron shielding.
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10.1118/1.2940192
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pubmed_701_14490
|
Much is written about the scope of nurses' professional practice. This article examines the ways in which clinical nurse specialists in stoma care may strive to extend their practice without losing sight of their ideals.
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10.12968/bjon.1995.4.17.1001
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pubmed_1040_8288
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In this paper, we have traced changes in the patterns of first marriage in the United States for cohorts of men and women born in 1880 through 1965 and for the years from 1900 through 1983. There were striking changes in marriage rates associated with each of the world wars and with the depression of the 1930s. In addition to these short-term fluctuations, a long-term shift in marriage rates is observed over the period from after World War II until about 1970. By the end of the 1970s, however, marriage rates had returned to levels similar to those observed before the war. The basic similarity in the timing of changes in marriage rates across age levels and for both men and women, blacks and whites, is a striking characteristic of these marriage curves. There are also, however, important differences among these groups with respect to the magnitude and slopes of the shifts. The postwar marriage boom was strongest among the young (those under age 24) and among whites. Similarly, the declines in marriage rates observed in the 1970s were greatest among the young. The marriage rates for teenagers display trends that diverge in many respects from those of older persons. For example, the marriage rates of male teenagers did not show the "peaks" and "valley" associated with World War II for older age groups and female teenagers. Moreover, there is little sign of the postwar marriage boom among black teenagers of either sex. Indeed, the marriage rates of black teenagers began to decline soon after the war, and by the 1970s the marriage rates of both male and female black teenagers had fallen below those of their white counterparts, reversing the pattern that had existed through the first half of this century. During the twenty-five or so years of the postwar marriage boom, which we believe can be characterized best as a period phenomenon, there were trends-eddies within the mainstream-which are probably most easily interpreted as the consequence of a cohort effect.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed_1040_8288
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pubmed_403_11966
|
OBJECTIVES
Serologic techniques can serve as a complement to diagnose SARS-CoV-2 infection. The objective of our study was to compare the diagnostic performance of six immunoassays to detect antibodies against SARS-CoV-2: three lateral flow immunoassays (LFAs), one ELISA and two chemiluminescence assays (CLIAs).
METHODS
We evaluated three LFAs (Alltest, One Step and SeroFlash), one ELISA (Dia.Pro) and two CLIAs (Elecsys and COV2T). To assess the specificity, 60 pre-pandemic sera were used. To evaluate the sensitivity, we used 80 serum samples from patients with positive PCR for SARS-CoV-2. Agreement between techniques was evaluated using the kappa score (k).
RESULTS
All immunoassays showed a specificity of 100 % except for SeroFlash (96.7 %). Overall sensitivity was 61.3 %, 73.8 %, 67.5 %, 85.9 %, 88.0 % and 92.0 % for Alltest, One Step, SeroFlash, Dia.Pro, Elecsys and COV2T, respectively. Sensitivity increased throughout the first two weeks from the onset of symptoms, reaching sensitivities over 85 % from 14 days for all LFAs, being One Step the most sensitive (97.6 %), followed by SeroFlash (95.1 %). Dia.Pro, Elecsys and COV2T showed sensitivities over 97 % from 14 days, being 100 % for COV2T. One Step showed the best agreement results among LFAs, showing excellent agreement with Dia.Pro (agreement = 94.2 %, k = 0.884), COV2T (99.1 %, k = 0.981) and Elecsys (97.3 %, k = 0.943). Dia.Pro, COV2T and Elecsys also showed excellent agreement between them.
CONCLUSIONS
One Step, Dia.Pro, Elecsys and COV2T obtained the best diagnostic performance results. All these techniques showed a specificity of 100 % and sensitivities over 97 % from 14 days after the onset of symptoms, as well as excellent levels of agreement.
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10.1016/j.jviromet.2020.114047
|
pubmed_788_4345
|
BACKGROUND
This study was done to investigate the potential additional role of virtual reality, using three-dimensional (3D) echocardiographic holograms, in the postoperative assessment of tricuspid valve function after surgical closure of ventricular septal defect (VSD).
METHODS
12 data sets from intraoperative epicardial echocardiographic studies in 5 operations (patient age at operation 3 weeks to 4 years and bodyweight at operation 3.8 to 17.2 kg) after surgical closure of VSD were included in the study. The data sets were analysed as two-dimensional (2D) images on the screen of the ultrasound system as well as holograms in an I-space virtual reality (VR) system. The 2D images were assessed for tricuspid valve function. In the I-Space, a 6 degrees-of-freedom controller was used to create the necessary projectory positions and cutting planes in the hologram. The holograms were used for additional assessment of tricuspid valve leaflet mobility.
RESULTS
All data sets could be used for 2D as well as holographic analysis. In all data sets the area of interest could be identified. The 2D analysis showed no tricuspid valve stenosis or regurgitation. Leaflet mobility was considered normal. In the virtual reality of the I-Space, all data sets allowed to assess the tricuspid leaflet level in a single holographic representation. In 3 holograms the septal leaflet showed restricted mobility that was not appreciated in the 2D echocardiogram. In 4 data sets the posterior leaflet and the tricuspid papillary apparatus were not completely included.
CONCLUSION
This report shows that dynamic holographic imaging of intraoperative postoperative echocardiographic data regarding tricuspid valve function after VSD closure is feasible. Holographic analysis allows for additional tricuspid valve leaflet mobility analysis. The large size of the probe, in relation to small size of the patient, may preclude a complete data set. At the moment the requirement of an I-Space VR system limits the applicability in virtual reality 3D echocardiography in clinical practice.
|
10.1186/1476-7120-5-8
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pubmed_949_3526
|
OBJECTIVE
To find the factors related with the research activities of primary care (PC) doctors in Catalonia, especially their motivation and the obstacles to research perceived by the doctors themselves.
DESIGN
An observational, crossover study.
SETTING
Primary care doctors in Catalonia.
PARTICIPANTS
The number of doctors (1,286) was divided into two: a) doctors who had published between 1989 and 1994 (n = 146), b) doctors who had not published.
INTERVENTIONS
A survey concerning personal and workplace variables was carried out by post.
RESULTS
The reply percentage was 49.5% (63.7% among those who had published and 44.85% among those who had not). The multivariant analysis showed a significant link between publishing and postgraduate residence training (MIR), the fact of working in a teaching centre and working in a centre with more than ten doctors.
CONCLUSIONS
Research is close related to postgraduate residence training (MIR), work in a teaching unit and PC centres with over ten doctors. Care load, lack of time and difficulty in getting financing were the main obstacles to research given by the doctors polled.
|
pubmed_949_3526
|
pubmed_354_10208
|
BACKGROUND
The Patient Dignity Inventory (PDI) is based on an empirically-driven dignity model that has been developed and used for clinically assessing the various sources of dignity-related distress. In a recent review, it received the highest score as a useful instrument in both practice and research in palliative care. The PDI has been adapted to and validated for use in various countries, but not yet Sweden.
AIMS
To translate the PDI into Swedish, including cultural adaptation for clinical use.
METHODS
A multi-step process of translation, negotiated consensus, expert group discussion (n=7: four invited experts and three researchers) and cognitive interviewing (n=7: persons with palliative care needs).
FINDINGS
Discussion, by the expert reviewers, of both linguistic and cultural issues regarding the content and readability of the translated Swedish version resulted in revisions of items and response alternatives, focusing mainly on semantic, conceptual, and experiential equivalence. A pilot version for cognitive interviews was produced. The analysis of data showed that most of the items were judged to be relevant by the persons with palliative care needs.
CONCLUSION
The process of translation and adaptation added clarity and consistency. The Swedish version of the PDI can be used in assessing dignity-related distress. The next step will be to test this Swedish version for psychometric properties in a larger group of patients with palliative care needs before use in research.
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10.12968/ijpn.2019.25.7.334
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pubmed_431_4336
|
In the past 25 years, academic leaders and accreditation bodies in internal medicine and pediatrics have made multiple efforts to increase residents' exposure to ambulatory primary care medicine, to bring hospital-based residency training more in line with the career paths of graduates. Current proposals continue the trend of increasing ambulatory exposure through providing more clinical hours in the outpatient setting as a pedagogic strategy to improve residents' practical skills in providing quality care in outpatient settings. Resident clinics, however, are often understaffed and dysfunctional. Under these circumstances, the work environment encourages some residents to learn only that providing high-quality primary care is a frustrating and unrewarding form of labor. Leaders in medicine have used innovative organizational strategies to improve residents' outpatient experiences. Model primary care residency programs and clinics have been created. The diffusion of model primary care clinical practices and structures is, however, limited by the strain of generating sufficient clinical revenue to run an academic medical center efficiently and reliably in the current environment. Increased outpatient exposure, without attention to the quality of practice settings, is potentially counterproductive, generating an unintended consequence that is the opposite of the goals of policy: it may reinforce residents' interest in subspecialty practice.
|
10.1097/ACM.0b013e31816be3ab
|
pubmed_756_22165
|
This study aimed to evaluate the predictive performance of genetic risk models based on risk loci identified and/or confirmed in genome-wide association studies for type 2 diabetes mellitus. A systematic literature search was conducted in the PubMed/MEDLINE and EMBASE databases through April 13, 2012, and published data relevant to the prediction of type 2 diabetes based on genome-wide association marker-based risk models (GRMs) were included. Of the 1,234 potentially relevant articles, 21 articles representing 23 studies were eligible for inclusion. The median area under the receiver operating characteristic curve (AUC) among eligible studies was 0.60 (range, 0.55-0.68), which did not differ appreciably by study design, sample size, participants' race/ethnicity, or the number of genetic markers included in the GRMs. In addition, the AUCs for type 2 diabetes did not improve appreciably with the addition of genetic markers into conventional risk factor-based models (median AUC, 0.79 (range, 0.63-0.91) vs. median AUC, 0.78 (range, 0.63-0.90), respectively). A limited number of included studies used reclassification measures and yielded inconsistent results. In conclusion, GRMs showed a low predictive performance for risk of type 2 diabetes, irrespective of study design, participants' race/ethnicity, and the number of genetic markers included. Moreover, the addition of genome-wide association markers into conventional risk models produced little improvement in predictive performance.
|
10.1093/aje/kwt123
|
pubmed_757_26481
|
In this study, we report the lowest energy structure of bare Cu13 nanoclusters as a pair of enantiomers at room temperature. Moreover, we compute the enantiomerization energy for the interconversion from minus to plus structures in the chiral putative global minimum for temperatures ranging from 20 to 1300 K. Additionally, employing nanothermodynamics, we compute the probabilities of occurrence for each particular isomer as a function of temperature. To achieve that, we explore the free energy surface of the Cu13 cluster, employing a genetic algorithm coupled with density functional theory. Moreover, we discuss the energetic ordering of isomers computed with various density functionals. Based on the computed thermal population, our results show that the chiral putative global minimum strongly dominates at room temperature.
|
10.3390/molecules26185710
|
pubmed_884_5345
|
Clinical and experimental evidence indicates a possible role for vitamin A deficiency in the pathogenesis of bronchogenic carcinoma. We, therefore, measured serum vitamin A levels in 67 newly diagnosed non-resectable lung cancer patients. In 43 of these patients daily vitamin A intake was also determined. Serum vitamin A levels were within the normal range of the general population of 66 of the 67 patients. Eighteen of 43 patients had daily vitamin A intakes less than 5000 IU/day while 25 patients had daily intake above this level. The serum vitamin A level did not correlate with histologic subtype, extent of disease or presence or absence of hepatic metastases. While these data suggest that vitamin A deficiency was not implicated in pulmonary carcinogenesis, more definitive conclusions await prospective evaluation of high risk individuals followed serially for many years.
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10.1016/s0304-3835(78)93357-8
|
pubmed_568_22682
|
Carcinosarcoma is an aggressive tumor that can develop in any organ but is rarely observed in the urinary tract. Given the radioresistant nature of carcinosarcoma and the rapidly regrowing tumor after primary surgery, carcinosarcomas that developed in the body showed poor outcomes regardless of aggressive management. However, the specific optimal treatment for periurethral carcinosarcoma remains unknown. The present study reports a rare case of periurethral carcinosarcoma with metastasis of the skull after receiving surgery for primary tumors with adjuvant concurrent chemoradiation therapy.
|
10.1016/j.eucr.2021.101699
|
pubmed_830_10648
|
OBJECTIVES
We explore how alternative and complementary care use is affected by wait list length and availability of conventional care in Canada.
DESIGN
We use data from the 2003 Canadian Community Health Survey, Statistics Canada and the Fraser Institute to explore the effect of longer wait times on the use of alternative therapies in general and for specific therapies: Registered Massage Therapy, Chiropractics, Physiotherapy, Homeopathy and Acupuncture.
OUTCOME MEASURES
We use binary variables indicating whether the individual used various types of alternative care in the year preceding the survey.
RESULTS
Wait times for specialists are associated with lower probabilities of using alternative care, but the effect are usually not statistically significant. Longer wait times for non-emergency surgery are associated with lower probabilities of using alternative care when using data from CANSIM, but very small higher probabilities of using alternative care when using data from the Fraser Institute which includes wait times for treatments for other procedures than non-emergency surgery. We find positive but extremely small effects for total wait times from the Fraser Institute. Individuals reporting unmet health care needs are more likely to use alternative care while individuals who do not have a regular physician are less likely to use it.
CONCLUSIONS
Reporting unmet health care needs or no family physician have more of an impact on the use of alternative therapies than wait lists do. The evidence is not clear as to whether alternative care is sometimes used as a substitute to conventional care rather than a complement.
|
10.1016/j.ctim.2012.06.001
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pubmed_372_2253
|
Ferumoxytol is an intravenous iron oxide nanoparticle formulation that has been approved by the U.S. Food and Drug Administration (FDA) for treating anemia in patients with chronic kidney disease. In recent years, ferumoxytol has also been demonstrated to have potential for many additional biomedical applications due to its excellent inherent physical properties, such as superparamagnetism, biocatalytic activity, and immunomodulatory behavior. With good safety and clearance profiles, ferumoxytol has been extensively utilized in both preclinical and clinical studies. Here, we first introduce the medical needs and the value of current iron oxide nanoparticle formulations in the market. We then focus on ferumoxytol nanoparticles and their physicochemical, diagnostic, and therapeutic properties. We include examples describing their use in various biomedical applications, including magnetic resonance imaging (MRI), multimodality imaging, iron deficiency treatment, immunotherapy, microbial biofilm treatment and drug delivery. Finally, we provide a brief conclusion and offer our perspectives on the current limitations and emerging applications of ferumoxytol in biomedicine. Overall, this review provides a comprehensive summary of the developments of ferumoxytol as an agent with diagnostic, therapeutic, and theranostic functionalities.
|
10.7150/thno.67375
|
pubmed_698_12517
|
This study examined the effects of conditions (that is, the fee structure and the easy of obtaining a dental appointment) on patient understanding and cooperation in clinical practice for dental hygiene and dental students. A questionnaire was given sequentially to 1483 patients attending the Tokyo Medical and Dental University dental hospital on "clinical education and patient satisfaction". Direct participants consisted of 650 patients, of which 213 (32.8%) were male and 422 (64.9%) female. The remaining 15 (2.3%) did not specify their gender. Patients who were satisfied with care received by dentists tended to be older compared to patients who were dissatisfied with dentists. The difference was significant (p < 0.001). Acceptable conditions for patients such as fees and appointments at the clinical session had an effected on patient acceptance of clinical training. The findings of this study suggest that patient satisfaction should be considered as part of the reasons for patients accepting dental care by students in their clinical education programs. Fees and appointment schedules strongly affect patient acceptance of clinical education.
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pubmed_698_12517
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pubmed_743_6972
|
Blumea laciniata is widely used as a folk medicine in Asia, but relevant literature on it is rarely reported. We confirmed that polyphenol extract (containing chlorogenic acid, rutin, and luteolin-4-O-glucoside) from B. laciniata (EBL) showed strong antioxidant ability in vitro. Hence, in this work, we applied Caenorhabditis elegans to further investigate the antioxidant and anti-ageing abilities of EBL in vivo. The results showed that EBL enhanced the survival of C. elegans under thermal stress by 12.62% and sharply reduced the reactive oxygen species level as well as the content of malonaldehyde. Moreover, EBL increased the activities of antioxidant enzymes such as catalase and superoxide dismutase. Additionally, EBL promoted DAF-16, a transcription factor, into the nucleus. Besides, EBL extended the lifespan of C. elegans by 17.39%, showing an anti-ageing effect. Different mutants indicated that the insulin/IGF-1 signaling pathway participated in the antioxidant and anti-ageing effect of EBL on C. elegans.
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10.3390/antiox10111744
|
pubmed_1140_14571
|
The purpose of this study was to evaluate pain perception rates in pediatric patients by comparing computerized injection device and traditional injection procedure. In a clinical trial, by using a crossover design, sixty-four patients were randomly assigned to receive, in consecutive sessions, dental anesthetic techniques with either traditional or computerized device. Visual Analogue Scale qualification and heart rate monitoring as physiologic indicator of pain response were used for the evaluation. Results showed that traditional syringe injections were more painful than computerized injection device (p < 0.001). Results suggested that computerized injection device reduces pain perception compared to the traditional syringe during the dental anesthetic management.
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10.17796/jcpd.29.3.jgh607l870051882
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pubmed_737_20874
|
Omnidirectional and broadband light harvesting is critical to photovoltaics due to the sun's movement and its wide spectral range of radiation. In this work, we demonstrate distinctive indium-tin-oxide nanowhiskers that achieve superior angular and spectral characteristics for crystalline silicon solar cells using angle-resolved reflectance spectroscopy. The solar-spectrum weighted reflectance is well below 6% for incident angles of up to 70° and for the wavelength range between 400nm and 1000nm. As a result, the nanowhisker coated solar cell exhibits broadband quantum efficiency characteristics and enhanced short-circuit currents for large angles of incidence.
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10.1364/OE.19.00A219
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pubmed_1044_19507
|
BACKGROUND
Results of ACL reconstruction are influenced by both patient and surgical variables. Until now a significant amount of studies have focused on the influence of surgical technique on primary outcome, often leaving patient variables untouched. This study investigates the combined influence of patient and surgical variables through multivariate analysis.
METHODS
Single-center retrospective cohort study. All patients who underwent primary ACL hamstring reconstruction within a 5-year period were included. Patient characteristics (gender, age, height, weight, BMI at time of surgery) and surgical variables (surgical technique, concomitant knee injury, graft diameter, type of femoral and tibial fixation) were collected. Patients were asked about Tegner Activity Scale (TAS), complications and revision surgery. Multivariate logistic regression was used to study risk factors. First graft failure and potential risk factors (patient and surgical) were univariately assessed. Risk factors with a p-value ≤ 0.05 were included in the multivariate model.
RESULTS
Six hundred forty-seven primary ACL hamstring reconstructions were included. There were 41 graft failures (failure rate 6.3%). Patient gender, age, height and preoperative TAS had a significant influence on the risk of failure in the univariate analysis. The multivariate analyses showed that age and sex remained significant independent risk factors. Patients with a failed ACL reconstruction were younger (24.3 vs 29.4 years, OR 0.937), with women at a lower risk for failure of their ACL reconstruction (90.2% males vs 9.8% females, female OR 0.123). ACL graft diameter and other surgical variables aren't confounders for graft failure.
CONCLUSION
This study shows that patient variables seem to have a larger influence on the failure rate of ACL hamstring reconstructive surgery than surgical variables. Identification of the right patient variables can help us make more informed decisions for our patients and create patient-specific treatment protocols. Young men's higher risk of failure suggests that these patients may benefit from a different reconstruction technique, such as use of a patellar tendon or combined ligament augmentation.
LEVEL OF EVIDENCE
Retrospective cohort III.
|
10.1186/s12891-022-05547-8
|
pubmed_425_10260
|
There are many diagnostic methods to assist clinicians in assessing adnexal masses on ultrasound. After suggesting a standardized terminology and measurement technique to evaluate adnexal masses, the International Ovarian Tumor Analysis (IOTA) group has developed different strategies such as the Simple Rules and Assessment of Different Neoplasias in the adneXa (ADNEX) model, which have been shown to outperform other available methods. Besides differentiating between benign neoplasms and malignancies, the ADNEX model can also give the predicted risk for different subtypes of malignant adnexal masses, which is clinically very relevant for guiding patient management.
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10.1016/j.ogc.2019.07.003
|
pubmed_920_26232
|
BACKGROUND
The health benefits of breastfeeding are well known. However, some ill babies including those admitted to the neonatal intensive care unit (NICU) cannot be directly breastfed. In this situation, expressed breast milk (EBM) can be used. However, breast milk is not always sterile and may be contaminated by many microorganisms. EBM contamination is probably attributed to improper technical and hygienic factors and may pose significant threats to the newborn baby. The present study aimed to document the prevalence of EBM contamination in NICU and to uncover the relevant risk factors.
SUBJECTS AND METHODS
The study included 118 mothers who could express breast milk for their own neonates admitted to the NICU. A checklist was used to document the steps the mothers followed during expression of milk and all steps of handling until the EBM reached the NICU. A 1 mL sample of EBM was obtained and sent to the microbiology laboratory within 20 minutes. Data obtained from the present study are expressed as number and percentage or mean ± standard deviation (SD). Statistical calculations were computed using SPSS 25.
RESULTS
In the present study, 106 (89.8%) out of the assessed 118 EBM samples were contaminated. Hygienic factors related to EBM contamination included hand only wash, possible recontamination of hands during turning taps off, lack of using cotton pads or cloth piece on nipple and breast cleaning by water only. Other factors related to EBM contamination included container cleaning by water only, fresh milk refrigeration after > 4 hours, adding freshly expressed warm breast milk to refrigerated milk expressed earlier in the same day, milk transport in plastic bags with ice packs and longer transportation time. In the contaminated samples, the most commonly isolated organisms included Staphylococcus aureus (55.7%),Staphylococcus epidermidis (21.7%) and Enterobacter (11.6%).
CONCLUSION
The present study identified bacterial contamination in about 90% of EBM samples delivered to NICU infants. Factors related to EBM contamination include hygienic, storage and transport factors.
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10.2147/PHMT.S311632
|
pubmed_1122_12787
|
OBJECTIVE
Assessment of loss of bone density (BD) 1 year after a 2-year period of hormone replacement therapy (HRT) with two doses of Tibolone as compared to placebo in early post-menopausal women.
METHODS
Sixty-four out of 84 women (1-3 years following spontaneous menopause) who completed a 2-year randomised, placebo controlled study to evaluate effects of Tibolone participated in this follow-up study. Quantitative computed tomography was used to exclusively measure trabecular BD, microdensitometry of the mid-phalangeal shaft was used for estimation of cortical BD and biochemical markers of bone metabolism were assessed, 1 year after discontinuation of Tibolone. The study group received either placebo (n = 16), 1.25 mg/day Tibolone (n = 25) or 2.5 mg/day Tibolone (n = 23).
RESULTS
Observations revealed a significantly greater decrease in trabecular BD during the post-trial year in both treatment groups compared to the placebo group (for 1.25 mg/day Tibolone, -6.0%, 95% CI -8.4 to -3.5; for 2.5 mg/day Tibolone, -10.0%, 95% CI: -12.9 to -6.9). In contrast, there was no significant difference in loss of phalangeal BD in both treatment groups compared to placebo. Biochemical markers (serum alkaline phosphatase, urinary excretion of hydroxyproline and calcium) do not suggest an increased bone turnover comparing Tibolone groups to placebo, 1 year after cessation of Tibolone.
CONCLUSION
The present study suggests an increased loss of trabecular but not cortical BD as compared to the placebo group in the first year after cessation of HRT with Tibolone in early post-menopausal women.
|
10.1016/s0378-5122(98)00089-9
|
pubmed_476_7958
|
Observational studies reveal substantial variability in microbiome composition across individuals. Targeted studies in gnotobiotic animals underscore this variability by showing that some bacterial strains colonize deterministically, while others colonize stochastically. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, in this paper we show that for the model organism Drosophila melanogaster, interactions between bacteria can affect the microbiome assembly process, contributing to a baseline level of microbiome variability even among isogenic organisms that are identically reared, housed, and fed. In germ-free flies fed known combinations of bacterial species, we find that some species colonize more frequently than others even when fed at the same high concentration. We develop an ecological technique that infers the presence of interactions between bacterial species based on their colonization odds in different contexts, requiring only presence/absence data from two-species experiments. We use a progressive sequence of probabilistic models, in which the colonization of each bacterial species is treated as an independent stochastic process, to reproduce the empirical distributions of colonization outcomes across experiments. We find that incorporating context-dependent interactions substantially improves the performance of the models. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration and should inform the design of synthetic fecal transplants and dosing regimes.
|
10.1073/pnas.2115877119
|
pubmed_517_17300
|
It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.
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10.3390/v2010283
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pubmed_977_17500
|
HYPOTHESIS
The emerging aqueous-based Cerberus emulsion droplets with multi-domains behave as an excellent platform to design cyto-mimetic compartmentalization for fabrication of anisotropic biomimetic materials and microreactors. However, the ultralow water/water interfacial tension impedes fabrication of aqueous Cerberus droplets in batch-scale and precisely topology regulation especially under lack of deep understanding of w/w interface properties.
EXPERIMENTS
Aqueous-based ternary phase diagram composed by salt, hydrophilic polymer and fluorocarbon compound is determined. Different emulsions employing the multiple aqueous solutions as internal phase and vegetable oil as continuous phase, are prepared by traditional vortex mixing based on the diagram. The construction mechanism of (W1 + W2 + W3)/O Cerberus droplets and relationship between droplet topology and the diagram are investigated.
FINDINGS
Diverse categories of aqueous-based emulsions from single emulsions, Janus emulsions, to Cerberus emulsions are delicately controlled in the same system based on the diagram. Various morphologies of Cerberus droplets such as linear and fan-like configurations are obtained, although spreading coefficient based on interfacial tension indicates preference of onion-like configuration. The viscosity plays an unexpected role in the construction of Cerberus droplets due to highly sensitive water/water interfaces within the droplets. Moreover, an empirical equation is perfectly applied, which endows quantitative prediction and control of lobe volume ratio within Cerberus droplets.
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10.1016/j.jcis.2022.06.178
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pubmed_929_6389
|
INTRODUCTION
To determine changes in anxiety perceived in students during their first experience injecting local anaesthetic and assess the variability in the perception in the teaching/learning experience as surgeons and patients in relation to gender.
MATERIAL AND METHODS
This cross-sectional study was carried out on students enrolled in the Anaesthesia and Resuscitation course at the University of Barcelona. A descriptive and bivariate analysis was carried out using McNemar and Fisher tests. The level of significance was set at a P-value of <.05.
RESULTS
Out of 85 students, a total of 71 responses were obtained. Overall, significant anxiety changes associated with the inferior alveolar nerve block were observed, specifically, before and during (P = .003), before and after (P < .001), and during and after (P < .001) the injection. The calm/relaxed category showed significant differences between before and after (P < .001) and during and after (P < .001) the procedure. Opinions and responses from male and female students differed statistically in relation to the injection on each other as preparation for real work situations (P < .023), recognition of landmarks (P < .001), determination of the insertion points (P = .032) and the need for supervision (P = .043).
CONCLUSIONS
This study showed that the overall, students felt more anxious before being injecting with the anaesthetic and the students learning to give the local anaesthetic to each other is an appropriate learning method. No gender-related differences were observed in the participants.
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10.1111/eje.12503
|
pubmed_105_14676
|
Numerous studies have focused on the understanding of rapid automatized naming (RAN), which can be applied to predict reading abilities and developmental dyslexia in children. Eye tracking technique, characterizing the essential ocular activities, might have the feasibility to reveal the visual and cognitive features of RAN. However, traditional measures of eye movements ignore many dynamical details about the visual and cognitive processing of RAN, and are usually associated with the duration of time spent on some particular areas of interest, fixation counts, revisited fixation counts, saccadic velocities, or saccadic amplitudes. To cope with this drawback, we suggested an entropy-based method to measure eye movements for the first time, which first mapped eye movements during RAN in a time-series and then analyzed the time-series by a proper definition of entropy from the perspective of information theory. Our findings showed that the entropy was more sensitive to reflect small perturbation (e.g., rapid movements between focuses in the presence of skipping or omitting some stimulus during RAN) of eye movements, and thus gained better performance than traditional measures. We also verified that the entropy of eye movements significantly deceased with the age and the task complexity of RAN, and significantly correlated with traditional eye-movement measures [e.g., total time of naming (TTN)] and the RAN-related skills [e.g., selective attention (SA), cognitive speed, and visual-motor integration]. Our findings may bring some new insights into the understanding of both RAN and eye tracking technique itself.
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10.3389/fnhum.2022.945406
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pubmed_866_12963
|
BACKGROUND
The study evaluated the feasibility and safety of the exercise intervention and physical test procedures of our ongoing randomized controlled trial, examining the effect of physical exercise in newly diagnosed patients with multiple myeloma.
METHODS
Patients are randomized 1:1 to a control group (usual care) or an intervention group (usual care and exercise) by block randomization with stratification of planned treatment, WHO performance status, and study site. The exercise intervention consists of eight supervised exercise sessions combined with home-based exercise over a 10-week period. Bone disease is systematically evaluated to determine limitations regarding physical testing and/or exercise. Feasibility outcome measures were study eligibility, acceptance, and attrition, and furthermore attendance, adherence, tolerability, and safety to the exercise intervention. Additionally, test completion, pain, and adverse events during the physical test procedures were evaluated. Outcome assessors were blinded to allocation.
RESULTS
Of 49 patients screened, 30 were included. The median age was 69 years, range 38-90, 77% were males, and 67% had bone disease. Study eligibility was 82%, acceptance 75%, and attrition 20%. Attendance at supervised exercise sessions was 92%, and adherence to supervised exercise sessions and home-based exercise sessions was 99% and 89%, respectively. No serious adverse events attributed to exercise or physical tests were reported. All patients completed the physical tests, except for two patients, where physical test procedures were modified due to bone disease.
DISCUSSION
The exercise intervention and physical test procedures were feasible and safe in patients with multiple myeloma, even in older patients with multiple myeloma and in patients with myeloma bone disease.
TRIAL REGISTRATION
ClinicalTrials.gov. ID NCT02439112. Registered on May 7, 2015.
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10.1186/s40814-019-0518-2
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pubmed_1010_562
|
Almost 70 years after establishing the concept of primary immunodeficiency disorders (PIDs), more than 320 monogenic inborn errors of immunity have been identified thanks to the remarkable contribution of high-throughput genetic screening in the last decade. Approximately 40 of these PIDs present with autoimmune or auto-inflammatory symptoms as the primary clinical manifestation instead of infections. These PIDs are now recognized as diseases of immune dysregulation. Loss-of function mutations in genes such as FOXP3, CD25, LRBA, IL-10, IL10RA, and IL10RB, as well as heterozygous gain-of-function mutations in JAK1 and STAT3 have been reported as causative of these disorders. Identifying these syndromes has considerably contributed to expanding our knowledge on the mechanisms of immune regulation and tolerance. Although whole exome and whole genome sequencing have been extremely useful in identifying novel causative genes underlying new phenotypes, these approaches are time-consuming and expensive. Patients with monogenic syndromes associated with autoimmunity require faster diagnostic tools to delineate therapeutic strategies and avoid organ damage. Since these PIDs present with severe life-threatening phenotypes, the need for a precise diagnosis in order to initiate appropriate patient management is necessary. More traditional approaches such as flow cytometry are therefore a valid option. Here, we review the application of flow cytometry and discuss the relevance of this powerful technique in diagnosing patients with PIDs presenting with immune dysregulation. In addition, flow cytometry represents a fast, robust, and sensitive approach that efficiently uncovers new immunopathological mechanisms underlying monogenic PIDs.
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10.3389/fimmu.2019.02742
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pubmed_272_12436
|
We report that Gata-2 is expressed in a sexually dimorphic fashion during mouse gonadogenesis. Gata-2 transcripts accumulate rapidly in the fetal ovary from 11.5 days post coitum (dpc) onwards, but are not detected in the fetal testis throughout the period studied (10.5-15.5 dpc). Ovarian expression of Gata-2 ceases by 15.5 dpc. Examination of ovaries from embryos homozygous for the extreme allele of c-kit(W(e)) (Nature, 335, 88; Cell, 55, 185) demonstrates that ovarian Gata-2 expression is dependent upon the presence of germ cells. Comparative in situ hybridisation using the germ cell marker Oct4 (EMBO J., 8, 2543) indicates that Gata-2 transcripts are restricted to the germ cell lineage at 13.5 dpc.
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10.1016/s0925-4773(01)00602-5
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pubmed_21_7117
|
For nonmodel organisms, genome-wide information that describes functionally relevant variation may be obtained by RNA-Seq following de novo transcriptome assembly. While sequencing has become relatively inexpensive, the preparation of a large number of sequencing libraries remains prohibitively expensive for population genetic analyses of nonmodel species. Pooling samples may be then an attractive alternative. To test whether pooled RNA-Seq accurately predicts true allele frequencies, we analysed the liver transcriptomes of 10 bank voles. Each sample was sequenced both as an individually barcoded library and as a part of a pool. Equal amounts of total RNA from each vole were pooled prior to mRNA selection and library construction. Reads were mapped onto the de novo assembled reference transcriptome. High-quality genotypes for individual voles, determined for 23,682 SNPs, provided information on 'true' allele frequencies; allele frequencies estimated from the pool were then compared with these values. 'True' frequencies and those estimated from the pool were highly correlated. Mean relative estimation error was 21% and did not depend on expression level. However, we also observed a minor effect of interindividual variation in gene expression and allele-specific gene expression influencing allele frequency estimation accuracy. Moreover, we observed strong negative relationship between minor allele frequency and relative estimation error. Our results indicate that pooled RNA-Seq exhibits accuracy comparable with pooled genome resequencing, but variation in expression level between individuals should be assessed and accounted for. This should help in taking account the difference in accuracy between conservatively expressed transcripts and these which are variable in expression level.
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10.1111/1755-0998.12186
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pubmed_589_2231
|
Web and mobile (mHealth) interventions have promise for improving health outcomes, but engagement and attrition may be reducing effect sizes. Because social networks can improve engagement, which is a key mechanism of action, understanding the structure and potential impact of social networks could be key to improving mHealth effects. This study (a) evaluates social network characteristics of four distinct communication channels (discussion board, chat, e-mail, and blog) in a large social networking intervention, (b) predicts membership in online communities, and (c) evaluates whether community membership impacts engagement. Participants were 299 cancer survivors with significant distress using the 12-week health-space.net intervention. Social networking attributes (e.g., density and clustering) were identified separately for each type of network communication (i.e., discussion board, blog, web mail, and chat). Each channel demonstrated high levels of clustering, and being a community member in one communication channel was associated with being in the same community in each of the other channels (φ = 0.56-0.89, ps < 0.05). Predictors of community membership differed across communication channels, suggesting that each channel reached distinct types of users. Finally, membership in a discussion board, chat, or blog community was strongly associated with time spent engaging with coping skills exercises (Ds = 1.08-1.84, ps < 0.001) and total time of intervention (Ds = 1.13-1.80, ps < 0.001). mHealth interventions that offer multiple channels for communication allow participants to expand the number of individuals with whom they are communicating, create opportunities for communicating with different individuals in distinct channels, and likely enhance overall engagement.
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10.1089/cyber.2015.0359
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pubmed_773_5141
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The article describes the results of roentgenological analysis of 905 patients having no pathological manifestations in the basin of the inferior mesenteric artery. The percutaneous catheterization of the aorta after Seldinger was made in all the patients. The authors have established that the typical variant of the artery is characterized by its appearance at the level of the third lumbar vertebrum body, by the branching of the trunk downwards to the left at an angle of 26,6 degrees +/- 0,2 (6-6,31 degrees) and by the main type of branching. The described rentgenological features of the vessel are helpful for the correct recognizing of the vessel in angiograms made in clinical conditions. The authors are likely to be the first to distinguish 10 variations of the branching of the inferior mesenteric artery and to give a detailed information on projection relationships of this vessel.
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pubmed_773_5141
|
pubmed_81_1221
|
Molting is a natural process, which birds undergo to rejuvenate their reproductive organs. The US poultry egg production industry has used feed withdrawal to effectively induce molt; however, susceptibility of Salmonella Enteritidis has encouraged the development of alternative methods. Previous research conducted in our laboratory showed that alfalfa is effective at molt induction and provides equivalent postmolt production numbers and quality when compared with feed withdrawal. In the attempt to further increase the efficacy of alfalfa molt diet and decrease the chicken susceptibility to Salmonella Enteritidis during molt, fructooligosaccharide (FOS) was added to a combination of 90% alfalfa and 10% layer ration in 2 levels (0.750 and 0.375%). Ovary and liver colonization by Salmonella Enteritidis in 3 and 2 of the 4 trials, respectively, were reduced (P <or= 0.05) in hens fed FOS-containing diets compared with hens subjected to feed withdrawal. Significant decreases in ce-cal Salmonella Enteritidis counts were also observed in 2 of the 4 trials. In 3 of the 4 trials, the same diets did not affect (P > 0.05) the production of cecal total volatile fatty acids when compared with hens undergoing feed withdrawal. However, in all 3 alfalfa molt diets, the concentrations of lactic acid were greater (P <or= 0.05) than hens with feed withdrawal, but no differences (P > 0.05) were observed among hens fed alfalfa combined with FOS and hens fed alfalfa/layer ration without FOS. Overall, given the similarities between hens fed 0.750% FOS (H) and 0.375% FOS (L), molt diets combined with the lower level of FOS should be sufficient.
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10.3382/ps.2007-00166
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pubmed_859_23534
|
The Paα line (1875.13 nm) in the near-infrared (NIR) region was evaluated to apply Stark broadening of the line spectrum to the electron density measurement of the small-pellet ablation cloud in Heliotron J, a medium-sized helical-axis heliotron device. Paα is three-to-four times broader than the visible Hβ line (486.13 nm) for the same electron density. Using a portable NIR spectrometer, preliminary proof-of-concept experiments determined the marginal density, below which the broadening was undetectable. The lower detection density limit can be decreased using a narrower entrance slit or a denser grating.
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10.1063/5.0101885
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pubmed_866_7481
|
Several resorbable fixation systems are used for osteosynthesis in craniofacial surgery. Recently, ultrasonic-assisted pinned resorbable systems have been introduced; however, few studies have described the associated complications during the long-term follow-up until complete resorption. In this study, we investigated the complications of craniofacial surgery using the ultrasonic-assisted pinned resorbable system with a follow-up of at least 30 months. Among patients who underwent craniofacial surgery using a commercially available ultrasonic-assisted pinned resorbable system between 2014 and 2016, those with follow-up visits for at least 30 months were included in this study. We investigated the development of complications such as local infection, exposure of the device, and reoperation related to the implant. Twenty-four patients aged 6 months to 69.4 years (median: 3.5 years) were followed up for more than 30 months. None of the patients required reoperation regardless of implants. Further, no infection or device exposure was seen among all patients. However, two patients aged 6 and 22 months who underwent cranioplasty for craniosynostosis and another patient aged 148 months who underwent cranioplasty for cranial defect exhibited plate-related bulging in the scalp during the course of resorption between 7 and 12 months of follow-up. The bulges were characterized by swelling without pain or redness and resolved spontaneously within 18 months of follow-up, which was considered to occur after complete absorption of the plate. In conclusion, subcutaneous swelling is related to resorbable plates and has a benign clinical course. We recommend that patients be informed of this phenomenon preoperatively to relieve their anxiety.
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10.1016/j.bjps.2019.10.009
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pubmed_635_25092
|
Effects of bromocriptine and sulpiride were observed on encoding and retrieval of spatial memory in Wistar rats using Hebb-Williams complex maze. Rat was placed in entry chamber and allowed to reach reward chamber. Ten trials were given each day per rat for 3 consecutive days. Within-day encoding score indicative of learning and between-day retrieval score indicative of memory were calculated. Effects of bromocriptine and sulpiride were observed on encoding and retrieval of spatial memory. General learning index was calculated to compare the effect on spatial memory between groups. Bromocriptine increased while sulpiride decreased within-day encoding index but had no effect on retrieval index. In general learning index, sulpiride group showed more errors whereas bromocriptine group did not show any difference as compared to control. These results suggest that dopamine D2 receptors are involved in memory encoding but not retrieval. Also general learning is under positive modulation by D2 receptors.
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pubmed_635_25092
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pubmed_660_17162
|
This article describes a liquid chromatographic/tandem mass spectrometric method, based on the use of precursor ion scan as the acquisition mode, specifically developed to detect indole-derived cannabinoids (phenylacetylindoles, naphthoylindoles and benzoylindoles) in biological fluids (saliva, urine and blood). The method is designed to recognize one or more common "structural markers", corresponding to mass spectral fragments originating from the specific portion of the molecular structure that is common to the aminoalkylindole analogues and that is fundamental for their pharmacological classification. As such, the method is also suitable for detecting unknown substances, provided they contain the targeted portion of the molecular structure. The pre-treatment procedure consists in a liquid/liquid extraction step carried out at neutral pH: this is the only pretreatment in the case of analyses carried out in saliva, while it follows an enzymatic hydrolysis procedure in the case of urine samples, or a protein precipitation step in the case of blood samples. The chromatographic separation is achieved using an octadecyl reverse-phase 5 μm fused-core particle column; while the mass spectrometric detection is carried out by a triple-quadrupole instrument in positive electrospray ionization and precursor ion scan as acquisition mode, selecting, as mass spectral fragments, the indole (m/z 144), the carbonylnaphthalenyl (m/z 155) and the naphthalenyl (m/z 127) moieties. Once developed and optimized, the analytical procedure was validated in term of sensitivity (lower limits of detection in the range of 0.1-0.5 ng mL(-1)), specificity (no interference was detected at the retention times of the analytes under investigation), recovery (higher than 65% with a satisfactory repeatability: CV% lower than 10), matrix effect (lower than 30% for all the biological specimens tested), repeatability of the retention times (CV% lower than 0.1), robustness, and carry over (the positive reference samples at a concentration 20 times the LLOD value did not affect the blank samples). The suitability of the proposed procedure, both as a targeted and an untargeted approach, was verified by analyzing samples containing synthetic cannabinoids and/or their metabolites and samples obtained from the incubation of synthetic cannabinoids with human liver microsomes.
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pubmed_660_17162
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pubmed_1059_138
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Serotonin -- depleting lesions involving nucleus raphe medianus markedly prolonged ethanol-induced sleep in rats. Lesioned animals showed increased general activity and decreased serotonin and 5-hydroxy-indoleacetic acid concentrations in the forebrain.
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pubmed_1059_138
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pubmed_245_22782
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The contribution of the host immune system to the efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal prospective study of 33 individuals with chronic HCV treated with combination pegylated IFN-α, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine whether kinetics of the host response could predict sustained virologic response (SVR). We show that characteristics of the host immune system present before treatment were correlated with successful therapy. Augmentation of adaptive immune responses during therapy was more impressive among those achieving SVR. Most importantly, active memory T cell proliferation before therapy predicted SVR and was associated with the magnitude of the HCV-specific responses at week 12 after treatment start. After therapy initiation, the most important correlate of success was minimal monocyte activation, as predicted by previous in vitro work. In addition, subjects achieving SVR had increasing expression of the transcription factor T-bet, a driver of Th1 differentiation and cytotoxic effector cell maturation. These results show that host immune features present before treatment initiation predict SVR and eventual development of a higher frequency of functional virus-specific cells in blood. Such host characteristics may also be required for successful vaccine-mediated protection.
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10.4049/jimmunol.1701364
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pubmed_234_19311
|
The pregnancy among adolescent women in Mexico is close than half million by year, this problem could be attended through health education in the Mexican medical care system. Since 1995 the Instituto Nacional de Perinatologia has a free training program only for adolescents designed to improve the health care medical procedures and reduces some perinatals health risks. This paper shows the structural design, functioning strategies and results of its application. Through a pre codificated 48 item list, were analyzed transversally the clinical records of 234 adolescents engraved themselves to the course. Two groups were formed: the "A" group with the patients attended at least to three sessions (106) and the group "B" with the ones who did not (128). The data analysis was made by contrasting each item between the groups using the appropriate statistical tests. The group "A" had greater average in scholarship, the moreover socioeconomic characteristics and gynecoobstetric background did not show significant differences. Group "B" had a higher proportion of adolescent with aggregated pathology to the pregnancy. We too observed significant differences in the proportions of complications during the pregnancy evolution and in the postpartum period. The acceptance on the pregnancy by the adolescent, her family and by her couple also showed significant differences. The average weight of the newborns were greater statistically in the "A" group. The proportions of family planning methods acceptance was higher in the same group, who has too shorter intra-hospitalary stay. This evaluation shows good fitness with the adolescents education expectatives and performance and favorable associations with some perinatals health risks.
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pubmed_234_19311
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pubmed_898_24810
|
Clinical and research interest in sarcopenia has burgeoned internationally, Asia included. The Asian Working Group for Sarcopenia (AWGS) 2014 consensus defined sarcopenia as "age-related loss of muscle mass, plus low muscle strength, and/or low physical performance" and specified cutoffs for each diagnostic component; research in Asia consequently flourished, prompting this update. AWGS 2019 retains the previous definition of sarcopenia but revises the diagnostic algorithm, protocols, and some criteria: low muscle strength is defined as handgrip strength <28 kg for men and <18 kg for women; criteria for low physical performance are 6-m walk <1.0 m/s, Short Physical Performance Battery score ≤9, or 5-time chair stand test ≥12 seconds. AWGS 2019 retains the original cutoffs for height-adjusted muscle mass: dual-energy X-ray absorptiometry, <7.0 kg/m2 in men and <5.4 kg/m2 in women; and bioimpedance, <7.0 kg/m2 in men and <5.7 kg/m2 in women. In addition, the AWGS 2019 update proposes separate algorithms for community vs hospital settings, which both begin by screening either calf circumference (<34 cm in men, <33 cm in women), SARC-F (≥4), or SARC-CalF (≥11), to facilitate earlier identification of people at risk for sarcopenia. Although skeletal muscle strength and mass are both still considered fundamental to a definitive clinical diagnosis, AWGS 2019 also introduces "possible sarcopenia," defined by either low muscle strength or low physical performance only, specifically for use in primary health care or community-based health promotion, to enable earlier lifestyle interventions. Although defining sarcopenia by body mass index-adjusted muscle mass instead of height-adjusted muscle mass may predict adverse outcomes better, more evidence is needed before changing current recommendations. Lifestyle interventions, especially exercise and nutritional supplementation, prevail as mainstays of treatment. Further research is needed to investigate potential long-term benefits of lifestyle interventions, nutritional supplements, or pharmacotherapy for sarcopenia in Asians.
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10.1016/j.jamda.2019.12.012
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pubmed_789_21491
|
OBJECTIVES
To determine the effect of Kangaroo Mother Care (KMC) of small duration of 15 min in decreasing pain in preterm neonates between 32-36 wk 6 d on heel prick by a 26 gauge needle.
METHODS
Randomized controlled double masked crossover trial involving 50 neonates, between 32 wk and 36 wk 6 d gestation and weighing less than 2500 g, within 10 d of birth, vitally stable, breathing without assistance or on Continuous positive airway pressure (CPAP), without any clinically evident neurological signs, not having received analgesics/sedatives within last 24 h and not fed within last 30 min and requiring heel pricking were eligible. Outcome measured was the Premature Infant Pain Profile (PIPP). Analysis was done using independent sample t test, with Bonferroni correction applied for comparing individual components of PIPP score.
RESULTS
The heart rate, behaviour and facial scores were statistically significant and lower in KMC group. But there was no statistically significant difference in oxygen saturation (SpO(2)). The difference(4.85) in PIPP score was clinically and statistically significant (p < 0.0001).
CONCLUSIONS
The findings suggest that short duration KMC (15 min) has stress reducing benefits. Preterm neonates above 32 wk gestational age can benefit from KMC to decrease pain from heel prick procedure.
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10.1007/s12098-012-0760-6
|
pubmed_440_6174
|
Overexpression of REST has been implicated in brain tumors, ischemic insults, epilepsy, and movement disorders such as Huntington's disease. However, owing to the lack of a conditional REST overexpression animal model, the mechanism of action of REST overexpression in these disorders has not been established in vivo. We created a REST overexpression mouse model using the human REST (hREST) gene. Our results using these mice confirm that hREST expression parallels endogenous REST expression in embryonic mouse brains. Further analyses indicate that REST represses the dopamine receptor 2 (Drd2) gene, which encodes a critical nigrostriatal receptor involved in regulating movement, in vivo. Overexpression of REST using Drd2-Cre in adult mice results in increased REST and decreased DRD2 expression in the striatum, a major site of DRD2 expression, and phenocopies the spontaneous locomotion deficits seen upon global DRD2 deletion or specific DRD2 deletion from indirect-pathway medium spiny neurons. Thus, our studies using this mouse model not only reveal a new function of REST in regulating spontaneous locomotion but also suggest that REST overexpression in DRD2-expressing cells results in spontaneous locomotion deficits.
|
10.1038/s41598-018-29441-3
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pubmed_129_2081
|
The transcriptional regulation of the rat gonadotropin subunit genes was investigated under different regimens of GnRH administration in vitro. Anterior pituitary fragments (8-10/gland) from either intact or ovariectomized CD female rats were treated in static culture with 0.1 or 1 nM GnRH or on perifusion columns with pulsatile GnRH (25 ng pulse every 30 or 60 min) for 1-6 h. Gene transcription rates were measured in nuclear run-off assays, and hemipituitaries from the same animals were matched in control and treatment groups. In static culture, only rates of alpha-subunit mRNA synthesis were stimulated at 1, 3, and 6 h from 64 +/- 10 (control) to 170 +/- 29 (3 or 6 h of GnRH) parts/million (ppm). There was no change in FSH beta mRNA synthesis (28 +/- 6 ppm), and significant stimulation of LH beta was seen only at 1 h (98 +/- 10 vs. 34 +/- 1 ppm for control) with continuous GnRH. Similar results were obtained with both GnRH doses and with pituitaries from either intact or ovariectomized rats. In addition, continuous 1 nM GnRH administration to perifusion columns for 4 or 6 h resulted in no changes in the transcription rate for LH beta (44 +/- 10 vs. 40 +/- 12 ppm for control) or FSH beta (29 +/- 6 vs. 36 +/- 9 ppm for control), but consistent stimulation for alpha-subunit (240 +/- 29 vs. 71 +/- 16 ppm for control). Markedly different results were observed with pulsatile GnRH administration. In perifusion studies, LH beta mRNA synthesis was stimulated 2- to 2.5-fold after 1 h of pulses and 3- to 4-fold after 3 or 6 h. A slight (2-fold) stimulation was noted for FSH beta mRNA synthesis only after 1 h of pulsatile GnRH, while alpha-subunit gene transcription was elevated 2-fold after 1 h and 4- to 5-fold after 3 or 6 h of pulsatile GnRH. GnRH pulses in vivo may also be crucial to maintain gonadotropin mRNA synthesis, since administration of a GnRH antagonist ([Nal-Lys] GnRH; 20 micrograms/100 g BW) suppressed the transcription rate of all three genes to 10-25% of control values after 4 or 24 h. TSH beta mRNA synthesis was not changed by any GnRH treatment, and LH secretion was consistently stimulated by GnRH. No significant differences in transcription rate were noted between GnRH pulse intervals of 30 or 60 min in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
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10.1210/mend-4-10-1444
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pubmed_134_5661
|
The effects of ( Z)-2[ p -(1,2-diphenyl-1-butenyl)phenoxy]-N ,N -dimethylamine citrate (tamoxifen) on cell survival and the expression of neurotrophic factors (NTF) were investigated in rat C6 glioma cells (C6). C6 cells do not express the estrogen receptor. Cytotoxic effect was detected from 24 h after the treatment with 10 microM tamoxifen and increased with time in a dose-dependent manner. C6 cells treated with tamoxifen also displayed various morphological types such as elliptical, round and aggregated form. As the treatment time increased, the proliferation of C6 cells was reduced remarkably and most of them became the round or aggregated form. To examine the relationship of the expression of NTF and the cytotoxicity of tamoxifen, the mRNA level of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and basic fibroblast growth factor (bFGF) was measured after 24 h treatment with tamoxifen by RT-PCR. The expression of mRNA of BDNF or GDNF in C6 cells treated with various concentrations of tamoxifen was comparable to controls. The expression of bFGF mRNA was significantly reduced in C6 cells treated with 10 or 15 microM tamoxifen. The results suggest that tamoxifen exerts cytotoxic effect on estrogen receptor-negative C6 cells through the inhibition of the transcription of bFGF.
|
10.1007/s11060-004-0984-z
|
pubmed_1082_20100
|
A critical evaluation of 3 years' experience using laboratory screening to detect neutrophil dysfunction is described. Neutrophil dysfunctions in patients with recurrent bacterial infections were investigated by using the following screening tests: (1) neutrophil chemotaxis towards N-formylmethionyl peptides (FMLP) and the complement fragment C5a; (2) neutrophil production of superoxide anions (O2-) in response to phorbol myristate acetate and opsonized zymosan particles; and (3) examination of May-Grünwald and myeloperoxidase cytochemical staining of peripheral blood smears. These tests were carried out in 100 patients suffering from infections and suspected of having altered neutrophil functional competence. A minority of patients was found to have well defined neutrophil dysfunction syndromes: chronic granulomatous disease (four cases), Chediak-Higashi disease (one case) and myeloperoxidase deficiency (one case). Of the remaining 94 patients, in whom infections localized to airways and/or skin predominated, 53 cases were found to have impaired chemotaxis (41 cases) or partial defects of the O2- production. Defects of chemotaxis toward FMLP and those towards both FLMP and C5a were the most frequent abnormalities. No defect was found in the other 41 patients. Moreover, impaired neutrophil chemotaxis was found in some patients with selective IgA deficiency (five cases) or immotile cilia syndrome (seven cases). The results suggest that (a) additional screening tests are required to ameliorate the efficiency of the diagnostic work-up of the patients suspected to have neutrophil dysfunction; and (b) further evaluation, also at the molecular level, should be considered at least in selected cases of non-classified neutrophil dysfunction in order to clarify diagnosis and plan rational therapeutic strategies.
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10.1111/j.1365-2362.1995.tb01987.x
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pubmed_625_19460
|
In 2015, the Centers for Disease Control and Prevention reported a substantial increase in the number of acute hepatitis B virus (HBV) infections in the United States. Although national guidelines recommend vaccination of adults at high risk for HBV infection, the prevalence of undetectable immunity (i.e., susceptibility) in this population remains unknown. In this study, we analyzed a nationally representative sample using the National Health and Nutrition Examination Survey to evaluate the prevalence, trend, and predictors of undetectable vaccine-induced antibodies against HBV surface antigen (<10 mIU/mL) among high-risk adults from 2003-2014. Among adults at high risk for HBV infection, the prevalence of undetectable immunity decreased from 83.2% in 2003-2004 (95% confidence interval [CI]: 81.3-85.0) to 69.4% (about 64 million) in 2013-2014 (95% CI: 66.0-72.6). The prevalence decreased significantly in individuals with multiple sex partners or sexually transmitted disease and in pregnant women. However, there were no significant changes in men who have sex with men (MSMs), intravenous drug users (IDUs), hepatitis C virus (HCV)-infected and patients with diabetes, and those with elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT). Mexican Americans had the highest prevalence of undetectable immunity (77.6%, 95% CI: 72.6-81.9), followed by non-Hispanic whites (70.1%, 95% CI: 66.9-73.1). Older age, lower socioeconomic status, and having at least 1 high-risk factor were associated with a higher risk of undetectable immunity, whereas an increased risk among the foreign-born disappeared after multivariable adjustment. Conclusion: Approximately 64 million high-risk adults in the United States remain susceptible to HBV infection, especially MSMs, IDUs, diabetics, HCV patients, and populations with elevated AST/ALT. To eliminate HBV, efforts should be made to increase screening and vaccination in high-risk adults.
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10.1002/hep.30285
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pubmed_992_5483
|
OBJECTIVE:
To assesses the statistical association between exposure to tobacco marketing and tobacco consumption among adolescents in South America, by using data from the Global Youth Tobacco Survey.
MATERIALS AND METHODS:
Using data from the Global Youth Tobacco Survey (GYTS), the exposure to tobacco marketing at the school level was studied from advertising in TV, radio, massive public events and street advertisement. Tobacco behaviour was considered. The total pooled sample used was 134 073 youths from Argentina, Bolivia, Chile, Peru, Brazil, Uruguay, Suriname, Colombia, Guyana, Ecuador, Paraguay and Venezuela.
RESULTS:
The exposure to tobacco marketing is positively and significantly associated to the probability of youths experimenting with tobacco (at least once in their lifetime). For regular smokers, exposure to tobacco marketing is positively and significantly associated to smoking intensity.
CONCLUSIONS:
These results call for the implementation of strong restrictions on tobacco advertisement of various types in South American countries.
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10.21149/7735
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pubmed_866_6221
|
We used the Template for Intervention Description and Replication (TIDieR) to find evidence that intervention reporting in urology randomized controlled trials is suboptimal. Action to improve intervention reporting is warranted and we advise extending TIDieR into Consolidated Standards for Reporting Trials guidelines.
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10.1016/j.eururo.2019.10.029
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pubmed_626_19028
|
BACKGROUND AND OBJECTIVES
Anesthetic induction with inhalational agents using a facemask has gained attention since the introduction of sevoflurane. At the same time, the influence of adding nitrous oxide on the pattern of induction and recuperation deserves attention, especially regarding recovery of the cognitive function. The objective of this study was to evaluate the cognitive effects of inhalational anesthetic induction with sevoflurane alone or associated with nitrous oxide in adults.
METHODS
Twenty adult volunteers, ASA physical state I, without a history of psychiatric disorders or prior use of benzodiazepines, were enrolled in the study. After answering the Mini-Mental State Examination (MMSE), Group I received 5% sevoflurane until a bispectral index (BIS) of 60 was achieved. Group II received nitrous oxide in increments of 10% until it achieved 50% followed by the administration of sevoflurane until a BIS of 60 was achieved. Arterial blood pressure, heart rate, pulse oxymetry, SEF 95% (Spectral Edge Frequency), induction time, and anesthetic recovery time were evaluated.
RESULTS
Time of induction showed no differences between both groups. Group II showed greater hemodynamic stability and smaller SEF 95% values when BIS achieved 60. The time for recovery of cognitive function was similar in both groups, as well as the incidence of nausea and vomiting. There were no cases of apnea. Group II demonstrated greater incidence of psychomotor agitation during induction.
CONCLUSIONS
Sevoflurane alone or in association with nitrous oxide is an adequate option for inhalational anesthetic induction or outpatient sedation in adults, maintaining spontaneous ventilation, and providing a fast recuperation of the cognitive function.
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pubmed_626_19028
|
pubmed_257_12451
|
In patients with thyrotoxic myopathy, histological investigation showed the decrease in mean diameter of skeletal muscles, and increased collateral branching of distal axons. The percentage of afflicted fibers was not high with focal pathology. The signs of true reinnervation were absent. Electroneuromyographic investigation confirmed mild myopathy. The authors discuss the possible participation of cyclic nucleotide system disorders in muscular weakness in these patients.
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pubmed_257_12451
|
pubmed_928_4978
|
The ability of strains of the B. fragilis group, isolated from the oral cavity and intestine of marmosets, to produce bacteriorin-like substances in solid medium, in terms of auto-, iso- and heteroantagonism, was evaluated. Antagonistic activity was exhibited by 52% of the intestinal strains, 3 of which showed autoantagonistic activity. Three out of 9 oral strains isolated, tested against themselves, showed simultaneous isoantagonism to 4 indicator strains; but not autoantagonism. The same 9 oral strains, when tested against 16 reference strains, revealed interspecific activity only against 2 Gram-positive microorganisms. Higher activity, evaluated by the size of the inhibition halo, was observed in BHI-S agar, and greatest inhibition was obtained after 72 h of incubation.
|
10.1016/0923-2508(92)90004-8
|
pubmed_364_16134
|
BACKGROUND AND AIMS
There is a growing need for valid, efficient, and easy scoring scales to rate the quality of cohort studies. We aimed to develop and validate a quality assessment score to be used for cohort studies.
METHODS
We followed a rigorous process to establish content, face, and construct validity. Most questions were scored at 0 or 1. Inter-rater reliability and test-retest reliability were assessed using the Spearman correlation coefficient (rs) and Cohen's κ statistic. Internal consistency was measured using the Kuder-Richardson formula 20 (KR20).
RESULTS
The final tool consists of 9 questions with a maximum score of 10. The inter-rater reliability was high with the Spearman correlation coefficient (rs = .66). Agreement for inclusion was 90%. Test-retest reliability was high. For rater 1, rs = .91, κ = .38 for scores, and κ = 1 for inclusion. For rater 2, r = .94, 80% agreement for scores, and 100% agreement for inclusion. Internal consistency was reasonable based on 2 studies: KR20 = .21 and KR20 = .65. The novel scale rated highest in efficiency, understandably, ease of use, and ease of interpretation when compared with 3 other scales.
CONCLUSIONS
This novel scale has favorable performance characteristics, is efficient to conduct, and is easy to interpret and will be very helpful for physicians and researchers conducting systematic reviews and meta-analyses.
|
10.1016/j.gie.2020.10.007
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pubmed_617_2174
|
During productive infection, herpes simplex virus type 1 (HSV-1) induces the formation of discrete nuclear foci containing cellular chaperone proteins, proteasomal components, and ubiquitinated proteins. These structures are known as VICE domains and are hypothesized to play an important role in protein turnover and nuclear remodeling in HSV-1-infected cells. Here we show that VICE domain formation in Vero and other cells requires the HSV-1 immediate-early protein ICP22. Since ICP22 null mutants replicate efficiently in Vero cells despite being unable to induce VICE domain formation, it can be concluded that VICE domain formation is not essential for HSV-1 productive infection. However, our findings do not exclude the possibility that VICE domain formation is required for viral replication in cells that are nonpermissive for ICP22 mutants. Our studies also show that ICP22 itself localizes to VICE domains, suggesting that it could play a role in forming these structures. Consistent with this, we found that ICP22 expression in transfected cells is sufficient to reorganize the VICE domain component Hsc70 into nuclear inclusion bodies that resemble VICE domains. An N-terminal segment of ICP22, corresponding to residues 1 to 146, is critical for VICE domain formation in infected cells and Hsc70 reorganization in transfected cells. We previously found that this portion of the protein is dispensable for ICP22's effects on RNA polymerase II phosphorylation. Thus, ICP22 mediates two distinct regulatory activities that both modify important components of the host cell nucleus.
|
10.1128/JVI.01686-09
|
pubmed_1090_20297
|
The Doppler ultrasonic estimation of cardiac output in man is reviewed. Minimal requirements for accurate measurements are discussed, and the published results of reproducibility studies and validation studies are summarized and analysed. Analysis of Doppler records has a coefficient of repeat determination of 5-8% for aortic or LV outflow tract measurements and this is higher for other sites. Short-term variability varies from 4 to 10%, and that over days to weeks from 9 to 14%. Thus a single measurement may vary up to +/- 28% over time with no true change in cardiac output. For cardiac output determination, the Doppler methods show accuracies varying from 10 to 22% (coefficient of variation of the differences between methods) indicating that a single aortic based measurement only reliably lies within +/- 28% compared with other 'standard' methods, and during exercise the accuracy is less (+/- 44%). Doppler methods are safe, fairly reproducible and reasonably accurate methods for measuring cardiac output in selected patients provided signal quality is adequate during recording.
|
10.1093/eurheartj/11.suppl_i.49
|
pubmed_392_14358
|
In songbirds, song has traditionally been considered a vocalization mainly produced by males. However, recent research suggests that both sexes produce song. While the function and structure of male black-capped chickadee (Poecile atricapillus) fee-bee song have been well-studied, research on female song is comparatively limited. Past discrimination and playback studies have shown that male black-capped chickadees can discriminate between individual males via their fee-bee songs. Recently, we have shown that male and female black-capped chickadees can identify individual females via their fee-bee song even when presented with only the bee position of the song. Our results using discriminant function analyses (DFA) support that female songs are individually distinctive. We found that songs could be correctly classified to the individual (81%) and season (97%) based on several acoustic features including but not limited to bee-note duration and fee-note peak frequency. In addition, an artificial neural network was trained to identify individuals based on the selected DFA acoustic features and was able to achieve 90% accuracy by individual and 93% by season. While this study provides a quantitative description of the acoustic structure of female song, the perception and function of female song in this species requires further investigation.
|
10.1121/10.0006532
|
pubmed_689_10229
|
Developmental temperature plays important roles in the expression of insect traits through thermal developmental plasticity. We exposed the aphid parasitoid Aphidius colemani to different temperature regimes (10, 20, or 28 °C) throughout larval development and studied the expression of morphological and physiological traits indicator of fitness and heat tolerance in the adult. We showed that the mass decreased and the surface to volume ratio of parasitoids increased with the development temperature. Water content was not affected by rearing temperature, but parasitoids accumulated more lipids when reared at 20 °C. Egg content was not affected by developmental temperature, but adult survival was better for parasitoids reared at 20 °C. Finally, parasitoids developed at 20 °C showed the highest heat stupor threshold, whereas parasitoids developed at 28 °C showed the highest heat coma threshold (better heat tolerance CTmax1 and CTmax2, respectively), therefore only partly supporting the beneficial acclimation hypothesis. From a fundamental point of view, our study highlights the role of thermal plasticity (adaptive or not) on the expression of different life history traits in insects and the possible correlations that exist between these traits. From an applied perspective, these results are important in the context of biological control through mass release techniques of parasitoids in hot environments.
|
10.3390/insects12100852
|
pubmed_179_14537
|
Molecular networking of non-targeted tandem mass spectrometry data connects structurally related molecules based on similar fragmentation spectra. Here, we report the Chemical Proportionality (ChemProp) contextualization of molecular networks. ChemProp scores the changes of abundance between two connected nodes over sequential data series (e.g., temporal or spatial relationships), which can be displayed as a direction within the network to prioritize potential biological and chemical transformations or proportional changes of (biosynthetically) related compounds. We tested the ChemProp workflow on a ground truth data set of a defined mixture and highlighted the utility of the tool to prioritize specific molecules within biological samples, including bacterial transformations of bile acids, human drug metabolism, and bacterial natural products biosynthesis. The ChemProp workflow is freely available through the Global Natural Products Social Molecular Networking (GNPS) environment.
|
10.1021/acs.analchem.1c01520
|
pubmed_69_15853
|
The s-cis-trans isomerism of two furan derivatives [2-acetyl- (AF) and 2-acetyl-5-methylfuran, (AMF)] was analyzed, using data from the deconvolution of their carbonyl absorption band in two solvents (CH(2)Cl(2) and CH(3)CN). These infrared data showed that the O,O-trans conformers predominate in the less polar solvent (CH(2)Cl(2)), but these equilibria change in a more polar solvent (CH(3)CN) leading to a slight predominance of the O,O-cis conformers, in agreement with the theoretical calculations. The later results were obtained using B3LYP-IEFPCM/6-31++g(3df,3p) level of theory, which taking into account the solvent effects at IEFPCM (Integral Equation Formalism Polarizable Continuum Model). Low temperature (13)CNMR spectra in CD(2)Cl(2) (ca. -75 °C) showed pairs of signals for each carbon, due to the known high energy barrier for the cis-trans interconversion leading to a large predominance of the trans isomers, which decreases in acetone-d(6). This was confirmed by their (1)HNMR spectra at the same temperatures. Moreover, despite the larger hyperconjugative interactions for the O,O-cis isomers, obtained from NBO data, these isomers are destabilized by the their Lewis energy.
|
pubmed_69_15853
|
pubmed_171_20554
|
Human telomere length is controlled by a negative feedback loop based on the binding of TRF1 to double-stranded telomeric DNA. The TRF1 complex recruits POT1, a single-stranded telomeric DNA-binding protein necessary for cis-inhibition of telomerase. By mass spectrometry, we have identified a new telomeric protein, which we have named POT1-interacting protein 1 (PIP1). PIP1 bound both POT1 and the TRF1-interacting factor TIN2 and could tether POT1 to the TRF1 complex. Reduction of PIP1 or POT1 levels with shRNAs led to telomere elongation, indicating that PIP1 contributes to telomere length control through recruitment of POT1.
|
10.1101/gad.1215404
|
pubmed_703_25459
|
Liver fibrosis occurs in most types of chronic liver diseases and is characterized by excessive accumulation of extracellular matrix proteins, leading to disruption of tissue function and eventually organ failure. Transforming growth factor (TGF)-β represents an important pro-fibrogenic factor and aberrant TGF-β action has been implicated in many disease processes of the liver. Endoglin is a TGF-β co-receptor expressed mainly in endothelial cells that has been shown to differentially regulates TGF-β signal transduction by inhibiting ALK5-Smad2/3 signalling and augmenting ALK1-Smad1/5 signalling. Recent reports demonstrating upregulation of endoglin expression in pro-fibrogenic cell types such as scleroderma fibroblasts and hepatic stellate cells have led to studies exploring the potential involvement of this TGF-β co-receptor in organ fibrosis. A recent article by Meurer and colleagues now shows that endoglin expression is increased in transdifferentiating hepatic stellate cells in vitro and in two different models (carbon tetrachloride intoxication and bile duct ligation) of liver fibrosis in vivo. Moreover, they show that endoglin overexpression in hepatic stellate cells is associated with enhanced TGF-β-driven Smad1/5 phosphorylation and α-smooth muscle actin production without altering Smad2/3 signaling. These findings suggest that endoglin may play an important role in hepatic fibrosis by altering the balance of TGF-β signaling via the ALK1-Smad1/5 and ALK-Smad2/3 pathways and raise the possibility that targeting endoglin expression in transdifferentiating hepatic stellate cells may represent a novel therapeutic strategy for the treatment of liver fibrosis.
|
10.1007/s12079-011-0154-y
|
pubmed_71_16436
|
This paper investigates how variability in partial foraging preferences for patch types can be used as a behavioral indicator of the energetic value of that patch type, and of overall food availability in the territory. The species studied was the lesser spotted woodpecker (Dendrocopos minor) and the patch types it uses are four groups of tree species (oak Quercus robur, birch Betula pendula, B. pubescens, alder Alnus glutinosa, and lime Tilia cordata), in which it feeds upon wood-living insect larvae. We partition the variation in foraging preferences into three scales. Firstly, within territories, the foraging preference for a tree species group was positively related to the prey density in that species group. That is, the preferences measure the patch types' energetic profitabilities. This result should be general in cases like the present, where the costs of using different alternatives do not differ substantially. It may therefore be the preferred behavioral indicator in determining the relative benefits associated with different alternatives. Secondly, between the seven years of study, much of the variation in tree species group preferences was attributable to measured fluctuations in the density of one important prey species (Argyresthia goedarthella, Argyresthidae, Lepidoptera), which occurred in some years on birch, in others on alder, and in one year was virtually absent. Thus, in concordance with the previous result, the values of these tree species groups fluctuated between years according to prey density. Thirdly, between territories, we found that the preference for one tree species, lime, was higher in areas where it was more abundant. We attribute this to the fact that the density (per patch) of at least one important prey species (Stenostola dubia, Cerambycidae, Coleoptera) on lime increased with the abundance of its host tree species in the territory. That is, the overall food availability was higher in territories where lime was more common. Hence, the preference for lime estimates overall food availability. This conclusion is strengthened by two additional facts: the preference for lime correlates positively (1) with the average giving-up density of food, which has previously been shown to estimate overall food availability in the territories, and (2) with reproductive success, at least during the early stages of reproduction.
|
10.1007/s004420000596
|
pubmed_847_16365
|
PURPOSE
The 2021 European Society of Cardiology guidelines on acute and chronic heart failure (HF) recommend that non-dihydropyridine calcium channel blockers (NDCC) should be avoided in patients with HF with reduced ejection fraction. It also emphasizes that beta-blockers only be initiated in clinically stable, euvolemic patients. Despite these recommendations, NDCC and beta-blockers are often still employed in patients with AF with rapid ventricular response and acute decompensated HF. The relative safety and efficacy of these therapies in this setting is unclear.
METHODS
To address the question of the safety and efficacy of NDCC and beta-blockers for acute rate control in decompensated HF, we provide a perspective on the literature of NDCC and beta-blockers in chronic HF with reduced and preserved ejection fraction and AF, including trials on the management of AF with rapid ventricular response with and without HF.
RESULTS
Robust data demonstrates mortality benefits when beta-blockers are used in patients with chronic HF with reduced ejection fraction. The data that inform the contraindication of NDCC in HF with reduced ejection fraction are outdated and were not primarily designed to address the efficacy and safety of rate control of AF in patients with HF. Several studies indicate that for acute rate control, NDCC and beta-blockers are both efficacious therapies, especially in the setting of tachycardia-induced cardiomyopathy.
CONCLUSION
Future studies are needed to assess the safety and efficacy of beta-blockers and NDCC in both acute and chronic AF with HF with reduced and preserved ejection fraction.
|
10.1007/s10557-022-07334-y
|
pubmed_529_8937
|
PURPOSE
To establish the most effective methods of postoperative surveillance to detect early recurrence of lung adenocarcinoma.
METHODS
The subjects of this retrospective study were 485 patients with p-stage I-III lung adenocarcinoma, who underwent postoperative surveillance. We examined the sites and detection modes of recurrence and calculated the recurrence-free probabilities. Patients with stage I disease were divided into low- and high-risk recurrence groups using a risk score calculated by assigning points proportional to risk factor regression coefficients.
RESULTS
Of the 112 patients with recurrence, 86 had intrathoracic recurrence. Routine computed tomography (CT) revealed recurrence in 60 patients. The recurrence-free probability curves showed that 95% of recurrences were identified within the first 4 years after resection in patients with stage II/III disease. In patients with stage I disease, the predictors of recurrence included male sex, positive pleural lavage cytology, moderate-to-poor differentiation, and visceral pleural invasion. Postoperative recurrences were detected throughout the follow-up period in the high-risk group.
CONCLUSIONS
Routine chest CT plays an important role in the postoperative surveillance of lung adenocarcinoma. We recommend intensive follow-up during the early post-resection period for patients with advanced stage disease and long-term follow-up for high-risk patients with stage I disease.
|
10.1007/s00595-017-1537-3
|
pubmed_1112_21976
|
We assessed the host-use pattern of the sponge-endosymbiotic bivalve Vulsella vulsella and its demographic consequences in an inland sea in Okinawa Island, Japan. Vulsella vulsella utilized only one massive globular sponge species Spongia sp. as a host, and no Spongia sp. without V. vulsella were found. Individual sponges contained 9-248 live bivalves and 0-222 dead bivalves. The densities of live and dead bivalves in individual sponges were approximately constant irrespective of sponge size, indicating that available space is very scarce inside each sponge. The size distribution of bivalves was skewed to small, young individuals less than 30 mm in shell height, although the estimated largest possible size was 106 mm. The bivalve population at each sampling date was composed of three yearly cohorts, and recruitment of juveniles occurred in the summer. The bivalves became sexually mature as males within one year after recruitment and changed sex from male to female as they grew. The size and sex distributions of the bivalve were largely similar among sponges regardless of sponge size, suggesting that the recruitment, growth, longevity, and sex change of the bivalve were strictly regulated, probably by the high water temperature and strong waves generated by typhoons in summer months.
|
10.2108/zsj.29.585
|
pubmed_394_6840
|
Bacterial meningitis remains a major cause of morbidity, mortality and neurodisability in childhood, particularly in the developing world where effective vaccines against the usual pathogens responsible for the disease are not in routine use. To describe the patterns and outcome of bacterial meningitis among children admitted into the University College Hospital (UCH), Ibadan, Nigeria. All children who satisfied the case definition for meningitis, admitted into the paediatric wards of the University College Hospital, UCH, Ibadan over a period of 30 months were prospectively enrolled and blood and CSF samples were taken for bacteriological analyses. A total of 97 children, 62 males and 35 females were studied. Their ages ranged between 2 months and 12 years, mean age 33.0 (SD=41.7) months, with 80.4% of the cases below the age of 5 years. Haemophilus influenzae type b (Hib) was the leading pathogen, found in 16 (55.1%) of the 29 cases of definite meningitis. Other isolates include Streptococcus pneumoniae (24.1%), Klebsiella spp (7.0%), Staphylococcus aureus (7.0%), Escherichia coli (3.4%) and Pseudomonas spp. (3.4%). Hib and pneumococcus showed varying degrees of resistance to chloramphenicol, penicillin and cotrimoxazole. Twenty six (26.8%) of the cases died and 67.6% of the survivors developed significant neurological sequele. Bacterial meningitis remains a major cause of childhood mortality and neurodisability. Hib and pneumococcus remain the major pathogens responsible for this dreadful disease in Ibadan, Nigeria. The increasing emergence of antibiotic resistance calls for institution of adequate control measures, particularly routine childhood immunisation against the disease.
|
pubmed_394_6840
|
pubmed_378_273
|
This paper presents a highly stereoselective synthesis of trifluoro- or difluoromethylated olefins via an S(N)2' type fluorination or reductions of gem-difluorinated vinyloxiranes. Their fluorination with HF-Py furnished trifluoromethylated allylic alcohols with exclusive E selectivity. On the other hand, their reduction with DIBAL-H afforded difluoromethylated E-allylic alcohols predominantly, whereas the corresponding Z isomers were formed exclusively by treatment with BH3.THF.
|
10.1021/jo060089c
|
pubmed_361_4240
|
Soluble immune response suppressor (SIRS) is a nonspecific immunosuppressive lymphokine produced by Lyt-2+ lymphocytes after exposure to Con A, IFN-alpha, or IFN-gamma. The N-terminal 21 residues of SIRS have recently been elucidated and antisera specific for this sequence have been raised in rabbits by using a synthetic peptide coupled to an immunogenic carrier protein. In a series of experiments, we have established that this antiserum blocks the suppressive activity of Con A- or IFN-activated suppressor cells. These data establish that Con A- or IFN-activated suppressor cells exert some or all of their suppressive effects via SIRS. Further studies show that SIRS acts primarily during the induction of CTL and not at the effector phase. Last, we show that SIRS is not involved in the radiation-resistant Ag-specific suppressor cell circuit that can be induced during the in vitro MLR.
|
pubmed_361_4240
|
pubmed_974_2569
|
The study of environmental samples requires a preservation system that stabilizes the sample structure, including cells and biomolecules. To address this fundamental issue, we tested the cell alive system (CAS)-freezing technique for subseafloor sediment core samples. In the CAS-freezing technique, an alternating magnetic field is applied during the freezing process to produce vibration of water molecules and achieve a stable, super-cooled liquid phase. Upon further cooling, the temperature decreases further, achieving a uniform freezing of sample with minimal ice crystal formation. In this study, samples were preserved using the CAS and conventional freezing techniques at 4, -20, -80 and -196 (liquid nitrogen) °C. After 6 months of storage, microbial cell counts by conventional freezing significantly decreased (down to 10.7% of initial), whereas that by CAS-freezing resulted in minimal. When Escherichia coli cells were tested under the same freezing conditions and storage for 2.5 months, CAS-frozen E. coli cells showed higher viability than the other conditions. In addition, an alternating magnetic field does not impact on the direction of remanent magnetization in sediment core samples, although slight partial demagnetization in intensity due to freezing was observed. Consequently, our data indicate that the CAS technique is highly useful for the preservation of environmental samples.
|
10.1111/1758-2229.12238
|
pubmed_902_18061
|
Chemical lasers pumped by the reaction of atomic fluorine with molecular hydrogen emit power from rotation-vibration transitions of excited HF with upper levels as high as upsilon = 3. Collisional processes compete with stimulated emission for the energy of the excited HF. A simplified analysis is presented here for intensity, energy, and chemical efficiency of a class of such lasers. Results are obtained in closed form. A comparison with more exact computer solutions establishes the validity of the analysis despite its simplifications. A comprehensive parametric study examines the relative importance of initial conditions, optical cavity parameters, and rate coefficients for pumping and deactivation reactions.
|
10.1364/AO.11.002047
|
pubmed_181_16550
|
This study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin (ACM) by covalently coupling it with amino-oxyacetic acid (AOA) to generate an active intermediate, AOA-ACM. AOA-ACM was conjugated with self-assembled human serum albumin (HSA) nanoparticles constructed using tris(2-carboxyethyl)phosphine (TCEP) as disulfide bond breaking molecules in an 'opening stage-intermediate-closing stage' route, in which the hydrophobic interaction, interchange of sulfhydryl and hydrogen bond may be the key factors in the assembling process. Conjugation between ACM and albumin nanoparticles was found to occur at an ACM ketone site using 1H-NMR and 13C-NMR matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass analysis indicated that the drug loading efficiency of ACM conjugated with HSA nanoparticles (NPs-ACM) was 7.4% (molar ratio = 6:1). The release of NPs-ACM was pH dependent. In vivo studies indicated that NPs-ACM exhibited fourfold higher tumor targeting capability on S180-tumor-bearing mice compared with the free ACM (p < 0.05). The cytotoxictiy and cardiotoxicity of NPs-ACM was reduced compared with the free ACM. Albumin carrier altered the blood pharmacokinetics and distribution of ACM. Hence, the NPs-ACM prodrug is ideal tumor targeting drug carriers for ACM, and the easy approach developed in this study for active intermediate and prodrug preparation can be applied to other pharmacological substances containing ketone groups. The method of preparing HSA-blank nanoparticles through TCEP reduction could be adopted to improve the water solubility of lipophilic drugs and their tumor-targeting specificity by fabricating HSA-lipophilic drug nanoparticles.
|
10.1088/0957-4484/27/46/465602
|
pubmed_466_12903
|
The authors describe the first case of giant intracranial aneurysm in a child with tuberous sclerosis. The subject of vascular disease in this condition is reviewed.
|
10.1097/00004728-198503000-00031
|
pubmed_503_9042
|
Nitrous oxide (N2O) is produced by denitrification, i.e. by microbial reduction of nitrate (NO3-). Our previous studies have established an analytical method for demonstrating the existence of N2O in exhaled air, and we showed that levels of N2O in exhaled air increase with age after puberty. However, the source of this change and its biological significance are still unclear. The purpose of this study was to examine whether the oral microorganisms are the main source of N2O. We measured exhaled N2O in 35 young adults (aged 19-29 years) and 34 older adults (aged 61-79 years) before and after mouth cleansing. N2O was measured using an infrared-photoacoustic analyzer equipped with an optical filter (UA0985, 2215 cm-1). Participants were classified as producers and non-producers according to the levels of exhaled N2O relative to the level in the atmosphere. N2O production differed significantly between the young adult producers and the older adult producers. Mouth cleansing resulted in an immediate reduction in exhaled N2O in both groups. We only found seven (20.0%) producers in the young, and 32 (94.1%) producers in the older after mouth washing. The differences before and after mouth cleansing were significant in both groups (P < 0.01 in the young and P < 0.05 in the older). The oral cavity is a major source of N2O. However, since approximately half-levels of N2O were still observed in exhaled air after mouth, cleansing, there may exist another N2O source in the human body.
|
10.1016/s0048-9697(98)00353-2
|
pubmed_636_24382
|
BACKGROUND
Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves), a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death.
METHODS
Hydro-methanolic extract of curry leaves (CLE) was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau's method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes.
RESULTS
CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells.
CONCLUSIONS
Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death. Therefore, identification of active component(s) from the leaf extract could lead to the development of anti-cancer agents which could be useful in the treatment of different types of cancers.
|
10.1186/1472-6882-13-7
|
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