index
stringlengths
10
17
text
stringlengths
101
18k
doi
stringlengths
2
72
pubmed_52_7589
The development of high-load, oligomeric benzylsulfonium salts, generated via ring-opening metathesis polymerization, and their utility in facile benzylations of various nucleophiles is reported. These oligomeric sulfonium salts exist as free-flowing powders and are stable at room temperature. After the benzylation event, purification is attained via simple dry load/filtration, followed by solvent removal to deliver products in excellent yield and purity.
10.1021/jo0620260
pubmed_736_908
The spread of a particular strain of Pseudomonas aeruginosa through a pediatric burn unit was monitored using serological typing and antibiotic susceptibility data.
10.1128/am.27.6.1167-1169.1974
pubmed_386_5588
OBJECTIVES The purpose of this study was to evaluate the long-term outcomes of the Ross procedure in a nationwide follow-up. METHODS This retrospective study involved all children treated with the Ross procedure in Finland between 1994 and 2009. The clinical records were reviewed for demographic and anatomical characteristics, Ross operation data, surgical history and status at the latest follow-up. The median follow-up time was 11.5 (range 2.4-19.2) years. RESULTS Fifty-one patients underwent either the Ross (n = 37) or the Ross-Konno (n = 14) procedure at a median age of 4.8 (range 0.02-16.3) years, including 13 infants (<1 year of age). The indication for the Ross procedure was aortic valve stenosis, regurgitation or both, which was observed in 29, 24 and 47% of patients, respectively. The early mortality (before hospital discharge) rate was 10% (31% in infants) and the late mortality rate 6% (15% in infants). Higher mortality was discovered in patients treated with the Ross-Konno procedure (P = 0.001). The most common cause for reintervention was pulmonary homograft stenosis. The rate of freedom from right ventricular outflow tract reintervention was 98% at 5 years, 83% at 10 years and 59% at 15 years. The rate of freedom from autograft reintervention was 98% at 5 and 10 years, and 81% at 15 years. At the latest follow-up visit, mild-to-moderate aortic root dilatation was reported in 52% of patients, and 4 patients had undergone autograft-related reinterventions. Trivial autograft valve regurgitation was commonly seen, but only 1 patient developed severe autograft regurgitation requiring mechanical valve replacement 15.9 years after the Ross operation. CONCLUSIONS The most common reason for reintervention after the Ross procedure in children is homograft stenosis. Aortic root dilatation and autograft valve regurgitation are relatively common but rarely lead to reinterventions before adulthood. Intraoperative complications and complex cardiac anatomy are associated with high mortality in infants undergoing the Ross-Konno procedure. In our centre, the Ross procedure has provided good long-term results in this challenging group of paediatric patients.
10.1093/ejcts/ezv004
pubmed_849_235
It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease.
10.3390/nu7064271
pubmed_494_2625
PURPOSE To determine the effectiveness and potential side effects of oral, vaginal, and sublingual intake of misoprostol on cervical dilatation prior to fractional curettage in patients with postmenopausal bleeding. METHODS Seventy-six patients with postmenopausal bleeding during a period of 18 months were included in this randomized controlled trial. Patients were given 400 microg of misoprostol through the vaginal, oral, and sublingual routes, 12 h prior to the fractional curettage procedure. The degree of cervical dilatation, duration of the procedure, the side effects and complications were noted. RESULTS When compared with the control group, misoprostol administered orally or sublingually was found to have a significant effect on cervical dilatation (P < 0.05). Of the three groups, nausea was found to be more common in the orally administered misoprostol group. CONCLUSIONS We conclude that the oral or sublingual application of misoprostol prior to fractional curettage in patients with postmenopausal bleeding decreases the need for cervical dilatation.
10.1007/s00404-008-0787-0
pubmed_632_4133
The electrodeposition of nanocrystalline Ni–Fe alloy coatings and associated nucleation/growth processes are investigated on the glassy carbon (GC) electrode in 1-butyl-3-methylimidazolium-hydrogen sulfate ([BMIM]HSO4) ionic liquid (IL). Cyclic voltammetric data suggest that the co-electrodeposition of Ni–Fe alloys is quasi-reversible. Moreover, chronoamperometry results indicate that the electrodeposition proceeds via a simultaneous nucleation and three-dimensional growth mechanism. In addition, the effects of electrodeposition potential and electrolyte temperature on the coating thickness and Fe content are also studied. The microstructure and composition of the Ni–Fe alloy coatings on Cu substrate are investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS). SEM observations show that these electrodeposits present a dense and compact structure, EDS analysis indicates that the coatings are composed of Ni and Fe, XRD pattern shows the coatings are crystalline with a face-centred cubic (fcc) structure. Tafel plots reveal that the Ni–Fe alloy prepared from [BMIM]HSO4 IL presents better corrosion resistance than that of pure Ni.
10.1166/jnn.2017.12719
pubmed_970_16507
Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species.
10.1074/jbc.RA120.013316
pubmed_299_3116
Cell rapidly adapts to the harsh environment under certain conditions such as hypothermia and stress via activity of certain specific cold-shock proteins. Two cold shock proteins, RNA-binding motif protein 3 (RBM3) and coldinducible RNA binding proteins (CIRP), have been unveiled in human cells. RBM3, which is able to regulate their expression at the level of translation by binding to different transcripts, allows the cell to respond rapidly to environmental signals. Additionally, expression of RBM3 is induced under mild to moderate hypothermia, and stress. Stress-response pathways play an essential role in cancer. In different types of cancer, RBM3 is up regulated and correlated with favourable clinic- pathological features. RBM3 plays certain functions such as anti-apoptotic, cell proliferation enhancement, and a proto-oncogene function. Furthermore, Hypothermia-induced neuroprotection up- regulates RBM3 in neuronal cells. In this review, the multifunctional nature of RMB3 is outlined through summarizing the evidences from in vitro and in vivo studies.
10.2174/0929866523666160628090340
pubmed_973_13399
The CHO1-encoded phosphatidylserine synthase from Saccharomyces cerevisiae is phosphorylated and inhibited by protein kinase A in vitro. CHO1 alleles bearing Ser(46) --> Ala and/or Ser(47) --> Ala mutations were constructed and expressed in a cho1Delta mutant lacking phosphatidylserine synthase. In vitro, the S46A/S47A mutation reduced the total amount of phosphorylation by 90% and abolished the inhibitory effect protein kinase A had on phosphatidylserine synthase activity. The enzyme phosphorylation by protein kinase A, which was time- and dose-dependent and dependent on the concentration of ATP, caused a electrophoretic mobility shift from a 27-kDa form to a 30-kDa form. The two electrophoretic forms of phosphatidylserine synthase were present in exponential phase cells, whereas only the 27-kDa form was present in stationary phase cells. In vivo labeling with (32)P(i) and immune complex analysis showed that the 30-kDa form was predominantly phosphorylated when compared with the 27-kDa form. However, the S46A/S47A mutations abolished the protein kinase A-mediated electrophoretic mobility shift. The S46A/S47A mutations also caused a 55% reduction in the total amount of phosphatidylserine synthase in exponential phase cells and a 66% reduction in the amount of enzyme in stationary phase cells. In phospholipid composition analysis, cells expressing the S46A/S47A mutant enzyme exhibited a 57% decrease in phosphatidylserine and a 40% increase in phosphatidylinositol. These results indicate that phosphatidylserine synthase is phosphorylated on Ser(46) and Ser(47) by protein kinase A, which results in a higher amount of enzyme for the net effect of stimulating the synthesis of phosphatidylserine.
10.1074/jbc.M110.100727
pubmed_510_2885
The present research evaluated the psychometric properties of a brief self-report instrument designed to assess appraisal of diabetes. Two hundred male subjects completed the Appraisal of Diabetes Scale (ADS) and provided blood samples that were subsequently assayed to provide an index of glycemic control (i.e., glycosylated hemoglobin). Subjects also completed either (a) additional measures of diabetes-related health beliefs, diabetic daily hassles, perceived stress, diabetic adherence, and psychiatric symptoms or (b) the ADS on two additional occasions. Results indicated that the ADS is an internally consistent and stable measure of diabetes-related appraisal. The validity of the measure was supported by correlational analyses which documented the relationship between the ADS and several related self-report measures.
10.1007/BF00844767
pubmed_886_17704
OBJECTIVES Increasing admission and prevalence rates of bipolar disorder (BD) are a matter of controversy in international child and adolescent psychiatry. We seek to contribute to this discussion by presenting data obtained in a population of German children and adolescents. METHODS Nationwide, whole population changes in inpatient admissions of BD and other psychiatric disorders between 2000 and 2007 were analyzed in individuals aged up to 19 years using registry data from the German Federal Health Monitoring System. RESULTS Inpatient admissions for BD in individuals aged up to 19 years increased from 1.13 to 1.91 per 100,000 or 68.5% between 2000 and 2007 (odds ratio: 1.69; 95% confidence interval: 1.41-2.02), with a nonsignificant decline in children less than 15 years and the largest relative increase in adolescents aged 15-19 years. Inpatient rates for depressive disorders increased by 219.6% and for hyperkinetic disorder by 111.3%. Conduct disorders increased by 18.1%, considerably less than the 38.1% general rise for all mental disorders in children and adolescents. The only significant decline in a diagnostic category occurred for psychotic disorders (-11.8%). BD inpatient admission represented only 0.22% of all mental disorder admissions in 2000 and 0.27% in 2007. CONCLUSIONS An elevation of inpatient admissions of BD in Germany in adolescents was detected, exceeding the general trend for increased mental disorder admissions. The results may indicate a higher clinical awareness and appreciation of mood symptoms at earlier ages and, in part, a reconceptualization of previously diagnosed psychotic disorders in youth. However, a diagnosis of BD in youngsters is still extremely rare in Germany. Diagnoses were based on the judgment of the treating physician. A correction for multiple admissions in the data set is not possible.
10.1111/j.1399-5618.2010.00794.x
pubmed_943_8517
A 64-year-old woman had severe vulvovaginitis develop while she was receiving intravaginal nystatin therapy for Candida glabrata infection. Mucocutaneous adverse effects have rarely been reported with nystatin despite long years of use. This complication should be included in the differential diagnosis of clinical failure of intravaginal nystatin therapy.
10.1067/mob.2001.115112
pubmed_793_4088
Laboratory studies indicate that the unicellular green alga Chlorella salina CU-1 could be cultivated in treated sewage effluent with high salinity. The high protein content (51% dry weight), and the relatively complete amino acid profile of the cells, suggest that this alga might be an ideal organism to be used for single cell protein production from high-salinity sewage.
10.1007/BF01965971
pubmed_575_8753
Ethylparaben (EtP) and propylparaben (PrP) are common preservatives and well-known endocrine-disrupting chemicals. Studies have demonstrated that they can reduce female fertility, but the underlying mechanism, especially that on embryo implantation, is still poorly understood. Endometrial decidualization is a critical event for embryo implantation. In this study, we aimed to explore the effects of EtP/PrP on endometrial decidualization. Pregnant mice were dosed daily by oral gavage with EtP at 0, 400, 800 and 1600 mg/kg or with PrP at 0, 625, 1250 and 2500 mg/kg from Day 1 of pregnancy until sacrifice. The results showed that the rate of pregnant mice with impaired embryo implantation, whose number of implantation sites was less than 7, was significantly increased after exposure to 1600 mg/kg EtP or 2500 mg/kg PrP. Further study found that the expression of endometrial decidualization markers HOXA10, MMP9 and PR was significantly downregulated in 1600 mg/kg EtP group and 2500 mg/kg PrP group. Notably, serum oestrogen and progesterone levels were significantly increased, whereas the expression of uterine oestrogen receptor and progesterone receptor was decreased following 1600 mg/kg EtP or 2500 mg/kg PrP exposure. In the breeding test, fewer offspring were found after females were exposed to 1600 mg/kg EtP or 2500 mg/kg PrP in early pregnancy. This demonstrated that exposure to EtP/PrP interfered with embryo implantation by compromising endometrial decidualization in early-stage pregnant mice. Disorders of reproductive hormones and hormone receptor signals could be responsible for impaired decidualization. This study broadened the understanding on the biological safety of EtP and PrP.
10.1002/jat.4208
pubmed_471_3357
Zeolite analcime (EMANA) was synthesized through the hydrothermal method by using carbothermal reduction electrolytic manganese residue (CR-EMR). The structural properties of EMANA and CR-EMR were studied using various characterization techniques. After hydrothermal synthesis, the CR-EMR became super-microporous, and the surface area increased by 4.76 times than before. Among the various synthesized zeolites, 6 h-synthesized EMANA was selected as the best adsorbent for macrolide antibiotics in aqueous solution. The adsorption performance of EMANA on the adsorption capacity was examined by using various experimental parameters, such as contact time (0⁻24 h), initial concentration (50⁻300 mg/L), temperature (30⁻50 °C) and pH (3⁻13). The experimental results were also analyzed by the Langmuir and Freundlich adsorption models, with the latter obtaining better representation. The adsorption process could be described well by the pseudo-second-order model, even under a low concentration (50 mg/L). This result suggests that the adsorption process of macrolide antibiotics is due to chemisorption. According to the Fourier Transform infrared spectroscopy (FT-IR) results, the adsorption of zeolite was mainly due to its hydroxyl group, which played an important role during the adsorption process. Moreover, EMANA is more suitable for treatment of roxithromycin (ROX) than azithromycin (AZM), because ROX has more adsorption sites for the hydroxyl group.
10.3390/ma11112133
pubmed_1030_12083
Partly because of its antioxidant and anti-inflammatory properties, cocoa flavanols have been examined in reversing age-related cognitive deficits. Epidemiological studies indicate a relation between flavonoid intake and prevention of dementia. In confirmation of this relation, several pharmacological studies show faster speed of responding and better executive performance in flavanol-treated aged or young subjects. The lack of any effect appears in some studies, especially in young subjects, perhaps due to the use of groups with high educational levels and the possibility of a ceiling effect. In several studies, neuropsychological ameliorations were followed by increases in cerebral blood flow. These results are in line with those of animal experimentation, since improvements have been found in motor and spatial performance of young and aging mice or rats as well as animal models of Alzheimer's disease and Parkinson's disease. Improvements are also reported in biologic markers of Alzheimer's disease, in particular an increase soluble Aβ and a decrease in tau hyperphosphorylation.
10.2174/1874609815666220819145845
pubmed_634_13274
Currently, the use of synthetic pesticides is the main method of plant protection applied in agri- and horticulture. However, its excessive use leads to the development of pesticide resistance, a contamination of the environment, toxicity to non-target organisms, and risks for human health. With the ultimate aim of contributing to the develop of a more sustainable pest management, we used the natural product germacrone (compound 1), reported to possess significant insecticidal activity, as starting material for the generation of molecular diversity (2-24). Some of the generated derivatives are natural compounds, such as 1,10-epoxygermacrone (2), 4,5-epoxygermacrone (3), gajutsulactone A (7), germacrol (11), isogermacrone (14), 9-hydroxyeudesma-3,7(11)dien-6-one (19), eudesma-4,7(11),dien-8-one (20), eudesma-3,7(11)-dien-8-one (21) and eudesma-4(15),7(11)-dien-8-one (22). Compounds, 7,11-9,10-diepoxigermacr-4,5-en-8-ol (17), 7,11-epoxieudesma-4,7(11)-dien-8-one (23) and 7,11-epoxieudesma-3,7(11)-dien-8-one (24) are described for the first time. The biocidal activity of most of these compounds was assayed against the tick Hyalomma lusitanicum. The acaricidal effects of compound 24 were four times higher than that of germacrone (1). Compound 2 is an insect antifeedant a thousand times more potent than germacrone against Rhopalosiphum padi, which makes this substance a promising selective antifeedant against this cereal pest.
10.3390/molecules24162898
pubmed_846_7458
The influence of asymptomatic neuroviral infection produced by the 17D vaccine strain of yellow fever virus on the conditional reflex development of intracerebrally inoculated BALB/c mice was studied. In the virus-infected animals, the development of a conditional reflex in the labyrinth was hampered, on the one hand, by weakening of the inhibition process in the brain due to viral infection which was manifested by regular reproduction of "excess" information and perseverance; on the other hand, the development of the conditional reflex was made difficult because of the disturbance of the mechanisms providing for prolonged permanent level of awakeness. The observed changes were not accompanied by marked pathomorphological lesions in the CNS.
pubmed_846_7458
pubmed_481_8245
OBJECTIVE To evaluate the correspondence between DSM-III-R and DSM-IV definitions of attention-deficit/hyperactivity disorder (ADHD) in clinically referred children. Results of the field trials led to the hypothesis that there would be a strong correspondence between DSM-III-R and DSM-IV subtypes. METHOD The sample consisted of all children and adolescents consecutively referred to a pediatric psychopharmacology clinic (N = 405). Children were comprehensively evaluated with structured diagnostic interviews assessing both DSM-III-R and DSM-IV ADHD. DSM-III-R symptoms were used to approximate DSM-IV subtypes. Kappa statistics and conditional probabilities were used to examine the correspondence between DSM-III-R and DSM-IV ADHD. RESULTS Ninety-three percent of children who received a DSM-III-R diagnosis of ADHD also received a DSM-IV ADHD diagnosis. The kappa coefficient assessing the agreement between DSM-III-R and DSM-IV ADHD was .73 (z = 14.6, p < .0001). The kappa coefficient assessing the agreement between the DSM-III-R-approximated subtypes and the actual DSM-IV subtypes was .71 (z = 15, p < .0001). CONCLUSION These results confirm previous findings and indicate that the change from DSM-III-R to DSM-IV results in minimal changes in case identification and provides support for diagnostic continuity between the two classification systems.
10.1097/00004583-199712000-00016
pubmed_372_17283
Three-dimensional (3D) extrusion bioprinting typically requires an ad hoc trial-and-error optimization of the ink composition toward enhanced resolution. The ink solutions are solidified after leaving cone-shaped or cylindrical nozzles. The presence of ink instability not only hampers the extrusion resolution but also affects the behavior of embedded cellular components. This is a key factor in selecting (bio)inks and bioprinting design parameters for well-established desktop and handheld bioprinters. In this work, we developed an analytical solution for the process of ink deposition and compared its predictions against numerical simulations of the deposition. We estimated the onset of ink instability as a function of ink rheological properties and nozzle geometry. Our analytical results suggest that enhancing the shear-thinning behavior of the ink shortens the toe region of the deposition. Such an extrusion process is often desired, as it leads to faster depositions. However, we demonstrated that such conditions increase the possibility of lateral buckling of the strand once touching the substrate defined as instability in this study. The present study serves as a benchmark for detailed simulations of the extrusion process for optimal bioprinting.
10.1115/1.4053404
pubmed_39_14852
OBJECTIVES This study examines factors affecting reliability, or consistency of assessment scores, from an objective structured clinical examination (OSCE) in neurology through generalizability theory (G theory). METHODS Data include assessments from a multistation OSCE taken by 194 medical students at the completion of a neurology clerkship. Facets evaluated in this study include cases, domains, and items. Domains refer to areas of skill (or constructs) that the OSCE measures. G theory is used to estimate variance components associated with each facet, derive reliability, and project the number of cases required to obtain a reliable (consistent, precise) score. RESULTS Reliability using G theory is moderate (Φ coefficient = 0.61, G coefficient = 0.64). Performance is similar across cases but differs by the particular domain, such that the majority of variance is attributed to the domain. Projections in reliability estimates reveal that students need to participate in 3 OSCE cases in order to increase reliability beyond the 0.70 threshold. CONCLUSIONS This novel use of G theory in evaluating an OSCE in neurology provides meaningful measurement characteristics of the assessment. Differing from prior work in other medical specialties, the cases students were randomly assigned did not influence their OSCE score; rather, scores varied in expected fashion by domain assessed.
10.1212/WNL.0000000000002053
pubmed_39_5243
BACKGROUND In glioblastoma (GBM), the gene for epidermal growth factor receptor (EGFR) is frequently amplified. EGFR mutations also are common, including a truncation mutation that yields a constitutively active variant called EGFR variant (v)III. EGFRvIII-positive GBM progresses rapidly; however, the reason for this is not clear because the activity of EGFRvIII is attenuated compared with EGF-ligated wild-type EGFR. We hypothesized that EGFRvIII-expressing GBM cells selectively express other oncogenic receptors that support tumor progression. METHODS Mining of The Cancer Genome Atlas prompted us to test whether GBM cells in culture, which express EGFRvIII, selectively express vascular endothelial growth factor receptor (VEGFR)2. We also studied human GBM propagated as xenografts. We then applied multiple approaches to test the effects of VEGFR2 on GBM cell growth, apoptosis, and cellular senescence. RESULTS In human GBM, EGFR overexpression and EGFRvIII positivity were associated with increased VEGFR2 expression. In GBM cells in culture, EGFRvIII-initiated cell signaling increased expression of VEGFR2, which prevented cellular senescence and promoted cell cycle progression. The VEGFR-selective tyrosine kinase inhibitor cediranib decreased tumor DNA synthesis, increased staining for senescence-associated β-galactosidase, reduced retinoblastoma phosphorylation, and increased p27(Kip1), all markers of cellular senescence. Similar results were obtained when VEGFR2 was silenced. CONCLUSIONS VEGFR2 expression by GBM cells supports cell cycle progression and prevents cellular senescence. Coexpression of VEGFR2 by GBM cells in which EGFR signaling is activated may contribute to the aggressive nature of these cells.
10.1093/neuonc/nov243
pubmed_306_18299
Heart failure (HF) is the end stage of several pathological cardiac conditions including myocardial infarction, cardiac hypertrophy and hypertension. Various molecular and cellular mechanisms are involved in the development of HF. At the molecular level, the onset of HF is associated with reprogramming of gene expression, including downregulation of the alpha-myosin heavy chain (α-MHC) gene and sarcoplasmic reticulum Ca (2+) ATPase genes and reactivation of specific fetal cardiac genes such as atrial natriuretic factor and brain natriuretic peptide. These deviations in gene expression result in structural and electrophysiological changes, which eventually progress to HF. Cardiac arrhythmia is caused by altered conduction properties of the heart, which may arise in response to ischemia, inflammation, fibrosis, aging or from genetic factors. Because changes in the gene transcription program may have crucial consequences as deteriorated cardiac function, understanding the molecular mechanisms involved in the process has become a priority in the field. In this context, various studies besides having identified different DNA methylation patterns in HF patients, have also focused on specific disease processes and their underlying mechanisms, also introducing new concepts such as epigenomics. This review highlights specific genetic mutations associated with the onset and progression of HF, also providing an introduction to epigenetic mechanisms such as histone modifications, DNA methylation and RNA-based modification, and highlights the relation between epigenetics, arrhythmogenesis and HF.
10.3389/fgene.2013.00219
pubmed_517_20933
BACKGROUND The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. METHODS Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR. RESULTS Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3 CONCLUSION These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.
10.1186/1471-2393-11-74
pubmed_224_2994
Persons born in 1905 and living in the municipality of Stockholm were, in 1971, invited to a health check-up. The participants in this investigation were 3 years later invited to a follow-up-control. In this, 4,930 persons participated, i.e. approx. 50% of Stockholmers born in 1905, the original target population. In a questionnaire administered in connection with the 1974 health check-up 4% of the men and 7% of the women claimed to have symptoms suggesting a depressive syndrome. These 284 persons were examined psychiatrically, as well as 178 who had claimed the same symptoms 3 years earlier, and 127 who constituted a control group, in all 589 persons. In nearly all cases the depressed mood was judged to be a sign of neurotic condition. Severe untreated depressive states were not observed. In most cases retirement as such seemed not to have had any negative effect on the mental health of the examinees. Fifty-nine subjects stated that their mental problems had begun after the health examination in 1971, i.e. after the age of 65. The majority of subjects with mental disorders had developed their problems much earlier. It would appear that a general health control for elderly people in a major urban area does not reach those pensioners who are most depressed.
10.1111/j.1600-0447.1983.tb00327.x
pubmed_74_15581
OBJECTIVE Examine the associations of maternal thyroid hormones, maternal dietary information, and newborn T4 levels with cognitive outcomes in mid-childhood. METHODS We studied 921 children born 1999-2003 at gestational age ≥ 34 weeks, who were participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We examined maternal dietary information, maternal thyroid hormone levels, and neonatal levels of T4. Research staff performed cognitive testing in mid-childhood (median age 7.7 years). RESULTS We included 514 women with measured first trimester thyroid hormone concentrations (mean 10.2 weeks); 15% of women had a thyroid stimulating hormone (TSH) level ≥ 2.5 mU/L, and 71% were college graduates. Newborn T4 was collected from 375 infants (mean 17.6 μg/dl; SD 4.0), on day 2 (mean 1.9 days; SD 0.7) as part of the newborn screening program. Mean (SD) verbal and nonverbal IQ, memory, and motor scores of children were 113.2 (14.3), 107.1 (16.7), 17.1 (4.4), and 92.5 (16.6) points, respectively. In multivariable analysis, first trimester maternal thyroid function (total T3, total T4, free T4, thyroid stimulating hormone (TSH) or total thyroid peroxidase (TPO) antibody levels) or newborn T4 were not associated with any of the cognitive outcomes in mid-childhood after adjustment for sociodemographic and perinatal variables. CONCLUSIONS FOR PRACTICE Maternal or neonatal thyroid hormone levels were not associated with cognitive outcomes in mid-childhood in this population with generally normal thyroid function. As we studied a highly educated cohort residing in an iodine-sufficient area, findings may not be generalizable.
10.1007/s10995-019-02867-5
pubmed_527_17044
Health reformers have an established record of losing. Going into 2009, there were plenty of reasons to believe that they would fail again. A polarized political environment, soaring budget deficits, and myriad other obstacles stood in the way. Yet the Obama administration and congressional Democrats defied the odds. Democrats won the 2009-10 health reform battle by successfully applying lessons learned from past failures, including the importance of neutralizing interest-group opposition. The result is historic legislation that, given the constraints imposed by both the U.S. political and health systems, is probably as good as it gets.
10.1377/hlthaff.2010.0447
pubmed_444_3442
A liquid chromatography method coupling diode-array and fluorescence detectors (DAD and FLD, respectively) has been developed for the simultaneous quantification of 32 phenolic compounds (PCs) in winemaking products. With the combination of both detectors it was possible to determine phenolic acids, flavanols, flavonols, stilbenes and other PCs in the matrices under study. An excitation wavelength of 290 nm was selected and three different emission wavelengths (315, 360 and 400 nm) were recorded. The method provided detection and quantification limits (LODs and LOQs) within the ranges of 0.01-1.46 mg/L and 0.03-4.9 mg/L, respectively. The LODs and LOQs using FLD for flavanols, stilbenes and phenyl ethanol analogues were improved between 65 and 1000% as compared with DAD. The combination of DAD with FLD increased both, sensitivity and the ability to reduce interfering signals. The developed method was applied for the characterization of PCs of wines, bunch stems and grape canes.
10.1016/j.foodchem.2020.128030
pubmed_362_1274
A straightforward and practical strategy for pyridylation of inert N-heterocycles, enabled by ammonium cation and electrochemical, has been described. This protocol gives access to various N-fused heterocycles and bidentate nitrogen ligand compounds, through dual-proton-coupled electron transfer (PCET) and radical cross-coupling in the absence of exogenous metal and redox reagent. It features broad substrate scope, wide functional group tolerance, and easy gram-scale synthesis. Various experiments and density functional theory (DFT) calculation results show the mechanism of dual PCET followed by radical cross-coupling is the preferred pathway. Moreover, ammonium salt plays the dual role of protonation reagent and electrolyte in this conversion, and the resulting product 9-(pyridin-4-yl)acridine compound can be used for fluorescence recognition of Fe2+ and Pd2+ with high sensitivity.
10.1016/j.isci.2022.104253
pubmed_319_16758
BACKGROUND Although every state prohibits persons aged <21 years from driving with any measurable amount of blood alcohol, many young persons still drink and drive. Additionally, fatal crash data indicate that most teen drivers with positive (>0.00%) blood alcohol concentrations (BACs) who are involved in fatal crashes have BACs ≥0.08%, the level designated as illegal for adult drivers. METHODS CDC analyzed data from the 1991-2011 national Youth Risk Behavior Surveys (YRBS) to describe the trend in prevalence of drinking and driving (defined as driving one or more times when they had been drinking alcohol during the 30 days before the survey) among U.S. high school students aged ≥16 years. The 2011 national YRBS data were used to describe selected subgroup differences in drinking and driving, and 2011 state YRBSs data were used to describe drinking and driving prevalence in 41 states. RESULTS During 1991-2011, the national prevalence of self-reported drinking and driving among high school students aged ≥16 years declined by 54%, from 22.3% to 10.3%. In 2011, 84.6% of students who drove after drinking also binge drank. Drinking and driving prevalence varied threefold across 41 states, from 4.6% in Utah to 14.5% in North Dakota; higher prevalences were clustered among states in the upper Midwest and along the Gulf Coast. CONCLUSIONS Although substantial progress has been made during the past 2 decades to reduce drinking and driving among teens, in 2011, one in 10 students aged ≥16 years reported driving after drinking during the past 30 days. Most students who drove after drinking alcohol also binge drank. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE Effective interventions to reduce drinking and driving among teens include enforcement of minimum legal drinking age laws, zero tolerance laws (i.e., no alcohol consumption allowed before driving for persons aged <21 years), and graduated driver licensing systems.
pubmed_319_16758
pubmed_311_9298
STUDY DESIGN Retrospective radiographic study. OBJECTIVE To investigate the growth of the vertebrae around distal instrumented vertebra (DIV) in patients with early-onset scoliosis (EOS) who underwent dual growing rod (DGR) treatment. SUMMARY OF BACKGROUND DATA Previous studies indicated that DGR was likely to preserve or even stimulate the spinal growth. However, report pertaining to the effect of growing rod on the growth of individual vertebral body is rare. METHODS The EOS patients treated with DGR who had at least four lengthenings and 5-year follow-up were enrolled. Spine radiographs at index surgery and final follow-up were reviewed. The height, width, and depth of vertebral body from DIV-2 to DIV+2, and the height of the adjacent intervertebral space (IVS) were measured. The percentage of growth was calculated. RESULTS Thirty-one patients (mean age, 6.2 ± 2.5 years old) met the inclusion criteria, 74.2% (23/31) of whom were female. The average follow-up was 6.2 years (range, 5.0-10.4 yr). The measured vertebrae were divided into DIV group (n = 65), DIV- group (DIV-1 and DIV-2, n = 60), and DIV+ group (DIV+1 and DIV+2, n = 47). There were 33, 90, and 78 measured IVSs in DIV, DIV-, and DIV+ group, respectively. The total percentage growth of vertebral height was significantly higher in DIV- group than that in DIV and DIV+ groups (56.6 ± 20.3% vs. 45.6 ± 18.0% and 42.7 ± 16.2%, respectively, P ≤ 0.001). The vertebrae in DIV- group also had the highest annual height growth rate (8.7 ± 2.6% vs. 7.0 ± 2.4% and 6.6 ± 2.0%, respectively, P ≤ 0.001). A significant decrease of IVS height was observed in DIV- and DIV groups (P ≤ 0.001). CONCLUSION Traditional DGR with periodical distraction stimulated the longitudinal growth of the two segments immediately above DIV in patients with EOS. DGR technique had a negative effect on the development of intervertebral discs within distracted levels. LEVEL OF EVIDENCE 3.
10.1097/BRS.0000000000002957
pubmed_715_7569
BACKGROUND Sarcoidosis, which occurs most commonly in African American women, is a granulomatous multisystem disorder affecting the skin, lungs, and central nervous system. In a previous immunohistochemistry study of keloids, a scar granuloma stained highly positive for glioma-associated oncogene homologue (gli)-1. OBSERVATION This observation led us to study whether gli-1, one of the vertebrate zinc finger transcription factor genes of the gli superfamily, is expressed in granulomatous skin disorders such as cutaneous sarcoidosis, granuloma annulare (GA), and necrobiosis lipoidica diabeticorum (NLD). Immunohistochemistry studies for gli-1 were performed on biopsy specimens from patients with cutaneous sarcoidosis, GA, and NLD. All sarcoid lesions were highly positive for gli-1 expression, and 75% of the cells demonstrated positivity with a stain intensity of 3 on a scale of 1 to 3. The gli-1 expression was confined to cutaneous granulomas. CD68 staining was highly positive in the sarcoid lesions as well. Similarly, GA and NLD lesions were uniformly positive for gli-1 expression. CONCLUSIONS We found that gli-1 is inappropriately expressed in granulomatous lesions of the skin such as cutaneous sarcoidosis, GA, and NLD. These findings provide a rationale for clinical trials of inhibitors of gli-1 signaling, including tacrolimus and sizolimus, for the treatment of cutaneous sarcoidosis and other granulomatous disorders of the skin.
10.1001/archderm.141.2.259
pubmed_2_11232
PURPOSE Phosphodiesterase type 5 inhibitors were recently introduced as a new treatment option for men with lower urinary tract symptoms. Safety and clinical effectiveness are well documented but the mode of action is still unclear. We determined and compared the expression of phosphodiesterase type 5 in the spinal cord of normal (sham operated) rats and rats with partial urethral obstruction induced bladder overactivity. We also assessed the urodynamic effects of intravenously and intrathecally administered sildenafil in the rats to determine whether phosphodiesterase type 5 inhibitors exert effects on the sacral spinal cord. MATERIALS AND METHODS A total of 65 male Sprague-Dawley rats were used for molecular/morphological and functional experiments. Bladder overactivity was induced via surgical partial urethral obstruction in 39 of 65 rats. Spinal phosphodiesterase type 5 expression was assessed by histology and polymerase chain reaction. The effects of sildenafil administered intravenously or intrathecally were studied urodynamically. RESULTS Phosphodiesterase type 5 was expressed in various regions of the lumbosacral spinal cord, including the sacral regions of micturition control. Expression was similar in normal rats and rats with partial urethral obstruction/bladder overactivity. In normal rats intravenous and intrathecal sildenafil had no urodynamic effect. When administered intravenously and intrathecally to rats with partial urethral obstruction/bladder overactivity, sildenafil decreased micturition frequency and bladder pressure. Doses tested intrathecally had no effect when given intravenously. CONCLUSIONS Phosphodiesterase type 5 is expressed in the rat spinal cord. Intravenous sildenafil may exert part of its urodynamic effect in rats with partial urethral obstruction/bladder overactivity via an effect on the sacral spinal cord.
pubmed_2_11232
pubmed_859_17928
One of the key steps in many metal complex-catalyzed hydroboration reactions is B-H bond activation, which results in metal hydride formation. Anionic ligands that include multiple lone pairs of electrons, in cooperation with a metal center, have notable potential in redox-neutral B-H bond activation through metal-ligand cooperation. Herein, using an easily prepared NpyridineNimineNpyrrolide ligand (L2)-, a series of divalent NiIIX(NNN) complexes were synthesized, with X = bromide (2), phenoxide (3), thiophenoxide (4), 2,5-dimethylpyrrolide (5), diphenylphosphide (6), and phenyl (7). The complexes were characterized using 1H and 13C NMR spectroscopy, mass spectrometry, and X-ray crystallography and employed as precatalysts for nitrile dihydroboration. Superior activity of the phenoxy derivative (3) [vs thiophenoxy (4) or phenyl (7)] suggests that B-H bond activation occurs at the Ni-X (vs ligand Ni-Npyrrolide) bond. Furthermore, stoichiometric treatment of 2-7 with a nitrile showed no reaction, whereas stoichiometric reactions of 2-7 with pinacolborane (HBpin) gave the same Ni-H complex for 2, 3, and 5. Considering that only 2, 3, and 5 successfully catalyzed nitrile dihydroboration, we suggest that the catalytic cycle involves a conventional inner sphere pathway initiated by substrate insertion into Ni-H.
10.1021/acs.inorgchem.2c03273
pubmed_1055_4624
The Springhouse series of Nurse Reviews is organised according to the phases of the nursing process and aims to provide nursing solutions for a wide range of patient problems. Each multiauthored American text has different clinical consultants and tries to present the current nursing knowledge and practice for a particular nursing specialty.
10.7748/ns.3.39.43.s63
pubmed_480_4245
Herboxidiene is a potent inhibitor of spliceosomes. It exhibits excellent anticancer activity against multiple human cancer cell lines. Herein, we describe an enantioselective synthesis of a desmethyl derivative and the corresponding carba-derivatives of herboxidiene. The synthesis involved Suzuki coupling of a vinyl iodide with boronate as the key reaction. For the synthesis of carba-derivatives, the corresponding optically active cyclohexane-1,3-dicarbonyl derivatives were synthesized using an enantioselective desymmetrization of meso-anhydride. The biological properties of these derivatives were evaluated in an in vitro splicing assay.
10.1039/c6ob00725b
pubmed_183_21965
An activity-induced increase in energy expenditure theoretically disturbs energy balance (EB) by creating an acute energy deficit. Compensatory responses could influence the weight loss associated with the energy deficit. Individual variability in compensation for perturbations in EB could partly explain why some individuals fail to lose weight with exercise. It is accepted that the regulatory system will readily defend impositions that promote a negative EB. Therefore, a criticism of exercise interventions is that they will be ineffective and futile methods of weight control because the acute energy deficit is counteracted. Compensation for exercise-induced energy deficits can be categorized into behavioral or metabolic responses and automatic or volitional. An automatic compensatory response is a biological inevitability and considered to be obligatory. An automatic compensatory response is typically a metabolic consequence (e.g., reduced resting metabolic rate) of a negative EB. In contrast, a volitional compensatory response tends to be deliberate and behavioral, which the individual intentionally performs (e.g., increased snack intake). The purpose of this review is to highlight the various metabolic and behavioral compensatory responses that could reduce the effectiveness of exercise and explain why some individuals experience a lower than expected weight loss. We propose that the extent and degree of compensation will vary between individuals. That is, some individuals will be predisposed to compensatory responses that render them resistant to the weight loss benefits theoretically associated with an exercise-induced increase in energy expenditure. Therefore, given the inter-individual variability in behavioral and metabolic compensatory responses, exercise prescriptions might be more effective if tailored to suit individuals.
10.1038/oby.2007.164
pubmed_74_8159
The current empirical study explores the linkage between carbon dioxide (CO2) emissions, average temperature, cultivated area, consumption of fertilizer, and rice production in Pakistan. For this research, the annual time series data from 1968 to 2014 were used to enhance the validity of the empirical outcomes. The cointegration analysis with the auto-regressive distributed lag (ARDL) bounds testing approach is applied to explore the effects of climate change on rice production. Additionally, the estimated long-run outcomes are verified by employing fully modified ordinary least squared (FMOLS) and canonical cointegrating regression (CCR) approaches. The empirical outcomes revealed that the selected important study variables are cointegrated demonstrating the existence of long-run linkages among them. The main fruitful outcomes of this study are that rice production in Pakistan is positively affected by the carbon dioxide (CO2) emissions in both long-run and short-run.
10.1007/s11356-019-07486-9
pubmed_1046_9750
To test their virus susceptibility and capacity as transmission vectors, Japanese Culicoides species were artificially fed a mixture of Akabane virus (AKAV) and bovine blood, and virus recovery was attempted from infected midges 9-11 d post-exposure. Culicoides tainanus, C. punctatus, C. humeralis, C. jacobsoni, C. oxystoma, and C. asiana were found to be orally susceptible to AKAV. Virus titers in single infected midges of C. tainanus, C. oxystoma, C. punctatus, and C. jacobsoni ranged from 100.75 to 104.0 TCID50 (tissue culture infectious dose). The titers in the infected C. oxystoma were significantly higher than those in the other infected species. Viral RNA was detected from both midges testing positive and those testing negative for infectious virus particles, but the viral RNA copies in the infectious virus-negative midges were significantly lower than those in the infectious virus-positive midges. Lower viral amplification, limited dissemination or both caused by tissue barriers might occur in infected midges from which infectious viruses were undetectable. A fully disseminated infection was developed in orally infected C. oxystoma and C. tainanus. This finding indicates their capacity to transmit AKAV, assuming that salivary gland barriers have limited effects on viral entry to and replication in salivary gland tissue. This result also suggests that the other orally susceptible species are potentially competent for AKAV transmission and would be considered active vectors of its spread.
10.1093/jme/tjy201
pubmed_196_15218
With the aid of extrusion-based biofabrication strategies, neural stem/progenitor cell-laden hydrogel structures can be fabricated for use in neural research. Extrusion-based strategies can be altered in order to fulfill various requirements. In this study, mouse neural progenitor cell (NE-4C) behaviors in multiple extrusion-based fabricated microenvironments were investigated. Extrusion-based bioprinted cell-laden structures and coaxially extruded core-shell cell fibers were successfully fabricated. Cell distribution and morphology were observed in different structures with scanning electron microscopy (SEM). Genes and proteins related to cell differentiation were examined using quantitative polymerase chain reaction (qPCR) and western blot (WB). The results show that compared with NE-4Cs cultured in petri dishes, the abundance of nestin was 6.28 ± 1.38 times higher in bioprinted structures and the abundances of Tuj-1 and GFAP were 3.14 ± 1.38 and 2.11 ± 0.21 times higher in cell fibers, respectively, indicating that NE-4Cs showed stronger differentiation tendency in cell fibers and weaker tendency in printed structures. This study may provide guidance in selecting fabrication strategies for use in neural research.
10.1088/1748-605X/ab3b4b
pubmed_874_17517
Candida catheter-related bloodstream infection (CRBSI) is a biofilm-related disease, which is usually refractory because antifungals show limited effect. With medical development and increase in number of compromised hosts, CRBSI became more frequent. Candida, which is one of the opportunistic pathogens, ranks the fourth causative organism of bacteremia. The onset of bacteremia is greatly associated with the presence of catheter. Repeated blood cultures and the central venous catheter (CVC) tip culture are done for the definitive diagnosis of Candida CRBSI. Additionally serological examinations such as (1 --> 3)-beta-D-glucan and mannan antigen are also useful for early diagnosis. It is important for the appropriate treatment to remove CVC, which is an artificial contaminated material, and administer antifungals promptly. As to the choice of antifungals, we should also take into account the ability of antibiofilm effect of antifungals as well as immunological state of host including neutropenia, prior administration of azoles, isolated or estimated Candida species, sensitivity against antifungals, administration route, pharmacokinetics (bioavailability, metabolic and excretion pathway, distribution) and drug interaction. As to complication of Candida bacteremia, first we should check endophthalmitis, which occurs frequently and leads to the loss of eyesight, as well as infective endocarditis, arthritis, metastatic infections such as embolic pneumonia and suppurative thrombotic phlebitis of catheter insertion site. Lastly we emphasize that the appropriate treatment based on the character of Candida bacteremia and biofilm leads to favorable prognosis.
pubmed_874_17517
pubmed_38_318
PURPOSE With the now routine use of computerized tomography angiography with 3-dimensional reconstruction in the donor evaluation, renal volume can be easily determined using volume calculating software. We evaluated whether donor renal volume could predict recipient renal function. MATERIALS AND METHODS Clinical data of all donor and recipient pairs undergoing live donor kidney transplantation at our institution between January 2006 and October 2009 were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software, and correlated to transplant recipient nadir and 1-year serum creatinine. Multivariate regression analysis was performed to adjust for demographic and clinical variables. RESULTS During the study period 114 patients underwent live donor renal transplantation. Recipient nadir and 1-year serum creatinine levels were significantly correlated with the volume of donated kidney even after adjusting for age, body mass index, body surface area and donor creatinine clearance. Kidney volume also retained significance after excluding recipients from analysis who experienced acute rejection episodes. CONCLUSIONS Larger kidney volumes calculated using 3-dimensional computerized tomography with volume calculating software are correlated with lower recipient nadir and 1-year serum creatinine levels.
10.1016/j.juro.2010.09.098
pubmed_906_3571
Following natural infection with Bartonella, dogs and humans develop comparable disease manifestations including endocarditis, peliosis hepatis, and granulomatous disease. As the immunologic response to infection in these hosts has not been clearly established, data presented here was derived from the experimental infection of six specific pathogen free (SPF) beagles with a known pathogenic strain of Bartonella. Six dogs were inoculated intravenously with 10(9)cfu of B. vinsonii ssp. berkhoffii and six control dogs were injected intravenously with an equivalent volume of sterile saline. Despite production of substantial levels of specific antibody, blood culture and molecular analyses indicated that Bartonella established chronic infection in these dogs. Flow cytometric analysis of monocytes indicated impaired bacterial phagocytosis during chronic Bartonella infection. There was also a sustained decrease in the percentage of CD8+ lymphocytes in the peripheral blood. Moreover, modulation of adhesion molecule expression (downregulation of L-selectin, VLA-4, and LFA-1) on CD8+ lymphocytes suggested quantitative and qualitative impairment of this cell subset in Bartonella-infected dogs. When compared with control dogs, flow cytometric analysis of lymph node (LN) cells from B. vinsonii infected dogs revealed an expanded population of CD4+ T cells with an apparent naïve phenotype (CD45RA+/CD62L+/CD49D(dim)). However, fewer B cells from infected dogs expressed cell-surface MHC II, implicating impaired antigen presentation to helper T cells within LN. Taken together, results from this study indicate that B. vinsonii establishes chronic infection in dogs which may result in immune suppression characterized by defects in monocytic phagocytosis, an impaired subset of CD8+ T lymphocytes, and impaired antigen presentation within LN.
10.1016/s0165-2427(01)00372-5
pubmed_880_305
This article draws on the findings from a mixed methods study with practitioners who qualified from joint training programmes in learning disability nursing and social work and explores the impact on professional identity of such programmes. Although several joint programmes are well established, very little research has been carried out with those who have qualified from them. These practitioners have experienced a kind of training quite unlike that offered by singular education programmes, incorporating a dual socialisation process, which has been neither analysed nor theorised. The study reported in this article comprised a postal survey to graduates from five programmes followed by in depth semi-structured interviews. Survey data were analysed by use of SPSS, while the interviews were analysed by use of a content analysis approach. The article discusses findings in relation to theoretical conceptions of professional status, boundaries and identity and relates these to the perceptions of respondents about their professional identities. It explores the ambiguities and uncertainties inherent in this type of professional training programme and argues that these reflect aspects of the current context of professions as a whole. The article concludes that a new professional identity is emerging in learning disability practice, generated by such programmes.
10.3109/13561820.2011.571352
pubmed_444_16955
The aim of this study was to verify the structural relationship between health perceptions, sports participation, and health promoting behavior in adolescents. A total of 507 adolescents living in Seoul, Republic of Korea, in 2020, participated in this study. This study was conducted using a preliminary survey and a main survey. In the preliminary survey, the reliability and validity of the scales used in this study were analyzed, and in the main survey, the relationships between individual variables were verified. Specifically, descriptive statistical analysis, path analysis, and mediating effect analysis were conducted in the main survey. The results of the study are as follows: first, health perceptions were found to have a positive effect on sports participation (p < 0.001). Furthermore, health perceptions were found to have no direct effect on health promoting behavior (p = 0.554), while sports participation was found to have a positive effect on health promoting behavior (p < 0.001). Additionally, sports participation completely mediated the relationship between health perceptions and health promoting behavior. Based on the results of this study, suggestions are presented on how to enhance health perceptions in adolescents who are in a critical period for forming healthy life habits, and to prepare measures to encourage sports participation.
10.3390/ijerph17186744
pubmed_902_21934
OBJECTIVE To evaluate the efficacy and safety of proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux disease (GERD) in infants <1 year of age. DATA SOURCES A literature search was conducted through PubMed (up to December 2009), International Pharmaceutical Abstracts (1970-December 2009), and The Cochrane Library (up to December 2009) using combinations of the following key search terms: proton pump inhibitor, GERD, infant, children, pediatric, omeprazole, rabeprazole, lansoprazole, esomeprazole, and pantoprazole. Reference citations from identified articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION All double-blind, placebo-controlled trials published in English that evaluated the safety and efficacy of PPIs in infants with GERD were included in this review. Trials involving children older than 12 months were not included. DATA SYNTHESIS GERD is a source of pain and discomfort in adults; yet, in infants, symptoms that are thought to be indicative of painful stimuli have no clear cause-and-effect relationship with infant GERD. PPIs are beneficial in relieving symptoms of GERD in the adult population, but their usefulness in decreasing GERD-associated behaviors in infants is still questionable, despite a large increase in PPI prescribing for children <1 year of age. In all studies reviewed, infants treated with PPIs did not experience a significant decrease in behaviors perceived to be caused by GERD. The largest placebo-controlled trial to date found that rates of adverse events were increased in the PPI group compared with the placebo group, whereas the other trials reviewed reported no difference in adverse effects with the use of PPIs. CONCLUSIONS Clinical trials reveal that PPI therapy is not an effective treatment for common infant GERD-associated symptoms. Evidence supporting safety of PPI use in infants is conflicting, and more large-scale, randomized, placebo-controlled trials are necessary to better establish the role of PPIs in infant GERD.
10.1345/aph.1M519
pubmed_91_12146
The noticeable improvement in the supply of glucose and oxygen to surviving cancer cells located far from the capillary region (primarily very slowly proliferating or non-proliferating cancer cells) can be taken as the main reason for cancer recurrence in the wake of successful tumour treatment with destruction of a high percentage of cancer cells. On the basis of theoretical and experimental research work on substrate supply, cell kinetics and therapy mechanisms in the intercapillary region, therapeutic steps are formulated which act on cancer cells situated at a greater distance from the capillaries and, therefore, against the genesis of cancer recurrence as such.
pubmed_91_12146
pubmed_334_7295
The cytoskeletal protein, actin, has its structure and function regulated by cofilin. In the absence of an atomic resolution structure for the actin/cofilin complex, the mechanism of cofilin regulation is poorly understood. Theoretical studies based on the similarities of cofilin and gelsolin segment 1 proposed the cleft between subdomains 1 and 3 in actin as the cofilin binding site. We used radiolytic protein footprinting with mass spectrometry and molecular modeling to provide an atomic model of how cofilin binds to monomeric actin. Footprinting data suggest that cofilin binds to the cleft between subdomains 1 and 2 in actin and that cofilin induces further closure of the actin nucleotide cleft. Site-specific fluorescence data confirm these results. The model identifies key ionic and hydrophobic interactions at the binding interface, including hydrogen-bonding between His-87 of actin to Ser-89 of cofilin that may control the charge dependence of cofilin binding. This model and its implications fill an especially important niche in the actin field, owing to the fact that ongoing crystallization efforts of the actin/cofilin complex have so far failed. This 3D binary complex structure is derived from a combination of solution footprinting data and computational approaches and outlines a general method for determining the structure of such complexes.
10.1073/pnas.0611283104
pubmed_804_9035
Haploid mouse embryonic stem cells (ESCs), in which a single hit mutation is sufficient to produce loss-of-function phenotypes, have provided a powerful tool for forward genetic screening. This strategy, however, can be hampered by undesired autodiploidization of haploid ESCs. To overcome this obstacle, we designed a new methodology that facilitates enrichment of homozygous mutant ESC clones arising from autodiploidization during haploid gene trap mutagenesis. Haploid mouse ESCs were purified by fluorescence-activated cell sorting to maintain their haploid property and then transfected with the Tol2 transposon-based biallelically polyA-trapping (BPATrap) vector that carries an invertible G418 plus puromycin double selection cassette. G418 plus puromycin double selection enriched biallelic mutant clones that had undergone autodiploidization following a single vector insertion into the haploid genome. Using this method, we successfully generated 222 homozygous mutant ESCs from 2208 clones by excluding heterozygous ESCs and ESCs with multiple vector insertions. This relatively low efficiency of generating homozygous mutant ESCs was partially overcome by cell sorting of haploid ESCs after Tol2 BPATrap transfection. These results demonstrate the feasibility of our approach to provide an efficient platform for mutagenesis of ESCs and functional analysis of the mammalian genome.
10.1093/nar/gky183
pubmed_670_21380
A method for non-haem iron analysis in bone marrow aspirates using graphite furnace atomic absorption spectrophotometry has been developed. Bone marrow aspirates were obtained from patients with various disorders. A good correlation is observed between chemical and cytological assessment of total non-haem iron in bone marrow. An intra-assay coefficient of variation of 9.0% was observed. The ferritin-iron concentration was also determined and a CVduplo of 11% was found. The ferritin iron concentration increased with an increasing total iron content until saturation of ferritin appeared to be reached at about 3 g ferritin per kg protein. It was concluded that the quantitative determination of bone marrow iron can be of value in the diagnosis and investigation of both hypo- and hyper-ferraemic disorders.
10.1515/cclm.1991.29.6.381
pubmed_804_5051
PURPOSE To evaluate the safety, efficacy, and feasibility of transcatheter arterial embolization (TAE) in the treatment of lower gastrointestinal bleeding (LGIB). METHODS Study group comprised all patients receiving angiography for LGIB in the Helsinki University Hospital during the period of 2004-2016. Hospital medical records provided the study data. Rebleeding, complication, and mortality rates (≤ 30 days) were the primary outcomes. Secondary outcomes included need for blood transfusions, durations of intensive care unit and hospital admissions, incidence of delayed rebleeding, and long-term complications, as well as overall survival. RESULTS During the study period, angiography for LGIB was necessary on 123 patients. Out of 123, 55 (45%) underwent embolization attempts. TAE was technically successful in 53 (96%). Rebleeding occurred in 14 (26%). The complication rate was 36%, minor complications occurring in 10 (19%) and major in nine (17%). Major complications resulted in bowel resection in seven (13%). Post embolization ischemia was the most common single complication seen in nine (17%). The mortality rate was 6%. Survival estimates of 1 and 5 years were 79 and 49%. DISCUSSION LGIB is a severe physiological insult occurring in patients who are often elderly and moribund. Although major post embolization complications occur, transcatheter arterial embolization should be the first-line approach over surgery in profuse LGIB in patients with hemodynamic instability, when colonoscopy fails or is unavailable, or when computerized tomography angiography detects small intestinal bleeding.
10.1007/s11605-018-3728-7
pubmed_207_15121
Steroid 11 beta-hydroxylase is encoded by two homologous genes, CYP11B1 and CYP11B2, located on chromosome 8q21-22. CYP11B1 encodes a specific cytochrome P-450 (P-450c11) necessary for cortisol biosynthesis, with predominantly 11 beta-hydroxylase and moderate 18-hydroxylase activity, whereas CYP11B2 encodes another isozyme (P-450cmo) necessary for aldosterone biosynthesis, with 11 beta-hydroxylase, 18-hydroxylase and 18-oxidase activities (the latter two termed corticosterone methyl-oxidase I and II; CMO-I and II, respectively). Two steroid biosynthetic defects, both relatively frequent in Israel, are caused by specific mutations in each of these genes. 11 beta-Hydroxylase deficiency is frequent among Jews from Morocco (1 in 5000 to 7000 births), and is characterized by virilization, hypertension, impaired cortisol biosynthesis, and increased deoxycorticosterone and androgens. Affected individuals have a single base substitution in exon 8 of CYP11B1, codon 448, from CGC (arginine) to CAC (histidine). This sequence, normally absent in CYP11B2, constitutes a true point mutation within the heme binding domain of CYP11B1 that results in marked impairment of enzymatic activity. The clinical expression is characterized by a wide range of variability in the signs of both androgen and mineralocorticoid excess, even though an identical mutation was found in all but one of the affected alleles examined. CMO-II deficiency is frequent among Jews from Iran (1 in 4000 births), and is characterized by a typical salt-wasting syndrome, increased 18-hydroxycorticosterone, impaired aldosterone biosynthesis, and a high ratio of these steroids. No mutation was found in CYP11B1, but all individuals affected were homozygous for two missense mutations in CYP11B2. The first, in exon 3, codon 181, from CGG (arginine) to TGG (tryptophane) is a mutation that completely abolishes both CMO-I and II activities, whereas the second, in exon 7, codon 386, from GTG (valine) to GCG (alanine) is a more conservative substitution that produces only a minimal reduction in CMO-I activity. Individuals homozygous for either one of these mutations are asymptomatic.
10.1016/0960-0760(93)90128-j
pubmed_638_15088
Microbial isolate Z143-1 found to be associated with an unidentified tunicate was characterized due to its significant antimicrobial activity. Z143-1 is similar to Pseudovibrio ascidiaceicola and Pseudovibrio denitrificans in morphological, physiological and biochemical characteristics, except for its ability to ferment glucose and produce a characteristic red pigment. Fatty acid methyl ester analysis revealed a predominance of the fatty acid 18:1 omega7c at 80.55%, at levels slightly lower than the Pseudovibrio denitrificans type strain DN34(T) (87.7%). The mol% G+C of Z143-1 is 54.02, relatively higher than the Pseudovibrio denitrificans type strain DN34(T) and Pseudovibrio ascidiaceicola with mol% G+C of 51.7 and 51.4, respectively. However, phylogenetic analysis of the 16S rRNA gene sequence of Z143-1 showed 100% similarity with the Pseudovibrio denitrificans type strain DN34(T). In this study, the bacterium Z143-1 is reported as a new strain of Pseudovibrio denitrificans. While there is no report of a secondary metabolite for Pseudovibrio denitrificans, Z143-1 produces the red pigment heptylprodigiosin, also known as 16-methyl-15-heptyl-prodiginine, which shows anti-Staphylococcus aureus activity.
10.1111/j.1574-6968.2007.00950.x
pubmed_1119_19371
The levels of the lipid peroxidation product malondialdehyde (MDA) and the activity of transaminases and alkaline phosphatases were estimated in the sera of 25 thermally injured patients at various time intervals after injury. The level of MDA was increased during the early postburn period, whereas the activities of transaminases and alkaline phosphatase became elevated later after injury. It is concluded that an increased concentration of lipid peroxidation product (MDA) in the early postburn period may affect the spleen, liver and kidney, resulting in the release of enzymes into blood stream. Such damage may be checked by the antioxidants superoxide dismutase or allopurinol.
10.1016/0305-4179(95)92131-u
pubmed_334_526
Quantum close-coupling scattering calculations of rotational energy transfer (RET) of rotationally excited H(2)O due to collisions with He are presented for collision energies between 10(-6) and 1000 cm(-1) with para-H(2)O initially in levels 1(1,1), 2(0,2), 2(1,1), and 2(2,0) and ortho-H(2)O in levels 1(1,0), 2(1,2), and 2(2,1). Quenching cross sections and rate coefficients for state-to-state RET were computed. Both elastic and inelastic differential cross sections are also calculated and compared with relative experimental results giving generally good agreement in all cases, but less so for inelastic results. Significant differences in the computed collisional parameters, obtained on three different potential energy surfaces (PESs), were found particularly in the ultracold regime. In the thermal regime, the rate coefficients calculated on each of the surfaces are generally in better agreement and comparable, but typically larger, than those obtained in a previous calculation. Unfortunately, a lack of absolute differential or integral inelastic experimental data prevents firm determination of a preferred PES.
10.1063/1.2720390
pubmed_744_12076
OBJECTIVE To describe the prevalence and evaluate the risk of echocardiogram-determined valvulopathy in patients who received fenfluramine and phentermine in an effort to lose weight, in comparison with normal control subjects. METHODS A historical cohort study was conducted in a clinical obesity-management practice. A total of 164 patients (88% women) who were treated with fenfluramine-phentermine for weight loss had echocardiographic evaluations. A subsample was cross-validated. RESULTS The prevalence of mild or greater aortic regurgitation was 18.3%, and the prevalence of moderate or greater mitral regurgitation was 3.7%. The prevalences of mild or greater tricuspid and pulmonary valve regurgitation, valve thickening, and pulmonary hypertension were 23.2%, 5.5%, 10.4%, and 6.7%, respectively. No significant increases in risk were found for moderate or greater regurgitation of any valve. Patients had at least a 3-fold risk for mild or greater aortic regurgitation (standardized morbidity ratio [SMR] = 3.03; 95% confidence interval [CI] = 2.05 to 4.33) and a 2-fold risk for tricuspid regurgitation (SMR = 2.24; 95% CI = 1.58 to 3.06) in comparison with normal healthy adults. Age and duration of drug therapy predicted increased risk for aortic regurgitation. Four patients who had moderate or greater aortic regurgitation had taken the fenfluramine-phentermine combination continuously for 454, 615, 645, and 984 days. CONCLUSION Use of serotonergic anorexiant medications may increase risk for mild or greater aortic and tricuspid regurgitation, although selection bias and obesity as causes of the association cannot be ruled out. Age and duration of drug therapy were predictors of aortic valvulopathy. Population-based studies are needed to confirm these preliminary findings.
10.4158/EP.5.1.17
pubmed_294_22622
After labelling DNA with the specific vital fluorophore Hoechst 33342, oocytes, isolated by puncture from antral follicles in adult mice, have two essentially different configurations of their nuclear fluorescence images. These have been called SN (where the nucleolus is surrounded by chromatin) and NSN (where the nucleolus is not surrounded by chromatin). Intermediate configurations are also found, although with a lower frequency. The proportion of each class is on the average equal and depends neither on the presence of cumulus cells nor on the age of the mouse. Electron microscopy confirms several ultrastructural differences between these two nuclear configurations, namely, the structure of the nucleolus, which is vacuolated in NSN-type and compact in SN-type oocytes. Using video-enhanced fluorescence microscopy at low level of excitation light, we could follow directly in vitro the meiotic maturation of both classes, without impairing their viability. We show that in germinal vessicle (GV) state, the chromatin does not change from one configuration into the other and that both classes are able to mature to metaphase II, although the maturation has slightly different characteristics.
10.1002/mrd.1080360110
pubmed_740_23059
'Ageing well' has been highlighted as an important research area by the World Health Organization. In the UK, healthy ageing has been identified as a priority research area by multiple Research Councils and is a key NHS priority. Sarcopaenia, the decline of muscle mass/strength and a key component of healthy ageing, can have a major impact on quality of life and is associated with premature mortality. Increasing protein intake at all stages of the life course may help to reduce the rate of muscle decline and the onset of associated health conditions. However, there is a lack of understanding of the social, demographic and psychological drivers of food choices surrounding protein intake. This report describes the multidisciplinary approach that has been adopted by the Protein for Life project to create a framework for the development of palatable, cost-effective higher-protein foods suitable for an ageing population.
10.1111/nbu.12312
pubmed_320_655
X-ray emission from the Cygnus Loop was observed in the energy region around 0.2 to 1 kiloelectronvolt with a collector that focused x-rays along one dimension while scanning across the nebula. The total integrated intensity is 1.3x 10(-8) erg per square centimeter per second. The one-dimensional x-ray structure has the same angular size-about 3 degrees-as the outermost boundaries of the optical filaments. There is no increase in x-ray emission at the center of the nebula nor at the strong feature that is seen in certain radio maps. The x-ray spectrum is consistent with thermal radiation from a hot plasma at a temperature of about 4 x 10(6) degrees K with evidence for a line at 19 angstroms corresponding to the 2p-->1s transition of O VIII.
10.1126/science.172.3981.369
pubmed_626_9873
Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-limiting enzyme of heme degradation. The HO products carbon monoxide and bilirubin not only provide antioxidant cytoprotection, but also have potent anti-inflammatory and immunomodulatory functions. Although HO-1 has previously been shown to be induced by various stimuli via activation of the p38 MAPK signaling pathway, the role of this protein kinase for HO-1 gene regulation is largely unknown. In the present study, it is demonstrated that pharmacological inhibitors of p38 induced HO-1 expression in monocytic cells. Moreover, basal HO-1 gene expression levels were markedly higher in untreated murine embryonic fibroblasts (MEF) from p38alpha(-/-) mice compared with those from wild-type mice. Transfection studies with luciferase reporter gene constructs indicate that increased HO-1 gene expression via inhibition of p38 was mediated by the transcription factor Nrf2, which is a central regulator of the cellular oxidative stress response. Accordingly, inhibitors of p38 induced binding of nuclear proteins to a Nrf2 target sequence of the HO-1 promoter, but did not affect HO-1 protein expression and promoter activity in Nrf2(-/-) MEF. Genetic deficiency of p38 led to enhanced phosphorylation of ERK and increased cellular accumulation of reactive oxygen species. In addition, pharmacological blockage of ERK and scavenging of reactive oxygen species with N-acetylcysteine reduced HO-1 gene expression in p38(-/-) MEF, respectively. Taken together, it is demonstrated that pharmacological inhibition and genetic deficiency of p38 induce HO-1 gene expression via a Nrf2-dependent mechanism in monocytic cells and MEF.
10.4049/jimmunol.0900006
pubmed_305_12656
OBJECTIVES The purpose of the present study was the systematic investigation of numerical and morphological aberrations of teeth in the wisdom teeth region in neurofibromatosis type 1 patients. MATERIAL AND METHODS The panoramic radiographs of 179 patients were analysed for supernumerary molars and dysplastic wisdom teeth with special reference to facial tumour type. The results were compared to radiographic findings obtained in panoramic radiographs of age- and sex-matched controls. RESULTS The total number of dysplastic or supernumerary molars was 21 (17 individuals, 4.75%) and predominantly a finding of the maxilla (maxilla: 15, mandible: 1, maxilla and mandible: 1). Differences of dental findings between neurofibromatosis type 1 (NF1) patients (n = 15) and the control group (n = 2) were statistically significant (P < 0.01). All individuals with supernumerary molars were diagnosed as being affected with NF1. This difference achieved statistical significance when it was considered that the event may occur at least once per quadrant, and thus the individual potentially needs to be considered four times (P = 0.0038). CONCLUSIONS This investigation revealed that supernumerary molars and aberrations in wisdom tooth form are more common in patients than in age- and sex-matched controls. There is no association between these findings and a specific feature of the disease, id est facial manifestation of a trigeminal nerve sheath tumour (plexiform neurofibroma). The cause of this phenomenon is unknown. A review of these dental findings on other neurofibromatosis type 1 study groups should be attempted.
10.5037/jomr.2017.8405
pubmed_177_11120
OBJECTIVE To assess the radiological and functional outcome of arthrodesis of the 4th and 5th finger using the APEX™ (Extremity Medical, Parsippany,NJ)intermedullary interlocking screw system in patients with severe recurrence of Dupuytren's disease. MATERIAL AND METHOD The DASH questionnaire and the VAS scale were used to assess the clinical outcomes. The angle of arthrodesis, fusion time and implant fixation were evaluated on x-rays. The patients were monitored for complications during surgery and the follow-up period. RESULTS The sample comprised 6 patients. Mean follow up was 19.6 months. All of the patients presented clinical and radiological evidence of fusion at 8 weeks, with fusion angles of 30° (3) and 45° (3). There were no complications and none of the implants had to be removed. The functional outcomes in these patients were poor. CONCLUSION The system offers a reliable method for IPJ arthrodesis at a precise angle. It promotes stable fixation that does not require prolonged immobilisation. It can be used together with other procedures on the hand with severe recurrence of DD. The functional outcomes for this group of patients using this device were poor.
10.1016/j.recot.2017.10.012
pubmed_615_4397
Human exposure to arsenic (As) via rice consumption is of increasing concern. In the present study, the extraction and HPLC-ICP-MS analysis for As speciation in rice were investigated. A simple extraction with water and digestion with α-amylase followed by the analysis using ion-paring mode HPLC separation was developed. The method showed good extraction efficiencies (generally >80%) and column efficiencies (>90%) for rice samples. The optimization of mobile phase showed well separated peaks of As species. The limits of quantification (LOQ) of As(III), As(V), MMA, and DMA that were calculated based on sample mass were 1.6, 2.0, 2.0, and 1.6 μg kg(-1), respectively. A total of 185 rice samples (various types of rice) collected from different four regions in Thailand and some other Asian countries were analyzed. The total As and inorganic As in rice samples were in the ranges of 22.51-375.39 and 13.89-232.62 μg kg(-1), respectively. The estimated weekly intake of inorganic As from rice by Thai people accounted for 13.91-29.22% of the provisional tolerable weekly intake (PTWI).
10.1021/jf4014873
pubmed_289_24186
This study was designed to investigate chemical characterization of the water-soluble polysaccharides extracted from Keemun black tea (KBTP), and their antioxidant and hepatoprotective effects against CCl4-induced oxidative damage in mice. HPLC analysis revealed that KBTP is the typical acidic heteropolysaccharides and consisted of nine monosaccharides. Furthermore, KBTP showed highly ferric-reducing antioxidant power and scavenging effects against DPPH, OH and O2(-) in vitro. Administration of KBTP (200, 400 and 800 mg/kg bw) in mice ahead of CCl4 injection could observably antagonize the CCl4-induced increases in serum ALT, AST, TG and TC, and the hepatic MDA and 8-iso-PGF2a levels, respectively. Mice with KBTP pretreatment displayed a better profile of hepatosomatic index and the improved GSH and SOD activities in comparison with CCl4-intoxicated mice. These biochemical results were further supported with liver histopathological assessment, revealing that KBTP has an observable prevention of liver damage induced by CCl4 in mice.
pubmed_289_24186
pubmed_470_20398
BACKGROUND Compared to younger women, women 65+ will experience the greatest increase in new breast cancer cases. In 1991, Medicare began offering partial reimbursement for screening mammography every 2 years. METHODS In 1999, the National Cancer Institute (NCI) conducted a telephone survey on breast cancer, mammography, and Medicare reimbursement with a sample of households containing women ages 65+ using random-digit-dialing. Results were weighted to provide nationally representative estimates of U.S. women 65+. NCI compared 1999 results with similar data from a 1992 AARP survey. RESULTS Of the 814 women surveyed, 88% had had at least one mammogram in their lifetime; within this group, 80% had received their most recent mammogram 2 years ago or less. Only 57%, however, knew about recommendations to have a mammogram every 1-2 years. Approximately one-third indicated that they were not as concerned about getting breast cancer as when they were younger, and/or that women without risk factors could be less vigilant about mammograms. More than 75% were aware of Medicare coverage, but only 58% had used Medicare to help pay for their last mammogram. Minority women were almost twice as likely to be unaware of Medicare coverage. RECOMMENDATIONS (1) Highlight that breast cancer risk increases with age (and does not decline in the absence of risk factors) and communicate the correct frequency for having mammograms; (2) expand primary care physicians' roles in promoting mammography screening for women 65+; and (3) provide Medicare coverage information to older women, particularly those not taking advantage of this benefit.
10.1300/J013v36n04_01
pubmed_389_8640
OBJECTIVE The purpose of this study was to understand the contemporary trends of splenectomy in blunt splenic injury (BSI) and to determine if angiography and embolization (ANGIO) may be impacting the splenectomy rate. BACKGROUND The approach to BSI has shifted to increasing use of nonoperative management, with a greater reliance on ANGIO. However, the impact ANGIO has on splenic salvage remains unclear with little contemporary data. METHODS The National Trauma Data Bank was used to identify patients 18 years and older with high-grade BSI (Abbreviated Injury Scale >II) treated at Level I or II trauma centers between 2008 and 2014. Primary outcomes included yearly rates of splenectomy, which was defined as early if performed within 6 hours of ED admission and delayed if greater than 6 hours, ANGIO, and mortality. Trends were studied over time with hierarchical regression models. RESULTS There were 53,689 patients who had high-grade BSI over the study period. There was no significant difference in the adjusted rate of overall splenectomy over time (24.3% in 2008, 24.3% in 2014, P value = 0.20). The use of ANGIO rapidly increased from 5.3% in 2008 to 13.5% in 2014 (P value < 0.001). Mortality was similar overtime (8.7% in 2008, 9.0% in 2014, P value = 0.33). CONCLUSION Over the last 7 years, the rate of angiography has been steadily rising while the overall rate of splenectomy has been stable. The lack of improved overall splenic salvage, despite increased ANGIO, calls into question the role of ANGIO in splenic salvage on high-grade BSI at a national level.
10.1097/SLA.0000000000002246
pubmed_130_676
INTRODUCTION Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. METHODS A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment. RESULTS Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower (p < 0.05) being 196 µL/min (IQR 178-213) for phlorizin-treated animals compared to 238 µL/min (IQR 233-268) in controls. Median fractional dialysate glucose concentration at 60 min (D/D 0) was significantly higher (p < 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63-0.67) compared to 0.61 (IQR 0.60-0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane. CONCLUSION Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells.
10.1177/08968608221080170
pubmed_666_24230
BACKGROUND Exercise is considered an effective intervention to relieve chronic back pain. However, it is still unknown whether specific exercise patterns vary in terms of their efficiency and effectiveness. AIM To investigate the differential health and economic effects of intensity, specificity and degree of subjective perceived physical exertion across five exercise patterns (endurance, gymnastics, fitness, back gymnastics, multimodal back exercise) in adults with back pain. DESIGN Longitudinal observational cohort study over a period of 24 months. SETTING Various non-therapeutic exercise facilities (e.g. outdoor, fitness centers, health insurance programs, sports clubs) across one federal state of Germany (Baden-Wuerttemberg). POPULATION Adults with back pain (N.=2,542, Mean =46.9 years, 66% females, graded chronic back pain [GCPS] 1=40.5%, GCPS 2=27.3%, GCPS 3=20.7%, GCPS 4=11.5%). METHODS Self-reported back pain (functional restrictions and pain = back pain function score, [BPFS]) and characteristics of exercising behavior (frequency, duration, type, physical exertion) were assessed at baseline and at 6, 12, 18 and 24 months. Direct medical costs for back disorders (international classification of diseases, dorsopathies: M40-M54) were compiled from health insurance records. RESULTS Moderate- to high-intensity exercise patterns were effective in reducing back pain, particularly at lower levels of subjective perceived physical exertion. At these intensity levels, multimodal back exercise (i.e. exercising the spine-stabilizing muscles specifically, ergonomic training) was 14.5 times more effective than non-back specific fitness exercise in reducing BPFS. The beneficial effects of both exercise types increased with the initial severity of back pain. However, only multimodal back exercise (moderate- to high-intensity/high back specificity) was associated with a significant decrease in direct medical costs for back pain. CONCLUSIONS Targeted exercise of the spine-stabilizing musculature at moderate to high intensities without maximum perceived exertion is effective and efficient in reducing back pain. CLINICAL REHABILITATION IMPACT The combination of high-intensity and high-specificity exercises yielded a significant reduction in medical costs. However, the intensities in terms of muscular load in endurance training and gymnastics may not be sufficient to reduce back pain effectively.
10.23736/S1973-9087.20.05975-4
pubmed_240_7052
BACKGROUND In sub-Saharan Africa, problems of access to relevant and high-quality facility-based statistics hinder the assessment of safe motherhood programs. The objective of this study was to assess the quality of data collected in referral hospitals in Mali and Senegal after the routine information system (RIS) was strengthened. METHODS This was a multicenter observational study conducted during the pre-intervention period of a randomized controlled trial (trial QUARITE). The RIS was strengthened based on technical, organizational and behavioral factors. We included all women who gave birth in the 46 referral hospitals from October 1, 2007 to October 30, 2008. The completeness, completion and accuracy rates were monitored every 3 months in each hospital. The cost of investment needed to strengthen the existing RIS was also determined. RESULTS The mean completeness rate ranged from 94 to 97% depending on the study period. The completion and accuracy rates increased during the study period from 72% and 79% to 87% and 93%, respectively (significant differences). The average investment per hospital was less than 1% of state subsidies for public hospitals. CONCLUSION Strengthening the existing information system has set up an economically and technologically appropriate system for monitoring maternal and perinatal health in Senegal and Mali. We encourage policy makers and researchers from countries with limited resources to invest in RIS to improve and monitor the performance of health systems.
pubmed_240_7052
pubmed_547_19952
In both dividing and interphase cells, microtubules are remodeled in response to signal transduction pathways triggered by a variety of stimuli. Members of the Rho family of small GTPases have emerged as key intermediates in transmitting signals to cortical factors that mediate capture of dynamic microtubules at specific sites. The specificity of cortical capture appears to be controlled by microtubule tip proteins and cortical receptors that bind these proteins. Recent studies suggest that some of the proteins interacting with microtubule tips behave as bridging proteins between the microtubule tip proteins and their cortical receptors. Such bridging proteins may enhance cortical capture of microtubules directly or indirectly through interactions with the actin cytoskeleton.
10.1016/j.ceb.2003.11.010
pubmed_277_10047
Bilateral medial temporal lobe resection in man results in a persistent impairment of recent memory whenever the removal is carried far enough posteriorly to damage portions of the anterior hippocampus and hippocampal gyrus. This conclusion is based on formal psychological testing of nine cases (eight psychotic and one epileptic) carried out from one and one-half to four years after operation. The degree of memory loss appears to depend on the extent of hippocampal removal. In two cases in which bilateral resection was carried to a distance of 8 cm posterior to the temporal tips the loss was particularly severe. Removal of only the uncus and amygdala bilaterally does not appear to cause memory impairment. A case of unilateral inferior temporal lobectomy with radical posterior extension to include the major portion of the hippocampus and hippocampal gyrus showed no lasting memory loss. This is consistent with Milner and Penfield's negative findings in a long series of unilateral removals for temporal lobe epilepsy. The memory loss in these cases of medial temporal lobe excision involved both anterograde and some retrograde amnesia, but left early memories and technical skills intact. There was no deterioration in personality or general intelligence, and no complex perceptual disturbance such as is seen after a more complete bilateral temporal lobectomy. It is concluded that the anterior hippocampus and hippocampal gyrus, either separately or together, are critically concerned in the retention of current experience. It is not known whether the amygdala plays any part in this mechanismi, since the hippocampal complex has not been removed alone, but always together with uncus and amygdala.
10.1176/jnp.12.1.103
pubmed_817_23003
Background: Being a parent of a child with a developmental disability (DD; e. g., cerebral palsy, autism) comes with great challenges and apprehensions. Mothers and fathers of children with DD are experiencing heightened levels of psychological distress, physical health problems, financial difficulties, social isolation, and struggles with respect to traditional parenting roles. In relation to the latter, the involvement of fathers in caregiving in today's society is increasing and is highlighted by its importance and positive contribution to the development of their children. However, fathers of children with DD report feeling excluded and marginalized by healthcare providers (HCPs) when arranging for and getting involved in healthcare services for their children. Currently, there is limited evidence as to what factors influence those experiences. We aimed to explore barriers to and facilitators of positive and empowering healthcare experiences, from the perspectives of fathers of children with DD and HCPs. Methods: A mixed-method approach, such as quantitative (survey) and qualitative (semi-structured interview) strategies, was used. Participants were fathers of children with DD and HCPs working in childhood disability. Data analysis consisted of using descriptive statistics and an inductive-thematic analysis of emergent themes. Results: Fathers (n = 7) and HCPs (n = 13, 6 disciplines) participated. The fathers indicated that while they were moderate to very much satisfied with their interactions with HCPs, they reported that HCPs were only sometimes attentive to them during interactions. Fathers also revealed that positive interactions with HCPs in relation to their children had multiple benefits. Several themes related to barriers and facilitators of optimal interactions and parent-professional relationships emerged. These included session factors (time, attention), personal factors (knowledge of the condition, child and healthcare system, acceptance vs. denial, previous experiences, culture, stereotypes, pre-existing beliefs, stress levels, working schedule), and family dynamics. The participants offered several insights into the different strategies that can be implemented to promote optimal interactions between fathers and HCPs. Conclusion: We identified several barriers, facilitators, and improvement strategies for optimal interactions and enhanced parent-professional relationships from the perspectives of fathers and HCPs. These can be integrated by existing clinical settings in efforts to enhance current clinical practices and improve child- and parent-related outcomes.
10.3389/fresc.2021.709262
pubmed_750_1104
Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity. Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.
10.5306/wjco.v9.i8.167
pubmed_190_14380
Based on the review and recommendation of the American Diabetes Association's Subcommittee on Ethical Scientific Publications (ESP), Diabetes Care formally retracts the above-cited article. For reasons described below, the published data are considered to be unreliable. According to an investigation and analysis of the data conducted by Shiga University of Medical Science (report received 25 November 2013), 10.1% of the albumin-to-creatinine ratio (ACR) data reported in the article did not match original patient records. In the valsartan and amlodipine groups, respectively, 12.5% and 8.1% of the ACR data reported in the article differed from patient records. Close examination of these differences showed that ACR values reported for the valsartan group were smaller, and those for the amlodipine group were larger, than values reported in patient records; these differences "worked to the advantage of valsartan." The investigative panel of Shiga University of Medical Science concluded that the above-cited article is "inappropriate for [a] scientific paper."
10.2337/dc14-rt03
pubmed_630_24921
BACKGROUND Unresectable mature teratoma is an incurable disease associated with significant morbidity. Given the rarity of the disease, long-term outcomes for patients receiving systemic therapy have not been well described. PATIENTS AND METHODS The present study was a retrospective analysis with long-term follow-up data of the patient cohort with unresectable mature teratoma treated in the nonrandomized phase II study of palbociclib for the treatment of metastatic, retinoblastoma protein-expressing refractory germ cell tumors. Patient clinical data were obtained from the medical records and by communication with the enrolled patients and referring medical providers. Major medical events for the treatment of germ cell tumor, including before, during, and after study treatment, were recorded. The major clinical events of interest included the initiation of systemic therapy, radiation therapy, surgical debulking, or other invasive procedures. The study endpoints included the prestudy period and study period clinical event rates, event-free survival, and radiographic progression-free survival. RESULTS Long-term follow-up data were obtained for 12 patients with unresectable mature teratoma. The median prestudy period follow-up period was 19.7 months, and the median study follow-up period was 38.0 months. The median number of palbociclib treatment cycles was 11. The prestudy major clinical event rate was 2.27 events annually (95% confidence interval [CI], 1.66-3.13 events), and the study period event rate was 0.62 events annually (95% CI, 0.36-1.09 events). The median progression-free survival was 5.3 months (95% CI, 1.8-22.6 months), and the median event-free survival duration was 16.2 months (95% CI, 3.0-24.3 months). CONCLUSION Unresectable mature teratoma is associated with significant long-term cumulative morbidity. The initiation of palbociclib might result in a clinically meaningful delay in disease-related major clinical events. These findings lend further support to the therapeutic activity of cyclin-dependent kinase 4/6 inhibition in this incurable patient population.
10.1016/j.clgc.2016.03.010
pubmed_737_12342
Bradycardia or asystole that occur during some seizures may be life threatening as a leading cause of SUDEP. A patient with right and left temporal lobe onset seizures and preceding bardycardia or asystole is presented. He had bilateral hippocampal atrophy on MRI. The unreliability of ictal bradycardia or asystole as a lateralizing sign in patients with partial epilepsy and the role of interictal autonomic activity in heart rate changes during seizures are discussed.
10.1016/j.eplepsyres.2011.05.008
pubmed_652_24505
AIMS AND BACKGROUND Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. METHODS AND STUDY DESIGN A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. RESULTS With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). CONCLUSIONS Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.
10.1700/1578.17206
pubmed_362_5345
BACKGROUND Differentiation syndrome (DS) is an inflammatory complication seen in some patients with acute promyelocytic leukemia (APL) undergoing differentiation therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). It is unknown how DS occurs, but it is believed that it is caused by inflammatory cytokines release from differentiating leukemic cells. High mobility group box-1 (HMGB1) is a DNA-binding protein that acts as a cytokine outside of cells and may play a role in inflammation. This study was conducted to determine whether HMGB1 polymorphisms (rs1360485, rs2249825 and rs1060348) are associated with the incidence of differentiation syndrome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic trioxide. METHODS One hundred and thirty APL patients and 100 healthy controls were included. Seventeen patients with differentiation syndrome were selected according to the PETHEMA criteria. Tetra-primer ARMS polymerase chain reaction (tetra-ARMS PCR) was used to determine the genotype distribution of polymorphisms. DNA sequencing was done to validate the results. RESULTS In both healthy and APL patients, AA was the most frequent genotype in rs1360485 followed by AG and GG. CC, CG, and GG were the most frequent genotypes in rs2249825 polymorphism in the order mentioned. CC was more frequent than CT, and CT was more frequent than TT in rs1060348. There was no correlation between HMGB1 polymorphisms and the incidence of differentiation syndrome based on genetic models (p-value > 0.05). CONCLUSIONS HMGB1 polymorphisms are not probably associated with DS development in APL patients treated with ATRA and ATO.
10.1007/s11033-022-07386-1
pubmed_36_13165
INTRODUCTION A practice hypothyroid register is part of the quality and outcomes framework. In literature, the prevalence of hypothyroidism is stated to be 2% but the prevalence, defined from quality and outcomes framework data, is 3.2% in the UK and 3.6% in Plymouth. We sought to investigate the diagnosis of hypothyroidism and reasons for prescription of thyroxine to patients on the hypothyroid register in Plymouth. METHODS A letter was sent to the 10 practices with the highest prevalence of hypothyroidism requesting a list of patients on their registers. The hospital pathology system was used to identify those with biochemically documented hypothyroidism (defined as thyroid stimulating hormone >10 mU/L) For two large practices the clinical records of the remaining patients were reviewed to ascertain the reasons for prescription of thyroxine and whether it led to symptomatic improvement. RESULTS Seven practices responded with 1246 patients on their registers, of whom 43.6% had documented hypothyroidism. A review of notes of patients on the register, but without documented hypothyroidism, showed <25% to have an improvement in symptoms after prescription of thyroxine. Tiredness was the most common symptom prompting prescription of thyroxine. CONCLUSION Of the patients on the register, only 43.6% had documented biochemical evidence of hypothyroidism and, from notes review of those without documented hypothyroidism, at least two-thirds may have been prescribed thyroxine outwith current national guidance. If this is correct, it has significant resource implications, impacts upon the workload of primary care, pharmacy and the laboratory service and may have clinical implications for patients.
10.1177/0004563214568686
pubmed_819_13602
MBA-15.4 and MBA-15.6 cell lines are marrow stromal clonal subpopulations and represent various stages of differentiation of the osteoblastic family. These cells vary in terms of morphology, proliferation rate, synthesis of matrix proteins as collagen and noncollagenous proteins, and by their responses to hormones and growth factors. Their differential properties directly reflect the clonal cells' ability to form bone in vivo. When the cells were transplanted at an ectopic site, under the kidney capsule, MBA-15.4 line formed small foci of bone whereas MBA-15.6 cell line formed massive woven bone during the same period of time. In this study, we focused on the histomorphometric analysis of ectopic ossicles formed by the clonal cell lines. Assessments of bone mass changes involved measurements of cellular components, osteoid, and formation of primary bone. The bony tissue formed was condensed, no hemopoiesis was noted, and the ossicle was not remodeled. The histology studies were used for quantitative analysis of the ossicle formation and describe the dynamics of ossicles formed by the individual cell types.
10.1007/s002239900119
pubmed_799_17102
Chronic exposure to nicotine has been shown to increase binding to high affinity nicotinic cholinergic receptors in rat brain, but the effect of this treatment on the low affinity alpha7 nicotinic receptors has been less well characterized. Male Sprague-Dawley rats were treated with saline or nicotine (6 mg/kg/day, by osmotic minipump) for 14 days. Frozen brain sections were then prepared and processed for quantitative autoradiography using [(125)I]alpha-bungarotoxin to measure the effect of this treatment on low affinity nicotinic receptors. Nicotine exposure increased [(125)I]alpha-bungarotoxin binding in 26 of 52 brain regions analyzed; increases ranged from 10 to 70% over saline controls. Increases were seen in all areas of the brain, but were more prominent in forebrain areas, and especially in cerebral cortex. These data demonstrate that low affinity alpha7 nicotinic receptors are also up-regulated by chronic nicotine. This phenomenon may be relevant to the heavy use of tobacco products in diseases like schizophrenia, and needs to be considered in the design of pharmaceuticals directed at this receptor system.
10.1016/j.neulet.2006.05.010
pubmed_302_11760
The mechanism of CD40/CD154-induced chemokine production and its potential role in renal inflammatory disease were explored. Human proximal tubule cells maintained in primary culture were used as the experimental model. With the use of immunocytochemistry, confocal microscopy, and a cell fractionation assay, the CD40 receptor was found to be expressed in the cell membrane of the epithelial cell, and, on engagement by CD154, its cognate ligand, translocated to the cytoplasmic compartment. Engagement of CD40 by CD154 stimulated interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production, which proceeded via receptor activation of the extracellular signal-regulated kinase (ERK)1/2, stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways. CD40 ligation also engaged tumor necrosis factor receptor-activating factor 6 (TRAF6), as evidenced by colocalization of the activated receptor with TRAF6 in the cytoplasmic compartment, translocation of both proteins from the insoluble to the soluble cell fraction, and coimmunoprecipitation of the two proteins only under ligand-stimulated conditions. Furthermore, an antisense oligodeoxyribonucleotide targeted against TRAF6 mRNA blunted p38 and SAPK/JNK but not ERK1/2 MAPK activities, as well as IL-8 and MCP-1 production, arguing that TRAF6 is an upstream activator. The zinc chelator TPEN, but not the calcium chelator BAPTA, obliterated CD154-evoked MAPK activity and chemokine production, providing indirect evidence for protein-protein interactions playing a critical role in CD40 signaling in these cells. We conclude that in human proximal tubule cells, CD40 and TRAF6 reside in separate low-density, detergent-insoluble membrane microdomains, or rafts, and on activation translocate and associate with one another probably via zinc-finger domains in the soluble or cytoplasmic compartment. TRAF6, in turn, activates SAPK/JNK and p38 MAPK phosphorylation, which in turn stimulates IL-8 and MCP-1 production in these cells.
10.1152/ajprenal.00291.2001
pubmed_849_22373
Electrospun fibrous substrates mimicking extracellular matrices can be prepared by electrospinning, yielding aligned fibrous matrices as internal fillers to manufacture artificial nerves. Gelatin aligned nano-fibers were prepared by electrospinning after tuning the collector rotation speed. The effect of alignment on cell adhesion and proliferation was tested in vitro using primary cultures, the Schwann cell line, RT4-D6P2T, and the sensory neuron-like cell line, 50B11. Cell adhesion and proliferation were assessed by quantifying at several time-points. Aligned nano-fibers reduced adhesion and proliferation rate compared with random fibers. Schwann cell morphology and organization were investigated by immunostaining of the cytoskeleton. Cells were elongated with their longitudinal body parallel to the aligned fibers. B5011 neuron-like cells were aligned and had parallel axon growth when cultured on the aligned gelatin fibers. The data show that the alignment of electrospun gelatin fibers can modulate Schwann cells and axon organization in vitro, suggesting that this substrate shows promise as an internal filler for the design of artificial nerves for peripheral nerve reconstruction.
10.3390/ijms160612925
pubmed_312_17136
beta 1- and beta 2-adrenergic receptors coexist in atria of humans and a variety of other species. The significance of these receptors and the quantitative extent to which beta 2-adrenergic receptors contribute to the electrophysiologic effects of catecholamines acting at beta-adrenergic receptors have not been determined. In the present study, the beta 1-selective antagonist ICI 89,406 and the beta 2-selective antagonist ICI 118,551 were used to determine the relative densities of beta 1- and beta 2-adrenergic receptors on membranes prepared from dog atria and the contribution that each subtype makes to isoproterenol-induced shortening of action potential duration measured at 75% repolarization (APD75). Computer-aided nonlinear regression analysis of the inhibition of the specific binding of [125I]iodopindolol and the inhibition of isoproterenol-stimulated APD75 shortening by these antagonists showed that a two-site model fits the data better than a one-site model (P less than 0.0001). The affinity constants for each selective antagonist determined by inhibition of APD75 shortening were similar to those determined in studies of the inhibition of the specific binding of [125I]iodopindolol to beta 1- and beta 2-adrenergic receptors. beta 2-Adrenergic receptors made up approximately equal to 25% of the total number of beta-adrenergic receptors but mediated approximately equal to 50% of the electrophysiologic effect of isoproterenol. The inhibition of the binding of [125I]iodopindolol and of the APD75 shortening by propranolol, a nonselective antagonist, was best fit by a one-site model. In other experiments, dogs were treated with reserpine and atropine to eliminate complications caused by the presence of endogenous norepinephrine and acetylcholine. Results obtained with atria from these animals were similar to those obtained in studies with control atria. These data suggest that beta 2-adrenergic receptors as well as beta 1-adrenergic receptors are involved in mediating the electrophysiologic effects of catecholamines in dog atrial muscle and that both beta 1- and beta 2-adrenergic receptors are present on atrial muscle cells.
10.1073/pnas.82.13.4521
pubmed_780_6669
Almost all complement component 9 (C9) deficiency in Japan shows Arg95 Stop mutation of C9 gene. Therefore, we studied the prevalence of Arg95Stop mutation of C9 gene among 78 patients with SLE to elucidate the association of SLE and C9 deficiency. The Arg95Stop carrier frequency showed no significant difference between SLE patients and controls. Thus, C9 deficiency is not implicated in SLE susceptibility.
10.1191/096120300678828523
pubmed_235_9892
Traumatic brain injury (TBI) is a widespread and expensive problem globally. The standard diagnostic workup for new TBI includes obtaining a noncontrast computed tomography image of the head, which provides quick information on operative pathologies. However, given the limited sensitivity of computed tomography for identifying subtle but meaningful changes in the brain, magnetic resonance imaging (MRI) has shown better utility for ongoing management and prognostication after TBI. In recent years, advanced applications of MRI have been further studied and are being implemented as clinical tools to help guide care. These include functional MRI, diffusion tensor imaging, MR perfusion, and MR spectroscopy. In this review, we discuss the scientific basis of each of the above techniques, the literature supporting their use in TBI, and how they may be clinically implemented to improve the care of TBI patients.
10.3390/medsci9010010
pubmed_347_16824
INTRODUCTION Aboriginal and Torres Strait Islander children have higher rates of disability than non-Indigenous children and are considered doubly disadvantaged, yet there is very little data reflecting prevalence and service access to inform design and delivery of services. Failing to address physical, social, and psychological factors can have life-long consequences and perpetuate longstanding health disparities. METHODS A narrative literature review was undertaken to identify peer reviewed literature describing factors impacting on the prevention, recognition, and access to support and management of disability in Indigenous Australian children. RESULTS Twenty-seven peer-reviewed journal articles met inclusion criteria. The majority of articles focused on the hearing loss and learning disabilities consequent of otitis media. Few articles reported data on urban or metropolitan Indigenous populations or described interventions. Individual/community-, provider-, and systems level factors were identified as impacting on recognition and management of disability in young Indigenous children. CONCLUSIONS Given the burden of childhood disability, the limited literature retrieved is concerning as this is a barometer of activity and investment. Solutions addressing childhood disability will require collaboration between health, social and educational disciplines as well as an increased investment in prevention, identification and promotion of access.
10.1186/1475-9276-12-7
pubmed_568_17307
Ants are eusocial insects and have evolved sensitive chemosensory systems for social communication. However, the effect of heavy metal contamination on the olfactory sensitivity of ants remains largely unknown. Here, we investigated the survival and olfactory response of Solenopsis invicta under cadmium (Cd) exposure. As a result, exposure to dietary Cd at different concentrations (100, 300 and 500 mg/L) caused higher Cd accumulation and lower survival of the ants compared with the control (0 mg/L). Cd exposure induced diverse expression patterns of odor binding protein genes (SiOBPs) in S. invicta antenna. Specifically, the expression of SiOBP4, SiOBP11, SiOBP12 and SiOBP16 was increased by 1.84-, 1.14-, 0.83- and 1.76-fold, respectively, at 300 mg/L Cd, while SiOBP7 and SiOBP9 were suppressed as Cd concentration increased. Electroantennography (EAG) and behavioral bioassays were performed to further evaluate the effect of Cd contamination on the olfactory sensitivity of S. invicta workers to 2, 4, 6-trimethylpyridine (TMP) and 2-ethyl-3,6(5)-dimethylpyrazine (EDP), the two frequent functional semiochemicals for S. invicta. The results showed that under no Cd exposure, S. invicta workers exhibited strong EAG response and apparent residing repellence to TMP and EDP, but Cd exposure suppressed EAG response and deprived the behavioral repellence to TMP and EDP of the workers, suggesting that Cd exposure decreases the olfactory sensitivity of S. invicta to these two functional semiochemicals. Further fluorescence competitive binding assay revealed that SiOBP7 had strong binding affinity to TMP and EDP, suggesting that the decrease in olfactory sensitivity may be attributed to the inhibitory effect of Cd exposure on SiOBP7. Overall, our results suggest that Cd exposure may not only directly decrease the survival of ants, but also affect their olfactory recognition.
10.1016/j.envpol.2021.117359
pubmed_1110_4556
Evidence suggests that only a small minority of youth offenders will continue their behaviour in the longer term and largely independent of any interventions they may receive (Bateman, 2011; Haines & Case, 2015). Hence, "screening out" this larger low-risk cohort could have a positive impact upon the individual through a reduction in stigmatisation/labelling and free up resources for higher risk clients. This article outlines development of the Ceredigion Youth Screening Tool (CYSTEM)-developed and tested to address the two facets of criminality and vulnerability-closely aligned to the eight key risk indicators identified in the Risk-Needs-Responsivity (R-N-R) literature (Andrews & Bonta, 2010). Initial results with two cohorts of 372 young people indicate good convergent and discriminative validity in screening out the lowest level referrals, while also identifying 90% of potential future offenders. More importantly, CYSTEM is able to screen out approximately 35% of the low-risk offenders that are unlikely to require formal evaluation and/or intervention. It is suggested that the streamlining of this process using CYSTEM reduces demand on staff time and decreases the stigmatisation of young people referred for minor offences. Potential improvements to the tool and future developments in statistical risk prediction are also discussed.
10.1177/0306624X17752299
pubmed_1133_4489
Since its introduction in 2009 femtosecond laser-assisted cataract surgery (FLACS) has promised to revolutionize cataract surgery. Despite its promise, the assessment of FLACS's perceived benefits has proven to be far more complicated than initially might have been thought. Most studies to date have not provided validation of FLACS technology as a clinically significant advancement on our current techniques. We review FLACS technology and outcomes including detailed analysis of safety, efficacy, cost effectiveness and future prospects using data from the literature and our own published clinical experience.
10.22608/APO.2017159
pubmed_10_4381
Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4(+)Foxp3(+) regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model. In this model, xenografts undergo acute humoral xenograft rejection (AHXR) typically on day 3 or cell-mediated rejection approximately on day 7 if AHXR is inhibited by Lef treatment. Recipients were treated with Lef (n=6), IL-33 (n=6), IL-33 combined with Lef (n=6), or left untreated (n=6) for survival studies. Heart grafts were monitored until they stopped beating. Mouse heterotopic grafts were performed, and recipients were sacrificed on days 2 and 7 for histological and flow cytometric analyses. The combination of IL-33 and Lef significantly prolonged the grafts from 17.3±2.3 to 2.8±0.4 days, compared to untreated controls. IL-33 administration with Lef, while facilitating Th2-associated cytokines (IL-4 on day 2 but not day 7), also decreased IFN-γ on day 2 and day 7, compared with Lef treatment only. Furthermore, IL-33 with Lef administration caused an expansion of suppressive CD4(+)Foxp3(+) Tregs in rats. The IL-33 and Lef combination therapy resulted in significantly prolonged graft survival, associated with markedly decreased Th1 cells and increased IL-10 levels. In addition, the combination therapy significantly decreased the percentage of CD-45(+) B cells on days 2 and 7, compared with monotherapy. These findings reveal a new immunoregulatory property of IL-33. Specifically, it facilitates regulatory cells, particularly functional CD4(+)Foxp3(+) Tregs that underlie IL-33-mediated cardiac xenograft survival. Moreover, it can decrease Th1 cells and cytokine expression of Th1 T cells in xenograft recipients, for example IFN-γ.
10.1038/labinvest.2016.54
pubmed_489_7091
BACKGROUND AND PURPOSE New diffusion-weighted imaging (DWI) lesions are common in patients with acute ischemic stroke. They are associated with an initial nonsingle lesion pattern. Previous studies have not analyzed this association in detail. We differentiated nonsingle lesions in 1 vascular supply territory only (scattered lesion pattern) from nonsingle lesions in ≥2 vascular supply territory (multiple territory lesion -pattern). METHODS Patients with an acute ischemic stroke underwent 3 MRI (3T) examinations: on admission, on the following day, and 4 to 7 days after symptom onset. First, DWI lesions were delineated manually by raters blinded to clinical details. Second, DWI images were coregistered and analyzed visually for new hyperintensities. The initial lesion pattern was categorized as single, scattered, or multiple territory. RESULTS Of 340 patients enrolled, 43% had a single lesion pattern, 40% had a scattered lesion pattern, and 17% had a multiple territory lesion pattern. In multivariable analysis, the categorical variable lesion pattern was independently associated with new DWI lesions (odds ratio multiple territory lesion pattern, 3.64 [95% confidence interval, 1.75-7.58]; odds ratio scattered lesion pattern, 1.96 [95% confidence interval, 1.09-3.56]). Patients with multiple territory lesion pattern had significantly more often diabetes mellitus, and their new lesions were more often located remotely from the initial area of hypoperfusion compared with patients with scattered lesion pattern. CONCLUSION Lesion pattern on initial image is an independent risk factor for new DWI lesions. The risk for new DWI lesions is highest in patients with multiple territory lesion pattern.
10.1161/STROKEAHA.111.000810
pubmed_664_5841
OBJECTIVE To give a preliminary experimental evidence and to prove chitosan and allogeneic morselized bone as potential bone substitutions in repairing rabbit radius segmental defect. METHODS Chitosan and allogeneic morselized bone were mixed with various ratios (1:5, 1:10, 1:25, 1:50, and 1:100). After preparation, the physical and chemical properties of the composites were preliminary detected; the composites at the ratios of 1:50 and 1:25 had good physical and chemical properties and were used for the animal experiment. The radius segmental defects of 15 mm in length were made in 50 adult New Zealand white rabbits (weighing 2.5-3.0 kg), then the animals were divided into 2 groups. In groups A and B, chitosan/allogeneic morselized bone composites were implanted at the ratio of 1:50 and 1:25, respectively. After 1, 2, 4, 8, and 12 weeks of operation, the gross, histological, immunohistochemical observations were performed. Before the rabbits were sacrificed, X-ray films were taken; the serum calcium and alkaline phosphatase (ALP) concentration were measured; and the biomechanical measurement was carried out at 12 weeks. RESULTS The results of gross observation were essentially consistent with those of the X-ray films. The histological observation showed that the bone formation was earlier in group A than in group B; the amount of new bone formation in group A was more than that in group B; and the bone forming area in group A was bigger than that in group B (P < 0.05) at 4 and 8 weeks after operation. The immunohistochemical staining showed that vascular endothelial growth factor and insulin-like growth factor receptor II proteins expressed in the cytoplasm of 2 groups after 4 and 8 weeks, and the expression in group A was higher than that in group B (P < 0.05). There was no significant difference in the serum calcium concentration between 2 groups at each time point (P > 0.05). After 4 and 8 weeks, the ALP concentration in group A was significantly higher than that in group B (P < 0.05). After 12 weeks, the radius maximum bending loads of groups A and B were (299.75 +/- 27.69) N and (278.54 +/- 17.09) N, respectively, showing significant difference (t=4.045, P=0.002). CONCLUSION The composite of chitosan and allogeneic morselized bone has good osteogenic activity and can be used as a bone tissue engineering scaffold, and the optimum ratio of chitosan to allogeneic morselized bone was 1:50.
pubmed_664_5841
pubmed_364_14955
Crystals arise as the result of the breaking of a spatial translation symmetry. Similarly, translation symmetries can also be broken in time so that discrete time crystals appear. Here, we introduce a method to describe, characterize, and explore the physical phenomena related to this phase of matter using tools from graph theory. The analysis of the graphs allows to visualizing time-crystalline order and to analyze features of the quantum system. For example, we explore in detail the melting process of a minimal model of a period-2 discrete time crystal and describe it in terms of the evolution of the associated graph structure. We show that during the melting process, the network evolution exhibits an emergent preferential attachment mechanism, directly associated with the existence of scale-free networks. Thus, our strategy allows us to propose a previously unexplored far-reaching application of time crystals as a quantum simulator of complex quantum networks.
10.1126/sciadv.aay8892
pubmed_1141_6213
OBJECTIVE Pregnancies complicated by diabetes are frequently characterized by an increased volume of amniotic fluid, and the pathophysiologic mechanism of this increase is not known. Our goal was to evaluate the relationship between amniotic fluid glucose concentration and the amniotic fluid index in pregnancies complicated by insulin-treated diabetes and to compare it with that seen in normal pregnancies. STUDY DESIGN Amniotic fluid index and amniotic fluid glucose levels were measured before elective repeated cesarean delivery in 41 women with insulin-treated diabetes and in 35 women without diabetes. Only singleton gestations without anomalous fetuses were included. Women with diabetes were hospitalized for approximately 4 weeks before delivery, during which time glycemic control was optimized. Amniotic fluid index and amniotic fluid glucose concentration were correlated with each other and were compared between the groups with and without diabetes. RESULTS The mean amniotic fluid index was significantly increased in the diabetes group (16.6 +/- 5.0 cm in the diabetes group vs 13.4 +/- 3.5 cm in the control group; P =.002). The amniotic fluid glucose concentration was also significantly greater in the diabetes group than in the control group (39 +/- 17 mg/dL in the diabetes group vs 24 +/- 11 mg/dL in the control group; P <.001). Among women with diabetes the amniotic fluid glucose concentration was significantly correlated with the amniotic fluid index (r = 0.32; P =.04), a correlation not found among the control women. The mean fasting blood glucose concentration among the women with diabetes for the week before amniocentesis was 82 +/- 11 mg/dL. CONCLUSION The amniotic fluid index parallels the amniotic fluid glucose level among women with diabetes. This finding raises the possibility that the hydramnios associated with diabetes is a result of increased amniotic fluid glucose concentration.
10.1016/s0002-9378(00)70343-7
pubmed_539_12181
Colesevelam hydrochloride (colesevelam) is a novel, potent, bile acid-binding agent that has been shown to lower LDL cholesterol a mean of 19% at a dose of 3.8 g/d. We studied the pharmacokinetics of colesevelam coadministered with six drugs: digoxin and warfarin, agents with narrow therapeutic indices; sustained-release verapamil and metoprolol; quinidine, an antiarrhythmic with a narrow therapeutic index; and valproic acid, an antiseizure medication. Six individual studies were single-dose, crossover, with or without a 4.5-g dose of colesevelam. Plasma levels were determined using validated analytical methods. Values for the ratio of ln[AUC(0-t)] with and without colesevelam were 107% for quinidine, 102% for valproic acid, 89% for digoxin, 102% for warfarin, 82% for verapamil, and 112% for metoprolol. Values for the ratio of ln[Cmax] with and without colesevelam were 107% for quinidine, 92% for valproic acid, 96% for digoxin, 99% for warfarin, 69% for verapamil, and 112% for metoprolol. The 90% confidence intervals for these ratios and for values of ln[AUC(0-inf)] that could be determined were within the 80-125% range, with the exception of verapamil. In this study, verapamil had great interindividual variability, with a 28-fold range in Cmax and an 11-fold range in AUC(0-t). In summary, pharmacokinetic studies with colesevelam did not show clinically significant effects on absorption of six other coadministered drugs.
10.1023/a:1007831418308
pubmed_504_3217
INTRODUCTION After having an acute myocardial infarction (AMI), racial and ethnic minorities have less access to care, decreased rates of invasive treatments such as percutaneous coronary intervention (PCI), and worse outcomes compared with white patients. The objective of this study was to determine whether the Affordable Care Act's expansion of Medicaid eligibility was associated with changes in racial disparities in access, treatments, and outcomes after AMI. METHODS Quasi-experimental, difference-in-differences-in-differences analysis of non-Hispanic white and minority patients with acute myocardial infarction in California and Florida from 2010-2015, using linear regression models to estimate the difference-in-differences. This population-based sample included all Medicaid and uninsured patients ages 18-64 hospitalized with acute myocardial infarction in California, which expanded Medicaid through the Affordable Care Act beginning as early as July 2011 in certain counties, and Florida, which did not expand Medicaid. The main outcomes included rates of admission to hospitals capable of performing PCI, rates of transfer for patients who first presented to hospitals that did not perform PCI, rates of PCI during hospitalization and rates of early (within 48 hours of admission) PCI, rates of readmission to the hospital within 30 days, and rates of in-hospital mortality. RESULTS A total of 55,991 hospital admissions met inclusion criteria, 32,540 of which were in California and 23,451 were in Florida. Among patients with AMI who initially presented to a non-PCI hospital, the likelihood of being transferred increased by 12 percentage points (95% CI 2 to 21) for minority patients relative to white patients after the Medicaid expansion. The likelihood of undergoing PCI increased by 3 percentage points (95% CI 0 to 5) for minority patients relative to white patients after the Medicaid expansion. We did not find an association between the Medicaid expansion and racial disparities in overall likelihood of admission to a PCI hospital, hospital readmissions, or in-hospital mortality. CONCLUSIONS The Medicaid expansion was associated with a decrease in racial disparities in transfers and rates of PCI after AMI. We did not find an association between the Medicaid expansion and admission to a PCI hospital, readmissions, and in-hospital mortality. Additional factors outside of insurance coverage likely continue to contribute to disparities in outcomes after AMI. These findings are crucial for policy makers seeking to reduce racial disparities in access, treatment and outcomes in AMI.
10.1371/journal.pone.0241785
pubmed_1105_4624
OBJECTIVES This study evaluates: (1) the change in whole salivary secretion rates of nasopharyngeal carcinoma patients before, during, and after radiotherapy, especially during the first week of irradiation; (2) the recovery capability of salivary glands up to 2 years postirradiation; and (3) the possible prognostic factors affecting salivary gland functions. STUDY DESIGN Fifty patients who completed conventional radiotherapy using either once-per-day or hyperfractionated technique were included. Both unstimulated and stimulated whole salivary flow rates and ratios (flow rate compared with baseline) were measured before, during, 1, 3, and 6 months, and 1 and 2 years after radiotherapy. Multivariate analysis of potential prognostic factors affecting the salivary secretion ratio was made. RESULTS Salivary glands were very radiosensitive and responded to radiation very early. After 720 cGy at the fourth day of the 8-week treatment, the unstimulated and stimulated salivary flow rates had decreased by 40%-50%. The nadir was reached in many patients after 3600 cGy (4 weeks). A second phase of decrease in salivary secretion was noted after completion of radiotherapy. CONCLUSIONS Different mechanisms may be responsible for salivary response after low and high dose of radiation. This study shows no recovery of salivary secretion during the follow-up period, and the best strategy for managing radiation-induced salivary gland damage may be reduction of radiation dose to the glands.
10.1016/j.tripleo.2005.01.011
pubmed_467_20074
Thermal coagulation of abnormal tissues has evolved as a therapeutic technique for different diseases including cancer. Tissue heating beyond 55 °C causes coagulation that leads to cell death. Noninvasive diagnosis of thermally coagulated tissues is pragmatic for performing efficient therapy as well as reducing damage of surrounding healthy tissues. We propose a noninvasive, elasticity-based photoacoustic spectral sensing technique for differentiating normal and coagulated tissues. Photoacoustic diagnosis is performed for quantitative differentiation of normal and coagulated excised chicken liver and muscle tissues in vitro by characterizing a dominant frequency of photoacoustic frequency spectrum. Pronounced distinction in the spectral parameter (i.e., dominant frequency) was observed due to change in tissue elastic property. We confirmed nearly two-fold increase in dominant frequencies for the coagulated muscle and liver tissues as compared to the normal ones. A density increase caused by tissue coagulation is clearly reflected in the dominant frequency composition. Experimental results were consistent over five different sample sets, delineating the potential of proposed technique to diagnose biological tissue coagulation and thus monitor thermal coagulation therapy in clinical applications.
10.3390/diagnostics10030133
pubmed_612_13177
Corneal endothelial cells (CECs) facilitate the function of maintaining the transparency of the cornea. Damage or dysfunction of CECs can lead to blindness, and the primary treatment is corneal transplantation. However, the shortage of cornea donors is a significant problem worldwide. Thus, cultured CEC therapy has been proposed and found to be a promising approach to overcome the lack of tissue supply. Unfortunately, CECs in humans rarely proliferate in vivo and, therefore, can be extremely challenging to culture in vitro. Several promising cell isolation and culture techniques have been proposed. Multiple factors affecting the success of cell expansion including donor characteristics, preservation and isolation methods, plating density, media preparation, transdifferentiation and biomarkers have been evaluated. However, there is no consensus on standard technique for CEC culture. This review aimed to determine the challenges and investigate potential options that would facilitate the standardization of CEC culture for research and therapeutic application.
10.2217/rme-2020-0202