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pubmed_663_24430
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Elucidating kinetic information (rate constants) from temporally resolved hyperspectral confocal fluorescence images offers some very important opportunities for the interpretation of spatially resolved hyperspectral confocal fluorescence images but also presents significant challenges, these being (1) the massive amount of data contained in a series of time-resolved spectral images (one time course of spectral data for each pixel) and (2) unknown concentrations of the reactants and products at time = 0, a necessary precondition normally required by traditional kinetic fitting approaches. This paper describes two methods for solving these problems: direct nonlinear (DNL) estimation of all parameters and separable least squares (SLS). The DNL method can be applied to reactions of any rate law, while the SLS method is restricted to first-order reactions. In SLS, the inherently linear and nonlinear parameters of first-order reactions are solved in separate linear and nonlinear steps, respectively. The new methods are demonstrated using simulated data sets and an experimental data set involving photobleaching of several fluorophores. This work demonstrates that both DNL and SLS hard-modeling methods applied to the kinetic modeling of temporally resolved hyperspectral images can outperform traditional soft-modeling and hard/soft-modeling methods which use multivariate curve resolution-alternating least squares (MCRALS) methods. In addition, the SLS method is much faster and is able to analyze much larger data sets than the DNL method.
|
10.1366/000370209787391950
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pubmed_1077_20545
|
Bovine brucellosis was first reported in Peninsular Malaysia in 1950. A subsequent survey conducted in the country revealed that the disease was widespread. Current knowledge on the potential risk factors for brucellosis occurrence on cattle farms in Malaysia is lacking. Therefore, we conducted a case-control study to identify the potential herd-level risk factors for bovine brucellosis occurrence in four states in the country, namely Kelantan, Pahang, Selangor and Negeri Sembilan. Thirty-five cases and 36 controls of herds were selected where data on farm management, biosecurity, medical history and public health were collected. Multivariable logistic regression identified that Brucella seropositive herds were more likely to; have some interaction with wildlife (OR 8.9, 95% CI = 1.59-50.05); originated from farms where multiple species such as buffalo/others (OR 41.8, 95% CI = 3.94-443.19) and goat/sheep (OR 8.9, 95%Cl = 1.10-71.83) were reared, practice extensive production system (OR 13.6, 95% CI 1.31-140.24) and have had episodes of abortion in the past (OR 51.8, 95% CI = 4.54-590.90) when compared to seronegative herds. Considering the lack of information on the epidemiology of bovine brucellosis in peninsular Malaysia and absence of information on preventing the inception or spread of the disease, this report could contribute to the on-going area-wise national brucellosis eradication program.
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10.1371/journal.pone.0108673
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pubmed_181_22402
|
Through hypoiodite catalysis, oxidative cyclisation of Michael adducts of chalcones with 1,3-dicarbonyl compounds for divergent synthesis of either furans or cyclopropanes is developed. The selective synthesis of major products is achieved depending on the use of different reaction conditions or substrates.
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10.1039/c6cc06624k
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pubmed_0_24248
|
Bullous pemphigoid is the most frequent autoimmune blistering disease, usually affecting elderly patients. Most cases are idiopathic. We report a case of bullous pemphigoid developing four weeks after a boiling water burn, initially at the site of the burn, then elsewhere.
|
10.1097/SMJ.0b013e3181efb58c
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pubmed_698_2333
|
The cases of 3 patients with pyomyositis associated with hematological disorders are reported. A 40-year-old man in the blastic phase of chronic myelogenous leukemia and 2 men aged 46 and 71 years with neutropenia due to myelodysplastic syndromes all reported high fever and severe local myalgia and had marked elevation of C-reactive protein. Magnetic resonance imaging revealed muscle abscesses or fasciitis, and the findings led to the diagnosis of pyomyositis. Methicillin-resistant Staphylococcus aureus was isolated from the abscesses of 2 patients, and surgical drainage proved more effective than did antimicrobial agents. It should be recognized that pyomyositis is a possible source of infection in patients with hematological disorders.
|
10.1007/BF02983216
|
pubmed_482_19850
|
BACKGROUND
We sought to describe lung cancer prevalence and mortality in relation to socioeconomic deprivation and rurality.
METHODS
We conducted a population-based cross-sectional analysis of prevalent lung cancers from a statewide all-payer claims dataset from 2012 to 2016, lung cancer deaths in Maine from the state death registry from 2012 to 2016, rurality, and area deprivation index (ADI), a geographic area-based measure of socioeconomic deprivation. Analyses examined rate ratios for lung cancer prevalence and mortality according to rurality (small and isolated rural, large rural, or urban) and ADI (quintiles, with highest reflecting the most deprivation) and after adjusting for age, sex, and area-level smoking rates as determined by the Behavioral Risk Factor Surveillance System.
RESULTS
Among 1 223 006 adults aged 20 years and older during the 5-year observation period, 8297 received lung cancer care, and 4616 died. Lung cancer prevalence and mortality were positively associated with increasing rurality, but these associations did not persist after adjusting for age, sex, and smoking rates. Lung cancer prevalence and mortality were positively associated with increasing ADI in models adjusted for age, sex, and smoking rates (prevalence rate ratio for ADI quintile 5 compared with quintile 1 = 1.41, 95% confidence interval [CI] =1.30 to 1.54) and mortality rate ratio = 1.59, 95% CI = 1.41 to 1.79).
CONCLUSION
Socioeconomic deprivation, but not rurality, was associated with higher lung cancer prevalence and mortality. Interventions should target populations with socioeconomic deprivation, rather than rurality per se, and aim to reduce lung cancer risk via tobacco treatment and control interventions and to improve patient access to lung cancer prevention, screening, and treatment services.
|
10.1093/jncics/pkaa011
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pubmed_248_637
|
Sublingual immunotherapy (SLIT) has been recommended as a viable alternative to subcutaneous injection therapy in the treatment of airway allergies, though more data is needed from well-controlled studies for documenting its efficacy in different ethnic populations. Ninety-seven children (age range 6-12 years), mild-to-moderate asthma with a single sensitization to mite allergen, were enrolled from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with standardized mite extracts, which contain Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.). Patients were double blinded and randomly assigned to either a SLIT or placebo group. Following 24 weeks of study period, symptom and medication scores, lung function tests, skin prick tests, total serum IgE, and specific IgE to D.p. and D.f. were recorded. The results showed that there was statistically significant difference between these two groups in the analysis of daily (P=0.011), nighttime (P=0.028), and daytime (P=0.009) asthmatic scores after 24 weeks of treatment. Patients receiving SLIT improved their forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and peak expiratory flow (PEF) as compared to baseline (P=0.042, P=0.048, and P=0.001, respectively). No differences were found in skin prick test, total serum IgE and specific IgE to D.p. and D.f. Tolerance with high-dose SLIT was good with few minor adverse events reported. Our results indicated that a 24-week SLIT is of clinical benefit to mite-sensitive asthmatic children in Taiwan.
|
10.1016/j.rmed.2005.11.016
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pubmed_92_22879
|
Guidelines for non-clinical studies of prophylactic vaccines against infectious diseases have been published widely, but similar guidelines for therapeutic vaccines, and especially therapeutic peptide vaccines, have yet to be established. The approach to non-clinical safety studies required for therapeutic vaccines differs from that for prophylactic vaccines due to differences in the risk-benefit balance and the mechanisms of action. We propose the following guidelines for non-clinical safety studies for therapeutic peptide vaccines. (i) Since the main safety concern is related to the immune response that might occur at normal sites that express a target antigen, identification of these possible target sites using in silico human expression data is important. (ii) Due to the strong dependence on HLA, it is not feasible to replicate immune responses in animals. Thus, the required non-clinical safety studies are characterized as those detecting off-target toxicity rather than on-target toxicity.
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pubmed_92_22879
|
pubmed_434_20910
|
This paper describes the methodology and the evaluation of a 3D skeletonization algorithm applied on brain vascular structure. This method is based on the application of the minimum cost-spanning tree using Dijkstra's algorithm and seems well appropriate to tubular objects. We briefly describe the different steps, from the segmentation to the skeleton analysis. Besides, we propose an original evaluation scheme of the method based on digital phantom and clinical data. The final aim of this work is to provide a symbolic description framework applied to cerebro-vascular structures.
|
10.1109/IEMBS.2010.5626112
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pubmed_452_13277
|
As the smartphone has become an indispensable device in modern lives, consequential psychosocial problems such as smartphone addiction have been getting attention worldwide, especially regarding adolescents. Based on its positive effect on young individuals' mental health, mind subtraction meditation has been widely applied to many school-based programs in South Korea. This study aims to identify the effects of a school program based on mind subtraction on the smartphone addiction of adolescents. A total of 49 high school sophomores, 24 from the experimental group (mean age = 16), and 25 from the control group (mean age = 16) are included in this case-control study. The experimental group is given the meditation program sessions in the morning, two times a week for 20 min per session, for a total of 12 weeks. The experimental group shows improvements regarding the 'smartphone addiction' section (p < 0.001), for instant satisfaction (p < 0.001) and long-term satisfaction (p < 0.001). Concerning the 'self-control' section and decreasing stress (p < 0.001), problem focusing (p < 0.001), and social support navigation (p = 0.018), there are improvements in these 'stress coping strategies' sections. This study directly shows the positive effect of mind subtraction meditation on smartphone addiction in adolescents and, thus, provides guidance to the future development of smartphone addiction prevention programs for young individuals.
|
10.3390/ijerph17093263
|
pubmed_636_16181
|
OBJECTIVES
To reveal change patterns in self-reported lifestyle data for 9 years, and examine the characteristics of changes by type of lifestyle and ageing.
METHODS
The authors used the lifestyle data of 7,080 male workers aged 20-59 who received checkups for 9 years. The proportions of change patterns during the 9 years were determined in seven health practices; smoking, eating breakfast, sleeping hours, working hours, physical exercise, eating nutritional balanced diets, and mental stress.
RESULTS
Among seven health practices, the keep rate of good health practice was highest for the non-smoking (90.8 %), followed by eating breakfast (69.0 %);and the lowest was physical exercise (13.7 %). The keep rate of poor health practice was highest for smoking (73.8 %), followed by non-physical exercise (67.1 %). The lowest rate of multiple changes during 10 years was smoking (7.1 %); the highest was mental stress (68.5 %).
CONCLUSIONS
As for the life style on smoking and eating breakfast seemed to be stable, using the data obtained at a specific point in time wouldn't much affect the results. On the contrary, for other life styles, they showed poor continuity during 9 years, so it would be necessary to take into consideration the time point of data collection.
|
10.1007/s12199-012-0324-4
|
pubmed_434_19631
|
Given the importance of trucking to the economic well being of a country and the safety concerns posed by the trucks, a study of large-truck crashes is critical. This paper contributes by undertaking an extensive analysis of the empirical factors affecting injury severity of large-truck crashes. Data from a recent, nationally representative sample of large-truck crashes are examined to determine the factors affecting the overall injury severity of these crashes. The explanatory factors include the characteristics of the crash, vehicle(s), and the driver(s). The injury severity was modeled using two measures. Several similarities and some differences were observed across the two models which underscore the need for improved accuracy in the assessment of injury severity of crashes. The estimated models capture the marginal effects of a variety of explanatory factors simultaneously. In particular, the models indicate the impacts of several driver behavior variables on the severity of the crashes, after controlling for a variety of other factors. For example, driver distraction (truck drivers), alcohol use (car drivers), and emotional factors (car drivers) are found to be associated with higher severity crashes. A further interesting finding is the strong statistical significance of several dummy variables that indicate missing data - these reflect how the nature of the crash itself could affect the completeness of the data. Future efforts should seek to collect such data more comprehensively so that the true effects of these aspects on the crash severity can be determined.
|
10.1016/j.aap.2010.07.007
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pubmed_862_4656
|
The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis. Here we describe the computational design of eight enzymes that use two different catalytic motifs to catalyse the Kemp elimination-a model reaction for proton transfer from carbon-with measured rate enhancements of up to 10(5) and multiple turnovers. Mutational analysis confirms that catalysis depends on the computationally designed active sites, and a high-resolution crystal structure suggests that the designs have close to atomic accuracy. Application of in vitro evolution to enhance the computational designs produced a >200-fold increase in k(cat)/K(m) (k(cat)/K(m) of 2,600 M(-1)s(-1) and k(cat)/k(uncat) of >10(6)). These results demonstrate the power of combining computational protein design with directed evolution for creating new enzymes, and we anticipate the creation of a wide range of useful new catalysts in the future.
|
10.1038/nature06879
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pubmed_644_22694
|
Elimination of corticosteroid-related morbidity has been a goal of transplant clinicians from the earliest days of renal transplantation more than 50 years ago. Over the past decade, this goal has begun to be realized. Herein, we describe our efforts to eliminate corticosteroid therapy from maintenance immunosuppression-efforts that have spanned 15 years and have included design and conduct of five multicenter trials and over ten single center trials with over 650 patients at the University of Cincinnati. These efforts have led to a near complete elimination of corticosteroid-related morbidity, and, importantly, a more precise definition of the risk/benefit assessments of corticosteroid withdrawal in individual patient populations, which has allowed individualization and tailoring of corticosteroid-free immunosuppression.
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pubmed_644_22694
|
pubmed_916_19466
|
As modern and ancient DNA sequence data from diverse human populations accumulate, evidence is increasing in support of the existence of beneficial variants acquired from archaic humans that may have accelerated adaptation and improved survival in new environments - a process known as adaptive introgression. Within the past few years, a series of studies have identified genomic regions that show strong evidence for archaic adaptive introgression. Here, we provide an overview of the statistical methods developed to identify archaic introgressed fragments in the genome sequences of modern humans and to determine whether positive selection has acted on these fragments. We review recently reported examples of adaptive introgression, grouped by selection pressure, and consider the level of supporting evidence for each. Finally, we discuss challenges and recommendations for inferring selection on introgressed regions.
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10.1038/nrg3936
|
pubmed_628_10131
|
A microbial biosensor was developed for monitoring microbiologically influenced corrosion (MIC) of metallic materials in industrial systems. The Pseudomonas sp. isolated from corroded metal surface was immobilized on acetylcellulose membrane and its respiratory activity was estimated by measuring oxygen consumption. The microbial biosensor was used for the measurement of sulfuric acid in a batch culture medium contaminated by microorganisms. A linear relationship between the microbial sensor response and the concentration of sulfuric acid was observed. The response time of biosensor was 5 min and was dependent on the immobilized cell loading of Pseudomonas sp., pH, temperature and corrosive environments. The microbial biosensor response was stable, reproducible and specific for sensing of sulfur oxidizing bacterial activity.
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10.1016/s0956-5663(01)00203-2
|
pubmed_388_8068
|
The presence of abnormal levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG) in the cerebrospinal fluid (CSF) of some patients with affective disorders may indicate abnormal norepinephrine metabolism in these patients. The authors evaluated the relationship between norepinephrine and MHPG in CSF and found that both are present in increasing levels as more CSF is removed from the lumbar puncture needle. Norepinephrine and MHPG are closely related, although norepinephrine levels are more variable within and between subjects. Both norepinephrine and MHPG levels in CSF should provide important information about norepinephrine metabolism in affective disorders.
|
10.1176/ajp.134.5.565
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pubmed_614_16479
|
The Fanconi anemia (FA) proteins are involved in a signaling network that assures the safeguard of chromosomes. To understand the function of FA proteins in cellular division events, we investigated the interaction between Stathmin-1 (STMN1) and the FA group C (FANCC) protein. STMN1 is a ubiquitous cytosolic protein that regulates microtubule dynamics. STMN1 activities are regulated through phosphorylation-dephosphorylation mechanisms that control assembly of the mitotic spindle, and dysregulation of STMN1 phosphorylation is associated with mitotic aberrancies leading to chromosome instability and cancer progression. Using different biochemical approaches, we showed that FANCC interacts and co-localizes with STMN1 at centrosomes during mitosis. We also showed that FANCC is required for STMN1 phosphorylation, as mutations in FANCC reduced serine 16- and 38-phosphorylated forms of STMN1. Phosphorylation of STMN1 at serine 16 is likely an event dependent on a functional FA pathway, as it is reduced in FANCA- and FANCD2-mutant cells. Furthermore, FA-mutant cells exhibited mitotic spindle anomalies such as supernumerary centrosomes and shorter mitotic spindles. These results suggest that FA proteins participate in the regulation of cellular division via the microtubule-associated protein STMN1.
|
10.1371/journal.pone.0140612
|
pubmed_189_1176
|
Because of the relative lack of understanding of the neurobiological mechanisms that drive toxic effects of cadmium in bone, the purpose of this study was to characterize a preclinical model of chronic cadmium exposure. Adult male C57BL/6 J mice were exposed to cadmium 25 mg/L (as CdCl2) in drinking water for 16 weeks. During this time, pain-related behaviors including hindpaw mechanical sensitivity and vertical rears were evaluated every four weeks. We assessed changes in bone microarchitecture at the femoral neck and L5 vertebra by microcomputed tomography and quantified the density of nerve fibers expressing PGP 9.5 (a pan-neuronal marker) and CGRP (a marker of sensory nerve fibers subfamily) at the femoral neck and glabrous skin of the hindpaw using immunohistochemistry. Cadmium exposure produced mechanical hypersensitivity in both hindpaws along with decreased rearing activity (surrogate for musculoskeletal-related pain) without affecting the horizontal activity (a measure of locomotor behavior) in comparison to the control group. Intraperitoneal acute treatment with morphine and gabapentin reversed pain-related behaviors in cadmium-exposed mice. Furthermore, exposure to cadmium resulted in significant trabecular bone deterioration at the femoral neck and L5 vertebra. We also observed a significant reduction in the density of both CGRP+ and PGP 9.5+ nerve fibers in the femoral neck, but not in the hindpaw glabrous skin, suggesting tissue-dependent neurotoxicity. This model may help in developing a mechanism-based understanding of the factors that generate and maintain musculoskeletal pain and bone loss caused by chronic cadmium exposure and in translating these findings into new therapies for treating cadmium-induced bone toxicity.
|
10.1016/j.neuro.2022.01.009
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pubmed_730_21312
|
Free-flow electrophoresis (FFE) has been applied to the separation and purification of a variety of proteins and polypeptides: bee venom, tumor necrosis factor, interleukin-1beta, interferon-gamma and superoxide dismutase. FFE at constant pH and conductivity of the carrying buffer is shown to be efficient at various separation schemes. In some cases, the method allows us to obtain proteins with a purity of more than 90% at a productivity of 20-30 mg/h. An electrophoretic apparatus with a new, multi-sectional construction of the electrophoretic chamber and a system for cross-displacement of carrying buffer in the chamber is described.
|
10.1002/elps.1150190712
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pubmed_441_6026
|
The authors describe 3 clinical cases of Ewing's papilloma. The first presented with unilateral epistaxis related to a tumour implanted on the nasal septum. This was widely resected under general anesthesia. Ten years later there has been no recurrence. The second case began with nasal obstruction due to the presence of Ewing's papillomatosis in the posterior part of the right nasal fossa with marked dysplastic changes leading to a wide surgical operation by lateral rhinotomy, revealing a second process, a cavernous hemangioma. Such a combination had never been described. Finally, the third case of Ewing's papilloma began with sinusitis with polyps, which were removed in a first stage, but a second wide excision was necessary as a result of recurrence. The histological and clinical characteristics of Ewing's papilloma are reviewed.
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pubmed_441_6026
|
pubmed_494_18081
|
INTRODUCTION
It was the aim of the present study to evaluate root canal samples for the presence and numbers of specific species as well as for total bacterial load in teeth with chronic apical periodontitis using quantitative real-time polymerase chain reaction (PCR).
METHODS
Forty adult patients with one radiographically documented periapical lesion were included. Twenty teeth presented with primary infections and 20 with secondary infections, requiring retreatment. After removal of necrotic pulp tissue or root canal filling, a first bacterial sample was obtained. Following chemo-mechanical root canal preparation a second sample was taken and a third sample was obtained after 14 days of intracanal dressing with calcium hydroxide. Analysis by real-time PCR enabled the quantification of total bacterial counts and of nine selected species.
RESULTS
Root canals with primary infections harbored significantly more bacteria (by total bacterial count) than teeth with secondary infections (P < 0.05). Mean total bacterial count in the retreatment group was 2.1 x 10(6) and was significantly reduced following root canal preparation (3.6 x 10(4)) and intracanal dressing (1.4 x 10(5)). Corresponding values for primary infections were: 4.6 x 10(7), 3.6 x 10(4), and 6.9 x 10(4). The numbers of the selected bacteria and their detection frequency were also significantly reduced.
CONCLUSION
Root canals with primary infections contained a higher bacterial load. Chemo-mechanical root canal preparation reduced bacterial counts by at least 95%.
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10.1111/j.1399-302X.2008.00440.x
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pubmed_1086_5466
|
Two members of the family of low-density lipoprotein receptors (i.e., very low-density lipoprotein [VLDL] receptor and apolipoprotein E [apoE] type 2 receptor) are expressed in brain, where they bind and transduce reelin, a secreted glycoprotein that shares structural analogies with extracellular matrix proteins. In the developing fetal brain, reelin-signal transduction is critical for the correct positioning of neurons and the formation of appropriate synaptic connections, whereas in the mature brain, reelin participates in the mediation of experience-dependent synaptic plasticity. An important "downstream" consequence of the reelin-signal transduction cascade is inhibition of the phosphorylation of tau, a protein that regulates microtubule assembly and stability. Importantly, hyperphosphorylated tau comprises the paired helical filament, whose pathological deposition as neurofibrillary tangles is implicated in Alzheimer's disease; hyperphosphorylated tau is also implicated in the pathogenesis of other neurodegenerative disorders. Isoforms of apoE may affect the binding of reelin to its cell surface receptors and, thereby, influence tau phosphorylation, whereas insulin, insulin-like growth factor-1, and the lithium ion have actions within the cell at the level of the specific tyrosine kinases involved in the phosphorylation of tau. These data support the exploration of pharmacotherapeutic interventions designed to prevent or reduce the burden of hyperphosphorylated tau. Impaired reelin-signal transduction due to an actual deficiency of reelin expression may occur in at least some patients with psychotic disorders, especially schizophrenia; conceivably, hyperphosphorylation of tau would result from deficient transduction of reelin in schizophrenia. Schizophrenia has been conceptualized as a neurodevelopmental disorder of impaired synaptic "connectivity", whose consequence does not become fully apparent until late adolescence or early adulthood. In summary, hyperphosphorylation of tau may be an underlying point of pathological convergence for several neuropsychiatric disorders, and prevention of tau hyperphosphorylation may be an important therapeutic target.
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10.1016/j.pnpbp.2006.04.007
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pubmed_1_20152
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[Purpose] The purpose of this study was to investigate the effects of action observation training (AOT) on cerebral hemodynamic changes including cerebral blood flow velocity (CBFV) and cerebral blood flow volume (CBFvol) in healthy subjects. [Subjects] Fifteen healthy subjects participated in this study. [Methods] All subjects were educated regarding AOT, and systolic peak velocity (Vs) as well as mean flow velocity (Vm) in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) were evaluated using functional transcranial doppler with a 2-MHz probe, before and after performing AOT. [Results] Healthy subjects showed significant differences in Vs and Vm in the MCA, ACA, and PCA after AOT compared with those before AOT. [Conclusion] Our findings indicate that AOT has a positive effect in terms of an increase in CBFV and CBFvol in healthy subjects, since the brain requires more blood to meet the metabolic demand during AOT.
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10.1589/jpts.27.1379
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pubmed_1094_20869
|
Length and weight data from 3 months to 6 years of age from 466 participants in the Fels Longitudinal Study of Growth were used to fit the Jenss non-linear growth curve. Six (1%) of the Fels participants had extremely outlying values for length parameters, and 20 (4%) had outlying values for weight parameters. The general pattern in the outliers is for average or below average size in infancy, followed by unusually rapid growth or weight gain in childhood. This outlier pattern is associated with significantly higher mean stature or weight at 18 years of age. The results for the majority of the participants are similar to those found in 229 children from the Harvard Growth Study, except for the non-linear intercept for length and the linear intercept for weight. Significant sex differences have not previously been reported for Jenss parameters, perhaps because previous applications have used much smaller sample sizes.
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10.1002/ajhb.1310030107
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pubmed_1012_3236
|
We synthesized a novel series of benzocycloalkene derivatives and evaluated their binding affinities to melatonin receptors. To control the spatial position of the amide group, one of the important pharmacophores, we incorporated an endo double bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S-configurations) at position 1. The indan derivatives with the S-configuration at position 1 were the most promising in terms of potency and selectivity for the human melatonin receptor (MT(1) site), while compounds with the R-configuration showed little potential. Our next attempt was to investigate the most favorable conformation of the methoxy group, the other important pharmacophore for binding to the MT(1) receptor. The introduction of a methyl group at position 5 of the indene ring conserved affinity; however, at position 7, it caused a decrease in affinity. These results suggested that the substitution at position 7 forced the methoxy group to adopt an unfavorable orientation. The optimization of the condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6-methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human MT(1) receptor (K(i) = 0.041 nM) but no significant affinity for the hamster MT(3)receptor (K(i) = 3570 nM). In addition, a practical synthetic method of chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]alkanamides employing asymmetric hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been established.
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10.1021/jm020114g
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pubmed_351_10807
|
In this study we investigated the relationship between the size of adenoids and/or tonsils and obstructive sleep apnea syndrome (OSAS) in 19 children aged 3 to 7 years. After clinical examination by an ENT specialist, electrocardiogram (ECG), vectorcardiogram (VCG) and echocardiogram (EC) were performed while the patients were awake, and static charge sensitive bed (SCSB) method recording (noninvasive monitoring of ballistocardiogram, respiration and body movements) while asleep. After adenoidectomy and/or tonsillectomy, the volume of the tonsils and the adenoids was determined. RVH was found in 4 out of 19 children (21%). RVH findings correlated highly with the number of apneas but, surprisingly, not with measured adenotonsillar size in those children. However, at 6 months of follow-up, the VCG and EC changes had returned to normal. These results suggest that RVH is more common in children suffering from upper airway obstruction than previously believed, and that factors other than adenotonsillar size also have an influence on upper airway obstruction.
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pubmed_351_10807
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pubmed_277_21597
|
BACKGROUND/PURPOSE
Apoptosis, or programmed cell death, is essential in maintaining normal homeostasis of tissues. The process of apoptosis is controlled by numerous pro- and antiapoptotic factors. Variations in expression of such factors may account for some variations in tumor behavior. This study evaluates the expression of apoptotic mRNA species in pediatric renal tumors to determine whether a pattern of differential apoptosis gene expression correlates with tumor grade and type.
METHODS
Twenty-five frozen tissue specimens were obtained from patients undergoing biopsy or resection of pediatric renal tumors before chemotherapy: Wilms' tumor stage II (WT-II, n = 4); Wilms' tumor stage III/IV (WT-III/IV, n = 4); clear cell sarcoma of the kidney stage III (CCSK, n = 2); rhabdoid tumor of the kidney stage III/IV (RTK, n = 4); and normal kidney (NK, n = 11). An RNase Protection Assay (RPA) was performed for 19 pro- and antiapoptotic mRNA species to detect and quantify expression (percentage of GAPDH expressed). Expression of specific mRNAs of interest were confirmed by Western Blot (WB).
RESULTS
The expression of apoptotic mRNA species varied markedly between tumors. WT-II expressed greater amounts of proapoptotic receptor mRNA than CCSK or RTK. (Fas, 17.0+/-2.7% v. 2.5+/-0.5% v. 3.3+/-0.9%; P<.02; DR5, 77.0+/-8.8% v. 13.5+/-0.5% v. 27.0+/-4.8; P<.001; TNF-R, 71.3+/-17.0% v. 21.0+/-4.0% v. 29.0+/-5.0%; P<.07, respectively). Surprisingly, antiapoptotic factors (e.g., bcl-2 and bcl-xl) were not overexpressed in poor prognostic tumors (CCSK, RTK) compared with those with good prognosis (WT). Expression of TRAIL (a ligand for DR4 and DR5) was significantly lower in CCSK and RTK than in normal kidney (9.5+/-1.5% v. 56.1+/-10.1%; P = .01).
CONCLUSIONS
Proapoptotic receptors are expressed at greater levels in good prognostic tumors, and this finding is compatible with their clinical behavior. Knowledge of differential apoptotic gene expression is of potential value in predicting prognosis and treating such tumors with targeted ligands.
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10.1016/s0022-3468(00)90047-2
|
pubmed_226_22349
|
G protein-coupled receptors (GPCRs) are the largest family of transmembrane proteins that relay extracellular signals across the plasma membrane and elicit an intricate cascade of cellular signaling events. A significantly large fraction of available drugs target GPCRs in order to exert fine control over functional outcomes from these receptors in pathological conditions. In this context, endocytosis and intracellular trafficking of GPCRs stringently regulate signaling outcomes from GPCRs within physiologically relevant spatiotemporal regimes. The membrane microenvironment around GPCRs has recently emerged as a key player in receptor function. Cholesterol is the single most abundant lipid in the eukaryotic plasma membrane and plays a central role in membrane organization and dynamics, with far-reaching functional implications in cellular physiology. In this review, we discuss current excitements in GPCR endocytosis and trafficking, with an emphasis on the role of membrane cholesterol. We envision that a detailed understanding of the contribution of membrane lipids such as cholesterol in spatiotemporal regulation of GPCR signaling would enable the development of therapeutic interventions fine-tuned to receptors residing in specific membrane microenvironments.
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10.1007/s12551-021-00878-7
|
pubmed_1134_14181
|
Research on autobiographical memory (AM) and the ability to retrieve specific autobiographical events in euthymic depressed patients yielded divergent results. The main goal of the present study was to further explore episodic specificity of AM among fully remitted depressed patients. Twenty euthymic depressed patients and 20 matched healthy controls were given a semi-structured interview, which assesses episodic specificity of positive and negative autobiographical memories regarding event and details' specificity, autonoetic consciousness (remember/know procedure) and visual perspective (field/observer procedure). Results showed an impairment of episodic specificity of AM in euthymic depressed patients. This impairment was explained by a field perspective deficit for positive memories only. These results suggest that euthymic patients continue to exhibit discrepancy between their current self and their self for positive past behaviors, which maintains an unfavorable view of their current self. Specific cognitive interventions may improve the self-relevance of their positive memories.
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10.1016/j.brat.2007.12.007
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pubmed_704_4861
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Background Heart failure with preserved ejection fraction (HFpEF) constitutes half of hospitalized heart failure cases and is commonly associated with obesity. The role of natriuretic peptide levels in hospitalized obese patients with HFpEF, however, is not well defined. We sought to evaluate change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels by obesity category and related clinical outcomes in patients with HFpEF hospitalized for acute heart failure. Methods and Results A total of 89 patients with HFpEF hospitalized with acute decompensated heart failure were stratified into 3 obesity categories: nonobese (body mass index [BMI] <30.0 kg/m2, 19%), obese (BMI 30.0-39.9 kg/m2, 29%), and severely obese (BMI ≥40.0 kg/m2, 52%), and compared for percent change in NT-proBNP during hospitalization and clinical outcomes. Clinical characteristics were compared between patients with normal NT-proBNP (≤125 pg/mL) and elevated NT-proBNP. Admission NT-proBNP was inversely related to BMI category (nonobese, 2607 pg/mL [interquartile range, IQR: 2112-5703]; obese, 1725 pg/mL [IQR: 889-3900]; and severely obese, 770.5 pg/mL [IQR: 128-1268]; P<0.01). Severely obese patients had the largest percent change in NT-proBNP with diuresis (-64.8% [95% CI, -85.4 to -38.9] versus obese -40.4% [95% CI, -74.3 to -12.0] versus nonobese -46.9% [95% CI, -57.8 to -37.4]; P=0.03). Nonobese and obese patients had significantly worse 1-year survival compared with severely obese patients (63% versus 76% versus 95%, respectively; P<0.01). Patients with normal NT-proBNP (13%) were younger, with higher BMI, less atrial fibrillation, and less structural heart disease than those with elevated NT-proBNP. Conclusions In hospitalized patients with HFpEF, NT-proBNP was inversely related to BMI with the largest decrease in NT-proBNP seen in the highest obesity category. These findings have implications for the role of NT-proBNP in the diagnosis and assessment of treatment response in obese patients with HFpEF.
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10.1161/JAHA.119.015738
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pubmed_347_9511
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The pocket proteins retinoblastoma protein (pRb), p107 and p130 are the key targets of oncoproteins expressed by DNA tumor viruses. Some of these viral proteins contain an LXCXE motif that mediates the interaction with the three pocket proteins and the inhibition of the pRb SUMOylation. Kaposi's sarcoma herpesvirus (KSHV) contains at least two proteins that can regulate pRb function but, so far, a KSHV-encoded protein targeting p107 and p130 has not been identified. Here, we show that the KSHV latent protein LANA2 binds to pRb, p107 and p130. LANA2 contains an LXCXE motif that is required for bypassing pRb-mediated cell-cycle arrest and for inhibiting pRb SUMOylation. Finally, we demonstrate that, in addition to pRb, both p107 and p130 can be SUMOylated, and this modification is also inhibited by LANA2 in an LXCXE-dependent manner. These results demonstrate, for the first time, the SUMOylation of p107 or p130 and, so far, they represent the first example of a KSHV protein able to interact with the three pocket proteins and to inhibit their conjugation to SUMO.
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10.1038/onc.2012.603
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pubmed_191_12136
|
BACKGROUND
Cytomegalovirus (CMV) causes life-threatening infections in immunocompromised patients, especially those with acquired immunodeficiency or organ transplants. Therefore, early detection of CMV is important to guide the clinical management of actively infected patients. Because detection of replicative transcripts indicates that the virus is in the process of being replicated in the infected cell, we applied a novel, sensitive, ligation-dependent (LD)-PCR method to detect CMV immediate-early (IE) messenger RNA (mRNA), an indicator of viral replication.
METHODS AND RESULTS
Viral mRNAs were released from infected cells by incubation in 5 M guanidinium thiocyanate, and IE mRNAs were captured onto magnetic beads through oligo(dT) capture probes. Two hemiprobes, each containing an IE mRNA-complementary region and a region for PCR primer binding, were captured by binding to the IE mRNA. These hemiprobes, bound on an IE mRNA in juxtaposition to one another, were linked together by a DNA ligase to form a full probe that served as the template for PCR amplification. This approach detected IE mRNAs in CMV-propagating cells, but not in supernatants containing only viral DNAs. Thirty-one clinical specimens were tested by LD-PCR; 18 specimens were positive (ten specimens, bronchoalveolar lavage [BAL]; five specimens, urine; two specimens, blood; one specimen, biopsy), 17 of which were confirmed by culture. Three culture-positive samples (two specimens, urine; one specimen, BAL) were missed by LD-PCR, and one urine sample was positive by LD-PCR but negative by culture.
CONCLUSION
LD-PCR assay is a reliable test for the early diagnosis of active CMV infection in patient specimens.
|
10.1054/modi.2001.29878
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pubmed_444_21717
|
INTRODUCTION
Denosumab, a monoclonal antibody that inhibits the receptor activator of nuclear factor-kappa (RANK) ligand, has been reported to reduce tumor size and progression, promote bone mineralization reconstruction, and increase bone density in patients with giant-cell tumor of bone (GCTB). However, information regarding the histopathological findings of spinal GCTB following denosumab therapy and the time course of the treatment is limited.
CASE REPORT
We report the case of a 58-year-old woman with progressive low back pain for 3 months before admission. Radiological and histological examinations revealed L4 GCTB. The patients received 10 courses of denosumab, and the tumor was subsequently resected. The therapy resulted in reduction of tumor mass and replacement of the lesions with bone tissue, particularly at the extravertebral and intracanal mass lesions. Histological examination of resected vertebra revealed a notable decrease in the number of RANK-positive and cyclooxygenase-2-positive cells. However, few RANK-positive cells were present around the woven bone.
CONCLUSION
Denosumab therapy for spinal GCTB is effective for reducing the tumor stage, surgical complications, and neurological impairment progression; however, it does not lead to total elimination of GCT cells, and careful consideration is needed in terms of the surgical procedure and post-operative denosumab therapy.
|
10.13107/jocr.2020.v10.i02.1706
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pubmed_747_6821
|
The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by sensory endings in the left ventricle activated by intracoronary injection of nicotine or veratridine into left anterior descending (LAD) or circumflex (Cx) coronary arteries in the dog. Injection of nicotine or veratridine into the Cx consistently resulted in larger decreases in heart rate, arterial pressure, and in gracilis perfusion pressure than were observed following injection of the same dose into the LAD. Vagotomy abolished the cardioinhibitory and vasodepressor responses to intracoronary nicotine or veratridine. The weight of left ventricle perfused by LAD or Cx was not different (43.5 +/- 1.65 and 44.5 +/- 2.2 g, respectively. These data indicate that chemical activation of sensory endings with vagal afferents in the inferoposterior left ventricle of the dog results in larger cardionhibitor and vasodepressor responses than result from activation of respects in the anterior left ventricle. Further, these data provide strong evidence that these sensory endings which are chemically activated are preferentially distributed to the inferoposterior left ventricle.
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10.1152/ajpheart.1978.235.2.H188
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pubmed_632_7239
|
PURPOSE
To test the feasibility and safety of injecting a high-contrast hydrogel marker at the head of the pancreas (HOP) and duodenum interface and assesses the marker visibility on cone beam computed tomography (CBCT) to localize this important boundary during image guided radiation therapy in a porcine model.
METHODS AND MATERIALS
This was a 2-stage study. The feasibility/visibility stage evaluated the ability to place the hydrogel using endoscopic ultrasound guidance on 8 swine (4 euthanized at post-injection day 8, 4 euthanized at post-injection day 22) and assessed the quality of visibility of the marked location on CBCT in the longer-surviving group. The risk assessment stage evaluated the toxicity of targeted intrapancreatic injections (3 swine) and intramural duodenal wall injections (3 swine) to assess toxicity of a misplaced hydrogel injection. All swine underwent postmortem examination and histopathologic studies.
RESULTS
The HOP-duodenum interface was successfully marked using hydrogel in 6 of the 8 swine. Histopathologic examination of the 6 successful hydrogel injections showed mild/minimal (4 cases) or moderate (2 cases) reactive inflammation isolated to the injection site. Of the 4 swine survived to 22 days, 3 demonstrated successful hydrogel placement at the HOP-duodenum interface, and this marked location was clearly visible for positional guidance on CBCT. There was no evidence of pancreatitis or duodenal toxicity in the swine undergoing targeted intrapancreatic or intramural duodenum injections for the risk assessment stage.
CONCLUSIONS
We demonstrate the feasibility and safety of injecting a hydrogel marker to highlight the HOP-duodenum interface that has acceptable visibility on CBCT. This technique, translated to humans, enables on-board visualization of this important boundary between the radiation target and dose-limiting, radiosensitive duodenum, facilitating efforts to safely deliver dose-escalated radiation therapy.
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10.1016/j.ijrobp.2018.02.024
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pubmed_740_2820
|
The purpose of this study was to investigate the reliability of residue ratings on Fiberoptic Endoscopic Evaluation of Swallowing (FEES). We also examined rating differences based on experience to determine if years of experience influenced residue ratings. A group of 44 raters watched 81 FEES videos representing a wide range of residue severities for thin liquid, applesauce, and cracker boluses. Raters were untrained on the rating scales and simply rated their overall impression of residue amount on a visual analog scale (VAS) and a five-point ordinal scale in a randomized fashion across two sessions. Intra-class correlation coefficients, kappa coefficients, and ANOVAs were used to analyze agreement and differences in ratings. Residue ratings on both the VAS and ordinal scales had acceptable inter- and intra-rater reliability. Inter-rater agreement was acceptable (ICC > 0.7) for all comparisons. Intra-rater agreement was excellent on the VAS scale (rc = 0.9) and good on the ordinal scale (k = 0.78). There was no significant difference between expert ratings and other raters based on years of experience for cracker ratings (p = 0.2119) and applesauce ratings (p = 0.2899), but there was a significant difference between clinicians on thin liquid ratings (p = 0.0005). Without any specific training, raters demonstrated high reliability when rating the overall amount of residue on FEES. Years of experience with FEES did not influence residue ratings, suggesting that expert ratings of overall residue amount are not unique or specialized. Rating the overall amount of residue on FEES appears to be a simple visual-perceptual task for puree and cracker boluses.
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10.1007/s00455-018-9883-x
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pubmed_984_14573
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The field of interventional oncology includes tumor ablation as well as the use of transcatheter therapies such as embolization, chemoembolization, and radioembolization. Terminology and reporting standards for tumor ablation have been developed. The development of standardization of terminology and reporting criteria for transcatheter therapies should provide a similar framework to facilitate the clearest communication among investigators and provide the greatest flexibility in comparing established and emerging technologies. An appropriate vehicle for reporting the various aspects of catheter directed therapy is outlined, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings. Methods for standardizing the reporting of outcomes toxicities, complications, and other important aspects that require attention when reporting clinical results are addressed. It is the intention of the group that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication for reporting the various aspects of transcatheter management of hepatic malignancy that will translate to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes.
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10.1016/j.jvir.2009.04.021
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pubmed_806_8292
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The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN.
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10.3389/fncel.2015.00047
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pubmed_947_16580
|
KDM6A, an X chromosome-linked histone lysine demethylase, was reported to be frequently mutated in many tumor types including breast and bladder cancer. However, the functional role of KDM6A is not fully understood. Using MCF10A as a model of non-tumorigenic epithelial breast cells, we found that silencing KDM6A promoted cell migration and transformation demonstrated by the formation of tumor-like acini in three-dimensional culture. KDM6A loss reduced the sensitivity of MCF10A cells to therapeutic agents commonly used to treat patients with triple-negative breast cancer and also induced TGFβ extracellular secretion leading to suppressed expression of cytotoxic genes in normal human CD8+ T cells in vitro. Interestingly, when cells were treated with TGFβ, de novo synthesis of KDM6A protein was suppressed while TGFB1 transcription was enhanced, indicating a TGFβ/KDM6A-negative regulatory axis. Furthermore, both KDM6A deficiency and TGFβ treatment promoted disorganized acinar structures in three-dimensional culture, as well as transcriptional profiles associated with epithelial-to-mesenchymal transition and metastasis, suggesting KDM6A depletion and TGFβ drive tumor progression.
IMPLICATIONS
Our study provides the preclinical rationale for evaluating KDM6A and TGFβ in breast tumor samples as predictors for response to chemo and immunotherapy, informing personalized therapy based on these findings.
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10.1158/1541-7786.MCR-21-0402
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pubmed_1070_7638
|
OBJECTIVES
To conduct a survey of the working of the Wetmore TB Clinic and to evaluate and analyze the follow-up data of the patient population diagnosed with latent TB infection (LTBI) at the Louisiana Office of Public Health (OPH) Region 1 Wetmore TB Clinic.
METHODS
This data analysis, initiated as a student practicum course, is based on a chart review of patients attending the Wetmore TB Clinic between 1 January 2006 and 30 June 2007. Only those patients with a diagnosis of LTBI were included in the survey.
RESULT
The total survey population in this data analysis consisted of 380 LTBI patients. Results were analyzed for demographic data, TB risk factors, referral sources and treatment outcomes. Forty-three per cent of all the patients with LTBI displayed at least one of these risk factors. Adherence rates for LTBI treatment were low, at 19%.
CONCLUSIONS
Post-Katrina New Orleans presents a challenging environment for TB control. This study forms a basis for further planning, provision and evaluation of services to this population. Its results and conclusions could be reflective of similar issues pertaining to public health TB clinics in other cities where displacement of patients, movement of migratory transient workers and disbanded infrastructure due to natural or man-made disasters could pose a problem.
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pubmed_1070_7638
|
pubmed_879_26750
|
Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 μM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 μM) and standard (2.26 μM) medium with 200 μM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 μM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 μM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 μM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 μM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 μM).
|
10.1093/mutage/geab041
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pubmed_938_6013
|
We recently demonstrated that cortical microsomes from spontaneously hypertensive rats metabolize arachidonic acid via cytochrome P450 to omega- and omega-1 hydroxylated compounds, 19- and 20-hydroxyeicosatetraenoic acids (HETE). The vascular activities of 20-HETE and the two isomers of 19-HETE were examined in rat aortic rings. The HETEs produced concentration-dependent contractions of the aortic rings. The contraction elicited by 20-HETE was abolished partially by removal of endothelium and was inhibited completely by treatment with indomethacin and reversed to a relaxation response by treatment with the endoperoxide and thromboxane receptor antagonist SQ 29548. These data suggest that the vascular effects of 20-HETE depend on subsequent metabolism by cyclooxygenase.
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pubmed_938_6013
|
pubmed_642_3291
|
PURPOSE
The present study aimed to explore if food perception can be influenced by sound mastication level when the external ear canal was occluded.
METHODS
Fifty-nine adults (38 women) with normal hearing, smell, and taste participated in the study. They tasted five crispy and five soft food items over two sessions: one with and one without an earplug inserted in the external ear canal. Participants were asked to rate freshness and taste of the food as well as their willingness to eat more of it and how much they usually like this kind of food. The sound pressure level related to the food mastication was recorded with a probe microphone placed in the external ear canal.
RESULTS
Compared to the open ear canal condition, levels of the mastication sounds were higher when the participants had their ears occluded, as well as for crispy than for soft food. Regarding food freshness, food appreciation, and willingness to eat more of the same food, there was no significant difference concerning food type, ear condition, and sex. For soft foods, men rated their usual liking of this food higher when they were wearing ear plugs compared to the opened condition.
CONCLUSION
Plugging the ear canals led to increased mastication sound levels. Participants did not seem to consider these additional acoustic cues when they rated food freshness, food appreciation, and willingness of eating the specific food. Only men seemed to take these cues into account when they rated their habit consumption of soft food.
|
10.1007/s00405-019-05296-w
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pubmed_163_14056
|
Dehydration can have negative effects on animal physiological performance, growth, reproduction, and survival, and most animals seek to minimize these effects by reducing water losses or seeking water sources. Much-but not all-of the research on animal water balance comes from dryland ecosystems. However, animals inhabiting mesic regions may also experience desiccating conditions, for example within urban heat islands or during heatwaves and droughts. Here we examined how spatial variation in impervious surface and spatial and temporal variation in microclimate impact water demand behavior of terrestrial arthropods and mollusks in three areas of mesic Northwest Ohio, with analysis of taxa that exhibited the greatest water demand behavior. Water demand behavior was measured as the frequency that individuals were observed at an artificial water source (a moistened pouch), relative to the frequency at a control (a dry pouch). Overall, terrestrial arthropods and mollusks were found about twice as often at the water source than at the control (equivalent to 86 more observations on the wet pouch than on dry at each site, on average), with ants accounting for over 50% of the overall response in urban areas. Daily fluctuations in vapor pressure deficit (VPD) best predicted daily variation in water demand behavior, with increased demand at higher VPD. Mean VPD was generally highest near urbanized areas, but effects of VPD on water demand behavior were generally lower in urbanized areas (possibly related to reductions in overall abundance reducing the potential response). On certain days, VPD was high in natural areas and greenspaces, and this coincided with the highest arthropod water demand behavior observed. Our results suggest that terrestrial arthropod communities do experience periods of water demand within mesic regions, including in greenspaces outside cities, where they appear to respond strongly to short periods of dry conditions-an observation with potential relevance for understanding the effects of climate change.
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10.1371/journal.pone.0260070
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pubmed_474_9867
|
The occurrence of three pathological entities of the cervical spine--ankylosing hyperostosis, calcification of the posterior longitudinal ligament, congenitally narrowed cervical canal--in a single patient is reported. This combination of pathology led to a severely narrowed cervical canal and a spine with abnormal mobility at non-fused levels. Minor trauma to the patient resulted in permanent quadriplegia.
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pubmed_474_9867
|
pubmed_573_3613
|
PURPOSE
The aim of this study was to assess whether migration of thallium-201 ((201)Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of (201)Tl.
PROCEDURES
10 healthy volunteers and 21 patients enrolled in the study (19 males and 12 females; 26-71 years old). The causes of olfactory dysfunction in the patients were head trauma (n = 7), upper respiratory tract infection (n = 7), and chronic rhinosinusitis (n = 7). (201)TlCl was administered unilaterally to the olfactory cleft, and SPECT-CT was conducted 24 h later. Separate MRI images were merged with the SPECT images. (201)Tl olfactory migration was also correlated with the volume of the olfactory bulb determined from MRI images, as well as with odor recognition thresholds measured by using T&T olfactometry.
RESULTS
Nasal (201)Tl migration to the olfactory bulb was significantly lower in the olfactory-impaired patients than in healthy volunteers. The migration of (201)Tl to the olfactory bulb was significantly correlated with odor recognition thresholds obtained with T&T olfactometry and correlated with the volume of the olfactory bulb determined from MRI images when all subjects were included.
CONCLUSIONS
Assessment of the (201)Tl migration to the olfactory bulb was the new method for the evaluation of the olfactory nerve connectivity in patients with impaired olfaction.
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10.1371/journal.pone.0057671
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pubmed_123_661
|
The effect of NG-nitro-L-arginine methylester (NAME) and N-mono-methyl-L-arginine (NMMA), inhibitors of nitric oxide (NO) synthase on penile erection and yawning induced by N-methyl-D-aspartic acid (NMDA) injected in the paraventricular nucleus of the hypothalamus (PVN) was studied in male rats. NAME (75-150 micrograms) and NMMA (250-500 micrograms), but not N-monomethyl-D-arginine (D-NMMA)(250-500 micrograms) prevented both responses in a dose-dependent manner when given intracerebroventricularly (i.c.v.) 15 min before NMDA (50 ng). NMDA-induced penile erection and yawning was also prevented by the guanylate cyclase inhibitor methylene blue (200-400 micrograms i.c.v.), but not by the NO scavenger methemoglobin (50-100 micrograms i.c.v.). NAME (10-20 micrograms), but not Methylene blue or methemoglobin (10-20 micrograms), prevented NMDA-induced responses also when injected in the PVN 15 min before NMDA. The present results suggest that NMDA-induced penile erection and yawning is mediated by an increased NO synthesis in the PVN.
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10.1016/0304-3940(94)90922-9
|
pubmed_788_17944
|
INTRODUCTION
Several cross-sectional and cohort studies have reported an association between serum markers of inflammation such as C-reactive protein, and coronary heart disease in Caucasian populations. We aimed to investigate the relationship between levels of serum C-reactive protein (hs-CRP) and the presence of coronary artery disease (CAD) in Iranian patients undergoing coronary angiography.
METHODS
Serum hs-CRP, fasting lipid profile and blood glucose levels were measured in 110 patients (61 males and 49 females) undergoing routine coronary angiography. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including post-menopausal status and smoking habit were assessed by questionnaire.
RESULTS
Of the 110 subjects undergoing angiography, 74 (67.28%) had significant CAD (CAD+) and 36 (32.72%) were classified as having insignificant CAD (CAD-). Mean age (p<0.01), waist circumference (p<0.01) and LDL (p<0.05) and median values of hs-CRP (p<0.01) and triglycerides (p<0.05) were higher in the patients CAD+ than in the subjects CAD-. The proportion of women who were postmenopausal was also significantly higher in the CAD+ group. Age (p<0.01), waist circumference (p<0.05) and hs-CRP (p<0.05) were significant CAD predictive factors from logistic regression analysis. Serum hs-CRP concentrations were significantly higher in smokers compared to non-smokers (p<0.05), low density lipoprotein (LDL) (r=0.31, p<0.001), and serum triglycerides (r=0.191, p<0.05) correlated with serum hs-CRP. The median value of serum hs-CRP increased with the severity of the disease, but failed to reach statistical significance.
CONCLUSION
Serum hs-CRP is an independent predictor of angiographically defined CAD in an Iranian population. Measurement of the serum hs-CRP level may improve risk stratification among patients suspected of having CAD. The strong correlations between serum hs-CRP with LDL and smoking may be due to the putative pro-inflammatory effects of these two parameters. The association with serum triglycerides may be indirect and related to insulin resistance and adiposity.
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pubmed_788_17944
|
pubmed_164_17426
|
Cell-free extracts of Prochloron didemni were assayed for ribulose 1,5-bisphosphate (RuBP) carboxylase (EC 4.1.1.39) and phosphoribulokinase (EC 2.7.1.19), two key enzymes in the reductive pentose-phosphate cycle. In an RuBP-dependent reaction, the production of two molecules of 3-phosphoglycerate per molecule of CO2 fixed was shown. Phosphoribulokinase activity was demonstrated by the production of ADP from ribulose 5-phosphate (Ru5P) and ATP and by measurement of ATP-, Ru5P-dependent (14)CO2 fixation in the presence of excess spinach RuBP carboxylase. When Prochloron RuBP carboxylase was purified from cell-free extracts by isopycnic centrifugation in reoriented linear 0.2 to 0.8 M sucrose gradients, the enzyme sedimented to a position which corresponded to that for the 520,000-dalton spinach enzyme. After polyacrylamide gel electrophoresis (PAGE) of Prochloron enzyme, a major band of enzyme activity corresponded to that for the spinach enzyme. Considerably more additional carboxylase activity was found in a less mobile species than was the case for spinach RuBP carboxylase. Sodium dodecyl sulfate-PAGE of the Prochloron enzyme indicates that it is composed of both large (molecular weight, MW=57,500) and small (MW=18,800) subunits.
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10.1007/BF00397328
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pubmed_511_1686
|
Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.
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10.1016/j.clcc.2017.12.004
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pubmed_897_20457
|
We live in an era of great change, and it is inevitable that the family physician will be caught up in this process. Many alternative futures are open to us; of these, the conserver society is perhaps the most attractive. Having briefly examined some of the major alternative futures for our society, and for medicine within that society, this paper defines the conserver society and describes some of its major health implications. The family physician needs to support and encourage the development of such a society for the sake of health, and should be prepared to accept new roles in community development.
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pubmed_897_20457
|
pubmed_682_10752
|
The dynamic nature of technological developments invites us to rethink the learning spaces. In this context, science education can be enriched by the contribution of new computational resources, making the educational process more up-to-date, challenging, and attractive. Bioinformatics is a key interdisciplinary field, contributing to the understanding of biological processes that is often underrated in secondary schools. As a useful resource in learning activities, bioinformatics could help in engaging students to integrate multiple fields of knowledge (logical-mathematical, biological, computational, etc.) and generate an enriched and long-lasting learning environment. Here, we report our recent project in which high school students learned basic concepts of programming applied to solving biological problems. The students were taught the Python syntax, and they coded simple tools to answer biological questions using resources at hand. Notably, these were built mostly on the students' own smartphones, which proved to be capable, readily available, and relevant complementary tools for teaching. This project resulted in an empowering and inclusive experience that challenged differences in social background and technological accessibility.
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10.1371/journal.pcbi.1006473
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pubmed_402_6779
|
Inflammatory cytokines may play a pathogenic role in the development of congestive heart failure (CHF). Elevated circulating levels of inflammatory cytokines have been reported in CHF, but most studies have focused on only a few cytokine parameters. However, the activity of these cytokines are modulated by soluble cytokine receptors and cytokines with anti-inflammatory activities, and in the present study several of these interacting factors were examined simultaneously in 38 CHF patients with various degrees of heart failure and in 21 healthy controls. Patients with CHF had increased plasma concentrations of tumor necrosis factor (TNF)alpha, interleukin-6, soluble TNF receptors and the soluble interleukin-6 receptor, glycoprotein (gp)130. They also had elevated ratios of TNFalpha/soluble TNF receptors and interleukin-6/soluble gp130 as well as enhanced interleukin-6 bioactivity in serum, suggesting inflammatory net effects. In addition to raised circulating levels of inflammatory cytokines, CHF patients with severe heart failure also had abnormalities in the levels of anti-inflammatory cytokines, with decreased levels of transforming growth factor beta1 and inadequately raised interleukin-10 in relation to the elevated TNFalpha concentrations. This dysbalance between inflammatory and anti-inflammatory cytokines was also found in monocyte supernatants from CHF patients. The abnormalities in the cytokine network were most pronounced in patients with the most severe heart failure, and several of the immunologic parameters, in particular soluble gp130, were correlated with variables reflecting deranged hemodynamic status. The present study analyzing the complexity of the cytokine network in CHF, demonstrates profound disturbances in the levels of both inflammatory and anti-inflammatory mediators with a marked dysbalance favoring inflammatory effects.
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10.1016/s0002-9149(98)00872-8
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pubmed_572_25777
|
OBJECTIVES
Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars.
METHODS
Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015-2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%.
FINDINGS
The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%.
CONCLUSIONS
The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits.
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10.1136/bmjopen-2016-013543
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pubmed_1023_9966
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A stereological analysis was made of synapses in the left and right hemispheres of chick medial hyperstriatum ventrale (MHV) 24h after passive avoidance training (PAL) and in water trained controls (W-control). The synaptic parameters examined were (D), the mean length of the postsynaptic thickening; (NV.syn), the number of synapses per unit volume of neuropil; (VV.syn), the volume density of the pre-synaptic bouton; (NV.ves), the number of synaptic vesicles per unit volume of neuropil and (ves.syn), the mean number of synaptic vesicles per pre-synaptic bouton. No significant differences exist in NV.syn between the left or right hemispheres of W-control and trained chicks, nor is NV.syn influenced by training. However, in W-control chicks D in the right MHV is significantly greater (12%) than in the left MHV and this difference disappears on training. There are no differences in VV.syn between left and right hemispheres of W-control chicks but following training VV.syn is 22.7% greater in the left MHV than in the right MHV. Training als influences the number of synaptic vesicles; in W-control chicks NV.ves in the right MHV is 12.25% greater than in the left MHV but following training these differences are reversed. When the data are expressed as numbers of vesicles per synapse (ves.syn), values for the left hemisphere of trained chicks exceed those in the right hemisphere by a staggering 61.38%. These results are discussed in the context of biochemical and electrophysiological studies which suggest that there is lateralization of the memory trace.
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10.1016/0165-3806(84)90048-8
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pubmed_852_1517
|
OBJECTIVE
Although physical activity modulates the hypothalamic-pituitary-ovarian axis, the few studies that have investigated whether physical activity is associated with age at natural menopause have yielded mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women overall and by smoking history.
METHODS
We investigated the association between long-term physical activity (h/wk/y) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former light smoker, former heavy smoker, current light smoker, and current heavy smoker) as an effect modifier was evaluated.
RESULTS
In a multivariable model adjusted for body mass index at age 18 years, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (P(trend) = 0.005). Higher body mass index at age 18 years (P(trend) = 0.0003) and older age at menarche (P(trend) = 0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs non-Hispanic whites; HR, 1.17; 95% CI, 1.09-1.26), current smokers (vs never smokers; HR, 1.68; 95% CI, 1.60-1.75 for current light smokers; HR, 1.38; 95% CI, 1.33-1.44 for current heavy smokers), and older age at first full-term pregnancy (HR(≥29, 2+ full-term pregnancies) vs HR(<29, 2+ full-term pregnancies), 1.10; 95% CI, 1.06-1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older age at natural menopause among heavy smokers only (HR(highest quartile) vs HR(lowest quartile), 0.88; 95% CI, 0.81-0.97; P(trend) = 0.02 for former heavy smokers; HR(highest quartile) vs HR(lowest quartile), 0.89; 95% CI, 0.80-0.99; P(trend) = 0.04 for current heavy smokers).
CONCLUSIONS
Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.
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10.1097/GME.0b013e31826ce3d4
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pubmed_82_21223
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Health status, the way of life and nourishment of 84 vegans in Siberian village (Krasnoyarsk region) were studied and compared with those of 26 meat-eaters. The investigation included work with a questionnaire, clinico-diagnostic and laboratory research. It was shown that a vegetarian diet improves the serum lipid spectrum (cholesterol, LPLD, cholesterol of LPNP, atherogenic coefficient), normalizes weight and cardiovascular system. The vegans had normal levels of vitamin B12 and serum Fe but the calcium level in this group was lowered as compared with the control group. The pathology of internals (nephroptosis, lithic diathesis, tendency to lithogenesis) was observed. Apparently, the high serum Zn levels found in both groups aren't directly caused by the diet but by climate and geographic factors.
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pubmed_82_21223
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pubmed_244_21652
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Multiple factors are known to contribute to the pathogenesis of cerebral ischemic injury, including microRNAs (miRNAs). However, the precise mechanism of miRNAs involvement in cerebral ischemia remains largely unclear. In the current study, we found that miR-217 was significantly upregulated in ischemic stroke models, and the upregulation of miR-217 was associated with the development of post-stroke cognitive impairment. Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. In vitro experiments showed that miR-217 promoted aggregation of histone deacetylase 5 (HDAC5) in cell nuclei by targeting MEF2D, which led to decreased expression of interleukin (IL)-10. In addition, miR-217 inhibited the expression of NADH dehydrogenase subunit 6 (ND6) in a MEF2D-dependent manner. Overexpression of MEF2D can reverse oxygen-glucose deprivation (OGD)-induced downregulation of ND6 and OGD-mediated neuronal apoptosis, and also reduce the elevated generation of reactive oxygen species (ROS) induced by OGD. Additionally, we found that in vivo administration of MEF2D overexpression plasmids increased IL-10 production and ameliorated cognitive impairment after cerebral ischemia. Taken together, these findings reveal a novel pathogenetic mechganism of cerebral ischemia-related brain injury involving the miR-217/MEF2D/HDAC5 axis and the miR-217/MEF2D/ND6 axis.
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10.1016/j.brainres.2020.146835
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pubmed_340_11073
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Despite the fact that both peritoneal (PF) and follicular (FF) fluids have a common ovarian origin, FF is a natural inducer of sperm acrosome reaction (AR) while PF is not. To better understand these effects, concentrations of oestradiol, progesterone and proteins in peri-ovulatory PF and FF were determined and compared. PF was aspirated by laparoscopy at the peri-ovulatory stage from women with unexplained infertility. FF was collected from patients undergoing IVF and pooled. PF and FF were tested for the presence of antisperm antibodies. Oestradiol and progesterone were measured by enzyme immunoassay, and total protein concentration was determined and analysed. The AR was determined in spermatozoa that were exposed to PF alone, progesterone-supplemented PF, progesterone, control medium, or ethanol. No antisperm antibodies were found in any fluid tested. Oestradiol and progesterone and concentrations in PF were significantly lower than in FF. Protein concentration was also significantly lower in PF than in FF, but no differences were observed between the electrophoretic patterns. When capacitated spermatozoa were exposed to progesterone-supplemented PF there was a significant increase in the percentage of AR with respect to those in PF, control medium or ethanol. These results suggest that the lack of AR-stimulating activity of PF was related to its lower progesterone concentration compared with FF.
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10.1016/s1472-6483(10)60616-5
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pubmed_1134_22622
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We discuss the use of parallel-access optical disks for high-speed pattern-recognition systems. Three practical configurations that make use of the unique properties of optical disks are discussed. A practical incoherent disk-based correlator is described, and its performance illustrated by use of both matched filters and computer-generated minimum average correlation energy filters.
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10.1364/ao.36.002388
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pubmed_223_23869
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Two meta-xylyl linked tetrakis-benzimidazolium salts (L1-L2) as multidentate ligands and two respective silver complexes (C1 and C2) were synthesized. A multistep reaction was done at room temperature, starting with simple benzimidazole and alkyl halides, going through precursors and salt formation by reflux and finally in situ deprotonation of tetrabenzimidazolium salts with Ag2O to yield respective tetra-nuclear Ag(I)-N-heterocyclic Carbene (NHC) complexes. Propyl and butyl groups were bonded at the terminal positions of tetra-azolium open chain salts. Characterization of compounds was done by analytical and spectroscopic techniques. On the basis of spectroscopic data, a chemical structure with open chains having four Ag(I) ions sandwiched between NHC layers was established. Potential of synthesized complexes (C1 & C2) for wound contraction was evaluated and compared with standard wound contraction gel. Percentage wound contraction of both complexes was found very close to that of standard drug used in parallel.
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10.1515/znc-2020-0069
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pubmed_202_8137
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A thermostable DNA polymerase was prepared from Bacillus caldotenax by using a four-step chromatography procedure. The protein exists as a monomer of M(r) 94,000, has a pI of 4.9 and has no associated 3'-5' or 5'-3'-exonuclease activities or endonuclease activity. The temperature optimum of the enzyme was about 70 degrees C and the pH for maximum activity was about 7.5. The enzyme has an absolute requirement for a bivalent cation, and maximum activity was obtained at the unusually high concentration of 70 mM-MgCl2. Mg2+ could be replaced by MnCl2 or CoCl2, with decreased activity, at the lower optimal concentrations of 1 mM and 2.5 mM respectively. Enzyme activity was inhibited in the presence of 2',3'-dideoxy-TTP, arabinosyl-CTP and aphidicolin. Enzyme activity was stimulated with KCl concentrations of about 100 mM, and concentrations of univalent salts above about 150 mM inhibited activity. The enzyme could use activated calf thymus DNA, poly(dA).p(dT)10 or primed single-stranded phage M13 DNA as a template and maximum activity was obtained with poly(dA).p(dT)10. The enzyme was inactive on unprimed single-stranded DNA, double-stranded DNA and polyribonucleotide template/primer. The apparent Km values for individual dNTPs, determined with the other dNTPs at saturating concentrations, were 5.7 microM (dCTP), 6.3 microM (dATP, dGTP) and 6.4 microM (dTTP). The Km value for the overall incorporation of each dNTP from an equimolar mixture of all four dNTPs was 24.7 microM. The kcat. value was about 1.05 s-1. The kcat./Km value was 0.16-0.18 M-1.s-1 for individual dNTPs and 0.04 for the incorporation of an equimolar mixture of all four dNTPs. Some of the properties of the enzyme show it may be classified as an alpha-Type DNA polymerase.
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10.1042/bj2870971
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pubmed_107_14895
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We examined effects of high doses of monosodium glutamate (MSG) on extracellular glutamate levels in rat striata, using in vivo microdialysis. Parenteral doses (0.5, 1.0 and 2.0, but not 0.25, g/kg, i.p.) caused dose- and time-dependent increases, peaking after 40 min (at 174 +/- 47%, 485 +/- 99% and 1021 +/- 301% of basal levels, respectively). In contrast, dietary MSG (1.49 +/- 0.10 g/kg/h) was ineffective.
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10.1016/0006-8993(94)91309-9
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pubmed_266_21544
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A general solution for the RS EPR deconvolution problem has been derived. This solution permits the use of arbitrary magnetic field scans. As a result, constraints on the current experimental designs can be lifted. For example, a trapezoidal waveform can be used to accelerate the scan rate without affecting the signal bandwidth. The assumptions made to develop the previous algorithms are mathematically validated.
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10.1016/j.jmr.2020.106801
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pubmed_412_17835
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Two important signaling systems involved in the growth and development of plants, those triggered by the photoreceptor phytochrome and the hormone abscisic acid (ABA), are involved in the regulation of expression of the NPR1 gene of Lemna gibba. We previously demonstrated that phytochrome action mediates changes in ABA levels in L. gibba, correlating with changes in gene expression evoked by stimulation of the phytochrome system. We have now further characterized phytochrome- and ABA-mediated regulation of L. gibba NPR1 gene expression using a transient particle bombardment assay, demonstrating that regulatory elements controlling responses to both stimuli reside within 156 nucleotides upstream of the transcription start. Linker scan (LS) analysis of the region from -156 to -70 was used to identify two specific requisite and nonredundant cis-acting promoter elements between -143 to -135 (LS2) and -113 to -101 (LS5). Mutation of either of these elements resulted in a coordinate loss of regulation by phytochrome and ABA. This suggests that, unlike the L. gibba Lhcb2*1 promoter, in which phytochrome and ABA regulatory elements are separable, the phytochrome response of the L. gibba NPR1 gene can be attributed to alterations in ABA levels.
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10.1104/pp.116.4.1299
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pubmed_103_24225
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Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A-D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery.
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10.3390/ijms18030491
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pubmed_471_11654
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Understanding fate and transport of plant protection products (PPPs) that enter vegetated streams from agricultural fields is important for both exposure assessment and risk attenuation, yet limited knowledge is available. The present laboratory study investigated sorption processes governing mass transfer of three common PPPs between water and aquatic plant phases at flow-through exposure conditions (transient aqueous-phase PPP-peak of 4 h 25 min) using three temperature regimes. The exposure produced rapid sorption of PPPs to plants, followed by a gradual depuration from plants. Dynamic sorption kinetics depended on temperature, plant species, and physicochemical properties of the PPPs. Sorption to plants contributed to a 10% reduction of the water-phase peak concentrations of the PPPs. However, being reversible, the attenuation effect was limited to the residence time of the PPPs in the systems. Results of the present study highlight that effectivity of aquatic plants in the attenuation of PPP loads may vary greatly depending on hydrodynamic properties of aquatic systems.
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10.1016/j.chemosphere.2018.10.186
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pubmed_402_13476
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In animals, UTP feedback inhibition of carbamyl phosphate synthetase II (CPSase) controls pyrimidine biosynthesis. Suppressor of black (Su(b) or rSu(b)) mutants of Drosophila melanogaster have elevated pyrimidine pools, and this mutation has been mapped to the rudimentary locus. We report that rSu(b) is a missense mutation resulting in a glutamate to lysine substitution within the second ATP binding site (i.e. CPS.B2 domain) of CPSase. This residue corresponds to Glu780 in the Escherichia coli enzyme (Glu1153 in hamster CAD) and is universally conserved among CPSases. When a transgene expressing the Glu-->Lys substitution was introduced into Drosophila lines homozygous for the black mutation, the resulting flies exhibited the Su(b) phenotype. Partially purified CPSase from rSu(b) and transgenic flies carrying this substitution exhibited a dramatic reduction in UTP feedback inhibition. The slight UTP inhibition observed with the Su(b) enzyme in vitro was due mainly to chelation of Mg2+ by UTP. However, the Km values for glutamate, bicarbonate, and ATP obtained from the Su(b) enzyme were not significantly different from wild-type values. From these experiments, we conclude that this residue plays an essential role in the UTP allosteric response, probably in propagating the response between the effector binding site and the ATP binding site. This is the first CPSase mutation found to abolish feedback inhibition without significantly affecting other enzyme catalytic parameters.
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10.1006/jmbi.1999.2618
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pubmed_361_2429
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Using a synthetic oligonucleotide primer complementary to human prostate-specific antigen mRNA, we found that an additional sequence possibly similar to human glandular kallikrein-1 could be read by a primer-extension sequencing technique. We were able to confirm the identity of that additional sequence with another oligonucleotide primer complementary to a specific region of the human glandular kallikrein-1 mRNA sequence. Northern blot analysis with 2 oligonucleotide probes respectively specific for prostate-specific antigen and human glandular kallikrein-1 mRNAs showed that the length of both mRNAs was similar at 1.5 kb. The level of human glandular kallikrein-1 mRNA relative to that of prostate-specific antigen could be estimated as approx. 10-20%. This study constitutes the first evidence that the human glandular kallikrein-1 gene is expressed at a high level in a human tissue.
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10.1016/0014-5793(88)80315-6
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pubmed_630_3606
|
OBJECTIVE
To evaluate the tactics of surgical treatment of patients with coronary heart disease and atherosclerotic lesions of cerebral vessels in dependence of risk stratification of heart and brain complications.
MATERIAL AND METHODS
One hundred and fifty-six patients were examined. Cerebral and coronary blood flow and functional state of the brain and heart were studied. According to treatment characteristics, 3 groups were singled out: patients of the 1(st) group underwent simultaneous surgery of coronary and brachiocephalic arteries, patients of the 2(nd) group were first operated for brachiocephalic arteries, in the 3(rd) group, bypass graft was performed in the first stage.
RESULTS AND CONCLUSION
A role of coronary and brachiocephalic arteries, functional state of the myocardium and brain in the postoperative risk was established. The authors suggest the algorithm for choosing the order of priority of surgical interventions on coronary and brachiocephalic arteries.
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10.17116/jnevro20161162122-28
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pubmed_57_20122
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Biological hydrogen (H2) production by dark and photo-fermentative organisms is a promising area of research for generating bioenergy. A large number of organisms have been widely studied for producing H2 from diverse feeds, both as pure and as mixed cultures. However, their H2 producing efficiencies have been found to vary (from 3 to 8 mol/mol hexose) with physiological conditions, type of organisms and composition of feed (starchy waste from sweet potato, wheat, cassava and algal biomass). The present review deals with the possibilities of enhancing H2 production by integrating metabolic pathways of different organisms-dark fermentative bacteria (from cattle dung, activated sludge, Caldicellulosiruptor, Clostridium, Enterobacter, Lactobacillus, and Vibrio) and photo-fermentative bacteria (such as Rhodobacter, Rhodobium and Rhodopseudomonas). The emphasis has been laid on systems which are driven by undefined dark-fermentative cultures in combination with pure photo-fermentative bacterial cultures using biowaste as feed. Such an integrative approach may prove suitable for commercial applications on a large scale.
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10.1007/s12088-012-0287-6
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pubmed_156_15464
|
RATIONALE
Previous work indicates that female rats initiate cocaine use sooner than male rats and reach significantly higher break points (BPs) for a single injection of cocaine under a progressive ratio (PR) schedule compared to male rats.
OBJECTIVES
The present study extends previous work examining sex differences to the acquisition of methamphetamine (METH) (0.02 mg/kg) and maintenance of METH-maintained responding under a PR schedule.
METHODS
An automated priming procedure that has previously been shown to be sensitive to sex differences was used for the acquisition of drug self-administration. A PR schedule that has been shown to be sensitive in detecting sex differences in maintenance levels of cocaine-reinforced responding was used for the maintenance phase of the experiment.
RESULTS
A greater percentage of female rats met the acquisition criterion for METH (0.02 mg/kg) self-administration compared to male rats (55.6% versus 11.1%, respectively), and they did so at a significantly faster rate. Under stable fixed-ratio 1 (FR1) conditions (after acquisition and 5 days before the PR schedule) female rats responded for significantly more METH (0.02 mg/kg) infusions compared to males. Dose-response curves obtained under the PR schedule during maintenance indicated that female rats self-administered significantly more METH infusions compared to male rats.
CONCLUSIONS
These data suggest that female rats are more vulnerable to the acquisition of METH self-administration, and they are more motivated to self-administer METH compared to male rats under a PR schedule during the maintenance phase.
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10.1007/s00213-003-1670-0
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pubmed_220_146
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The three-dimensional NMR structures of eight cyclic octapeptide analogues of somatostatin (SRIF) are described. These analogues, with the basic sequence H-c[Cys(3)-Phe(6)-Xxx(7)-Yyy(8)-Lys(9)-Thr(10)-Zzz(11)-Cys(14)]-OH (the numbering refers to the position in native SRIF), with Xxx(7) being Phe/Ala/Tyr, Yyy(8) being Trp/DTrp/D-threo-beta-Me2Nal/L-threo-beta-Me2Nal, and Zzz(11) being Phe/Ala, exhibit potent and highly selective binding to human SRIF type 4 (sst(4)) receptors. The conformations reveal that the backbones of these analogues do not have the usual type-II' beta-turn reported in the literature for sst(2)-subtype-selective analogues. Instead, the structures contain a unique arrangement of side chains of Yyy(8), Lys(9), and Phe(6) or Phe(11). The conformational preferences and results from biological analyses of these analogues (parts 1-3 of this series, Rivier et al., Erchegyi et al., and Erchegyi et al., J. Med. Chem. 2003, preceding papers in this issue) allow a detailed study of the structure-activity relationship of SRIF. The proposed consensus structural motif at the binding pocket for the sst(4)-selective analogues requires a unique set of distances between an indole/2-naphthyl ring, a lysine side chain, and another aromatic ring. This motif is necessary and sufficient to explain the binding affinities of all of the analogues studied and is distinct from the existing model suggested for sst(2)/sst(5) selectivity.
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10.1021/jm030246p
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pubmed_326_10257
|
OBJECTIVE
To assess endometrial response to parenteral levonorgestrel in hormone replacement therapy by means of morphological criteria and immunohistochemical staining of insulin-like growth factor-binding protein-1 (IGFBP-1).
DESIGN
Endometrial samples were collected from 35 postmenopausal women after 12 to 22 months of continuous combined estrogen-progestin therapy. All subjects were treated with parenteral progestin. A group of 8 women was treated with a subdermal levonorgestrel-releasing implant, and 27 women had a levonorgestrel-releasing intrauterine device (IUD). Sections of formalin-fixed paraffin-embedded biopsies were used for immunohistochemistry and after hematoxylin-eosin staining for routine histologic examination.
RESULTS
Atrophic epithelium with pronounced decidual reaction in the stroma was detected by histologic examination in all endometrial samples obtained from 27 women treated with the levonorgestrel-releasing IUD. In contrast, the endometrium was proliferative in seven of eight (87.5 percent) biopsies obtained from women treated with the levonorgestrel-releasing implant. Immunoreactive IGFBP-1 was detected in decidualized stromal cells in all endometrial samples obtained during intrauterine levonorgestrel therapy, whereas only one of eight samples obtained from women treated with subdermal levonorgestrel exhibited weak staining for IGFBP-1.
CONCLUSIONS
Our data show that both the morphological and biochemical response of post- menopausal endometrium to parenteral levonorgestrel was strikingly different, depending on the route of progestin administration, and that the decidual reaction and epithelial atrophy induced by intrauterine levonorgestrel were associated with expression IGFBP-1 in decidualized stromal cells.
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10.1016/s0015-0282(16)58213-2
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pubmed_500_12306
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To assess a possible relation between the suprachiasmatic nucleus (SCN) and the locus coeruleus (LC), a study with evoked potentials was performed in the rat. An evoked potential was recorded in the SCN area after electrical stimulation of the LC. Also, an evoked potential was recorded in the LC after electrical stimulation of the SCN area. The results indicate specificity of the projecting regions and of the activated regions, suggesting the existence of a possible bidirectional communication between the LC and the SCN. The pathways possibly involved are discussed.
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10.1016/0361-9230(89)90210-4
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pubmed_618_4534
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The objective of this study was to investigate the pretreatment effects of high-fibre substrate on particle size distribution in a full-scale agricultural biogas plant (BGP). Two digesters, one fed with pretreated material and one with untreated material, were investigated for a period of 90days. Samples from different positions and heights were taken with a special probe sampling system and put through a wet sieve. The results show that on average 58.0±8.6% of the particles in both digesters are fine fraction (<0.063mm). A higher amount of particles (13.1%) with a length >4mm was measured in the untreated digester. However, the volume distribution over all positions and heights did not show a clear and uniform distribution of particles. These results reveal that substrate pretreatment has an effect on particle size in the fermenting substrate, but due to the uneven distribution mixing, is not homogeneous within the digester.
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10.1016/j.biortech.2014.09.037
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pubmed_1103_1843
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Depression is the most frequent psychiatric disease associated with chronic somatic disorders. Diagnosis, however, is frequently difficult to make, due on one hand to the presence of symptoms that depression and chronic somatic disorders have in common, and on the other hand to the assumption shared by the physician and its patient that depression is a normal reaction to a somatic illness. Accurate diagnosis is nevertheless necessary in order to initiate the appropriate treatment. A review of pharmacological treatments of depression related to frequent chronic somatic disorders is presented.
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pubmed_1103_1843
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pubmed_875_3421
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The Bibionidae are a family belonging to the suborder Bibionomorpha with four genera and 17 species known from Colombia. This work expands the distribution of these species to other localities in the country.
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10.11646/zootaxa.4122.1.5
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pubmed_1119_21752
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The KAT1 channel is a hyperpolarization-activated K+ channel cloned from the higher plant Arabidopsis. The deduced amino acid sequence suggests that its structural organization is similar to that of the Shaker-like K+ channel activated by depolarization. Electrophysiological properties of the KAT1 channel expressed in Xenopus oocytes indicate that voltage-dependent activation of the KAT1 channel is not caused by the divalent ion block and that it is intrinsic to the channel. Activity of the KAT1 channel progressively decreases upon patch excision. This rundown of the channel is accompanied by a large shift in the voltage dependence of the channel to a more negative direction. The voltage dependence is also regulated by pH, ATP, and cGMP.
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10.1085/jgp.105.3.309
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pubmed_895_8462
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BACKGROUND
A new dietary supplement, Fatigue Reviva™, has been recently developed to address issues related to amino acid depletion following illness or in conditions of sub-health where altered amino acid homeostasis has been associated with fatigue. Complex formulations of amino acids present significant challenges due to solubility and taste constraints. This initial study sets out to provide an initial appraisal of product palatability and to gather pilot evidence for efficacy.
METHODS
Males reporting symptoms of sub-health were recruited on the basis of being free from any significant medical or psychological condition. Each participant took an amino acid based dietary supplement (Fatigue Reviva™) daily for 30 days. Comparisons were then made between pre- and post-supplement general health symptoms and urinary amino acid profiles.
RESULTS
Seventeen men took part in the study. Following amino acid supplementation the total Chalder fatigue score improved significantly (mean ± SEM, 12.5 ± 0.9 versus 10.0 ± 1.0, P<0.03). When asked whether they thought that the supplement had improved their health, 65% of participants responded positively. A subgroup of participants reported gastrointestinal symptoms which were attributed to the supplement and which were believed to result from the component fructooligosaccharide. Analysis of urinary amino acids revealed significant alterations in the relative abundances of a number of amino acids after supplementation including an increase in valine, isoleucine and glutamic acid and reduced levels of glutamine and ornithine. Discriminant function analysis of the urinary amino acid data revealed significant differences between the pre- and post-supplement urine excretion profiles.
CONCLUSIONS
The results indicated that Fatigue Reviva™ was palatable and that 65% of the study group reported that they felt the product had improved their health. The product could provide an effective tool for the management of unexplained fatigue and symptoms of sub-health. Further product development may yield additional options for those patients susceptible to fructooligosaccharide.
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10.1186/1475-2891-12-115
|
pubmed_762_21746
|
Current knowledge of the genetic diversity of simian immunodeficiency virus (SIVcpz) infection of wild chimpanzees (Pan troglodytes) is incomplete since few isolates, mostly from captive apes from Cameroon and Gabon, have been characterized; yet this information is critical for understanding the origins of human immunodeficiency virus type 1 (HIV-1) and the circumstances leading to the HIV-1 pandemic. Here, we report the first full-length SIVcpz sequence (TAN1) from a wild chimpanzee (Pan troglodytes schweinfurthii) from Gombe National Park (Tanzania), which was obtained noninvasively by amplification of virion RNA from fecal samples collected under field conditions. Using reverse transcription-PCR and a combination of generic and strain-specific primers, we amplified 13 subgenomic fragments which together spanned the entire TAN1 genome (9,326 bp). Distance and phylogenetic tree analyses identified TAN1 unambiguously as a member of the HIV-1/SIVcpz group of viruses but also revealed an extraordinary degree of divergence from all previously characterized SIVcpz and HIV-1 strains. In Gag, Pol, and Env proteins, TAN1 differed from west-central African SIVcpz and HIV-1 strains on average by 36, 30, and 51% of amino acid sequences, respectively, approaching distance values typically found for SIVs from different primate species. The closest relative was SIVcpzANT, also from a P. t. schweinfurthii ape, which differed by 30, 25, and 44%, respectively, in these same protein sequences but clustered with TAN1 in all major coding regions in a statistically highly significant manner. These data indicate that east African chimpanzees, like those from west-central Africa, are naturally infected by SIVcpz but that their viruses comprise a second, divergent SIVcpz lineage which appears to have evolved in relative isolation for an extended period of time. Our data also demonstrate that noninvasive molecular epidemiological studies of SIVcpz in wild chimpanzees are feasible and that such an approach may prove essential for unraveling the evolutionary history of SIVcpz/HIV-1 as well as that of other pathogens naturally infecting wild primate populations.
|
10.1128/jvi.77.3.2233-2242.2003
|
pubmed_886_15352
|
Sorafenib was the first multikinase inhibitor to be approved for use in renal cell cancer (RCC) in the US (2005) and in Europe (2006). In the Treatment Approaches in Renal Cell Cancer Global Evaluation Trial (TARGET), sorafenib showed a significant progression-free survival advantage over placebo in patients with advanced RCC. Incidence rates of adverse events were significantly higher with sorafenib than with placebo. Management of adverse events is an essential component of care to prevent negative impact on patient quality of life and dose modification of sorafenib therapy. This report, based on an expert panel discussion held in February 2009, presents recommendations for the management of skin rash, hand-foot skin reaction, diarrhea, and hypertension, and strategies to help lessen the frequency and severity of these events. In addition, general recommendations for dose modifications are discussed. The goal of these management recommendations is to optimize sorafenib therapy for advanced RCC.
|
10.1016/j.critrevonc.2010.03.006
|
pubmed_970_1486
|
Aging is associated with changes in brain functional patterns as well as cognition. The present research sought to investigate longitudinal changes in whole brain functional connectivity strength (FCS) and cognitive performance scores in very old cognitively unimpaired individuals. We studied 34 cognitively normal elderly individuals at both baseline and 4-year follow-up (baseline age = 78 ± 3.14 years) with resting-state functional magnetic resonance imaging (r-fMRI), structural MRI scans, and neuropsychological assessments conducted. Voxel-based whole brain FCS was calculated and we found that bilateral superior parietal and medial frontal regions showed decreased FCS, while the supplementary motor area (SMA) and insula showed increased FCS with age, along with a decrease in bilateral prefrontal cortical thickness. The changes of FCS in left precuneus were associated with an aging-related decline in global cognition. Taken together, our results suggest changes in FCS with aging with the precuneus as a hub and this may underlie changes in global cognition that accompany aging. These findings help better understand the normal aging mechanism.
|
10.3389/fnagi.2020.00071
|
pubmed_291_3624
|
BACKGROUND/METHODS
A door-to-door ('every door') study was carried out to assess the incidence and prevalence rates of epilepsy, stroke, Bell's palsy and cerebral palsy, as well as the prevalence of dementia, extrapyramidal syndromes, muscle and neuromuscular disorders, cerebellar ataxia and primary nocturnal enuresis among the urban and rural populations of Al Kharga district, New Valley, Egypt. The study was carried out in 3 stages from June 1, 2005 to May 31, 2009. A door-to-door screening including every door was carried out using a standardized questionnaire, which was administered by 3 neurologists to all inhabitants (62,583) of Al Kharga district. The study was designed to assess the prevalence, incidence and risk factors of major neurological disorders in Al Kharga district and aimed to reduce the burden of these neurological disorders in the entire region.
RESULTS/CONCLUSIONS
This study clarified that dementia, primary nocturnal enuresis, epilepsy, stroke and cerebral palsy are the most common neurological disorders. On the other hand, Bell's palsy, extrapyramidal syndromes, cerebellar ataxia, muscle dystrophies and myasthenia gravis are less common neurological disorders in Al Kharga district.
|
10.1159/000320240
|
pubmed_197_3204
|
Provision of indirect restorations is associated with more complaints and litigation than any other area of dentistry. In the third part of this series we identify possible causes of such complaints. We explore each of the stages from clinical assessment to treatment, highlighting areas which may trigger litigation when they are not addressed carefully - particularly in relation to cosmetic dentistry. The article is illustrated with clinical examples drawn from the authors' personal experience. With patients' ever-increasing expectations, the pressure to deliver quality dentistry has never been higher and will not diminish.
|
10.1038/sj.bdj.2010.675
|
pubmed_81_5565
|
The IGFs mediate their effects on cell function through the type I IGF receptor and numerous intracellular signalling molecules, including the phosphatidylinositol 3-kinase (PI-3K)/Akt pathway. The type I IGF receptor also binds to the caveolae protein caveolin-1, but the impact of caveolae on IGF/PI-3K/Akt signalling remains controversial. We have examined the effect of complete (knockout) and partial (knockdown) caveolin-1 deficiency on cellular IGF effects mediated via the PI-3K/Akt pathway. Under basal conditions, caveolin-1-deficient mouse embryonic fibroblast cells [MF(-/-)] incorporated significantly more [3H]thymidine than wild-type mouse embryonic fibroblast cells [MF(+/+)]; however, small hairpin RNA-mediated knockdown of caveolin-1 (80% reduction) in 3T3L1 fibroblasts had no effect on basal proliferation. Interestingly, IGF-I induced proliferation was similar in MF(-/-) and MF(+/+) cells, whereas caveolin-1 knockdown promoted a hyperproliferative response to IGF-I [pkDCav3T3L1(80) 12.4+/-0.4-fold; pkDShuffle3T3L1 4.3+/-0.2-fold induction; P<0.01]. Immunoblot analysis showed that caveolin-1 knockdown had no affect on Akt expression or activation. However, in MF(-/-) cells, IGF-I-stimulated phosphorylation of Akt was reduced despite up-regulated Akt levels. Further investigation demonstrated that caveolin knockout up-regulated Akt-2 and Akt-3 isoform expression, but Akt-1 expression was down-regulated; interestingly, coimmunoprecipitation studies revealed Akt-1 as the predominant isoform to be phosphorylated in response to IGF-I. In summary, caveolin-1 deficiency promotes a hyperproliferative response to IGF-I that is unrelated to Akt expression/activation. However, cells that lack caveolin are able to respond appropriately to IGF-I through compensatory changes in Akt isoform expression. These data posit caveolin-1 as a component of the IGF/PI-3K/Akt signalling modulus regulating cellular proliferation with implications for diseases, including cancers, which have altered caveolin expression.
|
10.1210/en.2007-1211
|
pubmed_431_2143
|
A 47 year-old man, who had a history of pelvic radiotherapy for the treatment of testicular tumour 30 years ago, was referred with minor tissue loss of the right lower extremity, grade III, category 5 of the Rutherford classification. His groin region presented with severe radiation damage. Arteriography demonstrated the occlusion of external iliac and femoral arteries. Revascula-risation was performed in the lateral decubitus position, with a ringed polytetrafluoroethylene (PTFE) graft bypass between normal common iliac and popliteal arteries through the greater sciatic foramen. Quick healing was observed. Patient is well 6 months postoperatively. Immediate and 6 month postoperative imaging demonstrated the good patency of the graft. A duplex ultrasound performed 6 month postoperatively showed no significant compression while the patient was in the sitting position.
|
pubmed_431_2143
|
pubmed_6_1217
|
Methylsiloxanes (MSs) are a significant source of indoor environmental pollution due to their high production level and widespread application, and pose a potential health risk. Given the special vulnerability of children to environmental contaminants, assessment of indoor MSs exposure in children is quite essential. In this study, we assessed internal exposure doses and external exposure levels of MSs in children from industrial and residential areas in southwestern China. Indoor air, indoor dust, and personal care product (PCP) samples were collected to evaluate indoor non-dietary MSs exposure in children through various pathways. The concentrations of MSs in indoor environments of industrial areas were approximately one to four orders of magnitude higher than those of residential areas. Sun protection products contained the highest concentrations of MSs. Relatively high levels of cyclic methylsiloxanes (CMSs) were found in plasma of children from industrial areas, which were one to two orders of magnitude higher than those in children from residential areas. The highest MSs levels in plasma were detected in infants (0-1 year), with values of 1.4 × 102 ng/mL and 1.3 × 102 ng/mL for CMSs (D4-D6) and linear methylsiloxanes (LMSs) (L5-L16), respectively. The internal exposure dose of infants in residential areas is driven by major unknown sources of MSs. The average daily doses via inhalation and dust ingestion in children from industrial areas were one to three orders of magnitude higher than in those from residential areas, indicating that these children should be considered a highly exposed population. Inhalation and dust ingestion were both major exposure pathways to MSs for children of all age groups in industrial areas, whereas dermal absorption from PCPs was the predominant exposure pathway for children of all age groups in residential areas (except for infants). Although the exposure risk to D4 and D5 was at an acceptable level for all children studied, the total daily exposure doses of these two cyclic compounds via inhalation for infants in the industrial areas was near the chronic reference dose. Meanwhile, MSs may accumulate in infant plasma within a short period of time (<6 months). Therefore, infants should be the focus of greater attention in future research. As indoor environments may pose high risks for infants in industrial areas, they should be the focus of future research.
|
10.1016/j.envint.2021.106672
|
pubmed_34_4303
|
Bone graft substitutes often exhibit poor bone regeneration in large defects because of inadequate vascularization. Studies have shown that if blood supply is compromised, application of osteogenic factors alone could not induce successful healing. This study was to evaluate the effects of vascular endothelial growth factor, which combined with a coralline scaffold, on vascularization, scaffold resorption and osteogenesis in a rabbit radius critical size defect model. The scaffold was either coated with a control-plasmid DNA (group 1), coated with VEGF-plasmid DNA (group 2), loaded with mesenchymal stem cells (BMSC) transfected with control plasmid (group 3) or with both stem cells and the VEGF plasmid (group 4). X-rays were taken every 4 weeks up to week 16, when animals were euthanized. The volume of new bone was measured by mu-CT scans and blood vessels were counted after anti-CD31 staining of endothelial cells. The results from the solitary VEGF- and VEGF-transfected cells (groups 2 and 4) demonstrated significantly enhanced vascularization, osteogenesis and resorption of the carrier when compared to the control group. The highest degree of osteogenesis was found when the carrier was loaded with BMSC (group 3), whereas VEGF-transfected cells led to the highest vascularization and fastest resorption of the bone substitute. Additionally, VEGF-transfected BMSC led to a more homogenous vascularization of the defect. The results indicate that VEGF can be a helpful factor to improve healing in large bone defects, in which bone substitutes will otherwise not be vascularized and replaced by fresh bone.
|
10.1016/j.bone.2007.06.018
|
pubmed_179_13686
|
Pollination is provided by biodiversity and maintains global food production. We investigated the effects of vegetation cover on the abundance of floral visitor and vine (Vitis labrusca Raf.) production. We expected an increase in both floral visitor frequencies and vineyard yields with an increase in native vegetation cover in the landscape. We also investigated different scenarios of visitor abundance with and without honeybees (Apis mellifera L.). We surveyed floral visitors from ten vineyard plots with different native cover surrounding them and related both visitors and native vegetation to fruit set. Considering some of these vineyards, we compared physical and chemical traits of berries to understand how they vary according to native vegetation. Floral visitor abundance was positively related to native vegetation cover. However, considering only native bee abundance, we found a dual (hyperbolic) response. Apis mellifera (L.) Africanized was the most abundant species and had the highest number of interactions; however, when removed from the network analysis, the relationship between vineyards and native bees became more specialized. The fruit size and mass of berries differed among vineyards, as did some chemical traits related to commercial quality of fruits, such as soluble solids, pH and flavonoids. Vineyards surrounded by intermediate areas of native vegetation present a balance between resource availability from vineyards and native vegetation. Apis and non-Apis (such as flies and small bees) floral visitors, known to have different effects on vine pollination, could hypothetically provide variation in vine production and quality. Considering a near 20% native vegetation increment, there was an enhancement, on average, of ten-fold more berries per bunch, the changing physical and chemical fruit traits by vegetation increment could also increase the aggregate value of vines and the value of pollination services in the economy.
|
10.1111/plb.13327
|
pubmed_1_17838
|
BACKGROUND
As an increasing number of states liberalize cannabis use and develop laws and local policies, it is essential to better understand the impacts of neighborhood ecology and marijuana dispensary density on marijuana use, abuse, and dependence. We investigated associations between marijuana abuse/dependence hospitalizations and community demographic and environmental conditions from 2001 to 2012 in California, as well as cross-sectional associations between local and adjacent marijuana dispensary densities and marijuana hospitalizations.
METHODS
We analyzed panel population data relating hospitalizations coded for marijuana abuse or dependence and assigned to residential ZIP codes in California from 2001 through 2012 (20,219 space-time units) to ZIP code demographic and ecological characteristics. Bayesian space-time misalignment models were used to account for spatial variations in geographic unit definitions over time, while also accounting for spatial autocorrelation using conditional autoregressive priors. We also analyzed cross-sectional associations between marijuana abuse/dependence and the density of dispensaries in local and spatially adjacent ZIP codes in 2012.
RESULTS
An additional one dispensary per square mile in a ZIP code was cross-sectionally associated with a 6.8% increase in the number of marijuana hospitalizations (95% credible interval 1.033, 1.105) with a marijuana abuse/dependence code. Other local characteristics, such as the median household income and age and racial/ethnic distributions, were associated with marijuana hospitalizations in cross-sectional and panel analyses.
CONCLUSIONS
Prevention and intervention programs for marijuana abuse and dependence may be particularly essential in areas of concentrated disadvantage. Policy makers may want to consider regulations that limit the density of dispensaries.
|
pubmed_1_17838
|
pubmed_710_2996
|
One of the key challenges when developing magnesium rechargeable batteries (MRB) is to develop Mg-intercalation cathodes exhibiting higher redox potentials with larger specific capacities. Although Mg-transition-metal spinel oxides have been shown to be excellent candidates as MRB cathode materials by utilizing the valence change from trivalent to divalent of transition metals starting from Mg insertion, there is no clear evidence to date that Mg can be indeed extracted from the initial spinel hosts by utilizing the change from trivalent to quadrivalent. In this work, we clearly present various experimental evidences of the electrochemical extraction of Mg from spinel MgMn2O4. The present electrochemical charge, i.e., extraction treatment of Mg, was performed in an ionic liquid at 150 °C to ensure Mg hopping in the spinel host. Our analyses show that Mg can be extracted from Mg1-xMn2O4 up to x = 0.4 and, afterwards, successively be inserted into the Mg-extracted (demagnesiated) host via a two-phase reaction between tetragonal and cubic spinels. Finally, we also discuss the difference in electrochemical features between LiMn2O4 and MgMn2O4.
|
10.1039/c9cp04461b
|
pubmed_299_20095
|
PURPOSE OF REVIEW
Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic neurohypophysis. PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset. In this review, recent advances with respect to the cause of PSIS, clinical characteristics leading to earlier diagnosis, and management are outlined.
RECENT FINDINGS
Diagnosis of PSIS is often delayed probably because clinical findings such as neonatal hypoglycemia, cholestasis, and/or micropenis as well as decreasing growth velocity are not appropriately and timely validated. Recently, molecular defects in various genes have been associated with PSIS albeit in a small number of cases. These findings suggest that PSIS belongs to the spectrum of holoprosencephaly-related defects. Phenotype-genotype discordance and the existence of asymptomatic carriers of a given molecular aberration indicate that penetrance may be modified favorably or unfavorably by the presence of other genetic and/or environmental factors.
SUMMARY
PSIS constitutes an antenatal anatomical defect. Neonatal hypoglycemia, cholestasis, and/or micropenis with or without growth deficit should raise the possibility of combined pituitary hormone deficiency, a life-threatening condition in cases of coexisting cortisol deficiency. It is important to search for molecular defects in all PSIS cases, as precise identification of the cause is a prerequisite for genetic counseling.
|
10.1097/MOP.0000000000000378
|
pubmed_784_19387
|
Children evaluated by an interdisciplinary team that provided data on psychiatric disturbance, language handicaps, and psychoeducational assessment were placed in special education classes following the complete evaluation. Discriminant analysis as a special case of multiple regression analysis determined that mean reading achievement score, pre-evaluation classroom placement, and to a lesser degree, Performance IQ predicted classroom placement. Overall, correct classroom predictions approached 90 percent. These findings highlight the value of interdisciplinary evaluation to educators and mental health professionals.
|
10.1007/BF00709755
|
pubmed_103_276
|
BACKGROUND
To determine potential effects of autophagy activation on hypoxia-reoxygenation (H/R) induced damage of a rat alveolar epithelial cell line.
METHODS
CCL149 cells were subjected to autophagy agonist (rapamycin, Rap), autophagy inhibitor (3-methyladenine, 3-MA) or PBS for 1 h before H/R treatment for 2 h, 4 h and 6 h. The optimal concentration of Rap (150 nM, 200 nM and 250 nM) or 3-MA (5 mM, 10 mM and 15 mM) was obtained from MTT assay. Autophagy was determined by fluorescence microscopy of eRFP-LC3 positive cells, transmission electron microscopy of autophagosome, western blot of LC3, AMPK, Beclin-1, HDAC6 and p62 proteins. Endoplasmatic reticulum stress was indicated by detecting expressions of BIP, XBP-1 and CHOP via western blot.
RESULTS
Rap at concentration of 250 nM before H/R increased the autophagy formation with more eRFP-LC3 positive cells and higher expressions of LC3-II, Beclin-1, HDAC6 and p62, but lower expressions of BIP, XBP-1 and CHOP in H/R treated CCL149. This effect seemed to be still obvious after H/R exposure for 6 h. The contrary results were obtained by treatment with 5 mM 3-MA.
CONCLUSION
Rap might be a promising agent before mechanical ventilation or reperfusion to prevent re-damage in hypoxia related lung diseases.
|
10.1159/000455953
|
pubmed_924_1612
|
OBJECTIVES
Although anxiety exists concerning the perceived risk of transmission of bloodborne viruses after community-acquired needlestick injuries, seroconversion seems to be rare. The objectives of this study were to describe the epidemiology of pediatric community-acquired needlestick injuries and to estimate the risk of seroconversion for HIV, hepatitis B virus, and hepatitis C virus in these events.
METHODS
The study population included all of the children presenting with community-acquired needlestick injuries to the Montreal Children's Hospital between 1988 and 2006 and to Hôpital Sainte-Justine between 1995 and 2006. Data were collected prospectively at Hôpital Sainte-Justine from 2001 to 2006. All of the other data were reviewed retrospectively by using a standardized case report form.
RESULTS
A total of 274 patients were identified over a period of 19 years. Mean age was 7.9 +/- 3.4 years. A total of 176 (64.2%) were boys. Most injuries occurred in streets (29.2%) or parks (24.1%), and 64.6% of children purposely picked up the needle. Only 36 patients (13.1%) noted blood on the device. Among the 230 patients not known to be immune for hepatitis B virus, 189 (82.2%) received hepatitis B immunoglobulin, and 213 (92.6%) received hepatitis B virus vaccine. Prophylactic antiretroviral therapy was offered beginning in 1997. Of the 210 patients who presented thereafter, 82 (39.0%) received chemoprophylaxis, of whom 69 (84.1%) completed a 4-week course of therapy. The use of a protease inhibitor was not associated with a significantly higher risk of adverse effects or early discontinuation of therapy. At 6 months, 189 were tested for HIV, 167 for hepatitis B virus, and 159 for hepatitis C virus. There were no seroconversions.
CONCLUSIONS
We observed no seroconversions in 274 pediatric community-acquired needlestick injuries, thereby confirming that the risk of transmission of bloodborne viruses in these events is very low.
|
10.1542/peds.2008-0290
|
pubmed_220_13665
|
This article describes a qualitative study that examined the family centre public health role of health visitors and the child-centre public health role of school nurses. A telephone survey of key health visitor and school nurse informants in the West Midlands was undertaken. Respondents to the survey were asked to give examples of practice that related to Holman's (1992) public health typology. A wealth of data were obtained, which included 344 different examples of practice interventions. The majority of examples of practice given by the respondents were categorized as primary preventive interventions. The least represented concerned community empowerment and health protection. The findings of the survey give evidence of the current transitional nature health visitor and school nurse practice. Identified is some reorientation in practice and adoption of currently advocated models of public health, which have community participation, empowerment, and health protection as essential features.
|
10.12968/bjcn.2003.8.11.11819
|
pubmed_374_22590
|
BACKGROUND
Although many studies have suggested the association between elevated blood pressure and atrial fibrillation (AF), how the relationship between systolic blood pressure (SBP) and AF differ by antihypertensive treatment has been unclear. Therefore, this study aimed to explore the relationship between SBP and AF in hypertensive patients with or without antihypertensive treatment.
METHODS
This was a cross-sectional study that enrolled 7,808 hypertensive patients aged ≥18 years old in 2013 in Guangdong, China. AF was screened and diagnosed by rest 12-lead electrocardiogram (ECG) or by self-reported. Patients were categorized into 5 groups according to a 10 mmHg increment in SBP. We then performed logistic regression and restricted cubic spline regression to evaluate the relationship between SBP and AF.
RESULTS
Out of 7,808 participants (women 52.9%, mean age 62.3 years), 78 cases of AF were identified. Both univariate and multivariate logistic regression illustrated that SBP associated with a lower chance of AF in all participants when SBP was treated as a continuous variable (P<0.05) or as a categorical variable (P for trend <0.001). Similar trend was found in patients with antihypertensive therapy (P for trend <0.001) but not for those without antihypertensive medications.
CONCLUSIONS
Our findings suggested that higher SBP is associated with lower likelihood of AF among all hypertensive patients and participants with antihypertensive treatment.
|
10.21037/apm-19-649
|
pubmed_625_24699
|
The extent and pattern of glycosylation on therapeutic antibodies can influence their circulatory half-life, engagement of effector functions, and immunogenicity, with direct consequences to efficacy and patient safety. Hence, controlling glycosylation patterns is central to any drug development program, yet poses a formidable challenge to the bio-manufacturing industry. Process changes, which can affect glycosylation patterns, range from manufacturing at different scales or sites, to switching production process mode, all the way to using alternative host cell lines. In the emerging space of biosimilars development, often times all of these aspects apply. Gaining a deep understanding of the direction and extent to which glycosylation quality attributes can be modulated is key for efficient fine-tuning of glycan profiles in a stage appropriate manner, but establishment of such platform knowledge is time consuming and resource intensive. Here we report an inexpensive and highly adaptable screening system for comprehensive modulation of glycans on antibodies expressed in CHO cells. We characterize 10 media additives in univariable studies and in combination, using a design of experiments approach to map the design space for tuning glycosylation profile attributes. We introduce a robust workflow that does not require automation, yet enables rapid process optimization. We demonstrate scalability across deep wells, shake flasks, AMBR-15 cell culture system, and 2 L single-use bioreactors. Further, we show that it is broadly applicable to different molecules and host cell lineages. This universal approach permits fine-tuned modulation of glycan product quality, reduces development costs, and enables agile implementation of process changes throughout the product lifecycle.
|
10.1080/19420862.2018.1527665
|
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