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pubmed_554_18138 | Targeting and translocation of proteins to the appropriate subcellular compartments are crucial for cell organization and function. Newly synthesized proteins are transported to mitochondria with the assistance of complex targeting sequences containing either an N-terminal pre-sequence or a multitude of internal signals. Compared with experimental approaches, computational predictions provide an efficient way to infer subcellular localization of a protein. However, it is still challenging to predict plant mitochondrially localized proteins accurately due to various limitations. Consequently, the performance of current tools can be improved with new data and new machine-learning methods. We present MU-LOC, a novel computational approach for large-scale prediction of plant mitochondrial proteins. We collected a comprehensive dataset of plant subcellular localization, extracted features including amino acid composition, protein position weight matrix, and gene co-expression information, and trained predictors using deep neural network and support vector machine. Benchmarked on two independent datasets, MU-LOC achieved substantial improvements over six state-of-the-art tools for plant mitochondrial targeting prediction. In addition, MU-LOC has the advantage of predicting plant mitochondrial proteins either possessing or lacking N-terminal pre-sequences. We applied MU-LOC to predict candidate mitochondrial proteins for the whole proteome of Arabidopsis and potato. MU-LOC is publicly available at http://mu-loc.org. | 10.3389/fpls.2018.00634 |
pubmed_297_20649 | In general, biological macromolecules require significant dynamical freedom to carry out their different functions, including signal transduction, metabolism, catalysis and gene regulation. Effectors (ligands, DNA and external milieu, etc) are considered to function in a purely dynamical manner by selectively stabilizing a specific dynamical state, thereby regulating biological function. In particular, proteins in presence of these effectors can exist in several dynamical states with distinct binding or enzymatic activity. Here, we have reviewed the efficacy of ultrafast fluorescence spectroscopy to monitor the dynamical flexibility of various proteins in presence of different effectors leading to their biological activity. Recent studies demonstrate the potency of a combined approach involving picosecond-resolved Forster resonance energy transfer, polarisation-gated fluorescence and time-dependent stokes shift for the exploration of ultrafast dynamics in biomolecular recognition of various protein molecules. The allosteric protein-protein recognition following differential protein-DNA interaction is shown to be a consequence of some ultrafast segmental motions at the C-terminal of Gal repressor protein dimer with DNA operator sequences OE and OI. Differential ultrafast dynamics at the C-terminal of λ-repressor protein with two different operator DNA sequences for the protein-protein interaction with different strengths is also reviewed. We have also systemically briefed the study on the role of ultrafast dynamics of water molecules on the functionality of enzyme proteins alpha-chymotrypsin and deoxyribonuclease I. The studies on the essential ultrafast dynamics at the active site of the enzyme alpha-chymotrypsin by using an anthraniloyl fluorescent extrinsic probe covalently attached to the serine-195 residue for the enzymatic activity at homeothermic condition has also been reviewed. Finally, we have highlighted the evidence that a photoinduced dynamical event dictates the molecular recognition of a photochromic ligand, dihydroindolizine with the serine protease alpha-chymotrypsin and with a liposome (L-a-phosphatidylcholine). | pubmed_297_20649 |
pubmed_545_25624 | When current conditions are probabilistically less suitable for successful reproduction than future conditions, females may prevent or delay reproduction until conditions improve. Throughout human evolution, social support was likely crucial to female reproductive success. Women may thus have evolved fertility regulation systems sensitive to cues from the social environment. However, current understanding of how psychological phenomena might affect female ovarian function is limited. In this study, we examined whether cues of reduced social support-social ostracism-impact women's hormone production. Following an in-lab group bonding task, women were randomly assigned to a social exclusion (n = 88) or social inclusion (n = 81) condition. After social exclusion, women with low background levels of social support experienced a decrease in estradiol relative to progesterone. In contrast, socially-included women with low background social support experienced an increase in estradiol relative to progesterone. Hormonal changes in both conditions occurred specifically when women were in their mid-to-late follicular phase, when baseline estradiol is high and progesterone is low. Follow-up analyses revealed that these changes were primarily driven by changes in progesterone, consistent with existing evidence for disruption of ovarian function following adrenal release of follicular-phase progesterone. Results offer support for a potential mechanism by which fecundity could respond adaptively to the loss or lack of social support. | 10.1016/j.yhbeh.2021.104934 |
pubmed_182_10288 | BACKGROUND
Subcortical small vessel disease and vascular risk factors are associated with motor and cognitive impairment. In this study we examined the relationship between these factors and the severity of motor impairment and dementia in pathologically-confirmed Parkinson's disease (PD).
METHODS
The extent and severity of small vessel disease (SVD) was assessed pathologically in 77 patients with PD. The severity of motor impairment was determined using a cumulative index derived from longitudinal measures of Hoehn and Yahr score. The presence of dementia was scored using the Clinical Dementia Rating. The presence or absence of vascular risk factors and stroke were also recorded. Interactions were assessed using stepwise multiple regression analyses.
RESULTS
Significant correlations were demonstrated between perivascular pallor in the globus pallidus interna and the Hoehn and Yahr stage and between increasing Braak PD stage, the number of vascular risk factors and dementia. Among the vascular risk factors, hypertension was the only variable to independently correlate with dementia. SVD pathology did not correlate with dementia in our cohort.
CONCLUSIONS
This study demonstrates an association between SVD and motor impairment, and between vascular risk factors, particularly hypertension, and dementia in PD and highlights the need to manage vascular co-morbidities in PD patients. | 10.1016/j.jocn.2018.10.029 |
pubmed_178_2513 | Rat alveolar macrophages (AM) fused and formed multinucleated giant cells (MGC) when incubated with lymphokines released from mitogen-stimulated syngeneic lymphocytes. Several functions of these MGC populations were evaluated in vitro. MGC populations phagocytized opsonized sheep red blood cells to a lesser degree than unfused AM. The tumoricidal activity of MGC populations was compared with that of unfused AM after both populations had been treated with lipopolysaccharide (LPS) or lymphokines devoid of fusion factor activity. Results showed that MGC populations lost tumoricidal properties more rapidly than unfused AM. Treatment of MGC with LPS enhanced the production and release of lymphocyte-activating factor(s) (IL-1, interleukin 1) that augmented the blastogenic response of lymphocytes to phytohemagglutinin. These studies suggest that one possible function of MGC that lack phagocytic and tumoricidal properties may be in maintenance of granuloma formation by IL-1 production. | pubmed_178_2513 |
pubmed_678_20640 | The aim of this article was to obtain the application parameters and conditions of in situ sodium persulfate/calcium peroxide oxidation. For the purposes of remediation, soil from a total petroleum hydrocarbons (TPH)-contaminated site was collected and prepared to reflect the actual stratum condition in a newly developed soil remediation modeling apparatus. Application methods of soil mixture, natural infiltration, direct injection and groundwater circulation were used to simulate in situ sodium persulfate oxidation in TPH-contaminated soil. Results showed that the transfer capability of Na2S2O8 in simulated soil was strong Na2S2O8 migrated to the saturated layer after 3 days of in situ injection, which then continued both horizontal and vertical migration. After 7 days the oxidant was widespread in the saturated layer with a radius of influence of 0.4 m. It was found that mixing CaO2/Fe2+/CA with soil and spraying Na2S2O8 can effectively repair the surface-contaminated soil, and the longitudinal migration of Na2S2O8 in the reaction process can further strengthen the remediation of the upper layer soil. Due to the buffering effect of the soil, the effect of oxidation on the pH and temperature of different soil layers was small, but detectable in comparison to natural environmental factors. | 10.1080/09593330.2017.1296029 |
pubmed_873_16898 | Membranes are recognized as a key component in many environment and energy-related applications, but conventional membranes are challenged to satisfy the growing demand for ever more energy-efficient processes. Janus membranes, a novel class with asymmetric properties on each side, have recently emerged and represent enticing opportunities to address this challenge. With an inner driving force arising from their asymmetric configuration, Janus membranes are appealing for enhancing energy efficiency in a variety of membrane processes by promoting the desired transport. Here, the fundamental principles to prepare Janus membranes with asymmetric surface wettability and charges are summarized, and how they work in conventional and unconventional membrane processes is demonstrated. | 10.1002/adma.201801495 |
pubmed_812_10411 | The effect of ternary complexation of naproxen, a poorly water soluble anti-inflammatory drug, with hydroxypropyl-beta-cyclodextrin and the basic aminoacid L-arginine on the drug dissolution properties has been investigated. Equimolar binary (drug-cyclodextrin or drug-arginine) and ternary (drug-cyclodextrin-arginine) systems were prepared by blending, cogrinding, coevaporation, and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry. The dissolution behavior of naproxen from the different products was evaluated by means of a continuous flow through method. The results of solid state studies indicated the presence of strong interactions between the components in ternary coevaporated and coground systems, which were both of totally amorphous nature. In contrast, the presence of either free drug or free arginine was detected when the third component (cyclodextrin or aminoacid) was physically mixed, respectively, to the drug-arginine binary system (as physical mixture, coevaporate, or coground product) or to the drug-cyclodextrin binary system (as physical mixture, coevaporate, or coground product). All ternary combinations were significantly (P<0.001) more effective than the corresponding binary drug-cyclodextrin and drug-arginine systems in improving the naproxen dissolution rate. The best performance in this respect was given by the ternary coevaporate, with about 15 times increase in terms of both drug relative dissolution rate and dissolution efficiency. The synergistic effect of the simultaneous use of arginine and cyclodextrin on the dissolution rate of naproxen was attributed to the combined effects of inclusion in cyclodextrin and salt formation, as well as to a specific role played by arginine in this interaction. | 10.1016/j.ejpb.2004.05.005 |
pubmed_795_9888 | Volume loss following breast-conserving surgery (BCS) is the key reason for major local deformity and a bad cosmetic outcome. Latissimus dorsi miniflaps can be used to reconstruct central and upper quadrant resection defects, replacing the volume excised with autogenous tissue. Partial mastectomy, axillary dissection, flap harvest and reconstruction of the resection defect is performed as a one-stage procedure through a single lateral incision. This oncoplastic approach allows extensive local excision during BCS without cosmetic penalties in a group of patients normally treated by mastectomy. | 10.1053/ejso.2002.1350 |
pubmed_244_16722 | AIMS
Serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is known to be associated with cardiometabolic diseases. This study is aimed to evaluate the association between the TG/HDL-C ratio and incident type 2 diabetes with a large-sample, community-based Korean cohort over 12 years.
METHODS
Among 10,038 participants, a total of 8655 participants aged 40 to 69 years without diabetes were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline TG/HDL-C ratio was divided into quartiles. Newly developed type 2 diabetes was defined by any of the following: a fasting plasma glucose level ≥ 126 mg/dL; a glucose level ≥ 200 mg/dL 2-hours after a 75 g oral glucose tolerance test; an HbA1c ≥ 6.5%; or treatment with anti-diabetic therapy. The hazard ratios (HRs) with 95% confidence intervals (CIs) for incident type 2 diabetes were calculated using multivariate Cox proportional hazards regression models after adjusting for potentially confounding variables.
RESULTS
During the 12-year follow-up period, type 2 diabetes developed in 1437 subjects (16.6%, 1437/8655), with incidence rate of 2.8-5.0 (over 2 years). Compared to the reference first quartile, the HRs (95% CIs) of incident type 2 diabetes in the second, third, and fourth quartiles increased in a dose-response manner after adjusting for potentially confounding variables.
CONCLUSIONS
High TG/HDL-C ratio at baseline may be a useful surrogate indicator of future incident type 2 diabetes. | 10.1016/j.diabres.2020.108150 |
pubmed_886_3846 | We describe a 10-year-old boy who developed a pseudoaneurysm in the territory of the left hepatic artery after blunt trauma to the abdomen, which was prophylactically embolized. He was discharged early and was able to return to activities of daily life. In view of the potentially fatal complication of severe hemorrhage from a missed hepatic pseudoaneurysm rupture, recognition and early embolization of a traumatic pseudoaneurysm of hepatic artery are recommended. This decreases morbidity, mortality, and length of hospital stay and allows for early mobilization especially in children who are difficult to restrain in bed. | 10.1016/j.jpedsurg.2010.01.021 |
pubmed_74_288 | Two-dimensional (2D) layered transition metal dichalcogenides (TMDs) such as WS2 are promising materials for nanoelectronic applications. However, growth of the desired horizontal basal-plane oriented 2D TMD layers is often accompanied by the growth of vertical nanostructures that can hinder charge transport and, consequently, hamper device application. In this work, we discuss both the formation and suppression of vertical nanostructures during plasma-enhanced atomic layer deposition (PEALD) of WS2. Using scanning transmission electron microscopy studies, formation pathways of vertical nanostructures are established for a two-step (AB-type) PEALD process. Grain boundaries are identified as the principal formation centers of vertical nanostructures. Based on the obtained insights, we introduce an approach to suppress the growth of vertical nanostructures, wherein an additional step (C)-a chemically inert Ar plasma or a reactive H2 plasma-is added to the original two-step (AB-type) PEALD process. This approach reduces the vertical nanostructure density by 80%. It was confirmed that suppression of vertical nanostructures goes hand in hand with grain size enhancement. The vertical nanostructure density reduction consequently lowers film resistivity by an order of magnitude. Insights obtained in this work can contribute toward devising additional pathways, besides plasma treatments, for suppressing the growth of vertical nanostructures and improving the material properties of 2D TMDs that are relevant for nanoelectronic device applications. | 10.1021/acsami.9b19716 |
pubmed_81_15332 | OBJECTIVES
Traumatic brain injury is a leading cause of death in children. On the basis of evidence of better outcomes, the American College of Surgery Committee on Trauma recommends that children with severe traumatic brain injury receive care at high-level trauma centers. We assessed rates of adherence to these recommendations and factors associated with adherence.
METHODS
We studied population and hospital discharge data from 2001 from all of the health care referral regions (n = 68) in 6 US states (Florida, Massachusetts, New Jersey, New York, Texas, and Virginia). We identified children with severe traumatic brain injury by using International Classification of Diseases, Ninth Revision, Clinical Modification, codes and American College of Surgery Committee on Trauma criteria. We defined "high-level centers" as either level I or pediatric trauma centers. We considered an area to be well regionalized if >or=90% of severe traumatic brain injury hospitalizations were in high-level centers. We also explored how use of level II trauma centers affected rates of care at high-level centers.
RESULTS
Of 2117 admissions for severe pediatric traumatic brain injury, 67.3% were in high-level centers, and 87.3% were in either high-level or level II centers. Among states, 56.4% to 93.6% of severe traumatic brain injury admissions were in high-level centers. Only 2 states, Massachusetts and Virginia, were well regionalized. Across health care referral regions, 0% to 100% of severe traumatic brain injury admissions were in high-level centers, and only 19.1% of health care referral regions were well regionalized. Only a weak relationship existed between the distance to the nearest high-level center and regionalization. The age of statewide trauma systems had no relationship to the extent of regionalization.
CONCLUSIONS
Despite evidence for improved outcomes of severely injured children admitted to high-level trauma centers, we found that almost one third of the children with severe traumatic brain injury failed to receive care in such centers. Only 2 of 6 states and less than one fifth of 68 health care referral regions were well regionalized. This study highlights problems with current pediatric trauma care that can serve as a basis for additional research and health care policy. | 10.1542/peds.2007-3399 |
pubmed_935_10561 | Human meiotic chromosomes, from spermatocytes and ovocytes, are described after observations of whole mount preparations under E.M. Small testicular and ovarian fragments are put in distillated water, then macerated; the cell suspension is spread on the surface of sheet copper grids covered with formvar plus collodion films. After dehydratation interesting stages are selected under L.M. before observations under E.M. Zygotene and pachytene are the most common stages. During pachytene the chromomeres are well individualized; the synaptonemal complex may be observed; chromatin fibers connect the chromosomes to nuclear pores, interchromosomal fibers joint the bivalents. Zygotene and pachytene bivalents are very similar in the male and the feminine germ cells. | 10.1007/BF00287051 |
pubmed_1020_5041 | Purpose
To determine whether the neutrophil-to-lymphocyte ratio (NLR) aids in the detection of obstructive sleep apnea (OSA) in patients with type B aortic dissection (TBAD).
Methods
324 patients with TBAD or type B aortic intramural hematoma (TB-AIMH) underwent an overnight sleep study. We divided the eligible 256 studied subjects into three groups: group A (n = 109, TBAD patients with OSA), group B (n = 68, TB-AIMH patients with OSA), and group C (n = 79, TBAD patients without OSA). Baseline characteristics, biochemical and sleep parameters, and STOP-Bang questionnaire scores were collected. To assess the predictive efficacy of potential variables, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used.
Results
The study found that about 58% of TBAD patients and 54% of TB-AIMH patients had OSA, a majority of whom had moderate to severe OSA (95.41% and 89.71%, respectively). In the comparison of sleep parameters between patients with TBAD and TB-AIMH, no other than apnea and hypopnea index (AHI) made a significant difference. The multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratio (NLR) (odds ratio (OR): 3.614, 95% confidence interval (CI): 2.273-5.748, and P < 0.05) and STOP-Bang scores (OR: 1.97, 95% CI: 1.34-2.90, and P < 0.05) were both independent predictors for OSA in patients with TBAD. ROC curves showed NLR had higher sensitivity (65% versus 59%) and specificity (86% versus 57%) for OSA than the STOP-Bang questionnaire. Furthermore, NLR was positively correlated with AHI through the Spearman test (r = 0.398 and P < 0.05).
Conclusion
NLR was an independent predictor of OSA in TBAD patients with higher sensitivity and specificity than the STOP-Bang questionnaire, and it was positively associated with AHI. NLR may aid in the diagnosis and risk stratification of OSA in TBAD patients. | 10.1155/2021/8492468 |
others_148_3120 | The compatibility of glucose-6-phosphatedehydrogenase, glutamatedehydrogenase, malatedehydrogenase (MDH) and a proteolytic enzyme isolated from Tetraselmis (Platymonas) subcordiformis with organic and inorganic solutes was tested in vitro. Only MDH showed considerable NaCl-sensitivity. All four enzymes exhibited no or only little inhibition of activity in the presence of up to 100 mM DMSP-Cl. MDH was further characterized. MDH hydrating activity under substrate saturation was equally inhibited by 100 mM NaCl or DMSP-Cl. Activity rates at low oxalacetate concentrations in the presence of DMSP-Cl or equimolar NaCl were also reduced compared with controls without additional solutes. However, DMSP-Cl was less inhibitory than NaCl. The inhibition by NaCl was also mitigated by increasing substrate concentration. The ratio of reducing to oxidizing MDH-activity was altered by NaCl from 7 with no NaCl present to 28 at 500 mM NaCl. DMSP-Cl (200 mM) altered this ratio to a lesser degree than equimolar NaCl. A possible regulation mechanism of MDH is altered by NaCl but not by DMSP-Cl. It is proposed that NaCl inhibits MDH-activity and alters regulation of the enzyme by malate. Presence of DMSP-Cl or increased substrate levels can minimize these effects. © 1991, Gustav Fischer Verlag, Stuttgart. All rights reser | 10.1016/S0176-1617(11)80735-2 |
pubmed_629_24509 | In vertebrates, the endocannabinoid signaling pathway is an important lipid regulatory pathway that modulates a variety of physiological and behavioral processes. N-Acylethanolamines (NAEs) comprise a group of fatty acid derivatives that function within this pathway, and their signaling activity is terminated by an enzyme called fatty acid amide hydrolase (FAAH), which hydrolyzes NAEs to ethanolamine and their corresponding free fatty acids. Bioinformatic approaches led to the identification of plant homologues of FAAH that are capable of hydrolyzing NAEs in vitro. To better understand the role of NAEs in plants, we identified T-DNA knockouts to Arabidopsis FAAH (AtFAAH; At5g64440) and generated plants overexpressing AtFAAH. Here we show that seeds of AtFAAH knockouts had elevated levels of endogenous NAEs, and seedling growth was hypersensitive to exogenously applied NAE. On the other hand, seeds and seedlings of AtFAAH overexpressors had lower endogenous NAE content, and seedlings were less sensitive to exogenous NAE. Moreover, AtFAAH overexpressors displayed enhanced seedling growth and increased cell size. AtFAAH expression and FAAH catalytic activity increased during seed germination and seedling growth, consistent with the timing of NAE depletion during seedling establishment. Collectively, our results show that AtFAAH is one, but not the only, modulator of endogenous NAE levels in plants, and that NAE depletion likely participates in the regulation of plant growth. | 10.1073/pnas.0603571103 |
pubmed_564_14562 | Changes of lipopolysaccharide (LPS) of Coxiella burnetii strain Priscilla during chick embryo yolk sac passaging were observed by SDS-PAGE and immunoblot analysis. The course of LPS phase variation was similar to that found in other C. burnetti strains, i.e. a conversion of the phase I to the intermediate phase II after 10 passages. The intermediate phase II LPS of Priscilla strain was also detectable by immunoblot analysis using immune serum against Priscilla strain in the 30th passage. | 10.1111/j.1574-6968.1993.tb06528.x |
pubmed_836_24261 | OBJECTIVE
To determine if there is a difference in the perception of pain and functional disability between African Americans and Whites at any given radiographic severity of osteoarthritis (OA). Ethnic differences in utilization of joint replacement may reflect differences in the perception of symptoms of OA.
METHODS
A cross-sectional survey included 596 male veterans (44% African Americans and 56% Whites) with chronic moderate to severe knee and/or hip pain at the General Medicine Clinics. The average age of the total cohort was 65.63 +/- 9.5 years. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain and function were the primary outcome measures of interest. All knee and or hip radiographs were graded using the Kellgren-Lawrence (K/L) grading system.
RESULTS
African Americans and Whites were comparable with respect to age (65 +/- 9.5 vs 66 +/- 9, respectively); body mass index > or = 30 kg/m2 (53.9% vs 58.8%); Lequesne severity score (11 +/- 4 vs 11 +/- 4); geriatric depression score (4.5 +/- 3.3 vs 5.0 +/- 3.8) and Charlson Comorbidity Index (2.3 +/- 2 vs 2.5 +/- 2). African Americans had lower socioeconomic status with fewer high school graduates (57% vs 71%, p = 0.001), lower employment rate (8.4% vs 14.7%, p = 0.017), and lower total household incomes (41.4% vs 20.4% reported income < $10,000, p = 0.000). African Americans and Whites were not different in mean scores for WOMAC pain and WOMAC function when stratified by joint space narrowing, osteophyte and Kellgren Lawrence grades. After controlling for important covariates, ethnicity was not a significant predictor of WOMAC pain and function.
CONCLUSION
In this sample of male veterans, African Americans and Whites perceived the same degree of pain and functional difficulties at any given radiographic severity of OA. Differences in the perception of symptoms cannot explain the observed ethnic disparity in utilization of joint replacement. | pubmed_836_24261 |
pubmed_9_2443 | Sugar-3-phosphates are related to aspects of diabetes which depend on protein glycosylation events. Sorbitol-3-phosphate and fructose-3-phosphate occur in normal and diabetic individuals, and glucose-3-phosphate is a potential intermediate in their biosynthesis. Almost nothing is known about enzyme pathways for their metabolic turnover. We have found that part of the phosphohydrolytic activity on glucose-3-phosphate in rat liver supernatants corresponds to a specific, Mg(2+)-dependent, glucose-3-phosphatase much less or not active on other phosphate esters, including glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, fructose-6-phosphate and p-nitrophenyl-phosphate. This finding opens a route to a better understanding of the metabolism and role of sugar-3-phosphates. | 10.1016/0014-5793(94)80383-8 |
pubmed_1077_7209 | We address the problem of removing video color tone jitter that is common in amateur videos recorded with hand-held devices. To achieve this, we introduce color state to represent the exposure and white balance state of a frame. The color state of each frame can be computed by accumulating the color transformations of neighboring frame pairs. Then, the tonal changes of the video can be represented by a time-varying trajectory in color state space. To remove the tone jitter, we smooth the original color state trajectory by solving an L1 optimization problem with PCA dimensionality reduction. In addition, we propose a novel selective strategy to remove small tone jitter while retaining extreme exposure and white balance changes to avoid serious artifacts. Quantitative evaluation and visual comparison with previous work demonstrate the effectiveness of our tonal stabilization method. This system can also be used as a preprocessing tool for other video editing methods. | 10.1109/TIP.2014.2358880 |
pubmed_715_20387 | Salvia miltorrhiza Bunge is a traditional Chinese medicine and has long been used for treating liver and heart diseases in China. Salvianic acid A is the main active component of Salvia miltorrhiza Bunge. In the present study, the ability of salvianic acid A in scavenging free radicals, inhibiting lipid peroxidation and mitochondrial membrane permeability transition, as well as respiration and protein thiol oxidation in rat liver mitochondria, was evaluated. The results show that salvianic acid A scavenges superoxide anions in a dose-dependent manner (IC50 52 microg/ml). Salvianic acid A could scavenge lipid free radicals and inhibit lipid peroxidation as effectively as Vitamin E. Salvianic acid A also inhibited the mitochondrial membrane permeability transition assessed as the extent of mitochondrial swelling. Salvianic acid A inhibited the oxidation of mitochondrial protein thiols involved in the mitochondrial membrane permeability transitions. We conclude that salvianic acid A is able to reduce lipid peroxidation in the mitochondrial membrane by scavenging free radicals, and inhibit mitochondrial membrane permeability transition by reducing protein thiol oxidation. These data indicated the pharmacological potential of salvianic acid A against pathological processes related to oxidative stress. | 10.1016/j.jep.2004.11.036 |
pubmed_626_19423 | We have measured the influence of mesoporous silica (MCM-41 and SBA-15) nanoparticles and dense silica nanoparticles on epinephrine oxidation, a pH-dependent reaction, whose rate is small in acidic or neutral solutions but much greater at higher pH. The reaction was measured by monitoring adrenochrome at 480 nm, the product of epinephrine oxidation. In distilled water (dH(2)O) with no particles present, the oxidation of epinephrine occurs slowly but more rapidly at higher pH. The presence of MCM-41 or silica spheres does not accelerate the oxidation, but SBA-15 does, showing that the difference in the structures of nanomaterials leads to differing effects on the epinephrine oxidative process. In phosphate buffered saline (PBS, pH = 7.4), epinephrine undergoes a much quicker oxidation, and, in this case, the presence of SBA-15 and MCM-41 makes it even more rapid. Silica spheres have no noticeable influence on the oxidation in PBS or in dH(2)O. The possibility that the catalytic effect of mesoporous silica nanoparticles (MSN) could result from the residue of templating chemicals, however, can be excluded due to the postsynthesis calcinations. Experiments with dithionite, added either earlier than or at the same time as the epinephrine addition, show that fast oxidation takes place only when dithionite and epinephrine are simultaneously added into PBS solution. This confirms a vital role of oxygen radicals (probably *O(2)(-)) in the oxidation of epinephrine. These oxygen radicals are likely to form and accumulate within the phosphate buffer or in the presence of MSN. Comparing the three kinds of silica nanoparticles applied, we note that mesoporous SBA-15 and MCM-41 materials own much larger surface area than solid silica particles do, whereas MCM-41 possesses a much narrower pore size (0.4-fold) than SBA-15. It seems, therefore, that large surface area, characteristic mesoporosity, and surface structures aid in the deposit of oxygen radicals inside MSN particles, which catalyze the epinephrine oxidation in a favorable phosphate environment. | 10.1021/la900958f |
pubmed_58_8649 | BACKGROUND
This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners.
METHODS
The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline.
DISCUSSION
The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations.
TRIAL REGISTRATION
NCT02672150 . Retrospectively registered on 22 January 2016. | 10.1186/s40352-018-0068-3 |
pubmed_761_10877 | Pediatric feeding disorders (PFDs) lack a universally accepted definition. Feeding disorders require comprehensive assessment and treatment of 4 closely related, complementary domains (medical, psychosocial, and feeding skill-based systems and associated nutritional complications). Previous diagnostic paradigms have, however, typically defined feeding disorders using the lens of a single professional discipline and fail to characterize associated functional limitations that are critical to plan appropriate interventions and improve quality of life. Using the framework of the World Health Organization International Classification of Functioning, Disability, and Health, a unifying diagnostic term is proposed: "Pediatric Feeding Disorder" (PFD), defined as impaired oral intake that is not age-appropriate, and is associated with medical, nutritional, feeding skill, and/or psychosocial dysfunction. By incorporating associated functional limitations, the proposed diagnostic criteria for PFD should enable practitioners and researchers to better characterize the needs of heterogeneous patient populations, facilitate inclusion of all relevant disciplines in treatment planning, and promote the use of common, precise, terminology necessary to advance clinical practice, research, and health-care policy. | 10.1097/MPG.0000000000002188 |
pubmed_326_1991 | Current theories of sexual differentiation maintain that ovarian estrogen prevents masculine development of the copulatory system in birds, whereas estrogen derived from testicular androgens promotes masculine sexual differentiation of neuroanatomy and sexual behavior in mammals. Paradoxically, some data suggest that the neural song system in zebra finches follows the mammalian pattern with estrogenic metabolites of testicular secretions causing masculine development. To test whether the removal of estrogen from males during early development would prevent the development of masculine song systems, zebra finches were treated embryonically with an inhibitor of estrogen synthesis. In addition, this treatment in genetic female zebra finches induced both functional ovarian and testicular tissue to develop, thus allowing the assessment of the direct effects of testicular secretions on song system development. In males, the inhibition of estrogen synthesis before hatching had a small but significant effect in demasculinizing one aspect of the neural song system. In treated females, the song systems remained morphologically feminine. These results suggest that masculinization of the song system is not determined solely by testicular androgens or their estrogenic metabolites. | 10.1073/pnas.93.11.5264 |
pubmed_92_12810 | In this paper, we present a unified statistical framework for modeling both saccadic eye movements and visual saliency. By analyzing the statistical properties of human eye fixations on natural images, we found that human attention is sparsely distributed and usually deployed to locations with abundant structural information. This observations inspired us to model saccadic behavior and visual saliency based on super-Gaussian component (SGC) analysis. Our model sequentially obtains SGC using projection pursuit, and generates eye movements by selecting the location with maximum SGC response. Besides human saccadic behavior simulation, we also demonstrated our superior effectiveness and robustness over state-of-the-arts by carrying out dense experiments on synthetic patterns and human eye fixation benchmarks. Multiple key issues in saliency modeling research, such as individual differences, the effects of scale and blur, are explored in this paper. Based on extensive qualitative and quantitative experimental results, we show promising potentials of statistical approaches for human behavior research. | 10.1109/TIP.2014.2337758 |
pubmed_30_15390 | A massive cerebral release of amino acids and ammonia was found in early-onset dementia of Alzheimer type. Aspartate and glycine were liberated in high concentrations, whereas glutamate remained rather unchanged. This excess cerebral protein catabolism is due to a 44% reduction in cerebral glucose metabolism. Whereas glutamate and other glucoplastic amino acids may substitute glucose, elevated aspartate may contribute to neuronal damage. The results are discussed with respect to a possible neuronal insulin/insulin receptor deficiency. | 10.1007/BF01258634 |
pubmed_121_16064 | Background
The COVID-19 pandemic has given rise to more virtual simulation training. This study aimed to review the effectiveness of virtual simulations and their design features in developing clinical reasoning skills among nurses and nursing students.
Method
A systematic search in CINAHL, PubMed, Cochrane Library, Embase, ProQuest, PsycINFO, and Scopus was conducted. The PRISMA guidelines, Cochrane's risk of bias, and GRADE was used to assess the articles. Meta-analyses and random-effects meta-regression were performed.
Results
The search retrieved 11,105 articles, and 12 randomized controlled trials (RCTs) were included. Meta-analysis demonstrated a significant improvement in clinical reasoning based on applied knowledge and clinical performance among learners in the virtual simulation group compared with the control group. Meta-regression did not identify any significant covariates. Subgroup analyses revealed that virtual simulations with patient management contents, using multiple scenarios with nonimmersive experiences, conducted more than 30-minutes and postscenario feedback were more effective.
Conclusions
Virtual simulations can improve clinical reasoning skill. This study may inform nurse educators on how virtual simulation should be designed to optimize the development of clinical reasoning. | 10.1016/j.ecns.2022.05.006 |
pubmed_529_24869 | Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events. These AF patients may be denied oral anticoagulants, whilst evidence shows that the absolute benefits of oral anticoagulants are greatest in patients at highest risk. NOACs are an alternative to VKAs to prevent stroke in patients with "non-valvular AF", and NOACs may offer a greater net clinical benefit compared with VKAs, particularly in these high-risk patients. Physicians have to learn how to use these drugs optimally in specific settings. We review concrete clinical scenarios for which practical answers are currently proposed for use of NOACs based on available evidence for patients with kidney disease, elderly patients, women, patients with diabetes, patients with low or high body weight, and those with valve disease. | 10.1007/s12325-017-0550-7 |
pubmed_1019_14578 | We present a systematic investigation of the accuracy of the various theories and basis sets that can be applied to study the interaction of Cl(-) ions with Ar atoms. It is conclusively shown that gaseous ion mobility can distinguish among theoretical ion-neutral interaction potentials. Based on the conclusions, high-level ab initio potential energy curves are obtained for all of the Cl(-)-RG (RG = He-Rn) complexes. Spectroscopic constants have been derived from these potentials and are compared to a range of theoretical and experimental data, to which they generally show good agreement. General trends are discussed in comparison to other halogen-rare gas complexes previously studied. The potentials also have been tested by using them to calculate transport coefficients for Cl(-) moving through a bath of RG atoms. | 10.1063/1.3598472 |
pubmed_988_1055 | Over the past ten years the evolution of medical x-ray films has been toward films with reduced intensifying-screen light crossover in order to reduce blur and obtain higher spatial resolution. For films with very low crossover, misleading and incorrect sensitometric data may be obtained for film contrast evaluation and processor control if a simulated light sensitometer with a single-sided, light-exposing device is used. Screen light exposures were made using an inverse square, intensity-scale sensitometer. Simulated light exposures were made using a widely used single-sided, simulated-light sensitometer commonly used for film processor quality control, and a new simulated-light sensitometer capable of producing either single- or double-sided sensitometric exposures. The films used included one single-emulsion film and three double-emulsion medical x-ray films with light-crossover values ranging from approximately 3% to 30%. Sensitometric data showed a significant distortion (bump) in the characteristic curve for the 3% light-crossover film exposed with the single-sided, simulated-light sensitometer. | 10.1118/1.596468 |
pubmed_656_24571 | The new heart transplantation (HT) allocation policy was introduced on 10/18/2018. Using the UNOS registry, we examined early outcomes following HT for restrictive cardiomyopathy, hypertrophic cardiomyopathy, cardiac sarcoidosis, or cardiac amyloidosis compared to the old system. Those listed who had an event (transplant, death, or waitlist removal) prior to 10/17/2018 were in Era 1, and those listed on or after 10/18/2018 were in Era 2. The primary endpoint was death on the waitlist or delisting due to clinical deterioration. A total of 1232 HT candidates were included, 855 (69.4%) in Era 1 and 377 (30.6%) in Era 2. In Era 2, there was a significant increase in the use of temporary mechanical circulatory support and a reduction in the primary endpoint, (20.9 events per 100 PY (Era 1) vs. 18.6 events per 100 PY (Era 2), OR 1.98, p = .005). Median waitlist time decreased (91 vs. 58 days, p < .001), and transplantation rate increased (119.0 to 204.7 transplants/100 PY for Era 1 vs Era 2). Under the new policy, there has been a decrease in waitlist time and waitlist mortality/delisting due to clinical deterioration, and an increase in transplantation rates for patients with infiltrative, hypertrophic, and restrictive cardiomyopathies without any effect on post-transplant 6-month survival. | 10.1111/ctr.14109 |
pubmed_298_15148 | BACKGROUND
Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial.
METHODS
The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association between colonoscopy findings and aspirin, statin, or aspirin/statin use.
RESULTS
In our total population including all races, aspirin user had an increased risk for having two or more adenomas (OR =1.73, 95% CI: 1.00, 2.99, P=0.05) and presence of an adenoma in the proximal colon (OR =1.66, 95% CI: 1.07, 2.58, P=0.02). In the total study population, those who used both statin and aspirin had an increased risk for having two or more adenomas (OR =2.56, 95% CI: 1.21, 5.39, P=0.01). In the Hispanic population, users of both medications had an increased risk for having two or more adenomas (OR =19.04, 95% CI: 1.30, 280.09, P=0.03), adenoma present in the distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01) and largest adenoma in distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01).
CONCLUSIONS
Aspirin use and aspirin/statin use was associated with abnormal colonoscopy findings, particularly in the Hispanic population. These findings may be due to environmental factors such as dietary, colonic flora, or genetic susceptibility. The findings warrant further investigational research, particularly in Hispanics. | 10.3978/j.issn.2078-6891.2014.010 |
pubmed_614_11744 | Mesenchymal stem cells (MSCs) have drawn much attention amongst stem cell researchers in the past few decades. The ability of the MSC to differentiate into cells of mesodermal and non-mesodermal origins has made them an attractive approach for cell-based therapy and regenerative medicine. The MSCs have immunosuppressive activities that may have considerable therapeutic values in autoimmune diseases. However, despite the many beneficial effects reported, there is a growing body of evidence, which suggests that MSCs could be a culprit of enhanced tumour growth, metastasis and drug resistance in leukaemia, via some modulatory effects. Many controversies regarding the interactions between MSCs and leukaemia still exist. Furthermore, the role of MSCs in leukemogenesis and its progression remain largely unknown. Hence it is important to understand how the MSCs modulate leukaemia before these cells could be safely used in the treatment of leukaemia patients. | pubmed_614_11744 |
pubmed_573_10994 | Cartilaginous tumours of the extremities are commonly seen in radiographs. Enchondroma is the most frequently encountered tumour. Since the vast majority of enchondromas are asymptomatic, they are typically discovered as incidental findings or along with a pathologic fracture. The authors propose a pictorial review to illustrate the imaging features of cartilaginous bone lesions of the hand and their specificities, and discuss the main differential diagnoses. | pubmed_573_10994 |
pubmed_653_11777 | Mania and hypomania involve dysfunctional beliefs about the self, others, and the world, as well about affect regulation. The present study explored the impact of these beliefs on self-defining memories and self-defining future projections of individuals with a history of hypomanic symptoms. The main findings showed that a history of hypomanic symptoms was related to enhanced retrieval of memories describing positive relationships and to reduced future projections about relationships, suggesting both a need for social bonding and a striving for autonomy. Moreover, hypomania-prone individuals tended to describe more recent events and to produce self-defining memories with references to tension that were more integrated in their self-structure. All of these findings support the presence of conflicting dysfunctional beliefs and the importance of memories containing references to tension in hypomania. | 10.1016/j.concog.2012.02.007 |
pubmed_536_12344 | Production of singlet molecular oxygen ((1)O(2)) in the aerobic oxidation of ascorbic acid catalyzed by copper ion was measured and characterized using [4'-(9-anthryl)-2,2':6',2''-terpyridine-6,6''-diyl]bis(methylenenitrilo)tetrakis(acetate)-Eu(3+) (ATTA-Eu(3+)) as a highly sensitive and selective time-resolved luminescence probe for (1)O(2). The (1)O(2) produced in the reaction was further characterized and confirmed by (i) chemical trapping of (1)O(2) with 9,10-diphenylanthracene (DPA), the corresponding endoperoxide was detected by HPLC and (ii) spin trapping of (1)O(2) with 2,2,6,6-tetramethyl-4-piperidinol (TMP-OH), the corresponding free radical of TMP-OH oxide (TMPO) was detected by electron spin resonance (ESR) spectroscopy. The effects of deuterium oxide, sodium azide and histidine on the (1)O(2) signal were investigated. The mechanism investigation of (1)O(2) production implied that the ascorbic acid-Cu(I) complex formed in the reaction could be an important intermediate for the (1)O(2) production. The reaction of ascorbic acid with copper ion monitored by (1)H NMR and absorption spectroscopy demonstrated the formation of a copper ion-ascorbic acid complex. Except for Cu(2+) and Cu(+)-ascorbic acid systems, no detectable (1)O(2) was produced in other transition metal cation-ascorbic acid systems in the studied range. | 10.1016/j.talanta.2006.10.021 |
others_173_9885 | The objective of this study was to assess the diagnostic accuracy of C-reactive protein (CRP), procalcitonin (PCT), and cellular immune markers levels in sepsis. This was a prospective observational study in adult intensive care unit (ICU) patients, between 2012 and 2014. The 8-color flow cytometric biomarker panel included CD64, CD163, and HLA-DR. Index test results were compared with sepsis, using receiver operating characteristic curve analyses. Multivariate logistic regression assessed the relationship of sets of markers with the probability of sepsis. Of 219 enrolled patients, 120 had sepsis. C-statistic was the highest for CRP (0.86) followed by neutrophil CD64 expression (0.83), procalcitonin (0.82), and Acute Physiology and Chronic Health Evaluation (APACHE) IV (0.72). After adjustment for APACHE IV, the combination of CRP, PCT, and neutrophil CD64 measure remained a significant predictor of sepsis with an excellent AUC (0.90). In a targeted ICU population at increased risk of sepsis, CRP, PCT, and neutrophil CD64 combined improve the diagnostic accuracy of sepsis. © 2016 Elsevier I | 10.1016/j.diagmicrobio.2015.10.003 |
pubmed_306_16769 | Aberrant activation of fibroblast growth factor receptors (FGFR) contributes to breast cancer growth, progression, and therapeutic resistance. Because of the complex nature of the FGF/FGFR axis, and the numerous effects of FGFR activation on tumor cells and the surrounding microenvironment, the specific mechanisms through which aberrant FGFR activity contributes to breast cancer are not completely understood. We show here that FGFR activation induces accumulation of hyaluronan within the extracellular matrix and that blocking hyaluronan synthesis decreases proliferation, migration, and therapeutic resistance. Furthermore, FGFR-mediated hyaluronan accumulation requires activation of the STAT3 pathway, which regulates expression of hyaluronan synthase 2 (HAS2) and subsequent hyaluronan synthesis. Using a novel in vivo model of FGFR-dependent tumor growth, we demonstrate that STAT3 inhibition decreases both FGFR-driven tumor growth and hyaluronan levels within the tumor. Finally, our results suggest that combinatorial therapies inhibiting both FGFR activity and hyaluronan synthesis is more effective than targeting either pathway alone and may be a relevant therapeutic approach for breast cancers associated with high levels of FGFR activity. In conclusion, these studies indicate a novel targetable mechanism through which FGFR activation in breast cancer cells induces a protumorigenic microenvironment. | 10.1158/0008-5472.CAN-13-2469 |
pubmed_989_13738 | Through early and proactive laboratory testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes novel coronavirus 2019, Taiwan has demonstrated an efficient and rapid control response to contain the outbreak. Two days after the World Health Organization announced the complete viral genome sequence, the national laboratory of the Taiwan Centers for Disease Control developed a specific real-time reverse transcription polymerase chain reaction (real-time RT-PCR) test for SARS-CoV-2. The national laboratory network was further strengthened through the recruitment of medical centers and regional hospitals distributed throughout most geographical regions of the country. Ultimately, a network of 60 laboratories with a capacity of 7,342 real-time RT-PCR tests per day was established. Between January 14 and August 5, 2020, a total of 158,772 tests were conducted, corresponding to 120,487 cases. Test results were obtained within 24 hours, enabling an efficient and rapid control response. | 10.1089/hs.2020.0056 |
pubmed_311_10587 | Necrostatin-1 (Nec-1) is a specific small molecule inhibitor of receptor-interacting protein kinase 1 (RIPK1) that specifically inhibits phosphorylation of RIPK1. RIPK1 regulates inflammation and cell death by interacting with receptor-interacting serine/threonine protein kinases 3(RIPK3). We hypothesized that Nec-1 may have anti-inflammatory efficacy in patients with osteoarthritis (OA), as the pathophysiology of OA involves the activation of inflammation-related signaling pathways and apoptosis. In this study, we explored the effects of Nec-1 on interleukin (IL)-1β-induced inflammation in mouse chondrocytes and the destabilised medial meniscus (DMM) mouse model. Inhibiting RIPK1 with Nec-1 dramatically suppressed catabolism both in vivo and in vitro, but did not inhibit changes in subchondral bone. Nec-1 abolished the in vitro increases in matrix metalloproteinase (MMP) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTs5) expression induced by IL-1β. However, adding high-mobility group box 1 (HMGB1) partially abrogated this effect, indicating the essential role of HMGB1 and Nec-1 in the protection of primary chondrocytes. Furthermore, Nec-1 decreased the expression of Toll-like receptor 4 (TLR4) and stromal cell-derived factor-1 (SDF-1), and attenuated the interaction between TLR4 and HMGB1. Western blot results suggested that Nec-1 significantly suppressed IL-1β-induced NF-κB transcriptional activity, but not MAPK pathway. Micro-computed tomography, immunohistochemical staining, and Safranin O/Fast Green staining were used in vivo to assess the degree of destruction of OA cartilage. The results show that NEC-1 can significantly reduce the degree of destruction of OA cartilage. Therefore, Nec-1 may be a novel therapeutic candidate to treat OA. | 10.3389/fphar.2018.01378 |
pubmed_257_3743 | Between 1982 and 1987, 43 patients with variceal bleeding due to extrahepatic portal obstruction were treated by repeated endoscopic injection sclerotherapy using 1% polidocanol intravariceally. This decreased rebleeding, as evidenced by a decrease in bleeding risk factor (BRF), mean transfusion requirement, and mean number of transfusions per patient per month of follow-up. Differences between pre- and postsclerotherapy parameters were significant (p less than 0.001). The varices were eradicated in 86% of patients. The mean sclerotherapy sessions required were 7.68 +/- 2.39 (SD). Complications were infrequent. Forty-three patients were followed from 5 to 68 months: cumulative survival was 97.7% and varices recurred in 16%. Sclerotherapy avoided a second operation in 21 postsurgical patients. Sclerotherapy for managing variceal bleeding due to extrahepatic portal obstruction is a reasonable alternative to surgery. | 10.1016/s0016-5107(89)72798-x |
pubmed_317_22025 | Physicians should consider barotrauma and decompression illness (DCI) in any patient presenting after a recent scuba dive, even apparently shallow dives. If and when DCI is suspected, clinicians should act without delay to transfer the patient to a recompression facility, even if diagnostic certainty has not been attained. We present a case of hyperbaric injury in an asthmatic woman who had an atypical presentation in view of the depth of dive. | 10.7861/clinmedicine.15-1-99 |
pubmed_875_15937 | It has been shown that metformin dose-dependently inhibits the development of colon tumors induced by 1,2-dimethylhydrazine (DMH) in rats. The metformin effect manifested itself as a decrease in the amount and average size of tumors, increased degree of their differentiation, and reduction of invasion depth, which was more pronounced in the group of animals that received metformin at a dose of 100 mg/kg of body weight as compared with rats treated with metformin at a dose of 300 mg/kg. | 10.1134/S0012496616030017 |
pubmed_106_14272 | Natural-resistance associated macrophage protein 1 (Nramp1) encodes a transmembrane phagolysosomal protein exerting resistance toward infections with intracellular pathogens by a mechanism not fully elucidated so far. We used the murine macrophage cell line RAW264.7, stably transfected with functional (RAW-37) or nonfunctional (RAW-21) Nramp1, to study for differences in the expression of NO, a central antimicrobial effector molecule of macrophages. Following stimulation with IFN-gamma and LPS, Nramp1-expressing cells exhibit higher enzymatic activity of inducible NO synthase (iNOS) and increased cytoplasmic iNOS mRNA levels than RAW-21 cells. Time-course experiments showed that iNOS-mRNA levels remain increased in RAW-37 cells after prolonged cytokine stimulation while they decrease in RAW-21 cells. Reporter gene assays with iNOS-promoter luciferase constructs demonstrated an increased and prolonged promoter activity in Nramp1-resistant vs susceptible cells. This was paralleled by increased IFN regulatory factor 1 (IRF-1) expression and binding affinity to the iNOS promoter in RAW-37 cells, which may be related to enhanced STAT-1 binding affinity in these cells. A point mutation within the IRF-1 binding site of the iNOS promoter abolished the differences in iNOS transcription between RAW-21 and RAW-37 cells. Cells carrying functional Nramp1 express increased amounts of NO, which may be related to STAT-1-mediated stimulation of IRF-1 expression with subsequent prolonged activation of iNOS transcription. Enhanced NO expression may partly underlie the protection against infection with intracellular pathogens by Nramp1 functionality. | 10.4049/jimmunol.171.4.1994 |
pubmed_580_19269 | We previously described the behaviour of different cobalt forms, i.e., cobalt nanoparticles (CoNP), cobalt microparticles (CoMP) and cobalt ions (Co(2+)), in culture medium (dissolution, interaction with medium components, bioavailability) as well as their uptake and intracellular distribution in Balb/3T3 mouse fibroblasts (Sabbioni, Nanotoxicology, 2012). Here, we assess the cytotoxicity and morphological transformation of CoNP compared not only to Co(2+), but also to CoMP and to released Co products. Cytotoxicity reached maximum at 4-h exposure, with ranking CoMP > CoNP > Co(2+). However, if we consider toxicity as a function of intracellular Co, toxicity of the ionic forms seems to prevail over the particles. Co forms other than Co(2+) released from particles had toxicity intermediate between particles and ions. Alterations in concentrations of essential elements (Cu, Mg, Zn) in cells exposed to Co particles may contribute to toxicity. Both CoMP and CoNP (but not Co(2+) and other released Co forms) induced morphological transformation (CoMP > CoNP). This was dependent on reactive oxygen species production and lipid peroxidation, as indicated by inhibition of type III foci with ascorbic acid. The present results suggest that the previously demonstrated massive mitochondrial and nuclear Co internalisation and DNA adduct formation by CoMP and CoNP (Sabbioni, Nanotoxicology, 2012) induce toxicity and transformation. On the contrary, the role of ions released by particles in culture medium is negligible. Thus, both the chemical and the physical properties of Co particles contribute to cytotoxicity and morphological transformation. | 10.3109/17435390.2013.796538 |
pubmed_41_5340 | Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/μL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway. | 10.1371/journal.pone.0185602 |
pubmed_483_10058 | The specific objective of this study was to evaluate whether rhBMP-2-loaded bio-scaffolds can be used as effective rhBMP-2 carriers in the implantation of bone defect sites or poor bone quality in host bone. The rhBMP-2 release pattern test showed slow results in both groups, and a 1:9 ratio composition with a high water-absorption rate was selected for in vivo study. All animals euthanized after 9 weeks. The new bone formation and bone quantity and quality of fibular samples were examined. The results showed that the rhBMP-2 powder gel composite improved the new bone formation in the cortical bone and the marrow space. The length of new bone formation ratio of the rhBMP-2 loaded composite group was significantly higher than the powder gel group. The composite of powder gel seems to be a nice carrier, and slow release of rhBMP-2 can promote new bone formation in a segmental cortical bone defect after implantation. | 10.1080/09205063.2019.1601871 |
pubmed_510_17079 | This is a case report of a 25-year-old female with recurrent episodes of transient cerebral ischemia accompanied by transient hemiparesis. Cardiac ultrasound examination revealed a small left-ventricular tumor located between the chordae tendineae. The echocardiographic finding was subsequently confirmed by surgery. The entire tumor was removed and the mitral valve remained intact. Due to the histological and immunohistochemical findings a papillary fibroelastoma was diagnosed. The early and late postoperative course was without event. | pubmed_510_17079 |
pubmed_1019_7011 | Cyclin-Dependent Kinase 1 (CDK1) is the major M-phase kinase known also as the M-phase Promoting Factor or MPF. Studies performed during the last decade have shown many details of how CDK1 is regulated and also how it regulates the cell cycle progression. Xenopus laevis cell-free extracts were widely used to elucidate the details and to obtain a global view of the role of CDK1 in M-phase control. CDK1 inactivation upon M-phase exit is a primordial process leading to the M-phase/interphase transition during the cell cycle. Here we discuss two closely related aspects of CDK1 regulation in Xenopus laevis cell-free extracts: firstly, how CDK1 becomes inactivated and secondly, how other actors, like kinases and phosphatases network and/or specific inhibitors, cooperate with CDK1 inactivation to assure timely exit from the M-phase. | 10.4061/2011/523420 |
pubmed_540_4875 | Evolutionary organization of the arterial wall into layers occurred concomitantly with the emergence of a highly muscularized, pressurized arterial system that facilitates outward hydraulic conductance and mass transport of soluble substances across the arterial wall. Although colliding circulating cells disperse potential energy within the arterial wall, the different layers counteract this effect: (1) the endothelium ensures a partial barrier function; (2) the media comprises smooth muscle cells capable of endocytosis/phagocytosis; (3) the outer adventitia and perivascular adipocytic tissue are the final receptacles of convected substances. While the endothelium forms a physical and a biochemical barrier, the medial layer is avascular, relying on the specific permeability properties of the endothelium for metabolic support. Different components of the media interact with convected molecules: medial smooth muscle cells take up numerous molecules via scavenger receptors and are capable of phagocytosis of macro/micro particles. The outer layers-the highly microvascularized innervated adventitia and perivascular adipose tissue-are also involved in the clearance functions of the media: the adventitia is the seat of immune response development, inward angiogenesis, macromolecular lymphatic drainage, and neuronal stimulation. Consequently, the clearance functions of the arterial wall are physiologically essential, but also may favor the development of arterial wall pathologies. This review describes how the walls of large conductance arteries have acquired physiological clearance functions, how this is determined by the attributes of the endothelial barrier, governed by endocytic and phagocytic capacities of smooth muscle cells, impacting adventitial functions, and the role of these clearance functions in arterial wall diseases. | 10.1161/ATVBAHA.122.317759 |
pubmed_992_8927 | Training with pointe shoes is an integral part of professional dance education and ambitious hobby dancing. Pointe shoes - developed more than hundred years ago and almost unaltered since then - are highly specific and strike a balance between aesthetics, function, protection, and health care. Therefore, pointe readiness should be tested prior to all dance training or career training. Medical specialists are often confronted with this issue. Specific anatomical dance technique-orientated general conditional and coordinative preconditions as well as dance-technical prerequisites must be met by pointe readiness tests in order to keep traumatic injuries or long-term damage at a minimum. In addition to a (training) history, medical counselling sessions have come to include various tests that enable a reliable decision for or against pointe work. This article suggests adequate testing procedures (STT TEST), taking account of professional dancing as well as hobby dancing. | 10.1055/s-0043-106983 |
pubmed_687_20222 | Excessive accumulation of fat is harmful to human health. The preadipocyte differentiation is a critical process of fat development. Studying the expression profiles of genes related to preadipocyte differentiation contributes to understanding of the mechanism of fat accumulation. Despite being considered an ideal animal model for studying adipogenesis, little is known about the gene expression profiles at different stages during preadipocyte differentiation in rabbits. In the present study, rabbit preadipocytes were cultured in vitro and induced for differentiation, and gene expression profiles of adipocytes collected at days 0, 3, and 9 of differentiation were analyzed by RNA-seq. We identified 1352 differentially expressed genes (DEGs) when comparing day 3 with day 0 and identified 888 DEGs when comparing day 9 with day 3. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the PPAR signaling pathway and PI3K-Akt signaling pathway were significantly enriched by the DEGs that up-regulated within the period of day 0 - day 3, and the GO terms and KEGG pathways that were associated with cell cycle were enriched by the DEGs that up-regulated within the period of day 3 - day 9. The DEGs that specifically up-regulated within the period of day 0 - day 3 might play roles in the cytoplasm, and the DEGs that specifically up-regulated within the period of day 3 - day 9 might act in the nucleus. The protein-protein interaction (PPI) network constructed by DEGs showed that hub node genes might modulate rabbit preadipocyte differentiation via regulating cell cycle. | 10.16288/j.yczz.19-265 |
pubmed_72_23239 | Persistent or chronic immune thrombocytopenias (P/C-ITP) are acquired blood disorders lasting more than 3 months or 1 year, respectively. The pathogenesis of these disorders is thought to be immunological. We hypothesized that some patients with P/C-ITP might have an intrinsic megakaryopoiesis defect. We identified a group of P/C-ITP patients with acquired isolated mild thrombocytopenia (30-100 × 10(9) /l), undetectable anti-platelet antibodies, negative autoimmune investigations and no need for treatment. We examined in vitro megakaryocyte differentiation and compared these patients' results with those of acute-ITP patients and healthy controls. No difference in proliferation, ploidy or expression of surface markers was found. In contrast, P/C-ITP patients had significantly fewer proplatelet-forming megakaryocytes. This novel observation demonstrated that some patients diagnosed with P/C-ITP have an intrinsic megakaryopoiesis defect independent of the bone-marrow environment. Further investigations are needed to dissect mechanisms underlying this impaired proplatelet formation in these patients. | 10.1111/bjh.13444 |
pubmed_219_1986 | Analysis of short tandem repeats (STR) is the predominant method for post-transplant monitoring of donor engraftment. It can enable early detection of disease relapse, level of engraftment and provide useful information on the graft-versus-host disease (GVHD)/graft-versus-tumour (GVT) effect, facilitating therapeutic intervention. Harmonization and standardization of techniques and result interpretation is essential to reduce the impact of laboratory variability on both clinical management and the results of multi-centre clinical trials. However, the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) has highlighted significant issues inherent in STR testing that impact upon inter- and intra- laboratory variation. We present here consensus best practice guidelines and recommendations for STR chimerism testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 11 UK and Eire clinical laboratories. This document uses data obtained from the UK NEQAS LI Post-Stem Cell Transplant (SCT) Chimerism Monitoring Programme. | 10.1111/bjh.13073 |
pubmed_856_17827 | Optical frequency conversion provides a fundamental and important approach to manipulate light in frequency domain. In such a process, manipulating the frequency of light without changing information in other degrees of freedom of light will enable us to establish an interface between various optical systems operating in different frequency regions and have many classical and quantum applications. Here we experimentally demonstrate a frequency conversion with maintaining polarization and orbital angular momentum (OAM) by successfully upconverting various polarization-OAM composite states in a nonlinear Sagnac interferometer. Our scheme offers a new possibility for building different wave band interfaces in more degrees of freedom. | 10.1364/OL.419753 |
pubmed_851_25918 | Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia. Objectives: To assess TB case finding, including human immunodeficiency virus (HIV) associated interventions and treatment outcomes, before (January 2013-March 2014), during (April 2014-June 2015) and after (July-December 2015) the Ebola virus disease outbreak. Design: A cross-sectional study and retrospective cohort analysis of outcomes. Results: The mean quarterly numbers of individuals with presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola (n = 7032, 12%), Ebola (n = 6147, 10%) and post-Ebola (n = 6795, 8%). For all forms of TB, stratified by category and age group, there was a non-significant decrease in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods. There were significant decreases in numbers of cases with smear-positive pulmonary TB (PTB) from the pre-Ebola period (n = 855), to the Ebola (n = 640, P < 0.001) and post-Ebola (n = 568, P < 0.001) periods. The proportions of patients tested for HIV, found to be HIV-positive and started on antiretroviral therapy decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14% and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB patients were: 80% pre-Ebola, 69% Ebola (P < 0.001) and 73% post-Ebola (P < 0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion: The principal negative effects of Ebola were the significant decreases in diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral therapy uptake and poor treatment success. Ways to prevent these adverse effects from recurring in the event of another Ebola outbreak need to be found. | 10.5588/pha.16.0097 |
pubmed_457_25001 | OBJECTIVE
The study was designed to identify pathogenic TSC1 or TSC2 gene mutations and provide solid evidence for the diagnosis of tuberous sclerosis complex (TSC).
METHODS
11 unrelated Chinese patients with TSC were investigated in the present study. Characteristic skin lesions such as hypomelanotic macules and the central nervous system features such as the epilepsy, cortical tubers and subependymal nodules were the most common symptoms that were observed in the patients. All exons and exon-intron boundaries of the TSC1 and TSC2 gene of the patients were amplified by PCR.
RESULTS
A total of 11 different TSC2 and one TSC1 mutations were identified in the present study, of which five TSC2 and 1 TSC1 gene mutations were novel. Among the 11 patients, 10 harbored TSC2 mutations, whereas only one patient had a TSC1 gene mutation. The identification of TSC1/TSC2 gene mutations confirmed the diagnosis of the 11 patients with TSC.
CONCLUSIONS
Our study has expanded the spectrum of TSC1 and TSC2 gene mutations causing TSC. The identification of the TSC1/TSC2 gene mutations confirmed the diagnosis of the 11 patients with TSC. | 10.1016/j.clineuro.2017.01.015 |
pubmed_744_18169 | We measured cellular and humoral responses to conserved regions of Plasmodium falciparum merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) at different times during and after acute infection in matched groups of Gabonese children who presented with either mild or severe malaria. We used an MSP-1(19) recombinant protein and peptides corresponding to conserved epitopes in MSP-1 and MSP-2 N- and C-terminal regions. The prevalences of peptide-induced cell-mediated responses were maximal in both groups when they were healthy, but were consistently higher in the mild malaria group, whereas peptide-specific antibody responses were consistently highest in the severe malaria group. Recombinant MSP-1(19) protein-specific antibody levels in the 2 groups were similar both prior to and 1 month post-treatment but declined later when the children were healthy and parasite-free, to a significantly lower level in those admitted with severe malaria, reflecting the profile of the predominant MSP-1(19)-specific immunoglobulin G1 isotype. This finding implies a defect in the ability of children with a history of severe malaria to maintain an antibody response putatively associated with immunity to P. falciparum malaria. | 10.1016/s0035-9203(03)90090-3 |
pubmed_1030_24633 | Hydrogel ink formulations based on rheology additives are becoming increasingly popular as they enable 3-dimensional (3D) printing of non-printable but biologically relevant materials. Despite the widespread use, a generalized understanding of how these hydrogel formulations become printable is still missing, mainly due to their variety and diversity. Employing an interpretable machine learning approach allows the authors to explain the process of rendering printability through bulk rheological indices, with no bias toward the composition of formulations and the type of rheology additives. Based on an extensive library of rheological data and printability scores for 180 different formulations, 13 critical rheological measures that describe the printability of hydrogel formulations, are identified. Using advanced statistical methods, it is demonstrated that even though unique criteria to predict printability on a global scale are highly unlikely, the accretive and collaborative nature of rheological measures provides a qualitative and physically interpretable guideline for designing new printable materials. | 10.1002/advs.202202638 |
others_332_581 | Composting of the macrophytes Eichhornia crassipes (water hyacinth) and Egeria densa (Brazilian elodea) has been proposed as a final disposal, following their mechanical removal in the lake Fúquene (Ubaté, Cundinamarca). Microorganisms, isolated and selected by antagonism, were evaluated as inoculants to accelerate the composting and to stimulate plant growth. In microbial biopreparations of bacteria, actinomycetes and fungi, maximum amylolytic activities were found of 2,422 U L -1, 1,744 U L -1 and 1,426 U L -1, respectively; cellulolytic activities of 233.2 U L -1, 668 U L -1 and 701.4 U L -1 and proteolytic activities of 660 U mg -1, 520 U mg -1 and 400 U mg -1. In test of these biopreparations in windrow composting of aquatic macrophytes waste, the best result was obtained with a concentration of 2%. The assay conducted on seedlings of radish (Raphanus sativus L) under greenhouse conditions (P <0.05), using the following treatments: microbial inoculants, compost inoculated to 2%, pure or mixed with soil (1:1), peat 50% and chicken manure at 33% mixed with soil, showed that actinomycetes stimulated plant growth significantly, as did chicken manure and bacteria. Microbial inoculants role for growth, development and nutrients assimilation in radish, was evident, and also for accelerating polluting macrophytes composting process | 10.4067/S0718-95162011000200005 |
pubmed_505_7570 | To clarify the role of chymase in adhesion formation, we investigated whether a chymase inhibitor could prevent adhesion formation after surgery in hamsters. Hamsters received a lesion produced by uterus scraping. A specific chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]oxazole-4-carboxylicacid (TY-51184), or placebo was injected into the abdomen before closing and scores for adhesion formation were assessed at 1, 4, and 12 weeks. A single peritoneal administration of TY-51184 significantly decreased the adhesion scores even at 12 weeks (placebo, 2.80+/-0.20; chymase inhibitor, 1.60+/-0.31). Thus, chymase inhibitors may be a novel strategy to prevent adhesion formation. | 10.1016/j.ejphar.2003.11.009 |
pubmed_634_1305 | BACKGROUND
Equitable access to mental healthcare is a priority for many countries. The National Health Service in England uses a weighted capitation formula to ensure that the geographical distribution of resources reflects need.
AIMS
To produce a revised formula for estimating local need for secondary mental health, learning disability (intellectual disability) and psychological therapies services for adults in England.
METHOD
We used demographic records for 43 751 535 adults registered with a primary care practitioner in England linked with service use, ethnicity, physical health diagnoses and type of household, from multiple data-sets. Using linear regression, we estimated the individual cost of care in 2015 as a function of individual- and area-level need and supply variables in 2013 and 2014. We sterilised the effects of the supply variables to obtain individual-need estimates. We aggregated these by general practitioner practice, age and gender to derive weights for the national capitation formula.
RESULTS
Higher costs were associated with: being 30-50 years old, compared with 20-24; being Irish, Black African, Black Caribbean or of mixed ethnicity, compared with White British; having been admitted for specific physical health conditions, including drug poisoning; living alone, in a care home or in a communal environment; and living in areas with a higher percentage of out-of-work benefit recipients and higher prevalence of severe mental illness. Longer distance from a provider was associated with lower cost.
CONCLUSIONS
The resulting needs weights were higher in more deprived areas and informed the distribution of some 12% (£9 bn in 2019/20) of the health budget allocated to local organisations for 2019/20 to 2023/24. | 10.1192/bjp.2019.185 |
pubmed_655_3560 | The role of radiation therapy in the treatment of malignant melanoma has evolved substantially over time. Years ago, malignant melanomas were generally considered radioresistant. Over time, the palliative value of radiation therapy was established. Most recently it also has become clear that judiciously applied therapy may be curative in either an adjuvant setting or for small-volume disease. | 10.1016/s0889-8588(05)70027-7 |
others_278_1969 | The large components of DNA-dependent RNA polymerases (RNAPs) of Archaea, Bacteria and Eucarya were used as molecular markers for the reconstruction of phylogenetic trees. Preferred phylogenetic trees of the three domains of organisms were determinded by a combination of the three major types of inference methods (pairwise distances, maximum parsimony and maximum likelihood) applying the fuzzy logic data analysis method. The preferred phylogenetic trees for the Archaea and Bacteria show branching topologies which differ significantly from the topologies found using ribosomal RNAs as probes: the tree of the Archaea allows a unique location of a characteristics splitting event replacing the largest RNAP subunit (B) of the thermophilic sulfur archaea by two fragments (B′ and B″) in methanogens and halophiles; the tree of the Bacteria shows the lineage of the extreme thermophile Aquifex pyrophilus at a branching point located far away from the root of this domain — clearly not supporting the hypothesis that hyperthermophilia is a relic of primordial environmental conditions. The preferred branching topology of the universal phylogenetic tree reconstructed from the sequences of the second largest components (B) of the three eucaryal RNAPs (Pol I, Pol II and Pol III), the archaeal RNAP components B or B′ plus B″, respectively, and the bacterial RNAP components, β, confirmed the topology formerly inferred from another set of RNAP components: components A of the eucaryal RNAPs, archaeal components A′ plus A″, and bacterial β′ components. The preferred branching topology of this universal tree is characterized by an internodal stretch separating the archaeal lineage and the lineage of the eucaryal Pols II and Pols III on the one hand, from the bacterial lineage and the lineage of the eucaryal Pols I on the other hand. The latter topology led us to the fusion hypothesis for the formation of the Eucarya. © 1994, Gustav Fischer Verlag, Stuttgart · Jena · New York. All rights reser | 10.1016/S0723-2020(11)80335-8 |
pubmed_762_9305 | This work develops a mathematical model for the atrioventricular (AV) node in the human heart, based on recordings of electrical activity in the atria (the upper chambers of the heart) and the ventricles (the lower chambers of the heart). Intracardiac recordings of the atrial and ventricular activities were recorded from one patient with atrial flutter and one with atrial fibrillation. During these arrhythmias, not all beats in the atria are conducted to the ventricles. Some are blocked (concealed). However, the blocked beats can affect the properties of the AV node. The activation times of the atrial events were regarded as inputs to a mathematical model of conduction in the AV node, including a representation of AV nodal concealment. The model output was compared to the recorded ventricular response to search for and identify the best possible parameter combinations of the model. Good agreement between the distribution of interbeat intervals in the model and data for durations of 5 min was achieved. A model of AV nodal behavior during atrial flutter and atrial fibrillation could potentially help to understand the relative roles of atrial input activity and intrinsic AV nodal properties in determining the ventricular response. | 10.1006/bulm.2002.0313 |
pubmed_914_24469 | Neuropathy is one of the many complications of diabetes mellitus, along with micro- and macroangiopathy. Chronic sensorimotor distal symmetric polyneuropathy is the most common form between neuropathies; more than 30% of the diabetic patients are affected by this complication. Treatment is based on three cornerstones: (1) multifactorial intervention aimed at normoglycemia; (2) drugs that target pathogenic mechanisms and (3) symptomatic treatment. Among pathogenic treatments, alpha-lipoic acid and benfotiamine are available in several countries. Neuropathic pain, which affects 8-26% of diabetic patients, exerts a substantial impact on the quality of life. Among the centrally acting analgesic drugs, tricyclic antidepressants, carbamazepine, gabapentin and opioids have been mainly used to treat neuropathic pain. More recently, significant pain relief has been reported using agents such as duloxetine, a dual selective serotonin noradrenaline reuptake inhibitor, and pregabalin, an anticonvulsant, a specific modulator of the alpha2delta subunit of the voltage-dependent calcium channels. Until now, at least 50 new molecular entities have reached clinical stage of development. Strategies that may show promise over existing treatments include topical therapies, analgesic combinations and, in future, gene-related therapies. | pubmed_914_24469 |
pubmed_588_2802 | Cnidarians are the simplest metazoans with a nervous system. They are well known for their regeneration capacity, which is based on the restoration of a signalling centre (organizer). Recent work has identified the canonical Wnt pathway in the freshwater polyp Hydra, where it acts in organizer formation and regeneration. Wnt signalling is also essential for cnidarian embryogenesis. In the sea anemone Nematostella vectensis 11 of the 12 known wnt gene subfamilies were identified. Different wnt genes exhibit serial and overlapping expression domains along the oral-aboral axis of the embryo (the 'wnt code'). This is reminiscent of the hox code (cluster) in bilaterian embryogenesis that is, however, absent in cnidarians. It is proposed that the common ancestor of cnidarians and bilaterians invented a set of wnt genes that patterned the ancient main body axis. Major antagonists of Wnt ligands (e.g. Dkk 1/2/4) that were previously known only from chordates, are also present in cnidarians and exhibit a similar conserved function. The unexpectedly high level of genetic complexity of wnt genes evolved in early multi-cellular animals about 650 Myr ago and suggests a radical expansion of the genetic repertoire, concurrent with the evolution of multi-cellularity and the diversification of eumetazoan body plans. | 10.1038/sj.onc.1210052 |
pubmed_695_16784 | Fluorescent tools such as green fluorescent protein (GFP) have been used extensively as reporters in biochemistry and microbiology, but GFP and other conventional fluorescent proteins are restricted to aerobic environments. This limitation precludes fluorescence studies of anaerobic ecologies including polymicrobial communities in the human gut microbiome and in soil microbiomes, which profoundly affect health, disease, and the environment. To address this limitation, we describe the first implementation of two bilin-binding fluorescent proteins (BBFPs), UnaG and IFP2.0, as oxygen-independent fluorescent labels for live-cell imaging in anaerobic bacteria. Expression of UnaG or IFP2.0 in the prevalent gut bacterium Bacteroides thetaiotaomicron (B. theta) results in detectable fluorescence upon the addition of the bilirubin or biliverdin ligand, even in anaerobic conditions. Furthermore, these BBFPs can be used in two-color imaging to differentiate cells expressing either UnaG or IFP2.0; UnaG and IFP2.0 can also be used to distinguish B. theta from other common gut bacterial species in mixed-culture live-cell imaging. BBFPs are promising fluorescent tools for live-cell imaging investigations of otherwise inaccessible anaerobic polymicrobial communities. | 10.1016/j.crmicr.2020.04.001 |
pubmed_436_4067 | A common mammalian defense mechanism employed to prevent systemic dissemination of invasive bacteria involves occlusion of local microvasculature and encapsulation of bacteria within fibrin networks. Acquisition of plasmin activity at the bacterial cell surface circumvents this defense mechanism, allowing invasive disease initiation. To facilitate this process, S. pyogenes secretes streptokinase, a plasminogen-activating protein. Streptokinase polymorphism exhibited by S. pyogenes isolates is well characterized. However, the functional differences displayed by these variants and the biological significance of this variation has not been elucidated. Phylogenetic analysis of ska sequences from 28 S. pyogenes isolates revealed 2 main sequence clusters (clusters 1 and 2). All strains secreted streptokinase, as determined by Western blotting, and were capable of acquiring cell surface plasmin activity after incubation in human plasma. Whereas culture supernatants from strains containing cluster 1 ska alleles also displayed soluble plasminogen activation activity, supernatants from strains containing cluster 2 ska alleles did not. Furthermore, plasminogen activation activity in culture supernatants from strains containing cluster 2 ska alleles could only be detected when plasminogen was prebound with fibrinogen. This study indicates that variant streptokinase proteins secreted by S. pyogenes isolates display differing plasminogen activation characteristics and may therefore play distinct roles in disease pathogenesis. | 10.1096/fj.08-109348 |
others_340_8844 | Static locked nailing was used to repair fractures of the femoral diaphysis in 15 dogs. The implant consists of a 5, 6, or 7 mm diameter stainless steel rod made up of two parts: the body of the nail, in which there are 13 threaded holes, and a piece without holes that contains a slot for anchoring the jig. Good limb function was obtained after less than 3 weeks in 12 dogs and these dogs remained sound throughout the study. Radiographic examination revealed fracture healing in 11 of the dogs, between 8 and 16 weeks after surgery. One dog was not returned for follow-up evaluation until 22 weeks after surgery; complete healing was apparent from radiographic examination. The remaining three dogs had to have additional operations, one because of lameness caused by excessive length of the distal screws, one because of a nonunion, and the third because of a sequestrum. Fracture healing in these dogs was observed at 18, 21, and 24 weeks respectively. Loosening of one screw and angulation of the bone occurred in one dog. These complications had no adverse effects on clinical outcome. ©Copyright 1996 by The American College of Veterinary Surgeons | 10.1111/j.1532-950X.1996.tb01434.x |
pubmed_275_1749 | Signs banning all cell phone use are still ubiquitous in hospitals, but recent studies show that global bans may not be necessary. | 10.1097/00006247-200504000-00016 |
pubmed_690_3313 | Foetal rat skin rapidly closes an open wound in organ culture and in vivo, this possibly being unique to organs still in the morphogenetic stage. In the present study, examination was made of morphological changes in foetal rat skin during closure of open wounds inflicted at day 16 of gestation. Phase-contrast microscopy of open-wounded skin cultured in vitro indicated inward spreading of the peripheral skin to be responsible for wound closure. Wound closure in vitro was inhibited by cytochalasin B (10 micrograms/ml), not by hydroxyurea (2 mM), indicating prenatal wound closure to be mediated by regulation of the microfilament system rather than cell proliferation. During wound closure in vitro and in vivo, light and scanning electron microscopy of the peripheral skin showed cells in the periderm, the outermost layer of the foetal epidermis, to elongate centripetally and en masse, whereas the shape of underlying epidermal cells not to change. Numerous spindle-shaped cells and fibrous matrices in the mesenchyme were redistributed, becoming oriented along the wound edge. Following isolation of the mesenchyme and epidermis by treatment with Dispase and separate culturing, the capacity for wound closure in vitro was found to be retained only by the mesenchyme. Cellular activity within the mesenchyme, rather than in the epidermis, would thus appear essential to wound closure in foetal rat. | 10.1242/dev.114.3.573 |
pubmed_268_11662 | The objective of this study was to determine the effect of nimodipine on infarct development and local brain pH after middle cerebral artery occlusion in the rat. Female Fischer-344 rats were subjected to permanent occlusion of the left middle cerebral artery by electrocoagulation. After 6, 12, or 24 hours, brains were frozen, and infarct size, degree of edema formation, and local brain pH were quantified by standard histology or the umbelliferone technique, respectively. In control rats, cortical infarct size was increased from 29.5 microliters at 6 hours to 72.5 microliters at 24 hours after vessel occlusion. In striatum only, an insignificant increase from 15.2 to 24.7 microliters in infarct volume was observed during this period. Edema increased from 7% to 22% in cortical and from 4% to 39% in the striatal infarct areas during this time. Nimodipine (0.1 mg/kg s.c.), given 45 minutes before and again 8 and 16 hours after middle cerebral artery occlusion, did not alter infarct size at 6 hours but considerably improved outcome at later times. Edema formation was lower at 12 hours in the group treated with the calcium antagonist (p less than 0.05). By contrast, effects on local brain pH were seen as early as 6 hours after the vessel occlusion. Nimodipine greatly reduced the areas exhibiting the lowest pH values beyond pH 6.0 (p less than 0.05). Similar effects by nimodipine on brain pH were observed in the 12-hour series, whereas at 24 hours after middle cerebral artery occlusion, a shift to more alkalotic values was noted with no overt differences between control and drug-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_268_11662 |
pubmed_854_20360 | Although human bone marrow stromal cells (MSCs) have been used for clinical bone reconstruction, how the physiological status of patients and culture conditions of MSCs affect the result of bone reconstruction must be clarified to use MSCs in a clinical stage. If in vitro parameters of the status of MSCs may be correlate with in vivo bone formation capability, the better cells for clinical bone reconstruction can be defined by the parameters. In order to explore the parameters and define the optimum cells for clinical use, the proliferation and differentiation capabilities in vitro and the in vivo bone formation capability of MSCs were analyzed. An age-related proliferation capability was found. The in vitro alkaline phosphatase activity of bone formation finding groups was higher than that of the no bone formation group. This may be provide a parameter to obtain the optimum cells for clinical use to benefit improving the cure efficiency. In this study, it is preferable that MSCs of passage 1 have stronger osteogenic potential than those of passage 2 and 3 in vitro, and might be suitable for clinical application to bone tissue engineering. | pubmed_854_20360 |
pubmed_576_8654 | The vein of Galen aneurysmal malformation (VGAM) is a rare cerebro-vascular disorder in neonates. It is characterized by an abnormal direct communication between one or several cerebral arteries and the vein of Galen. It may appear in the neonatal period or afterwards. Three cases of patients affected by VGAM with different clinical expression are presented. Two of them were treated successfully with endovascular embolization. It was not possible to provide the same treatment to the third patient for an intractable congestive heart failure already existing when VGAM was diagnosed. | pubmed_576_8654 |
pubmed_34_21148 | The hypothesis of the present study was that bacterial communities would differentiate under Eucalyptus camaldulensis and that an enhancement of arbuscular mycorrhizal (AM) density would minimize this exotic plant species effect. Treatments consisted of control plants, preplanting fertilizer application and AM inoculation. After 4 months of culture in autoclaved soil, E. camaldulensis seedlings were either harvested for growth measurement or transferred into containers filled with the same soil but not sterilized. Other containers were kept without E. camaldulensis seedlings. After 12 months, effects of fertilizer amendment and AM inoculation were measured on the growth of Eucalyptus seedlings and on soil microbial communities. The results clearly show that this plant species significantly modified the soil bacterial community. Both community structure (assessed by denaturing gradient gel electrophoresis profiles) and function (assessed by substrate-induced respiration responses including soil catabolic evenness) were significantly affected. Such changes in the bacterial structure and function were accompanied by disturbances in the composition of the herbaceous plant species layer. These results highlight the role of AM symbiosis in the processes involved in soil bio-functioning and plant coexistence and in afforestation programmes with exotic tree species that target preservation of native plant diversity. | 10.1111/j.1574-6941.2007.00363.x |
pubmed_281_20791 | Coastal sediments are considered as hotspots of microplastics (MPs), with substantial MPs stocks found in blue carbon habitats such as mangroves and tidal marshes, where wave-damping vegetation reduces sediment erosion and enhances accretion. Here, we examined the effects of such bio-geomorphic feedbacks in shaping MPs burial, through a year-round field study in a mangrove habitat along the coast of South China. The results revealed that MPs abundance decreased significantly with the increase of cumulative sediment erosion as the strength of bio-geomorphic feedbacks declined. More shapes and colors of MPs were found at locations with weaker waves and less sediment erosion, where the average particle size was also higher. Our findings highlight the importance of bio-geomorphic feedbacks in affecting both the abundance and characteristics of the buried MPs. Such knowledge extends our understanding of MPs transport and burial from the perspective of bio-geomorphology, which is essential to assess and predict MPs accumulation patterns as well as its impacts on ecosystem functioning of the blue carbon habitats. | 10.1016/j.scitotenv.2022.160220 |
pubmed_487_2365 | Miniproteins are adequate models to study various protein-structure modifying effects such as temperature, pH, point mutation(s), H-bonds, salt bridges, molecular packing, etc. Tc5b, a 20-residue Trp-cage protein is one of the smallest of such models with a stable 3D fold (Neidigh J. W. et al. (2002) Nat. Struct. Biol. 9, 425-430). However, Tc5b exhibits considerable heat-sensitivity and is only stable at relatively low temperatures. Here we report a systematic investigation of structural factors influencing the stability of Tc5b by solving its solution structure in different environments, varying temperature, and pH. The key interactions identified are the hydrophobic stacking of the aromatic rings of Tyr3 and Trp6 and the salt bridge formed between Asp9 and Arg18. To verify the importance of these interactions, selected variants (mutated, glycosylated and truncated) of Tc5b were designed, prepared, and investigated by NMR. Indeed, elimination of either of the key interactions highly destabilizes the structure. These observations enabled us to design a new variant, Tc6b, differing only by a methylene group from Tc5b, in which both key interactions are optimized simultaneously. Tc6b exhibits enhanced heat stability and adopts a stable fold at physiological temperature. | 10.1021/bi701371x |
pubmed_1064_21368 | Signal intensity nonuniformities in high field MR imaging limit the ability of MRI to provide quantitative information and can negatively impact diagnostic scan quality. In this paper, a simple method is described for correcting these effects based on in vivo measurement of the transmission field B1+ and reception sensitivity maps. These maps can be obtained in vivo with either gradient echo (GE) or spin echo (SE) imaging sequences, but the SE approach exhibits an advantage over the GE approach for correcting images over a range of flip angles. In a uniform phantom, this approach reduced the ratio of the signal SD to its mean from around 30% before correction to approximately 6% for the SE approach and 9% for the GE approach after correction. The application of the SE approach for correcting intensity nonuniformities is demonstrated in vivo with human brain images obtained using a conventional spin echo sequence at 3.0 T. Furthermore, it is also shown that this in vivo B1+ and reception sensitivity mapping can be performed using segmented echo planar imaging sequences providing acquisition times of less than 2 min. Although the correction presented here is demonstrated with a simultaneous transmit and receive volume coil, it can be extended to the case of separate transmission and reception coils, including surface and phase array coils. | 10.1002/mrm.20354 |
pubmed_15_12484 | This paper reports the thermoluminescence (TL) analysis performed on the oyster shells powder. TL response of (60)Co gamma-rays irradiated samples were studied in the range from 80 Gy to 8 kGy doses. TL signal of irradiated shell powder was higher as compared to the unirradiated control samples, which allowed to identify the irradiated oysters. Results show that the oyster shells have good TL properties and can be useful for the identification of irradiated seafood as well as for the evaluation of the treatment dose. | pubmed_15_12484 |
pubmed_397_2310 | OBJECTIVE
To characterize the pattern of surgical antimicrobial prophylaxis in the Czech Republic.
METHOD
Cross sectional survey with a self-administered postal questionnaire. Data collected included use of antimicrobial prophylaxis, surgical site infection rate, pathogens causing surgical site infection and demographics of the institution. Descriptive and multivariate analyses were performed.
SETTING
Hospital, surgical departments in the Czech Republic.
MAIN OUTCOME MEASURE
Prevalence of surgical antimicrobial use, factors associated with use, the profile of antimicrobial use, timing, route, dosage regimen and duration of initiated prophylaxis.
RESULT
The response rate was 55.5%. Surgical antimicrobial prophylaxis was used in 97.5% of departments, and 85% departments justified prophylaxis based on guideline. The timing of the first dosage was within 2 h of operation in 95.0% of departments and 36.7% of all departments administered more than 2 doses of SAP in operations that lasted less than 4 h of all respondents. The three most common prophylactic antimicrobial agent used were cefazolin, co-amoxiclav and cefuroxime amongst the 26 single antimicrobial agents and 16 antimicrobial combinations. Penicillins and enzyme inhibitor was the most frequent class used. Surgical antimicrobial prophylaxis was administered intravenously in 82.5% of all cases. The regimen used varied markedly in dose and duration prescribed. The surgical site infection rate occurred. 1-5% in 71.7% of departments. Most departments identified the causative pathogen at all times. Staphylococcus aureus was the most frequent pathogen of surgical site infection and was detected in 90.8% of all departments. There was significant association between Pseudomonas aeruginosa with cefuroxime use and Bacteriodes fragilis with co amoxiclav use.
CONCLUSION
This survey has identified several areas for improvement in surgical antimicrobial prophylaxis in the Czech Republic. Particular areas of concern include route of administration, duration and timing of first dosage of SAP, and the inappropriate use of broad-spectrum antimicrobials. | 10.1007/s11096-005-5971-8 |
pubmed_150_20478 | AIM
The integrated glucose-insulin (IGI) model is a semi-mechanistic physiological model which can describe the glucose-insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin-only-treated type 2 diabetes mellitus (T2DM) patients and identify patient-specific covariates.
METHODS
Data from four clinical studies were pooled, including glucose and insulin concentration-time profiles from T2DM patients on stable treatment with metformin alone following mixed-meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control.
RESULTS
The IGI model was expanded by four patient-specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady-state glucose, insulin-dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady-state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge.
CONCLUSIONS
The IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient-specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies. | 10.1111/bcp.13069 |
pubmed_527_244 | Giardia lamblia, which is an important parasitic cause of diarrhea, uses activated forms of glucose to make glycogen and activated forms of mannose to make glycophosphosphoinositol anchors. A necessary step for glucose activation is isomerization of glucose-6-phosphate to glucose-1-phosphate by a phosphoglucomutase (PGM). Similarly, a phosphomannomutase (PMM) converts mannose-6-phosphate to mannose-1-phosphate. While whole genome sequences of Giardia predict two PGM candidates, no PMM candidate is present. The hypothesis tested here is that at least one of the two Giardia PGM candidates has both PGM and PMM activity, as has been described for bacterial PGM orthologs. Nondenaturing gels showed that Giardia has two proteins with PGM activity, one of which also has PMM activity. Phylogenetic analyses showed that one of the two Giardia PGM candidates (Gl-PGM1) shares recent common ancestry with other eukaryotic PGMs, while the other Giardia PGM candidate (Gl-PGM2) is deeply divergent. Both Gl-PGM1 and Gl-PGM2 rescue a Saccharomyces cerevisiae pgm1Delta/pgm2Delta double deletion strain, while only Gl-PGM2 rescues a temperature-sensitive PMM mutant of S. cerevisiae (sec53-ts). Recombinant Gl-PGM1 has PGM activity only, whereas Gl-PGM2 has both PGM and PMM activities. We conclude that Gl-PGM1 behaves as a conventional eukaryotic PGM, while Gl-PGM2 is a novel eukaryotic PGM that also has PMM activity. | 10.1093/glycob/cwq081 |
pubmed_123_19064 | OBJECTIVE
A blocking monoclonal antibody to intercellular adhesion molecule-1 (ICAM-1), CL18/6, previously has been demonstrated to inhibit neutrophil attachment to isolated vascular endothelium and cardiomyocytes. Due to the well known participation of ICAM-1 in the inflammatory responses associated with myocardial ischemia/reperfusion injury, we investigated if CL18/6 could attenuate myocardial ischemia/reperfusion injury in vivo.
METHODS
Saline (3-5 ml, i.v., n = 6), non-blocking control MAb CL18/1D8 or CL18/6 (both 0.5 mg kg-1, i.v., n = 4) were administered prior to coronary occlusion (1 h) and subsequent reperfusion (5 h) produced by inflation of a coronary balloon angioplasty catheter in isoflurane-anesthetized, closed-chest dogs. Heart rate and arterial pressure were measured, and regional myocardial blood flow (rMBF), and myeloperoxidase activity (MPO) to index local neutrophil sequestration, were determined. Myocardial infarct size (IS) was evaluated using the tetrazolium staining technique and expressed as a percent of area at risk (AR).
RESULTS
Changes in heart rate and arterial pressure were insignificant throughout the experiment. rMBF (mean +/- s.e.m.) in the ischemic subendocardium for each treatment group was: Saline (0.07 +/- 0.02 ml min-1 g-1); CL18/1D8 (0.04 +/- 0.02); CL18/6 (0.06 +/- 0.02). IS/AR% was: saline (37 +/- 3%); CL18/1D8 (39 +/- 9%); CL18/6 (15 +/- 4%*); * = significantly different from CL18/1D8 and saline, P < 0.05. MPO assayed from AR immediately adjacent to the infarct was significantly reduced below infarct MPO only in the CL18/6 treated group-36%).
CONCLUSIONS
The results indicate that CL18/6 antagonism of ICAM-1 provided cardioprotection associated with reduced neutrophil activity in vulnerable myocardium, and suggest that ICAM-1 mediated neutrophil sequestration in endangered cardiac tissue is an important mechanism of myocardial ischemia/reperfusion injury. | pubmed_123_19064 |
pubmed_525_20824 | Genomic imprinting is defined as a gamete of origin-specific epigenetic modification of DNA leading to differential gene expression in the zygote. Several imprinted genes have been identified and some of them are associated with tumor development. We investigated the expression and the imprinting status of IGF2 and H19 genes in 47 uterine leiomyomas. Using allelic transcription assay, we detected the expression of the IGF2 gene in 10 of a total of 15 informative cases. No loss of imprinting, as determined by the finding of biallelic expression, was detected in any case. The expression of H19 gene was detected in 10 of 20 informative cases and the imprinting pattern was also maintained in all of them. Our data suggest that alterations in IGF2 and H19 genes expression by loss of imprinting do not occur in uterine leiomyomas. | 10.1006/gyno.1999.5483 |
pubmed_617_6106 | Cardiac arrest (CA) is the primary cause of death in industrialized countries. Successful resuscitation rate is estimated of about 40%, but a good neurological outcome remains difficult to achieve. The majority of resuscitated victims suffers of a pathophysiological entity termed as "post resuscitation disease". Today's efforts are mainly pointed to the chain of survival, often devoting less attention to post-resuscitation care. Resuscitated patients are often victims of nihilistic therapeutic approach, with clinicians failing to promptly institute strategies that mitigate the ischemia-reperfusion injury to vital organs. Only after 72 hours prognostication can be realistically attempted. Neurological evaluation relies on a combination of clinical, instrumental and laboratoristic parameters, since no one alone holds a specificity of 100%. Biochemical markers, such as neuron specific enolase and S-100b, may contribute to predict prognosis after CA. To the contrary, when used individually the necessary precision remains poorly characterized. Biochemical studies suffer from substantial methodological differences hampering attempts to summarize their findings. We review the information available on biochemical markers of brain damage for neurological prognostication after CA. | 10.2741/s90 |
others_314_101535 | Nucleotide-binding domain-leucine-rich repeat-type immune receptors (NLRs) protect plants against pathogenic microbes through intracellular detection of effector proteins. However, this comes at a cost, as NLRs can also induce detrimental autoimmunity in genetic interactions with foreign alleles. This may occur when independently evolved genomes are combined in inter- or intraspecific crosses, or when foreign alleles are introduced by mutagenesis or transgenesis. Most autoimmunity-inducing NLRs are encoded within highly variable NLR gene clusters with no known immune functions, which were termed autoimmune risk loci. Whether risk NLRs differ from sensor NLRs operating in natural pathogen resistance and how risk NLRs are activated in autoimmunity is unknown. Here, we analyzed the DANGEROUS MIX2 risk locus, a major autoimmunity hotspot in Arabidopsis thaliana. By gene editing and heterologous expression, we show that a single gene, DM2h, is necessary and sufficient for autoimmune induction in three independent cases of autoimmunity in accession Landsberg erecta. We focus on autoimmunity provoked by an EDS1-YFPNLS fusion protein to functionally characterize DM2h and determine features of EDS1-YFPNLS activating the immune receptor. Our data suggest that risk NLRs function reminiscent of sensor NLRs, while autoimmunity-inducing properties of EDS1-YFPNLS are in this context unrelated to the proteins functions as immune regulator. We propose that autoimmunity may, at least in some cases, be caused by spurious, stochastic interactions of foreign alleles with co-incidentally matching risk NLRs | 10.1101/2020.11.01.363895 |
others_10_15240 | In the US, over 95 million people have been infected with COVID and over 1 million have died. 10% of Californians are infected with COVID with higher rates reported among Latinx, Pacific Islanders, and low-income people. Higher death rates have been reported among African Americans. People living with Alzheimer’s Disease (AD) are also more likely to be infected with COVID. African Americans with AD have three times the COVID rate of Whites. Homecare workers who care for moderate to severe AD in home and community settings are frontline essential workers who manage complex AD-related problems like incontinence. Little is known about communication and problem-solving processes between homecare workers and families of people with AD to manage continence at home. This report describes the challenges facing homecare workers illustrated by an African American family caring for a relative with advanced AD during pandemic. © The Author(s) 2022 | 10.1177/23337214221129736 |
pubmed_723_19637 | This study presents a novel tool, ThSSim, for simulation of thermal stratification (ThS) in reservoirs. ThSSim is a simple and flexible reduced-order model-based the basis function (RMBF) that combines CE-QUAL-W2 (W2) and proper orthogonal decomposition (POD). In a case study, it was used to simulate water temperature in the Karkheh Reservoir (KR), Iran, for the period 2019-2035. ThSSim consists of two space- and time-dependent components that add predictive ability to the RMBF, a major refinement that extends its practical applications. Water temperature simulations by the W2 model at three-hour time intervals for the KR were used as input data to the POD model to develop ThSSim. To add predictive ability to ThSSim and considering that space-dependent components are not a function of time, we extrapolated the first three time-dependent components by September 30, 2035. We checked the predictive ability of ThSSim against water temperature profiles measured during eight sampling campaigns. We then applied ThSSim to simulate water temperature in the KR for 2019-2035. Simulated water temperature values matched well those measured and obtained by W2. ThSSim results showed an increasing trend for surface water temperature during the simulation period, with a reverse trend observed for water temperature in the bottom layers for three seasons (spring, summer and autumn). The results also indicated decreasing and increasing trends in onset and breakdown of thermal stability, respectively, so that the duration of ThS increased from 278 days in 2019 to 293 days in 2035. ThSSim is thus useful for reservoir temperature simulations. Moreover, the approach used to develop ThSSim is widely applicable to other fields of science and engineering. | 10.1038/s41598-019-54433-2 |
pubmed_1025_6150 | The Golgi is an essential membrane-bound organelle in the secretary pathway of eukaryotic cells. In mammalian cells, the Golgi stacks are integrated into a continuous perinuclear ribbon, which poses a challenge for the daughter cells to inherit this membrane organelle during cell division. To facilitate proper partitioning, the mammalian Golgi ribbon is disassembled into vesicles in early mitosis. Following segregation into the daughter cells, a functional Golgi is reformed. Here we summarize our current understanding of the molecular mechanisms that control the mitotic Golgi disassembly and postmitotic reassembly cycle in mammalian cells. | pubmed_1025_6150 |
pubmed_391_472 | HindIII cleaved human intestinal spirochete genomic DNA was cloned into the plasmid vector pBluescript. The inserts from three of these clones (pRB.C33, pRB.C47 and pRB.F11) successfully hybridized with DNA from the nine human intestinal spirochetes used in this study. The fourth insert (from clone pRB.A8) failed to hybridize with DNA from two of these isolates (HRM4 and HRM9), and, all four of the inserts hybridized with the M1 strain of swine intestinal spirochete Treponema innocens. Hybridization with DNA from the P18 strain of Treponema hyodysenteriae was observed only for the probe pRB.F11. No hybridization was detected with the human strain of Borrelia burgdorferi. With these probes we were thus able to demonstrate, in southern blot experiments, a restriction site polymorphism among the isolates of the human intestinal spirochetes we tested. | 10.1007/BF00144800 |
pubmed_498_23156 | The utilization of robotic systems has been increasing in the last decade. This increase has been derived by the evolvement in the computational capabilities, communication systems, and the information systems of the manufacturing systems which is reflected in the concept of Industry 4.0. Furthermore, the robotics systems are continuously required to address new challenges in the industrial and manufacturing domain, like keeping humans in the loop, among other challenges. Briefly, the keeping humans in the loop concept focuses on closing the gap between humans and machines by introducing a safe and trustworthy environment for the human workers to work side by side with robots and machines. It aims at increasing the engagement of the human as the automation level increases rather than replacing the human, which can be nearly impossible in some applications. Consequently, the collaborative robots (Cobots) have been created to allow physical interaction with the human worker. However, these cobots still lack of recognizing the human emotional state. In this regard, this paper presents an approach for adapting cobot parameters to the emotional state of the human worker. The approach utilizes the Electroencephalography (EEG) technology for digitizing and understanding the human emotional state. Afterwards, the parameters of the cobot are instantly adjusted to keep the human emotional state in a desirable range which increases the confidence and the trust between the human and the cobot. In addition, the paper includes a review on technologies and methods for emotional sensing and recognition. Finally, this approach is tested on an ABB YuMi cobot with commercially available EEG headset. | 10.3390/s21144626 |
pubmed_581_10714 | We investigated whether a taurine-ribose derivative, N-(D-ribopyranosyl)taurine sodium salt, inhibits the differentiation process of preadipocytes or modulates the expression of cytokines from adipocytes as does taurine chloramine (TauCl) in vitro. To know the inhibitory effects of taurine-ribose (Tau-Ribose) on differentiation process and adipokine expression, preadipocytes were incubated with Tau-Ribose in differentiation medium for 14 days. Differentiated adipocytes were also stimulated at the concentration of IL-1β 1 ng/ml with addition of Tau-Ribose. After 7 days of incubation, the levels of adiponectin, leptin, IL-6, and IL-8 were measured from the culture supernatants. At concentrations of 10-40 mM, Tau-Ribose dose-dependently inhibited the process of adipogenesis. The treatment of Tau-Ribose decreased the expression of transcription factors, which are necessary for adipogenesis and are known as adipocyte marker. Treatment with Tau-Ribose significantly modulated the production of IL-8 and IL-6. However, it did not modulate the production of adiponectin and leptin in IL-1β-activated adipocytes. As with taurine chloramine, Tau-Ribose also inhibited STAT-3 signaling, independent of MAPK signaling. In conclusion, Tau-Ribose inhibits the signaling pathway of STAT-3 and can change adipokines production; thus, it may have a potential as an agent for treating obesity-related diseases. | 10.1007/978-94-024-1079-2_52 |
pubmed_271_8523 | Two studies investigated the effects of being forgotten on the target of memory. In Study 1, undergraduate women (N = 96) who had completed a lab session two days prior, were randomly assigned to be remembered, forgotten, complimented, or to a control group. In the absence of effects on mood or social self-esteem, being forgotten resulted in lower meaning in life. In Study 2, participants (N = 47) who had completed a group exercise were informed two days later that no one remembered them, that everyone remembered them, or that no one wanted to work with them. Being forgotten led to lower meaning in life than being remembered but did not differ from being excluded. Being forgotten may be considered a type of incipient ostracism that influences meaning in life but not mood or state social self-esteem. | 10.1080/00224545.2010.522620 |
pubmed_536_19744 | Cardiac sarcoidosis (CS) is a rare but potentially fatal condition that may present with a wide range of clinical manifestations including congestive heart failure, conduction abnormalities, and most notably, sudden death. Recent advances in imaging technology allow easier detection of CS, but the diagnostic guidelines with inclusion of these techniques have yet to be written. It has become clear that minimally symptomatic or asymptomatic cardiac involvement is far more prevalent than previously thought. Because of the potential life-threatening complications and potential benefit of treatment, all patients diagnosed with sarcoidosis should be screened for cardiac involvement. Patients with CS and symptoms such as syncope need an aggressive workup for a potentially life-threatening etiology, and often require implantable cardioverter-defibrillator therapy. CS patients without arrhythmic symptoms are still at risk for sudden death and may warrant an implantable cardioverter-defibrillator for primary prevention reasons. Although corticosteroids are regarded as the first-line drug of choice, therapy for CS is not yet standardized, and it is unclear at this point whether asymptomatic patients require therapy. Randomized clinical trials are clearly warranted to answer these very important patient care questions, and are endorsed fully by the authors. | 10.1016/j.ahj.2008.09.009 |
pubmed_573_11648 | The aminoacyl-tRNA synthetases (aaRSs) are essential components of the protein synthesis machinery responsible for defining the genetic code by pairing the correct amino acids to their cognate tRNAs. The aaRSs are an ancient enzyme family believed to have origins that may predate the last common ancestor and as such they provide insights into the evolution and development of the extant genetic code. Although the aaRSs have long been viewed as a highly conserved group of enzymes, findings within the last couple of decades have started to demonstrate how diverse and versatile these enzymes really are. Beyond their central role in translation, aaRSs and their numerous homologs have evolved a wide array of alternative functions both inside and outside translation. Current understanding of the emergence of the aaRSs, and their subsequent evolution into a functionally diverse enzyme family, are discussed in this chapter. | 10.1007/128_2013_423 |
pubmed_505_8931 | BACKGROUND
We used transcutaneous (TC) carbon dioxide (CO2) monitoring to prospectively evaluate changes in respiratory status after interscalene anesthesia in 45 adults (40 successful and 5 unsuccessful blocks).
METHODS
TC-CO2 oxygen saturation and respiratory rate were recorded every minute for 5 minutes before block and every 2 minutes for a total of 30 minutes (15 data sets) after injection of the local anesthetic solution.
RESULTS
After successful block, TC-CO2 increased from 41 +/- 5 mm Hg to a maximum value of 44 +/- 6 mm Hg (P < 0.0001) and the respiratory rate increased from 14 +/- 2 breaths/min to a maximum of 20 +/- 4 breaths/min (P < 0.001). The increase in TC-CO2 was > or = 5 mm Hg in 11 patients and > or = 10 mm Hg in 4 patients, with a maximum increase of 12 mm Hg. Of the 600 TC-CO2 data points recorded (15 each from the 40 patients with a successful block), 62 (10.3%) showed a TC-CO2 value of 50 mm Hg or greater, with a maximum value of 57 mm Hg. No significant change in TC-CO2 or respiratory rate was seen in the five patients with unsuccessful block.
CONCLUSION
After interscalene blockade, we found an increase in respiratory rate and hypercarbia that resulted in no clinically significant effect. | 10.1097/01.SMJ.0000054425.08030.B0 |
pubmed_194_563 | A sesquiterpene isolated from the roots of Aristolochia indica (Linn.) was found to exert 100% interceptive activity and 91.7% anti-implantation activity in mice at a single oral dose of 100 mg/kg b. wt. No toxic effect was found at the dose levels used. | 10.1007/BF01918832 |
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