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pubmed_422_21248 | A new trapped ion cell design for use with Fourier transform ion cyclotron resonance mass spectrometry is described. The design employs 15 cylindrical ring electrodes to generate trapping potential wells and 32 separately assignable rod electrodes for excitation and detection. The rod electrodes are positioned internal to the ring electrodes and provide excitation fields that are thereby linearized along the magnetic field over the entire trapped ion volume. The new design also affords flexibility in the shaping of the trapping field using the 15 ring electrodes. Many different trapping well shapes can be generated by applying different voltages to the individual ring electrodes, ranging from quadratic to linearly ramped along the magnetic field axis, to a shape that is nearly flat over the entire trap volume, but rises very steeply near the ends of the trap. This feature should be useful for trapping larger ion populations and extension of the useful range of ion manipulation and dissociation experiments since the number of stages of ion manipulation or dissociation is limited in practice by the initial trapped ion population size. Predicted trapping well shapes for two different ring electrode configurations are presented, and these and several other possible configurations are discussed, as are the predicted excitation fields based on the use of rod electrodes internal to the trapping ring electrodes. Initial results are presented from an implementation of the design using a 3.5 T superconducting magnet. It was found that ions can be successfully trapped and detected with this cell design and that selected ion accumulation can be performed with the utilization of four rods for quadrupolar excitation. The initial results presented here illustrate the feasibility of this cell design and demonstrate differences in observed performance based upon different trapping well shapes. | 10.1002/(SICI)1096-9888(200001)35:1<85::AID-JMS910>3.0.CO;2-7 |
pubmed_150_14040 | Despite their unparalleled biodiversity, the genomic resources available for beetles (Coleoptera) remain relatively scarce. We present an integrative and high quality annotated transcriptome of the beetle Callosobruchus maculatus, an important and cosmopolitan agricultural pest as well as an emerging model species in ecology and evolutionary biology. Using Illumina sequencing technology, we sequenced 492 million read pairs generated from 51 samples of different developmental stages (larvae, pupae and adults) of C. maculatus. Reads were de novo assembled using the Trinity software, into a single combined assembly as well as into three separate assemblies based on data from the different developmental stages. The combined assembly generated 218,192 transcripts and 145,883 putative genes. Putative genes were annotated with the Blast2GO software and the Trinotate pipeline. In total, 33,216 putative genes were successfully annotated using Blastx against the Nr (non-redundant) database and 13,382 were assigned to 34,100 Gene Ontology (GO) terms. We classified 5,475 putative genes into Clusters of Orthologous Groups (COG) and 116 metabolic pathways maps were predicted based on the annotation. Our analyses suggested that the transcriptional specificity increases with ontogeny. For example, out of 33,216 annotated putative genes, 51 were only expressed in larvae, 63 only in pupae and 171 only in adults. Our study illustrates the importance of including samples from several developmental stages when the aim is to provide an integrative and high quality annotated transcriptome. Our results will represent an invaluable resource for those working with the ecology, evolution and pest control of C. maculatus, as well for comparative studies of the transcriptomics and genomics of beetles more generally. | 10.1371/journal.pone.0158565 |
pubmed_470_11433 | In situ measurements of Fe and Mn by dialysis and diffusive gradients in thin-films (DGT) in 5 lakes (pH 4.7-7.5, ionic strength 0.3-5 mmol l(-1)) and Cu and Zn in an acidic and circumneutral lake were compared to results from on site filtration. For the most acidic lake (pH 4.7) all measurements agreed, indicating an absence of colloids and negligible complexation by organic matter. There was little difference in the Mn concentrations measured by the three techniques for any lake, consistent with it being free from complexation. Zn measured by dialysis in circumneutral water was only slightly higher than DGT measurements, appropriate to only partial complexation. Substantial differences between dialysis and DGT for Cu were consistent with complexation by fulvic and humic substances, though not to the extent predicted by the speciation code WHAM. To achieve a good fit it was necessary to adjust the pK for Cu-fulvic binding from 0.8 to 1.3 and to assume that fulvic substances dominated. The presence of low molecular weight strong binding ligands would also be consistent with the data. Differences between the three measurement methods were greatest for Fe, attributable to the presence of large oxyhydroxide colloids, organic complexation and low molecular weight, reactive hydrolysis products. Fe and Mn concentrations measured by DGT on samples returned to the laboratory were much lower than in situ concentrations, illustrating the need for in situ measurements. While use of two in situ techniques provided useful information on the speciation of these natural waters, further refinements are required for unambiguous characterization of the solution. The use of DGT with a more restricted gel that excludes complexes with humic substances should provide complementary information to in situ dialysis. | 10.1021/es0200995 |
pubmed_467_16154 | Brain structural plasticity is an extraordinary tool that allows the mature brain to adapt to environmental changes, to learn, to repair itself after lesions or disease, and to slow aging. A long history of neuroscience research led to fascinating discoveries of different types of plasticity, involving changes in the genetically determined structure of nervous tissue, up to the ultimate dream of neuronal replacement: a stem cell-driven "adult neurogenesis" (AN). Yet, this road does not seem a straight one, since mutable dogmas, conflicting results and conflicting interpretations continue to warm the field. As a result, after more than 10,000 papers published on AN, we still do not know its time course, rate or features with respect to other kinds of structural plasticity in our brain. The solution does not appear to be behind the next curve, as differences among mammals reveal a very complex landscape that cannot be easily understood from rodents models alone. By considering evolutionary aspects, some pitfalls in the interpretation of cell markers, and a novel population of undifferentiated cells that are not newly generated [immature neurons (INs)], we address some conflicting results and controversies in order to find the right road forward. We suggest that considering plasticity in a comparative framework might help assemble the evolutionary, anatomical and functional pieces of a very complex biological process with extraordinary translational potential. | 10.3389/fnins.2020.00075 |
pubmed_1090_20696 | A familial variant of male pseudohermaphroditism different from the classical form of the complete testicular feminization syndrome was studied. The three affected 46, XY sibling (16,18 and 20 years old) exhibited female phenotype identical to that of a 17 years old patient with the classical form, included as a control. The major endocrine and biochemical differences observed in this family, as compared with the classical form, includes: a. Markedly elevated serum levels of LH and FSH; b. Non-elevated serum testosterone levels; c. Poor testicular hCG responsiveness; d. Abnormally elevated baseline and hCG-stimulated androstenedione: testosterone ratio; e. Slight pituitary responsiveness to androgens; f. presence of residual androgen uptake by cultured fibroblasts derived from genital skin. These differences were more evident in the two older patients. All subjects presented a lack of nitrogen retention following testosterone administration. These results were interpreted as demonstrating a testicular impairment of testosterone biosynthesis in the older subjects of this family, which resulted in an unusual gonadotropin profile. The altered androstenedione: testosterone ratio suggests a secondary partially decreased activity of testicular 17-hidroxysteroid dehydrogenase, as demonstrated in TFM mice and rats. The overall data indicate an age-dependent variability in the expression of androgen insensitivity in this family, thus demonstrating the wide biochemical heterogeneity of the androgen resistant syndromes. | pubmed_1090_20696 |
pubmed_308_25056 | Parkinson's disease (PD) is a progressive neurological disorder characterized by a large number of motor and non-motor features and is known as the second most common neurodegenerative disorder after Alzheimer's disease. The hallmark pathology of PD is the damage and death of dopamine-producing neurons in the substantia-nigra of midbrain. Intrastriatal transplants of fetal mesencephalon derived DAergic neurons have provided proof-of-principle for the cell replacement strategy and have demonstrated reinnervation of the denervated striatum. However, ethical, technical, and practical limitations of deploying fetal DAergic neurons as the source for cell therapy in PD have ceased the spread of this procedure into clinical practice. Embryonic stem (ES) cells have emerged as a therapeutic alternative that can proliferate extensively and generate dopamine-producing neurons. To this extent and to surmount the obstacles related to embryonic neural cells, many investigations have focused on using pluripotent stem cells for the derivation of DAergic neurons. In the present study, a mouse embryonic stem (mES) R1 cell line was generated which could stably co-express Nurr1 (an essential transcription factor in DAergic neuron development) and GPX-1 (a neuroprotective enzyme against oxidative stress). The Nurr1/GPX-1-expressing ES cells (Nurr1/GPX-1-ES) were differentiated into DAergic-like cells via a three-dimensional culture environment consisting of Poly-ε-Caprolactone (PCL) nanofibrous scaffolds embedded by Matrigel (Mtg) in the presence of specific signaling molecules. DAergic neuron-specific genes were highly expressed in ES-derived DAergic neurons cultured and differentiated on PCL/Mtg scaffolds. Reverse-phase HPLC confirmed that the Nurr1/GPX-1-ES-cells differentiated on PCL/Mtg electrospun scaffolds could efficiently and exclusively secrete dopamine in response to stimulus. In conclusion, our results demonstrated that PCL/Matrigel nanofibrous scaffolds could efficiently support and promote the generation of functional DAergic-like cells from Nurr1/GPX-1-ES cells. The results of this study may have an impact on future tissue engineering for cell therapy of PD. | 10.1007/s12035-016-9726-4 |
pubmed_142_24327 | Type I signal peptidase (SPase) is essential for viability in wild-type bacteria because the terminal step of the bacterial general secretory pathway requires its proteolytic activity to release proteins from their membrane-bound N-terminal leader sequences after translocation across the cytoplasmic membrane. Here, we identify the Staphylococcus aureus operon ayrRABC (SA0337 to SA0340) and show that once released from repression by AyrR, the protein products AyrABC together confer resistance to the SPase inhibitor arylomycin M131 by providing an alternate and novel method of releasing translocated proteins. Thus, the derepression of ayrRABC allows cells to bypass the essentiality of SPase. We demonstrate that AyrABC functionally complements SPase by mediating the processing of the normally secreted proteins, albeit in some cases with reduced efficiency and either without cleavage or via cleavage at a site N-terminal to the canonical SPase cleavage site. Thus, ayrRABC encodes a secretion stress-inducible alternate terminal step of the general secretory pathway. IMPORTANCE : Addressing proteins for proper localization within or outside a cell in both eukaryotes and prokaryotes is often accomplished with intrinsic signals which mediate membrane translocation and which ultimately must be removed. The canonical enzyme responsible for the removal of translocation signals is bacterial type I signal peptidase (SPase), which functions at the terminal step of the general secretory pathway and is thus essential in wild-type bacteria. Here, we identify a four-gene operon in S. aureus that encodes an alternate terminal step of the general secretory pathway and thus makes SPase nonessential. The results have important implications for protein secretion in bacteria and potentially for protein trafficking in prokaryotes and eukaryotes in general. | pubmed_142_24327 |
pubmed_1032_1170 | Fossil fuels used in energy mix continues to dictate world heat usage. Demand for heat is considered as substantial contributor to carbon emissions and energy-related emissions equivalent to 12.5 Gt of carbon emissions. Data on heat is limited and therefore, a study on the causal correlation between energy use and emissions would provide policy guidance on how to decarbonize the heat sector to achieve Paris's Greenhouse Effect Treaty. Most empirical works aggregated energy consumption and ignore spatial dependence and heterogeneity in a panel dataset. Our study, however, disaggregated energy into renewable and non-renewable to find their distinct influence on emissions, which were tested for spatial dependence and heterogeneity and applied potential emissions as environmental impact. Using FGLS and PCSE estimators for the period 1971-2013, our findings revealed that the increase in renewable energy use and industrialization improves the ecological structure of emerging economies while the increase in population, economic expansion, and non-renewable energy use increases the carbon stock. We accordingly, investigated causation direction with pooled mean group estimator. Rising economic power states therefore encourage to ensure energy efficiency and replace fuel use with renewable source for heating to reduce carbon stock. | 10.1007/s11356-019-04140-2 |
pubmed_285_17957 | BACKGROUND
Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease characterized by abnormal smooth muscle-like cell (LAM cell) proliferation in the lung stroma. The origin of LAM cells is still unknown. The gold-standard immunohistochemical diagnostic for LAM is an immunopositive reaction to the HMB-45 antibody.
MATERIALS AND METHODS
We aimed to evaluate 15 diagnostic open-lung biopsy specimens of pulmonary LAM. Based on the LAM histologic score (LHS), we distinguished two groups of histological severity: early- and advanced-stage LAM. The expression of HMB-45, estrogen receptor (ER), progesterone receptor (PR), β-catenin, E-cadherin, podoplanin (D2-40), mini-chromosome maintenance protein 3 (MCM3), and epidermal growth factor receptor (EGFR) was evaluated immunohistochemically. Fluorescence in situ hybridization (FISH) was performed in order to investigate amplification of the EGFR gene in LAM cells.
RESULTS
The expression of ER and EGFR was significantly higher in advanced than in early-stage LAM. Amplification of the EGFR gene was not detected in any of the 15 studied cases. There was a strong-positive correlation between the expression of PR, ER, β-catenin, E-cadherin, and the standard marker of LAM, HMB45.
CONCLUSION
We conclude that together with LHS, ER may be considered a useful tool for evaluating the progression of LAM. β-Catenin and E-cadherin seem to be new potential specific markers of LAM cells. The increased expression of EGFR in LAM cells is not associated with EGFR gene amplification, although it may be a marker of disease progression; the role of this receptor in LAM pathogenesis should be further investigated. Positive reaction of LAM cells with podoplain demonstrates the existence of an additional lymphatic endothelial lineage in LAM cells. | pubmed_285_17957 |
pubmed_832_18886 | BACKGROUND
Small cell lung cancer (SCLC) is the most fatal malignancy for which more effective therapies are urgently needed. Overexpression of myeloid cell leukemia-1 (Mcl-1) has been demonstrated to be one of the most common genetic alterations among different types of tumor/cancer, which induces resistance against various anti-cancer therapies including cisplatin. The study aimed to explore the role of Mcl-1 in the prognosis and resistance to anti-cancer therapy in patients with SCLC.
METHODS
Patients with SCLC were recruited from those enrolled/treated in Sun Yat-sen University Cancer Center. Their specimens were collected for immunohistochemical evaluation. We compared the baseline characteristics, response to chemotherapy and overall survival (OS) of the patients with different expression levels of Mcl-1.
RESULTS
The expression level of Mcl-1 was significantly lower in patients with limited stage SCLC than in those with extensive stage SCLC (P=0.014). Based on the median value of Mcl-1 expression level, the patients were divided into high and low Mcl-1 groups, respectively. Univariate analysis revealed that low Mcl-1 expression was associated with a significant improvement in OS, with a hazard ratio (HR) of 0.538. Multivariate analysis confirmed the independent prognostic value of Mcl-1 expression level (P=0.014). Moreover, we found a significantly close relationship between higher Mcl-1 expression level and shorter time to progression (TTP) of the patients received chemotherapy (P=0.040).
CONCLUSIONS
Our findings demonstrated that Mcl-1 expression level was a prognostic biomarker for survival outcomes and cancer progression in the patients with SCLC. Thus, it could be used as a valuable biomarker in identifying those patients with high risk of treatment failure. | 10.21037/atm-20-2305 |
pubmed_720_15145 | Background: Greater understanding of the roles of tumor necrosis factor-α, IL-1β, IL-10, and the IL-23/T-helper (Th) 17 and IL-12/Th1 pathways in immune dysregulation in moderate/severe hidradenitis suppurativa (HS) has helped in developing new regimens. We aim to review the use of different immunomodulatory therapies used to manage HS. Methods: A comprehensive literature search was conducted on the PubMed and Clinicaltrials.gov databases from 1 January 1947 to 31 December 2018. Only clinical trials, case reports, case series and retrospective analyses published in the English language were included. Results: Our search yielded 107 articles and 35 clinical trials, of which 15 are still ongoing. The tumor necrosis factor-α inhibitors adalimumab and infliximab were the most comprehensively studied agents. Published data from clinical trials support the efficacy of adalimumab, infliximab, anakinra, ustekinumab, bermekimab and apremilast but not etanercept and MEDI8968. Clinical trials for CJM112 have been completed, with results awaiting publication. Trials are underway for secukinumab, IFX-1, INCB054707 and bimekizumab. Biologics used in smaller cohorts include canakinumab, golimumab and rituximab. Most agents are well tolerated and demonstrate a good safety profile, with the most commonly reported adverse event being infections. Discussion and conclusions: To date, adalimumab is the only biologic which has been approved by the United States Food and Drug Administration for HS. However, other agents also show promise, with further trials underway to evaluate their efficacy, tolerability and safety profiles. Different clinical measurement scores and endpoints used to make direct comparison difficult. Longitudinal surveillance and pooled registry data are paramount to evaluate the long-term safety profile and efficacy of therapy. | 10.2147/BTT.S199862 |
pubmed_470_11871 | BACKGROUND AND PURPOSE
During recent years, survival of patients with invasive bladder cancer has been improved by early diagnosis and radical treatment. Urinary lithiasis is not rare in patients who have been submitted to radical cystectomy and urinary diversion. We have demonstrated the effectiveness and safety of SWL for these patients.
PATIENTS AND METHODS
We studied 11 patients who presented to our lithotripsy department suffering from urinary lithiasis after radical cystectomy. They were all cancer free at the time of treatment, and all underwent SWL on the Dornier HM-3 lithotripter as a first-line treatment. The mean stone burden was 1.85 cm(2), and the stone-to-patient ratio was 1:1.
RESULTS
The stone-free rate 1 month after SWL was 63.7%. Patients who were not stone free underwent a second SWL, and the stone-free rate after the second SWL session was 81.8%. We performed percutaneous nephrolithotripsy in one patient after the second SWL session because of the large stone burden remaining (3.2 cm(2)). The remaining patient was submitted to ureterolithotomy.
CONCLUSION
Application of SWL gives very good results in the treatment of urinary lithiasis in patients with a urinary diversion. Indeed, the results are equivalent to those achieved in patients without urinary diversion. | 10.1089/08927790260472854 |
pubmed_100_25094 | The disruption of normal mitosis by histone deacetylase inhibitors is a significant contributor to the anticancer effects of these drugs. However, the mechanism by which these drugs affect mitosis is poorly understood. A number of recent papers have now thrown considerable light onto how these drugs elicit this very distinctive cell cycle disruption. | 10.4161/cc.10.16.16953 |
pubmed_364_19862 | In this article, we propose a dataset about the energy consumption of mobile devices that was collected as part of a "Tour de France" with an electrical wheelchair. Part of these data was used to propose a mathematical model based on an experimental methodology of the energy consumed in mobile devices. Based on these precise measurements in a real environment, we have elaborated predictive models of energy consumption. The objective of this paper is to make accessible the data related to these publications to other researchers in several fields of science (computer science, telecommunications, meteorological science, artificial intelligence, statistics...). To our knowledge, this is the first publication of a dataset recording real world energy consumption data in mobile devices. | 10.1016/j.dib.2020.106334 |
pubmed_960_18695 | PURPOSE
To describe magnetic resonance imaging (MRI) findings at long-term follow-up after rotator cuff (RC) tear using standard MRI sequences without fat saturation.
MATERIAL AND METHODS
Twenty-eight patients aged 55.8+/-7.6 underwent MRI examination 4.6+/-2.1 years after surgery for RC tear. Standard sequences in oblique coronal, oblique sagittal, and axial planes were obtained. The RC, including re-tears and tendon degeneration, was independently evaluated by two observers. Thickness of the supraspinatus tendon and narrowing of the subacromial space were measured. The clinical outcome was evaluated with the Constant score and compared with the MRI findings.
RESULTS
The RC tear was traumatic in 18 (64%) patients and degenerative in 10 (36%). At follow-up, 11 (39%) had normal RC tendons with good clinical outcome. Four (14%) patients had painful tendinosis without RC tear. A full-thickness RC tear was found in 7 (25%) patients and a partial tear in 6 (21%). In one patient with a full-thickness tear, and in two with partial tear, tendinosis was found in another of the RC tendons. The subacromial space was narrowed in 13 (46%) of the patients. A narrowing of the subacromial space correlated with re-tear (P<0.05).
CONCLUSIONS
The RC may be evaluated with standard MRI sequences without fat saturation at long-term follow-up. A normal appearance of the RC is correlated with good clinical outcome, while re-tear and tendinosis are associated with pain. | 10.1080/02841850410006092 |
pubmed_100_14339 | OBJECTIVE
To clarify whether headache, and particularly migraine, belongs to the spectrum of neurologic manifestations of systemic lupus erythematosus (SLE), the archetypal autoimmune disease.
METHODS
Consecutive SLE patients were matched 1:1 for age, gender, and level of education with healthy control subjects. A representative subgroup of SLE patients were also matched with patients suffering from multiple sclerosis (MS), a nervous system-specific autoimmune disease. All study participants were assessed for headache present in the previous year. Anxiety, depression, and quality of life were also estimated at baseline. During the following year, all participants were assessed every 3 months using specific headache diaries.
RESULTS
Seventy-two SLE/control pairs and 48 MS patients completed 12 months of follow-up. Prevalence of migraine, with or without aura, was similar between SLE patients (21%), MS patients (23%), and controls (22%), as was the prevalence of frequent tension-type headache. Duration and severity of migraine attacks were milder in SLE patients than controls. Only chronic tension-type headache was significantly more prevalent in SLE patients (12.5%) compared to controls (1.4%). MS patients also presented increased frequency of chronic tension-type headache (8.3%). No associations of any headache type with particular clinical manifestations, autoantibody, or disease activity, either in SLE or MS patient groups, were found. Irrespective of the presence of headache, anxiety symptoms and impaired quality of life were more frequent among SLE than MS patients or controls.
CONCLUSION
Migraine should be no longer considered a neurologic manifestation of systemic or organ-specific autoimmunity. Increased migraine prevalence in these patients found in previous studies could be due to methodological weaknesses. | 10.1111/j.1526-4610.2011.01962.x |
pubmed_546_6092 | PURPOSE
Pulsed dose rate (PDR) treatment is a new approach that associates the physical advantages of high-dose-rate (HDR) technology with the potential radiobiological advantages of low-dose-rate (LDR) brachytherapy. This retrospective study analyzes the feasibility, toxicity, and preliminary oncologic results in a series of 43 patients treated with PDR interstitial brachytherapy.
METHODS AND MATERIALS
Twenty-four patients with pelvic, 17 patients with head and neck, and 2 patients with breast cancers were treated. Twenty-eight patients had primary and 15 recurrent tumors; 14 had received prior external irradiation to the same site. The doses per pulse at the prescription isodose were 0.4-1 Gy (median 0.5 Gy), delivered using a single cable-driven 0.3-1.0 Ci 192-iridium source (PDR Nucletron Micro-Selectron).
RESULTS
The median treated volumes (at the prescribed isodose) were 28 cc for pelvic, 8.33 cc for head and neck, and 40 cc for breast malignancies. Of 14,499 source and 14,499 dummy source transfer procedures, 3 technical machine failure events were observed (0.02%). Grade 3 acute toxicities were seen in 5/43 patients (4 oral stomatitis, 1 vaginal mucositis) and grade 4 acute toxicity in one patient (rectovaginal fistula). Grade 3-4 late complications were observed in 4/41 (9.8%) patients: 1 pubic fracture, 1 rectovaginal fistula, 1 vesicovaginal fistula and 1 local necrosis. With a median follow-up of 18 months, 10/41 patients progressed locoregionally (6 pelvic, 4 head and neck), 3 developed local recurrence and distant metastasis (3 pelvic), 3 only distant metastasis (2 pelvic, 1 head and neck). Two patients are lost to follow-up.
CONCLUSION
PDR interstitial brachytherapy for pelvic, head and neck, and breast malignancies is feasible and the acute and late toxicities seem acceptable. Although the physical advantages of PDR are clear, further follow-up is required to determine how results compare with those obtained with standard LDR brachytherapy. | 10.1016/s0360-3016(98)00525-2 |
pubmed_1033_12422 | A nanoscale slipped sandwich of Tb(10) is formed from the reaction of 5-bromo-3-methoxysalicylaldehyde (HL) with TbCl(3)x6H(2)O and Zn(OAc)(2)x2H(2)O. The compound also features an unusual example of a coordinated methylhemiacetal which is derived from HL. | 10.1039/B405981F |
pubmed_733_5725 | UNLABELLED
The hypoglycemic drug, troglitazone (TGZ) has antioxidant activity. Superoxide dismutase (SOD) removes superoxide produced by cells. We measured the response of SOD-like activity (deltaSOD) to ascorbic acid (AA) or TGZ using electron spin resonance at various glucose concentrations in polymorphonuclear leukocytes from 18 type 2 diabetic patients and 18 healthy controls. In control and diabetic subjects, ASOD in response to AA was dose-dependent (maximal effect at 100 ng/ml). Maximal response occurred 2 min after AA addition (50 ng/ml). In cells from diabetic patients, ASOD with 25 ng/ml AA was significantly less than for healthy controls. The deltaSOD with AA changed little at glucose concentration from 0 to 200 mg/dl. In patient and control cells, higher glucose concentrations (400 to 800 mg/dl) reduced ASOD with AA. Response patterns with TGZ resembled those with AA. deltaSOD with AA correlated positively with glycosylated hemoglobin A1c.
CONCLUSIONS
The present data suggest that an amerioration of blood glucose on high levels in diabetic patients plays an important role in an antioxidant efficacy of TGZ and AA on leukocytes in patients. | 10.1016/s0024-3205(02)01513-8 |
pubmed_1030_2784 | Section Head
Clinical/translational cancer immunotherapy.
Background
The goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small-cell lung cancer (NSCLC).
Methods
Utomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored. Tumor responses by RECIST1.1 were assessed by baseline and on-treatment scans. Tumor biopsies were collected for detection of programmed cell death ligand 1, CD8, 4-1BB, perforin, and granzyme B, and gene expression analyzed by next-generation sequencing. CD8+ T cells from healthy donors were stimulated with anti-CD3 ± utomilumab and compared with control.
Results
Patients with melanoma (n=43) and NSCLC (n=20) received utomilumab 0.24 mg/kg (n=36), 1.2 mg/kg (n=26), or 10 mg/kg (n=1). Treatment-emergent AEs (TEAEs) occurred in 55 (87.3%) patients and serious TEAEs in 18 (28.6%). Five (7.9%) patients discontinued owing to TEAEs. Thirty-two (50.8%) patients experienced treatment-related AEs, mostly grade 1-2. Objective response rate: 2.3% in patients with melanoma; no confirmed responses for patients with NSCLC. Ten patients each with melanoma (23.3%) or NSCLC (50%) had stable disease; respective median (95% confidence interval, CI) progression-free survival was 1.8 (1.7-1.9) and 3.6 (1.6-6.5) months. Utomilumab exposure increased with dose. The incidences of antidrug and neutralizing antibodies were 46.3% and 19.4%, respectively. Efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity appeared to be blunted at higher doses.
Conclusions
Utomilumab was well tolerated, but antitumor activity was low in patients who previously progressed on ICIs. The potential of 4-1BB agonists requires additional study to optimize efficacy while maintaining the tolerable safety profile. | 10.3389/fimmu.2022.897991 |
pubmed_410_6443 | Natural and intuitive interfaces that monitor and promote upper limb task-specific training need to be developed. This article presents the development and testing of a touch-based game system for training and assessment of unilateral (ULR) and bilateral (BLR) reaching movements. Interaction becomes intuitive and simple by introducing in-game touch and pressure onto virtual targets projected on a custom-made large touch panel. A custom-made App integrates exergames and a biomechanical model with advanced algorithms for movement analysis. It processes and manages data from a motion-tracking sensor and a large touch panel equipped with 1222 (26 × 47) piezoresistive sensors, including high-speed readout electronics and algorithms to measure touch points and contact forces during fingertip interaction. An experiment was conducted to evaluate the experience, motivation, and movements of healthy and stroke subjects when interacting with the proposed system. The panel height, dispersion of virtual targets, and required contact force were customized based on motor skills of each group of subjects. Both groups of subjects showed high level of motivation and user experience when interacting with the virtual environments. Stroke subjects performed the task slower and traveled a similar path length than healthy subjects, but with shorter range of motion. The mechanical work and potential energy profiles of both groups are consistent with those achieved when reaching real objects. The proposed contact-based exergames are a feasible solution for performing natural and intuitive therapeutic ULR and BLR exercises. They elicit appropriate reaching movements and contact forces in healthy and stroke subjects. The spatial and temporal attributes of the proposed solution can be customized to influence the movement and energy expenditure of specific joints. | 10.1089/g4h.2021.0115 |
pubmed_94_16174 | The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity ("the Phe43 cavity") located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc.IMPORTANCE The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics. | 10.1128/mBio.00280-20 |
pubmed_400_23109 | Cre initiates recombination by preferentially exchanging the bottom strands of the loxP site to form a Holliday intermediate, which is then resolved on the top strands. We previously found that the scissile AT and GC base pairs immediately 5' to the scissile phosphodiester bonds are critical in determining this order of strand exchange. We report here that the scissile base pairs also influence the Cre-induced DNA bends, the position of which correlates with the initial site of strand exchange. The binding of one Cre molecule to a loxP site induces a approximately 35 degrees asymmetric bend adjacent to the scissile GC base pair. The binding of two Cre molecules to a loxP site induces a approximately 55 degrees asymmetric bend near the center of the spacer region with a slight bias toward the scissile A. Lys-86, which contacts the scissile nucleotides, is important for establishing the bend near the scissile GC base pair when one Cre molecule is bound but has little role in positioning the bend when two Cre molecules are bound to a loxP site. We present a model relating the position of the Cre-induced bends to the order of strand exchange in the Cre-catalyzed recombination reaction. | 10.1074/jbc.M302272200 |
pubmed_788_20324 | OBJECTIVE
To investigate the effects of mechanical ventilation on Toll like receptor 4 (TLR4) in rat's alveolar macrophages (AM).
METHODS
Eighteen clean grade adult male SD rats weighting 230-240 g were randomly divided into three groups (n=6): autonomous breathing group(R group), small tidal volume (V(T)) mechanical ventilation group (M group, V(T)=6 ml/kg) and large V(T) mechanical ventilation group (N group, V(T)=40 ml/kg). The animals were anesthetized with intraperitoneal 20% urethane 8 ml/kg, tracheostomized and mechanically ventilated [inhalation: exhalation (I:E)=1:1, with positive end-expiratory pressure (PEEP)=0, fraction of inspired oxygen (FiO(2))=0.21]. The respiratory rate was adjusted, and end-tidal carbon dioxide partial pressure (P(ET)CO(2)) was maintained at 35-45 mm Hg (1 mm Hg=0.133 kPa). Arterial blood samples were taken for blood gas analysis at the beginning of the experiment and 1, 2 and 3 hours after the experiment. The experiment was terminated, and pathomorphology score, pulmonary tissue wet/dry (W/D) weight ratio, white blood cells count (WBC) in bronchoalveolar lavage fluid (BALF) were determined at 3 hours. The rats were sacrificed by bloodletting after experiment. Then the rats' BALF and pulmonary albumin permeability (PAP) were determined. The expression of AM TLR4 mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). AM TLR4 protein expression was determined by immunohistochemistry.
RESULTS
Over ventilation, elevated pH and lower partial pressure of carbon dioxide in arterial blood (PaCO(2)) were observed in N group at 1 hour, and other indexes were normal. The pulmonary pathomorphology score, pulmonary W/D weight ratio, WBC in BALF, PAP, and the mRNA expression of TLR4 and the protein of TLR4 in AM in the N group were greatly increased as compared with the R group (all P<0.01), while they were not significantly changed in the M group (all P>0.05).
CONCLUSION
Large V(T) mechanical ventilation induced injury of lungs and up-regulated TLR4 expression in rat's AM. Small V(T) mechanical ventilation avoided above-mentioned changes. | pubmed_788_20324 |
pubmed_178_13340 | Two immunohistochemical methods were used to detect the presence of luteinizing hormone (LH) on the cells of chicken granulosa. Using a peroxidase-labelled anti-rabbit serum together with anti-chicken LH serum raised in rabbits, a strong positive response was obtained with granulosa cells from small and large pre-ovulatory follicles obtained from the mid-cycle. Similarly, by using an available antiserum to human follicle stimulating hormone (FSH), a slightly weaker response was obtained with cells from both large and small follicles. After incubating cells with ovine LH, ovine FSH and ovine prolactin, there was no detectable difference with the method used in reaction with their respective antisera to cells which had received no incubation, implying that chicken gonadotrophins were displaced only partially from their receptors by mammalian gonadotrophic hormones. Pre-incubation of the cells with human chorionic gonadotrophin gave negative results with anti-hCG serum. Using a fluorescent-labelled antibody method, similar results were obtained except that the distribution of the receptors on the granulosa cell for LH or FSH appeared to be different. With the LH, the fluorescence formed a halo around the cell in contrast to the overall fluorescence with FSH. | 10.1007/BF01003339 |
pubmed_496_18378 | The development of clinical skills for nursing students is a critical component of any undergraduate nursing program. Providing sufficient quality experience for students to develop competence has been recognised as a problem in skill acquisition. At the same time, peer learning has been identified as a valuable strategy for teaching and learning. Nurse academics at a Sydney university recognized these facts and implemented a peer learning strategy into existing first and third year nursing therapeutics units of study. This innovative approach linked the Australian Nursing Council Inc (ANCI) standards of practice to skills acquisition, resulting in third year students increasing their understanding of the relevance of these competency standards to practice. The peer learning strategy involved partnering first and third year students for clinical skills practice sessions. Evaluation of the peer learning approach indicated students valued the experience. | 10.1016/j.nedt.2005.08.001 |
pubmed_634_25585 | INTRODUCTION
The sponging of microRNAs by a long non-coding RNA (lncRNA) away from their coding gene targets is a conceptually-simple, yet biologically-complex method of lncRNA-mediated gene regulation. Currently, predictions of genes that participate in sponge-based regulation are largely based on sequence homology alone, which may not adequately reflect the cellular environment in which lncRNA:miRNA pairs interact. The vast number of potential interactions generated by these predictions impedes the identification of functional gene regulatory relationships, which necessitates an approach that considers biological context. XIST, the female-specific lncRNA canonically involved in silencing the X chromosome, has been suggested by many studies to act as a miRNA sponge. The sex-specificity of XIST provides the opportunity to study the biological feasibility of proposed XIST-miRNA interactions. Here we take a comprehensive approach by considering factors that affect possible regulation through XIST-miRNA sponging.
RESULTS
To identify the most feasible candidates in a particular tissue (lung adenocarcinomas), we considered protein-coding genes that (1) were positively correlated with XIST expression within sexes, (2) were targeted by miRNAs shared with XIST, and (3) expressed in lung adenocarcinoma. This revealed a robust set of 124 genes potentially positively regulated by XIST through the sequestration of 804 shared miRNAs. We then used the basic sex-specific nature of XIST to compare the changes in miRNA-target gene relationships in endogenously high-XIST and low-XIST systems to discover a high-confidence set of only 13 miRNA-gene pairs. As XIST is expressed exclusively in the nucleus, we validated the nuclear presence of several of these high-confidence miRNAs using RT-qPCR, confirming the co-localization required for XIST to interact with these species.
CONCLUSIONS
We use a biology-driven approach to identify genes defended from miRNA-based inhibition by the lncRNA XIST. Importantly, we identify that only a small subset of miRNAs predicted by sequence homology alone have the capacity to mediate the XIST-target gene axis, as they are enriched in the nucleus and able to co-localize with XIST for sponging. Our results reinforce the necessary consideration of biological features in future studies of lncRNA:miRNA interactions. | 10.1371/journal.pone.0221371 |
pubmed_74_7531 | BACKGROUND
There is rising public concern over the widening health inequalities in many countries. The aim of this study was to clarify the associations of socioeconomic status (SES)-related variables, such as levels of household disposable income and employment status, and lifestyle factors with mental health conditions among Japanese adults aged 40 to 69.
METHODS
A cross-sectional study of 3085 participants (1527 males and 1558 females) was undertaken by using a self-administered questionnaire that included the Japanese version of the 12-item General Health Questionnaire (GHQ-12) and questions related to socioeconomic and lifestyle factors.
RESULTS
The prevalence of poor mental health conditions, represented by a GHQ-12 score of 4 or more, was 33.4% among males and 40.4% among females. Males whose annual household disposable income was less than 2 million yen had significantly higher GHQ-12 scores than those with an annual household disposable income above 2 million yen. As per binary logistic regression analyses, short sleep duration and the absence of physical exercise were significantly related to poor mental health conditions among both males and females. Among females, a household disposable income of less than 2 million yen could be a risk factor for poor mental health conditions. Age and habitual drinking were inversely associated with poor mental health conditions.
CONCLUSIONS
Low levels of household disposable income and unhealthy lifestyle factors were significantly associated with mental health conditions. These results suggest the importance of improving unhealthy lifestyle behaviours and developing effective health promotion programmes. In addition, there is a need for social security systems for people from different socioeconomic backgrounds. | 10.1186/s12889-019-8022-4 |
pubmed_855_23356 | Evidence-based medicine is currently a fashionable term. The evidence that warfarin is safe, effective, and cost beneficial in preventing stroke in AF, DVT treatment, and DVT prophylaxis is mounting. However, the evidence that warfarin remains underutilized in these conditions is also mounting. There is new evidence that supports conservative management of overanticoagulation without bleeding. The amount of time, if any, that patients are off warfarin for various procedures is being reduced. Warfarin interactions with other agents continue to be reported so that practitioners can avoid or treat them. Even the contraindication of warfarin in pregnancy is being reexamined. Those with expertise in anticoagulation therapy have an imperative to inform colleagues about the evidence in favor of warfarin. | 10.1177/107602969900500402 |
pubmed_158_19463 | OBJECTIVE
To obtain information from the members of the boards of devolved health care authorities on their motivations, attitudes and approaches, to evaluate their relative orientations to the expectations of provincial governments, local providers and community members, and to evaluate the influence of members' being employees in health care or social services and being willing to stand for election.
DESIGN
Mail survey conducted in cooperation with the devolved authorities during the summer of 1995.
SETTING
Three provinces (Alberta, Saskatchewan and Prince Edward Island) with established boards and 2 provinces (British Columbia and Nova Scotia) with immature boards.
PARTICIPANTS
All 791 members of the boards of devolved authorities in the 5 provinces, of whom 514 (65%) responded.
OUTCOME MEASURES
Respondents' declared motivations, levels of confidence in board performance and attitudes toward accountability; differences between members who were willing to run for election to boards and others and differences between members who were employees in health care or social services and others.
RESULTS
The main motivations of board members were an interest in health care and a desire to be part of decision-making and their main concern was inadequacy of data for decision-making. Almost all (93%) felt that they made good decisions, and 69% thought that they made better decisions than those previously made by the provincial government. Most (72%) felt that they were accountable to all of the local citizens, although nearly 30% stated that they represented the interests of a specific geographic area or group. Attitudes toward their provincial governments were polarized, with half agreeing and half disagreeing that provincial rules restrict the board members. The board members who were employed in health care and social services and those who were willing to stand for election did not differ substantially from their counterparts, although potential electoral candidates were less likely than others to feel accountable to provincial-level constituencies (such as taxpayers and the minister of health) and more likely to represent the interests of a specific geographic area or group. Only a modest number of differences were found among members from different provinces.
CONCLUSIONS
Board members' strong feelings of accountability to and representation of local citizens could counteract the structural influences leading board members to favour the interests of provincial governments and providers. | pubmed_158_19463 |
pubmed_786_19770 | Binding of tissue inhibitor of metalloproteinase-2 (TIMP-2) to pro-MMP-2 and mature membrane type-1 MMP (MT1-MMP) on the cell surface is required for activation of MMP-2. It has been reported that following binding to cell surface receptors, TIMP-2 undergoes endocytosis and extensive degradation in lysosomes. The purpose of this study was to reexamine the fate of TIMP-2 following binding to transfected HT1080 cell surface MT1-MMP at 4 degrees C. Following 37 degrees C incubation, 125I-TIMP-2 release, endocytosis, and degradation were characterized under varying conditions. More than 85% of the total 125I-TIMP-2 bound to cells was released as intact functional molecules; <15% was degraded. Transfection of HT1080 cells with dominant negative mutant dynamin cDNA resulted in delayed endocytosis and release of 125I-TIMP-2 from cells. Pharmacologic agents that induce clustering of cell surface receptors (concanavalin A) and interfere with endosomal/lysosomal function (bafilomycin A(1)) resulted in enhanced binding of 125I-TIMP-2 to cell surface receptors. Abrogation of activation of proMT1-MMP with a furin inhibitor prevented binding and endocytosis of 125I-TIMP-2. Biotinylation of cell surface MT1-MMP followed by Western blotting confirmed the presence of mature MT1-MMP on the cell surface and degraded MT1-MMP in the intracellular compartment. In conclusion, these studies demonstrate that TIMP-2 is released from cells primarily as an intact functional molecule following binding to MT1-MMP on the cell surface. | 10.1016/j.yexcr.2003.10.007 |
pubmed_647_17032 | Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell- but not B cell-dependent because PDL1-specific antibody treatment caused fetal rejection in B cell-deficient but not in RAG-1-deficient females. Blockade of PDL1 also resulted in a significant increase in the frequency of IFN-gamma-producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN-gamma levels in placental homogenates by ELISA. Finally, PDL1-deficient females exhibited decreased allogeneic fetal survival rates as compared with littermate and heterozygote controls and showed evidence of expansion of T helper type 1 immune responses in vivo. These results provide the first evidence that PDL1 is involved in fetomaternal tolerance. | 10.1084/jem.20050019 |
pubmed_1022_23642 | OBJECTIVE
Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.
DESIGN AND METHODS
Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy.
RESULTS
Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6-1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5-1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4-1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1-1.7; P = 0.12).
CONCLUSIONS
There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use. | 10.1371/journal.pone.0081997 |
pubmed_944_10737 | The role of the nonbonded CH···π interaction in the hydrogen abstraction from glycerol by the coenzyme B(12)-independent glycerol dehydratase (GDH) was examined using the QM/MM (ONIOM), MP2, and CCSD(T) methods. The studied CH···π interaction included the hydrogen atom of the -C(2)H(OH)- group of the glycerol substrate and the tyrosine-339 residue of the dehydratase. A contribution of this interaction to the stabilization of the transition state for the transfer of a hydrogen atom from the adjacent terminal C(1)H(2)(OH) group to cysteine 433 was determined by ab initio HF, MP2, and CCSD(T) calculations with the aug-cc-pvDZ basis set for the corresponding methane/benzene, methanol/phenol, and glycerol radical/phenol subsystems. The calculated CH···π distance, defined as the distance between the H atom and the center of the phenol ring, shortened from 2.62 to 2.52 Å upon going from the ground- to the transition-state of the GDH-catalyzed reaction. However, this shortening was not accompanied by the expected lowering of the CH···π interaction free energy. Instead, this interaction remained weak (about -1 kcal/mol) along the entire reaction coordinate. Additionally, the mutual orientation of the CH group and the phenol ring did not change significantly during the reaction. These results suggest that the phenol group of the tyrosine-339 does not contribute to lowering the activation barrier in the enzyme, but do not exclude the possibility that tyrosine 339 facilitates proper orientation of glycerol for the electrostatic catalysis, or inhibits side-reactions of the reactive glycerol radical intermediate. | 10.1021/jp202687g |
pubmed_329_3637 | There is a move towards the adoption of district-wide approaches to pressure sore prevention, with prevention policies incorporating solutions to the problems encountered by services such as ambulance, X-ray, theatre, and A&E ( 1 , 2 , ). | 10.7748/ns.7.21.11.s74 |
pubmed_58_17212 | BACKGROUND
In recent years, there has been an increasing interest in the determinants of subjecti ve well-being and happiness. In that context, life satisfaction is one of the measures used to assess subjective well-being, with emphasis in adult population.
OBJECTIVE
Adapt and validate (cultu rally and linguistically) the Canadian "Satisfaction with Life adapted for Children" (SWLS-C) in Chilean adolescents, in order to assess their global judgement about their own lives.
PATIENTS AND METHODS
Cross-sectional study, with adolescents between 10 to 18 years old, of both sexes and three socioeconomic levels in the Metropolitan region of Chile. After a process of translation and back translation, the scale SWLS-C was applied in 3 groups: cognitive interviews (n = 23) to evaluate se mantics, content, reliability and construct validity, a second group was used as pretest (n = 24) and a third for the validation of the test (n = 200). Factor analysis was performed and measurement of convergent and divergent validity.
RESULTS
The internal consistency of the scale through Cronbach's alpha was 0.815, with item-total correlations between 0.51 and 0.7. The correlation between scale items varies between 0.390 and 0.607. In the main component analysis, all items met the require ment of a factor greater than 0.3. The inverse correlation between SWLS-C and CDI was significant, with a linear R2 of 0.465.
CONCLUSIONS
The Chilean version of the SWLS-C shows adequate psycho metric properties, construct validity, confirming its unidimensional character and the need to keep each item of the Canadian version. SWLS-C, in its Chilean version, is suitable to be self-applied in adolescent population. Further studies are needed to provide further evidence. | 10.4067/S0370-41062018000100051 |
pubmed_857_6418 | The steroid secretory activity of cultured ovarian follicles of Rana dybowskii and the activities of relevant steroidogenic enzymes were examined during the natural hibernation period (October-February). Enzyme activities were measured indirectly by monitoring the conversion of exogenous substrates to products by isolated follicles. Follicles were incubated for 6 h in amphibian Ringer in the presence or absence of frog pituitary homogenate (FPH, 0.1 pituitary/2 ml) and/or various steroid precursors. Progesterone (P4), 17 alpha-hydroxyprogesterone (17 alpha-OHP) or testosterone (T) secreted by the follicles into the medium were measured by RIA. In the presence of FPH, high levels of P4 were produced by follicles at the early and mid-hibernation period (695 and 898 pg/follicle, respectively) whereas markedly elevated levels of P4 were produced during late hibernation (1,393 pg/follicle) (just prior to or breeding season, February). In contrast, high levels of T were produced by the follicles early in hibernation (1,206 pg/follicle) while negligible levels were produced in late hibernation (69 pg/follicle). Higher levels of 17 alpha-OHP were produced by follicles at early and mid hibernation (594 and 705 pg/follicle, respectively) than in later hibernation (221 pg/follicle). Addition of exogenous pregnenolone markedly increased P4 levels in a dose-dependent manner when added to follicles at early and late stages of hibernation: FPH addition further enhanced conversion of pregnenolone. Similarly, addition of androstenedione (AD) increased T levels in a dose-dependent manner by these follicles. However, following addition of exogenous P4, less 17 alpha-OHP was produced by follicles collected in late hibernation as compared to those collected earlier.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1002/jez.1402670305 |
pubmed_646_4662 | We report two infants with bilateral basal ganglia-thalamic lesions subsequent to prolonged fetal bradycardia. Cardiotocogram revealed severe bradycardia lasting for more than 20 min in both. They demonstrated a significant encephalopathy, abnormal muscle tones and signs of brainstem injury. Clinical or electrical seizures were not observed in either of them. CT during early neonatal period demonstrated decreased tissue attenuation in basal ganglia and thalami in the absence of extensive cortical changes. Both of them developed severe mental retardation and quadriplegia. MRI in late infancy demonstrated abnormal high intensity areas in bilateral basal ganglia, thalami and around central sulci on T2-weighted image. Close correlation between prolonged fetal bradycardia and basal ganglia-thalamic lesion was suggested. | 10.1016/s0378-3782(00)00072-4 |
pubmed_427_6781 | 1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type. | 10.1016/0005-2760(75)90019-3 |
pubmed_277_10547 | BACKGROUND
The teaching of infection control is gradually being introduced at dental schools in Mexico. However, most practicing dentists have limited access to current infection control standards. Deficiencies of knowledge with regard to blood-borne pathogens such as HIV and hepatitis B virus may influence attitudes toward infected individuals and reduce compliance with infection control recommendations.
OBJECTIVE
The purpose of this study was to assess (1) attitudes toward HIV-infected patients and hepatitis B virus-infected patients and (2) infection control knowledge and practices among dental practitioners in Mexico City.
METHOD
A total of 196 dentists were interviewed by means of a questionnaire with Likert-type scales and open-ended questions (response rate, 86.1%).
RESULTS
Most respondents had no previous social or professional contact with HIV-positive individuals. Nine percent indicated that they had knowingly treated HIV-positive patients. Perceived professional and moral obligations to treat HIV-positive patients were high. Thirty-five percent of the respondents perceived the risk of HIV infection as "considerable" to "very strong." The risk of hepatitis B infection was considered significantly higher than the risk of HIV infection (P <.01); however, 78% of the respondents had not been immunized against hepatitis B. Reported use of personal protective equipment was high. Most respondents used dry heat sterilization. The principal disinfectants used were quaternary ammonium compounds, bleach, and glutaraldehyde. Fifty-four percent of the respondents acknowledged that clinical precautions reduced occupational risks.
CONCLUSIONS
This survey revealed contradictory attitudes toward HIV-positive individuals and limited understanding of infection control recommendations. Educational and regulatory efforts are needed to promote better adherence to current infection control standards. | 10.1016/s0196-6553(00)90007-5 |
pubmed_777_176 | BACKGROUND AND AIM OF THE STUDY
Aortic valve sclerosis is fairly common and is currently seen as a marker of systemic atherosclerosis. For unclear reasons only a minority of those sclerotic valves will evolve to become stenotic suggesting that atherogenic factors alone are insufficient to explain the development of valve stenosis. We had reported in a model of cholesterol fed rabbits that a combination of high cholesterol with vitamin D supplementation was necessary to induce valve stenosis and significant calcium deposition whereas high cholesterol alone only induced a sclerosis of the valve. In this study, we further evaluated the role of vitamin D treatment in the development of aortic valve disease (sclerosis or stenosis) in this rabbit model.
METHODS
Rabbits were divided in 4 groups followed for 12 weeks: 1) no treatment; 2) cholesterol-enriched diet, 3) cholesterol-enriched diet + vitamin D2 (VD; 50000IU, daily) 4) VD alone for 12 weeks. Echocardiographic assessment of the aortic valve was done at baseline, and every 4 weeks thereafter. Aortic valve area, maximal and mean transvalvular gradients were recorded and compared over time. Immunohistological study of the valves of AS rabbits was also realized for several classical atherosclerosis markers.
RESULTS
Vitamin D2 treated animal did not develop any stenosis of the valve despite increased echogenicity due to diffuse calcium deposits on the leaflets without any atherosclerotic lesions. Only the combination of high cholesterol with VD resulted in a decrease of aortic valve area. Immunohistological analysis of aortic valves from VD rabbits showed the presence of calcium deposits, T-cell infiltration in addition to positive labeling for alpha-smooth muscle cell actin. We did not observe macrophage infiltration in aortic valve leaflets of VD rabbits.
CONCLUSION
Hypercholesterolemia or vitamin D supplements alone could not induce aortic valve stenosis in our animal model whereas the combination resulted in a decreased aortic valve area. These findings support the hypothesis that a combination of atherosclerotic and calcifying factors is necessary to induce aortic valve stenosis in this model. | pubmed_777_176 |
pubmed_996_19068 | Thirty-two men who participated in a trial of Zidovudine (> 500 CD4 cells/10(6) L) were surveyed regarding their reasons for participation in clinical trials. The major source of influence to enter the trial was the clinic doctor, and importance for self in participation was rated as the least important reason. Medical science and medical researchers were seen as the major beneficiaries. Being seen to do something about one's illness was also seen as being important and probability of delaying AIDS was rated lowest. Chance of occurrence of risks of treatment were rated as slightly below 50%. Results of Flesch and Fry tests of informed consent documents suggested that they were written in the style of a scientific article, required the readability level of a university graduate and that recall was imperfect. Those who saw more benefits in their trial participation appeared to be most knowledgeable. These data suggest that participation in this clinical trial was based on altruistic, rather than personal reasons and that participants had realistic perceptions of outcomes. | 10.1080/09540129408258027 |
pubmed_114_13278 | 11-Cis-3-dehydroretinal was found in the eye of crayfish, Procambarus clarkii. The 11-cis-3-dehydroretinal was isomerized to all-trans isomer by light-illumination, as was also 11-cis-retinal. Irradiation with deep-red light (lambda greater than 680 nm) selectively isomerized the 11-cis-3-dehydroretinal. The 3-dehydroretinal was not extracted with petroleum ether from the tissue after freeze-drying. These facts suggest that the 11-cis-3-dehydroretinal is the chromophore of crayfish visual pigment. The 3-dehydroretinal content varied with season, high level in winter and low in summer. The crayfish may have a vitamin A1-A2 visual pigment system similar to those of freshwater fishes and amphibians. | 10.1016/0042-6989(84)90149-4 |
pubmed_687_7992 | Death during pregnancy and postpartum in the United States is an issue of urgent and growing concern. Mortality from obstetric-related causes is on the rise, and pregnancy-associated homicide remains a leading cause of death. It is unknown how the context in which women live contributes to their risk of obstetric or violent death during pregnancy and the postpartum period. This study aimed to quantify incidence of mortality from obstetric-related causes and violent death during pregnancy and up to 1-year postpartum, and to identify associations between state-level violent crime rates and incidence of pregnancy-related mortality and pregnancy-associated homicide. We conducted a retrospective, ecologic analysis of all pregnancy-associated homicides in 17 states participating in the National Violent Death Reporting System from 2011 to 2015. Pregnancy-related mortality was identified by International Classification of Diseases-10 code for underlying cause of death in death records issued in the same states and years, data provided by the National Center for Health Statistics. We characterized decedents of both violent and nonviolent maternal death (n = 174 and 1,617, respectively). Five-year mortality ratios (deaths per 100,000 live births) were estimated for both pregnancy-related mortality and pregnancy-associated homicide in every state. Poisson regression models estimated associations between violent crime and maternal death, adjusting for area-level socioeconomic conditions. Both pregnancy-related mortality and pregnancy-associated homicide ratios were higher in states with higher rates of violent crime (relative risk [RR] = 1.05, 95% confidence interval [CI] = 1.01-1.12; RR = 1.17, 95% CI = 1.01-1.34, respectively). Broad population-wide violence prevention efforts may help reduce incidence of maternal mortality from both obstetric and violent causes. | 10.1089/jwh.2019.8072 |
pubmed_872_6767 | Law enforcement agencies use ion mobility spectrometers for the detection of explosives, drugs of abuse, and chemical warfare agents. Ion mobility spectrometry (IMS) has the advantages of short analysis times, detections in the parts per billion concentrations, and high sensitivity. On-site environmental analysis of explosives or explosive residues in water is possible with ion mobility spectrometers. Unfortunately, the direct analysis of low levels of explosives in water is difficult. Extraction provides a method for pre-concentrating the analytes and removing interferents. Coupling solid-phase extraction (SPE) with IMS is useful for the identification of trace amounts of explosives in water. Commercially available SPE disks were used. After extraction, the sample disk is inserted into the ion mobility spectrometer, where the analytes are thermally desorbed from the disk. Concentrations as low as one part per trillion were detected with a Barringer Ionscan 350. An external computer and acquisition software (LabVIEW, National Instruments) were used to collect data. SIMPLISMA (SIMPLe-to-use-Interactive Self-modeling Mixture Analysis) was applied to the data to resolve features that vary with respect to time. | 10.1366/000370203321535150 |
pubmed_731_5620 | Face perception depends on a dynamic interplay of a "holistic" Interactive Feature Processing (IFP) and a Local Feature Processing (LFP) style. However, it is unclear whether features are processed locally before they are integrated into a holistic percept (Fine-to-Coarse strategy), or whether local feature processing occurs only after a holistic percept is established (Coarse-to-Fine strategy). The present Event-Related Potentials study investigates whether IFP precedes LFP (Coarse-to-Fine) or vice versa (Fine-to-Coarse). Participants matched target features within face pairs (here the eye region), in which distracter features (nose and mouth) called for the same or a different response (congruent and incongruent, respectively). Psychophysical results replicated previous findings. That is, dissimilar target features are locally processed (LFP), which minimizes interference from surrounding incongruent distracters. Conversely, an IFP mode is elicited when similar target features are embedded in dissimilar contexts. In IFP mode, incongruent distracters do interfere with the processing of similar target features, thereby deteriorating task performance. Face inversion, which preserves input properties but disrupts high-level face perception, annihilated these incongruency effects. Psychophysical observations were reflected at the neural level. The IFP and LFP modes of face perception elicited distinct time-courses in occipito-temporal cortex. IFP was affected by inversion as soon as 176 ms post-stimulus onset (coinciding with the N170 peak). In contrast, the first robust indications of LFP occurred 120 ms later, at 296 ms. Thus, the contribution of IFP to high-level face perception appears to temporally precede LFP. Moreover, results showed that the IFP and LFP modes did not only operate in distinct time intervals, but also in different brain areas: activity associated with the IFP mode was right-lateralized, whereas the LPF mode engaged the left hemisphere. In sum, interactive "holistic" encoding of facial features temporally precedes their local analysis. This agrees with models suggesting a Coarse-to-Fine strategy for face perception, in line with generic descriptions of visual perception in which global scene analysis precedes the examination of local details. | 10.1016/j.biopsycho.2018.07.009 |
pubmed_498_8566 | Chromium toxicity is a major problem in agricultural soils that negatively affects a plant's metabolic activities. It reduces biochemical and antioxidant defence system's activities. In search of the solution to this problem a two-year pot experiment (completely randomized design with three replications), in three genetically different varieties of sorghum (SSG 59-3, HJ 513 and HJ 541) under Cr toxicity (2 and 4 ppm) was conducted to determine the effect of glycine betaine (50 and 100mM) and Arbuscular mycorrhizal fungi (AMF) on the antioxidant system (enzymes viz. superoxide dismutase, ascorbate peroxidase, catalase, glutathione reductase, peroxidase and metabolites viz. glutathione, ascorbate, proline, β-carotene) along with Cr accumulation and indices of oxidative stress parameters (polyphenol oxidase, hydrogen peroxide and malondialdehyde) at two growth stages (vegetative and grain filling). According to results; Cr stress (2 & 4 ppm) increased its accumulation and indices of oxidative stresses significantly (p≤0.05) in all varieties of sorghum at both growth stages. However, soil application of glycine betaine (GB) and AMF decreased Cr accumulation and indices of oxidative stress by increasing antioxidant enzymes and metabolites activities at both growth stages in all varieties. The combination of 100mM GB with AMF was observed most significant (p≤0.05) in decreasing oxidative stress and improved the antioxidant system's activities. The SSG 59-3 cultivar showed the lowest Cr accumulation (1.60 and 8.61 ppm), indices of oxidative stress and highest antioxidant system's activity among these three cultivars at both growth stages. Thus, SSG 59-3 was found most tolerant cultivars followed by HJ 513 and then HJ 541. These findings suggest that both GB and AMF, either individually or combined can play a positive role to reduce oxidative stress and increased antioxidant attributes under Cr toxicity in sorghum. | 10.1371/journal.pone.0253878 |
pubmed_461_3174 | A method is described for the large-scale purification of the Bacillus thuringiensis protein crystal by zonal gradient centrifugation. NaBr gradients are employed in a Beckman J21-B centrifuge equipped with a JCF-Z rotor. | 10.1128/aem.36.4.625-626.1978 |
pubmed_1141_12821 | We characterized short interspersed elements (SINEs), of the CORE-suprafamily in egg-laying (monotremes), pouched (marsupials) and placental mammals. Five families of these repeats distinguished by the presence of distinct LINE-related 3'-segments shared tRNA-like promoter and the central core region. The putative active elements were reconstructed from the alignment of genomic repeats representing molecular fossils of sequences that amplified in the past and since then underwent multiple mutations. Their mode of proliferation by retroposition was indicated by the presence of: (1) internal RNA PolIII promoter; (2) simple sequence repeated tail; (3) direct repeats; and (4) subfamilies recording the evolution of elements. The copy number of CORE-SINEs in placental genomes was estimated at about 300,000; they were highly divergent and apparently ceased to amplify before radiation of these lineages. On the other hand, among almost half a million fossil elements present in marsupials and monotremes, the youngest subfamilies could still be retropositionally active. CORE-SINEs terminate in sequence repeats of a few nucleotides similar to their 3'-segment LINE-homologues, CR1, L2 and Bov-B. These three LINE elements fall into clades distinct from that of L1 elements which, similar to their co-amplifying SINEs, end in a poly(A) tail. We propose a model in which new CORE-families, with distinct 3'-segments, are created at the RNA level due to template switching between LINE and CORE-RNA during reverse transcription. The proposed mechanism suggests that such an adaptation to the changing amplification machinery facilitated the survival and prosperity of CORE-elements over long evolutionary periods in different lineages. | 10.1006/jmbi.2000.3695 |
pubmed_983_18930 | BACKGROUND
In Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP.
METHODS
In this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16-85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph.
RESULTS
Initial treatment with FP was significantly (P = 0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season.
CONCLUSIONS
Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order. | 10.2332/allergolint.11-OA-0342 |
pubmed_402_9105 | This study reports the measurements of fluoxetine in discrete brain regions, blood, liver and hair of male rats injected with 10 mg/kg fluoxetine HCl for 15 consecutive days. Concentrations of the antidepressant were obtained by gas chromatography-mass spectrometry (GC-MS) methodology. In brain, fluoxetine levels were unevenly distributed, with the raphé nucleus containing the highest amounts relative to the hypothalamus or striatum. Fluoxetine was also measured in blood and liver roughly paralleling those ratios described in previous rodent studies. Of potential interest, fluoxetine was found to accumulate in rat hair after chronic treatment. Detection of fluoxetine in hair by GC-MS could be used as a marker for probative analyses. | 10.1016/s0024-3205(98)00622-5 |
pubmed_265_10046 | It was found that photoreduction of 5-bromouracil (BrU) occurs at 5'-ATBrU-3' sequence more efficiently than 5'-ABrU-3'. We introduced 5'-GG-3' sequence at the 5'-side of 5'-ATBrU-3' sequence and 5'-ABrU-3' sequence and investigated their photoreduction. As a result, dIz, an oxidation product originated from guanine cation radical, was detected. | pubmed_265_10046 |
pubmed_658_11793 | There has been renewed interest in impacts on physiologic systems in the middle and older age groups, especially from fractures and hypertension. Increased blood lead (BPb) levels in postmenopausal females, which are thought to arise from bone demineralization, may also relate to other health effects including hypertension. Taking advantage of natural differences in lead isotope signature between Australian sources of lead and those from other countries, a 2-year pilot study was performed in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim of the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodeling processes. Premenopausal subjects were a woman (and male partner) from Bosnia and two women from Colombia. The postmenopausal subject was a woman from Russia. Her male partner and one man from Sri Lanka were included. Multigenerational Australian subjects were 2 perimenopausal women and 1 postmenopausal woman. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for 7-9 months before, for 3 months during, and for up to 6 months after treatment with alendronate to inhibit bone resorption. Each subject thus acted as his or her own control. As predicted, there were significant decreases in the lead isotope ratio, (206)Pb/(204)Pb, for the migrant subjects during treatment compared with the pretreatment period (p < 0.01). After cessation of treatment, an increasing isotope ratio for the postmenopausal subject (and older male partner) occurred later than for premenopausal subjects, indicative of prolonged efficacy of the alendronate for the older subjects. The average BPb concentrations in migrant subjects decreased by about 20% during the treatment compared with the pretreatment period (p < 0.01). To our knowledge, these are the first BPb concentrations reported over monthly to quarterly intervals for environmentally exposed adults over an extended period. The changes in lead isotopic composition and lead concentration are consistent with a decrease in bone resorption and associated mobilization of lead during alendronate therapy. Older subjects at risk of fractures may benefit from treatment with antiresorptive therapy, such as the potent bisphosphonates, with the added bonus of lower release of lead from bones and thus less risk of the potential adverse health effects of increased BPb levels. | 10.1289/ehp.021101017 |
pubmed_1029_9536 | We classified cholesteatomas as attic cholesteatoma, developing from Shrapnell's membrane; tensa cholesteatoma, originating in pars tensa, which is subdivided into tensa retraction cholesteatoma involving the entire pars tensa, and sinus cholesteatomas, developing from a posterosuperior retraction (perforation). From 1964 to 1980, one-stage operations were carried out on 271 ears with sinus cholesteatomas. Follow-up included 90% of the patients, and the median observation time was 9.75 years. The recurrence rate was 10%. The recurrence rate was found to be independent of the mastoidectomy type employed. The best hearing results were obtained in ears with intact ossicular chain. We conclude that, wherever possible, sinus cholesteatoma should be removed through the auditory canal without mastoidectomy just as an intact ossicular chain should be preserved. "Canal wall up" and "canal wall down" appear to be equally valuable mastoidectomy types, and both methods must be employed to obtain optimum results. | 10.1001/archotol.1988.01860240078028 |
pubmed_506_6887 | The optimistic multigranulation T-fuzzy rough set model was established based on multiple granulations under T-fuzzy approximation space by Xu et al., 2012. From the reference, a natural idea is to consider pessimistic multigranulation model in T-fuzzy approximation space. So, in this paper, the main objective is to make further studies according to Xu et al., 2012. The optimistic multigranulation T-fuzzy rough set model is improved deeply by investigating some further properties. And a complete multigranulation T-fuzzy rough set model is constituted by addressing the pessimistic multigranulation T-fuzzy rough set. The full important properties of multigranulation T-fuzzy lower and upper approximation operators are also presented. Moreover, relationships between multigranulation and classical T-fuzzy rough sets have been studied carefully. From the relationships, we can find that the T-fuzzy rough set model is a special instance of the two new types of models. In order to interpret and illustrate optimistic and pessimistic multigranulation T-fuzzy rough set models, a case is considered, which is helpful for applying these theories to practical issues. | 10.1155/2014/927014 |
pubmed_1013_18741 | Arrhythmogenic right ventricular cardiomyopathy (ARVC) encompasses a group of conditions characterized by right ventricular fibrofatty infiltration, with a predominant arrhythmic presentation. First described in the late 1970s and early 1980s, it is now frequently recognized to have biventricular involvement. The prevalence is ∼1:2,000 to 1:5,000, depending on geographic location, and it has a slight male predominance. The diagnosis of ARVC is determined on the basis of fulfillment of task force criteria incorporating electrophysiological parameters, cardiac imaging findings, genetic factors, and histopathologic features. Risk stratification of patients with ARVC aims to identify those who are at increased risk of sudden cardiac death or sustained ventricular tachycardia. Factors including age, sex, electrophysiological features, and cardiac imaging investigations all contribute to risk stratification. The current management of ARVC includes exercise restriction, β-blocker therapy, consideration for implantable cardioverter-defibrillator insertion, and catheter ablation. This review summarizes our current understanding of ARVC and provides clinicians with a practical approach to diagnosis and management. | 10.1016/j.jacep.2021.12.002 |
pubmed_134_10461 | The location negative priming (NP) effect refers to the fact that the processing of a current target stimulus (probe trial) is delayed when it appears at a location that has recently contained a distractor event (prime trial), relative to when it occurs at a previously unoccupied position. One view is that the process causing the NP effect involves the inhibition of the internal representation of the prime-distractor event, and that the future processing of target stimuli that involve this event are prolonged because this distractor inhibition is persistent. In this study, we examined the possibility that the NP process (inhibition) could act proactively; specifically asking whether inhibition could be allocated to a location merely predicted to hold a future distractor event. To do this, we cued the probe distractor's location using an otherwise traditional location NP paradigm. No evidence of a proactive NP process was obtained. Probe-trial target latency was the same whether it appeared at the cued distractor location or at a new location, but was delayed when it occupied the prime-distractor location (NP effect). The location NP process is seemingly a reactive one, applying inhibition only when an actual distractor is present, much as past theories have implied. | 10.1007/s00426-004-0202-9 |
pubmed_140_16881 | Small GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components' feedback to upstream signaling factors remains largely elusive. Here, we report an intriguing finding that disruption of the Arp2/3-branched actin specifically reduces RhoA activity but upregulates its total protein abundance. We further dissect the mechanisms underlying these circumstances and identify the altered cortactin/p190RhoGAP interaction and weakened CCM2/Smurf1 binding to be involved in GTP-RhoA reduction and total RhoA increase, respectively. Moreover, we find that cytokinesis defects induced by Arp2/3 inhibition can be rescued by activating RhoA. Our study reveals an intricate feedback from the actin cytoskeleton to the small GTPase. Our work highlights the role of Arp2/3-branched actin in signal transduction aside from its function in serving as critical cytoskeletal components to maintain cell morphology and motility. | 10.3390/cells8101264 |
pubmed_5_12931 | Gene expression relevant to abnormal cell differentiation and altered cell cycle in endometrial epithelial cells was investigated immunohistochemically in developing mouse uteri exposed neonatally to diethylstilbestrol (DES). Female CD-1 mice were given daily s.c. injections of 2 microg of DES in corn oil or were given corn oil alone (control) at 1-5 days of age and euthanatized at 5, 6, 7, 8, 15, and 22 days of age. The endometrial epithelial cells of DES-treated mice at 5-8 days of age showed enhanced staining intensity for the estrogen receptor alpha (ER alpha), whereas the stromal cells showed decreased staining reaction; the epithelial cells showed that the protein encoded by the c-fos proto-oncogene, which plays a key role in regulating diverse estrogen-related cellular differentiation patterns, was enhanced. These cells also showed increased expression of lactoferrin, a sensitive protein marker of estrogen exposure, although the staining intensity decreased after exposure ended. The stain for p21 protein, a mitotic inhibitor which suppresses cyclin-dependent kinase activity, showed frequent positively stained cells in DES-treated mice at 5-15 days of age, whereas no accumulation of p53 protein of either wild or mutant type was detected immunohistochemically in these cells. These results indicate that suppressed cell cycle activity of endometrial epithelial cells and abnormal estrogen-related differentiation at the developmental stage following neonatal DES exposure may be caused, in part, by transient altered expression of ER alpha and expression of the p21 gene, which appears to be induced by a p53-independent mechanism. | 10.1177/019262330002800203 |
pubmed_80_21028 | Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that can lead to cirrhosis, liver transplant, and even hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble biomarkers of NASH are of great importance to advance the field. To this end, we performed analytical and clinical validation on a series of pro-inflammatory cytokines and chemokines implicated hepatic inflammation; IL-6, CRP, TNFα, MCP-1, MIP-1β, eotaxin, VCAM-1. Biomarker assays were validated for accuracy and precision. Clinical performance was evaluated in a random sample of 52 patients with biopsy-proven NAFLD/NASH. Patients were categorized into three groups according to their fibrosis stage; advanced (F3-F4), mild (F1-2) and no (F0) fibrosis. Serum IL-6 was increased in patients with advanced fibrosis (2.71 pg/mL; 1.26 pg/mL; 1.39 pg/mL p<0.01) compared to patients with mild or no fibrosis respectively. While, there was no significant difference noted in CRP, TNFα, MCP-1, MIP-1β, eotaxin among the three groups, VCAM-1 levels were increased by 55% (p<0.01) and 40% (p<0.05) in the advanced cohort compared to the mild and no fibrosis groups respectively. VCAM-1 also displayed good clinical performance as a biomarker of advanced fibrosis with an area under the receiver operating curve of 0.87. The VCAM-1 assay demonstrated robust accuracy and precision, and VCAM-1 outperformed IL-6, CRP, TNFα, and the chemokines MCP-1, MIP-1β, and eotaxin as a biomarker of advanced fibrosis in NASH. Addition of biomarkers such as IL-6 and VCAM-1 to panels may yield increased sensitivity and specificity for staging of NASH. | 10.1371/journal.pone.0217263 |
pubmed_572_7891 | BACKGROUND
Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration.
RESULTS
Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration.
CONCLUSIONS
Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome. | 10.1186/s12977-017-0363-4 |
pubmed_994_5826 | It is time to stop using the term concussion as it has no clear definition and no pathological meaning. This confusion is increasingly problematic as the management of 'concussed' individuals is a pressing concern. Historically, it has been used to describe patients briefly disabled following a head injury, with the assumption that this was due to a transient disorder of brain function without long-term sequelae. However, the symptoms of concussion are highly variable in duration, and can persist for many years with no reliable early predictors of outcome. Using vague terminology for post-traumatic problems leads to misconceptions and biases in the diagnostic process, producing uninterpretable science, poor clinical guidelines and confused policy. We propose that the term concussion should be avoided. Instead neurologists and other healthcare professionals should classify the severity of traumatic brain injury and then attempt to precisely diagnose the underlying cause of post-traumatic symptoms. | 10.1136/practneurol-2015-001087 |
pubmed_770_13157 | The etiology and the treatment of the aseptic necrosis of the lunate bone (M. Kienböck) is still today debated. In the literature we find more than twenty different procedures of treatment. Our follow-up of seven patients with Swanson Lunatum prosthesis showed subjectiv and functional good results whereas the radiological findings weren't satisfactory. | 10.1055/s-2008-1044890 |
pubmed_0_20991 | PURPOSE
To examine the potential confounding effect of biological maturation on the relations between chronological age and health-related quality of life in adolescent British females.
METHODS
Biological maturation, chronological age, and health-related quality of life were assessed in 366 British female students in years 7-10 (M = 13.0 years, SD = 0.8). The Kid-Screen 10 was used to assess health-related quality of life. Percentage of predicted adult height attained at measurement was used as an estimate of biological maturation.
RESULTS
Pearson product moment correlation demonstrated a statistically significant inverse relation between chronological age and health-related quality of life. This relation was, however, attenuated and non-significant once biological maturation was controlled for.
CONCLUSIONS
Researchers studying health-related quality of life in youth should consider and/or control for the potential confounding effect of biological maturation. | 10.1007/s11136-010-9743-0 |
pubmed_491_20772 | Pseudo-pseudo Meigs' syndrome (PPMS) has been reported to be a rare presentation of patients with systemic lupus erythematosus (SLE). However, such a presentation is not common in other forms of connective tissue disease. We presented a case of gross ascites, pleural effusion, and marked elevation of CA-125 level (PPMS-like features) that led to a diagnosis of MCTD. The patient responded to systemic steroid therapy. | 10.1177/0961203315606441 |
pubmed_631_17839 | We report the diagnosis of hereditary amyloidosis that affected a Belgian family that was initially diagnosed in a 73 year old woman. This patient was admitted with complaints of congestive heart failure. Cardiac work-up showed myocardial hypertrophy with zones of hyperintensity, suggestive for amyloidosis that was confirmed on a rectal biopsy. A hereditary form of amyloidosis was found by showing the Val30Met mutation within the transthyretin gene, that was also found in her asymptomatic son. This case shows that genetic testing is crucial in cases of unexplained amyloidosis and can help in the diagnosis and follow-up of patients and family members. | 10.2143/ACB.3268 |
pubmed_807_11282 | PURPOSE
To evaluate whether non-opioid antipyretic analgesics are associated with lower pain scores, opioid doses and side effects in pain patients in tertiary care.
METHODS
In a cross-sectional observational study, data from 519 Caucasians (197 men, 322 women; mean age 55.6 ± 15 years) who had undertaken pain therapy for various causes for 77.5 ± 90.8 months, obtained in three separate study centres, was analysed for actual 24-h pain scores, daily opioid doses and the occurrence of side effects.
RESULTS
Of the 519 patients, 352 received opioids and 260 antipyretic analgesics, from whom 154 received both classes and 304 only either class. The administration of non-opioid antipyretic analgesics was associated with higher average pain scores (4.6 ± 2.5 vs 3.9 ± 2.6; P = 0.01), tendentially higher average oral morphine equivalent doses (121.8 ± 162.2 vs 146.7 ± 242.4 mg/d; P = 0.25) and a similar incidence of side effects (P = 0.21). These results were correspondingly seen when analysing the three study centres separately as independent cohorts.
CONCLUSIONS
With the caution advised for cross-sectional data, the results dispute a clinical benefit of non-opioid antipyretic analgesics for most chronic pain patients in tertiary care and draw attention towards prospectively re-evaluating the utility of non-opioid antipyretic analgesics in tertiary pain care in a randomised placebo controlled trial. | 10.1007/s00011-010-0215-3 |
pubmed_1025_1237 | Remembering the location of objects, an integral part of everyday life, is known to decline with advancing age and early in the course of neurodegenerative dementia. Here, we aimed to test if object-location learning and its retention could be modified by noninvasive brain stimulation. In a group of 20 elderly (mean age 62.1 years) right-handed individuals, we applied transcranial direct current stimulation (tDCS; 20 minutes, 1 mA) over the right temporoparietal cortex, while subjects acquired the correct position of buildings on a street map using an associative learning paradigm. Each subject participated in a randomized and balanced order in 1 session of anodal tDCS and 1 session of sham stimulation, in a double-blind design with 2 parallel versions of the task. Outcome measures were learning success at the end of each session, and immediate as well as delayed (1 week) free recall. We found that subjects performed comparably in the learning task in the 2 conditions, but showed improved recall 1 week after learning with anodal tDCS compared with learning with sham stimulation. In conclusion, retention of object-location learning in the elderly may be modulated by noninvasive brain stimulation, a finding of potential relevance not only for normal aging but also for memory deficits in pathological aging. | 10.1016/j.neurobiolaging.2011.05.007 |
pubmed_1104_20887 | The possibility of creating and manipulating entangled states of systems of many particles is of significant interest for quantum information processing; such a capability could lead to new applications that rely on the basic principles of quantum mechanics. So far, up to four atoms have been entangled in a controlled way. A crucial requirement for the production of entangled states is that they can be considered pure at the single-particle level. Bose-Einstein condensates fulfil this requirement; hence it is natural to investigate whether they can also be used in some applications of quantum information. Here we propose a method to achieve substantial entanglement of a large number of atoms in a Bose-Einstein condensate. A single resonant laser pulse is applied to all the atoms in the condensate, which is then allowed to evolve freely; in this latter stage, collisional interactions produce entanglement between the atoms. The technique should be realizable with present technology. | 10.1038/35051038 |
pubmed_837_7257 | To assess the interaction of bilirubin with albumin and to determine the site of bilirubin toxicity in cells, a study was made of the O2- production of neonatal neutrophils (PMNs) by two different stimulators: (1) concanavalin A (Con A) plus cytochalasin D (Cyt D), which acts on the cell surface, and (2) phorbol myristate acetate, which acts intracellularly. PMNs that had been separated from cord blood were incubated for 60 min at 37 degrees C in the solution with different molar ratios of bilirubin/albumin (unbound bilirubin, ranging from 0.35 to 3.92 micrograms/dl). The unbound bilirubin was determined by peroxidase oxidation method. A PMN viability of more than 96% was maintained after the incubation in each of solutions. The O2- production rate of PMNs stimulated by Con A plus Cyt D was inhibited in the presence of unbound bilirubin levels as low as 1.12 micrograms/dl, and the rate decreased as the levels of unbound bilirubin rose. The O2- production rate stimulated by Con A plus Cyt D was more remarkably inhibited than that by phorbol myristate acetate, which directly activates intracellular protein kinase C. These findings suggest that bilirubin toxicity to PMN can be shown at levels of unbound bilirubin as low as those in hyperbilirubinemic sera, and the critical site at which bilirubin exerts its toxicity is mainly in membrane level rather than on intracellular functions. | 10.1159/000242720 |
pubmed_258_12232 | OBJECTIVE
Inflammatory bowel disease (IBD) is associated with psychiatric comorbidities. However, the association between IBD and suicidal ideation or suicide attempts has not been well established. This study aimed to perform a systematic review and meta-analysis to elucidate the relationship between IBD and suicidal ideation, suicide attempts, and suicide.
METHODS
We systematically searched five electronic databases - PubMed, Embase, CENTRAL, Web of Science, and PsycINFO - from their inception to January 28, 2022. Quality assessment, data synthesis, subgroup analyses, sensitivity analyses, and publication bias assessment were performed on the included studies.
RESULTS
We identified 28 studies with 1,047,755 patients with IBD. The pooled prevalence of suicidal ideation in patients with IBD was 17.3% (95% CI, 9.5%-25.2%). Patients with IBD were associated with an increased risk of suicide attempts (relative risk [RR], 1.39; 95% CI, 1.08-1.79) and suicide deaths (RR, 1.25; 95% CI, 1.09-1.43) than the controls without IBD. Patients with Crohn's disease subtypes, female IBD, pediatric-onset IBD, young adult IBD, and short-duration IBD had a particularly high risk for suicide.
CONCLUSION
Patients with IBD had a high prevalence of suicidal ideation and a significantly higher likelihood of suicide attempts and suicide. Caring for patients with IBD, including their mental health needs, may require concerted efforts among gastroenterologists and other healthcare providers. | 10.1016/j.jpsychores.2022.110983 |
pubmed_380_17445 | Anti-D titration is the first step in the evaluation of the RhD-sensitized patient. Traditionally, anti-D titration has been performed by tube agglutination. Gel microcolumn assay is a method that has gained widespread usage throughout the world, mainly for ABO/Rh typing, unexpected antibody screening and direct antiglobulin tests. As gel assay has become widely used as a routine method to detect red blood cell alloantibodies, a critical anti-D titer needs to be established. Seventy-nine known blood samples with anti-D (titers 1-32) were titrated simultaneously by the conventional tube test and the gel microcolumn assay. Red blood cells (R0r phenotype) were used, with a final concentration of 3% for tube and 0.8% for gel. Serial twofold dilutions (2-2.048) were prepared for each technique, followed by reading in antiglobulin phase. Anti-D titration in the gel microcolumn assay showed significantly higher titers (mean 3.4-fold) than the conventional tube test in all samples studied. Based on these data, it was not possible to determine a critical titer for anti-D titration by the gel microcolumn assay. | 10.1046/j.1365-2257.2003.00540.x |
pubmed_524_16981 | During storage of modified atmosphere packaged (MAP) meat, the initial microbiota grows to high cell numbers, resulting in perceptible spoilage after exceeding a specific threshold level. This study analyses, whether elevated oxygen consumption in the headspace of MA-packages would enable a prediction method for meat spoilage. We monitored the growth of single spoiling species inoculated on high-oxygen MAP beef and poultry, performed sensorial analysis and determined oxygen concentrations of the headspace via a non-invasive sensor spot technology. We detected microbial headspace oxygen consumption occurring prior to perceptible meat spoilage for certain species inoculated on beef steaks. However, headspace oxygen consumption and cell counts at the onset of spoilage were highly species-dependent, which resulted in a strong (Brochothrix thermosphacta) and moderate (Leuconostoc gelidum subspecies) decrease of the headspace oxygen content. No linear decrease of the headspace oxygen could be observed for Carnobacterium divergens and Carnobacterium maltaromaticum inoculated on poultry meat. We demonstrate the applicability of an incorporated oxygen sensor spot technology in MAP meat packages for detection of spoilage in individual packages prior to its perceptible onset. This enables individual package evaluation and sorting within retail, and consequently reduces meat disposal as waste. | 10.1111/lam.13473 |
pubmed_260_4473 | Chemical hardness, identified as the difference between the vertical first ionization potential I and the vertical electron affinity A, is analyzed in the context of the ionization theorems to derive expressions for its evaluation at different levels of approximation that arise as a direct consequence of the derivative discontinuity of the exchange-correlation potential. The quantities involved in these expressions incorporate indirectly the effects of the discontinuity, but their values may be calculated with any functional of the local density approximation, generalized gradient approximation, or optimized effective potential type, with or without derivative discontinuity, and with or without the correct asymptotic behavior. By comparison with the vertical energy difference values of I and A, which requires the calculation of the N-, (N-1)-, and (N+1)-electron systems, it is found, for a set of 14 closed shell molecules, that the difference between the eigenvalues of the highest occupied molecular orbitals of the N- and (N+1)-electron systems leads to rather accurate values, when the correct asymptotic behavior is incorporated, and that a second-order one-body perturbation approach that only requires information from the N-electron system leads to reasonable values. | 10.1063/1.2741529 |
pubmed_522_23210 | We evaluated a 15% paste formulation of ponazuril in outbred Swiss mice that were experimentally infected with Eimeria vermiformis. Thirty, 8-week-old female mice (approximately 20 g) were placed in one group of 10 mice and one group of 20 mice. Mice in both groups were gavaged with approximately 5,000 sporulated oocysts of E. vermiformis on day 0. Mice in group 2 (n=10) were treated orally on days 3 and 4 with ponazuril (suspended in 30% propylene glycol) at the rate of 20 mg/kg. Mice in group 1 (n=20) were gavaged with a similar volume of 30% propylene glycol. Rates of oocyst passage (oocysts/g feces) were determined on day 10 (peak patency) for treated and nontreated mice using a fecal aliquot oocyst counting technique. Oocysts were not observed in the feces of treated mice using the aliquot technique. Control mice passaged oocysts at a geometric mean rate of >104,000 oocysts/g feces. Control mice also produced significantly less feces on day 10. These results indicate that ponazuril is effective against E. vermiformis under the conditions utilized in this study, and that the E. vermiformis mouse model could be useful in predicting the efficacy of new anticoccidial drugs. | 10.1007/s00436-004-1263-9 |
pubmed_295_24766 | Although a nationwide lockdown was imposed in India amid COVID-19 outbreak since March 24, 2020, the COVID-19 infection is increasing day-by-day. Till June 10, 2021 India has recorded 29,182,072 COVID cases and 359,695 deaths. A number of factors help to influence COVID-19 transmission rate and prevalence. Accordingly, the present study intended to integrate the climatic parameters, namely ambient air temperature (AT) and relative humidity (H) with population mass (PM) to determine their influence for rapid transmission of COVID-19 in India. The sensibility of AT, H and PM parameters on COVID-19 transmission was investigated based on receiver operating characteristics (ROC) classification model. The results depicted that AT and H models have very low sensibility (i.e., lower area under curve value 0.26 and 0.37, respectively compared with AUC value 0.5) to induce virus transmission and discrimination between infected people and healthy ones. Contrarily, PM model is highly sensitive (AUC value is 0.912, greater than AUC value 0.5) towards COVID-19 transmission and discrimination between infected people and healthy ones and approximate population of 2.25 million must impose like social distancing, personal hygiene, etc. as strategic management policy. Therefore, it is predicted, India could be the next epicenter of COVID-19 outbreak because of its over population. | 10.1016/j.rinp.2021.104454 |
pubmed_403_10357 | Despite the increasing usage of porphyrinic metal-organic frameworks (MOFs) for combination therapy, the controlled encapsulation of inorganic nanoparticle-based therapeutics into such MOFs with specific structures has remained a major obstacle for improved tumor therapy. Here, we report the synthesis of a mesoporous MOF shell on the surface of gold nanorods (AuNRs), wherein a single AuNR is captured individually in single-crystalline MOFs with a controlled crystallographic orientation, for combinational phototherapy against solid tumors. The core-shell heterostructures have the benefits of a mesoporous structure and photoinduced singlet oxygen generation behavior characterized by the porphyrinic MOF shell, together with the plasmonic photothermal conversion characteristic of AuNRs. We demonstrated that the AuNR@MOF nanoplatform enables an efficient tumor treatment strategy by combining photodynamic therapy and photothermal therapy. We should emphasize that such systems could have applications beyond the field of cancer therapy, like plasmonic harvesting of light energy to induce and accelerate catalytic reactions within MOFs and multifunctional nanocarriers for agricultural formulations. | 10.1039/d0nr07681c |
pubmed_772_908 | BACKGROUND AND OBJECTIVES
Continuous spinal anesthesia via a spinal catheter allows adjusting the duration and extent of anesthesia to surgical needs, maintenance of hemodynamic stability, and good postoperative analgesia. This study was designed to determine the median effective local anesthetic dose of plain ropivacaine and bupivacaine administered intrathecally for interstitial brachytherapy of the lower abdomen using the Dixon up-and-down method.
METHODS
Forty patients were randomly allocated to receive either intrathecal bupivacaine 5 mg per mL or ropivacaine 10 mg per mL via a 24-gauge spinal catheter at the L3-4 interspace. The initial dose was 10 mg of bupivacaine or 20 mg of ropivacaine; the dosing intervals were 1 mg and 2 mg, respectively. Doses for subsequent patients were determined by the response of the previous patient in that group. Successful anesthesia was defined as a loss of sensation to a cold stimulus at the T6 level and full motor blockade within 20 minutes after administration of the local anesthetic.
RESULTS
The median effective local anesthetic dose for intrathecal bupivacaine was 11.2 mg (95% confidence interval [CI], 10.3-12.1) and 22.6 mg for ropivacaine (95% CI, 20.5-24.6). A relative analgesic potency ratio of 0.50 (95% CI, 0.44-0.56) was calculated between the median effective local anesthetic dose of intrathecal bupivacaine and ropivacaine.
CONCLUSIONS
Bupivacaine and ropivacaine are appropriate for continuous spinal anesthesia for interstitial radiation therapy procedures of the lower abdomen. In the dose-ranges investigated, intrathecal ropivacaine is approximately half as potent as bupivacaine. | 10.1016/j.rapm.2007.06.396 |
pubmed_785_15877 | OBJECTIVES
This study assesses the independent and combined effects of (1) perceived peer norms, (2) best friend use, and (3) being in the presence of others who use on middle school adolescents' consumption of marijuana and alcohol, and how the effects of these sources of social influence evolve over time as youth progress through middle school.
METHODS
The analytic sample consisted of 11,667 adolescents (50% female; >65% Hispanic) in 6th, 7th or 8th grade from 16 middle schools across three school districts in Southern California. Participants were assessed at 5 time points from 2008 to 2011.
RESULTS
All sources of social influence were predictive of alcohol and marijuana consumption. As youth grew older, spending time with other adolescents who drink increased adolescents' likelihood of drinking alcohol, whereas perceived norms became less influential. Furthermore, as adolescents spent more time around other youths who drink, the predictive value of perceived norms on alcohol consumption decreased. Similarly, as youth grew older, the influence of best friend's use and spending time with other adolescents who use marijuana remain stable, whereas perceived norms became less influential.
CONCLUSION
Findings suggest that perceived peer norms may be more influential in early adolescence; whereas proximal social determinants (e.g., being in the presence of other peers who consume) become more influential as youth enter middle adolescence. Prevention programs should continue to address misperception of norms with younger adolescents to decrease the chances of initiation, but also utilize strategies such as refusal skills and alternate coping mechanisms for older adolescents. | pubmed_785_15877 |
pubmed_455_2035 | The gerHABC operon of Bacillus anthracis, encoding a gerA-like family member of germinant sensors, was shown to be required for endospore germination in the presence of macrophages and in macrophage-conditioned media. The loss of the germination phenotype in macrophage cultures of B. anthracis gerH-null endospores was restored by complementation in trans with a wild-type copy of gerH expressed under the control of its own promoter. Using endospores from both the parental strain B. anthracis Sterne and an isogenic gerH-null strain, we partially characterized germinants secreted by macrophages into the extracellular medium. | 10.1128/IAI.71.7.3954-3959.2003 |
pubmed_707_9907 | Multiple alternative sites for distal ventriculoperitoneal shunts have been described including pleural, atrial, ureteral, fallopian, and gallbladder placement. In medically complex patients the sites for cerebrospinal fluid (CSF) diversion can be exhausted. We present a case where open retroperitoneal inferior vena cava cannulation was used for successful atrial catheter placement in a 17-month-old female. The patient had a complex abdominal, pulmonary, and vascular history precluding placement of the distal catheter in other sites or atrial placement through more peripheral venous cannulation. The patient underwent uncomplicated open retroperitoneal exposure of her inferior vena cava (IVC) with cannulation and placement of atrial catheter under fluoroscopic guidance. At the follow-up one year after surgery, the patient did not require revision with appropriate placement of the distal atrial catheter. | 10.7759/cureus.21555 |
pubmed_496_13779 | We show that in the mutual synchronization of periodic oscillators, besides an attracting torus, there is also a saddle torus that plays an equally important role. We demonstrate that the saddle and stable tori form an elegant structure, allowing for a variety of phenomena, both known and new, related to the origin and evolution of coexisting synchronous regimes (phase multistability). | 10.1103/PhysRevE.72.026214 |
pubmed_1074_15934 | Sharing lessons from high-performing hospitals facilitates quality improvement. High-performing hospitals have usually been identified using a small number of performance measures. The objective was to analyze how well 1,006 hospitals performed across a broader range of measures. Five measures were developed from publicly available data: adherence to processes of care, 30-day readmission rates, in-hospital mortality, efficiency, and patient satisfaction. For a subset of hospitals, the authors included two survey-based assessments of patient care quality, one by chief quality officers and one by frontline clinicians. In general, there was little correlation among the publicly available measures (r ≤ .10), though there was notable correlation between objective measures and survey-based measures (r = .23). Hospitals that performed well on a composite measure calculated from the publicly available measures were often not in the top quintile on most individual measures. This highlights the challenge in identifying high-performing hospitals to learn organizational-level best practices. | 10.1177/1077558710386115 |
pubmed_129_14454 | Tests based on the composition of gingival crevicular fluid (GCF) for detection of active periodontitis require a better understanding of sampling variables than currently exists. We have studied the effects of sample time and repetition on the presence and activity of aspartate aminotransferase (AST). Two 30-second samples of GCF were harvested within 10-minute intervals from 192 teeth with periodontitis. GCF sample size and AST activity were measured. GCF volume and AST activity of first samples were each approximately 10% greater than for second samples. The differences were significant. AST activity correlated positively with gingival index scores and probing pocket depth. Samples were also harvested from groups of 4 teeth during 5-, 10-, 20- and 30-s periods with 1-min intervals and varying sample order. For these samples, first samples contained the greatest amount of enzyme activity, regardless of sample time. When only first samples were considered, the 5- and 10-s samples showed more total activity than the 20- and 30-s samples, and differences were statistically significant. Flow rate for the 5-s sample was always higher than for all other samples, regardless of its position in the sampling sequence. Our observations are consistent with the existence of a reservoir of AST activity that is, in major part, depleted during the first 5 to 10 s of sampling, and that requires a time period of more than 10 min to reequilibrate. Five- to 10-s samples may distinguish active disease better than 20- or 30-s samples, since most of the activity is taken onto the strip in the first few seconds, and the activity is subsequently partly inactivated or diluted by the uptake of fluid less rich in enzyme activity. | 10.1111/j.1600-0765.1990.tb00910.x |
pubmed_1041_1223 | Parainfluenza virus (PIV) infections cause significant mortality in adults undergoing hematopoietic stem cell transplantation (HSCT). Children are more prone to PIV infections than adults; however, data on the epidemiology of these infections in children undergoing HSCT are limited. This study examined the incidence of symptomatic PIV infections, risk factors for lower respiratory tract infection (LRTI), and the impact on mortality after pediatric HSCT. A total of 1028 children who underwent HSCT between 1995 and 2009 were studied. PIV infections were detected in 46 of the 738 patients tested for respiratory infection (6.2%). PIV infection was the most common symptomatic respiratory viral infection in this population. On multivariate logistic regression analysis, receipt of an allogeneic transplant (P < .0001) and total body irradiation-based conditioning (P < .0001) were associated with increased risk of acquiring symptomatic PIV infection. Of the 46 HSCT patients with PIV infection, 18 (39%) had an LRTI. LRTI was associated with PIV infection in the first 100 days post-HSCT (P = .006), use of steroids (P = .035), and absolute leukocyte count (ALC) <100 cells/μL at the onset of infection (P < .0001). An ALC of <500 cells/μL was associated with prolonged viral shedding (P = .045). Six (13%) HSCT patients died of PIV infection. Mortality was associated with African-American ethnicity (P = .013), LRTI (P = .002), use of steroids (P < .0001), mechanical ventilation (P < .0001), and ALC <100 cells/μL at the onset of infection (P = .01). PIV infection causes significant morbidity and mortality in children undergoing HSCT. | 10.1016/j.bbmt.2011.03.001 |
pubmed_960_22604 | Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease. The review attempts to summarize the information available on host immune response to Mycobacterium tuberculosis. Since the main route of entry of the causative agent is the respiratory route, alveolar macrophages are the important cell types, which combat the pathogen. Various aspects of macrophage-mycobacterium interactions and the role of macrophage in host response such as binding of M. tuberculosis to macrophages via surface receptors, phagosome-lysosome fusion, mycobacterial growth inhibition/killing through free radical based mechanisms such as reactive oxygen and nitrogen intermediates; cytokine-mediated mechanisms; recruitment of accessory immune cells for local inflammatory response and presentation of antigens to T cells for development of acquired immunity have been described. The role of macrophage apoptosis in containing the growth of the bacilli is also discussed. The role of other components of innate immune response such as natural resistance associated macrophage protein (Nramp), neutrophils, and natural killer cells has been discussed. The specific acquired immune response through CD4 T cells, mainly responsible for protective Th1 cytokines and through CD8 cells bringing about cytotoxicity, also has been described. The role of CD-1 restricted CD8(+) T cells and non-MHC restricted gamma/deltaT cells has been described although it is incompletely understood at the present time. Humoral immune response is seen though not implicated in protection. The value of cytokine therapy has also been reviewed. Influence of the host human leucocyte antigens (HLA) on the susceptibility to disease is discussed. Mycobacteria are endowed with mechanisms through which they can evade the onslaught of host defense response. These mechanisms are discussed including diminishing the ability of antigen presenting cells to present antigens to CD4(+) T cells; production of suppressive cytokines; escape from fused phagosomes and inducing T cell apoptosis. The review brings out the complexity of the host-pathogen interaction and underlines the importance of identifying the mechanisms involved in protection, in order to design vaccine strategies and find out surrogate markers to be measured as in vitro correlate of protective immunity. | pubmed_960_22604 |
pubmed_205_19021 | Here, we discuss the relationship between protein sequence and protein structural similarity. It is established that a protein structural distance (PSD) of 2.0 is a threshold above which two proteins are unlikely to have a detectable pairwise sequence relationship. A precise correlation is established between the level of sequence similarity, defined by a normalized Smith-Waterman score, and the probability that two proteins will have a similar structure (defined by pairwise PSD<2). This correlation can be used in evaluating the likelihood for success in a comparative modeling procedure. We establish the existence of a correlation between sequence and structural similarity for pairs of proteins that are related in structure but whose sequence relationship is not detectable using standard pairwise sequence alignments. Although it is well known that there is a close relationship between sequence and structural similarity for pairwise sequence identities greater than about 30 %, there has been little discussion as to the possible existence of such a relationship for pairs of proteins in or below the twilight zone of sequence similarity (<25 % pairwise sequence identity). Possible implications of our results for the evolution of protein structure are discussed. | 10.1006/jmbi.2000.3974 |
pubmed_1070_5197 | AIM(S)
There is a need for nurse and midwifery managers to have an understanding of devolution and its implications for them and their colleagues. This paper will explain devolution, consider some health and social care policy including similarities and differences, and assess the impact of devolution on the nursing workforce and the regulation of nursing across the four countries of the United Kingdom (UK).
BACKGROUND
If managers are to manage effectively it is critical that they remain aware of emerging policy development and outcomes across the UK. It is now more important than ever that nurses maintain a keen eye on the impact divergent policy is having on practice as well as the UK nursing workforce.
EVALUATION
The impact of devolution across the UK will be explored using convergence and divergence as a framework; commencing by providing an overview of devolution and health, moving on to examine health policy in action across the four countries.
KEY ISSUES
Healthcare is highly political in nature. Devolution has implications for all, and adds to the complexity of health and social care provision. If managers are to manage effectively it is critical that they remain aware of emerging policy development and outcomes across the UK.
CONCLUSION
It is equally important that nurses, and nurse managers, develop and draw upon their political leadership skills, actively engaging in policy debates to ensure that when policies are translated into practice their outcomes are optimal in terms of quality, efficiency and sustainability. Implications for nursing management There is a need for nurse and midwifery managers to have an understanding of post-devolution structures and how they operate in order to work effectively, as well as to learn from the experiences of other parts of the UK. | 10.1111/j.1365-2834.2008.00909.x |
pubmed_924_10206 | Wnt/beta-catenin signaling is central to bone development and homeostasis in adulthood and its deregulation is associated with bone pathologies. Dickkopf-1 (DKK1), a soluble inhibitor of Wnt/beta-catenin signaling required for embryonic head development, regulates Wnt signaling by binding to the Wnt coreceptor lipoprotein-related protein-5 (LRP5)/Arrow. LRP5 mutations causing high bone mass syndromes disrupt DKK1-mediated regulation of LRP5. Forced overexpression of Dkk1 in osteoblasts causes osteopenia, disruption of the hematopoietic stem cell (HSC) niche, and defects in HSC function. Dkk1 also inhibits fracture repair. Studies suggest that DKK1 activation in osteoblasts is the underlying cause of glucocorticoid- and estrogen deficiency-mediated osteoporosis, and at least partially underlies the teratogenic effects of thalidomide on limb development. DKK1 induces proliferation of mesenchymal stem cells (MSC) in vitro and may play a role in the development of high-grade undifferentiated pleomorphic sarcomas derived from MSC and osteosarcomas. DKK1 has been implicated in causing erosive arthritis, the osteolytic phenotypes of multiple myeloma and metastatic breast cancer, and osteoblastic metastases of prostate cancer. Preclinical studies have shown that neutralizing DKK1/Dkk1 and/or enhancing Wnt/beta-catenin signaling may prove effective in treating bone pathologies. Here, we review the rapidly growing body of literature defining a pivotal role for DKK1 in bone health and disease. | 10.1182/blood-2008-03-145169 |
pubmed_459_10820 | Tetracycline therapy, when used in conjunction with surgery or root planing, has been shown to be effective in controlling the progression of juvenile periodontitis. However, the ability of tetracycline alone to control the disease has not been assessed. The present study evaluated the effects of tetracycline therapy, with supragingival plaque control, on clinical attachment levels and radiographic bone height in patients with clinical and radiographic evidence of juvenile periodontitis. The four patients (mean age 15.2 +/- 0.3 yrs) each demonstrated loss of attachment of greater than or equal to 2 mm at one or more probing sites and had accompanying radiographic evidence of early localized bone loss. Following an initial clinical evaluation consisting of pocket depths, attachment levels and standardized radiographs, the patients received systemic tetracycline therapy (1 gm/day for three to six weeks) and oral hygiene instruction. At the completion of antibiotic therapy, patients received a supragingival professional prophylaxis every two weeks for three months, whereupon the initial evaluation was repeated. On comparing the initial and three-month clinical and radiographic data, there were significant decreases in clinical and radiographic measurements. For a total of 85 affected probing sites around 26 teeth, 79% decreased in pocket depth by greater than or equal to 2 mm (with no sites increasing in pocket depth) and 69% gained clinical attachment (with only one site losing attachment of 1 mm). Radiographic measurements revealed an increase in both the height and area of coronal alveolar bone. The findings indicated that six weeks of systemic tetracycline therapy combined with supragingival plaque control was effective in the initial control of early juvenile periodontitis. | 10.1902/jop.1988.59.6.366 |
pubmed_409_12855 | Abnormalities of the CNS, such as arhinencephaly or holoprosencephaly, are common findings in trisomy 13 syndrome. However, neural tube defects (NTDs) are rarely reported. A review of 267 patients in the literature on reported CNS developmental defects in trisomy 13 syndrome showed only 6 patients with lumbosacral NTDs. No case of encephalocele or anencephaly was found. We report on 3 patients with spina bifida from the records of 34 necropsies of karyotyped trisomy 13 syndrome, which were found among 403,710 births. | 10.1002/ajmg.1320360429 |
pubmed_920_1040 | Macular edema is considered as a major cause of visual loss and blindness in patients with ocular fundus diseases. Optical coherence tomography (OCT) is a non-invasive imaging technique, which has been widely applied for diagnosing macular edema due to its non-invasive and high resolution properties. However, the practical applications remain challenges due to the distorted retinal morphology and blurred boundaries near macular edema. Herein, we developed a novel deep learning model for the segmentation of macular edema in OCT images based on DeepLab framework (OCT-DeepLab). In this model, we used atrous spatial pyramid pooling (ASPP) to detect macular edema at multiple features and used the fully connected conditional random field (CRF) to refine the boundary of macular edema. OCT-DeepLab model was compared against the traditional hand-crafted methods (C-V and SBG) and the end-to-end methods (FCN, PSPnet, and U-net) to estimate the segmentation performance. OCT-DeepLab showed great advantage over the hand-crafted methods (C-V and SBG) and end-to-end methods (FCN, PSPnet, and U-net) as shown by higher precision, sensitivity, specificity, and F1-score. The segmentation performance of OCT-DeepLab was comparable to that of manual label, with an average area under the curve (AUC) of 0.963, which was superior to other end-to-end methods (FCN, PSPnet, and U-net). Collectively, OCT-DeepLab model is suitable for the segmentation of macular edema and assist ophthalmologists in the management of ocular disease. | 10.1038/s41598-021-92458-8 |
pubmed_643_17410 | OBJECTIVE
To evaluate if serum Glutathione-S Transferase-Alpha (GSTA) can be used as a biomarker of intrahepatic cholestasis of pregnancy (IHCP).
METHODS
45 pregnant women with IHCP and 45 age and weight matched pregnant women as controls were enrolled and liver function tests including serum GSTA were measured. All cases and controls were followed for their maternal and foetal outcomes till delivery. Statistical analysis included unpaired t test, Mann-Whitney test and chi square test.
RESULTS
IHCP group showed higher mean serum GSTA concentrations compared to controls (85.6 ± 42.7 mcg/l vs. 40.6 ± 6.8 mcg/l; p < 0.001, CI 95%). A positive correlation was observed between serum GSTA and other markers of IHCP like serum bilirubin (r=0.346; p< 0.001), AST (r=0.708; p< 0.001), ALT (r=0.656; p< 0.001) and bile acids (r= 0.491; p< 0.001).Cut off value for GSTA of 47 mcg/l demonstrated good sensitivity (97.8%),specificity (88.9%), positive predictive value (89.8%) and accuracy (93.3%) to diagnose IHCP.
CONCLUSION
Serum GSTA may be a new promising, diagnostic tool with good accuracy compared to the routine markers for diagnosing IHCP. | pubmed_643_17410 |
pubmed_192_8223 | INTRODUCTION
This study is aimed at filling part of the knowledge gap on bicycling safety in the built environment by addressing two questions. First, are built environment features and bicyclist injury severity correlated; and if so, what built environment factors most significantly relate to severe bicyclist injuries? Second, are the identified associations varied substantially among cities with different levels of bicycling and different built environments?
METHODS
The generalized ordered logit model is employed to examine the relationship between built environment features and bicyclist injury severity.
RESULTS
Bicyclist injury severity is coded into four types, including no injury (NI), possible injury (PI), evident injury (EI), and severe injury and fatality (SIF). The findings include: (a) higher percentages of residential land and green space, and office or mixed use land are correlated with lower probabilities of EI and SIF; (b) land use mixture is negatively correlated with EI and SIF; (c) steep slopes are positively associated with bicyclist injury severity; (d) in areas with more transit routes, bicyclist injury is less likely to be severe; (e) a higher speed limit is more likely to correlate with SIF; and (f) wearing a helmet is negatively associated with SIF, but positively related to PI and EI. Practical applications: To improve bicycle safety, urban planners and policymakers should encourage mixed land use, promote dense street networks, place new bike lanes in residential neighborhoods and green spaces, and office districts, while avoiding steep slopes. To promote bicycling, a process of evaluating the risk of bicyclists involving severe injuries in the local environment should be implemented before encouraging bicycle activities. | 10.1016/j.jsr.2018.11.002 |
pubmed_545_1936 | Phytoremediation is one of the biological approaches for remediating textile dyeing effluents. The objective of this study is the use of Pistia stratiotes, an aquatic macrophyte, which was found to degrade the maximum of 83% of mixed azo dye. A phytoreactor was designed and constructed to scale up the process of phytoremediation by P. stratiotes to treat 40 mg/l of synthetic textile effluent. Continuous flow phytoreactor fed with 40 mg/l (cycle 1) which showed maximum decolorization of 84%, COD removal was about 61%, BOD which was reduced up to 71.9%, and TDS removal was about 72% respectively. Further to remove the residual color and toxic effects of the dyes, Phycoremediation was followed for the mixed azo dyes using the microalgae Chlorella vulgaris which showed a maximum decolorization of 99% in the batch study and 74% in the scale-up study where the treated effluent was at the most minimal discharge. Phytotoxicity tests showed 80% of germination in treated effluent, and the plants in untreated wastewater had inhibited growth that indicates only 30% of germination. Such combined biological treatment techniques were put forward to be the most eco-friendly technology, which is cost-effective and attain zero discharge of the textile effluent. | 10.1080/15226514.2020.1868398 |
pubmed_439_22363 | Lithium-ion batteries using either liquid electrolytes or solid electrolytes have been extensively studied in recent years, but both of these encounter safety risks such as flammability of liquid electrolytes and uncontrolled dendrite growth. In this study, a sandwich gel polymer electrolyte (SGPE) with a thermal shutdown function was developed to resolve the safety issues. By adjustment of surface pore size of the SGPE, lithium dendrite growth is suppressed. Due to the sandwich structure design, the SGPE can effectively respond to an overheating environment, regulate lithium ion transport and inhibit the penetration of lithium dendrite, demonstrating a remarkably high safety of the batteries, especially at high temperature or under thermal runaway circumstances. In addition, the LiFePO4/SGPE/Li battery exhibits a high reversible capacity of 135 mA h g-1 at 1C and maintains high capacity retention (>95%) after 200 charge-discharge cycles. This study shows a great advantage to handle thermal abuse and a stable lithium anode, suggesting a promising approach to the high safety lithium metal batteries. | 10.1039/d1ra02641k |
pubmed_969_1527 | The pharmacology of ethylenediamine (EDA) actions in the rat small intestine was examined using isolated gut-bath preparations of proximal segments of the duodenum, jejunum, and ileum. EDA evoked concentration-dependent tetrodotoxin-insensitive relaxations of the intestine, evidently by direct action on the muscularis. Such actions were simultaneous on the longitudinal and circular muscle layers. Investigation of EDA actions on the circular muscle showed that EDA actions were unrelated to any intrinsic GABAergic mechanisms. Moreover, EDA interacted with muscle sites distinct from ATP, histamine, bradykinin, muscarinic, and adrenergic receptors. The ability of EDA to relax the intestinal musculature was generally greater than the smooth muscle relaxant papaverine and substantially better than nicotinic stimulation of the intrinsic inhibitory neurones. It would appear that EDA may be useful as a direct acting smooth muscle relaxant for the study of the physiology-pharmacology of the rodent small intestine. | 10.1139/y91-029 |
pubmed_1118_11745 | Mesenchymal stromal cells (MSC) are a promising platform for regenerative medicine applications because of their multilineage differentiation abilities and ease of collection, isolation, and growth ex vivo. To meet the demand for clinical applications, large-scale manufacturing will be required using three-dimensional culture platforms in vessels such as stirred suspension bioreactors. As MSCs are an adherent cell type, microcarriers are added to the culture to increase the available surface area for attachment and growth. Although extensive research has been performed on efficiently culturing MSCs using microcarriers, challenges persist in downstream processing, including harvesting, filtration, and volume reduction, which all play a critical role in the translation of cell therapies to the clinic. The objective of this review is to assess the current state of downstream technologies available for microcarrier-based MSC cultures. This includes a review of current research within the three stages: harvesting, filtration, and volume reduction. Using this information, a downstream process for MSCs is proposed, which can be applied to a wide range of applications. | 10.1002/bit.28210 |
pubmed_186_16855 | BACKGROUND
Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide, despite gains in diagnostics and treatments made over the last three decades. Existing markers of ovarian cancer possess very limited clinical relevance highlighting the emerging need for identification of novel prognostic biomarkers as well as better predictive factors that might allow the stratification of patients who could benefit from a more targeted approach.
PATIENTS AND METHODS
A summary of molecular genetics of EOC.
RESULTS
Large-scale high-throughput genomic technologies appear to be powerful tools for investigations into the genetic abnormalities in ovarian tumors, including studies on dysregulated genes and aberrantly activated signaling pathways. Such technologies can complement well-established clinical histopathology analysis and tumor grading and will hope to result in better, more tailored treatments in the future. Genomic signatures obtained by gene expression profiling of EOC may be able to predict survival outcomes and other important clinical outcomes, such as the success of surgical treatment. Finally, genomic analyses may allow for the identification of novel predictive biomarkers for purposes of treatment planning. These data combined suggest a pathway to progress in the treatment of advanced ovarian cancer and the promise of fulfilling the objective of providing personalized medicine to women with ovarian cancer.
CONCLUSIONS
The understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required. | 10.1093/annonc/mdw083 |
pubmed_134_23612 | Clinical evidence suggests that idiosyncratic hepatitis following administration of halogenated volatile anesthetics is mediated by autoimmune responses. No murine model to study mechanisms of anesthetic-induced or any other form of drug-induced idiosyncratic hepatitis exists. Anesthetics are believed to trigger hepatitis by covalently linking a trifluoroacetyl (TFA) chloride hapten to hepatic proteins, forming haptenated self-proteins. To test this hypothesis, we developed a hapten-induced model of hepatitis by immunization with syngeneic S100 liver proteins covalently coupled to TFA (TFA-S100). We found that TFA-S100 induced hepatitis was more severe than disease induced by S100 plus adjuvants or by the adjuvant alone and was characterized by neutrophil, mast cell, and eosinophil infiltration. TFA-specific IgG1 antibodies directly correlated with hepatitis, whereas S100 autoantibodies did not. TNF-alpha, IL-1beta, and IL-6 released from splenocytes collected 2 weeks after TFA-S100 inoculation were increased resembling the elevated serum cytokines reported in patients with autoimmune hepatitis (AIH). Three weeks after inoculation, the peak of hepatitis, we noted decreased numbers of Kupffer cells and lower levels of IL-6 and IL-10 in the liver, cytokines produced by Kupffer cells. This is the first report, to our knowledge, of a hapten-induced model of hepatitis with immune and autoimmune features. | 10.1016/j.yexmp.2004.10.004 |
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