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pubmed_537_19492 | The ultrastructure of the midgut epithelial cells of Tetrodontophora bielanensis (Collembola) fed either with lead-, cadmium- or zinc-enriched food or kept under control conditions was compared by transmission electron microscopy (TEM). Atomic absorption spectrophotometry (AAS) showed accumulation of these three metals in the body tissues of the collembolans. Intracellular localization of zinc in the midgut epithelial cells was investigated by electron spectroscopic imaging (ESI) and electron energy loss spectroscopy (EELS). The presence of lead in the midgut tissue was shown by laser microprobe mass spectrometry (LAMMS). Under heavy metal conditions, the midgut cells showed different ultrastructural alterations, the degree of which was found to be dose-dependent. Independent of the type of the metal in the food, the endoplasmic reticulum appeared fenestrated or vesiculated, and often large vacuoles, which were shown to be ER-derived, occurred throughout the cells. Also the mitochondrial membranes were affected by heavy metal stress. In epithelial cells of individuals exposed to either lead or cadmium, an increase of myelin-like structures could be observed. In the case of exposure to zinc in the highest applied concentration, the cytoplasm showed condensation and portions of the microvillous border appeared destroyed. Additionally, an increase of mineral congregations (type-A spherites) could be observed under heavy metal influence. Intracellularly stored zinc could be localised at highly affected mitochondrial membranes, in the microvillous border, and in the heterochromatin. | 10.1016/0048-9697(95)05009-4 |
pubmed_895_18764 | BACKGROUND
Immune activation is one of the main features of HIV/Hepatitis C virus (HCV) infections and has been linked to the disturbance of the gut-associated lymphoid tissue (GALT). In chronic HIV infection, loss of GALT integrity results in translocation of microbial products and chronic immune activation. We explored the relationship between bacterial translocation and specific colonic proteins, including liver expressed antimicrobial peptide (LEAP 2) which may play a role in modulating the bacterial translocation process.
METHODS
A total of 40 subjects (10 HIV/HCV, 10 HIV, 10 HCV-infected patients and 10 controls) were enrolled and underwent serum and colonic tissue sampling. The levels of immune activation were evaluated by measuring plasma sCD27, and the levels of selected proinflammatory, Th2 and regulatory cytokines in both the plasma and supernatant of CD3-stimulated intraepithelial lymphocytes. We also evaluated LEAP-2 expression in the colon biopsies using Affymetrix Human Gene 1.0 ST (HuGene) and fluorescent immunohistochemistry.
RESULTS
Increased levels of sCD27 were observed in HIV/HCV coinfected (p=0.03) and HIV monoinfected (p=0.04) patients compared with controls consistent with the presence of immune activation. The chip array identified LEAP-2 expression as a key marker associated with immune activation. LEAP-2 expression in HIV, HCV and HIV/HCV-infected patients was significantly lower compared with controls, and was significantly negatively correlated (p=0.03, r=-0.44) with sCD27.
CONCLUSIONS
Our data suggests that HCV and HIV infections are associated with decreased expression of LEAP-2 in colonic tissue. This may represent a key mechanism for enhanced microbial translocation and immune activation in HIV/HCV-infected patients. | 10.1136/jclinpath-2013-201581 |
pubmed_933_6003 | The adsorption dynamics of atomic oxygen on a model beta-cristobalite silica surface has been studied by combining ab initio electronic structure calculations with a molecular dynamics semiclassical approach. We have evaluated the interaction potential of atomic and molecular oxygen interacting with an active Si site of a model beta-cristobalite surface by performing DFT electronic structure calculations. As expected, O is strongly chemisorbed, E(b) = 5.57 eV, whereas molecular oxygen can be weakly adsorbed with a high-energy barrier to the adsorption state of approximately 2 eV. The binding energies calculated for silica clusters of different sizes have revealed the local nature of the O,O(2)-silica interaction. Semiclassical collision dynamic calculations show that O is mainly adsorbed in single-bounce collisions, with a smaller probability for adsorption via a multicollision mechanism. The probability for adsorption/desorption (reflected) collisions at the three impact energies is small but not negligible at the higher energy considered in the trajectory calculations, about P(r) = 0.2 at E(kin) = 0.8 eV. The calculations give evidence of a complex multiphonon excitation-deexcitation mechanism underlying the dynamics of stable adsorption and inelastic reflection collisions. | 10.1021/jp9066026 |
pubmed_191_16112 | We present our experience using conchal composite grafts in major and minor nasal reconstruction. We believe that composite grafts have an important and under-utilized role as an adjunct to the paramedian forehead flap on total and subtotal nasal reconstruction, as well as in providing an internal lining and support in stenosis of the nasal vestibule. The use of a composite conchal graft as an inner lining and support is often preferential to a septal composite or hinge flap that often results in a septal perforation with its associated morbidity. We recognize that a composite conchal graft used for reconstruction of the alar margin provides a suboptimal result after several months. This is because it is not always possible to replace a whole aesthetic subunit and whilst the site the graft is harvested from often allows the correct contour to be chosen, the quality of skin is often different and this can be seen after several weeks when any post-operative oedema has settled. | 10.1258/0022215011909503 |
pubmed_692_21606 | Because psoriatic arthritis (PsA) is an inflammatory disease of joints, serum soluble biomarkers specific for chronic joint and bone inflammation may predict future disease severity and response to therapy, thereby informing stratified medicine approaches. The objectives of our systematic review were to determine whether serum soluble bone and cartilage turnover biomarkers are (1) associated with PsA or psoriatic spondyloarthropathy; and (2) associated with disease activity, disease severity, or clinical phenotype. Ten studies met eligibility criteria. Matrix metalloproteinase (MMP)-3, Dickkopf (DKK)-1, macrophage colony-stimulating factor (M-CSF), crosslinked telopeptide of collagen-1, and tumor necrosis factor-related apoptosis-inducing ligand were associated with PsA, with equivocal results for osteoprotegerin (OPG) and bone alkaline phosphatase (ALP). MMP-3, DKK-1, M-CSF, CPII:C2C (ratio of cartilage degradation vs byproduct formation), and possibly OPG were associated with PsA independently of psoriasis. C1-2C (a neoepitope released when type 2 cartilage is degraded by collagenases) was associated with both tender and swollen joint counts, and bone morphogenetic protein-4 with patient global assessment of disease, pain score, and the Bath Ankylosing Spondylitis Disease Activity Index. Bone ALP was associated with disease activity. M-CSF and receptor activator of nuclear factor-κB ligand were associated with several plain radiographic features. No studies have investigated biomarker associations specifically with axial PsA. | 10.3899/jrheum.140223 |
pubmed_614_9445 | Functional magnetic resonance imaging (fMRI) studies typically collapse data from many subjects, but brain functional organization varies between individuals. Here we establish that this individual variability is both robust and reliable, using data from the Human Connectome Project to demonstrate that functional connectivity profiles act as a 'fingerprint' that can accurately identify subjects from a large group. Identification was successful across scan sessions and even between task and rest conditions, indicating that an individual's connectivity profile is intrinsic, and can be used to distinguish that individual regardless of how the brain is engaged during imaging. Characteristic connectivity patterns were distributed throughout the brain, but the frontoparietal network emerged as most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid intelligence: the same networks that were most discriminating of individuals were also most predictive of cognitive behavior. Results indicate the potential to draw inferences about single subjects on the basis of functional connectivity fMRI. | 10.1038/nn.4135 |
pubmed_301_1328 | Two gene-targeted immunoglobulin heavy chain transgenic mouse strains, TgH(KL25) and TgH(VI10), expressing neutralizing specificities for lymphocytic choriomeningitis virus and vesicular stomatitis virus, respectively, have been generated. Three days after lymphocytic choriomeningitis virus infection, TgH(KL25) mice showed a thymus-independent neutralizing IgM response followed by thymus-dependent (TD) IgG. In contrast, WT mice mounted only a TD IgG response around day 80. These observations indicated that not only structural properties of the virus but also immunological parameters such as the frequency of B cells were indicative for the induction of thymus-independent versus TD Ig responses. Naïve vesicular stomatitis virusspecific Ig heavy chain transgenic mice displayed greatly elevated natural antibody titers. However, despite these high naïve titers, de novo activation of naïve CD4+ T and B cells was not blocked. Therefore, B cells giving rise to natural antibodies do not participate in virus-induced antibody responses. | 10.1073/pnas.2135542100 |
pubmed_163_9155 | BACKGROUND
The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals.
METHODS
MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com ) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders.
DISCUSSION
This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics.
SYSTEMATIC REVIEW REGISTRATION
Open Science Framework (OSF) registration DOI: https://doi.org/10.17605/osf.io/4n9d7 . | 10.1186/s13643-021-01854-8 |
pubmed_56_13990 | We herein report a kind of one-dimensional biocompatible fluorescent silicon nanorods (SiNRs) with tunable lengths ranging ∼100-250 nm, which can be facilely prepared through one-pot microwave synthesis. In addition to the strong fluorescence (quantum yield value: ∼15%) and negligible toxicity, the resultant SiNRs exhibit excitation wavelength-dependent photoluminescence whose maximum emission wavelength ranges from ∼450 to ∼600 nm under serial excitation wavelengths from 390 to 560 nm, providing feasibility for multicolor biological imaging. More significantly, the SiNRs are ultrahighly photostable, preserving strong and nearly unchanged fluorescence under 400 min high-power UV irradiation, which is in sharp contrast to severe fluorescence quenching of organic dyes (e.g., FITC) or II-VI quantum dots (QDs) (e.g., CdTe QDs and CdSe/ZnS QDs) within 15 or 160 min UV treatment under the same experiment conditions, respectively. Taking advantage of these attractive merits, we further exploit the SiNRs as a novel type of color converters for the construction of white light-emitting diodes (LED), which is the first proof-of-concept demonstration of LED device fabricated using the one-dimensional fluorescent silicon nanostructures. | 10.1021/jacs.6b00479 |
others_314_200443 | Deep neural networks display impressive performance but suffer from limited interpretability. Biology-inspired deep learning, where the architecture of the computational graph is based on biological knowledge, enables unique interpretability where real-world concepts are encoded in hidden nodes, which can be ranked by importance and thereby interpreted. In such models trained on single-cell transcriptomes, we previously demonstrated that node-level interpretations lack robustness upon repeated training and are influenced by biases in biological knowledge. Similar studies are missing for related models. Here, we test and extend our methodology for reliable interpretability in P-NET, a biology-inspired model trained on patient mutation data. We observe variability of interpretations and susceptibility to knowledge biases, and identify the network properties that drive interpretation biases. We further present an approach to control the robustness and biases of interpretations, which leads to more specific interpretations. In summary, our study reveals the broad importance of methods to ensure robust and bias-aware interpretability in biology-inspired deep learn | 10.1101/2023.07.17.549297 |
pubmed_788_20647 | Defects in erythrocyte ankyrin are the most common cause of typical, dominant hereditary spherocytosis (HS). Detection of ankyrin gene mutations has been complicated by allelic heterogeneity, large gene size, frequent de novo mutations, and associated mRNA instability. Using denaturing high-performance liquid chromatography (DHPLC)-based mutation detection, a mutation in the splice acceptor of exon 17 was discovered in a Turkish family. Reticulocyte RNA and functional minigene splicing assays in heterologous cells revealed that this mutation was associated with a complex pattern of aberrant splicing, suggesting that removal of intron 16 is important for ordered ankyrin mRNA splicing. As predicted by clinical, laboratory, and biochemical studies, the parents were heterozygous and the proband was homozygous for this mutation. These data indicate that DHPLC offers a highly sensitive, economic, and rapid method for mutation detection and, unlike previously suggested, homozygosity for a mutation associated with dominant ankyrin-linked HS may be compatible with life. | 10.1182/blood-2006-09-046573 |
others_210_12575 | Primary ovarian carcinoid tumors are rare neuroendocrine tumors representing a small percentage of malignant ovarian germ cell tumors, accounting for less than 0.1% of all ovarian carcinomas and 5% of all carcinoid tumors. These tumors arise in the intestine, with the appendix most frequently involved, and more rarely from the thymus, bronchus, stomach or pancreas. Because of their rarity, the diagnosis is often difficult until the patient undergoes an intraoperative histopathologic sample examination. During the surgery procedure of excision of the lesion, some hemodynamic instability could occur. The different type of carcinoid tumors of the ovary are the insular, trabecular, strumal or mucinous type (goblet cell). Despite imagery with CT and MRI preoperatively which recognizes solid characterisitics, the differential diagnosis with other ovary malignancies is very difficult. In cases of suspicion of a carcinoid, the perioperative management and diagnostic testing are crucial to delay the surgery. Better knowledge of this rare disease and its clinical manifestations may improve preoperative evaluation, minimize the pitfalls of management, and enable the surgery and anesthesiology team to take appropriate precautions for optimal surgical management. The authors present eight cases with ovarian tumors, which underwent a radical hysterectomy with bilateral adnexectomy and regional and para-aortical lymph node clearance. The histological examination revealed primary ovarian carcinoid tumors. © 2019 S.O.G. CANADA Inc.. All rights reser | 10.12892/ejgo4462.2019 |
pubmed_499_26285 | Water quality sampling is a key element in tracking water quality monitoring objectives. However, frequencies adapted by different agencies might not be sufficient to provide an accurate indication of water quality status. In this study, data from low- and high-resolution water quality datasets were analyzed to determine the extent to which monitoring objectives could be achieved with different sampling frequencies, with a view to providing recommendations and best practices for water quality monitoring frequency in places with limited resources with which to implement a high-frequency monitoring plan. Water quality data from two watersheds (Maumee River and Raisin River) located in the Western Lake Erie Basin (WLEB) were used since these watersheds have consistent records over substantial periods of time, and the water quality data available have a high resolution (at least daily). The water quality constituents analyzed included suspended solids (SS), total phosphorus (TP), soluble reactive phosphorus (SRP), and nitrate + nitrite (NO2+3). Sources of pollutants for watersheds located in the WLEB include contributions from point sources like discharges from sewage treatment plants and non-point sources such as agricultural and urban storm runoff. Weekly, bi-weekly, monthly, and seasonal datasets were created from the original datasets, following different sampling rules based on the day of the week, week of the month, and month of the year. The resulting datasets were then compared to the original dataset to determine how the sampling frequency would affect the results obtained in a water quality assessment when different monitoring objectives are considered. Results indicated that constituents easily transported by water (such as sediments and nutrients) require more than 50 samples/year to provide a small error (< 10%) with a confidence interval of 95%. Monthly and seasonal sampling were found appropriate to report a stream's prevailing water quality status and statistical properties. However, these resolutions might not be sufficient to capture long-term trends, in which case bi-weekly samples would be preferable. Limitations of low-resolution sampling frequency could be overcome by including rainfall events and random sampling during specific time windows as part of the monitoring plan. | 10.1007/s10661-022-10169-7 |
pubmed_911_7261 | The science and technology of making good quality holes in tubing is an important issue for the success of the application. The process options and their benefits and limitations are examined. | pubmed_911_7261 |
pubmed_107_19549 | Previous epidemiological studies have suggested that the LpA-I subfraction of HDL is more protective than the LpA-I:A-II subfraction against the development of cardiovascular disease. A possible basis for a specific anti-atherogenic function of LpA-I emerged from studies of cholesterol efflux from cultured mouse adipocytes. LpA-I efficiently removed excess cholesterol from the mouse adipocytes, while LpA-I:A-II was ineffective. On the other hand, LpA-I:A-II was able to stimulate cholesterol efflux from a number of other cell types including rodent macrophages. Because of previously reported differences in HDL stimulation of cholesterol clearance from macrophages of different origins, we determined whether LpA-I:A-II could induce cholesterol efflux from cultured human monocyte-macrophages. Our findings showed that LpA-I:A-II and HDL3 effectively stimulated cholesterol efflux from human monocyte-macrophages enriched with cholesterol by incubation with AcLDL. LpA-I:A-II also decreased by one-half the amount of cholesterol accumulated when macrophages were incubated with AcLDL and LpA-I:A-II together. Thus, it would appear that the differential anti-atherogenic effects of LpA-I:A-II and LpA-I do not derive from their effects on macrophage cholesterol efflux. Possibly these HDL subfractions differentially affect other biologic processes that modulate the development of cardiovascular disease. | 10.1016/0925-4439(94)00067-z |
pubmed_844_20959 | Following a mild cortical impact injury delivered by a piston to the right sensorimotor cortex of the anesthetized rat, we evaluated mantle loss, neuronal changes, and fiber track degeneration by deOlmos silver stains up to 8 weeks after injury. Darkened neurons indicating damage (chromatolysis) occurred widely throughout both hemispheres and were seen from 1 h to 8 weeks after injury. This effect might have occurred from pressure wave damage from piston impact, brain displacement or deafferentation. Cerebral mantle loss was variable but fiber track degeneration related to projection and corticofugal descending tracks associated with the right sensorimotor system was rather constant. Unexpectedly, considerable fiber track degeneration occurred within the cerebellum, especially the inferior vermis. Cells directly under the piston face were surprisingly well-preserved but axon degeneration studies showed that these apparently intact neuronal cell bodies were surrounded by a dense network of degenerating fiber tracks. The intact cells, therefore, may have been functionally cut off from the rest of the brain owing to interruption of their efferents and afferents. The increased susceptibility of axons compared to cell bodies seen with this focal injury is similar to that observed with diffuse brain injury. The early appearing, severe and widespread axon damage we observed suggests that amelioration of focal traumatic brain injury will have to be directed promptly to the preservation of axons as well as cell bodies. | 10.1016/s0006-8993(98)00107-3 |
pubmed_803_2261 | The purpose of this case report of cancer complicating Crohn's disease is to highlight the occult nature of these tumours. From the literature it is apparent that the majority are only discovered by the pathologist. As many are inconspicuous even on macroscopic examination an improved method of dissection is suggested. | 10.1111/j.1365-2559.1983.tb02250.x |
pubmed_625_23369 | The oncometabolite, D-2-hydroxyglutarate, accumulates in various cancers because of acquired mutations in isocitrate dehydrogenase 1 & 2. Here, we describe a new mechanism for D-2-hydroxyglutarate accumulation in breast cancer. It involves c-Myc signaling and alcohol dehydrogenase, iron-containing protein 1 (ADHFE1) and leads to metabolic reprogramming, de-differentiation, and increased mammary tumorigenesis. | 10.1080/23723556.2018.1432260 |
pubmed_1046_8261 | Tumor cell-derived vascular endothelial growth factor (VEGF)-C has been primarily implicated in promoting lymphangiogenesis by activating Flt-4 (VEGFR-3) expressed on lymphatic endothelial cells via a paracrine mechanism. Flt4 has also been shown to be expressed selectively in subsets of cancer cells. However, little is known about the functional role of VEGF-C/Flt4 signaling via an autocrine mechanism, as well as the clinicopathological implication of the VEGF-C/Flt4 axis and its downstream effector molecules, in head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). In the present study, we detected Flt-4 expression selectively in several HNSCC cell lines by quantitative PCR, and its internalization reflecting receptor activation was confirmed by immunocytochemistry in SAS and HO1U1 cells. Flt-4 stimulation upregulated the expression of contactin-1 (CNTN-1, a neural cell adhesion molecule) and VEGF-C itself in SAS cells, while Flt-4 inhibition downregulated the expression of CNTN-1 in both SAS and HO1U1 cells and that of VEGF-C itself in SAS cells. In vitro cell proliferation and migration assays using SAS cells demonstrated that both cell proliferation and migration were promoted by Flt-4 stimulation, while those were suppressed by Flt-4 inhibition. Clinicopathological factors and immunohistochemical expression of Flt-4, VEGF-C, and CNTN-1 in tumor cells were evaluated using surgical specimens from patients with tongue squamous cell carcinoma. We found a significant correlation of CNTN-1 expression with both VEGF-C and Flt-4 expression, but not between VEGF-C and Flt-4. Multivariate logistic regression analysis revealed that T classification (P = 0.003), lymphatic invasion (P = 0.024), and Flt-4 expression in tumor cells (P = 0.046) were independently predictive of neck lymph node metastasis. These results suggest that the VEGF-C/Flt-4 axis in tumor cells enhances tumor cell proliferation and migration via upregulating the expression of VEGF-C itself and CNTN-1 in an autocrine manner, thereby contributing to cancer progression of OSCC, including neck metastasis. Hence, targeting the VEGF-C/Flt-4 axis in tumor cells can be an attractive therapeutic strategy for the treatment of cancer. | pubmed_1046_8261 |
others_314_88472 | Correlation analysis is a fundamental technique to determine potential relationships within biological processes. However, many biological processes have been shown to function in a periodic manner. When modeling correlations, the fluctuations that are associated with periodicity cause significant issues. We have implemented a Phase Shift Correlation (PSC) algorithm, with a corresponding value PSCrho, to address the periodicity and phase variance associated with features that vary with the same frequency -- but are phase shifted. The phase shift could well indicate causality with one features quantitative change leading to the change in the other feature.
We applied the PSC algorithm to Ulcerative Colitis (UC) microbiome data and compared the resulting feature relationships with the equivalent Spearman correlation function results. PSC located many instances of higher phase shifted correlations, where the corresponding Pearson correlation was low | 10.1101/2020.07.01.174409 |
pubmed_407_5218 | Recent studies have demonstrated cytochrome P450 CYP1-mediated metabolism and CYP1-enzyme induction by naturally occurring flavonoids in cancer cell line models. The arising metabolites often exhibit higher activity than the parent compound. In the present study we investigated the CYP1-mediated metabolism of the citrus polymethoxyflavone nobiletin by recombinant CYP1 enzymes and MCF7 breast adenocarcinoma cells. Incubation of nobiletin in MCF7 cells produced one main metabolite (NM1) resulting from O-demethylation in either A or B rings of the flavone moiety. Among the three CYP1 isoforms, CYP1A1 exhibited the highest rate of metabolism of nobiletin in recombinant CYP microsomal enzymes. The intracellular CYP1-mediated bioconversion of the flavone was reduced in the presence of the CYP1A1 and CYP1B1-selective inhibitors α-napthoflavone and acacetin. In addition nobiletin induced CYP1 enzyme activity, CYP1A1 protein and CYP1B1 mRNA levels in MCF7 cells at a concentration dependent manner. MTT assays in MCF7 cells further revealed that nobiletin exhibited significantly lower IC50 (44 μM) compared to cells treated with nobiletin and CYP1A1 inhibitor (69 μM). FACS analysis demonstrated cell a cycle block at G1 phase that was attenuated in the presence of CYP1A1 inhibitor. Taken together the data suggests that the dietary flavonoid nobiletin induces its own metabolism and in turn enhances its cytostatic effect in MCF7 breast adenocarcinoma cells, via CYP1A1 and CYP1B1 upregulation. | 10.1016/j.fct.2012.06.030 |
pubmed_469_15558 | Our study reports two nontwin sisters with late-onset Lennox-Gastaut syndrome and chromosome 15q duplication, showing the evolution, symptoms, diagnosis, and treatment of these patients, with the aim of increasing knowledge about this extremely rare association. They had a variety of generalized seizures types, intellectual disability, electroencephalogram with generalized epileptiform discharges less than 3 Hz, dysmorphisms, and genetic studies with the presence of duplicated chromosome 15. Cases reported here may be related to chromosomal changes inherited from their asymptomatic mother. | 10.1055/s-0042-1743457 |
pubmed_484_13547 | SIBIL (Italian Online Bioethical Information System) is the database distributed on the net by the Istituto Superiore di Sanita through the homonymous system, conceived for a systematic dissemination of bioethical information, which is scattered in a multitude of informative resources, due to the interdisciplinary nature of the subject. The present work shows the structure and the main features of the database, which aims to provide a regular update on the national ethical debate through the collection of a wide range of documents. Emphasis is laid on the query mechanisms through practical suggestions which may contribute to a more precise searching, thus granting the retrieval of relevant documents. The article also describes the short-term development of the system, which is expected to take part in a European bioethical net in the near future. | pubmed_484_13547 |
pubmed_1014_11887 | Tumor cell plasticity is an event that has been observed in several malignancies. In fact, most of the solid tumors are characterized by cellular heterogeneity and undergo constant changes as the tumor develops. The increased plasticity displayed by these cells allows them to acquire additional properties, enabling epithelial-mesenchymal transitions, dedifferentiation and the acquisition of stem cell-like properties. Here we discuss the particular importance of an inflammatory microenvironment for the bidirectional control of cellular plasticity and the potential for therapeutic intervention. | pubmed_1014_11887 |
pubmed_222_4435 | A retrospective study analyzing etiological, clinical and hormonal aspects in a population of 45 patients (14 males and 31 females) with permanent hypogonadism was performed, the most important findings were: 1) The most common cause of hypogonadism was gonadal failure (60% of all patients). This included-twenty-three females and four males. Eighteen patients had XO, two XY and two more XX gonadal dysgenesis. In the remaining cases, three patients had bilateral agonadism and two had testicular atrophy secondary to radiochemotherapy. 2) Eighteen patients had hypogonadotropic hypogonadism (40% of the cases). Ten were males and eight females. Eleven patients had gonadotropin deficiency associated with other pituitary dysfunctions. Deficiency of GH was found in all cases. TSH in ten, ACTH in nine and ADH in five. An increase in prolactin was observed in seven patients. The etiology of the hypopituitarism was intracranial tumors in five cases, idiopathic in three, perinatal hypoxemia in two and hypoplastic pituitary in one. In the remaining seven cases, isolated gonadotropin deficiency was found. Four cases were idiopathic, two cases had demyelinating diseases and one beta-thalassaemia. 3) Mean levels of testosterone were 4.20 +/- 6.5 (0, 20) pg/ml. Meal levels of estradiol of the total group, gonadal failure patients and those with hypogonadotropic hypogonadism were 8.51 +/- 14.7 (0, 50), 9 +/- 16 (0, 50) and 7.12 +/- 10.98 (0, 29) pg/ml, respectively. 4) Mean basal levels of LH and FSH in patients with gonadal failure were 35.57 +/- 60.66 (5, 320) and 53.19 +/- 53.92 (4, 230) mUi/ml, respectively. In hypogonadotropic hypogonadism patients, mean basal and peak levels of LH were 0.98 +/- 1.24 (0, 5) and 3.45 +/- 3.94 (0, 12) mUi/ml, respectively. Mean basal and peak levels of FSH after LHRH stimulation were 1.43 +/- 1.88 (0, 6) and 3.85 +/- 4.85 (0, 17) mUi/ml, respectively. | pubmed_222_4435 |
pubmed_40_12120 | Metal oxides are of paramount importance in heterogeneous catalysis as either supports or active phases. Controlled synthesis of one-dimensional (1D) metal oxide nanostructures has received enormous attention in heterogeneous catalysis due to the possibility of tailoring the properties of metal oxides by tuning their shapes, sizes, and compositions. This feature article highlights recent advances in shape controlled synthesis of 1D metal oxide nanostructures and their applications in heterogeneous catalysis, with the aim of introducing new insights into the heterogeneous catalyst design. | 10.1039/c3nr02030d |
pubmed_98_10517 | Tea gray blight disease and its existing control measures have had a negative impact on the sustainable development of tea gardens. However, our knowledge of safe and effective biological control measures is limited. It is critical to explore beneficial microbial communities in the tea rhizosphere for the control of tea gray blight. In this study, we prepared conditioned soil by inoculating Pseudopestalotiopsis camelliae-sinensis on tea seedling leaves. Thereafter, we examined the growth performance and disease resistance of fresh tea seedlings grown in conditioned and control soils. Next, the rhizosphere microbial community and root exudates of tea seedlings infected by the pathogen were analyzed. In addition, we also evaluated the effects of the rhizosphere microbial community and root exudates induced by pathogens on the performance of tea seedlings. The results showed that tea seedlings grown in conditioned soil had lower disease index values and higher growth vigor. Soil microbiome analysis revealed that the fungal and bacterial communities of the rhizosphere were altered upon infection with Ps. camelliae-sinensis. Genus-level analysis showed that the abundance of the fungi Trichoderma, Penicillium, and Gliocladiopsis and the bacteria Pseudomonas, Streptomyces, Bacillus, and Burkholderia were significantly (p < 0.05) increased in the conditioned soil. Through isolation, culture, and inoculation tests, we found that most isolates from the induced microbial genera could inhibit the infection of tea gray blight pathogen and promote tea seedling growth. The results of root exudate analysis showed that infected tea seedlings exhibited significantly higher exudate levels of phenolic acids and flavonoids and lower exudate levels of amino acids and organic acids. Exogenously applied phenolic acids and flavonoids suppressed gray blight disease by regulating the rhizosphere microbial community. In summary, our findings suggest that tea plants with gray blight can recruit beneficial rhizosphere microorganisms by altering their root exudates, thereby improving the disease resistance of tea plants growing in the same soil. | 10.3389/fmicb.2021.774438 |
pubmed_891_14312 | The cotton mealybug Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) is an extremely polyphagous invasive pest that can cause serious damages to cultivated plants. The pest is native to America but invaded Asian and Mediterranean countries during the last decades. Tomato (Lycopersicon esculentum Mill., Solanaceae) is an economic relevant crop worldwide and its production can be threatened by numerous insect pests including P. solenopsis. We recorded for the first time P. solenopsis in association with tomato in greenhouse crops and urban landscapes in Sicily (Italy) during the fall season in 2020. The species was identified as P. solenopsis based on the morphological characters and DNA amplification of an ≈800 bp portion of mitochondrial cytochrome oxidase subunit I (mtCOI) gene. The phylogenetic analysis among the obtained P. solenopsis mtCOI sequences with those already available in GenBank suggests Asian countries as a potential source of new introduction. This is the first record of P. solenopsis attacking tomato plants in Italy and may represent a potential threat for tomato production in Europe and nearby countries. For this reason, actions should be taken to avoid the uncontrolled spread of this alien species. | 10.3390/insects12080675 |
pubmed_834_3739 | Although criteria have been established to assess the quality of sputum specimens, no criteria for assessing the quality of endotracheal suction aspirates (ETSA) exist. Therefore, we compared the Gram stain (GS) and culture results for 504 consecutive ETSA specimens. Results recorded for GS included the numbers of squamous epithelial cells (SEC) and polymorphonuclear leukocytes (PML) per low-power field (LPF) (magnification, x100) as well as the quantities and types of organisms per high-power field (HPF) (magnification, x1,000). Culture results were quantitated by organism. Only 15% of ETSA specimens tested by GS contained > 10 SEC per LPF, and 21, 20, and 59% had < or = 10, 11 to 24, and > or = 25 PML per LPF, respectively. For 40% of ETSA specimens, no organisms were visible by GS. Of these specimens, 40% were sterile, 48% grew normal oropharyngeal flora (NF) only, 5% grew 1+ NF (i.e., > 10 colonies in the first quadrant) and 1+ gram-negative rods (GNR), and 7% grew < or = 1+ GNR either alone or in mixed culture. The mean numbers of organisms recovered from ETSA with < or = 10 SEC per LPF and > 10 SEC per LPF were 2.35 and 4.05, respectively. We therefore recommend that ETSA specimens that show no organisms by GS be rejected, in addition to those with > 10 SEC per LPF. Application of these rejection criteria enabled us to reject 847 (41%) of 2,068 ETSA specimens over a 6-month period. This represents a saving of approximately $66,000/year in unnecessary laboratory charges to patients. | 10.1128/jcm.31.5.1027-1029.1993 |
pubmed_919_168 | We examine the role of electronic polarizability in water on short (tens of femtoseconds), intermediate (hundreds of femtoseconds), and long (approximately 1 ps) time scales by comparing molecular dynamics results to experimental data for vibrational spectroscopy of HOD in liquid D2O. Because the OH absorption frequency is sensitive to the details of the atomic forces experienced in the liquid, our results provide important quantitative comparisons for several popular empirical water potentials. When compared with their fixed-charge counterparts, the polarizable models give similar slower long time constants for the decay of vibrational correlations and re-orientational motion that is in better agreement with experiments. Polarizable potentials yield qualitatively dissimilar predictions for frequency fluctuations and transition dipole moment fluctuations at equilibrium. Models that confine the polarizability to the plane of the molecule (i.e., TIP4P-FQ) overestimate the width of the distribution describing frequency fluctuations by more than a factor of two. These models also underestimate the amplitude of the hydrogen-bond stretch at 170 cm(-1). A potential that has both an out-of-plane polarization and fluctuating charges, POL5-TZ, compares best with experiments. We interpret our findings in terms of microscopic dynamics and make suggestions that may improve the quality of emerging polarizable force fields for water. | 10.1073/pnas.0505206102 |
pubmed_1141_21998 | In 200 inpatients on regular neuroleptics, point prevalence of extrapyramidal syndromes, including Parkinson syndrome, akathisia and tardive dyskinesia (TD), was studied and found to be 20, 11 and 22%, respectively. A total of 46 patients have currently, and for a longer time, (average about 3years, median over 1year) been treated with clozapine, and 127 with typical neuroleptics (NLs). Comparing both groups, higher TD scores were found in the clozapine sample. Investigating the influence of a set of seven clinical variables on the TD score with the help of multiple regression analysis, the influence of the treatment modality disappeared, whereas the age proved to be the only significant variable. Studying the role of past clozapine therapy in patients currently on typical NLs and comparing 10 matched pairs of chronic patients with and without TD in whom a complete life-time cumulative dose of NLs was identified, a relationship between TD and length of current typical NL therapy and life-time typical NL dosage could be demonstrated. On the whole, long-term relatively extensive use of clozapine has not markedly reduced the prevalence of extrapyramidal syndromes in our psychiatric inpatient population. In particular, we failed to demonstrate a beneficial effect of clozapine on prevalence of TD. There are certainly patients who suffer from TD in spite of a long-term intensive clozapine treatment. | 10.1016/s0920-9964(99)00133-4 |
pubmed_50_9464 | Multiple comparison procedures combined with modeling techniques (MCP-Mod) (Bretz et al., 2005) is an efficient and robust statistical methodology for the model-based design and analysis of dose-finding studies with an unknown dose-response model. With this approach, multiple comparison methods are used to identify statistically significant contrasts corresponding to a set of candidate dose-response models, and the best model is then used to estimate the target dose. Power and sample size calculations for this methodology require knowledge of the covariance matrix for the estimators of the (placebo-adjusted) mean responses among the dose groups. In this article, we consider survival endpoints and derive an analytic form of the covariance matrix for the estimators of the log hazard ratios as a function of the total number of events in the study. We then use this closed-form expression of the covariance matrix to derive the power and sample size formulas. We discuss practical considerations in the application of these formulas. In addition, we provide an illustration with a motivating example on chronic obstructive pulmonary disease. Finally, we demonstrate through simulation studies that the proposed formulas are accurate enough for practical use. | 10.1111/biom.12968 |
pubmed_450_16683 | Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents' understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers' knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018-1.802). When asked why vaccination rates may be low in their community, the two most common responses were "fearful of side effects" and "ignorance/disinterest/laziness" (44% each). The factors influencing caregivers' demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates. | 10.1371/journal.pone.0150131 |
others_408_931 | otic pollination should be an important consideration when devising management plans for endangered plant species. In this study we documented inter-annual shifts in the suite of floral visitors to Clematis socialis, a federally endangered species. These pollinator shifts were correlated with shifts in climatic variables that we used as a proxy for the potential effects of climatic change. In addition, we characterized floral visitor behavior and conducted single-visit seed set experiments to assess the pollination effectiveness of floral visitors. Five insect species visited flowers of C. socialis: two lepidopteran species (Erynnis juvenalis and Hemaris diffinis) and three bee species (Anthophora ursina, Bombus pennsylvanicus and Xylocopa virginica). Due to their relatively greater frequency of flower visitation and high single-visit seed set (ca. 2.6-3 seeds/visit), two bee species (Anthophora ursina and Bombus pennsylvanicus) are considered to be the major pollinators of C. socialis. However, the relative importance of each pollinator species varied between years. Anthophora ursina was the most important pollinator in 1997, a year when C. socialis bloomed later in the spring. Queens of Boinbus pennsylvanicus were the primary pollinator during 1996, a year when C. socialis bloomed relatively early in the spring. We conclude that management plans that focus on the best pollinator of a suite of pollinators may not preserve the long-term reproductive integrity of endangered plants with generalized pollination systems. We further conclude that asynchrony between flowering season and pollinator activity patterns may be a risk factor associated with human-caused global climate chang | 10.1656/1528-7092(2003)002[0011:CIOCVO]2.0.CO;2 |
pubmed_153_24501 | In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-function knowledge is enhancing our understanding of early nutrition in the neonate. | 10.1146/annurev-nutr-071813-105721 |
pubmed_662_3168 | Antihypertensive drugs reduce cardiovascular morbidity and mortality. This was demonstrated by controlled clinical trials. While most complications are dramatically reduced it is not certain whether the incidence of myocardial infarction is decreased by treatment or whether the severity of the infarct is reduced. The prognosis in patients with borderline and mild hypertension varies widely depending on the number of other risk factors present. Patients with mild hypertension and low risk profiles may not obtain enough benefit from treatment to justify the side effects, inconvenience, and expense of such therapy. Such patients should be individually evaluated as to the need and desirability of treatment. Patients who are not treated with drugs should be seen for an annual follow-up to detect progression. Low sodium diets are effective but they are not practical because it is difficult to adhere to the required degree of sodium restriction. Weight-reducing diets also reduce blood pressure but compliance again is difficult, although it is worth advocating for the few patients who will maintain the diet more or less indefinitely. Between 1973 and 1977 in the United States there has been an 8% decline in deaths due to heart disease, a 17% decrease in deaths due to stroke, and an increase in average life expectancy from 71.3 to 72.8 years. Could this be the result of more widespread treatment? | 10.1161/01.hyp.3.6_pt_2.ii-230 |
pubmed_249_8636 | The purpose of this study was to specify how student attitudes toward different types of patients and the profession change during clinical rotations. A questionnaire was given to all medical students prior to 3rd-year rotations regarding their attitudes toward the medical profession and patient types. It was given again after students completed their 16-week medicine-surgery clerkship. Eighty-eight of 96 students responded to pre- and posttests. Students became less idealistic toward two patient groups: the elderly and people with chronic pain. After clerkship, students believed a greater percentage of the elderly were demented (26% increasing to 35%, p = .09 and that a greater percentage of patients with chronic pain are drug seekers (15% increasing to 24%, p = .004). The authors conclude that in the 3rd year of medical school students become less idealistic toward elderly patients, those with chronic pain, and the profession. | 10.1177/01632780122034795 |
pubmed_118_1259 | Behavior and events distributed in time can serve as markers that signal delays to future events. The majority of timing research has focused on how behavior changes as the time to some event, usually food availability, decreases. The primary objective of the two experiments presented here was to assess how behavior changes as time passes between two time markers when the first time marker was manipulated but the second, food delivery, was held constant. Pigeons were exposed to fixed-interval, response-initiated fixed-interval, and signaled response-initiated fixed-interval 15- and 30-s schedules of reinforcement. In Experiment 1, first-response latencies were systematically shorter in the signaled response-initiated schedules than response-initiated schedules, suggesting that the first response was a more effective time marker when it was signaled. In Experiment 2, responding in no-food (i.e. "peak") trials indicated that timing accuracy was equivalent in the three schedule types. Compared to fixed interval schedules, timing precision was reduced in the signaled response-initiated schedules and was lowest in response-initiated schedules. Results from Experiments 1 and 2 coupled with previous research suggest that the overall "informativeness" of a time marker relative to other events and behaviors in the environment may determine its efficacy. | 10.1002/jeab.226 |
pubmed_914_21533 | The hair tourniquet syndrome is a rare disorder. This syndrome has been described as involving the fingers, the toes and even the genitals. We report a case of hair tourniquet syndrome affecting multiple toes of an infant. After the hair fiber was removed there was a fast healing period and no signs of tissue necrosis were seen. The prompt diagnosis and treatment of the condition is vital to attain a good outcome and prevent further harm to the child. | 10.4103/0256-4947.67088 |
pubmed_378_20216 | Highly reproducible Fourier transform infrared (FTIR) spectra from both single onion (Allium cepa) cell walls and their constituent polymers were obtained under a variety of sampling conditions. The specificity of the chemical extraction sequence used in the preparation of the material was confirmed: pectins only are extracted by cyclohexanediaminetetraacetic acid and sodium carbonate, whereas xyloglucans are extracted by increasing concentrations of potassium hydroxide. There was very little contamination of the first potassium hydroxide extract with residual pectin. The low abundance of both phenolics and protein was also confirmed. The first sodium carbonate extraction almost completely removes esters remaining in the cell wall. We have demonstrated that FTIR spectroscopy can detect large conformational changes in pectic polymers on removal from the cell wall and on drying. FTIR spectroscopy provides a powerful and rapid assay for wall components and putative cross-links by identifying polymers and functional groups nondestructively in muro. The availability of micro-sampling and data acquisition techniques that permit subtraction of the blanket absorption of water make FTIR spectroscopy particularly suitable for studies of cell wall architecture. The use of polarizers with the microscope accessory permits determination of the orientation of particular functional groups with respect to the direction of cell elongation in carrot suspension cells. | 10.1104/pp.100.4.1940 |
pubmed_1096_23794 | BACKGROUND
In Uganda and elsewhere, the private sector provides an increasing and significant proportion of maternal and child health services. However, little is known whether private care results in better quality services and improved outcomes compared to the public sector, especially regarding care at the time of birth.
OBJECTIVE
To describe the characteristics of care-seekers and assess newborn care practices and services received at public and private facilities in rural eastern Uganda.
DESIGN
Within a community-based maternal and newborn care intervention with health systems strengthening, we collected data from mothers with infants at baseline and endline using a structured questionnaire. Descriptive, bivariate, and multivariate data analysis comparing nine newborn care practices and three composite newborn care indicators among private and public health facilities was conducted.
RESULTS
The proportion of women giving birth at private facilities decreased from 25% at baseline to 17% at endline, whereas overall facility births increased. Private health facilities did not perform significantly better than public health facilities in terms of coverage of any essential newborn care interventions, and babies were more likely to receive thermal care practices in public facilities compared to private (68% compared to 60%, p=0.007). Babies born at public health facilities received an average of 7.0 essential newborn care interventions compared to 6.2 at private facilities (p<0.001). Women delivering in private facilities were more likely to have higher parity, lower socio-economic status, less education, to seek antenatal care later in pregnancy, and to have a normal delivery compared to women delivering in public facilities.
CONCLUSIONS
In this setting, private health facilities serve a vulnerable population and provide access to service for those who might not otherwise have it. However, provision of essential newborn care practices was slightly lower in private compared to public facilities, calling for quality improvement in both private and public sector facilities, and a greater emphasis on tracking access to and quality of care in private sector facilities. | 10.3402/gha.v8.24251 |
pubmed_1119_21398 | Steroid receptors have been reported to bind to the nuclear matrix. The nuclear matrix is operationally defined as the residual nuclear structure that remains after extraction of most of the chromatin and all soluble and loosely bound components. To obtain insight in the molecular mechanism of the interaction of steroid receptors with the nuclear matrix, we studied the binding of several deletion mutants of the human androgen receptor (hAR) and the human glucocorticoid receptor (hGR) to the nuclear matrix. Receptor binding was tested for two different nuclear matrix preparations: complete matrices, in which most matrix proteins are retained during the isolation procedure, and depleted matrices, which consist of only a subset of these proteins. The results show that the C-terminal domain of the hAR binds tightly to both depleted and complete matrices. In addition, at least one other domain of the hAR binds to complete matrices but not to depleted matrices. In contrast to the hAR, the hGR binds only to complete matrices. For this interaction both the DNA-binding domain and the C-terminal domain of the hGR are required, whereas the N-terminal domain is not. We conclude that specific protein domains of the hAR and the hGR are involved in binding to the nuclear matrix. In addition, our results indicate that the hAR and the hGR are attached to the nuclear matrix through different molecular interactions. | 10.1002/jcb.240570312 |
pubmed_173_1032 | BACKGROUND
Disorders of serum sodium concentration are some of the most electrolyte abnormalities in the intensive care unit (ICU) patients. These disorders adversely affect the function of vital organs and are associated with increased hospital mortality.
PURPOSE
In the present study we aimed to evaluate the effects of serum sodium concentration abnormalities at the time of hospital admission on the clinical outcome of therapy in a cohort of critically ill poisoned patients.
METHODS
In this cross-sectional study, 184 critically ill poisoned patients aged >18 years and in the first 8 hours of their poisoning, hospitalized in the ICU of a tertiary care university hospital (Isfahan, Iran) between 2010-2012, were evaluated at the admission time and 24 hours later for serum sodium concentration abnormalities and its relationship with age, gender, consciousness status, ingested drugs and clinical outcome of therapy. The clinical outcome was considered as recovery and mortality. Logistic Regression analysis was performed for predictive variables including serum sodium concentration abnormalities in patients' clinical outcome.
FINDINGS
On admission, 152 patients (82.6%) were eunatremic, 21 patients (11.4%) were hyponatremic and 11 patients (6%) were hypernatremic. In the second day eunatremia, hyponatremia and hypernatremia was observed in 84.4%, 13% and 2.2% respectively. Age (OR=1.92; CI=1.18-3.12) and severity of toxicity (OR=1.32; CI=1.12-2.41) were predicting factors of mortality in ICU poisoning patients.
CONCLUSIONS
Serum sodium concentration abnormalities are prevalent in critically ill poisoned patient but do not seem to have a predictive value for the clinical outcome of therapy. | 10.5455/medarh.2015.69.240-243 |
pubmed_939_2848 | Most neurological disorders display impaired synaptic connectivity. Hence, modulation of synapse formation may have therapeutic relevance. However, the high density and small size of synapses complicate their quantification. To improve synapse-oriented screens, we analyzed the labeling performance of synapse-targeting antibodies on neuronal cell cultures using segmentation-independent image analysis based on sliding window correlation. When assessing pairwise colocalization, a common readout for mature synapses, overlap was incomplete and confounded by spurious signals. To circumvent this, we implemented a proximity ligation-based approach that only leads to a signal when two markers are sufficiently close. We applied this approach to different marker combinations and demonstrate its utility for detecting synapse density changes in healthy and compromised cultures. Thus, segmentation-independent analysis and exploitation of resident protein proximity increases the sensitivity of synapse quantifications in neuronal cultures and represents a valuable extension to the analytical toolset for in vitro synapse screens. | 10.1016/j.isci.2020.101542 |
pubmed_1018_17559 | Sensory neurons can establish topologically ordered projections in the central nervous system, thereby building an internal representation of the external world. We analyze how this ordering is genetically controlled in Drosophila, using as a model system the neurons that innervate the mechanosensory bristles on the back of the fly (the notum). Sensory neurons innervating the medially located bristles send an axonal branch that crosses the central nervous system midline, defining a 'medial' identity, while the ones that innervate the lateral bristles send no such branch, defining a 'lateral' identity. We analyze the role of the proneural genes achaete and scute, which are involved in the formation of the medial and lateral bristles, and we show that they have no effect on the 'medial' and 'lateral' identities of the neurons. We also analyze the role of the prepattern genes araucan and caupolican, two members of the iroquois gene complex which are required for the expression of achaete and scute in the lateral region of the notum, and we show that their expression is responsible for the 'lateral' identity of the projection. | 10.1242/dev.125.18.3563 |
pubmed_726_17545 | Infection with Burkholderia pseudomallei has been described, albeit rarely, patients in Bangladesh. Infection usually follows percutaneous inoculation or inhalation of the causative bacterium, which is present in soil and surface water in the endemic region. A 35-year-young male farmer presented with prolonged fever and significant weight loss. Patient gradually deteriorated despite getting different antibiotics including intravenous ceftriaxone and metronidazole. Panels of investigations were done which revealed no diagnostic confirmation except uncontrolled diabetes and multiple abscesses in different organs. Melioidosis was suspected and serum samples were positive for Burkholderia pseudomallei antibody. The case illustrates the importance of non-specific nature of the clinical presentation and high index of suspicion of uncommon diseases like melioidosis where the disease has not been considered as an endemic. | pubmed_726_17545 |
pubmed_489_25105 | Break-induced replication (BIR) is the pathway of homologous recombination (HR) conserved from phages to eukaryotes that serves to repair DNA breaks that have only one end. BIR contributes to the repair of broken replication forks and allows telomere lengthening in the absence of telomerase. Nonallelic BIR may lead to translocations and other chromosomal rearrangements. In addition, BIR initiated at sites of microhomology can generate copy number variations (CNVs) and complex chromosomal changes. The level of mutagenesis associated with DNA synthesis in BIR is significantly higher than during normal replication. These features make BIR a likely pathway to promote bursts of genetic changes that fuel cancer progression and evolution. | pubmed_489_25105 |
pubmed_224_3644 | Dropping of the tip of the nose after surgery is mainly the result of either too extensive resection of the alae or excessive resection of the septum. In the first case, the resulting round or hooked nose can be corrected by an auto or homologous cartilage graft. In the second case, following surgery to obtain functional improvement, the presence of an osteocartilaginous hump can be exploited to support the tip, or a conventional flap can be employed, composed of alar chondromucosal tissue. These remarks are but one particular feature of secondary surgery to the nose, a delicate surgery in full expansion. | pubmed_224_3644 |
pubmed_64_17938 | BACKGROUND
Fatigue is the most common and persistent symptom among women in the first five years after a breast cancer diagnosis. However, long-term prevalence of fatigue, among breast cancer survivors, needs further investigation.
AIM
To compare fatigue experienced by long-term breast cancer survivors with that in a reference population and to evaluate the determinants of that fatigue.
DESIGN AND SETTING
A cross-sectional cohort study of 350 breast cancer survivors ≥5 years after diagnosis and a reference population of 350 women matched by age and general practitioner.
METHOD
Fatigue was measured using the Multidimensional Fatigue Inventory (MFI-20), and a sum score of >60 (multidimensional fatigue) was the primary outcome. Logistic regression was applied to compare the prevalence of multidimensional fatigue between the survivor and reference populations, adjusted for body mass index (BMI) and for cardiovascular and psychological variables. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated. Logistic regression was applied to evaluate the determinants of multidimensional fatigue among the survivors.
RESULTS
Breast cancer survivors (median 10 years after diagnosis), more often experienced multidimensional fatigue than the reference population (26.6% versus 15.4%; OR, 2.0 [95%CI, 1.4-2.9]), even after adjusting for confounders. The odds of multidimensional fatigue were also higher among survivors with symptoms of depression (32.2% versus 2.7%; OR, 17.0 [95%CI, 7.1-40.5]) or anxiety (41.9% versus 10.1%; OR, 6.4 [95%CI, 3.6-11.4]).
CONCLUSION
One in four breast cancer survivors experience multidimensional fatigue and fatigue occurs more frequently than in women of the same age and general practitioner. This fatigue appears to be associated with symptoms of depression and anxiety. | 10.3390/cancers13061301 |
pubmed_42_3661 | Chronic ethanol consumption is associated with increased incidence of hepatic and pulmonary infections. To determine if this is correlated with altered macrophage activity, we analyzed the functional properties of cells isolated sequentially from the liver and lung of rats fed a liquid diet containing ethanol (35% of calories) or malto-dextrin control for 9-12 weeks. Hepatic and alveolar macrophages from control animals were found to exhibit distinct morphologic and functional properties. Thus, hepatic macrophages were highly vacuolated and appeared larger and more irregular in shape than alveolar macrophages. These cells also displayed greater phagocytic activity and random migration. In contrast, lung macrophages produced more superoxide anion and nitric oxide, and exhibited enhanced chemotactic activity toward the complement fragment C5a. Whereas administration of ethanol to rats for 9-12 weeks resulted in decreased chemotaxis and superoxide anion production by alveolar macrophages, cell adhesion molecule expression was reduced in hepatic macrophages. Nitric oxide production and inducible nitric oxide synthase protein expression were decreased in both macrophage populations. These effects were not observed after 3-6 weeks of ethanol administration to rats. Our results suggest that changes in macrophage functioning may play a role in decreased host defense following chronic ethanol exposure. | pubmed_42_3661 |
others_53_14436 | In this study the effect of humic acids and humic acids and garlic powder (Allium sativum L.) combination on performance parameters and carcass characteristic of broiler chickens were studied. A total of 120 Ross 308 broiler chickens were divided into 3 treatments (n=40). The control group of chickens was fed complete feed mixtures without any additives. Treatment T1 was fed complete feed mixtures containing 1% of humic acid. Treatment T2 was fed complete feed mixtures containing 1.8% of humic acid and 0.2% of garlic powder (Allium sativum L.). At the end of the experiment was average body weight (values in the order of the groups: 1796.4±188.1; 1999.1±355.8 and 1958.6±201.2 g±SD) significantly higher (P≤0.05) in both treatments groups compared to control group. In T1 was weight of gizzard (values in the order of the groups: 34.9±5.2; 43.1±9.4 and 38.9±7.0 g±SD) significantly higher (P≤0.05) compared to control group. Carcass weight, weight of heart weight of liver and carcass yield of treatments groups was higher, but differences in these indicators were not statistically significant (P≥0.05). The results of this experiment indicate that humic acids may by an alternative replacement of feed antibiotics. © 2016, University of Zagreb-Faculty of Agriculture. All rights reser | 10.5513/JCEA01/17.4.1826 |
pubmed_923_11315 | A 52-year-old woman developed persistent epiphora in her left eye after undergoing occlusion of the left puncta. Two attempts to reopen the puncta with a one-snip procedure and placement of punctal silicone plugs failed. The epiphora resolved and the puncta remained patent after the patient underwent a third one-snip procedure, supplemented with topical mitomycin during and after surgery. | pubmed_923_11315 |
pubmed_1041_22152 | PURPOSE
Detection rates of depression in obstetric care are generally low, and many women remain undiagnosed and do not receive adequate support. In many obstetric settings, screening tools for depression are not applied routinely and there is a great need to sensitize health care professionals for the patient at risk for enhanced levels of depression. The present study aimed at identifying commonly assessed patient characteristics that are associated with antenatal depression.
METHODS
One hundred and thirty seven women were screened using the Edinburgh Postnatal Depression Scale (EPDS) at the beginning of the second trimester at the outpatient department of a Tertiary University Hospital. Women were identified as at high risk for depression if scores were above a cut-off score of twelve. Obstetric history and outcome were extracted from patient files after delivery.
RESULTS
Twenty one percent of the sample screened as depression positive. Logistic regression with backwards elimination showed that the triad of nausea during pregnancy, reports of (premature) contractions and consumption of analgesics during pregnancy significantly predicted high depression scores with a positive predictive value of 84.3%. The relative risk for a depressed pregnant woman to regularly take analgesics during pregnancy was fourfold higher than for non-depressed women.
CONCLUSIONS
If depression screening is not part of routine prenatal care, systematic assessment of depression should be targeted for patients presenting with the markers identified in this study. | 10.1007/s00404-011-1872-3 |
pubmed_435_16731 | We present the case of a 69-year old man who was brought to the hospital after being found unconscious; last seen at baseline 9 hours prior. On admission he was found to be severely hypoglycemic and received prompt glucose administration, with no immediate neurological improvement. Stroke was suspected. A brain MRI revealed abnormal hyperintense signal involving the head and tail of the left hippocampus. After close neurological monitoring and supportive care in the ICU, his condition improved over time, leaving no residual focal deficits. This case highlights the presence of MRI changes in patients with severe hypoglycemia as it happens in hypoglycemic coma. | 10.11604/pamj.2019.32.131.17967 |
others_413_42619 | This study compares decision trees on two COVID-19 symptom datasets to assess their performance and feature importance in predicting and understanding infection patterns.
MethodsWe created decision trees on Israeli and Swedish COVID-19 infection datasets. Performance metrics were used to assess their predictive capabilities, and feature importance analysis identified significant variables in the decision-making process.
ResultsThe study observed different performance levels of decision trees on the COVID-19 datasets. The Swedish dataset achieved high accuracy and F1-score without hyperparameter tuning, while the Israeli dataset improved significantly with Extreme Gradient Boosting. Dataset characteristics impact the selection of an optimal decision tree algorithm. The key variable in both datasets was sore throat.
ConclusionThis study compares decision trees on COVID-19 infection datasets, emphasizing the importance of dataset characteristics in selecting an optimal algorithm. Identifying significant features enhances understanding of infection patterns, benefiting decision-making and prediction accuracy in infectious disease analysis | 10.1101/2023.06.02.23290867 |
pubmed_836_20613 | I examine spectral properties of a dissipative chaotic quantum map with the help of a recently discovered semiclassical trace formula. I show that in the presence of a small amount of dissipation the traces of any finite power of the propagator of the reduced density matrix, and traces of its classical counterpart, the Frobenius-Perron operator, are identical in the limit of variant Planck's over 2pi -->0. Numerically I find that even for finite variant Planck's over 2pi the agreement can be very good. This holds in particular if the classical phase space contains a strange attractor, as long as one stays clear of bifurcations. Traces of the quantum propagator for iterations of the map agree well with the corresponding traces of the Frobenius-Perron operator if the classical dynamics is dominated by a strong point attractor. (c) 1999 American Institute of Physics. | 10.1063/1.166447 |
pubmed_369_25170 | The M protein of POEMS syndrome is essentially λ light chain restricted. Several studies have demonstrated the restrict usage of immunoglobulin λ light chain variable region (IGLV) genes in patients with POEMS syndrome. However, these studies only included a limited number of cases, and it is not clear whether the clinical features are influenced by the IGLV gene in POEMS syndrome. Here we demonstrated that the clonal IGLV genes were strictly derived from IGLV 1-40 (11 patients, 36.7 %) and IGLV 1-44 (19, 63.3 %) gene in 30 patients with POEMS syndrome. We further evaluated the relationship between clinical features and IGLV genes. Our study showed that patients with IGLV 1-44 were older than those with IGLV 1-40, and patients with IGLV 1-40 had more severe neuropathy, hypertrichosis, and papilledema. It was suggested that the IGLV gene influenced clinical characteristics in POEMS syndrome. | 10.1007/s00277-012-1455-9 |
pubmed_16_24324 | INTRODUCTION
Recent studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Previous research using regional magnetic resonance spectroscopy methods to measure BMAT has reported inconsistent findings on the relationship between BMAT and dual-energy absorptiometry (DXA)-measured bone mineral density (BMD).
METHODS
In the present study, total body and pelvic BMAT were evaluated in 56 healthy women (age 18-88 yrs, mean +/- SD, 47.4 +/- 17.6 yrs; BMI, 24.3 +/- 4.2 kg/m(2)) with T1-weighted whole-body magnetic resonance imaging (MRI). BMD was measured using the whole-body DXA mode (GE Lunar DPX, software version 4.7).
RESULTS
A strong negative correlation was observed between pelvic BMAT and BMD (total-body BMD, R = -0.743, P < 0.001; pelvic BMD, R = -0.646, P < 0.001), and between total-body BMAT and BMD (total-body BMD, R = -0.443, P < 0.001; pelvic BMD, R = -0.308, P < 0.001). The inverse association between pelvic BMAT and BMD remained strong after adjusting for age, weight, total body fat, and menopausal status (partial correlation: total-body BMD, R = -0.553, P < 0.001; pelvic BMD, R = -0.513, P < 0.001). BMAT was also highly correlated with age (pelvic BMAT, R = 0.715, P < 0.001; total-body BMAT, R = 0.519, P < 0.001).
CONCLUSION
MRI-measured BMAT is thus strongly inversely correlated with DXA-measured BMD independent of other predictor variables. These observations, in the context of DXA technical concerns, support the growing evidence linking BMAT with low bone density. | 10.1007/s00198-006-0285-9 |
pubmed_1021_10125 | Tissue Blood Flow is measured by applying a combined procedure of two independent approaches based on heat clearance: the Pulse Decay Method and the Continuous Method. The Pulse Method allows absolute assessment of tissue BF with no need for calibration, and can be applied only if the tissue BF is steady during the period of measurement. On the other hand, the Continuous Method enables the observation of rapid changes in tissue BF, and can be applied under non steady-state conditions. Using the combined method, a continuous quantitative measurement of transient changes in tissue BF can be obtained. For this purpose, we have developed two experimental systems consisting of independent electronic units: a Pulse Unit and a Continuous Unit. A micro-computer with dedicated software controls the operation of the electronic units and calculates tissue BF on-line. In vitro measurements are performed and demonstrate the reliability of the methods. In vivo measurements in rat brain tissue are also performed and include physiological and pharmacological changes of local tissue BF. The results of the two heat clearance methods correlate well with tissue BF values measured by a third independent method, the Hydrogen Clearance Method. | 10.1115/1.2895424 |
others_115_8808 | The molecular mechanism underlying phototherapy and light treatment, which utilize various wavelength spectra of light, including near-infrared (NIR), to cure human and plant diseases, is obscure. Here we revealed that NIR light confers antiviral immunity by positively regulating PHYTOCHROME-INTERACTING FACTOR 4 (PIF4)-activated RNA interference (RNAi) in plants. PIF4, a central transcription factor involved in light signaling, accumulates to high levels under NIR light in plants. PIF4 directly induces the transcription of two essential components of RNAi, RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) and ARGONAUTE 1 (AGO1), which play important roles in resistance to both DNA and RNA viruses. Moreover, the pathogenic determinant βC1 protein, which is evolutionarily conserved and encoded by betasatellites, interacts with PIF4 and inhibits its positive regulation of RNAi by disrupting PIF4 dimerization. These findings shed light on the molecular mechanism of PIF4-mediated plant defense and provide a new perspective for the exploration of NIR antiviral treatment. © 2023 The Author(s) | 10.1016/j.xplc.2023.100644 |
pubmed_753_1139 | BACKGROUND
The relationship of Line-1 demethylation and the CD133 expression of cancer stem cells were discussed in hepatocellular carcinoma (HCC).
METHODS
In 95 HCC and matched nontumor tissues, we analyzed the methylation level of Line-1 by quantitative real-time methylation-specific polymerase chain reaction, and the expression of CD133 by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry.
RESULTS
Unmethylation of Line-1 increased from nontumor tissues (1.23 × 10(7) copies/μg DNA) toward HCC tissues (2.99 × 10(7) copies/μg DNA), but methylation of Line-1 kept 2 × 10(8) copies/μg DNA around in HCC and nontumor tissues. The methylation index (MI) of Line-1 decreased from 0.919 in nontumor samples to 0.755 in HCC. Results showed that cumulative survival was significantly shorter in HCC patients with MI < 0.76 than that in patients with MI ≥ 0.76. CD133 mRNA expression were higher in HCC tissues (mean -∆(Ct) = -5.751) than that in nontumor tissues (mean -∆(Ct) = -6.742). A total of 73 (76.8%) patients had demethylation of Line-1 (∆MI < 0), and 22 (23.2%) patients had hypermethylation of Line-1 (∆MI ≥ 0). HCC with demethylation of Line-1 had elevated CD133 expression in tumor rather than matched nontumor tissues (mean -∆(∆Ct) = 1.101), but HCC with hypermethylation of Line-1 was considered to be lower with CD133 expression in tumor (mean -∆(∆Ct) = -0.409).
CONCLUSIONS
Line-1 hypomethylation is the most common molecular abnormality during the carcinogenic process. Elevated expression of CD133 was associated with demethylation of Line-1 in HCC. | 10.1245/s10434-011-1599-1 |
pubmed_71_13520 | BACKGROUND AND OBJECTIVE
Nonmelanoma skin cancer (NMSC) is the most common human cancer. Because these tumors often affect the face, there is a strong need for both accurate removal of these neoplasms to prevent recurrence and maximal tissue preservation to prevent cosmetic or functional deformity. Polarization-enhanced reflectance and fluorescence imaging (PERFI) is a new bedside method that uses fluorescent chromophores to image NMSC. While the feasibility of the technique has been successfully demonstrated in ex vivo studies, this is the first pilot study to extend the use of PERFI to in vivo intraoperative imaging of NMSC.
MATERIALS AND METHODS
Subjects were recruited from a population of patients with biopsy-confirmed NMSC, scheduled for Mohs micrographic surgery. Eight cases were studied. Sterile methylene blue (MB) was diluted in anaesthetic solution and infused into the peritumoral space. Digital photographs of the lesion were taken and Mohs surgery was performed. Then, the surgical bed was re-imaged. Each excision was also imaged ex vivo and processed for routine histopathology. Optical images were processed and compared with histopathology.
RESULTS AND CONCLUSIONS
The injection of MB was well tolerated. We observed a transient blue staining of the treated area, which disappeared completely within 1 week in all of the patients. In all subjects, the contrast agent, MB, was preferentially retained in the tumor. The ex vivo images correlated well with histopathology. In vivo images qualitatively delineated the tumor margins. The results of our pilot trial indicate that PERFI may be useful for accurate and rapid delineation of NMSC during surgery. Lasers Surg. Med. 49:803-809, 2017. © 2017 Wiley Periodicals, Inc. | 10.1002/lsm.22686 |
others_15_7736 | In the UK, around 10-15% of the obstetric population have experienced prior caesarean delivery. This article provides a practical evidence-based approach to the antenatal and intrapartum management of such women. This review is primarily sourced from data presented in guidelines produced by UK (RCOG, NICE) and USA (ACOG, NIH) professional bodies. Antenatal counselling should incorporate an individualized assessment of the risks and benefits of ERCS (elective repeat caesarean section) and planned VBAC (vaginal birth after caesarean) modes of delivery. Planned VBAC is associated with slightly (0.25%) increased perinatal risk than planned ERCS, although absolute risks are low for both modes of delivery. This information, coupled with high rates of VBAC success (70%) and very low-risk of uterine scar rupture (0.5%), indicates planned VBAC is an appropriate option for the vast majority of multiparous women with previous caesarean delivery and is cost effective for the healthcare provider. Of significance, recent guidance from NICE (UK) adds a further dimension to decision making as it has stated that maternal request for caesarean section is permissible in certain circumstances. © 2012 Elsevier L | 10.1016/j.ogrm.2012.03.004 |
pubmed_72_25120 | Grandparents are increasingly becoming the primary carers of children orphaned by the HIV epidemic in South Africa. Traditional family roles are being reversed as aging family members take responsibility for the physical and psychosocial needs of children. This study uses qualitative research to explore the experiences of grandparents fostering children orphaned by AIDS in Richards Bay, KwaZulu-Natal Province, South Africa. The idea was born after a local HIV support organisation (Richards Bay Family Care) observed a trend within their organisation of grandparents increasingly becoming foster parents for orphans. An exploratory study was conducted in the organisation's three target areas (two rural villages and urban Richards Bay); the ultimate aim was to explore options for improving financial and emotional support for this group. The qualitative research methods included: four focus group discussions with foster-carers and community leaders (including two pocket-chart voting exercises); 12 in-depth interviews with grandparent foster-carers; and ten key-informant interviews, mostly with staff who provide support services. Data analysis was by thematic framework. The needs of the grandparent fostercarers varied: the rural participants were essentially concerned with meeting children's basic needs (housing, food and education), while those in urban areas more often felt pressure to provide emotional and psychological support for orphans. In both groups, women were at the forefront of foster care. Important problems identified by the grandparents were child discipline and a feeling of disharmony in the intergenerational relationship. Government foster care grants were identified as a regular source of income for especially the rural foster-carers. The findings may help programme managers better understand the differences in the needs of urban and rural foster parents. The experiences of grandparents as carers of orphans affected by HIV or AIDS are unique considering their age, frailty and poverty status. More research is needed on the role played by men in fostering children orphaned by AIDS. | 10.2989/AJAR.2009.8.2.6.858 |
pubmed_163_10521 | The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape. | 10.3389/fimmu.2021.744242 |
pubmed_1058_938 | The homeobox-containing gene EgHbx3 from Echinococcus granulosus is expressed in the stalk of protoscoleces. The expression of the homeobox-containing gene EgHbx3 from E. granulosus was studied in protoscoleces by in situ hybridisation techniques. A method for performing in situ hybridisations on whole mounted hydatic material is described. Our results show a clear positive signal at the protoscolex stalk, when using the antisense EgHbx3 probe. This signal is particularly strong in the proximal end of the stalk (with respect to the protoscolex). | 10.1016/s0020-7519(97)00082-9 |
pubmed_341_25708 | In this work, a versatile postmodification strategy based polydopamine (PDA) grafting is reported for improving CO2 separation performance of MOF membranes. Owning to the strong bioadhesion, PDA can be deposited on the UiO-66 membrane through a simple and mild process. Since PDA impregnation in invalid nanometer-sized pinholes and grain boundaries of the MOF membrane suppress nonselective gas transports, the modified PDA/UiO-66 membrane exhibits significantly enhanced CO2/N2 and CO2/CH4 selectivities of 51.6 and 28.9, respectively, which are 2-3 times higher than the reported MOF membranes with similar permeance. Meanwhile, because PDA modification do not change UiO-66 intrinsic pores and membrane thickness is submicrometer-sized, the CO2 permeance is 2-3 orders of magnitude larger than those membranes with similar selectivity, up to 3.7 × 10-7 mol m-2 s-1 Pa-1 (1115 GPU). Moreover, the PDA/UiO-66 membrane with good reproducibility has excellent long-term stability for CO2 capture under moist condition in 36 h measurement period. | 10.1021/acs.est.9b00408 |
pubmed_472_5326 | The lecture gives the state-of-the-art of the methodology of human pathology that is an area of the scientific and practice activity of specialists to produce and systematize objective knowledge of pathology and to use the knowledge in clinical medicine. It considers the objects and subjects of an investigation, materials and methods of a pathologist, and the results of his/her work. | 10.17116/patol201678550-55 |
pubmed_980_25285 | Guava (Psidium guajava) leaves are commonly used in the treatment of diseases. They are considered a waste product resulting from guava cultivation. The leaves are very rich in essential oils (EOs) and volatiles. This work represents the detailed comparative chemical profiles of EOs derived from the leaves of six guava varieties cultivated in Egypt, including Red Malaysian (RM), El-Qanater (EQ), White Indian (WI), Early (E), El-Sabahya El-Gedida (ESEG), and Red Indian (RI), cultivated on the same farm in Egypt. The EOs from the leaves of guava varieties were extracted by hydro-distillation and analyzed with GC-MS. The EOs were categorized in a holistic manner using chemometric tools. The hydro-distillation of the samples yielded 0.11-0.48% of the EO (v/w). The GC-MS analysis of the extracted EOs showed the presence of 38 identified compounds from the six varieties. The sesquiterpene compounds were recorded as main compounds of E, EQ, ESEG, RI, and WI varieties, while the RM variety attained the highest content of monoterpenes (56.87%). The sesquiterpenes, β-caryophyllene (11.21-43.20%), and globulol (76.17-26.42%) were detected as the major compounds of all studied guava varieties, while trans-nerolidol (0.53-10.14) was reported as a plentiful compound in all of the varieties except for the RM variety. A high concentration of D-limonene was detected in the EOs of the RM (33.96%), WI (27.04%), and ESEG (9.10%) varieties. These major compounds were consistent with those reported for other genotypes from different countries. Overall, the EOs' composition and the chemometric analysis revealed substantial variations among the studied varieties that might be ascribed to genetic variability, considering the stability of the cultivation and climate conditions. Therefore, this chemical polymorphism of the studied varieties supports that these varieties could be considered as genotypes of P. guajava. It is worth mentioning here that the EOs, derived from leaves considered to be agricultural waste, of the studied varieties showed that they are rich in biologically active compounds, particularly β-caryophyllene, trans-nerolidol, globulol, and D-limonene. These could be considered as added value for pharmacological and industrial applications. Further study is recommended to confirm the chemical variations of the studied varieties at a molecular level, as well as their possible medicinal and industrial uses. | 10.3390/molecules26010119 |
pubmed_319_6752 | Increased risk of anticancer chemotherapy in seriously obese patients is known. Obesity may be among factors that predict treatment-related toxicity during chemotherapy. We investigated whether functional changes in granulopoiesis may also contribute to increased myelotoxicity in addition to the known alterations of pharmacokinetic parameters in obesity. Hemopoiesis - as measured by cellularity, frequency of granulocyte-macrophage progenitors (CFU-GM) and total CFU-GM content of the femoral bone marrow - did not differ in obese, insulin resistant Zucker rats compared with Wistar rats. Nevertheless increased sensitivity of their CFU-GM progenitor cells to cytotoxic drugs was found by culturing them in vitro in the presence of carboplatin, doxorubicin and 5-fluorouracil. All drugs were more toxic on CFU-GM progenitor cells of insulin resistant Zucker rats than on CFU-GM cells of the control strain. This might be based on metabolic disorders, at least in part, because we could demonstrate a similar increase in toxicity of the studied anticancer drugs to the CFU-GM progenitors originated from the non-obese but insulin resistant Goto-Kakizaki rats in the same dose ranges. After in vivo administration of rosiglitazone, an insulin sensitizer, the anticancer drug sensitivity of CFU-GM progenitors of Goto-Kakizaki rats was decreased concurrently with improvement of insulin resistance. Although the increased treatment-related myelotoxicity and mortality are well-known among obese patients with malignant diseases, only the altered half lives, volumes of distribution and clearances of cytotoxic drugs are thought to be the underlying reasons. According to our knowledge the results presented here, are the first observations about an impaired granulopoiesis in obese animals. | pubmed_319_6752 |
pubmed_747_11400 | In uteri removed at hysterectomy the uterine arteries were injected with radioopaque media and the vascular configuration was correlated with reproductive histories. Patients whose uteri had two ascending uterine arteries on each side had significantly more abortions and smaller newborn infants than patients with a single ascending branch of the uterine artery. | 10.1111/j.1471-0528.1978.tb14950.x |
pubmed_427_3219 | A review of osteomyelitis in 54 patients treated at the Dr. Charles A. Janeway Child Health Centre over a 4-year period revealed equal frequencies of secondary and hematogenous osteomyelitis. Although the clinical picture in patients with hematogenous osteomyelitis was classic, patients with secondary osteomyelitis presented with an altered clinical response. Patients with secondary osteomyelitis have a history of an antecedent puncture wound or an inadequately treated contiguous focus of infection; antistaphylococcal antimicrobial therapy was ineffective for most because gram-negative bacilli were isolated in this group of patients. In contrast to patients with hematogenous osteomyelitis, who frequently respond to intensive antimicrobial therapy, those with secondary osteomyelitis will frequently require surgical intervention to eradicate the infection. | pubmed_427_3219 |
pubmed_828_1463 | OBJECTIVE
To evaluate the possibility of radial artery pressure and waveform as a convenient definition of pulsatile flow and the the effect of pulsatile perfusion during cardiopulmonary bypass (CPB) procedures.
METHODS
From March 2008 to December, Eighty patients underwent open heart surgery were randomly divided into a pulsatile group (P, n=45) and a nonpulsatile group (NP, n=35). Monitored by radial artery pressure and waveform, the pulsatile low was applied from the point of the aortic cross-clamp until its release in P group. A P group of patients whose radial artery pressure and waveform revealed "double peak" or "single peak" (>30 mm Hg, 1 mm Hg=0.133 kPa) were compared with NP group. Parameters examined were lactate, urine volume, high sensitivity C reactive protein, blood urea nitrogen, creatinine, blood uric acid, lactate dehydrogenase, glutamic oxalacetic transaminase, ratio of urine for occult blood test, prothrombin time and tracheal intubation time.
RESULTS
The waveform with "double peak" or "single peak" (>30 mm Hg) presented in 35 (77.78%) in P group. The urine volume during CPB was significantly higher in P group. The lactate (P<0.01) during CPB, high sensitivity C reactive protein (P<0.05), increasing extend of lactic acid dehydrogenase (P<0.05) and the prothrombin time (P<0.01) after CPB were significantly lower in P group. The blood uric acid after CPB was increased in P group and decreased in NP group.
CONCLUSIONS
Effective pulsatile flow can be generated by optimization of equipment and adjustment of pulsatile parameter. The radial artery pressure and waveform is a convenient definition of pulsatile flow. The pulsatile flow is predominant monitored by radial artery pressure and waveform. | pubmed_828_1463 |
others_125_10255 | Most human cells express two TNF and lymphotoxin (LT) membrane receptors (TNF-R), of 55 and 75 kDa. The regulatory effect of these two receptors on intercellular adhesion molecules (ICAM-1) expression was examined in various human cell lines in vitro, including human lymphokine-activated killer T cells (T-LAK) cells and HL-60 cells. Rabbit antihuman TNF-R antisera specific for each receptor were employed as probes to selectively stimulate 55- and 75-kDa TNF/LT membrane receptor production. These antisera compete with TNF/LT binding to each specific cell membrane receptor and have been found to bind to specific membrane receptors on various human cell lines in vitro. In the present study, we demonstrated biologic activity for anti-55-kDa TNF-R antiserum. For example, antibodies that bind to the 55-kDa TNF-R caused cytolysis of HeLa and ME-180 human cervical cancer cells and induced proliferation of MRC-5 human fibroblasts. In contrast, however, anti-75-kDa TNF-R antiserum demonstrated no bioactivity in these assays. In addition, no synergy or costimulation was observed when a combination of both anti-55- and anti-75-kDa TNF-R antisera were tested in these assay systems. Anti-55-kDa TNF-R antiserum up-regulated ICAM-1 expression on human HL-60, T-LAK, and THP-1 cells, whereas anti-75-kDa TNF-R antiserum had no effect. Unexpectedly, however, ICAM-1 expression was greatly enhanced by the addition of anti-75- kDa TNF-R to the anti-55-kDa TNF-R containing culture. This enhancing effect was also observed with human T-LAK cells and THP-1 monocytic leukemia cell, in | others_125_10255 |
pubmed_642_20898 | PURPOSE
Primary and secondary (P&S) syphilis in men who have sex with men (MSM) has been increasing; however, there is a lack of research on geographic factors associated with MSM P&S syphilis.
METHODS
We used multiple data sources to examine associations between social and environmental factors and MSM P&S syphilis rates at the state- and county-level in 2014 and 2015, separately. General linear models were used for state-level analyses, and hurdle models were used for county-level models. Bivariate analyses (P < .25) were used to select variables for adjusted models.
RESULTS
In 2014 and 2015 state models, a higher percentage of impoverished persons (2014 β = 1.24, 95% confidence interval, 0.28-2.20; 2015 β = 1.19; 95% confidence interval, 0.42-1.97) was significantly associated with higher MSM P&S syphilis rates. In the 2015 county model, policies related to sexual orientation (marriage, housing, hate crimes) were significant correlates of MSM P&S syphilis rates (P < .05).
CONCLUSIONS
Our state-level findings that poverty is associated with MSM P&S syphilis are consistent with research at the individual level across different subpopulations and various sexually transmitted diseases. Our findings also suggest that more research is needed to further evaluate potential associations between policies and sexually transmitted diseases. Geographic-level interventions to address these determinants may help curtail the rising syphilis rates and their sequelae in MSM. | 10.1016/j.annepidem.2019.01.013 |
pubmed_44_22157 | Transgenic animal models have provided a vital insight into the pathogenesis of cardiovascular disease, but functional cardiac assessment is often limited by high heart rates and small heart size. We hypothesized that in the presence of concentric left ventricular (LV) hypertrophy (LVH), load-sensitive measures of contractility may be misinterpreted as overestimating global cardiac function, because the normal function of excess sarcomeres may displace a greater volume of blood during contraction. Conductance catheter technology was used to evaluate pressure-volume (P-V) relationships as a load-insensitive method of assessing cardiac function in vivo in 18-wk-old heterozygous (mRen-2)27 transgenic rats (a model of LVH), compared with age-matched Sprague-Dawley (SD) controls. Anesthetized animals underwent echocardiography followed by P-V loop analysis. Blood pressure, body weight, and heart rate were higher in the Ren-2 rats (P < 0.05). Load-sensitive measures of systolic function, including fractional area change, fractional shortening, ejection fraction, and positive peak rate of LV pressure development, were greater in the Ren-2 than control animals (P < 0.05). Load-insensitive measures of systolic function, including the preload recruitable stroke work relationship and the end-systolic P-V relationship, were not different between Ren-2 and SD rats. Regional wall motion assessed by circumferential shortening velocity suggested enhanced circumferential fiber contractility in the Ren-2 rats (P = 0.02), but tissue Doppler imaging, used to assess longitudinal function, was not different between groups. Although conventional measures suggested enhanced systolic function in the Ren-2 rat, load-insensitive measures of contractility were not different between Ren-2 and SD animals. These findings suggest that the normal range of values for load-sensitive indexes of contractility needs to be altered according to the degree of LVH. To accurately identify changes in systolic function, we suggest that a combination of echocardiography with assessment of load-insensitive measures be used routinely. | 10.1152/ajpheart.00577.2005 |
pubmed_154_10161 | BACKGROUND
Recent studies have shown an association between an extended tau haplotype (H1) that covers the entire human tau gene and progressive supranuclear palsy or, more inconsistently, other neurodegenerative disorders, such as corticobasal degeneration, Parkinson disease, Alzheimer disease, and frontotemporal dementia (FTD). In addition, disease-causing mutations in the tau gene on chromosome 17 have been detected in some families with autosomal dominant FTD and parkinsonism. In FTD, the pathological accumulation of the microtubule-associated protein tau suggests that the tau gene may be a genetic risk factor for this disorder.
OBJECTIVE
To confirm or refute the association between the H1 haplotype or the H1H1 genotype of the tau gene and FTD.
DESIGN
Case-control study.
SETTING
Neurology departments of 12 French university hospitals.
PARTICIPANTS
One hundred unrelated patients with FTD and 79 controls.
METHODS
Tau genotype (contiguous polymorphisms in exons 1, 7, and 13 and in intron 9 used to reconstruct the extended haplotypes H1 and H2). Clinical examination, psychometric testing, laboratory tests, computed tomography and magnetic resonance imaging, single-photon emission computed tomography, and electroencephalography for patients with FTD.
RESULTS
The H1H1 genotype was significantly overrepresented in patients with FTD compared with controls (62% vs 46%; P=.01, 1-sided; odds ratio adjusted for age and sex, 1.95). After stratification according to apolipoprotein E (APOE) genotype, we found a significant interaction between APOE and tau genotypes (P=.03).
CONCLUSIONS
This study of the largest series of patients with FTD confirms the primary role of tau in FTD and establishes that the H1 haplotype of the tau gene and the E2 allele of APOE interact by an unknown mechanism that increases the risk of FTD. | 10.1001/archneur.59.6.935 |
pubmed_1021_9099 | We examined how lowpass filtering has an influence on nystagmus parameters: durations, amplitudes, and mean velocities of its slow and fast phases. We experimented with two types of common linear digital filters by using both nonrecursive and recursive filters, and with two types of nonlinear digital filters by using so-called standard median and hybrid median filters. We concluded that 70 Hz as strict cutoff frequency is high enough not to cause errors in the nystagmus parameters when information content in nystagmus signals is filtered above that cutoff frequency with linear filters. Using nonlinear filters good window lengths of filtering are equal to or less than about nine samples for a sampling frequency of 400 Hz which we applied. | pubmed_1021_9099 |
pubmed_632_23919 | Ethyl acetate extracts of seaweeds were chromatographically fractionated to yield 14-methyl pentyl tetrahydro-8-hydroxy-10-methylnaphthalene-8-carboxylate (1) and tetrahydro-4-isopropyl-9-(9, 14-dimethyldec-9-enyl)-pyran-1-one (2) from Sargassum ilicifolium, whereas Padina gymnospora afforded dihydro-2-(10-(hydroxymethyl)-7,15-dimethyl-9-oxoundec-11-enyl)-2-methyl-2H-pyran-1(4H)-one (3) and 1-(decahydro-1-hydroxy-7-methyl-8-vinylnaphthalen-2-yl)ethanone (4) as major constituents. Compound 1 displayed significantly higher antioxidant activity (IC50 < 1 mg/mL, p < 0.05) comparable to other analogues (IC50 > 1 mg/mL). The C20-22 polyunsaturated fatty acid (C20-22 PUFA) concentrate (CFA) prepared from the deep-sea dogfish liver oil was added with the studied compounds and physiochemical properties and fatty acid composition during an accelerated storage were evaluated. No significant reduction in C20-22 PUFAs (∼6%) in the CFA treated with 1 as compared to that with the control (∼35%) was recorded. A greater induction time was observed for the CFA supplemented with 1 (6.8 h) than other compounds (≤6 h) and control (∼1.6 h), maintaining the oxidation indices of the CFA within desirable limits. | 10.1016/j.foodchem.2018.03.144 |
pubmed_890_13187 | We report on the first calculation of magnetic catalysis at zero temperature in a fully nonperturbative simulation of the graphene effective field theory. Using lattice gauge theory, a nonperturbative analysis of the theory of strongly interacting, massless, (2+1)-dimensional Dirac fermions in the presence of an external magnetic field is performed. We show that in the zero-temperature limit, a nonzero value for the chiral condensate is obtained which signals the spontaneous breaking of chiral symmetry. This result implies a nonzero value for the dynamical mass of the Dirac quasiparticle. | 10.1103/PhysRevLett.117.266802 |
pubmed_727_3513 | 1 The psychotropic effects of a single oral dose of (--)-tryptophan (5 g) in human volunteers were investigated using a series of physiological and psychological tests. 2 Self-ratings of mood showed increase in drowsiness but no euphoria was detected. 3 Severe initial nausea occurred and headache increased; other bodily symptoms were unaffected. 4 Trptophan caused increased activity in the slow wavebands of the EEG but did not alter the other physiological measures. 5 The levels of total and free tryptophan in the plasma increased 8 and 20 fold respectively to peak levels 2 h after ingestion. | 10.1111/j.1365-2125.1975.tb01572.x |
pubmed_628_3978 | Complex equilibria in methanol/chloroform/dichloromethane solutions containing Zeise's anion, [PtCl(3)(C(2)H(4))](-) (1), the solvento species, trans-[PtCl(2)(C(2)H(4))(MeOH)] (2), and the dinuclear complex, trans-[PtCl(2)(C(2)H(4))](2) (3), have been studied by UV-vis, (1)H, and (195)Pt NMR spectroscopy, giving average values of K(Cl) = (1.6 +/- 0.2)10(3) M(-)(1) and K(S) = (0.16 +/- 0.02) M(-)(1) for the equilibrium constants between 2 and 1 and 3 and 2, respectively. The bridged complex 3 is completely split into monomeric solvento complexes 2 in methanol and in chloroform or dichloromethane solutions with [MeOH] > 0.5 M. Ethene exchange at the mononuclear complexes 1 and 2 was studied by (1)H NMR line-broadening experiments in methanol-d(4). Observed overall exchange rate constants decrease with an increase in free chloride concentration due to the displacement of the rapid equilibrium between 1 and 2 toward the more slowly exchanging parent chloro complex 1. Ethene exchange rate constants at 298 K for complexes 1 and 2 are k(ex1) = (2.1 +/- 0.1)10(3) M(-)(1) s(-)(1)and k(ex2) = (5.0 +/- 0.2)10(5) M(-)(1) s(-)(1), respectively, with corresponding activation parameters DeltaH(1)() = 19.1 +/- 0.3 kJ mol(-)(1), DeltaS(1)() = -117 +/- 1 J K(-)(1) mol(-)(1), DeltaH(2)() = 10.2 +/- 0.4 kJ mol(-)(1), and DeltaS(2)() = -102 +/- 2 J K(-)(1) mol(-)(1). The activation process is largely entropy controlled; the enthalpy contributions only amounting to approximately 30% of the free energy of activation. Ethene exchange takes place via associative attack by the entering olefin at the labile site trans to the coordinated ethene, which is either occupied by a chloride or a methanol molecule in the ground state. The intimate mechanism might involve a two-step process via trans-[PtCl(2)(C(2)H(4))(2)] in steady state or a concerted process via a pentacoordinated transition state with two ethene molecules bound to the platinum(II). | 10.1021/ic981020t |
pubmed_579_2497 | Information on virulence evolution is critical for understanding disease dynamics. Theory predicts that under certain evolutionary conditions virulence should increase; for example, during host-parasite coevolution. Although these theoretical predictions are supported by natural observations, tests of these hypotheses using experimental evolution have yielded confounding and contradictory results, with discrepancies often being seen among experiments. Here we provide a critical overview of experimental tests of hypotheses regarding virulence evolution and provide potential explanations for the contradictory results. We emphasise the key role of parasite transmission mechanisms that can explain many of the observed discrepancies among evolution experiments. Finally, we make suggestions for how evolution experiments could be conducted in the future to avoid potentially confounding factors. | pubmed_579_2497 |
pubmed_176_20863 | Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment. | 10.1038/ejhg.2011.11 |
pubmed_300_131 | Thoracoscopy has been used worldwide for many years by thoracic surgeons. Despite a long learning curve and technical demands of the procedure, thoracoscopy has several advantages, including better cosmesis, adequate exposure to all levels of the thoracic spine from T2 to L 1, better illumination and magnification at the site of surgery, less damage to the tissue adjacent to the surgical field, less morbidity when compared with standard thoracotomy in terms of respiratory problems, pain, blood loss, muscle and chest wall damages, consequent shorter recovery time, less postoperative pulmonary function impairment, and shorter hospitalization. Good results at short- and medium-term follow-up need to be confirmed at long-term follow-up. | 10.1016/j.ocl.2009.05.005 |
pubmed_1031_678 | The purpose of this study was to measure the effects of social and economic variables, disease-related variables, and child gender on the decisions of parents in Kerala, India, to seek care for their children and on their choice of providers in the allopathic vs. the alternative system. A case-control analysis was done using data from the Kerala section of the 1996 Indian National Family Health Survey, a cross-sectional survey of a probability sample of households conducted by trained interviewers with a close-ended questionnaire. Of the 469 children who were eligible for this study because they had at least one common symptom suggestive of acute respiratory illness or diarrhea during the 2 weeks before the interview, 78 (17%) did not receive medical care, while the remaining 391 (83%) received medical care. Of the 391 children who received medical care, 342 (88%) received allopathic medical care, and 48 (12%) received alternative medical care. In multivariable analyses, parents chose not to seek medical care for their children significantly more often when the illness was mild, the child had a specific diagnosis, the mother had previously made fewer antenatal visits, and the family had a higher economic status. When parents sought medical care for their children, care was sought significantly more often in the alternative provider system when the child was a boy, the family lived in a rural area, and the family had a lower social class. We conclude that, in Kerala, disease severity and economic status predict whether children with acute respiratory infection or diarrhea are taken to medical providers. In contrast, most studies of this issue carried out in other populations have identified economic status as the primary predictor of medical system utilization. Also in Kerala, the gender of the child did not influence whether or not the child was taken for treatment but did influence whether care was sought in the alternative or the allopathic system. | 10.1016/s0277-9536(02)00448-3 |
pubmed_996_19470 | Fluoxetine hydrochloride (Lovan, Eli Lilly and Company, Indianapolis, Indiana, USA), a specific serotonin uptake inhibitor, was compared with placebo in 458 obese outpatients in a 52-week double-blind randomized ten-site trial to study its effect on weight reduction. Patients in the fluoxetine and placebo groups were predominantly Caucasian (81% and 85%, respectively) and female (81% and 79%, respectively), with a mean body mass index (BMI) of 36.2 and 35.8 kg/m2, respectively, and a mean age of 43 years (both groups). Fluoxetine therapy (60 mg/day) resulted in statistically significantly (P < or = 0.05) greater mean weight loss than placebo to week 28. Although some patients continued to lose weight throughout the 52-week therapy period, maximum mean weight loss occurred at week 20. There was no treatment difference at 52 weeks. The change in visit frequency (biweekly to week 8, monthly to week 20, then bimonthly to week 52) may have affected results. Patients with higher baseline BMIs (> 40 kg/m2) attained and maintained a greater weight loss than patients with lower baseline BMIs (< 40 kg/m2). Two sites demonstrated greater efficacy than the study as a whole. The use of nutrition counselling at one site and behaviour modification at the other, or other site-to-site differences, may account for the improved efficacy. Fluoxetine was well tolerated and appeared to be safe therapy for the treatment of obesity with efficacy demonstrated for 28 weeks. | pubmed_996_19470 |
pubmed_160_2160 | Identification of the pathogenic cytokines that underlie the IL-23-dependent disease progression of experimental autoimmune encephalomyelitis has proven elusive. Evidence now points to GM-CSF. | 10.1038/ni.2044 |
pubmed_81_8983 | BACKGROUND
since 1999 data from pulmonary hypertension (PH) patients from all PH centres in Switzerland were prospectively collected. We analyse the epidemiological aspects of these data.
METHODS
PH was defined as a mean pulmonary artery pressure of >25 mm Hg at rest or >30 mm Hg during exercise. Patients with pulmonary arterial hypertension (PAH), PH associated with lung diseases, PH due to chronic thrombotic and/or embolic disease (CTEPH), or PH due to miscellaneous disorders were registered. Data from adult patients included between January 1999 and December 2004 were analysed.
RESULTS
250 patients were registered (age 58 +/- 16 years, 104 (41%) males). 152 patients (61%) had PAH, 73 (29%) had CTEPH and 18 (7%) had PH associated with lung disease. Patients <50 years (32%) were more likely to have PAH than patients >50 years (76% vs. 53%, p <0.005). Twenty-four patients (10%) were lost to followup, 58 patients (26%) died and 150 (66%) survived without transplantation or thrombendarterectomy. Survivors differed from patients who died in the baseline six-minute walking distance (400 m [300-459] vs. 273 m [174-415]), the functional impairment (NYHA class III/IV 86% vs. 98%), mixed venous saturation (63% [57-68] vs. 56% [50-61]) and right atrial pressure (7 mm Hg [4-11] vs. 11 mm Hg [4-18]).
DISCUSSION
PH is a disease affecting adults of all ages. The management of these patients in specialised centres guarantees a high quality of care. Analysis of the registry data could be an instrument for quality control and might help identify weak points in assessment and treatment of these patients. | 2008/25/smw-11915 |
pubmed_947_24713 | Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that acts as a regulator of oxygen (O2) homeostasis in metazoan species by binding to hypoxia response elements (HREs) and activating the transcription of hundreds of genes in response to reduced O2 availability. RNA polymerase II (Pol II) initiates transcription of many HIF target genes under non-hypoxic conditions but pauses after approximately 30-60 nucleotides and requires HIF-1 binding for release. Here we report that in hypoxic breast cancer cells, HIF-1 recruits TRIM28 and DNA-dependent protein kinase (DNA-PK) to HREs to release paused Pol II. We show that HIF-1α and TRIM28 assemble the catalytically-active DNA-PK heterotrimer, which phosphorylates TRIM28 at serine-824, enabling recruitment of CDK9, which phosphorylates serine-2 of the Pol II large subunit C-terminal domain as well as the negative elongation factor to release paused Pol II, thereby stimulating productive transcriptional elongation. Our studies reveal a molecular mechanism by which HIF-1 stimulates gene transcription and reveal that the anticancer effects of drugs targeting DNA-PK in breast cancer may be due in part to their inhibition of HIF-dependent transcription. | 10.1038/s41467-021-27944-8 |
pubmed_495_3371 | We report a retrospective study of 12 caucasian men infected with HIV who had developed Mycobacterium kansasii infection (Mk). All patients had a low blood lymphocyte CD4 count (1-130, mean 15/mm3) and ten met the diagnostic criteria for AIDS. The 12 patients had pulmonary symptoms (dyspnea, cough) and fever. On chest X-ray, nodular, interstitial or diffuse parenchymal infiltrates, mediastinal and hilar adenopathies were observed. Two patients had pleural effusion, but none had cavitary lung disease. Mk was isolated by culture of sputum (n = 7), blood (n = 3), bronchial biopsy (n = 2) or bone marrow (n = 1). No patient had clinical extra-pulmonary disease. Survival after diagnosis was in average 7 months. Potential for therapeutic response is reviewed and documented. | 10.1016/0248-8663(96)80783-1 |
pubmed_812_19181 | The prevalence of methylation of the p16, DAPK and RASSF1A genes was investigated in lung adenocarcinoma from smokers, former uranium miners and never smokers. The association between a common genetic alteration in adenocarcinoma, mutation of the K-ras gene and methylation of these genes, as well as survival was examined. Adenocarcinomas from 157 smokers, 46 never smokers and 34 former uranium miners were evaluated for methylation of the p16, DAPK and RASSF1A genes using the methylation-specific PCR assay. Comparisons were also made to prevalences of methylation of the MGMT gene and mutation of the K-ras gene previously examined in these tumors. The prevalence of methylation for all genes was similar between adenocarcinomas from smokers and never smokers, although the prevalence for methylation of the p16 gene tended to be higher in smokers compared to never smokers. A significantly higher prevalence for p16 methylation was seen in central vs. peripheral lung tumors. At least 1 gene was methylated in 35% of stage I tumors, whereas 2 and >/=3 genes were methylated in 40% and 16% of tumors, respectively. Methylation of all genes was independent of K-ras mutation, whereas methylation of the DAPK and RASSF1A genes was positively associated. Environmental tobacco smoke, the strongest lung cancer risk factor among never smokers, induces adenocarcinoma in part through inactivation of the p16, DAPK and RASSF1A genes. Adenocarcinomas may develop through 2 distinct processes: multiple gene inactivations through promoter hypermethylation and activation of the K-ras gene. | 10.1002/ijc.20761 |
pubmed_319_6159 | BACKGROUND
The aim of this study was to assess the nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) and the predictive role of colonization pressure (CP) in a low-prevalence healthcare setting.
METHODS
A retrospective analysis of MRSA infection rates from 2004 to 2009 at the Saudi Aramco Dhahran Health Center, Saudi Arabia, was performed. MRSA patient-days, susceptible patient-days, nosocomial incidence and CP were calculated for each month from January 2008 to December 2009.
RESULTS
During the study period, 878 cases of MRSA colonization/infection were identified. Of these cases, 777 (88.4%) and 101 (11.5%) were community-acquired MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) cases, respectively. A decrease in the number of HA-MRSA cases and an increase in the number of CA-MRSA cases were observed during the study period. The incidence of nosocomial infection per 1000 susceptible patient-days was 1.17 in 2008 and 0.7 in 2009. The monthly colonization pressure ranged from 0.1 to 1.62 throughout the 2-year period. Nosocomial transmission was observed in 13 months of the 24-month study period. No association between the CP of the preceding month and the incidence of nosocomial transmission in the subsequent month was observed.
CONCLUSION
In a setting of low MRSA prevalence, CP does not appear to be a useful predictor of nosocomial transmission or incidence. | pubmed_319_6159 |
pubmed_163_12888 | OBJECTIVE
To provide new insight into the training needs and resources required by hospital pharmacy resident tutors in Spain, as well as into their level of motivation and satisfaction with their teaching. Method: Google Forms® was used to design a survey addressed to hospital pharmacy resident tutors between January and March 2019. They survey consisted of generic (tutor, hospital, service) and specific questions (available resources, teaching activities, teaching satisfaction, training needs). A univariate exploratory analysis was conducted to study possible factors related to teaching satisfaction and motivation. Results: Replies were received from 83 tutors (rate of response: 52.8%), from 15/17 Spanish regions. The annual resident/tutor ratio was 4 (IQR = 2- 4). A total of 96.4% of tutors conducted interviews, of whom 65.1% did so quarterly. Other activities included the management of external training rotations (97.6%), planning of rotations (97.6%) and annual appraisals (96.4%). Only 17.1% of respondents were given time off their regular duties for their tutorship work, with 71.4% stating that the time they were allowed was insufficient. A total of 70.7% of tutors from eight Spanish regions where the granting of protected time was regulated said were not given any time off for their teaching endeavors. Most tutors declared to be satisfied (66.7%) and motivated (63%) with their teaching work. Motivation appeared to fall with age, and both motivation and satisfaction decreased as a function of the tutors' years of professional experience and when they were given no time off for their tutorship work or when the remuneration was low, without any relationship being identified between these factors. Tutors pointed out that work should be done to increase the number of hours assigned to tutorships (78%), preparing SEFH-validated training plans (76.8%), improving teaching techniques (65.9%), and decreasing the clinical workload (62.2%). Over the past 3 years, 69.1% of tutors had received training. This training was arranged by educational committees (63.3%), the Spanish regional authorities (42.4%) and SEFH (13.6%). All the training in clinical, teaching, and communicative competencies enjoyed wide acceptance (> 90%). The preferred delivery method was hybrid (partly on-line and partly onsite) (64.6%).
CONCLUSIONS
SEFH's tutors' group conducted its first national survey addressed to hospital pharmacy resident tutors. The survey showed that, although tutors are highly satisfied with their teaching activities, they ould like more training and to be able to devote more time to their tutorship work. It was also shown that a regulatory framework needs to be implemented in various Spanish regions and that compliance with existing regional regulations must be improved. | pubmed_163_12888 |
pubmed_934_14113 | BACKGROUND
This study examines differences in behavioral characteristics among individuals who are not depressed and individuals with subthreshold depression, and depression.
METHODS
We conducted structured interviews with 111 undergraduate students, who also completed self-report scales. The participants were divided into a non-depression group, a subthreshold depression group, and a depression group based on results of the structured interview and the BDI-II.
RESULTS
There were significant differences in avoidance between depression group and other two groups. Also, for the environmental rewards, there were significant difference between the non-depressed group and the other two groups.
LIMITATIONS
The sample of depressed participants was small. The overall sample consisted only undergraduate students.
CONCLUSIONS
This study reported that there are different behavioral characteristics among non-depression, subthreshold depression, and depression groups. Whereas depression group is characterized by high frequency of avoidance and low environmental rewards, subthreshold depression group is characterized by only low environmental rewards. | pubmed_934_14113 |
pubmed_259_22768 | Transcriptional expression of a gene or genes is absolutely required for induction of glucocorticoid-induced thymocyte apoptosis. We have previously shown that expression of T cell death-associated gene 8 (TDAG8) is quickly induced exclusively in the thymus after dexamethasone (DEX) treatment. Here, we present data that TDAG8 expression is induced prior to induction of DEX-mediated apoptosis. In contrast, TDAG8 expression in thymocytes was not induced in the process of gamma-irradiation-mediated apoptosis. TDAG8 expression accelerated only DEX-induced, but not TCR-mediated or gamma-irradiation-induced, thymocyte apoptosis in transgenic mice overexpressing TDAG8. Interestingly, these effects were specifically detected in CD4(+)CD8(+) double-positive thymocytes. Moreover, activation of caspase-3, -8 and -9 was enhanced in thymocytes of TDAG8 transgenic mice after DEX stimulation. In conclusion, TDAG8 expression is involved in glucocorticoid-induced signals to activate caspase-9, -8 and -3 for subsequent apoptosis induction in CD4(+)CD8(+) double-positive thymocytes. | 10.1093/intimm/dxg070 |
pubmed_486_21034 | BACKGROUND
Societal costs of low back pain (LBP) are high, yet few studies have been performed to identify the predictive factors of high societal costs among chronic LBP patients. This study aimed to determine which factors predict high societal costs in patients with chronic LBP.
METHODS
Data of 6,316 chronic LBP patients were used. In the main analysis, high societal costs were defined as patients in the top 10% of cost outcomes. Sensitivity analyses were conducted using patients in the top 5% and top 20% of societal costs. Potential predictive factors included patient expectations, demographic factors (e.g. age, gender, nationality), socio-economic factors (e.g. employment, education level) and health-related factors (e.g. body mass index [BMI], general health, mental health). The final prediction models were obtained using backward selection. The model's prognostic accuracy (Hosmer-Lemeshow X2 , Nagelkerke's R2 ) and discriminative ability (area under the receiver operating curve [AUC]) were assessed, and the models were internally validated using bootstrapping.
RESULTS
Poor physical health, high functional disability, low health-related quality of life, high impact of pain experience, non-Dutch nationality and decreasing pain were found to be predictive of high societal costs in all models, and were therefore considered robust. After internal validation, the models' fit was good, their explained variance was relatively low (≤14.1%) and their AUCs could be interpreted as moderate (≥0.71).
CONCLUSION
Future studies should focus on understanding the mechanisms associated with the identified predictors for high societal costs in order to design effective cost reduction initiatives.
SIGNIFICANCE
Identifying low back pain patients who are at risk (risk stratification) of becoming high-cost users and making appropriate initiatives could help in reducing high costs. | 10.1002/ejp.1488 |
pubmed_1081_21524 | Traumatic Brain Injury (TBI) is one of the most common causes of neurological damage in young populations. It has been previously suggested that one of the mechanisms that underlie brain injury is Axonal Outgrowth Inhibition (AOI) that is caused by altered composition of the gangliosides on the axon surface. In the present study, we have found a significant reduction of GM1 ganglioside levels in the cortex in a closed head traumatic brain injury model of a mouse, induced by a weight drop device. In addition, axonal regeneration in the brains of the injured mice was affected as seen by the expression of the axonal marker pNF-H and the growth cones (visualized by F-actin and β-III-tubulin). NeuN immunostaining revealed mTBI-induced damage to neuronal survival. Finally, as expected, spatial and visual memories (measured by the Y-maze and the Novel Object Recognition tests, respectively) were also damaged 7 and 30 days post injury. A single low dose of GM1 shortly after the injury (2 mg/kg; IP) prevented all of the deficits mentioned above. These results reveal additional insights into the neuroprotective characteristics of GM1 in prevention of biochemical, cellular and cognitive changes caused by trauma, and may suggest a potential intervention for mTBI. | 10.1038/s41598-018-31623-y |
pubmed_486_25770 | The National Institutes of Health's Clinical and Translational Science Awards (CTSA) institutes have been created, in part, to have a positive impact on collaboration and team science. This study is the first to examine the associations between a CTSA hub, the Michigan Institute for Clinical and Health Research (MICHR), and investigators' ego networks. We ran cross-sectional and panel models of the associations between consulting with MICHR and the ego network measure of two-step reach (TSR) - that is, colleagues of colleagues reachable in two steps - from a network of 2161 investigators who had co-submitted a grant proposal to an external sponsor in 2006. Our analyses covered the period 2004-2012, although some model specifications covered the shorter time period 2006-2010. Consulting with MICHR had positive associations with the size of and changes in an investigator's TSR across and over time, even controlling for research productivity and organizational affiliation. For example, over the period 2006-2010 an investigator who consulted with MICHR reached 44 more individuals than a non-consulting investigator. This study expands our understanding of the indirect impacts that clinical and translational science institutes have on investigators' scientific networks. This network-based approach might be useful in quantifying the impact of team science initiatives at the university level. | 10.1017/cts.2019.2 |
pubmed_616_5563 | MiR-216b is implicated in the development of multiple types of cancers, however, a role for miR-216b in colorectal cancer (CRC) remains elusive. The present study aimed to investigate the function and underlying mechanism of miR-216b in human CRC. In this study, we found miR-216b in CRC tissues and cell lines was markedly decreased compared with corresponding adjacent normal tissues (ANTs) and colonic mucosal epithelial cell line (FHC), and was obviously associated with the TNM stage, lymph node metastases, differentiation and poor overall survival (OS) (P<0.05). Furthermore, we demonstrated that miR-216b inhibited cell proliferation, migration, invasion and angiogenesis by targeting HMGB1 which was highly expressed in CRC. Additionally, we proved that miR-216b promoted the development and progression of CRC, at least partially through HMGB1-mediated JAK2/STAT3 pathway. Lastly, we showed that plasma miR-216b expression was reduced in CRC when compared to healthy controls and might be a potential diagnostic biomarker for CRC. The findings indicated that miR-216b might function as a suppressor in CRC and could serve as a promising diagnostic and prognostic biomarker for CRC. | pubmed_616_5563 |
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