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1.
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Background

Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies.

Methods

SIH was diagnosed with the following criteria: (i) evidence of CSF leakage by cranial magnetic resonance imaging (MRI) findings of intracranial hypotension and/or low CSF opening pressure; (ii) no recent history of dural puncture. We quantified CSF proteins by ELISA or Western blotting.

Results

Comparing with non-SIH patients, SIH patients showed significant increase of brain-derived CSF glycoproteins such as lipocalin-type prostaglandin D synthase (L-PGDS), soluble protein fragments generated from amyloid precursor protein (sAPP) and “brain-type” transferrin (Tf). Serum-derived proteins such as albumin, immunoglobulin G, and serum Tf were also increased. A combination of L-PGDS and brain-type Tf differentiated SIH from non-SIH with sensitivity 94.7% and specificity 72.6%.

Conclusion

L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH.

General significance

L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF.  相似文献   

3.
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Background

Besides its influence on survival, growth, proliferation, invasion and metastasis, cancer cell metabolism also greatly influences the cellular responses to molecular-targeted therapies.

Scope of the review

To review the recent advances in elucidating the metabolic effects of BRAF and MEK inhibitors (clinical inhibitors of the MAPK/ERK pathway) in melanoma and discuss the underlying mechanisms involved in the way metabolism can influence melanoma cell death and resistance to BRAF and MEK inhibitors. We also underlined the therapeutic perspectives in terms of innovative drug combinations.

Major conclusion

BRAF and MEK inhibitors inhibit aerobic glycolysis and induce high levels of metabolic stress leading to effective cell death by apoptosis in BRAF-mutated cancer cells. An increase in mitochondrial metabolism is required to survive to MAPK/ERK pathway inhibitors and the sub-population of cells that survives to these inhibitors are characterized by mitochondrial OXPHOS phenotype. Consequently, mitochondrial inhibition could be combined with oncogenic “drivers” inhibitors of the MAPK/ERK pathway for improving the efficacy of molecular-targeted therapy.

General significance

Metabolism is a key component of the melanoma response to BRAF and/or MEK inhibitors. Mitochondrial targeting may offer novel therapeutic approaches to overwhelm the mitochondrial addiction that limits the efficacy of BRAF and/or MEK inhibitors. These therapeutic approaches might be quickly applicable to the clinical situation.  相似文献   

5.

Background

Metalloproteins myeloperoxidase (MPO), ceruloplasmin (CP) and lactoferrin (LF) play an important role in regulation of inflammation and oxidative stress in vertebrates. It was previously shown that these proteins may work synergetically as antimicrobial and anti-inflammatory agents by forming complexes, such as MPO-CP and LF-CP. However, interaction of metalloprotein molecules with each other has never been characterized at a single-molecule level.

Methods

In this study, the pairwise interactions of MPO, CP and LF molecules were investigated at a single-molecule level using high-resolution atomic force microscopy (AFM). Highly oriented pyrolytic graphite surface (HOPG) modified with oligoglycine-hydrocarbon graphite modifier (GM) was used as a substrate for protein deposition.

Results

The procedure for reliable AFM investigation of metalloproteins and their complexes has been developed. Using this procedure, we have visualized, for the first time, single MPO, CP and LF molecules, characterized the morphology of MPO-CP and LF-CP complexes and confirmed the absence of direct contacts between MPO and LF molecules. Moreover, we have revealed the novel chainlike shape of MPO-CP conjugates.

Conclusions

GM-HOPG was shown to be a convenient substrate for AFM investigation of metalloproteins and their complexes. Direct AFM visualization of MPO-CP and LF-CP complexes, on the one hand, complements previous data obtained from the “bulk techniques” and, on the other hand, provides new insight into the ultrastructure of MPO-CP complexes.

General significance

The obtained results contribute to the better understanding of regulation of inflammation and oxidation stress mediated by collaborative action of the metalloproteins such as MPO, CP and LF.  相似文献   

6.

Background

A new patient monitoring technology called Visual Patient, which transforms numerical and waveform data into a virtual model (an avatar) of the monitored patient, has been shown to improve the perception of vital signs compared to conventional patient monitoring. In order to gain a deeper understanding of the opinions of potential future users regarding the new technology, we have analyzed the answers of two large groups of anesthetists using two different study methods.

Methods

First, we carried out a qualitative analysis guided by the “consolidated criteria for reporting qualitative research” checklist. For this analysis, we interviewed 128 anesthesiologists, asking: “Where do you see advantages in Visual Patient monitoring?” and afterward identified major and minor themes in their answers. In a second study, an online survey with 38 anesthesiologists at two different institutions, we added a quantitative part in which anesthesiologists rated statements based on the themes identified in the prior analysis on an ordinal rating scale.

Results

We identified four high-level themes: “quick situation recognition,” “intuitiveness,” “unique design characteristics,” and “potential future uses,” and eight subthemes.The quantitative questions raised for each major theme were: 1. “The Visual Patient technology enabled me to get a quick overview of the situation.” (63% of the participants agreed or very much agreed to this statement). 2. “I found the Visual Patient technology to be intuitive and easy to learn.” (82% agreed or very much agreed to this statement). 3. “The visual design features of the Visual Patient technology (e.g., the avatar representation) are not helpful for patient monitoring.” (11% agreed to this statement). 4. “I think the Visual Patient technology might be helpful for non-monitor experts (e.g., surgeons) in the healthcare system.” (53% of the participants agreed or strongly agreed).

Conclusion

This mixed method study provides evidence that the included anesthesiologists considered the new avatar-based technology to be intuitive and easy to learn and that the technology enabled them to get an overview of the situation quickly. Only a few users considered the avatar presentation to be unhelpful for patient monitoring and about half think it might be useful for non-experts.
  相似文献   

7.

Introduction

Molecular factors are differentially observed in various bent sectors of poplar (Populus nigra) woody taproots. Responses to stress are modulated by a complex interplay among different hormones and signal transduction pathways. In recent years, metabolomics has been recognized as a powerful tool to characterize metabolic network regulation, and it has been widely applied to investigate plant responses to biotic and abiotic stresses.

Objectives

In this paper we used metabolomics to understand if long term-bending stress induces a “spatial” and a “temporal” metabolic reprogramming in woody poplar roots.

Methods

By NMR spectroscopy and statistical analysis we investigated the unstressed and three portions of stressed root (above-bent, bent, and below-bent) sectors collected at 12 (T0), 13 (T1) and 14 (T2) months after stress induction.

Results

The data indicate a clear between-class separation of control and stressed regions, based on the metabolites regulation, during both spatial and temporal changes. We found that taproots, as a consequence of the stress, try to restore homeostasis and normal metabolic fluxes thorough the synthesis and/or accumulation of specific compounds related to mechanical forces distribution along the bent taproot.

Conclusion

The data demonstrate that the impact of mechanical stress on plant biology can efficiently be studied by NMR-based metabolomics.
  相似文献   

8.

Background

Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in > 80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence.

Methods

UV–Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics.

Results

TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K+ buffer, “hybrid 1” conformation yields kinetic constants on interaction with TMPyP4 one order lower than “hybrid 2”. The binding involves π–π stacking with external loop bases.

Conclusions

For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable.

General significance

G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules.  相似文献   

9.

Background

Bone marrow mesenchymal stromal cells (BM-MSCs) are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type.

Methods

A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used: “cytogenetic,” “leukemia,” “bone marrow,” and “mesenchymal stromal cells.”

Results

Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cells

Conclusions

Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.
  相似文献   

10.

Purpose

A review of readily available quantitative environmental data was conducted in order to determine the state of sustainability reporting and identify possible future research areas in Portugal.

Methods

Internet searches of articles written in English and published between 2001 and 2015 were conducted using the keywords “life-cycle assessment,” “LCA,” “water footprint,” “carbon footprint,” and “Portugal.” Additionally, reports from the Global Reporting Initiative (2015 only) were included in the search.

Results and discussion

It was found that 79% of reports found were published in the period 2011–2015. Several reports were found for the forestry, paper and pulp, food and beverage, energy and electricity, waste management, and automotive industries, while no reports were found for the textile, footwear and clothing, and base metal and mineral industries. As such, these are industries on which future studies might focus. No reports found were published by governmental organizations, although it is thought that expanding the search to include Portuguese language results would yields more results. The majority (68%) of companies reporting to the GRI adhered to the relevant guidelines.

Conclusions

A total of 72 reports were found (41 LCAs, water- or carbon footprints, and 31 GRI reports). It is unclear if there are other reports that may be restricted to “hidden” datasets or company specific archives. The aim of this report was to highlight those that were available to a non-specialist or international audiences trying to gain a greater understanding of the LCA space in Portugal.
  相似文献   

11.

Background

Aiming for autonomous living for the people after a stroke is the challenge these days especially for swallowing disorders or dysphagia. The most common cause of dysphagia is stroke. In France, stroke occurs every 4 minutes, which implies 13000 hospitalizations per year. Currently, continuous medical home monitoring of patients is not available. The patient must be hospitalized or visit the medical community for possible follow-up. It is in this context that E-SwallHome (Swallowing & Breathing: Modelling and e-Health at Home) project proposes to develop tools, from hospital care until the patient returns home, which are able to monitor in real time the process of swallowing.

Method

This paper presents a relevant health problem affecting patient recovering from stroke. We propose a frequency acoustical analysis for automatic detection of swallowing process and a non-invasive acoustic based method to differentiate between swallowing sounds and other sounds in normal ambient environment during food intake.

Result

The proposal algorithm for events detection gives a global rate of good detection of 87.31%. Classification of sounds of swallowing and other sounds based on Gaussian Mixture Models (GMM), using the leave-one-out approach according to the small amount of data in our database, gives a good recognition rate of swallowing sounds of 84.57%.

Conclusion

The proposal method has great potential to assist in the clinical evaluation using only swallowing sounds, which is a non-invasive technic for swallowing studies.  相似文献   

12.

Background

The major biological form of selenium is that of the co-translationally inserted amino acid selenocysteine (Sec). In Archaea, the majority of proteins containing Sec, selenoproteins, are involved in methanogenesis. However, the function of this residue is often not known because selenium-independent homologs of the selenoproteins can be employed, sometimes even in one organism.

Scope of review

This review summarizes current knowledge about the selenoproteins of Archaea, the metabolic pathways where they are involved, and discusses the (potential) function of individual Sec residues. Also, what is known about the “archaeal” way of selenoprotein synthesis, and the regulatory mechanism leading to the replacement of the selenoproteins with selenium-independent homologs, will be presented. Where appropriate, similarities with (and differences to) the respective steps employed in the other two domains, Bacteria and Eukarya, will be emphasized.

Major conclusions

Genetic and biochemical studies guided by analysis of genome sequences of Sec-encoding archaea has revealed that the pathway of Sec synthesis in Archaea and Eukarya are principally identical and that Sec insertion in Eukarya probably evolved from an archaeal mechanism employed prior to the separation of the archaeal and eukaryal lines of decent.

General significance

In light of the emerging close phylogenetic relationship of Eukarya and Archaea, archaeal models may be highly valuable tools for unraveling “eukaryotic” principles in molecular and cell biology.  相似文献   

13.

Background

It is important for clinicians to assess their patients’ purging behavior. Various methods of purging, such as self-induced vomiting are well-known. Because patients do not always report their purging behavior, knowing the clinical signs that indicate the behavior is useful. However, we have experienced patients who did not have the reported physical signs of self-induced vomiting because they used hoses instead of their fingers to purge their stomach contents, which they call “tube vomiting”. No other previous studies have reported the use of hoses as a purging tool.

Case presentation

We present as our main case a 20-year-old Japanese woman with anorexia nervosa who engaged in “tube vomiting.” Although she recovered well under medical treatment in our hospital, she began to lose weight and blood potassium soon after discharge. We found that she used a garden hose instead of her fingers to perform self-induced vomiting,. She inserted the hose into her stomach and evacuated the stomach contents through it, without pain. She learned this technique through a blog about eating disorders. We also present two other similar cases. In fact, many patients discuss “tube vomiting” on the internet.

Conclusion

Our experience suggests that a sudden decrease in the weight and blood potassium level could indicate “tube vomiting”. In addition, because many information resources are available on the internet, medical practitioners should be aware of these sites.
  相似文献   

14.

Background

Selenophosphate, the key selenium donor for the synthesis of selenoprotein and selenium-modified tRNA, is produced by selenophosphate synthetase (SPS) from ATP, selenide, and H2O. Although free selenide can be used as the in vitro selenium substrate for selenophosphate synthesis, the precise physiological system that donates in vivo selenium substrate to SPS has not yet been characterized completely.

Scope of review

In this review, we discuss selenium metabolism with respect to the delivery of selenium to SPS in selenoprotein biosynthesis.

Major conclusions

Glutathione, selenocysteine lyase, cysteine desulfurase, and selenium-binding proteins are the candidates of selenium delivery system to SPS. The thioredoxin system is also implicated in the selenium delivery to SPS in Escherichia coli.

General significance

Selenium delivered via a protein-bound selenopersulfide intermediate emerges as a central element not only in achieving specific selenoprotein biosynthesis but also in preventing the occurrence of toxic free selenide in the cell. This article is part of a Special Issue entitled “Selenium research in biochemistry and biophysics – 200 year anniversary”.  相似文献   

15.

Background

The identification of suitable patients is a common problem in clinical trials that is especially evident in tertiary care hospitals.

Methods

We developed and analysed a workflow, which uses routine data captured during patient care in a hospital information system (HIS), to identify potential trial subjects. Study nurses or physicians are notified automatically by email and verify eligibility.

Results

As a case study we implemented the system for acute myeloid leukemia (AML) trials in Münster. During a test period of 50 days 41 patients were identified by the system. 13 could be included as new trial patients, 7 were already included during earlier visits. According to review of paper records no AML trial patient was missed by the system. In addition, the hospital information system further allowed to preselect patients for specific trials based on their disease status and individual characteristics.

Conclusion

Routine HIS data can be used to support patient recruitment for clinical trials by means of an automated notification workflow.
  相似文献   

16.
17.

Background

Periodontitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides (AMPs) which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, viruses, and parasites, and cancerous cells have been linked to periodontitis. The AMPs even possess the caliber of immunomodulation, and are significantly responsive to innate immuno-stimulation and infections. LL-37 plays a salubrious role by preventing and in treatment of chronic forms of periodontitis.

Objective

In the present work we will review the role of antimicrobial peptide LL-37 in periodontitis.

Methods

A systematic search was carried out from the beginning till August, 2016 using the Pubmed search engine. The keywords included “LL-37,” “periodontitis,” “Papillon–Lefevre syndrome,” “Morbus Kostmann,” “Haim-Munk syndrome” along with use of Boolean operator “and.”

Results

The search resulted in identifying 67 articles which included articles linking LL-37 with periodontitis, articles on Papillon–Lefevre syndrome, Morbus Kostmann, Haim-Munk syndrome, LL-37 and periodontitis and articles on pathogenicity of periodontitis.

Conclusion

The literature search concluded that LL-37 plays a pivotal role in preventing and treatment of severe form of periodontitis.
  相似文献   

18.

Background

Specific apolipoprotein A-I variants are associated to severe hereditary amyloidoses. The organ distribution of AApoAI amyloidosis seems to depend on the position of the mutation, since mutations in residues from 1 to 75 are mainly associated to hepatic and renal amyloidosis, while mutations in residues from 173 to 178 are mostly responsible for cardiac, laryngeal, and cutaneous amyloidosis. Molecular bases of this tissue specificity are still poorly understood, but it is increasingly emerging that protein destabilization induced by amyloidogenic mutations is neither necessary nor sufficient for amyloidosis development.

Methods

By using a multidisciplinary approach, including circular dichroism, dynamic light scattering, spectrofluorometric and atomic force microscopy analyses, the effect of target cells on the conformation and fibrillogenic pathway of the two AApoAI amyloidogenic variants AApoAIL75P and AApoAIL174S has been monitored.

Results

Our data show that specific cell milieus selectively affect conformation, aggregation propensity and fibrillogenesis of the two AApoAI amyloidogenic variants.

Conclusions

An intriguing picture emerged indicating that defined cell contexts selectively induce fibrillogenesis of specific AApoAI variants.

General significance

An innovative methodological approach, based on the use of whole intact cells to monitor the effects of cell context on AApoAI variants fibrillogenic pathway, has been set up.  相似文献   

19.

Background

Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration.

Scope of review

We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems.

Major conclusions

Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines.

General significance

Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: “What is life?” This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato.  相似文献   

20.

Background and objective

Re-admission to hospital by the elderly is a frequent event that is associated with complications. The aim of this article is to describe a randomised clinical trial protocol which has the aim of describing and comparing the impact of a home-based intervention by Occupational Therapists (OT) in the likelihood of re-admission at 6 months.

Material and method

Randomised controlled trial conducted in medical units of the “Hospital Clínico de la Universidad de Chile” and “Hospital de la Fuerza Aérea de Chile”, with 217 patients aged 60 years or older admitted for acute or decompensated chronic disease, provided that they have a person of reference after hospital discharge. The control group consists of the usual care regarding post-discharge patients. This will be compared to the experimental group that includes a home visit from OT on two occasions over a six-month period, who will apply a multicomponent intervention. Informed consent will be requested with the sociodemographic and hospital admission information, functional (Barthel index; Lawton & Brody Scale) and cognitive performance (Short Portable Mental Status Questionnaire; Functional Activities Questionnaire; Confusion Assessment Method), and comorbidity (Cumulative Illness Rating Scale for Geriatrics). Both groups will receive a telephone follow-up at 4, 12 and 24 weeks after hospital discharge.

Results

The intervention will reduce the rate of hospital re-admissions by at least 40% at 6 months compared with usual care.

Conclusion

It will be useful to know the components that reduce the risk of hospital re-admissions and improve hospital discharge healthcare for elderly.  相似文献   

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