Pamela Anderson defends 'sexy' WikiLeaks founder Julian

We have somewhat greater incentives than many other firms to figure out the answers to these questions as the partners and employees of Founders Fund are collectively

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Upload and Search Theses and Dissertations - OpenThesis

Follow. index Submissions from 2017 2017. PDF. Spiritual Formation: A Model to Strengthen the Mission, Operation, and Commitment of African American Churches, Anthony

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SHATTERING GLASS - Booktalks Quick and Simple

Shattering Glass by Gail Giles - Shattering Glass is a suspenseful novel written by Gail Giles about the murder of a high school senior named Simon Glass.

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Sebastian blatt thesis format

International Journal of Engineering Research and Applications (IJERA) is an open access online peer reviewed international journal that publishes research ..

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FOUR ESSAYS ON LIBERTY

isaiah berlin four essays on liberty oxford university press london oxford new york

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Svbtle

Writing skills: Cause and effect. By Lexy Holt. Level: Intermediate, Upper intermediate Type: Teaching notes

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Guildportal antithesis examples

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Thesis Statements - Indiana University

What Is a Thesis Statement? We will be talking about thesis statements quite a bit this semester. We will be writing thesis statements, revising them, and using

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Creative Writing with Arts - NUI Galway

Located in NYC, The New School MFA Creative Writing degree program offers concentrations in fiction, nonfiction, poetry, arts writing & writing for children

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Nucor Building Systems - Pre Engineered Steel Buildings

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School of Communication - Graduate Studies

Lito ., es una organización dedicada a la gestión integral de excedentes industriales y residuos peligrosos, coherente con su misión, visión, principios y

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The Five-Paragraph Essay - CommNet

What this handout is about. The first step in any successful college writing venture is reading the assignment. While this sounds like a simple task, it can be a

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Current Local Time in Calgary, Alberta, Canada

All rights reserved. Official web site of The City of Calgary, located in Calgary, Alberta, Canada.

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-Dictionary > Definition: communication

Related WordsSynonymsLegend: Switch to new thesaurus Noun 1. written communication - communication by means of written symbols (either printed or handwritten) black

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Azie in Media Restaurant - Media, PA | OpenTable

Here's a list of the best places to eat in Singapore, with the best food porn. Your complete guide to the Singapore food scene

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Terms or directives for essays, reports, & answering questions

This article overviews strategies for assigning primary keys to a table within a relational database. In particular, it focuses on the issue of when to use natural

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Dissertation Formatting Guidelines - Doctoral Studies

Sample APA Research Paper Sample Title Page Running on Empty 1 Running on Empty: The Effects of Food Deprivation on Concentration and Perseverance

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Doctor of Business Administration | Online DBA Programs

Prepare for admission to USJ's School of Pharmacy. To be considered for admission to USJ's . program, you must first meet the following prerequisites.

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Ohio State football 2016 schedule

The Official Athletic Site of Ohio State Football, partner of CBS Sports Digital. The most comprehensive coverage of the Buckeyes on the web with highlights, scores

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Application Letter Vs. Cover Letter

A cover letter is a letter that you send to accompany your CV when you apply for job, whether advertised or when you are sending an unsolicited application.

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A Retrospective Analysis of Oxygen Desaturation during Acoustic Respiratory Rate Monitoring in Non-ICU Patients following Tracheal Extubation after General Anesthesia

Purpose. Acoustic respiratory rate (RRa) monitoring provides an accurate estimation of the respiratory rate (RR). We investigated the incidence of oxygen desaturation under RRa monitoring in a postoperative setting and identified its related factors. Methods. This study was a retrospective chart review of postoperative patients outside an intensive care unit setting. Using the data collected during the first 8 h postoperatively, patients were divided into oxygen desaturated (SpO2 10 s) and nondesaturated groups under oxygen administration. Multivariate analysis was used to determine oxygen desaturation-associated explanatory factors. Results. Oxygen desaturation was detected in 102 of 935 patients (10.9%). % vital capacity [odds ratio (OR), 0.885 per 10% increase; 95% confidence interval (CI), 0.790 to 0.992], coexisting chronic obstructive pulmonary disease (OR, 2.195; 95% CI, 1.088 to 4.428), and absence of a critical RRa change (RR > 30 or 2 min) (OR, 1.972; 95% CI, 1.226 to 3.172) were independently associated with oxygen desaturation. Conclusion. Postoperative oxygen desaturation was observed in more than 10% of the patients whose RR was monitored by RRa under oxygen therapy. It is more likely to occur in patients with impaired pulmonary function or morbid pulmonary status and can also occur in the absence of abnormal RR.

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Effects of Acute Exercise on Circulating Soluble Form of the Urokinase Receptor in Patients With Major Depressive Disorder

Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD) have increased plasma levels of the soluble form of the urokinase receptor (suPAR), a marker for low-grade inflammation. The aim of this study was to test the hypothesis that acute exercise would induce inflammatory response characterized by increased suPAR and elucidate whether patients with MDD display altered levels of suPAR in response to acute exercise. A total of 17 patients with MDD and 17 controls were subjected to an exercise challenge. Plasma suPAR (P-suPAR) was analyzed before, during, and after exercise. There was a significantly higher baseline P-suPAR in the patients with MDD, and the dynamic changes of P-suPAR during the exercise were significantly lower in the patients with MDD, compared with the controls. This study supports the hypothesis that an activation of systemic inflammatory processes, measured as elevated P-suPAR, is involved in the pathophysiology of depression. The study concludes that P-suPAR is influenced by acute exercise, most likely due to release from activated neutrophils.

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Integrative Analysis of MicroRNA-Mediated Gene Signatures and Pathways Modulating White Blood Cell Count in Childhood Acute Lymphoblastic Leukemia

MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA) target genes modulating white blood cell (WBC) count is lacking. Here, we analyzed miRNAs and gene expression data from pediatric patients with ALL to identify a signature of miRNAs involved in ALL and their mRNA target genes, molecular networks, and biological pathways modulating WBC. We discovered a signature of miRNAs differentially expressed in ALL and a signature of mRNA target genes distinguishing patients with high WBC from patients with low WBC. In addition, we identified molecular networks and biological pathways, among them PI3/AKT, JAK/STAT, IL-17, TGF-β, apoptosis, IL-15, STAT3, IGF-1, FGF, mTOR, VEGF, NF-kB, and P53 signaling pathways, enriched for or targeted by miRNAs. The discovered miRNAs and their target genes and pathways represent potential clinically actionable biomarkers and therapeutic targets.

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Vascular risk factors show link to development of Alzheimer’s

Middle aged people with a high number of vascular risk factors such as obesity, hypertension, diabetes, high cholesterol, and smoking are more likely to have elevated levels of brain amyloid in later...

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Spinal manipulation produces modest improvements in acute low back pain

Spinal manipulation therapy for acute low back pain is associated with modest improvements in pain and function, according to a systematic review and meta-analysis published in JAMA.1The authors said...

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Press Release : Latest data show a global increase of 13% in childhood cancer incidence over two decades

Latest data show a global increase of 13% in childhood cancer incidence over two decades

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Latest data show a global increase of 13% in childhood cancer incidence over two decades

An international study coordinated by the International Agency for Research on Cancer (IARC) and published today in The Lancet Oncology shows that in 2001-2010, childhood cancer was 13% more common than in the 1980s, reaching an annual incidence rate of 140 per million children aged 0-14 years worldwide.
Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F, Hesseling P, Shin HY, Stiller CA, and the IICC-3 contributors.
International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. Published online 11 April 2017.
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Effect of prophylactic placement of internal iliac artery balloon catheters on outcomes of women with placenta accreta: an impact study

Summary

We performed an impact study on the introduction of routine placement of internal iliac artery balloon catheters for the management of haemorrhage during caesarean section in women with placenta accreta. We identified 11 women, with prenatally diagnosed placenta accreta/increta/percreta before this change in practice, who acted as controls, and 30 women who had iliac artery balloons placed. The balloons were inflated in 27 cases. The median (IQR [range]) intra-operative blood loss was 1100 (800–2600 [500–6000]) ml in controls, compared with 1000 (600–2513 [400–15000]) ml in women with iliac artery balloons (p = 0.64). Six (54%) controls received intra-operative blood transfusion compared with 14 (47%) women with iliac artery balloons (p = 0.66). Caesarean hysterectomy was performed in 3 (27.3%) controls and 13 (43.3%) women with iliac artery balloons (p = 0.48). Balloon catheter insertion was associated with a shortened postoperative hospital stay, 6 (5–7 [4–12] days in controls vs. 5 (4–6 [3–10]) in the iliac artery balloon group (p = 0.033). General anaesthesia was used in six (54%) controls, but all women with iliac artery balloons. This study demonstrates that prophylactic balloon occlusion of the internal iliac arteries did not reduce intra-operative haemorrhage or caesarean hysterectomy in women with placenta accreta undergoing caesarean section. In addition, it has a significant impact on the choice of anaesthetic technique.

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Assigning homework to students

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:. History for AP Students

Application Areas. Revware is a leading metrology software and equipment manufacturer – reshaping your world, one product at a time.

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Essay Respect

Essay About Respect essay about respect To live without self respect is to live counting ones omissions and commissions] It is like lying down on an uncomfortable bed

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Equinox Voyages

5, Avenue Annakhil, Hay Riad Rabat - Maroc . Tél : 05 37 56 30 60. Fax : 05 37 56 39 09. info@

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Tutor Finder - Private Tutors in Maths, English, Science

Comparison is a rhetorical strategy in which a writer examines similarities and/or differences between two people, places, ideas, or objects.

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Forums - Pandora's Aquarium

The Persuasion Map is an interactive graphic organizer that enables students to map out their arguments for a persuasive essay or debate.

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Relationship (noun) definition and synonyms | Macmillan

Relationship marketing is a facet of customer relationship management (CRM) that focuses on customer loyalty and long-term customer engagement rather than shorter

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Gastenboek - Telenet Service

Oxbridge essays scampi shrimp recipe nobu-zzvc Samedi 14 mar 2015

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Culture: Music, TV & radio, books, film, art, dance

The essay is the most important part of a college appllication, see sample essays perfect for applying to schools in the US.

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Sarasota County Schools - Home

http:///sites/default/files/lessons/770_walking_ - Read closely to determine what the text says explicitly and to

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Reading Is Fun: Charlotte's Web Lesson Plans and Ideas

Donald Trump's Clueless Debate Answers Spawn #TrumpBookReport Tweets Pinocchio? He's no puppet. No puppet. You're the puppet.

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Essay Writing Service | Order research paper, dissertation

Tips for Writing. You're barely back from vacation and your teacher asks you to do a report or a research paper on a current issue. You believe strongly in the right

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You want to do an action research thesis?

LIST OF ECONOMICS HONOURS THESIS TOPICS IN AY2015/2016 # Thesis Topic Name of Supervisor(s) 1A Mechanism Design Approach to Commercial Banking Prof Sun

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Free world history Essays and Papers - 123helpme

Latest news and information from the World Bank and its development work on Water. Access facts, statistics, project information, development research from experts

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Citation Machine: Format & Generate Citations – APA, MLA

EasyBib Pro Features. APA, Harvard, Chicago, and 7,000 additional formats; No advertisements! Unlimited cloud backup of all your citations

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Social Work Personal Statement

All wiki articles on: Social work personal statements. The following 4 pages are in this category, out of 4 total. S. Personal Statement:Social Work 1

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Research | Department of Computer Science | University of

This will be of great use to Computer Science Engineering, Information Technology (IT), MCA and MSc Computers students for finding a latest and Advanced seminar topics.

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Breach of Contract and Lawsuits - FindLaw

Any kind of contract may be considered broken (breached) once one party unconditionally refuses to perform under the contract as promised, regardless of when

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George Bernard Shaw - Biographical

suny canton admissions essays university of utah admissions essay images uc berkeley haas phd admissions essay eternal sunshine of the spotless mind theme essay

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Revware – Reshape your world

Since November 1994, has helped over eleven million people protect themselves from scams... Scambusters is committed to helping you avoid getting

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The role of microRNA-93 regulating angiopoietin2 in the formation of malignant pleural effusion

Abstract

The biological roles of miRNAs in the development of malignant pleural effusion (MPE) are unclear. In this study, the miRNA microarray analysis was performed in two different prognosis groups of lung adenocarcinoma patients. Expression profiles of miRNAs in MPEs were identified. With the help of quantification PCR, we confirmed the expression differences of miRNAs and further analyzed their biological functions and relative target genes in vitro. The target gene of miR-93 was estimated by online database, and also, the protein was tested. The target gene and the binding sites of specific miRNA were estimated by online database. The combining capacity of binding sites was verified by luciferase reporter gene assay, and the target gene protein was tested by western blot. We detected 107 miRNAs with expression differences (n = 10) and confirmed significant expression differences in miR-93 and miR-146a in two groups of patients (n = 84). By manipulating miR-93 expression of human lymphatic endothelial cells (HLEC) and human umbilical vein endothelial cells (HUVEC), we discovered that high expression of miR-93 inhibited migration, proliferation, and angiogenesis. And also, miR-93 increased not only apoptosis, but also G1 phase cell block. By using luciferase reporter gene assay and western blot, we confirmed that angiopoietin2 (Ang2) was the target of miR-93. The data showed that miR-93 has an inhibiting effect on pleural effusion. By targeting Ang2, miR-93 regulates angiogenesis and lymphangiogenesis and plays a role in pathogenetic mechanism of MPE. MiR-93/Ang2 may shed light on potential new targets in cancer treatment.

The study identified that miR-93 has an inhibiting effect on pleural effusion. By targeting angiopoietin2, miR-93 regulates angiogenesis and lymphangiogenesis so as to play a role in pathogenetic mechanism of malignant pleural effusion. MiR-93/Ang2 may shed light on potential new targets in the cancer treatment.

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Cardiff and Swansea scan trial targets head cancers - BBC News

BBC News

Cardiff and Swansea scan trial targets head cancers BBC News Detailed imaging techniques are to help doctors target head and neck cancers more effectively, in a £720,000 clinical trial in Cardiff and Swansea. It aims to improve the treatment and survival rates of Velindre and Singleton hospital patients. The 3D ... and more »

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Bristol-Myers' Opdivo racks up latest NICE rejection, this time in head and neck cancer - FiercePharma

FiercePharma

Bristol-Myers' Opdivo racks up latest NICE rejection, this time in head and neck cancer FiercePharma Bristol-Myers Squibb's Opdivo hasn't even won marketing approval for head and neck cancer in England and Wales yet, but their cost watchdog is already shutting it out. The National Institute for Health and Care Excellence on Tuesday introduced the ... NHS head and neck cancer patients barred from OpdivoPharmaTimes NHS rules out giving 'life-saving' drug to patients with head and neck cancer because it is too EXPENSIVEMirror.co.uk UK cost agency turns down Bristol drug for head and neck cancerReuters The Institute of Cancer Research -NICE -PMLiVE all 13 news articles »

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Efficacy and safety of Specific Conjugate Particle (SCP)- Doxorubicinin Patients with Recurrent High-Grade Gliomas, a Randomized Clinical Study

The post Efficacy and safety of Specific Conjugate Particle (SCP)- Doxorubicinin Patients with Recurrent High-Grade Gliomas, a Randomized Clinical Study appeared first on Welcome to Avens.

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Young and old rats have different strategies of metabolic adaptation to Cu-induced liver fibrosis

Abstract

We investigated the role of pro- and antioxidant and immune systems in age-related adaptive reactions to chronic exposure to toxicants (copper ions). For this purpose, we administered multiple doses of copper sulfate to younger and older rats in order to induce liver fibrosis and then measured the parameters of proand antioxidant and immune systems and physiological indices. It was found that Cu-induced liver fibrosis was accompanied by oxidative stress and a significant reduction in cell-mediated immune activity. If oxidative stress was eliminated by the administration of exogenous antioxidants (mix factor), the physical capacity, body weight, and content of red blood cells in rats with fibrosis was recovered. The parameters of cell-mediated immune response recovered more effectively in older animals than in younger ones. The metabolic strategies of adaptation to toxic exposure were different in younger and older animals.

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The role of circadian rhythms and the “cellular clock” in age-associated diseases

Abstract

Circadian oscillations are characteristic of almost all processes in living organisms. Disturbances in circadian rhythms may constitute either a cause or a consequence of different diseases. The article analyzes literature data on the role of changes in the circadian rhythms and the expression of clock genes in the development of neurodegenerative and cardiovascular diseases, metabolic syndrome, and type 2 diabetes mellitus in human beings and animals.

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Morphological features of structural organization of the cerebellum cortex in old age

Abstract

In this scientific work, organometric, histological, immunomorphologic, and morphometric parameters of the cerebral cortex of 219 corpses of people (108 men and 111 women) of young and old age have been studied. A comparative analysis of the parameters of bulb-shaped neurons in these ages revealed a decrease of their height and width. It was found that the distance between nerve-cell bodies of the ganglionic layer increases with age, which is obviously associated with disorganization progression and the death of bulbshaped neurons. An increase in the number of immunopositive astrocytes for the glial fibrillary acidic protein, protide S-100, and vimentin in the granular layer and the molecular layer of the cerebral cortex and decline in the number of immunopositive bulb-shaped neurons for neuron-specific enolase and immunonegative for the S-100 protein and vimentin that can be regarded as a manifestation of neurodegeneration. Using immunohistochemical methods in research allows a more nuanced approach to the issues of morphological assessment of the cerebral cortex of elderly people and makes it possible to obtain more objective and complete information on postnatal morphogenesis.

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The contribution of stress and its mediators to the ontopathogeny of infections: a focus on the interactions of cytokines and glucocorticoids

Abstract

The present work is a bibliographical review of the participation of glucocorticoids, cytokines, and other bioregulators of stress in the ontogeny of the immune system and in the pathogeny of infections. In addition, the age-related dynamics of and gender differences in morbidity and mortality caused by three infectious diseases (AIDS, pulmonary tuberculosis and sepsis) were evaluated in southern Brazilian states during three chronological periods. The results obtained indicate the need to pay more attention to the subclinical role played by infectious agents in the etiopathogeny of other chronic degenerative age-related disorders.

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Age-related changes in microcirculation in the cortex of hypertonic rats

Abstract

We have studied the density of the microvascular system of the pia matter and perfusion and oxygen saturation of the sensorimotor cortex in hypertonic rats of different ages. We have found that the density of the microvascular system did not decrease, but increased, with age. The perfusion of the cortex decreased, and oxygen saturation of brain tissues increased. By the age of 12 months, the exploratory behavior of rats in an open-field test worsened significantly by all parameters.

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Mast cells and aging

Abstract

Mast cells (MCs) are present in the skin and mucous membranes, lymphoid organs, intestine wall, and brain, where they are located close to blood and lymphatic vessels and nerve terminals. As a source of a large number of biologically active substances, many of which are released quickly into the environment as a result of degranulation process, mast cells play an essential role in the regulation of physiological processes in the tissues where they are present. Changes in the MC population and activity in tissues during aging is associated with age-related changes of the skin and mucous membranes, as well as the development of centralnervous- system disorders such as itching, headache, joint and muscle pain, memory loss, attention deficit, depression, anxiety and depressive disorders, autism, Alzheimer’s disease, and multiple sclerosis.

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The features of lymph-node reaction to tissue damage in the lymph-drainage area in elderly rats

Abstract

Light microscopy has been used to study the reaction of submandibular lymph nodes (LNs) to surgical damage to the tissues of the maxillofacial region in elderly rats. Connective tissue was more abundant in the LNs of elderly rats than in those of mature animals, regardless of the time of observation (even before surgery). Moreover, the duration of the changes of the volume of the cortical plateau was increased in the old rats, whereas the duration of the changes in paracortex and lymphoid nodules devoid of germinal centers was reduced. The distinctive cytoarchitectonic features included a significant reduction of the number of lymphocytes, mitotic figures, and immuno- and plasmablasts concomitant with the elevation of the number of macrophages, cellular elements that showed signs of destruction, reticulocytes, and red blood cells.

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An endogenous decline in the homeostatic characteristics of two supraorganismal systems from the standpoint of the parametabolic theory of aging

Abstract

An endogenous decline in the homeostatic characteristics of supraorganismal systems is similar to individual aging. The similarity lies in the fact that this decline, as well as individual aging, is caused by negative consequences of specialization of individual elements constituting the system. These consequences in supraorganismal systems are analogous to the parametabolic processes of an aging individual.

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Comparative analysis of different geroprotective methods

Abstract

One hundred and ten patients of different ages have undergone a comparative analysis of the efficiency and safety of a number of geroprotective techniques, including the use of dry lead-carbonate baths, hyperbaric oxygenation, therapeutic massage, and reception of oligopeptide preparations containing complexes of lysyl-glutamyl-asparagin and glutamyl-asparagin-arginine complexes (Vezugen and Pinealon). The most pronounced positive impact on indicators of biological age was found during the combined use of these two oligopeptide complexes. The safest ones in terms of influence on a number of biochemical and immunological parameters and on the clinical state of patients were medical massage and oligopeptide preparations. The use of dry carbon dioxide baths and hyperbaric oxygenation, while having an undoubtedly positive influence on the indices of biological age, has a number of limitations and counterindications.

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On the discontinuous character of annuity curves. III. Two forms of viability variation in Drosophila melanogaster

Abstract

The validity of the two-component structure of annuity curves in Drosophila melanogaster (line Canton-S) observed in our previous studies has been confirmed. The structure is formed by a combination of a stable five-phase pattern and the variability of phase duration (the latter determines the variability of insect viability). Both the stable and the variable component were preserved over 60 generations of flies. The unconventional type of variability addressed in the present study exists along with the well-known type of variability related to the stochastic variation of the annuity curves. The variance of viability that characterizes the reaction norm remains unchanged in a series of generations as well. Thus, both types of variability can be classified as genetically determined phenomena.

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Lamin A and lamin-associated polypeptide 2 (LAP-2) in human skin fibroblasts in the process of aging

Abstract

Mutations of lamin genes lead to diseases, one of which is progeria. This disease is caused by violation of splicing of lamin A gene and accumulation of farnesylated prelamin A (progerin) in the nucleus. LAP-2 is an important factor that regulates and stabilizes the nucleoplasmic pool of lamin A. However, roles of lamin A and LAP-2 in renewal regulation of the population of fibroblasts in the human dermis in different age periods still have not been investigated. The purpose of this investigation was to define expression of lamin A and LAP-2 in human dermal fibroblasts at different ages. Lamin A and LAP-2 were detected in skin sections by indirect immunohistochemistry. It was found that the number of fibroblasts containing lamin A gradually decreased from 90.4 to 76.9% from 20 weeks of pregnancy to 85 years. It was revealed that 32% of dermal fibroblasts were positively stained for LAP-2 in the period from 20 weeks of pregnancy to 20 years, 37.8% in the period of 21–40 years, and 49–51% in the period of 41–85 years. Lamin A expression levels in fibroblast nuclei were essentially constant from 20 weeks of pregnancy to 85 years, while LAP-2 content in fibroblast nuclei was reducing from 0 to 20 years as compared with the embryonic period and was gradually increasing after 21 year. The total number of fibroblasts and PCNA-positive fibroblasts in the dermis decreased with age. The most significant decrease in the number of fibroblasts was observed from 20 weeks of pregnancy to 20 years. The results suggest involvement of lamin A and LAP-2 in the age-related decrease in the number of fibroblasts in the human dermis.

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Glycation, antiglycation, and deglycation: Their role in aging mechanisms and geroprotective effects (literature review)

Abstract

The biochemistry of glycation and its role in the disruption of cell metabolism and development of age-related pathologies have been reviewed in this manuscript based on literature data published, for the most part, in the last 5 years. The effects of antiglycation and deglycation actions of endogenous enzymes, as well as of exogenous chemical compounds of natural and synthetic nature on the process of aging, were evaluated.

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Comparative organometric characteristic of the cerebellum of the young and old age

Abstract

This scientific work is based on morphological research of the cerebellums of 219 corpses of people (108 men and 111 women) of young and senile age. Organometric, histological, and morphometric methods were used. During the study, a comparative analysis of the mass, linear dimensions, and thickness of the cerebral cortex in young and senile age was conducted. The regularities of age variability of organometric characteristic of the cerebellum were revealed, and they were found in the reduction of mass and linear dimensions of the cerebellum in people of senile age compared to younger people. It was determined that the thickness of the molecular and granular layers of the cerebellum was characterized by age-related decrease of the parameters. The results of the morphological study can serve as a basis for the identification of certain regularities of age anatomy of the cerebellum and have practical significance as indicators of the norm that allows using these data in diagnostic and therapeutic work.

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Molecular mechanisms of cell death in retina during development of age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a chronic progressive disease characterized by damage to the central retina zone. Changes in choriocapillaries, retinal pigment epithelium (RPE), and Bruch’s membrane (typical for aging) underlie AMD pathogenesis; however, the mechanisms launching the transfer of typical age-related changes in the pathological process are unknown. The death of photoreceptors and irreversible loss of vision become the results of pathological changes in RPE and choroid. In spite of intensive studies of AMD pathogenesis, information on molecular genetic preconditions of the events leading to the death of photoreceptors (as well as about the pathways of their death) is extremely limited; this complicates the search for efficient methods of AMD treatment (first of all, the most widely spread atrophic (“dry”) form of the disease). Recent studies demonstrated that not only apoptotic but also autophagic and necrotic signaling cascades are involved in the cellular death of retinal cells. The published data on three main forms of the programmed cell death (apoptosis, necrosis, and autophagy) and their role in AMD pathogenesis are summarized in the present review.

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Arterial stiffness in the light of thromboembolic complications in elderly patients with atrial fibrillation

Abstract

According to available data reported by numerous national and international studies, one of the parameters reflecting the degree of lesioning of the vascular wall is arterial stiffness, which makes a fundamental contribution to the risk of developing cardiovascular diseases and the total cardiovascular mortality, especially in the elderly. Patients with cardiac arrhythmias, especially with atrial fibrillation (AF), deserve our special care, since it is this group of patients that is susceptible to a high risk of developing primary and recurrent thromboembolic episodes. This category of patients had a very high risk of death and invalidation, considering the age factor and comorbidity of the pathology. The analysis of factors involved in the development of not only AF, but also its complications, is a task necessary to improve technologies of correction. In view of this, the parameter of vascular-wall stiffness, being one of the mechanisms involved in AF maintenance and a risk factor for the development of acute thromboembolic complications, primarily stroke, should be given very serious consideration. This survey aims to discuss the results of studies devoted to arterial stiffness in patients with atrial fibrillation (AF), as well as the issues related to the risk of developing thromboembolic complications in this category of patients.

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BARROLIMP , El Talar, Residuos Peligrosos / Especiales

Greens Blue Flame supplies propane tank installation services and propane delivery in the Houston, TX area. We also offer bulk commercial delivery.

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PageInsider - Information about all domains

is an Internet Radio station with daily live streaming video. The station plays Hard Rock, Classic Rock, and Punk Rock. MFNRocks streams music 24/7 365

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Essay and Dissertation Marking and Proofreading

Proofread grammar, check spelling and improve your writing quality for free.

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Little Village - Crain's Chicago Business

The essay is the most important part of a college appllication, see sample essays perfect for applying to schools in the US.

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'E SVN: raster trunk/illume/dicts' - MARC

is and in to a was not you i of it the be he his but for are this that by on at they with which she or from had we will have an what been one if would who has her

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Tagung Dermatologische Praxis 2017

Bei der Dermatologischen Praxis in Frankenthal konnten die Teilnehmer wieder aus einer Vielzahl an unterschiedlichen Veranstaltungen mit über 70 Referenten auswählen. Ein Schwerpunkt war am Samstag die Behandlung der Akne. Ebenfalls am Samstag hatten die Besucher auch Gelegenheit, sich in einem Workshop der Arbeitsgemeinschaft Ästhetische Dermatologie und Kosmetologie (ADK) aus erster Hand über wichtige Themen der ästhetischen Medizin zu informieren.

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Neue Therapieoption bei Acne vulgaris

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Narben effektiv behandeln

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Mit Nadeln gegen Narben

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Haartransplantation

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Neue Optionen der Teamarbeit in Kommunen

Eine Versorgung chronisch Kranker über alle Sektoren und Betreuungsbereiche hinweg ist in Deutschland meist noch Utopie. Doch mancherorts gibt es Keimzellen für neue Modelle mit Vorbildcharakter.

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Dermatokosmetika bei Akne: Was ist empfehlenswert?

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ADK aktiv bei dermatologischen Fortbildungen

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Heroin

Heroin: Semisynthetic drug derived from morphine. Discovered in 1874, it was introduced commercially in 1898 by the Bayer company in Germany. The name heroin was coined from the German heroisch meaning heroic, strong. Heroin is stronger (more potent) than morphine.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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The effects of high-intensity interval training vs. moderate-intensity continuous training on body composition in overweight and obese adults: a systematic review and meta-analysis

Summary

Objective

The objective of this study is to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) for improvements in body composition in overweight and obese adults.

Methods

Trials comparing HIIT and MICT in overweight or obese participants aged 18–45 years were included. Direct measures (e.g. whole-body fat mass) and indirect measures (e.g. waist circumference) were examined.

Results

From 1,334 articles initially screened, 13 were included. Studies averaged 10 weeks × 3 sessions per week training. Both HIIT and MICT elicited significant (p < 0.05) reductions in whole-body fat mass and waist circumference. There were no significant differences between HIIT and MICT for any body composition measure, but HIIT required ~40% less training time commitment. Running training displayed large effects on whole-body fat mass for both HIIT and MICT (standardized mean difference −0.82 and −0.85, respectively), but cycling training did not induce fat loss.

Conclusions

Short-term moderate-intensity to high-intensity exercise training can induce modest body composition improvements in overweight and obese individuals without accompanying body-weight changes. HIIT and MICT show similar effectiveness across all body composition measures suggesting that HIIT may be a time-efficient component of weight management programs.

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Effectiveness of interventions to promote physical activity and/or decrease sedentary behaviour among rural adults: a systematic review and meta-analysis

Summary

Physical inactivity and overweight and obesity are more prevalent among rural than urban populations. This study aimed to review published evidence of the effectiveness of interventions to increase physical activity (PA) and/or decrease sedentary behaviour (SB) among rural adults and to identify factors associated with effectiveness. Seven electronic databases were searched for controlled trials of a PA or SB intervention. Meta-analysis was conducted using random effects models and meta-regression. Thirteen studies were included in the qualitative synthesis (n = 4,848 participants) and 12 in the meta-analysis (n = 4,820). All studies were interventions to increase PA. Overall, there was no effect on PA (standardized mean difference [SMD] 0.11; 95% confidence interval [CI] −0.04, 0.25) or SB (SMD 0.07; 95% CI −0.33, 0.20). In PA subgroup analyses, studies employing objective outcome measures demonstrated effects in favour of the intervention (SMD 0.65, 95% CI 0.30, 1.00), while those using self-reported measures did not (SMD 0.00; 95% CI −0.11, 0.10). This review highlights significant gaps in our understanding of how best to promote PA and reduce SB among rural adults. Future studies should use objective measures of PA as study outcomes. The absence of interventions to decrease SB is of concern, with immediate action required to address this large knowledge gap.

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Zytologie in der dermatologischen Praxis

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Mustervorlage für Hygieneplan

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Atopisches Ekzem: Proaktiv behandeln!

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Wasserlöslicher Nagellack

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Nicht invasives Lifting

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Inhaltsverzeichnis

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Die Adhärenz junger Akne-Patienten verbessern — aber wie?

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Pigmentverändungen vorbeugen

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Sterbegeld muss versteuert werden

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Lichttherapie gegen Juckreiz: UV-B nicht mit UV-A kombinieren!

Bei Patienten mit Psoriasis oder atopischem Ekzem bringt es für den Juckreiz offenbar nichts, eine Phototherapie mit UV-B-Strahlen durch einen UV-A-Anteil zu ergänzen. Angesichts möglicher kumulativer Nebenwirkungen empfehlen Schweizer Forscher, die Indikation für den UV-A-Zusatz restriktiv zu stellen.

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„Es klappt ja doch mit Familie!“

Beruf und Familie — das funktioniert auch in eigener Praxis. Vielleicht sogar besser als im Krankenhaus. Diese Erkenntnis konnten junge Ärzte vom „Tag der Chancen" in Thüringen im März mitnehmen.

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„Ganzkörper-Lichttherapie oft zu früh abgesetzt“

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Medical School Admissions

Many years ago, former Yale President Kingman Brewster wrote that selecting future Yale students was a combination of looking for those who would make the most of the

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SmartCockpit - Airline training guides, Aviation

Looking for effective and simple topics for your argumentative essay? Have no clue how to find an interesting idea to write about? Check out the extensive list of

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To Kill A Mockingbird Essays

Starting an essay on Harper Lee’s To Kill a Mockingbird? Organize your thoughts and more at our handy-dandy Shmoop Writing Lab.

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:Christian Music News, Music News

Night at the Museum (2006) cast and crew credits, including actors, actresses, directors, writers and more.

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Wire Cutting Machine | Wire Cut edm

WIRE EDM “THE FUNDAMENTALS” BY DONALD B. MOULTON EDM NETWORK Sugar Grove, IL USA Today, as we embrace the 21st century, there are far greater demands for higher

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College English Essay Writing Service

Your English Language Learning Centre. Over 475 first class English lessons at different levels! Study English with our online lessons.

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Basilica San Clemente - Official Website

... in education ubc thesis checklist site enter site thesis for masters in education topics essay IS PARIS BURNING? – MAURICE JARRE 2 CD Set

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SparkNotes Free Online Test Prep and Study Guides for

We provide excellent essay writing service 24/7. Enjoy proficient essay writing and custom writing services provided by professional academic writers.

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How to Write a Research Introduction (with Sample Intros)

***Sample Institution IRB Approval*** State University Memorandum Research Support Office Eliot Hall, Room 426 (503) 555-5555, extension 555 Date: January 12, 2000

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Death Penalty Information, High School Curriculum

The recent botched executions are just the tip of the iceberg. The death penalty is and always has been a financial and moral disaster.

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CHRISTOLOGY Coastland University. APPROACHES TO

Christology in the Fourth Gospel compiled by Felix Just, ., . Introduction: The one who “comes from above” or is “sent from the Father

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Rates of reaction gcse chemistry coursework

PDF Investigating the rate of a reaction - Creative Chemistry Investigating the rate of a reaction 1. GCSE Chemistry Coursework: a simple way to measure the

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.Civil War: The US-Russian Alliance that Saved the

Confederate Flag, Pop-Culture Phenomenon. What can it mean to “remove” this symbol of the Confederacy when it’s become such a familiar, seemingly benign, part

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Digestive System | Everything You Need to Know, Including

! This tutorial introduces atoms in chemistry. Other sections include matter, elements, the periodic table, reactions, and biochemistry.

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Temple University - Official Site

temple university application essay prompt 2013 .rar file, living a meaningful life essay, difference between morality and ethics, thesis on impact of motivation on

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Vaccines: Are They Still Contributing to the Greater Good?

Safety speaker, safety and health training, safety and health consultant, safety and health seminars. FREE NEWSLETTER Sign up for Safety News You Can Use

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Implant | definition of implant by Medical dictionary

Find out how penile implants work, and their effectiveness in treating erectile dysfunction (erection problems)on

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Transcendentalism (Stanford Encyclopedia of Philosophy)

James Ferguson on Modernity, Development, and Reading Foucault in Lesotho. IR is of course not the only discipline with a global view. Anthropology, for one, has long

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World Clinical Laser Institute - Dental Lasers - Education

Do you have any news (courses, call for papers, job announcements, etc.) that you would like to publish on the . network website? You are welcome to write a post

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Arvine Pipe and Supply Co.

3D CAD Services Streamline Design Process. Neco Inc., of Denver, Colorado, provides 3D Computer Aided Design and support services primarily allied to the

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A presurgical study of lecithin formulation of green tea extract in women with early breast cancer

Epidemiologic data support an inverse association between green tea intake and breast cancer risk. Greenselect®Phytosome® (GSP) is a lecithin formulation of a caffeine-free green tea catechin extract. The purpose of the study was to determine the tissue distribution of Epigallocatechin-3-O-gallate (EGCG) and its effect on cell proliferation and circulating biomarkers in breast cancer patients. Twelve early BC patients received GSP 300 mg, equivalent to 44.9 mg of EGCG, daily for 4 weeks prior to surgery. The EGCG levels were measured before (free-) and after (total-) enzymatic hydrolysis by HPLC-MS/MS in plasma, urine, breast cancer tissue and surrounding normal breast tissue. Fasting blood samples were taken at baseline, before the last administration and 2 hours later. Repeated administration of GSP achieved levels of total-EGCG ranging from 17 to 121 ng/mL in plasma. Despite a high between-subject variability, total EGCG was detectable in all tumor tissue samples collected up to 8 ng/g. Median total-EGCG concentration was higher in the tumor as compared to the adjacent normal tissue (3.18 ng/g vs. 0 ng/g, P=0.02). Free-EGCG concentrations ranged from 8 to 65.8 ng/mL in plasma (P between last administration and 2 hours after <0.001). Free-EGCG plasma levels showed a significant positive correlation with the Ki-67 decrease in tumor tissue (P=0.02). No change in any other biomarkers was noted, except for a slight increase in testosterone levels after treatment. Oral GSP increases bioavailability of EGCG, which is detectable in breast tumor tissue and is associated with antiproliferative effects on breast cancer tissue.

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Combined Genetic Biomarkers and Betel Quid Chewing for Identifying High Risk Group for Oral Cancer Occurrence

Abstract We integrated genetic risk scores (GRS) and environmental factors for identifying high risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case - control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between genetic risk score and Betel quid (BQ) chewing. We employed receiver operating characteristic (ROC) curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1 and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores=4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ and cigarette: adjusted OR: 4.42 (95% CI: 1.34-14.55). The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR=70.77; 95% CI 8.70-575.73). The synergy index was 16.58(95% CI 2.27-70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence.

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Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant Women: An Extended Repository of Model Parameters for Physiologically Based Pharmacokinetic Modeling in Pregnancy

Abstract

Background

In the past years, several repositories for anatomical and physiological parameters required for physiologically based pharmacokinetic modeling in pregnant women have been published. While providing a good basis, some important aspects can be further detailed. For example, they did not account for the variability associated with parameters or were lacking key parameters necessary for developing more detailed mechanistic pregnancy physiologically based pharmacokinetic models, such as the composition of pregnancy-specific tissues.

Objectives

The aim of this meta-analysis was to provide an updated and extended database of anatomical and physiological parameters in healthy pregnant women that also accounts for changes in the variability of a parameter throughout gestation and for the composition of pregnancy-specific tissues.

Methods

A systematic literature search was carried out to collect study data on pregnancy-related changes of anatomical and physiological parameters. For each parameter, a set of mathematical functions was fitted to the data and to the standard deviation observed among the data. The best performing functions were selected based on numerical and visual diagnostics as well as based on physiological plausibility.

Results

The literature search yielded 473 studies, 302 of which met the criteria to be further analyzed and compiled in a database. In total, the database encompassed 7729 data. Although the availability of quantitative data for some parameters remained limited, mathematical functions could be generated for many important parameters. Gaps were filled based on qualitative knowledge and based on physiologically plausible assumptions.

Conclusion

The presented results facilitate the integration of pregnancy-dependent changes in anatomy and physiology into mechanistic population physiologically based pharmacokinetic models. Such models can ultimately provide a valuable tool to investigate the pharmacokinetics during pregnancy in silico and support informed decision making regarding optimal dosing regimens in this vulnerable special population.

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Target-Mediated Drug Disposition Pharmacokinetic–Pharmacodynamic Model of Bosentan and Endothelin-1

Abstract

Background and Objectives

Bosentan is a competitive antagonist on endothelin receptor A and B (ET_A and ET_B), displacing the endogenous binding partner endothelin-1 (ET-1) from its binding sites. After administration of escalating single doses of 10–750 mg as an intravenous (i.v.) infusion, bosentan showed dose-dependent pharmacokinetics (PK). The aim of this analysis was to develop a PK model of bosentan after i.v. administration including competitive antagonism with ET-1 and to analyze its influence on blood pressure and heart rate with a combined pharmacokinetic/pharmacodynamic (PK/PD) model.

Methods

PK/PD data from 70 young male Caucasian subjects were analyzed after single i.v. administration of 10, 50, 250, 500, and 750 mg of bosentan. Population analyses, simulations, and evaluation were performed using a non-linear mixed-effects modeling approach.

Results

The PK of bosentan was best described by a two-compartment, target-mediated drug disposition (TMDD) model. ET-1 plasma and urine profiles were successfully integrated into the bosentan two-compartment, TMDD model encompassing competition for the same receptor. A multiple-peak phenomenon of bosentan plasma concentrations after i.v. administration was best described by a diurnal expression or reappearance of ET receptors on the cell surface. Blood pressure was best described by an E _max model; heart rate was modeled as a compensatory effect of changes in blood pressure.

Conclusion

The developed competitive PK/PD model of bosentan and ET-1 after i.v. administration provides a first step towards understanding the complex PK properties of bosentan and offers a valuable tool for future PK/PD research.

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Modifications of nano-titania surface for in vitro evaluations of hemolysis, cytotoxicity, and nonspecific protein binding

Abstract

In the past decade, a variety of drug carriers based on mesoporous silica nanoparticles has been extensively reported. However, their biocompatibility still remains debatable, which motivated us to explore the porous nanostructures of other metal oxides, for example titanium dioxide (TiO₂), as potential drug delivery vehicles. Herein, we report the in vitro hemolysis, cytotoxicity, and protein binding of TiO₂ nanoparticles, synthesized by a sol–gel method. The surface of the TiO₂ nanoparticles was modified with hydroxyl, amine, or thiol containing moieties to examine the influence of surface functional groups on the toxicity and protein binding aspects of the nanoparticles. Our study revealed the superior hemocompatibility of pristine, as well as functionalized TiO₂ nanoparticles, compared to that of mesoporous silica, the present gold standard. Among the functional groups studied, aminosilane moieties on the TiO₂ surface substantially reduced the degree of hemolysis (down to 5%). Further, cytotoxicity studies by MTT assay suggested that surface functional moieties play a crucial role in determining the biocompatibility of the nanoparticles. The presence of NH₂– functional groups on the TiO₂ nanoparticle surface enhanced the cell viability by almost 28% as compared to its native counterpart (at 100 μg/ml), which was in agreement with the hemolysis assay. Finally, nonspecific protein adsorption on functionalized TiO₂ surfaces was examined using human serum albumin and it was found that negatively charged surface moieties, like –OH and –SH, could mitigate protein adsorption to a significant extent.

Graphical abstract

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Degradation of magnetite nanoparticles in biomimetic media

Abstract

Magnetic nanoparticles (NPs) of magnetite Fe₃O₄ obtained by coprecipitation (COP), thermal decomposition (DT), and commercial sample (CM) have been degraded in similar conditions to physiological medium at pH 4.7 and in simulated body fluid (SBF) at pH 7.4. The formation of the nanoparticles was confirmed by FTIR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). In view of medical and environmental applications, the stability of the particles was measured with dynamic light scattering. The degradation processes were followed with atomic absorption spectroscopy (EAA) and TEM. Magnetic measurements were carried out using vibrating sample magnetometry (VSM). Our results revealed that the structural and magnetic properties of the remaining nanoparticles after the degradation process were significantly different to those of the initial suspension. The degradation kinetics is affected by the pH, the coating, and the average particle size of the nanoparticles.

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Size- and density-controlled deposition of Ag nanoparticle films by a novel low-temperature spray chemical vapour deposition method—research into mechanism, particle growth and optical simulation

Abstract

Ag nanoparticles have attracted interest for plasmonic absorption enhancement of solar cells. For this purpose, well-defined particle sizes and densities as well as very low deposition temperatures are required. Thus, we report here a new spray chemical vapour deposition method for producing Ag NP films with independent size and density control at substrate temperatures even below 100 °C, which is much lower than for many other techniques. This method can be used on different substrates to deposit Ag NP films. It is a reproducible, low-cost process which uses trimethylphosphine (hexafluoroacetylacetonato) silver as a precursor in alcoholic solution. By systematic variation of deposition parameters and classic experiments, mechanisms of particle growth and of deposition processes as well as the low decomposition temperature of the precursor could be explained. Using the 3D finite element method, absorption spectra of selected samples were simulated, which fitted well with the measured results. Hence, further applications of such Ag NP films for generating plasmonic near field can be predicted by the simulation.

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Eating Habits - Maharishi Ayurveda Products International

Reverse Prediabetes with Better Eating Habits and Supplements. Thursday, February 14, 2008 by: Jack Challem Tags: diabetes, health news, Natural News

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Causal Essay Topics - Great Selection of Topics for Your

The unique value proposition of our essay service “Okay, what are you offering exactly?” might be you next question. If it is not, feel free to skip this

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10,000+ Speech Topics

Share the best love quotes collection by famous authors, poets, philosophers and more. Enjoy our Love Quote of the Day on the web, Facebook and blogs.

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Leadership training, leadership tips, theory, skills, for

Catalyst Resources. Catalyst creates and maintains a line of statistical based product called Quick Takes and infographics, which will provide more information on

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Historicism - Anthropological Theories - Department of

What Can I Do With a BA in English and Comparative Literature? The skills you gain from your English and Comparative Literature majors are more practically valuable

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Speech On Importance Of Reading Books Free Essays

Speech On Importance Of Reading Books. The joy of reading books can't be described in words. It's something that you can understand only by actual experience.

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Carshalton High School for Girls - Home

CCHS Teacher Training Opportunities. For information about Teacher Training Opportunities at Clacton County High School please visit our Teacher Training webpage.

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Where to Write for Vital Records - Homepage

Define write: to form letters or numbers on a surface with a pen, pencil, etc. — write in a sentence

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Memento Computer and Communication Sciences

EDIC Candidacy Exam: Exam president: Prof. Friedrich Eisenbrand Thesis director: IEEE Student Branch at EPFL invites you to the IEEE CAS/ED Student Workshop.

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Review The Ancestors Tale Richard Dawkins

4995879043233 Swing Low, Staple Singers, Stapsingers 9780340891070 0340891076 Hod Cat - Sceptre Catalogue Jul 9781560630821 1560630825 Babilonia Renace, Charles H Dyer

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Your Professional Essay Editor: Fast and Professional

Tired of your pen? Have totally no ideas on the topic? Choose our help writing a paper service. We write your essay or reaserch paper. Contact us right now.

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Focus On... - Oxford Islamic Studies Online

Genki - An Integrated Course in Elementary Japanese Answer Key [Second Edition] (2011, E. Banno, Y. Ikeda, Y. Ohno, C. Shinagawa, K. Tokashiki)

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Same-Sex Marriage - Essay - All Best Essays,Term Papers

Read this Social Issues Essay and over 86,000 other research documents. Same Sex Marriage. Marriage is an institution long recognized by our government under the

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Baroque-style - Kids Music Corner

From his first novel to his last, Dashiell Hammett never strayed far from the hard-boiled detective story he put on the map. Learn more at .

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FREE German Essay on my best friend: Mein bester Freund

SMARTCOCKPIT; Our #1 goal, since 2000, is to offer the most extensive online aviation resource to worldwide professional pilots. We desire to spread the undeniable

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National Junior Classical League - NJCL Latin Honor Society

Phi Theta Kappa is the world's largest and most prestigious honor society for two-year college students.

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Hearing Loop

Discover Deli with a Difference! Established in 1932, Deli Brands of America has a tradition of quality and value that is customers will taste the

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Department of History | School of Arts and Sciences

WRITING CHAPTER 1: THE INTRODUCTION OF YOUR CAPSTONE PROJECT, DOCTORAL DISSERTATION, OR MASTERS THESIS Our consultants assist students to focus

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Regulatory documents - Canadian Nuclear Safety Commission

Legalpundits Official Website - Get access to Online Legal Database, Acts, amendments, bills, circulars, notifications, documents, areas of law, ministry documents

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|Murray Bookchin: social anarchism, ecology and

An early advocate of free speech, women's equality and independence, birth control, and union organization.

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Novel selective {beta}1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease [Research]

β-Blockers reduce mortality and improve symptoms in people with heart disease; however, current clinically available β-blockers have poor selectivity for the cardiac β₁-adrenoceptor (AR) over the lung β₂-AR. Unwanted β₂-blockade risks causing life-threatening bronchospasm and reduced efficacy of β₂-agonist emergency rescue therapy. Thus, current life-prolonging β-blockers are contraindicated in patients with both heart disease and asthma. Here, we describe NDD-713 and -825, novel highly β₁-selective neutral antagonists with good pharmaceutical properties that can potentially overcome this limitation. Radioligand binding studies and functional assays that use human receptors expressed in Chinese hamster ovary cells demonstrate that NDD-713 and -825 have nanomolar β₁-AR affinity >500-fold β₁-AR vs. β₂-AR selectivity and no agonism. Studies in conscious rats demonstrate that these antagonists are orally bioavailable and cause pronounced β₁-mediated reduction of heart rate while showing no effect on β₂-mediated hindquarters vasodilatation. These compounds also have good disposition properties and show no adverse toxicologic effects. They potentially offer a truly cardioselective β-blocker therapy for the large number of patients with heart and respiratory or peripheral vascular comorbidities.—Baker, J. G., Gardiner, S. M., Woolard, J., Fromont, C., Jadhav, G. P., Mistry, S. N., Thompson, K. S. J., Kellam, B., Hill, S. J., Fischer, P. M. Novel selective β₁-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease.

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A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel [Research]

Voltage-gated sodium channels (Na_Vs) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial Na_Vs have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial Na_Vs. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic Na_Vs nonselective voltage-gated, Bacillus alcalophilus (Ns_VBa) and bacterial sodium channel from Bacillus halodurans (NaChBac) (IC₅₀ = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of Ns_VBa, whereas the local anesthetic drug lidocaine was shown to antagonize Ns_VBa without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of Ns_VBa, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and in silico analysis suggested that JZTx-27 trapped VSM of Ns_VBa in one of the deactivated states. In mammalian Na_Vs, JZTx-27 preferably inhibited the inactivation of Na_V1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic Na_Vs. More important, we proposed that JZTx-27 stabilized the Ns_VBa VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of Na_Vs.—Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V. DeCaen, P. G. Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.

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Amino acid polymorphisms in the fibronectin-binding repeats of fibronectin-binding protein A affect bond strength and fibronectin conformation [Molecular Biophysics]

The Staphylococcus aureus cell surface contains cell wall-anchored proteins such as fibronectin-binding protein A (FnBPA) that bind to host ligands (e.g. fibronectin; Fn) present in the extracellular matrix of tissue or coatings on cardiac implants. Recent clinical studies have found a correlation between cardiovascular infections caused by S. aureus and nonsynonymous single nucleotide polymorphisms (SNPs) in FnBPA. Atomic force microscopy (AFM), surface plasmon resonance (SPR), and molecular simulations were used to investigate interactions between Fn and each of eight, 20-mer peptide variants containing amino acids A, H, I, K, N, and Q at positions equivalent to 782 and/or 786 in Fn-binding repeat-9 (FnBR-9) of FnBPA. Experimentally measured bond lifetimes (1/koff) and dissociation constants (Kd = koff / kon), determined by mechanically dissociating the Fn-peptide complex at loading rates relevant to the cardiovascular system varied from the lowest-affinity H782A+K786A peptide (0.011 sec, 747 µM) to the highest-affinity H782Q+K786N peptide (0.192 sec, 15.7 µM). These AFM results tracked remarkably well to metadynamics simulations in which peptide detachment was defined solely by the free-energy landscape. Simulations and SPR experiments suggested that an Fn conformational change may enhance the stability of the binding complex for peptides with K786I or H782Q+K786I (Kdapp = 0.2 to 0.5 µM. as determined by SPR) compared with the lowest-affinity double alanine peptide (Kdapp = 3.8 µM). Together, these findings demonstrate that amino acid substitutions in FnBR-9 can significantly affect bond strength and influence the conformation of Fn upon binding. They provide a mechanistic explanation for the observation of nonsynonymous SNPs in fnbA) among clinical isolates of S. aureus that cause endovascular infections.

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Cardiogenic shock: The main cause of mortality in acute aluminum phosphide poisoning

Omid Mehrpour, Mohan Gurjar

Indian Journal of Critical Care Medicine 2017 21(4):246-247



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Malposition of the central venous catheter: A diagnostic dilemma

Sameer N Desai, Santosh K Dasar, V Mithali

Indian Journal of Critical Care Medicine 2017 21(4):235-237

A 50-year-old male was admitted to Intensive Care Unit with head and chest injury needed multiple central venous catheter (CVC) for the long-term intravenous access. Right internal jugular vein was cannulated uneventfully, and the tip of CVC was confirmed in the chest radiograph along the right border of the mediastinum. After few days, left subclavian vein was cannulated and the procedure was uneventful. However, the postprocedure Chest X-ray showed the CVC along the left border of mediastinum rather than the right border. Possibility of CVC in one of the tributaries of left brachiocephalic vein was thought. Due to uncertainty in position of left CVC, we inserted CVC in right-sided subclavian vein, which was in normal position along the right border of mediastinum. Left subclavian CVC was removed. Reviewing the patient's thoracic computed tomography scan revealed, patient had congenital anomaly and double superior vena cava that explained the abnormal course of left subclavian CVC along the left border of mediastinum.

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Respiratory multiplex polymerase chain reaction: An important diagnostic tool in immunocompromised patients

Amarjeet Kaur, Navin Kumar, Sharmila Sengupta, Yatin Mehta

Indian Journal of Critical Care Medicine 2017 21(4):192-198

Background: Viruses and atypical pathogens can cause significant respiratory illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR) has improved the diagnostic yield of pathogens, and it is easier to identify the co-infections also. The present study was done to evaluate the performance of MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients. Methods: Atotal of 177 BAL specimens collected over a 19 months period from immunocompromised patients with respiratory illness were analyzed with the MPCR and aerobic culture. Patients were divided into four according to the pathogens. Category V (only viral), Category NV (nonviral, i.e., bacteria and atypical), Category M (mixed, i.e., both viral and nonviral pathogen), and Category UK (unknown etiology). Results: MPCR identified the causative pathogen in 59.3% of patients while culture could identify only in 37.8% of patients. Most frequent etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus (21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK (27.1%). Mortality was significantly higher in patients of Category M having mixed infections. Conclusion: MPCR is highly sensitive and rapid tool which can be considered in the routine diagnostic algorithm of respiratory illness in immunocompromised patients.

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Not all febrile critical illness with rash is infective: Drug reaction may be a mimic

Ashok Kumar Pannu, MB Adarsh, Navneet Sharma

Indian Journal of Critical Care Medicine 2017 21(4):229-231

We report a case of ciprofloxacin-related drug rash with eosinophilia and systemic symptoms (DRESS) which was initially diagnosed and managed on the line of tropical fever. Later, a diagnosis of definite case of DRESS was made according to the RegiSCAR scoring system and the patient was managed with the removal of ciprofloxacin along with steroids. DRESS is a great masquerader. The diagnosis should be highly suspected in the presence of fever, skin rash, liver involvement, and hypereosinophilia.

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Correlation of serum vitamin D level with mortality in patients with sepsis

Prakash Vipul, Consul Shuchi, Agarwal Avinash, Gutch Manish, Kumar Sukriti, Prakash Ved

Indian Journal of Critical Care Medicine 2017 21(4):199-204

Background: Sepsis is the leading cause of mortality in the critically ill. Recently, it has been found in many studies that many trace elements and nutrients do have an effect on human body and if supplemented can improve the prognosis in patients with sepsis. Aim and Objectives: Primary objective: Whether low Vitamin D is associated with mortality. Secondary objective: To find out association of low Vitamin D levels and morbidity in terms of length of hospital and Intensive Care Unit (ICU) stay. Subjects and Methods: Following ethical approval, consent will be sought from either the patient or assent from a near relative. Successive patients admitted to the medical emergency and ICU at tertiary care health center who fulfill the following criteria for sepsis, within a 24 h time window, were included in the study. Results: Among 88 patients evaluated in our study 15 patients (18.2%) were found to have adequate Vitamin D levels and seven patients (8%) were found insufficient and rest 52 patients (73.9%) were found deficient in Vitamin D. Age of the patients ranged between 18 and 82 years with mean (±standard deviation) 45.02 ± 17.69 years. Mean Vitamin D level was found significantly higher among patients with positive outcome than those with unfavorable outcome (expiry) (t = 2.075, P = 0.04). On comparison of the length of hospital stay (morbidity) with Vitamin D levels, we found statistically significant inverse relation between Vitamin D levels and length of hospital stay. Conclusion: Vitamin D deficiency leads to increased risk of mortality in the critically ill along with prolonged hospital stay.

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Secondary Sjogren's syndrome presenting with distal tubular acidosis and quadriparesis

Kartik Munta, Manimala Rao Surath, K Seshikiran

Indian Journal of Critical Care Medicine 2017 21(4):243-244

A 52-year-old female patient was admitted to Intensive Care Unit with complaints of quadriparesis. Investigations revealed distal renal tubular acidosis (DRTA) secondary to Sjogren's syndrome with involvement of the parotid and thyroid glands. Laboratory investigations showed hyperchloremic metabolic acidosis and an alkaline urine pH with clinical signs of sicca syndrome. Sjogren's syndrome is associated with DRTA and occurrences of quadriparetic hypokalemia, nephrolithiasis, and osteomalacia can be prevented with early diagnosis and lifelong treatment with potassium and alkali replacement.

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Development and psychometric evaluation of the pre-hospital medical emergencies early warning scale

Abbasali Ebrahimian, Gholamreza Masoumi, Roohangiz Jamshidi-Orak, Hesam Seyedin

Indian Journal of Critical Care Medicine 2017 21(4):205-212

Introduction: The number of requests for emergency medical services (EMSs) has increased during the past decade. However, most of the transports are not essential. Therefore, it seems crucial to develop an instrument to help EMS staff accurately identify patients who need pre-hospital care and transportation. The aim of this study was to develop and evaluate the psychometric properties of the Pre-hospital Medical Emergencies Early Warning Scale (Pre-MEWS). Materials and Methods: This mixed-method study was conducted in two phases. In the first phase, a qualitative content analysis study was conducted to identify the predictors of medical patients' need for pre-hospital EMS and transportation. In the second phase, the face and the content validity as well as the internal consistency of the scale were evaluated. Finally, the items of the scale were scored and scoring system was presented. Results: The final version of the scale contained 22 items and its total score ranged from 0 to 54. Conclusions: Pre-MEWS helps EMS staffs properly understand medical patients' conditions in pre-hospital environments and accurately identify their need for EMS and transportation.

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Quality indicators compliance survey in Indian intensive care units

Munta Kartik, Palepu B. N. Gopal, Rahul Amte

Indian Journal of Critical Care Medicine 2017 21(4):187-191

Context: The quality of health care and outcomes of Intensive Care Unit (ICU) have been a major subject of discussion in the past decade. Quality indicators in ICUs maintain an order of uniformity and standard care of delivery across ICUs. Aims: In this study, we tried to analyze the percentage compliance of quality indicators in ICU across our country. Methods: Four hundred complete questionnaire forms were collected in two stages by means of conducting a survey and through email responses to the survey questionnaire. Data were tabulated and evaluated in percentage responses. Results: Monitoring of infection control measures such as hand hygiene (77%), monitoring of ICU-acquired infections (>75%), and quality and policy measures (>70%) were promising. Improvements are required in following end-of-life pathways (52%) and staffing patterns in ICU. ICU discharge timings (41%), standardized mortality ratio monitoring (39%), and multidisciplinary rounds (58%) in ICUs are few areas we need to develop further. Conclusion: The future of critical care looks promising with growing number of trained intensivists and hospitals functioning with an average ICU bed strength of 30–40. Such surveys need to be performed regularly to improve the patient care and safety across ICUs.

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Influence of admission source on the outcome of patients in an intensive care unit

Anirban Hom Choudhuri, Mitali Chakravarty, Rajeev Uppal

Indian Journal of Critical Care Medicine 2017 21(4):213-217

Aim of the study: The admission in the Intensive Care Unit (ICU) occurs from various sources, and the outcome depends on a complex interplay of various factors. This observational study was undertaken to describe the epidemiology and compare the differences among patients admitted in a tertiary care ICU directly from the emergency room, wards, and ICUs of other hospitals. Materials and Methods: A retrospective study was conducted on 153 consecutive patients admitted from various sources in a tertiary care ICU between July 2014 and December 2015. The primary endpoint of the study was the influence of the admission source on ICU mortality. The secondary endpoints were the comparison of the duration of mechanical ventilation, length of ICU stay, and the ICU complication rates between the groups. Results: Out of the 153 patients enrolled, the mortality of patients admitted from the ICUs of other hospital were significantly higher than the patients admitted directly from the emergency room or wards/operating rooms (60.5% vs. 48.2% vs. 31.9%; P = 0.02). The incidence of ventilator-associated lung injury was lower in the patients admitted directly from the emergency room (23.4% vs. 50% vs. 50%; P = 0.03). Multivariate logistic regression analysis revealed higher age, increased disease severity, longer duration of mechanical ventilation, and longer ICU stay as independent predictors of mortality in the patients shifted from the ICUs of other hospitals. Conclusion: The study demonstrated a higher risk of ICU mortality among patients shifted from the ICUs of other hospitals and identified the independent predictors of mortality.

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Hyperemia causing delayed recovery in traumatic brain injury

Shalini Nair, Ramanan Rajagopal

Indian Journal of Critical Care Medicine 2017 21(4):232-234

Subarachnoid hemorrhage is a common manifestation of traumatic brain injury. A clinical deterioration in Glasgow Coma Scale score without an accompanying radiological worsening is suggestive of vasospasm. However, hyperemia could be another possibility which can easily be considered with corroborating transcranial Doppler (TCD) features. This case report reiterates the value of TCD in such instances.

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Gender-based assessment of survival in trauma-hemorrhagic shock: A retrospective analysis of Indian population

Pankaj Verma, Sanjeev Bhoi, Upendra Baitha, Tej Prakash Sinha, Prakash Ranjan Mishra

Indian Journal of Critical Care Medicine 2017 21(4):218-223

Introduction: Trauma-hemorrhagic shock (THS) is a leading cause of death. Female rats and women experience better outcomes in terms of survival after major trauma as compared to males. There are limited data in Indian population. Authors studied the gender-based outcome of patients with Class IV hemorrhagic shock due to blunt trauma and the distribution of factors among males and females which are known to affect outcome. Materials and Methods: It was a retrospective study with data of trauma victims between January 2008 and July 2013. Road traffic crash (RTC), fall, or assault of all ages with Class IV hemorrhagic shock on arrival was included in the study, and data were collected on demographic, clinical, and laboratory parameters. Drowning, burns, penetrating injuries, and septic, neurogenic, and cardiogenic shock were excluded from the study. Results: Seven hundred and eighty-one patients were analyzed under three groups: (i) overall group including all patients (n = 781), (ii) male group (n = 609), and (iii) female group (n = 172). After adjusting all variables, mortality was significantly lower in females as compared to males following THS (P < 0.05). Age, blood pressure, pulse, male gender, and fall and RTC as mode of injury (MOI) were independent predictors of mortality (P < 0.05) in overall group. Among males, age, pulse, and RTC as a MOI were significant (P < 0.05), while in females, only systolic blood pressure (SBP) was independent predictor of mortality. Conclusion: Females had better survival as compared to males following THS. SBP was an independent predictor of mortality in females with THS.

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Acute yellow phosphorus poisoning causing fulminant hepatic failure with parenchymal hemorrhages and contained duodenal perforation

Reddy Ravikanth, S Sandeep, Babu Philip

Indian Journal of Critical Care Medicine 2017 21(4):238-242

White phosphorus is well known as a potent hepatotoxin and a severe local and systemic toxin causing damage to gastrointestinal, hepatic, cardiovascular, and renal systems. It is used in the manufacture of matches, fireworks, rodenticide, and fertilizers. Death results due to acute liver failure. Management of yellow phosphorus (YP) poisoning is supportive with no antidote available. Here, we present a case of acute YP poisoning in a 25-year-old female presenting with fulminant hepatic failure and duodenal perforation.

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Abrus precatorius poisoning: A retrospective study of 112 patients

Aishwarya Karthikeyan, S Deepak Amalnath

Indian Journal of Critical Care Medicine 2017 21(4):224-225

Abrus precatorius is a rare but important cause of plant poisoning, especially in tropical countries like India. Most of the published literature on Abrus is limited a few case reports. Hence, we did a retrospective study the clinical features and outcome of Abrus poisoning. Case records of patients admitted to medicine wards during 7 years were included in the study. A total of 112 patients were studied. The majority were females (78%), and most of the patients were between 13 and 30 years (81%). Diarrhea was the most common symptom (66%), and blood in stools was present in (33%). Six patients had died with a mortality rate of (5.35%).

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Symmetrical peripheral gangrene in severe Plasmodium vivax malaria

Prabhat Kumar, Ghazal Tansir, Harish Gupta, Juhi Dixit

Indian Journal of Critical Care Medicine 2017 21(4):245-246



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Thrombotic thrombocytopenic purpura in a case of dengue fever: A rare presentation

Abhijit S Gavali, Jayant Shelgaonkar, Sandip Bartakke

Indian Journal of Critical Care Medicine 2017 21(4):226-228

Here, we present an unusual occurrence of thrombotic thrombocytopenic purpura (TTP) in a case of dengue fever. Both the conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, as soon as, we diagnosed the patient as having TTP, we treated her with plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms and laboratory parameters also normalized. Hence, timely diagnosis and starting appropriate treatment immediately are key factors for successful outcome.

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The tissue dilator: A victim or the aggressor?

Prakash K Dubey

Indian Journal of Critical Care Medicine 2017 21(4):247-248



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GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment

The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downegulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells. In a system to dynamically visualize cellular metabolic responses mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor cells. Reducing GAD1 in metastatic cells by primary glia cell co-culture abolished the capacity of metastatic cells to utilize extracellular glutamine, leading to cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic or pharmacological disruption of the GABA metabolic pathway decreased the incidence of brain metastasis in vivo. Taken together, our results show how epigenetic changes in GAD1 expression alter local glutamate metabolism in the brain metastatic microenvironment, contributing to a metabolic adaption that facilitates metastasis outgrowth in that setting.

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IL-4 primes the dynamics of breast cancer progression via DUSP4 inhibition

The tumor microenvironment supplies pro-inflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL-4 secreted by adipose tissue and estrogen receptor-positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL-4 signaling with the IL-4Rα antagonist IL-4DM compromised breast cancer cell proliferation, invasion and tumor growth by downregulating MAPK pathway activity. IL-4DM reduced numbers of CD44+/CD24- cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-kB. Enforced expression of DUSP4 drove conversion of metastatic cells to non-metastatic cells. Mechanistically, RNAi-mediated attenuation of DUSP4 activated the ERK and p38 MAPK pathways, increased stem-like properties and spawned metastastic capacity. Targeting IL-4 signaling sensitized breast cancer cells to anti-cancer therapy and strengthened immune responses by enhancing the number of IFN-γ-positive cytotoxic T lymphocytes. Our results showed the role of IL-4 in promoting breast cancer aggressiveness and how its targeting may improve the efficacy of current therapies.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2p3Tj4u
via IFTTT