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SU NSG 430 Cardiac Tamponade Complex Care Nursing ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON SU NSG 430 Cardiac Tamponade Complex Care Nursing Create Your Own Case Study Discussion ForumInitial Post: For this discussion board post, you are to pick one topic that we have covered so far (ex: GI disturbances, arrhythmia etc.). You will create a case study or scenario revolving around this topic. You will need to come up with a patient, their history/situation and their clinical presentation. You can include any information that will help your reader understand what is going on with the patient. You should use references about the topic to help you create the situation. Then ask three questions, that you would like one of your colleagues to answer regarding your case study/scenario. These questions should be open ended and allow for critical thinking. SU NSG 430 Cardiac Tamponade Complex Care Nursing attachment_1 attachment_2 Chapter 17 Hematological and Immune Disorders Copyright © 2017 Elsevier Inc. All rights reserved. Anatomy and Physiology ? Hematopoiesis ? ? Blood cell formation Stem cells differentiate • Erythrocytes • Leukocytes • Thrombocytes Copyright © 2017 Elsevier Inc. All rights reserved. 2 Anatomy and Physiology (Cont.) Figure 17-1 ?Formation of the multiple different blood cells from the original pluripotent hematopoietic stem cell (PHSC) in the bone marrow. (From Hall J. Guyton and Hall Textbook of Medical Physiology. 13th ed. Philadelphia: Saunders. 2015.) Copyright © 2017 Elsevier Inc. All rights reserved. 3 Anatomy and Physiology (Cont.) ? Blood ? Plasma ? Solutes (e.g., ions) ? Serum proteins • Coagulation • Healing • Transport • Osmotic pressure ? Blood cells Copyright © 2017 Elsevier Inc. All rights reserved. 4 Anatomy and Physiology (Cont.) ? Erythrocytes: red blood cells (RBCs) ? ? ? Thrombocytes: platelets ? ? ? Erythropoietin stimulates production O2 transport Thrombopoietin stimulates production Clotting Leukocytes: white blood cells (WBCs) ? Fight infection and antigens ? Structure—granular and agranular ? Function—phagocyte or immunocyte Copyright © 2017 Elsevier Inc. All rights reserved. 5 Quick Quiz! What is another name for platelets? Erythrocytes B. Leukocytes C. Phagocytes D. Thrombocytes A. Copyright © 2017 Elsevier Inc. All rights reserved. 6 Granular Leukocytes ? Neutrophils ? ? Bacterial infections Eosinophils ? Allergens ? Parasites ? Basophils ? Allergic response ? Inflammatory response Copyright © 2017 Elsevier Inc. All rights reserved. 7 Agranular Leukocytes ? Monocytes ? ? Mature into macrophages Lymphocytes ? Defense against microorganisms ? Tumor immunity • Humoral—B lymphocytes • Cell-mediated—T lymphocytes ? Delayed hypersensitivity ? Autoimmune diseases ? Foreign tissue rejection Copyright © 2017 Elsevier Inc. All rights reserved. 8 Immune Anatomy and Physiology ? ? ? Immunity is the ability to resist and fight infection Antigen-antibody responses Autoimmune: body sees self as “nonself” and activates immune response Copyright © 2017 Elsevier Inc. All rights reserved. 9 Nonspecific Defenses ? Epithelial surfaces ? ? Intact skin and mucous membranes Inflammation and phagocytosis ? Initiated by cellular injury ? Tissue repair ? Cytokine and chemokine release ? Proinflammatory ? Antiinflammatory Copyright © 2017 Elsevier Inc. All rights reserved. 10 Specific Defenses ? ? Humoral immunity Cell-mediated immunity Copyright © 2017 Elsevier Inc. All rights reserved. 11 Humoral Immunity ? ? ? B lymphocytes Formation of antibodies Immunoglobulins ? IgG ? IgM ? IgA ? IgE ? IgD Copyright © 2017 Elsevier Inc. All rights reserved. 12 Cell-Mediated Immunity ? ? ? T lymphocytes Initiated by macrophages Cells ? ? ? Helper/inducer Suppressor Killer Copyright © 2017 Elsevier Inc. All rights reserved. 13 Hemostasis ? ? ? ? Platelets Blood proteins Vasculature Balance between clotting system and fibrinolytic system Copyright © 2017 Elsevier Inc. All rights reserved. 14 Coagulation Physiology Figure 17-3. Coagulation physiology. SU NSG 430 Cardiac Tamponade Complex Care Nursing Copyright © 2017 Elsevier Inc. All rights reserved. 15 Coagulation Pathway ? ? Cascade theory Initiating event ? ? ? Intrinsic pathway: injury to blood (factor XII) Extrinsic pathway: tissue injury (factor VII) Final common pathway ? Prothrombin to thrombin ? Fibrinogen to fibrin ? Clot Copyright © 2017 Elsevier Inc. All rights reserved. 16 Coagulation Pathway (Cont.) Figure 17-4 ?Coagulation cascade. (From McCance KL. Structure and function of the hematological system. In McCance KL, Huether SE, eds. Pathophysiology: The biologic basis for disease in adults and children. 7th ed. St. Louis: Mosby. 2014.) Copyright © 2017 Elsevier Inc. All rights reserved. 17 Fibrinolysis ? Stimulated by clot formation ? ? ? Thrombin released Stimulates conversion of plasminogen to plasmin Breakdown yields fibrin degradation products (FDPs), or fibrinogen split products (FSPs) Copyright © 2017 Elsevier Inc. All rights reserved. 18 Fibrinolysis (Cont.) Figure 17-5. Fibrinolysis. Copyright © 2017 Elsevier Inc. All rights reserved. 19 Hemostasis: Summary ? ? ? Activation of the coagulation cascade Formation of a stable fibrin clot Activation of the fibrinolytic system Copyright © 2017 Elsevier Inc. All rights reserved. 20 Assessment ? ? ? ? Past medical history Evaluation of patient concerns Physical examination Cues to hematological or immunological problems ? Altered oxygenation ? Bleeding ? Infection Copyright © 2017 Elsevier Inc. All rights reserved. 21 Assessment (Cont.) ? Diagnostic tests ? ? ? Complete blood count (CBC) with differential Coagulation profile Based on these findings, further testing may be required Copyright © 2017 Elsevier Inc. All rights reserved. 22 Erythrocyte Disorders Copyright © 2017 Elsevier Inc. All rights reserved. 23 Anemia ? Reduction of circulating RBCs or hemoglobin ? ? Poor tissue oxygenation Blood flow shunted to vital organs Copyright © 2017 Elsevier Inc. All rights reserved. 24 Causes of Anemia ? ? ? ? Blood loss (chronic or acute) Impaired production Increased RBC destruction Combination of these Copyright © 2017 Elsevier Inc. All rights reserved. 25 Quick Quiz! Anemia secondary to blood loss is: Aplastic B. Hemorrhagic C. Iron deficiency D. Hemolytic A. Copyright © 2017 Elsevier Inc. All rights reserved. 26 Types of Anemia ? ? ? ? ? ? ? ? Hemorrhagic Marrow failure Aplastic Hemolytic Sickle cell B12 deficiency Folic acid deficiency Iron deficiency—most common Copyright © 2017 Elsevier Inc. All rights reserved. 27 Assessment of Anemia ? Decreased circulating volume ? ? Signs of hypovolemia Decreased oxygenation ? Signs of hypoxemia ? Shortness of breath ? Compensatory mechanisms ? Increased heart rate ? Congestive heart failure may result Copyright © 2017 Elsevier Inc. All rights reserved. 28 Diagnosis of Anemia ? ? ? ? ? ? ? ? ? CBC Bone marrow biopsy Reticulocyte count (hemolytic) Transferrin (hemolytic) Haptoglobin (hemolytic) Electrophoresis (sickle cell) Schilling (B12) Folate (folic acid deficiency) Iron and ferritin (iron deficiency) Copyright © 2017 Elsevier Inc. All rights reserved. 29 Treatment of Anemia ? ? ? ? Depends on the cause and type Erythropoietin used to stimulate RBC production Splenectomy = hemolytic anemia Bone marrow transplantation = aplastic anemia Copyright © 2017 Elsevier Inc. All rights reserved. 30 Critical Thinking Challenge ? Many patients in the ICU have blood drawn frequently. SU NSG 430 Cardiac Tamponade Complex Care Nursing What strategies can be implemented to prevent anemia from occurring in these patients? Copyright © 2017 Elsevier Inc. All rights reserved. 31 Nursing Management of Anemia Diagnoses ? Decreased cardiac output ? Altered tissue perfusion ? Impaired gas exchange ? Risk for fluid volume excess or deficit ? Risk for infection Selected Interventions • Assess tachycardia, hypotension • Provide periods of rest • Administer O2 and monitor saturation • Monitor fluid volume status • Prevent infection Copyright © 2017 Elsevier Inc. All rights reserved. 32 WBC and Immune Disorders ? Immunocompromised patient ? Defect in WBC or immune physiology Copyright © 2017 Elsevier Inc. All rights reserved. 33 Immunocompromise ? ? ? ? Defects in WBCs or immune physiology Lack of normal defenses May be asymptomatic Infection is leading cause of death Copyright © 2017 Elsevier Inc. All rights reserved. 34 Immunocompromise (Cont.) ? ? ? Symptoms of infection are often absent Fever may be the only sign of infection Pain without signs of inflammation is also a cue Copyright © 2017 Elsevier Inc. All rights reserved. 35 Critical Thinking Challenge ? Discuss the following factors that contribute to immunocompromise as they relate to the critically ill patient: ? Invasive procedures ? Malnutrition ? Opportunistic pathogens ? Medications Copyright © 2017 Elsevier Inc. All rights reserved. 36 Quick Quiz! Immunocompromised patients may not demonstrate typical signs of infection. The only assessment that may indicate infection is: Fever B. Redness C. Swelling D. Purulent drainage A. Copyright © 2017 Elsevier Inc. All rights reserved. 37 Laboratory Analysis ? ? ? ? Leukopenia Low CD4 counts Decreased immunoglobulins No response to antigen skin test—anergy Copyright © 2017 Elsevier Inc. All rights reserved. 38 Medical Management ? Reverse the cause ? ? ? ? ? Cell replacement Bone marrow transplant Immunoglobulins Treat infections Nutrition Copyright © 2017 Elsevier Inc. All rights reserved. 39 Nursing Management ? ? ? ? ? ? Isolation Hygiene; wash hands Aseptic technique for procedures Good assessment for cues of infection Maintain skin integrity Optimum nutritional support Copyright © 2017 Elsevier Inc. All rights reserved. 40 Neutropenia ? Absolute neutrophil count less than 1500 cells/microliter ? ? ? ? Mild Moderate Severe Causes ? Overwhelming infection ? Radiation ? Inadequate production ? Exposure to chemicals and drugs ? High risk of infection Copyright © 2017 Elsevier Inc. All rights reserved. 41 Neutropenia Risks ? ? ? Overwhelming infection Radiation therapy Chemicals and drugs ? ? ? Antibiotics Chemotherapy Disease states Copyright © 2017 Elsevier Inc. All rights reserved. 42 Assessment of Neutropenia ? ? Classic symptoms of infection often absent Areas of heavy bacteria at risk for infection (mouth, perineum, IV sites, and catheter) Copyright © 2017 Elsevier Inc. All rights reserved. 43 Neutropenia Medical Management ? ? ? ? Prevent and treat infection Reverse cause Colony-stimulating factors Prophylactic antibiotics Copyright © 2017 Elsevier Inc. All rights reserved. 44 Neutropenia Nursing Management ? Similar to that used for immunocompromised patient Copyright © 2017 Elsevier Inc. All rights reserved. 45 Malignant WBC Disorders ? Leukemia ? ? Lymphoma ? ? Large number of immature cells Cancer affects lymphocytes Multiple myeloma ? Abnormal immunoglobulins Copyright © 2017 Elsevier Inc. All rights reserved. 46 Malignant WBC Disorders (Cont.) ? ? ? ? SU NSG 430 Cardiac Tamponade Complex Care Nursing Decreased number of functional WBCs Risk for infection Alteration in immune response Fever difficult to interpret Copyright © 2017 Elsevier Inc. All rights reserved. 47 Malignant WBC Disorders (Cont.) ? Symptoms often nonspecific ? Fatigue, malaise ? Myalgias ? Activity intolerance ? Night sweats ? Fever ? Other symptoms ? Bruising and bleeding ? Enlarged lymph nodes ? Thrombosis Copyright © 2017 Elsevier Inc. All rights reserved. 48 Malignant WBC Disorders (Cont.) ? Staging of disorders determines treatment ? ? ? ? Chemotherapy Biotherapy Bone marrow transplant Nursing care is based on treating and preventing infections Copyright © 2017 Elsevier Inc. All rights reserved. 49 Critical Thinking Challenge ? How are patients with malignant WBC disorders cared for differently than patients with other types of compromised immune systems? Copyright © 2017 Elsevier Inc. All rights reserved. 50 Immunodeficiency ? Primary ? ? Congenital abnormality Secondary ? Acquired Copyright © 2017 Elsevier Inc. All rights reserved. 51 Immunodeficiency: Acquired Immune Deficiency Syndrome (AIDS) ? ? ? ? Infection with human immunodeficiency virus (HIV) (retrovirus) Depletes helper T cells, CD4 cells, and macrophages Increased risk for opportunistic infections Transmitted via body fluids, blood, or blood products Copyright © 2017 Elsevier Inc. All rights reserved. 52 HIV Pathophysiology Figure 17-6. Human immunodeficiency virus (HIV) pathophysiology. CMV, Cytomegalovirus; CNS, central nervous system; ELISA, enzyme-linked immunosorbent assay; TB, tuberculosis. Copyright © 2017 Elsevier Inc. All rights reserved. 53 Diagnosis of AIDS ? ? CD4 count less than 200/microliter Indicator condition manifested Copyright © 2017 Elsevier Inc. All rights reserved. 54 Medical Interventions: HIV ? ? ? Antiretroviral medications Multidrug therapy has been more effective than monotherapy Supportive therapy: prevention of infection, nutritional support, analgesics, etc. Copyright © 2017 Elsevier Inc. All rights reserved. 55 Nursing Interventions: HIV ? ? ? ? Prevent infection Observe for adverse reactions to medications Provide psychosocial support Prevent transmission Copyright © 2017 Elsevier Inc. All rights reserved. 56 Critical Thinking Challenge ? ? Should visitors be restricted for the HIV-positive patient? Why or why not? Sometimes AIDS is diagnosed when the patient is admitted to the ICU with an opportunistic infection. Discuss the challenges of patient/family support in this situation. Copyright © 2017 Elsevier Inc. All rights reserved. 57 Bleeding Disorders ? Abnormality in stages of clotting ? Vasoconstriction ? Creation of platelet plug ? Development of clot ? Fibrinolysis ? ? Inherited or acquired Common in renal, hepatic, and gastrointestinal disorders; malnutrition Copyright © 2017 Elsevier Inc. All rights reserved. 58 Critical Thinking Challenge ? Describe the assessments for detecting bleeding disorders: ? Skin and mucous membranes ? Bodily fluids (How is this detected?) ? Internal bleeding (How is this detected?) Copyright © 2017 Elsevier Inc. All rights reserved. 59 Diagnosis of Bleeding ? CBC ? ? ? ? Hemoglobin Hematocrit Fibrinogen PT, aPTT Copyright © 2017 Elsevier Inc. All rights reserved. 60 Nursing Diagnoses ? ? ? ? ? Risk for Bleeding Ineffective Protection Ineffective Peripheral Tissue Perfusion Deficient Fluid Volume and Acute Pain Copyright © 2017 Elsevier Inc. All rights reserved. 61 Quick Quiz! The nurse is caring for a postoperative patient and notes “excessive” drainage on the abdominal dressing. A nursing intervention to assess the amount of blood loss is: Estimate the blood loss from the OR B. Monitor the WBC C. Weigh the abdominal dressings D. Weigh the patient daily A. Copyright © 2017 Elsevier Inc. All rights reserved. SU NSG 430 Cardiac Tamponade Complex Care Nursing 62 Nursing Management: Bleeding ? ? ? ? ? Assess blood loss Assess vital signs, hemodynamics, and perfusion Assess for signs and symptoms of hypovolemia Administer blood products and fluids Administer topical agents as needed Copyright © 2017 Elsevier Inc. All rights reserved. 63 ? Medical Management: Bleeding (Cont.) Whole blood • Albumin Packed RBCs • Granulocytes Leukocyte-poor RBCs • Plasma protein Platelets • Fresh frozen plasma ? Cryoprecipitate ? ? ? Review Table 17-11 to compare and contrast the products. Copyright © 2017 Elsevier Inc. All rights reserved. 64 Thrombocytopenia ? Decreased platelets ? ? ? Less than 100,000/microliter Risk for bleeding Treated with platelet transfusions Copyright © 2017 Elsevier Inc. All rights reserved. 65 Disseminated Intravascular Coagulation (DIC) ? ? ? ? Accelerated activation of clotting cascade Depletion of clotting factors Bleeding Secondary problem Copyright © 2017 Elsevier Inc. All rights reserved. 66 Pathophysiology of DIC ? ? ? ? ? ? Initiating event: procoagulants Stimulation of intrinsic or extrinsic pathway Clots in microvasculature Consumption of clotting factors Fibrinolysis FDPs: potent anticoagulants Copyright © 2017 Elsevier Inc. All rights reserved. 67 Pathophysiology of DIC (Cont.) Figure 17-7. Pathophysiology of disseminated intravascular coagulopathy. Copyright © 2017 Elsevier Inc. All rights reserved. 68 Etiology of DIC ? ? ? ? ? ? Infection Trauma (e.g., burns, crush) Obstetric conditions (e.g., abruptio placentae, amniotic fluid embolus, retained dead fetus) Hematological disorders Oncological disorders Other: shock or sepsis, acute respiratory distress syndrome Copyright © 2017 Elsevier Inc. All rights reserved. 69 Assessment of DIC ? ? ? Overt bleeding or oozing Occult bleeding Signs of platelet deficiency ? ? ? Petechiae Ecchymosis Decreased perfusion to organs ? Changes in mental status ? Infarction of tissue in digits and nose Copyright © 2017 Elsevier Inc. All rights reserved. 70 Laboratory Diagnosis: DIC ? ? ? ? ? ? ? Decreased platelets Decreased fibrinogen Prolonged PT, aPTT, thrombin time Elevated FDP or FSP Increased D-dimer Decrease in coagulating factors Decrease in hemoglobin and hematocrit Copyright © 2017 Elsevier Inc. All rights reserved. 71 Treatment of DIC ? ? Correct underlying cause Administer blood and components ? Platelets ? Fresh frozen plasma ? Cryoprecipitate ? Packed RBCs ? Stop abnormal coagulation ? Heparin: controversial when experiencing more hemorrhage than thrombosis Copyright © 2017 Elsevier Inc. All rights reserved. 72 Other Treatments of DIC ? ? SU NSG 430 Cardiac Tamponade Complex Care Nursing Antithrombin III (inhibits thrombin) Epsilon-aminocaproic acid (prevents fibrinolysis) Copyright © 2017 Elsevier Inc. All rights reserved. 73 Nursing Management of DIC ? ? ? ? ? ? Assess and prevent Conduct frequent laboratory analysis Administer blood products Assess circulation Relieve pain Assess for complications: shock, multisystem organ failure, impaired circulation Copyright © 2017 Elsevier Inc. All rights reserved. 74 Chapter 12 Shock, Sepsis, and Multiple Organ Dysfunction Syndrome Copyright © 2017 Elsevier Inc. All rights reserved. Introduction ? Shock is a clinical syndrome ? ? ? ? Life-threatening response to alterations in circulation Inadequate tissue perfusion Imbalance between cellular oxygen supply and demand Impacts all body systems ? Can lead to organ failure and death • Influenced by compensatory mechanisms • Influenced by successful interventions Copyright © 2017 Elsevier Inc. All rights reserved. 2 Review of Anatomy and Physiology ? Cardiovascular system ? Closed system: heart, blood, vascular bed • Vascular bed: arteries, arterioles, capillaries, venules, and veins ? Microcirculatory system ? Portion of the vascular bed between the arterioles and venules. Copyright © 2017 Elsevier Inc. All rights reserved. 3 Normal Anatomy and Physiology (Cont.) Copyright © 2017 Elsevier Inc. All rights reserved. 4 Pathophysiology ? ? Shock begins with cardiovascular system failure Alterations in at least one of four components: ? Blood volume ? Myocardial contractility ? Blood flow ? Vascular resistance Copyright © 2017 Elsevier Inc. All rights reserved. 5 Classification of Shock ? ? ? ? Hypovolemic Cardiogenic Obstructive Distributive (anaphylactic, neurogenic, septic) Copyright © 2013, 2009, 2005, 2001, 1997, 1993 by Saunders, an imprint of Elsevier Inc. 6 Stages of Shock Stage I: Initiation ? ? ? Hypoperfusion: inadequate delivery or extraction of oxygen No obvious clinical signs Early, reversible Copyright © 2017 Elsevier Inc. All rights reserved. 7 Stages of Shock Stage II: Compensatory ? ? Sustained reduction in tissue perfusion Initiation of compensatory mechanisms ? Neural: baroreceptors and chemoreceptors ? Endocrine: ACTH and ADH ? Chemical • Low oxygen tension • Hyperventilation and respiratory alkalosis Copyright © 2017 Elsevier Inc. All rights reserved. 8 Stag … Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

EKU OSH 110 Orientation to Safety Studies Work Related Injuries & Illnesses Worksheet ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON EKU OSH 110 Orientation to Safety Studies Work Related Injuries & Illnesses Worksheet Download the attached document and follow the instructions to complete Assignment 15. Rename the document, replacing. EKU OSH 110 Orientation to Safety Studies Work Related Injuries & Illnesses Worksheet Assignment 14 Work Related Injuries and Illnesses.docx Assignment 14 PowerPoint.pptx attachment_1 attachment_2 OSH 110 Orientation to Safety Studies Assignment 14 – Work Related Injuries & Illnesses Name: ????????????????????????? Date: Directions: Part A. Students for this assignment are required to research the following “occupational losses” in the form of work-related injuries and illnesses. You are to determine and provide the following information based on your research: Identify an occupation in which this injury or illness is found or likely to be found. (Be sure to be specific of the occupation) Identify the specific “hazard” and categorize the hazard (safety or health hazard) Identify how the worker may be exposed/risk to the hazard Determine a type of control, which can be implemented to prevent the injury or illness from occurring. Be sure to categorize the control measure as either an engineering control, administrative controls or PPE (a) Losses (b) Occupation (c) Hazard/Type (d) How Exposed (e)Type of Control (f) Control Measure (Engineering, Administrative or PPE_ 1. Metal Fume Fever 2. Asbestosis 3. Trigger Finger 4. Lead Poisoning 5. Carpal Tunnel 6. Hearing Loss 7. Cancer 8. HIV infection 9. Black Lung 10. Electrocution Part B: Identify a likely workplace injury or illness associated with the job title provided. You will have to examine specific job task or duties associated with each job title to determine the hazards they are exposed to. (a) Losses (b) Occupation (c) Hazard/Type (d) How Exposed (e) Controls 1. Material Handler 2. Concrete Masonry laborer 3. Coal Miner 4. Firearms Instructor 5. Firefighter 6. Welder 7. Garbage man 8. Wastewater Treatment operator 9. Electrician 10. Forklift Driver Definitions/Further instructions: Hazards: A danger or a risk which origins are either of a safety or health generally “Safety hazards” for this assignment are defined as hazards which can cause harm or loss immediately or spontaneously.. Generally cause harm from the outside- in. “Health hazards” for this assignment are defined as hazards, which can cause immediate harm or take long periods of time in which they cause harm or loss. They can be acute or chronic… Affect local effects or harming one organ or they can be systemic causing harm to an entire body system. Generally these hazards cause harm from the inside-out. Exposure or the risk of exposure is related to the how the worker came likely came into contact with the safety or health hazard. What can be done to prevent the worker from coming into contact or becoming exposed to the hazards Engineering Controls are those in which you engineer the hazard from coming into contact with the worker… Example enclosing a worker in booth… Administrative Controls are types of controls in which the worker is given warning or knowledge associated with the hazard or breaking up the workers exposure to the hazard. Examples include warning signs, training or only permitting a worker to be exposed to the hazard for 2 hours in a day. PPE means “personal protective equipment.” Gloves. Examples include: Hard hats…hearing protection.. Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

AAC and Those Who Are Deafblind Discussion ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON AAC and Those Who Are Deafblind Discussion This week you will engage in a discussion from the required webcast and handout on tactile learning strategies for children who are deafblind. From the webcast and handout on tactile learning strategies for children who are deafblind: AAC and Those Who Are Deafblind Discussion Discuss at least one variable / consideration discussed in the webcast that is relevant to individuals who are deafblind as well as those who are not deafblind, but have AAC needs. Discuss one specific / unique strategy for communicating with individuals who are deafblind. As usual, be sure your responses are different from your group members (i.e., you are not commenting on the same points). Reference: Must watch first 3. https://www.perkinselearning.org/videos/webcast/co… http://www.projectsalute.net/Learned/Learnedhtml/T… https://www.unr.edu/ndsip/ 2. This is a discussion between students. Please respond to the discussion. Hi all, (Any)1. One important variable discussed in the webcast that stood out to me is the idea that every child should have someone they trust for trust, support, security, and safety. I think that this can go for everyone, not just children but for adults as well. These traits are very important to a human and to their development. If a child cannot have trust in someone, they may never try new things. If there is no safety, then the boundaries will not be tested. Without support, there will be no courage to try new things. If there is no safety, there will be constant fear. Children who are deaf blind rely largely on these traits because they cannot see or hear anything around them. Children using AAC rely on these traits as well. AAC users face different challenges than those who are deaf blind. AAC needs to trust those professionals around them while using a device. AAC users need support when using a device they may not be adjusting well to. Security is needed so that AAC users communicate with partners, they can be sure they will receive feedback. AAC users need to feel safe in order to communicate with their partners. These traits can go a long way and are extremely universal. 2. One unique way of communicating with those who are deafblind is by using hand over hand guidance. This is done when a communication partner puts their hand over the child’s hand for them to feel an object (Chen & Downing, 2011). This way of communication is nice because it can be done as many times as needed and at any pace as well. It also allows individuals to use their sense of touch to then use their imagination to picture what they are touching. This form of communication gives individuals their own way of imagining and becoming familiar with an object of person. Hand over hand guidance also allows for an individual to feel key aspects and details which then allows them to differ things from one another. When using this strategy, it is important to allow the student to be able to become familiar with the object. The person guiding should not be going too fast or too slow, the opportunity to learn a new object needs to be done at an appropriate speed per the individual. attachment_1 attachment_2 attachment_3 Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Axial Members Beams Frames Excel Project ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON Axial Members Beams Frames Excel Project hi…….. how are you i need you to use mathlab if you need any thing just text me thanks IFS ME 474 BME 488 Axial Members Beams Frames Excel Project attachment_1 ME 474 / BME 488 Homework 6 Due: 03/30/2020 @ 6:00 PM When submitting this homework, include a pdf of your written work as well as any MATLAB (.m) or Excel (.xls, .xlsx) files used to solve the problems. Make sure your work is well documented and easy to follow. 1. A 20-ft-tall post is used to support advertisement signs at various locations along its height, as shown in the figure below. The post is made of structural steel with a modulus of elasticity of E = 29×106 lb/in2. Determine the displacements of the post at the points of load application and the stresses in the post. 2. The beam shown in the figure below is a wide-flange WI6×31 with a cross-sectional area of 9.12 in2 and a depth of 15.88 in. The second moment of area is 375 in4. The beam is subjected to a uniformly distributed load of 1000 lb/ft and a point load of 500 lb. The modulus of elasticity of the beam is E = 29×106 1b/in2. Determine the vertical displacement at node 3 and the rotations at nodes 2 and 3. Also, compute the reaction forces at nodes 1 and 2 and reaction moment at node 1. 3. The lamp frame shown in the figure below has hollow, square cross sections and is made of steel, with E = 29×106 lb/in2. Determine the endpoint deflection of the cross member where the lamp is attached. ???3 ? ??1 ?1 3 ???? = 12 ?? 3 ? ? ??1 3 ?1 ???? = 12 … You must proofread your paper. But do not strictly rely on your computer’s spell-checker and grammar-checker; failure to do so indicates a lack of effort on your part and you can expect your grade to suffer accordingly. Papers with numerous misspelled words and grammatical mistakes will be penalized. Read over your paper – in silence and then aloud – before handing it in and make corrections as necessary. Often it is advantageous to have a friend proofread your paper for obvious errors. Handwritten corrections are preferable to uncorrected mistakes. Use a standard 10 to 12 point (10 to 12 characters per inch) typeface. Smaller or compressed type and papers with small margins or single-spacing are hard to read. It is better to let your essay run over the recommended number of pages than to try to compress it into fewer pages. Likewise, large type, large margins, large indentations, triple-spacing, increased leading (space between lines), increased kerning (space between letters), and any other such attempts at “padding” to increase the length of a paper are unacceptable, wasteful of trees, and will not fool your professor. The paper must be neatly formatted, double-spaced with a one-inch margin on the top, bottom, and sides of each page. When submitting hard copy, be sure to use white paper and print out using dark ink. If it is hard to read your essay, it will also be hard to follow your argument. ADDITIONAL INSTRUCTIONS FOR THE CLASS Discussion Questions (DQ) Initial responses to the DQ should address all components of the questions asked, include a minimum of one scholarly source, and be at least 250 words. Successful responses are substantive (i.e., add something new to the discussion, engage others in the discussion, well-developed idea) and include at least one scholarly source. One or two sentence responses, simple statements of agreement or “good post,” and responses that are off-topic will not count as substantive. Substantive responses should be at least 150 words. I encourage you to incorporate the readings from the week (as applicable) into your responses. Weekly Participation Your initial responses to the mandatory DQ do not count toward participation and are graded separately. In addition to the DQ responses, you must post at least one reply to peers (or me) on three separate days, for a total of three replies. Participation posts do not require a scholarly source/citation (unless you cite someone else’s work). Part of your weekly participation includes viewing the weekly announcement and attesting to watching it in the comments. These announcements are made to ensure you understand everything that is due during the week. APA Format and Writing Quality Familiarize yourself with APA format and practice using it correctly. It is used for most writing assignments for your degree. Visit the Writing Center in the Student Success Center, under the Resources tab in LoudCloud for APA paper templates, citation examples, tips, etc. Points will be deducted for poor use of APA format or absence of APA format (if required). Cite all sources of information! When in doubt, cite the source. Paraphrasing also requires a citation. I highly recommend using the APA Publication Manual, 6th edition. Use of Direct Quotes I discourage overutilization of direct quotes in DQs and assignments at the Masters’ level and deduct points accordingly. As Masters’ level students, it is important that you be able to critically analyze and interpret information from journal articles and other resources. Simply restating someone else’s words does not demonstrate an understanding of the content or critical analysis of the content. It is best to paraphrase content and cite your source. LopesWrite Policy For assignments that need to be submitted to LopesWrite, please be sure you have received your report and Similarity Index (SI) percentage BEFORE you do a “final submit” to me. Once you have received your report, please review it. This report will show you grammatical, punctuation, and spelling errors that can easily be fixed. Take the extra few minutes to review instead of getting counted off for these mistakes. Review your similarities. Did you forget to cite something? Did you not paraphrase well enough? Is your paper made up of someone else’s thoughts more than your own? Visit the Writing Center in the Student Success Center, under the Resources tab in LoudCloud for tips on improving your paper and SI score. Late Policy The university’s policy on late assignments is 10% penalty PER DAY LATE. This also applies to late DQ replies. Please communicate with me if you anticipate having to submit an assignment late. I am happy to be flexible, with advance notice. We may be able to work out an extension based on extenuating circumstances. If you do not communicate with me before submitting an assignment late, the GCU late policy will be in effect. I do not accept assignments that are two or more weeks late unless we have worked out an extension. As per policy, no assignments are accepted after the last day of class. Any assignment submitted after midnight on the last day of class will not be accepted for grading. Communication Communication is so very important. There are multiple ways to communicate with me: Questions to Instructor Forum: This is a great place to ask course content or assignment questions. If you have a question, there is a good chance one of your peers does as well. This is a public forum for the class. Individual Forum: This is a private forum to ask me questions or send me messages. This will be checked at least once every 24 hours. IFS ME 474 BME 488 Axial Members Beams Frames Excel Project Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Training Event Help Prevent Back Injuries ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON Training Event Help Prevent Back Injuries 1.Imagine that you are leading a training event to help prevent back injuries, and you are teaching students the proper way to lift. Describe, in detail, your recommended steps for lifting a box from a tabletop and placing the box on the floor in a way that would not create any pain or ergonomics issue(s). Training Event Help Prevent Back Injuries Your response should be 200 words. 2.Each of us reacts habitually when we see money on the ground; we bend over and pick it up. Describe how you would get employees to avoid improper bending to pick up items from the ground in situations such as this. Use the four Es: empowerment, encouragement, education, and enlightenment. Your response should be 200 words. 3.Imagine that you are leading a training event to help prevent back injuries, and you are teaching students the proper way to lift. Describe, in detail, your recommended steps for lifting a box from a tabletop and placing the box on the floor in a way that would not create any pain or ergonomics issue(s). Your response should be 200 words. You must proofread your paper. But do not strictly rely on your computer’s spell-checker and grammar-checker; failure to do so indicates a lack of effort on your part and you can expect your grade to suffer accordingly. Papers with numerous misspelled words and grammatical mistakes will be penalized. Read over your paper – in silence and then aloud – before handing it in and make corrections as necessary. Often it is advantageous to have a friend proofread your paper for obvious errors. Handwritten corrections are preferable to uncorrected mistakes. Use a standard 10 to 12 point (10 to 12 characters per inch) typeface. Smaller or compressed type and papers with small margins or single-spacing are hard to read. It is better to let your essay run over the recommended number of pages than to try to compress it into fewer pages. Likewise, large type, large margins, large indentations, triple-spacing, increased leading (space between lines), increased kerning (space between letters), and any other such attempts at “padding” to increase the length of a paper are unacceptable, wasteful of trees, and will not fool your professor. The paper must be neatly formatted, double-spaced with a one-inch margin on the top, bottom, and sides of each page. When submitting hard copy, be sure to use white paper and print out using dark ink. If it is hard to read your essay, it will also be hard to follow your argument. ADDITIONAL INSTRUCTIONS FOR THE CLASS Discussion Questions (DQ) Initial responses to the DQ should address all components of the questions asked, include a minimum of one scholarly source, and be at least 250 words. Successful responses are substantive (i.e., add something new to the discussion, engage others in the discussion, well-developed idea) and include at least one scholarly source. One or two sentence responses, simple statements of agreement or “good post,” and responses that are off-topic will not count as substantive. Substantive responses should be at least 150 words. I encourage you to incorporate the readings from the week (as applicable) into your responses. Weekly Participation Your initial responses to the mandatory DQ do not count toward participation and are graded separately. In addition to the DQ responses, you must post at least one reply to peers (or me) on three separate days, for a total of three replies. Participation posts do not require a scholarly source/citation (unless you cite someone else’s work). Part of your weekly participation includes viewing the weekly announcement and attesting to watching it in the comments. These announcements are made to ensure you understand everything that is due during the week. APA Format and Writing Quality Familiarize yourself with APA format and practice using it correctly. It is used for most writing assignments for your degree. Visit the Writing Center in the Student Success Center, under the Resources tab in LoudCloud for APA paper templates, citation examples, tips, etc. Points will be deducted for poor use of APA format or absence of APA format (if required). Cite all sources of information! When in doubt, cite the source. Paraphrasing also requires a citation. I highly recommend using the APA Publication Manual, 6th edition. Use of Direct Quotes I discourage overutilization of direct quotes in DQs and assignments at the Masters’ level and deduct points accordingly. As Masters’ level students, it is important that you be able to critically analyze and interpret information from journal articles and other resources. Simply restating someone else’s words does not demonstrate an understanding of the content or critical analysis of the content. It is best to paraphrase content and cite your source. LopesWrite Policy For assignments that need to be submitted to LopesWrite, please be sure you have received your report and Similarity Index (SI) percentage BEFORE you do a “final submit” to me. Once you have received your report, please review it. This report will show you grammatical, punctuation, and spelling errors that can easily be fixed. Take the extra few minutes to review instead of getting counted off for these mistakes. Review your similarities. Did you forget to cite something? Did you not paraphrase well enough? Is your paper made up of someone else’s thoughts more than your own? Visit the Writing Center in the Student Success Center, under the Resources tab in LoudCloud for tips on improving your paper and SI score. Late Policy The university’s policy on late assignments is 10% penalty PER DAY LATE. This also applies to late DQ replies. Please communicate with me if you anticipate having to submit an assignment late. I am happy to be flexible, with advance notice. We may be able to work out an extension based on extenuating circumstances. If you do not communicate with me before submitting an assignment late, the GCU late policy will be in effect. I do not accept assignments that are two or more weeks late unless we have worked out an extension. As per policy, no assignments are accepted after the last day of class. Any assignment submitted after midnight on the last day of class will not be accepted for grading. Communication Communication is so very important. There are multiple ways to communicate with me: Questions to Instructor Forum: This is a great place to ask course content or assignment questions. If you have a question, there is a good chance one of your peers does as well. This is a public forum for the class. Individual Forum: This is a private forum to ask me questions or send me messages. This will be checked at least once every 24 hours. Training Event Help Prevent Back Injuries Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Compute the net present value of each project Compute the net present value of each project For this assignment, refer to the scenario located in “Problems – Series A” section 10-19A of Ch. 10, “Planning for Capital Investments” of Fundamental Managerial Accounting Concepts . This scenario puts you at task as a Senior Accountant for Donovan Enterprises to identify the preferred method and best investment opportunity for the company. Read the scenario in the textbook and complete the activity below.Problem 10-19A using net present value and internal rate of return to evaluate investment opportunities . ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS Dwight Donovan, the president of Donovan Enterprises, is considering two investment opportunities. Because of limited resources, he will be able to invest in only one of them. Project A is to purchase a machine that will enable factory automation; the machine is expected to have a useful life of four years and no salvage value. Project B supports a training program that will improve the skills of employees operating the current equipment. Initial cash expenditures for project A are $400,000 and for project B are $160,000. The annual expected cash inflows are $126,000 for project A and $52,000 for project B. Both investments are expected to provide cash inflow for the next four years. Donovan Enterprise’s desired rate of return is 8 percent. Required: a. Compute the net present value of each project. Which project should be adopted based on the net present value approach? Round your computations to two decimal points. b. Compute the approximately internal rate of return of each project. Which one should be adopted based on the internal rate of return approach? Round your rates to six decimal points. c. Compare the net present value approach with the internal rate of return approach. Which method is better in the given circumstances? Why? Use Excel®—showing all work and formulas—to compute the following: Compute the net present value of each project.Round your computations to 2 decimal points.Compute the approximate internal rate of return for each project. Round your rates to 6 decimal points Create a PowerPoint® presentation showing the comparison of the net present value approach with the internal rate of return approach calculated above. Complete the following in your presentation: Analyze the results of the net present value calculations and the significance of these results, supported with examples. Determine which project should be adopted based on the net present value approach and provide rationale for your decision. Analyze the results of the internal rate of return calculation and the significance of these results, supported with examples. Determine which project should be adopted based on the internal rate of return approach and provide rationale for your decision. Determine the preferred method in the given circumstances and provide reasoning and details to support the method selected. Synthesize results of analyses and computations to determine the best investment opportunity to recommend to the president of Donovan Enterprises. Cite references to support your assignment. Format your citations according to APA guidelines. Submit the Excel spreadsheet along with the presentation. Resources Center for Writing Excellence Reference and Citation Generator Grammar and Writing Guides 81517 (1) Answer preview to compute the net present value of each project Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Critical appraisal that demonstrates comprehension of two qualitative research studies Critical appraisal that demonstrates comprehension of two qualitative research studies Write a critical appraisal that demonstrates comprehension of two qualitative research studies. Use the ”Research Critique Guidelines – Part 1” document to organize your essay. Successful completion of this assignment requires that you provide rationale, include examples, and reference content from the studies in your responses. ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS Use the practice problem and two qualitative, peer-reviewed research article you identified in the Topic 1 assignment to complete this assignment. In a 1,000–1,250 word essay, summarize two qualitative studies, explain the ways in which the findings might be used in nursing practice, and address ethical considerations associated with the conduct of the study. Prepare this assignment according to the guidelines found in the APA Style Guide, located in the Student Success Center. An abstract is not required. This assignment uses a rubric. Please review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion. You must proofread your paper. But do not strictly rely on your computer’s spell-checker and grammar-checker; failure to do so indicates a lack of effort on your part and you can expect your grade to suffer accordingly. Papers with numerous misspelled words and grammatical mistakes will be penalized. Read over your paper – in silence and then aloud – before handing it in and make corrections as necessary. Often it is advantageous to have a friend proofread your paper for obvious errors. Handwritten corrections are preferable to uncorrected mistakes. Use a standard 10 to 12 point (10 to 12 characters per inch) typeface. Smaller or compressed type and papers with small margins or single-spacing are hard to read. It is better to let your essay run over the recommended number of pages than to try to compress it into fewer pages. Likewise, large type, large margins, large indentations, triple-spacing, increased leading (space between lines), increased kerning (space between letters), and any other such attempts at “padding” to increase the length of a paper are unacceptable, wasteful of trees, and will not fool your professor. The paper must be neatly formatted, double-spaced with a one-inch margin on the top, bottom, and sides of each page. When submitting hard copy, be sure to use white paper and print out using dark ink. If it is hard to read your essay, it will also be hard to follow your argument. Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Discussion: Endogenous Cannabinoid Receptors ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON Discussion: Endogenous Cannabinoid Receptors I just need to answer this question and cite the article. Endogenous cannabinoid receptors are found throughout the brain, and are clustered in specific regions (see Iversen, 2003). Knowing the behavioral and cognitive effects of THC, what can we conclude about how the physiology of the brain (i.e. where receptors are found, and what NTs/drugs bind to them) informs us about effects psychoactive compounds have on the body? Discussion: Endogenous Cannabinoid Receptors attachment_1 DOI: 10.1093/brain/awg143 Advanced Access publication April 8, 2003 Brain (2003), 126, 1252±1270 INVITED REVIEW Cannabis and the brain Leslie Iversen Department of Pharmacology, University of Oxford, Oxford, UK Summary include disruption of psychomotor behaviour, shortterm memory impairment, intoxication, stimulation of appetite, antinociceptive actions (particularly against pain of neuropathic origin) and anti-emetic effects. Although there are signs of mild cognitive impairment in chronic cannabis users there is little evidence that such impairments are irreversible, or that they are accompanied by drug-induced neuropathology. A proportion of regular users of cannabis develop tolerance and dependence on the drug. Some studies have linked chronic use of cannabis with an increased risk of psychiatric illness, but there is little evidence for any causal link. The potential medical applications of cannabis in the treatment of painful muscle spasms and other symptoms of multiple sclerosis are currently being tested in clinical trials. Medicines based on drugs that enhance the function of endocannabinoids may offer novel therapeutic approaches in the future. Keywords: cannabinoid CB1 receptor; D9-tetrahydrocannabinol; rimonabant (SR141716A); anandamide; 2-arachidonylglycerol Abbreviations: 2-AG = 2-arachidonylglycerol; DSI = depolarization-induced suppression of inhibition; FAAH = fatty acid amide hydrolase; Gi/o = G-proteins negatively linked to adenylate cyclase or to inositol phosphates; LTD = long-term depression; LTP = long-term potentiation; mGlu = metabotropic glutamate; NMDA = N-methyl-D-aspartate; THC = D9tetrahydrocannabinol Introduction A large literature exists on the effects of cannabis, with many of the earlier studies conducted in human subjects (Mendelson et al., 1976; Jones, 1978; Hollister, 1986). Unfortunately, much of this research would now be regarded as inadequately controlled and poorly designed. However, research on cannabis has been stimulated in recent years by the recognition that speci®c receptors exist in the brain that Brain 126 ã Guarantors of Brain 2003; all rights reserved recognize cannabinoids, and by the discovery of a series of endogenous cannabinoids that act as ligands for these receptors. As was the case with opiate research in the 1970s, research on a psychoactive drug of plant origin has revealed a hitherto unknown physiological control mechanism. This review will focus mainly on the more recent literature in this ®eld. Downloaded from by guest on June 18, 2015 The active compound in herbal cannabis, D9-tetrahydrocannabinol, exerts all of its known central effects through the CB1 cannabinoid receptor. Research on cannabinoid mechanisms has been facilitated by the availability of selective antagonists acting at CB1 receptors and the generation of CB1 receptor knockout mice. Particularly important classes of neurons that express high levels of CB1 receptors are GABAergic interneurons in hippocampus, amygdala and cerebral cortex, which also contain the neuropeptides cholecystokinin. Activation of CB1 receptors leads to inhibition of the release of amino acid and monoamine neurotransmitters. The lipid derivatives anandamide and 2-arachidonylglycerol act as endogenous ligands for CB1 receptors (endocannabinoids). They may act as retrograde synaptic mediators of the phenomena of depolarizationinduced suppression of inhibition or excitation in hippocampus and cerebellum. Central effects of cannabinoids Correspondence to: Leslie Iversen, Department of Pharmacology, University of Oxford, Mans®eld Road, Oxford OX1 3QT, UK E-mail: [email protected] Cannabis and the brain 1253 Fig. 2 Chemical structure of the CB1 selective antagonist drug rimonabant (SR141716A). Discussion: Endogenous Cannabinoid Receptors Fig. 1 Chemical structures of THC, the synthetic CB1 receptor agonist WIN 55,2122 and the endocannabinoids. Endogenous cannabinoids The cannabinoid system in brain Exogenous cannabinoids and their receptors The principal active component in the complex mixture of cannabinoids present in extracts of the plant Cannabis sativa is D9-tetrahydrocannabinol (THC) (Mechoulam, 1970) (Fig. 1). THC is a sticky resin that is not soluble in water. Smoking remains the most ef®cient means of delivering the drug and experienced users can titrate the dose by adjusting the frequency and depth of inhalation (Iversen, 2000). THC or cannabis extracts can also be taken orally in fat-containing foods or dissolved in a suitable pharmaceutical oil, but absorption is delayed and variable (Iversen, 2000). A series of man-made synthetic cannabinoids, some of which are more potent and more water soluble than THC, is also available (Pertwee, 1999) (Fig. 1). All of these compounds act as agonists at the CB1 cannabinoid receptor (Matsuda et al., 1990), which is the only one known to be expressed in the brain. A second cannabinoid receptor, CB2, is expressed only in peripheral tissues, principally in the immune system (Munro et al., 1993; Felder and Glass, 1998; Pertwee, 1999). THC and Following the discovery of speci®c cannabinoid receptors, a search was made for naturally occurring ligands of these receptors in mammalian tissues. This led to the discovery of a series of arachidonic acid derivatives with potent actions at cannabinoid receptors. These are: anandamide (N-arachidonyl-ethanolamine; Devane et al., 1992), 2-arachidonylglycerol (2-AG; Mechoulam et al., 1995; Sugiura et al., 1995; Stella et al., 1997) and 2-arachidonylglyceryl ether (HanusÏ et al., 2001) (Fig. 1). Of these, anandamide is the ligand that has been most extensively studied so far. The endogenous cannabinoids known as `endocannabinoids’ are present only in small amounts in the brain or other tissues. Like other lipid mediators (e.g. prostaglandins) they appear to be synthesized and released locally on demand (see below). Anandamide and the other endogenous cannabinoids are rapidly inactivated by a combination of a transporter mechanism and by the enzyme fatty acid amide hydrolase (FAAH) (Di Marzo et al., 1994; Piomelli et al., 1998; Giuffrida et al., 2001). Genetically engineered mice lacking FAAH displayed elevated levels of anandamide in brain and were supersensitive to the biological actions of anandamide (Cravatt et al., 2001). The discovery of agents that could interfere with the inactivation of endogenous cannabinoids may provide a novel means of pharmaco- Downloaded from by guest on June 18, 2015 the synthetic cannabinoids also act to some extent as agonists at the CB2 receptor. Both cannabinoid receptors are members of the G-protein coupled class, and their activation is linked to inhibition of adenylate cyclase activity (Howlett et al., 1988). A series of synthetic drugs is also now available that act as speci®c antagonists at CB1 or CB2 receptors (D’Souza and Kosten, 2001). One of these compounds, rimonabant(SR141716A), which acts selectively to block CB1 receptors (Rinaldi-Carmona et al., 1994; Compton et al., 1996), has been widely used in studies of the actions of cannabinoids in the CNS (Fig. 2). 1254 L. Iversen logically modifying cannabinoid function in the brain (Piomelli et al., 2000). Neuroanatomical distribution of CB1 receptors in brain The distribution of cannabinoid receptors was ®rst mapped in rat brain in autoradiographic studies, using the radioligand [H3]CP-55,940, which binds with high af®nity to CB1 sites (Herkenham et al., 1991) (Fig. 3). Discussion: Endogenous Cannabinoid Receptors The validity of using this radioligand was con®rmed by autoradiographic studies in CB1 receptor knockout mice, in which no detectable [H3]CP55,940 binding sites were observed (Zimmer et al., 1999). More recently, antibodies that target the C- or N-terminal regions of the CB1 receptor protein have been used for immunohistochemical mapping studies (Egertova et al., 1998; Pettit et al., 1998; Egertova and Elphick, 2000). Immunohistochemistry provides a superior degree of spatial resolution to autoradiography, but the overall pattern of distribution of CB1 receptors revealed by the two approaches is very similar (Elphick and EgertovaÂ, 2001). The mapping studies in rat brain showed that CB1 receptors are mainly localized to axons and nerve terminals and are largely absent from the neuronal soma or dendrites. The ®nding that cannabinoid receptors are predominantly presynaptic rather than postsynaptic is consistent with the postulated role of cannabinoids in modulating neurotransmitter release (see below). In both animals and man the cerebral cortex, particularly frontal regions, contains high densities of CB1 receptors. There are also very high densities in the basal ganglia and in the cerebellum (Fig. 3). In the limbic forebrain CB1 receptors are found particularly in the hypothalamus and in the anterior cingulate cortex. The hippocampus also contains a high density of CB1 receptors. The relative absence of the cannabinoid receptors from brainstem nuclei may account for the low toxicity of cannabinoids when given in overdose. The regional distribution of the CB1 receptor in brain correlates only poorly with the levels of anandamide and other endocannabinoids in different brain regions (Felder et al., 1996; Bisogno et al., 1999). However, measurements of endocannabinoids have yielded variable results, and a strict correlation would not be expected for ligands that are only produced on demand. There is a better correlation between the regional distribution of CB1 receptors and the enzyme FAAH. FAAH is widely distributed in CNS and other tissues, suggesting that its role is not con®ned to inactivating endogenous cannabinoids. Nevertheless, particularly high levels of FAAH were found in brain regions that are enriched in CB1 receptors, and immunohistochemical staining suggested a complementary relationship between FAAH and CB1 receptors at the synaptic level (Egertova et al., 1998; Elphick and EgertovaÂ, 2001). In cerebellum, hippocampus and neocortex FAAH was expressed at high levels in the somato-dendritic regions of neurons that were postsynaptic to CB1-positive axon terminals. The close and complementary relationship between CB1 receptors and FAAH led to the hypothesis that FAAH may participate in the inactivation of endogenous cannabinoids released locally at synapses Downloaded from by guest on June 18, 2015 Fig. 3 Distribution of cannabinoid CB1 receptors in rat brain revealed by an autoradiograph of the binding of radioactively labeled CP-55940 (a high af®nity agonist ligand) to a sagittal brain section. The brain regions labelled are: Cb = cerebellum; CbN = deep cerebellar nucleus; cc = corpus callosum; EP = entopeduncular nucleus; ® = ®mbria hippocampus; Fr = frontal cortex; FrPaM = frontoparietal cortex motor area; GP = globus pallidus; Hi = hippocampus; IC = inferior colliculus; LP = lateral posterior thalamus; Me = medial amygdaloid nucleus; PO = primary olfactory cortex; PCRt = parvocellular reticular nucleus; SNR = substantia nigra reticulate; Tu = olfactory tubercle; VP = ventroposterior thalamus. Discussion: Endogenous Cannabinoid Receptors Photograph kindly supplied by Dr Miles Herkenham, National Institute of Mental Health, USA. Cannabis and the brain (Elphick and EgertovaÂ, 2001). These authors postulated a retrograde cannabinoid signalling mechanism, whereby endogenous cannabinoids are released in response to synaptic activation, feedback to presynaptic receptors on these axon terminals, and are subsequently inactivated by FAAH after their uptake into the postsynaptic compartment. This hypothesis has been supported independently by neurophysiological ®ndings, as described below. Effects of cannabinoids on synaptic function Inhibition of neurotransmitter release of the duration of presynaptic action potentials as they invade axon terminals. Biosynthesis of endocannabinoids Despite their similar chemical structures, the endocannabinoids are produced through distinct biochemical pathways. The formation of anandamide is thought to result from the hydrolysis of the precursor N-arachidonoyl phophatidylethanolamine, catalysed by the phosphodiesterase enzyme phospholipase D (Di Marzo et al., 1994; Cadas et al., 1997). 2-AG, on the other hand, is produced by cleavage of an inositol-1,2-diacylglycerol, catalysed by phospholipase C. Although both anandamide and 2-AG can activate CB1 receptors, it is not clear whether both function as endocannabinoids, and whether their synthesis and release are independently controlled. The levels of 2-AG found in brain (2±10 nmol/g) are 50±1000 times higher than those of anandamide (10±50 pmol/g). There is some evidence for separate control of their biosynthesis. Stimulation of glutamate release from Schaffer collaterals in rat hippocampal slices increased levels of 2-AG, but not anandamide (Stella et al., 1997). On the other hand, another study using in vivo microdialysis probes showed that local administration of the dopamine D2 receptor agonist quinpirole caused an increased release of anandamide from rat striatum without affecting levels of 2-AG (Giuffrida et al., 1999). Indeed, despite the much higher tissue levels of 2-AG relative to anandamide and the availability of a very sensitive assay, no 2-AG could be detected at all in the striatal dialysate samples. In cultured rat cortical neurons activation of Ca2+ in¯ux by stimulation of glutamate N-methyl-D-aspartate (NMDA) receptors caused an increase in 2-AG formation but not anandamide (Stella and Piomelli, 2001). However, if NMDA activation was combined with a cholinergic agonist (carbachol) the formation of both endocannabinoids was increased. In both cases Ca2+ in¯ux was required for endocannabinoid synthesis. It is clear that much remains to be learned about the relative roles played by the different endocannabinoids. The biosynthesis of the most recently discovered third endocannabinoid, 2-arachidonylglyceryl ether, remains to be characterized. Endogenous cannabinoids act as retrograde signal molecules at synapses Important new insights into the physiological role of cannabinoids has emerged from neurophysiological studies published independently by three different research groups in 2001. A phenomenon known as depolarization-induced suppression of inhibition (DSI) has been known to neurophysiologists for some years (Alger and Pitler, 1995). It is a form of fast retrograde signalling from postsynaptic neurons back to inhibitory cells that innervate them, and is particularly prominent in the hippocampus and cerebellum. Three prop- Downloaded from by guest on June 18, 2015 The presynaptic localization of CB1 receptors suggests a role for cannabinoids in modulating the release of neurotransmitters from axon terminals, and this has been con®rmed by a substantial body of experimental data. Early reports (Gill et al., 1970; Roth, 1978) showed that THC inhibited acetylcholine release from electrically stimulated guinea pig ileum. Similar inhibitory effects of THC and other cannabinoids on the release of a variety of neurotransmitters from CNS neurons have been observed in many subsequent studies (Schlicker and Kathmann, 2001).Discussion: Endogenous Cannabinoid Receptors The neurotransmitters involved include L-glutamate, GABA, noradrenaline, dopamine, 5-HT and acetylcholine. The brain regions most often studied in vitro, usually in tissue slice preparations, have been cerebellum, hippocampus or neocortex. Neurotransmitter release has been studied directly in superfused preparations, and indirectly by measuring postsynaptic currents. Although most of these studies involved rat or mouse brain, a few studies have shown similar results using human brain tissue (Katona et al., 2000; Schlicker and Kathmann, 2001). Because THC is only poorly water soluble, the more soluble synthetic CB1 receptor agonists WIN552123, HU210 or CP55-2940 were used in these in vitro studies. The speci®city of the cannabinoid effects were con®rmed by demonstrating that the inhibitory effects of the agonists were completely blocked by the CB1-selective antagonist rimonabant. The cellular mechanisms involved in the inhibition of neurotransmitter release by cannabinoids remain unclear. Some have suggested that there is a direct inhibitory effect of CB1 receptor activation on N-type Ca2+ currents (Caul®eld and Brown, 1992; MacKie and Hill, 1992). However, the effect appears more likely to involve sites downstream of voltage-dependent Ca2+ channels, since a number of studies have shown that cannabinoids reduce the frequencies of miniature excitatory or inhibitory synaptic currents, which are Ca2+ independent, rather than altering their amplitude, which is Ca2+ sensitive (Schlicker and Kathmann, 2001). Deadwyler et al. (1995) suggested that the inhibitory effect of CB1 receptor activation on adenylate cyclase activity causes a decreased phosphorylation of A-type K+ channels by the cAMP-dependent enzyme protein kinase A. This, in turn, would activate the A-type K+ channels and cause a shortening 1255 1256 L. Iversen occluded by the CB1 receptor agonist WIN55,2122. Kreitzer and Regehr (2001b) went on to show that inhibitory inputs to rat cerebellar Purkinje cells from basket cells and stellate cells were subject to DSI, and that this was also blocked by AM-251 and occluded by WIN55,2122. The DSE phenomenon in the cerebellum is also linked to mGlu receptors. Maejima et al. (2001) reported that mGlu agonists acting on mouse Purkinje cells mimicked DSE, and the effects could be blocked by CB1 antagonists. These ®ndings suggest that endocannabinoids are involved in the rapid modulation of synaptic transmission in CNS by a retrograde signalling system that can in¯uence synapses in a local region of some 40 mm diameter, causing inhibitory effects on both excitatory and inhibitory neurotransmitter release that persist for tens of seconds. This may play an important role in the control of neural circuits, particularly in cerebellum and hippocampus (see below).Discussion: Endogenous Cannabinoid Receptors Exogenously administered THC or other cannabinoids cannot mimic the physiological effects of locally released endocannabinoids. Since they cause long-lasting activation of CB1 receptors in all brain regions, their overall effect is to cause a persistent inhibition of neurotransmitter release from those nerve terminals that express CB1 receptors, and as a consequence they temporarily occlude and prevent the phenomena of DSI and DSE. Effects of cannabinoids on CNS function Psychomotor control CB1 receptors are expressed at particularly high densities in the basal ganglia and cerebellum, so it is not surprising that cannabinoids have complex effects on psychomotor function (reviewed by RodrõÂguez de Fonseca et al., 1998). One of the earliest reports of the effects of cannabis extracts in experimental animals described the awkward swaying and rolling gait caused by the drug in dogs, with periods of intense activity provoked by tactile or auditory stimuli, and followed eventually by catalepsy and sleep (Dixon, 1899). In rodents cannabinoids tend to have a triphasic effect. Thus in rats low doses of THC (0.2 mg/kg) decreased locomotor activity, while higher doses (1±2 mg/kg) stimulated movements, and catalepsy emerged at doses of 2.5 mg/kg (SanÄudo-PenÄa et al., 2000). Similarly in mice, Adams and Martin (1996) described a `popcorn effect’ in animals treated with THC. Groups of mice are sedated by the drug, but will jump in response to auditory or tactile stimuli, as they fall into other animals these in turn jump, resembling corn popping in a popcorn machine. Interestingly, the CB1 receptor antagonist rimonabant stimulated locomotor activity in mice, suggesting that there is tonic activity in the endocannabinoid system that contributes to the control of spontaneous levels of activity (Compton et al., 1996). These effects of cannabinoids may be due, in part, to actions at cerebellar or striatal receptors. Patel and Hillard (2001) used tests of speci®c cerebellar functions to show that Downloaded from by guest on June … Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Conclusion and Additional areas of research ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON Conclusion and Additional areas of research Read the paper and make detailed slides discussing the conclusion as well as the additional areas of research covering the rubric bellow. I will also need speaker notes in the bottom of each slide describing the slide further (Things I would be saying when I present the slide). Conclusion and Additional areas of research Conclusions of Paper: What did the authors conclude? Do you agree with their conclusion? Did they provide sufficient evidence to prove their hypothesis? Additional areas of research related to this topic: What are some other areas of research/research papers that you discovered that are helpful to understand this research (this may also be covered in the background section) What other papers/additional research is being done on this topic? attachment_1 www.nature.com/scientificreports OPEN received: 19 October 2015 accepted: 26 January 2016 Published: 15 February 2016 3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction An Liu1,3,*, Guang-huai Xue2,3,*, Miao Sun4,*, Hui-feng Shao2,3, Chi-yuan Ma1, Qing Gao2,3, Zhong-ru Gou5, Shi-gui Yan1, Yan-ming Liu4 & Yong He2,3 Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screwlike scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe boneligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical. Ever since Charles Hull first proposed the three-dimensional (3D) printing process in 1986, the technology has developed rapidly and well beyond what originally seemed possible1. Nowadays, 3D printing has been utilized successfully in mechanical manufacturing and many areas of scientific research2. Many potential uses for 3D printing have emerged within the medical field, not only as far as tissue and organ regeneration research3 (blood vessels4, ears5, bones6), but also for customized medical devices such as splints and stents that can be printed in small clinics7. There are several factors that limit the use of 3D printers in practice, however; 3D printers necessary for medical applications are specialized or industrial equipment that require unique materials, for example, which drives up production costs and creates a high-level technical demand for skilled operators and specific operational conditions, and the inconvenience of communicating at length between hospitals and factories during the production process delays the length of time between fabrication and application. It was reported that only $11 million was invested in medical applications among the entire 3D printing industry which is worth around $700 million in total8. To allow medical professionals and their patients to benefit from 3D printing technologies, and to increase the market share value of 3D medical printing, it is crucial to develop methods that reduce production costs and increase the flexibility, maneuverability, and practicability of the process. 1 Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Conclusion and Additional areas of research China. 2State Key Laboratory of Fluid Power and Mechatronic Systems, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China. 3Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China. 4Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. 5 Zhejiang-California International Nanosystem Institute, Zhejiang University, Hangzhou 310058, China. *These authors contributed equally to this work. Correspondence and requests for materials should be addressed to S.-g.Y. (email: [email protected]) or Y.-m.L. (email: [email protected]) or Y.H. (email: [email protected]) Scientific Reports | 6:21704 | DOI: 10.1038/srep21704 1 www.nature.com/scientificreports/ Fused deposition modeling (FDM)9, when applied to the 3D printer, creates a desktop 3D printer (D3DP) that can be used at home, in schools, and by small businesses to fabricate customized products cost-effectively. D3DPs cost as little as $500, as opposed to the $15,000–30,000 price range for 3D printers used in academic institutions. If the D3DP can be successfully applied in the medical field, the possibility for cost-effective, personalized devices such as implants or grafts to be fabricated in-clinic is momentous. Doctors and specialists who employ such technology would represent the pioneering edge of the medical field. In a previous study conducted in our laboratory10, we were able to fabricate soft tissue prostheses using a D3DP; the prostheses, which showed smooth surfaces and intricate structures, cost only about $30. The results of this study have considerable implications as far as the future of maxillofacial repair technology. In the present study, we focused on fabricating surgical implants and applying them in operations to demonstrate that a surgeon can indeed customize and fabricate surgical implants his or herself using a D3DP. Our target operation was an anterior cruciate ligament (ACL) reconstruction using a hamstring tendon graft. This operation requires that the tendon graft within the bone tunnel heal appropriately. Tendon-to-bone tunnel healing occurs through new bone ingrowth that initially forms between the tendon and the bone. With the help of new bone mineralization and maturation, the graft’s biomechanical properties progressively increase – tendon graft healing within the bone tunnel thus mainly depends on the osteointegration of the tendon graft within the bone tunnel11. Bioabsorbable interference screws, made with polymers such as polylactic acid (PLA) and polyglycolic acid (PGA), are commonly used to provide a press fit between bone, graft, and screws initially, which then degrade mainly by hydrolysis as bone union gradually progresses12,13. According to clinical trials, PLA and PGA screws have been shown to persist in vivo for up to 5 years and result in complete resorption at 7 to 10 years14,15. The relatively slow degradation rate of bioabsorbable screws does not suit the speed of new bone formation, which leads to malformation of new bone around the tendon graft, where only calcified fibrous or fatty tissue replaces the screw in the bone tunnel15,16. It has been reported that 3D porous structure is a key point to promote bone ingrowth by providing sufficient growth space. Macropores (200–400 ? m)Conclusion and Additional areas of research enhance the migration of osteoblasts and osteoprogenitors into the scaffold and facilitate osteoid formation and mineralization17. Additionally, interconnected micropores (50–100 ? m) can increase vascularization and nutrient diffusion during bone reconstruction18. These structures cannot be well-controlled through conventional methods19,20, but surgeons and specialists can easily and precisely manipulate them using a D3DP. In this study, common PLA filament, the same as that used for bioabsorbable screws, was applied to D3DP manufacturing of a 3D, porous, screw-like scaffold in-clinic. The scaffold not only could fix the tendon graft, but also could provide adequate space for bone ingrowth around the graft. A simple surface modification was made using hydroxyapatite (HA) on the scaffold in order to enhance osteoconductivity and cellular adhesion21, and mesenchymal stem cells (MSCs), known as one of the most optimal cell sources for ACL regeneration due to their high potential for proliferation and collagen production22,23, were seeded onto the scaffold as cell therapy. We hypothesize that the 3D-printed, bioabsorbable screw-like scaffold loaded with MSCs can promote tendon graft healing within the bone tunnel by increasing bone ingrowth. We hope that the results of this study will increase the popularity of 3D-printed surgical devices by proving that they can be customized and fabricated feasibly, economically, and successfully in the clinic. Methods Fabrication and Characterization of PLA Screw-like Scaffold. The PLA screw-like scaffold was designed using Rhinoceros software (ver. 4.0, USA) according to a schematic, actual-size diagram of the implant and tendon graft based on a rabbit ACL reconstruction model (Fig. 1). Its digital dataset was saved as a stereolithography (STL) file. Slice software Slic3r24 was used to generate G code for the D3DP (Dot Go 3D Technology Corporation, Xiangtan, China) from the STL file. Melt PLA filament (Shenzhen Esond Technology Co., Ltd) was extruded through a heated metal nozzle (0.4 mm in diameter, moving horizontally and vertically) at 205 °C and deposited onto a receiving station to form the desired scaffolds. The scaffolds were then observed under a scanning electron microscope (SEM) (S-4800, Hitachi, Japan) to measure macropore sizes. The porosity of the scaffolds was determined using the Archimedes method, and the PLA scaffolds were weighed as dry weight (W1). The scaffolds were then immersed in a beaker of water and held under vacuum to force the liquid into the pores until no bubbles emerged, then re-weighed under water to determine the suspension weight (W2). The scaffolds were then carefully taken out of the beaker and any water on the surface was removed, then they were quickly re-weighed in air to determine the saturated wet weight (W3). The final porosity of the scaffolds was calculated via the following equation: porosity (%) =??(W3 ? W1)/(W3 ? W2) ×??100%. Six specimens were measured in total. HA Synthesis and Characterization. HA powders were synthesized by chemical precipitation using Ca(NO3)2·4 H2O and (NH4)2HPO4 as P and Ca precursors, respectively. Ca(NO3)2·4 H2O (Sigma-Aldrich, Australia) was dissolved in distilled water (0.5 mol/L) and adjusted to pH 10.5 with NH3·H2O. (NH4)2HPO4 (Sigma-Aldrich, USA) was dissolved in distilled water at density of 0.3 mol/L and pH 10.5, then the Ca(NO3)2 solution was added to the (NH4)2HPO4 solution dropwise. After stirring for 12 h, the precipitate was filtered and subsequently washed three times with distilled water followed by three washing steps with ethanol. Conclusion and Additional areas of research The remaining liquid was removed by vacuum filtration, and the precipitate was dried at 80 °C overnight. The resultant powders were calcined at 850 °C for 3 h to obtain HA powders. The calcined HA powders were then ground and sieved through 250 mesh sieves. The crystal morphology of the synthesized HA powder was observed using SEM, and the phase composition of HA was characterized by X-ray diffraction (XRD, Rigaku Co., Japan). Scientific Reports | 6:21704 | DOI: 10.1038/srep21704 2 www.nature.com/scientificreports/ Figure 1. Schematic diagrams of the implant and tendon graft within the bone tunnel in ACL reconstruction. (A) The 3D perspective of the bone tunnel in ACL reconstruction. (B) The transverse section view of the bone tunnel. (G: Graft; S: Screw-like scaffold; BT: Bone tunnel; M: Macropore). Surface Modification for PLA/HA Scaffold. Chitosan (CHI) was dissolved in 2% (v/v) acetic acid to obtain CHI solution (1% (w/v)). Sodium alginate (SA) solution (1% (w/v)) was prepared with distilled water. HA powders were added into the CHI and SA solutions, respectively, on a magnetic stirrer plate for 30 min to obtain 4% (w/w) HA/CHI solution and 4% (w/w) HA/SA solution. Sodium hydroxide (NaOH) solution (0.2% (w/w)) was mixed with equal volume of ethanol to prepare NaOH/ethanol solution. The PLA scaffolds were first dipped in the NaOH/ethanol solution under vacuum for 10 min to modify the scaffolds with stable negative charge, then washed twice with distilled water under vacuum, then freeze-dried for 30 min. Next, the scaffolds were immersed in 4% (w/w) HA/CHI solution to force solution into the pores until no bubbles emerged from the scaffolds (10 min) followed by centrifugation (1000 r/min, 5 min). The scaffolds were dried at room temperature for 20 min, then immersed in 4% HA/SA solution under vacuum. The same procedures were repeated for all samples. The PLA/HA scaffolds were then observed with SEM. Cell Culture In Vitro. MSCs were obtained from bone marrow aspirates of New Zealand Rabbits25. Cells of third passage were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) (Gibco, USA) in an incubator at 37 °C with 5% CO2. Pluronic F-127 was added into complete DMEM to prepare a 30% (w/v) solution at 4 °C. The solution was placed on a magnetic stirrer plate for 24 h to allow complete dissolution, then the solution was filter-sterilized through a 0.22 ? m pore size bottle-top filter and stored at 4 °C until use. After being sterilized with ethylene oxide, the PLA scaffolds and PLA/HA scaffolds were placed into 24-well tissue culture plates (TCPs) and immersed in DMEM with 10% FBS for 2 h, then each was seeded with 1 ×??105 MSCs. An equal number of 1 ×??105 MSCs suspended in Pluronic F-127 solution were seeded on the PLA/HA scaffolds at 4 °C to ensure the hydrogel penetrated the scaffold, then they were moved to the incubator for gelation. Cell Morphology. After 48-hour incubation, samples were washed with phosphate buffer solution (PBS) twice and fixed with 2.5% glutaraldehyde solution for 2 h. The fixed cells were washed with PBS three times and treated with 1% osmium tetroxide for 2 h, then dehydrated in ascending concentrations of ethanol (30, 50, 70, 80, 90, 95, 100 (v/v)) for 5 min, respectively. The samples were then immersed in isoamyl acetate for 20 min, then vacuum-dried at 40 °C for 4 h. Conclusion and Additional areas of research The specimens were coated with gold-palladium and dried, then the MSC morphology of each was observed using SEM. Cell Viability. MSC viabilities were analyzed with Cell Counting Kit-8 (CCK-8, Dojindo, Japan) assays at 1, 4, and 7 days. DMEM (0.5 mL) containing 10% CCK-8 was added into each well. After 120 min, 100 ? L of the abovementioned solution was transferred to a 96-well plate. A microplate reader (Infinite F50, TECAN, Switzerland) was used to measure solution absorbance at 450 nm, and absorbance values were corrected by subtracting the signal of a mixture of 90 ? L DMEM and 10 ? L CCK-8. Five specimens were prepared for each sample. Real-time Polymerase Chain Reaction (PCR) Analysis. Real-time PCR was used to detect the expression of several osteogenetic, differentiation-related marker genes (Col I, OCN, Sp7, and Runx2) at Day 7. Total RNA was extracted using Trizol reagent (Invitrogen) according to the manufacturer’s instructions. NanoDrop 2000c (Thermo Fisher Scientific Inc., USA) was used to determine the total RNA concentration. First-stranded complementary DNAs (cDNAs) were synthesized from 0.5 ? g of the isolated RNA by oligo(deoxythymidine) (oligo (dT)) using the DyNamoTM cDNA Synthesis Kit (Fermentas) and used as templates for real-time Scientific Reports | 6:21704 | DOI: 10.1038/srep21704 3 www.nature.com/scientificreports/ Gene Col I OCN SP7 RUNX2 GADPH Direction Primer sequence (5?–3?) Forward GCG GTG GTT ACG ACT TTG GTT Reverse AGT GAG GAG GGT CTC AAT CTG Forward GGC TCA GCC TTC GTG TCC AA Reverse CCC TGC CCG TCG ATC AGT T Forward GGC ACG AAG AAG CCA TAC TCT GT Reverse GGG AAA AGG CCG GGT AGT CAT Forward CCC AAG CAT TTC ATC CCT CAC T Reverse CAT ACC GAG GGA CAT GCC TGA Forward TCA CCA TCT TCC AGG AGC GA Reverse CAC AAT GCC GAA GTG GTC GT Table 1. The parameters of primers utilized for detecting osteogenetic gene expression. PCR. The PCR was performed on a final volume of 25 ? L containing 1 ? L cDNA, 0.5 ? L of each primer (forward and reverse), 12.5 ? L Power SYBR Master Mix (2× ) (Applied Biosystems, Foster City, CA, USA), and 10.5 ? L dd H2O with the Bio-Rad Real-time PCR System (Bio-Rad, Hercules, CA, USA), using glyceraldehydes -3-phosphatedehydrogenase (GADPH) as the house-keeping gene for normalization. The forward and reverse primer sequences utilized are listed in Table 1. The conditions of real-time PCR were 95 °C for 1 min, followed by 40 cycles at 95 °C for 10 s and 64 °C for 25 s. ® ACL Reconstruction. A total of 36 New Zealand male rabbits weighing 2.5–3.0 kg were utilized in this study according to standard guidelines approved by the Zhejiang University Ethics Committee (ZJU2014-1-05-093). All rabbits were randomly divided into the PLA group (PLA scaffold implantation, n =??12), PLA/HA group (PLA/ HA scaffold implantation, n =??12), or MSCs group (PLA/ HA scaffold loaded MSCs, n =??12). Next, 2 ×??105 of MSCs suspended in Pluronic F-127 solution were loaded on the PLA/HA screw-like scaffolds at 4 °C and cultured in vitro at 37 °C with 5% CO2 over 8 h for gelation and cell adhesion before implantation. The animals were subjected to general anesthesia with phenobarbital (30 mg/kg), followed by bilateral ACL reconstruction. The knee joint was accessed via a medial parapatellar approach through a midline longitudinal incision. After lateral patellar dislocation, the normal ACL was excised at femoral and tibial origins. Femoral and tibial tunnels were created with a 3.0 mm diameter drill-bit based on the footprints of the normal ACL. The long digital extensor tendon (2 mm in diameter and 3 cm in length) was harvested as the tendon graft. Both graft ends were braided with Dexon 3–0 suture and passed through the drilling holes, then graft ends were fixed to the tunnel exits with sutures tied over the neighboring periosteum.Conclusion and Additional areas of research The PLA, PLA/HA, or PLA/HA loaded MSCs screw-like scaffolds were then pressed into the femoral tunnel of each rabbit (Fig. 2). The rabbits were allowed free cage movement after the operation with intramuscular injection of penicillin (800,000 U) once daily for 3 consecutive days. The rabbits were sacrificed at 4 and 12 weeks (12 rabbits total, 6 at each time point) for magnetic resonance imagery (MRI), micro-computed tomography (micro-CT), and histological examinations. MRI Examination. All specimens were examined with a 7.0 T magnetic resonance imaging (MRI) system for small animals (Agilent VnmrJ 3.1, Agilent Technologies, USA) to observe graft and implant status in the transverse, coronal, and sagittal sections. The scan parameters were: number of sections =??20, section thickness =??1.00 mm, TR/TE =??600 ms/8 ms, acquisition matrix =??384 ×??192, and FOV =??40 mm ×??40 mm. Micro-CT Analysis. Micro-CT measurement was performed using a micro-CT system (vivaCT100, Scanco Medical, Switzerland; 80 kVp, 80 mA) for quantifying mineralized tissue ingrowth inside the bone tunnel (n =??5). Each specimen was scanned perpendicular to the long bone axis covering the entrance and exit of the femoral tunnel. To determine the amount and quality of the newly formed mineralized tissue over time, a 3-mm circular region of interest (ROI) inside the bone tunnel was chosen and three-dimensionally reconstructed using MicView software (Fig. 3). Histological Analysis. Samples were prepared for histological analysis, without decalcification, at each respective analysis point. The samples were fixed in 4% paraformaldehyde solution for 7 days, dehydrated with graded alcohols (70, 75, 80, 85, 90, 95, 100%), cleaned with toluene, and embedded in MMA. The embedded specimens were then sectioned in the anterioreposterior direction and parallel to the longitudinal axis of the long bone by saw microtome (SP1600, Leica, Germany). Finally, the sections were grinded and polished to 40–50 mm (Exakt-Micro-Grindin System, Leica, Germany) and stained with Von-Gieson to … Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

Advance Care Planning and Analysis Discussion ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON Advance Care Planning and Analysis Discussion Week 4 Discussion – Due Jun 8, 2019 11:59 PM NSG4068 Trends in Healthcare Policy CP02 Advance Care Planning and Analysis The discussion assignment provides a forum for discussing relevant topics for this week on the basis of the course competencies covered. South University NSG4068 Week 4 Advance Care Planning and Analysis Discussion For this assignment, make sure you post your initial response to the Discussion Area by the due date assigned . Advance Care Planning and Analysis Discussion To support your work, use your course and text readings and also use the South University Online Library . As in all assignments, cite your sources in your work and provide references for the citations in APA format. Start reviewing and responding to the postings of your classmates as early in the week as possible. Respond to at least two of your classmates’ initial postings. Participate in the discussion by asking a question, providing a statement of clarification, providing a point of view with a rationale, challenging an aspect of the discussion, or indicating a relationship between two or more lines of reasoning in the discussion. Cite sources in your responses to other classmates. Complete your participation for this assignment by the end of the week. Read the section titled “Reflective Practice: Pants on Fire” from chapter “Health Policy, Politics, and Professional Ethics” and address the questions below: How do you judge Palin’s quote? [“And who will suffer the most when they ration care? The sick, the elderly, and the disabled, of course. The America I know and love is not one in which my parents or my baby with Down Syndrome will have to stand in front of Obama’s death panel so his bureaucrats can decide, based on a subjective judgment of their level of productivity in society, whether they are worthy of health care. Such a system is downright evil.] Effective strategy to oppose Democrats’ plans for health care reform or unethical scaremongering? Reflect on what informs your judgment: commitment to advance care planning, analysis of facts, and/or political party loyalties? Is it right for nurses to endorse health reform legislation even if the legislation is not perfect? Does this apply to the recently failed American Health Care Act? Week 4 Discussion Discussion Topic Due June 8 at 11:59 PM You must proofread your paper. But do not strictly rely on your computer’s spell-checker and grammar-checker; failure to do so indicates a lack of effort on your part and you can expect your grade to suffer accordingly. Papers with numerous misspelled words and grammatical mistakes will be penalized. Read over your paper – in silence and then aloud – before handing it in and make corrections as necessary. Often it is advantageous to have a friend proofread your paper for obvious errors. Handwritten corrections are preferable to uncorrected mistakes. Use a standard 10 to 12 point (10 to 12 characters per inch) typeface. Smaller or compressed type and papers with small margins or single-spacing are hard to read. It is better to let your essay run over the recommended number of pages than to try to compress it into fewer pages. Likewise, large type, large margins, large indentations, triple-spacing, increased leading (space between lines), increased kerning (space between letters), and any other such attempts at “padding” to increase the length of a paper are unacceptable, wasteful of trees, and will not fool your professor. The paper must be neatly formatted, double-spaced with a one-inch margin on the top, bottom, and sides of each page. When submitting hard copy, be sure to use white paper and print out using dark ink. If it is hard to read your essay, it will also be hard to follow your argument. ADDITIONAL INSTRUCTIONS FOR THE CLASS Discussion Questions (DQ) Initial responses to the DQ should address all components of the questions asked, include a minimum of one scholarly source, and be at least 250 words. Successful responses are substantive (i.e., add something new to the discussion, engage others in the discussion, well-developed idea) and include at least one scholarly source. One or two sentence responses, simple statements of agreement or “good post,” and responses that are off-topic will not count as substantive. Substantive responses should be at least 150 words. I encourage you to incorporate the readings from the week (as applicable) into your responses. Weekly Participation Your initial responses to the mandatory DQ do not count toward participation and are graded separately. In addition to the DQ responses, you must post at least one reply to peers (or me) on three separate days, for a total of three replies. Participation posts do not require a scholarly source/citation (unless you cite someone else’s work). Part of your weekly participation includes viewing the weekly announcement and attesting to watching it in the comments. These announcements are made to ensure you understand everything that is due during the week. APA Format and Writing Quality Familiarize yourself with APA format and practice using it correctly. It is used for most writing assignments for your degree. Visit the Writing Center in the Student Success Center, under the Resources tab in LoudCloud for APA paper templates, citation examples, tips, etc. Points will be deducted for poor use of APA format or absence of APA format (if required). Cite all sources of information! When in doubt, cite the source. Paraphrasing also requires a citation. I highly recommend using the APA Publication Manual, 6th edition. Use of Direct Quotes I discourage overutilization of direct quotes in DQs and assignments at the Masters’ level and deduct points accordingly. As Masters’ level students, it is important that you be able to critically analyze and interpret information from journal articles and other resources. Simply restating someone else’s words does not demonstrate an understanding of the content or critical analysis of the content. It is best to paraphrase content and cite your source. LopesWrite Policy For assignments that need to be submitted to LopesWrite, please be sure you have received your report and Similarity Index (SI) percentage BEFORE you do a “final submit” to me. Once you have received your report, please review it. This report will show you grammatical, punctuation, and spelling errors that can easily be fixed. Take the extra few minutes to review instead of getting counted off for these mistakes. Review your similarities. Did you forget to cite something? Did you not paraphrase well enough? Is your paper made up of someone else’s thoughts more than your own? Visit the Writing Center in the Student Success Center, under the Resources tab in LoudCloud for tips on improving your paper and SI score. Late Policy The university’s policy on late assignments is 10% penalty PER DAY LATE. This also applies to late DQ replies. Please communicate with me if you anticipate having to submit an assignment late. I am happy to be flexible, with advance notice. We may be able to work out an extension based on extenuating circumstances. If you do not communicate with me before submitting an assignment late, the GCU late policy will be in effect. I do not accept assignments that are two or more weeks late unless we have worked out an extension. As per policy, no assignments are accepted after the last day of class. Any assignment submitted after midnight on the last day of class will not be accepted for grading. Communication Communication is so very important. There are multiple ways to communicate with me: Questions to Instructor Forum: This is a great place to ask course content or assignment questions. If you have a question, there is a good chance one of your peers does as well. This is a public forum for the class. Individual Forum: This is a private forum to ask me questions or send me messages. This will be checked at least once every 24 hours. Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10