What Is an Aside in Speech and Writing

In conversation or drama, an aside is a short passage that is spoken in an undertone or addressed to an audience. In written form, an aside may be set off by parentheses. Examples and Observations in Literature As we went in to dinner, Mrs. Ashcroft-Fowler said in a quiet aside to her husband, Has Meadows spoken? He shook his head rather gloomily and answered, No, he has said nothing yet. I saw them exchange a glance of quiet sympathy and mutual help, like people in trouble, who love one another.(Stephen Leacock, ​Are the Rich Happy, Further Foolishness)Every Tuesday I sit down with the speaker and the majority leader to discuss the weeks agenda. Well, discuss is probably the wrong word. They talk while I sit quietly and imagine their lightly salted faces frying in a skillet.(Kevin Spacey as Frank Underwood in an aside to the audience in Chapter 2 of House of Cards, 2013)He made us a list: wed need to get some black sesame seed, a specifically sized white porcelain bowl, a bottle of 100 (or stronger)-proof alcohol, and a large, new, six-inch kitchen knife. (I swear to you Im not making this up. He may have been making it up, but Im telling you exactly what happened.)(Paul Reiser, Fam ilyhood)I admired [C.S. Lewiss] use of parenthetical statements to the reader, where he would just go talk to you. Suddenly the author would address a private aside to you, the reader. It was just you and him. Id think, Oh, my gosh, that is so cool! I want to do that! When I become an author, I want to be able to do things in parentheses.(Neil Gaiman interviewed by Hank Wagner in Prince of Stories: The Many Worlds of Neil Gaiman)Simonides: Traitor, thou liest.Pericles: Traitor!Simonides: Ay, traitor.Pericles: Even in his throat -- unless it be the king --That calls me traitor, I return the lie.Simonides: [Aside] Now, by the gods, I do applaud his courage.(William Shakespeare, Pericles, Act II, scene five)Their marriage was like some horrible play. There were only two characters, but they never addressed each other directly. They did all their speaking in asides to the audience.(Christina Bartolomeo, Cupid and Diana: A Novel)If you are slow at this point, reader, to credit what I tel l you, it will not be remarkable. For I who observed it, can barely allow myself to believe.(Dante, Inferno, Canto 25) A Long Parenthetical Aside To the inevitable question of how a City Night School teacher of English as a second language to HIV-negative Somalian women (they have to be HIV negative or they would never get in; youre forced to take a test, which means that when we all get some perspective around the year 2050 or so, some old Somalian woman is going to sue the city for forced HIV testing and be awarded another bundle. This parenthetical aside has gone on too long, and now I must start again). To the inevitable question of how a Night School teacher of English as a second language affords two downtown rents, Julie said, Well, first of all. I dont live downtown...(Darren Greer, Still Life With June)Â   Punctuating Parenthetical Asides It is possible to enclose an entire, complete sentence with a pair of parentheses, something that cannot be done with a pair of dashes. Such a sentence could stand on its own, for instance in the midst of a paragraph, as a parenthetical aside to the sentence that preceded it. Of course, this parenthetical aside must be so complete that it merits its own sentence, a fairly unusual circumstance. As in: Im on a strictly vegetarian diet. (Well, not strictly, I do eat fish from time to time.) The doctors say it will do wonders for my heart.​ The aside is a complete thought, so it cannot fit in the midst of a sentence. Thus it is given its own sentence, made possible by parentheses.(Noah Lukeman, A Dash of Style: The Art and Mastery of Punctuation)

Resolving Conflict and Disagreements

Conflict tends to be a part of our lives and all too often, is inevitable. Emotions run high when dealing with differences over the best way to deal with differences.  Dealing with conflict and disagreement effectively is half the battle and can create positive outcomes. When conflict and disagreement are handled inappropriately, the outcome can be destructive and are rarely in the best interest of either party. At the same time, all of the parties are often under a lot of pressure.  There are more and more demands put on public education without enough resources, not only monetary but also human (not enough qualified personnel) and often those resources, but physical and the time of the professionals, are stretched thin.  At the same time, with the spread of information, often misinformation, parents sometimes pressure teachers and schools to try therapies or educational strategies that are not based on data and peer-reviewed research.   The Investments of Stakeholders Parents:   Often parents have powerfully conflicting emotions.  On one hand, they are extraordinarily protective while at the same time may feel shame or guilt over their childs disabilities.  Sometimes parents conceal these feelings, even from themselves, by coming on strong.  It is sometimes easy to become defensive, rather than hearing the love, concern and perhaps even guilt that the parents are communicating.  Teachers and Para-professionals:  Good teachers seek to do what is best for their students and take pride in their effectiveness as educators.  Sometimes we become thin-skinned if we think parents or administrators are questioning either our integrity or our commitment to the student.  Relax.  Its easier said than done, but we need to reflect rather than becoming overly reactive.  Administrators:  As well as being accountable to parents and students, administrators are also accountable to superiors who are charged with protecting the interests of the school districts, which may include keeping the costs of providing services down.  That is why they are often called the Local Education Authority (LEA) in our meetings.  Some administrators, unfortunately, dont understand that investing time and attention into their staff will produce better outcomes for everyone.   Strategies for Handling Conflicts and Disagreements Differences must be resolved - it is in the best interest of the child to do so. Remember, sometimes a disagreement occurs as a direct result of a misunderstanding. Always clarify the issues at hand. Parents and school staff members must work closely together to address the issues.Pro-active means of reducing conflict include sharing positive information about the student with parents in an ongoing manner.  It is essential for both parties to realize that the goals for the child are shared goals. Both must agree that the childs interest comes first.Avoid confrontation and deal specifically with solutions to the identified issues and be prepared to offer alternatives.Always deal with the issues rather than the emotions and the people involved. Acknowledging the emotions may be a positive way to diffuse them.  Decide on what you can compromise on, effective resolution usually requires some form of compromise on both parties behalf.Be sure that your expectations are realistic and reasonable.Specify both long term and short term goals and state when a follow-up visit should occur.All parties need to commit to the recommended solutions and agree jointly.All parties must rely on ea ch other, it is, therefore, essential to work out differences and work together regardless of how sensitive the issue is.

Swot Analysis Report - 1228 Words

Since 1994 Hilton acquired all of Bally Entertainment, making the largest gaming company in the world. In 1997 they founded an alliance with Ladbroke Group PLC in (now Hilton Group, owner of Hilton International and the rights to the Hilton name outside the US) to unify the Hilton brand worldwide. With a downturn in the gaming industry translating into sluggish results in Hilton’s gaming segment, the company spun off its gaming interests as Park Place Entertainment. In 1999 Hilton made a massive acquisition with the $3.7 billion purchase of Promus Hotel Corp. The following year Hilton sold its flamingo Casino-Kansas City, a remaining casino property left over from the Park Place spin off, to Isle of Capri Casinos for $33.5 million.†¦show more content†¦These hotels are owned by joint ventures of which the Company owns a minority or non-controlling interest. The Company has a right of first refusal to purchase additional equity interests in certain of these join t ventures. Managing and Franchising Operations: The Company managed 210 hotels, representing 53,776 rooms, which are wholly owned by others. Under the standard management agreement, the Company operates a hotel for the benefits of its owner, which either owner or leases the hotel and the associated personal property. The Company’s management fee is generally based on a percentage of each hotel’s gross revenue plus, in the majority of properties, an incentive fee based on operating performance. The Company franchised 1,612 hotels, representing 214,824 rooms, which are owned and operated by third parties. In general. Franchisees pay the Company an initial fee based on the number of rooms in a franchise hotel and a continuing fee based on a percentage of the hotel’s rooms revenue, which may be up to 5% of rooms revenue depending on the brand. Although HHC does not directly participate in the management of operation of franchise hotels, the Company conducts periodic inspe ctions to ensure that is standards are maintained and render advice with respect of hotel operations. Timeshare Operations: Hilton Grand Vacations Company and its related entities (HGVC), which the Company wholly owns, currently manages 18Show MoreRelatedLufthansa Cargo1170 Words   |  5 PagesBrochure More information from http://www.researchandmarkets.com/reports/1322865/ Lufthansa Cargo AG - Strategic SWOT Analysis Review Description: Lufthansa Cargo AG - Strategic SWOT Analysis Review Summary Lufthansa Cargo AG(Lufthansa Cargo) is a Germany-based company which provides cargo airline, air freight and logistics services. The company is engaaged in transporting cargo and mail from airport-to-airport. Lufthansa Cargo AG has a strategic partnership agreement with Fraport AG. The airlineRead MoreMarketing Planning Of H M986 Words   |  4 PagesFor Organisational Audit The Auditing team monitors HM financial reporting which includes monitoring the effectiveness of HM internal control along with management. The organisational work for HM includes handling auditing issues and financial reports published by HM The Auditing team constantly receives information with supporting documentation for decision-making from HM involving the Managing Directors with the company’s external auditors A further task of the Auditing team is to coverRead MoreRecommending a Marketing Mix for a Product or Service1604 Words   |  7 PagesRecommending a Marketing Mix for a Product or Service Executive Summary This report mainly talked about a product-Pepsi. In this report, the purpose was compared and contrasted which 4Ps is better to the Pepsi and wanted more people to buy it. The thesis was compare and contrasts the Pepsi with the competitor - Coca Cola. 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III - The Report: Vittorio Colao, CEO Of Vodafone. IV - Conclusion V - References â€Æ' Report Vodafone:- Introduction 2. Vodafone is a British multinational telecommunication Company. It is one of the oldest, largestRead MoreSwot Analysis Table. Strengthsweaknesses. †¢Quality Teachers779 Words   |  4 PagesSWOT ANALYSIS TABLE Strengths Weaknesses †¢ Quality teachers and school leaders †¢ High expectations for students †¢ Teacher motivation †¢ Rigorous teaching †¢ Strong relationship with central office †¢ Flexible †¢ Anticipating and preparing for future challenges †¢ Technology †¢ Communication †¢ Parental involvement †¢ Achievement gaps among student sub-groups. †¢ Lack of instructional programs beyond the academic opportunities for non†college bound students †¢ Reading and math scores needs improvement Opportunities

Nothing to Envy Book Review Essay - 3019 Words

Nothing to Envy 2/15/11 Nothing to Envy by Barbara Demick follows the lives of six North Koreans who have experienced a great deal of hardship and turmoil living under one of the most notorious communist regimes. Throughout the years these North Koreans lived through the death of their great Kim Il-Sung, the rise to power of his successor Kim Jong-Il, and the horrific famine that has left many in despair. Although North Korea is constantly in the news globally it is surprising to realize little is known about the country itself. Communist dictatorship has shut out the North part of the Korean peninsula from the outside world and has ruled with an iron fist. In the years following WWII Kim Il-Sung and†¦show more content†¦The family was considered to be part of the lower class system because Tae-woo is of South Korean origin. After he fought in the war he was taken as a POW in what was now part of North Korea and had to assimilate in the communist country. This meant he was sent to work in the mines and would never be able to achieve any higher ranking. This unfortunately was also the case for anyone related to Tae-woo, especially his children. No matter how hard they would study and work, they were to meet the same disappointment their father had faced. â€Å"Your song-bun, as the rating was called, took into account the backgrounds of your parents, grandparents, and even second cousins â€Å"(26). Even ordinary citizens were subjected to invasive screening in order to rank their political trustworthiness. Mi-ran began an innocent relationship with a young man named Jun-sang, who was a few years older than her. Although, Jun-sang came from a good family and was in turn in a higher class, he was intrigued by Mi-ran. They would often walk in the dark of the night, since there was rarely electricity, they were able to do so inconspicuously. She worked hard for her education and was even accepted into a teaching school. She grew tired of the small emaciated children she w ould see everyday. Children would many times come to school without any food and would ultimately stop coming to class. She did not like to think of reasons why they would not be in classShow MoreRelatedNothing From The Korean War On North Korea1399 Words   |  6 Pages Book Review Nothing to Envy: Ordinary lives in North Korea The novel,Nothing to Envy: Ordinary lives in North Korea, tells the stories of six North Korean citizens from Chongjin, third largest city in Democratic People s Republic of Korea. After the Korean War in the 60th, the aid from Communist China and Soviet Union caused industrial growth in North Korea. During this time the daughter of a South Korean Prisoner of War described the hardships she faces as a citizen with tainted blood. TheRead MoreSelf-Determination in Memoirs of a Geisha Essay1344 Words   |  6 PagesSelf-Determination in The Memoirs of a Geisha Memoirs of a Geisha tells the story of a young girl, Chiyo, who transcends her fishing-village roots to become one of Japans most appreciated geishas. Its a story which brings much life into the characters of the book, using many different climaxes as well as conflicts to show the many different relationship of the characters. Chiyo goes through many hardships throughout the reading, but once finally accepting her fate, she is finally determined to become the successfulRead MoreEssay on Changing Conceptions About What Emotion is939 Words   |  4 Pagestheir theories. Aristotle, who lived in the 4th century BC (384ï ½Å¾322), might be called the first cognitive theorist of emotion in western culture. 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At the age of 12 she moved to her mothers birth place, Milledgeville where most of her experiences came from and whereRead MorePsychoanalytic Ideas And Shakespeare By Inge Wise And Maggie Mills1420 Words   |  6 Pagesis on the book Psychoanalytic Ideas and Shakespeare, edited by Inge Wise and Maggie Mills, Published by Karnac Books , London , 2006 ; research and descriptions by numerous authors who wrote on the writing works of Shakespeare, Freud’s work on the psychological works on Shakespeare in general are used throughout the book . The authors focus on psychopathic fiction characters in six plays Hamlet, Macbeth, twilight nights, King Lear, and the Tempest. The book when you read the reviews and the inductionRead MoreNegative Consumer Behavior What is negative consumer behavior and what are the characteristics of a bad customer? 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Business Analysis Business Analytics Essay - 1990 Words

Business Analytics is focused on the latest business intelligence tools, technology and trends for business executives who plan, build, and use business intelligence products and solutions. Today great business intelligence and analytic technologies are allowing big companies to go big, go fast, go deep, go cheap and go mobile with business data. Business Analytics is used to analyze large amounts of data by applying statistical tools and techniques in order to generate business insights. The key to this ability is this company’s closed loop of testing, learning, and acting on new opportunities. In this company, Analytics has become such a focus that all analytical people were recently combined into one organizational unit. Thus the extensive use of analytical and business performance has transformed their ability to compete on analytics into a key point of differentiation and lasting competitive advantage. This company had to come up with viability of potential customers in the market, product research, and marketing campaigns and lead generation. All the activities expected of Siemens Healthcare company were attained through the help of analytics. Analysis I had interned in other companies in the past, but none the companies had an elaborate analytical driven marketing campaigns that were result oriented. The very concept of market analytics was new to me. The process enabled the project managers to evaluate the success of the marketing implementation through theShow MoreRelatedBusiness Analysis : Business Analytics Essay944 Words   |  4 PagesBusiness Analytics Business Analytics, is a system that use various techniques and processes to gather information to used be used to make business decisions. The data is used to answer a question. Often this is used in marketing. It helps to take away some of the â€Å"guess work† out of who market will target. This process has been credited with increasing the ability of organizations to be more competitive. Just as important as collecting data is the ability to interpret and apply the data. EssentialRead MoreBusiness Analysis : Business Analytics828 Words   |  4 PagesAbout Business Analytics Business Analytics is a comprehensive method used by businesses deploying sophisticated tools to access past, vast and complex information and then use the acquired data and information to better analyse the organisation and equip its managers with the ability to make a well informed business decision. (http://sydney.edu.au/business/business_analytics Name: Business Analytics Website Name: University of Sydney Year 2015) The Discipline of Business Analytics comprises of aRead MoreBusiness Analysis : Business Intelligence And Analytics1545 Words   |  7 PagesToday’s business environment is increasingly complex and dynamic and organizations must adapt to these changes in order to remain competitive. As a result, organizations must continually realign their operations to meet these business environment pressures and challenges by being as responsive as possible to both their customers and competitors. One such tool that organizations and businesses can enlist in order to build stronger capabilities, improve performance, undertake better decision makingRead MoreAnalysis Of Tencent : A Chinese Investment Company Established By Huateng Ma And Zhidong Zhang1743 Words   |  7 PagesInternet service users in China. The position of Tencent to competing on analytics is to use analytics to ensure the leader position above Chinese Internet companies. Also, it actually has the ability to compete with other companies on analytics. As one of biggest company in the world, Tencent has the great ability to get the data through their social media platforms. Business has different degrees including reporting and analytics. By the data they got, Tencent not only can get what is happening withRead MoreThe Association For Manufacturing Technology1728 Words   |  7 Pagesof our members’ businesses. As that active partner, AMT facilitates networking, collaboration, technology awareness, business opportunities, and productivity solutions.†[1] One of the main areas AMT invests a considerable amount of time and money towards satisfying its mission, is by leveraging business intelligence for internal operational improvement in addition to offering business intelligence products and services. Creating Competitive Advantage Within the Four Pillars Over the course of its entireRead MoreThe Year I Won Chess Nationals817 Words   |  4 Pageshelped me make the right moves. Years later, working at a management consulting startup as a business analyst, I helped clients, ranging fledgling startups to industry leaders, make well-informed decisions by providing them with data-backed business intelligence. Today, with over three years’ experience in Management and IT consulting I feel prepared to make the most out of a Master’s program in business analytics that would help me realize the power that data and the value that could be extracted fromRead MoreBrief Overview of Business Intelligence and How Walmart Uses It858 Words   |  4 PagesBrief Overview of Business Intelligence and How Walmart Uses It Walmart is the biggest retailer in the world and handles more than one million customer transactions every hour and generates more than 2.5 petabytes of data storage (Venkatraman amp; Brooks, 2012). To put this into perspective, this data is equivalent to 167 times the number of books in America’s Library of Congress (Venkatraman amp; Brooks, 2012). So how can Wal-Mart use this massive amount of data and what useful informationRead MoreHow Organizations Are Competing On Analytics Essay1785 Words   |  8 PagesOrganizations are competing on analytics not just because they can- business today is awash in data and data crunchers- but also because they should. At a time when firms in many industries offer similar products and services, and use comparable technologies, businesses are among the last remaining points of differentiation. And analytics competitors wring every last drop of value from those processes. So, like other companies, they know what products their customers want, the prices they are willingRead MoreBusiness Analysis : Large Amounts Of Data Essay2189 Words   |  9 PagesBusiness analysis is a significant aspect of any business and company. This is mainly because change is the only constant thing that needs to be constantly dealt with. Change can happen in both your target market and in the industry your business or company belongs to, and for your business to survive and succeed despite these changes, proper business analysis must be conducted at the right time. In such a cutthroat business environment, business analysis is essential in order to maintain competitivenessRead MoreSample Resume : Business Information1244 Words   |  5 PagesUniversity. With the use of business information resources, the information revolution is here - It creates a competitive advantage by providing companies with new ways to outperform their competitors. Knowledge is power and business information companies provide that. The process of involving in t he consolidation, analysis and communication of business information to assist the business decision makings captivates me. Globalization is one of the toughest challenges faced by the business today. The problems

Human Resource Management & Leadership-Free-Samples for Students

Questions: 1 Describe how this Initiative would Impact the Induction Program for new frontline Managers joining Ambulance Service NSW. 2 The focus of this Program has been on Managers. What learning and development now needs to be undertaken for the following positions to further support the change in focus for the Organisation? Answers: 1.This initiative would impact the induction program for the new frontline manages. The new things to be incorporated are: The frontline managers should be engaged early in the learning culture Personal analysis- In order to determine the importance of the Ambulance Management Qualification and its relevance it is required to undertake a personal analysis Evaluation- to determine the effectiveness, the frontline managers must be tested before and after the initiative being taken Performance analysis-the results of performance after the initiative should be analysed to identify the areas of improvement. It may include modifying the 12 day programme (O'Meara 2015) 2.Learning and development needs that are to be undertaken for- Frontline operational staff and Customer service staff- microanalysis and personal analysis of these staff is required because they do not participate in AMQ. Instead, they also manage staff Moreover, the macro analysis of the organisation has already been conducted but the task analysis was not conducted. Further, based on this analysis, there is need of development of tailored LD. It may include online learning to increase opportunities, leadership training, executive development and cross cultural training (Francis and Mazany 2013). References Francis, S.D. and Mazany, P.C., 2013. Developing elements of a learning organization in a metropolitan ambulance service: strategy, team development and continuous improvement.Health manpower management. O'Meara, P., 2015. Searching for paramedic academics: vital for our future, but nowhere to be seen!.Australasian Journal of Paramedicine,4(4).

Clinicopathological Correlates of Adrenal †Free Samples to Students

Question: Discuss about the Clinicopathological Correlates of Adrenal. Answer: Introduction: Elevated levels of cortisol hormone are mainly responsible for the occurrence of Cushing syndrome. Cortisol is mainly produced by adrenal glands in the body. Cortisol performs important functions in the body like regulation of blood pressure and normal functioning of cardiovascular system. Cortisol is also helpful in responding to stress and metabolizing carbohydrates, proteins and fats in the usable energy. However, elevated levels of cortisol, disrupt these physiological processes and lead to development of Cushing syndrome. Cortisol levels in MV might increase due to high levels of stress, malnutrition, depression and high levels of emotional stress. Cortisol levels in a person can also increase due to athletic training, alcoholism and panic disorders. High doses of anti-inflammatory medications like corticosteroids might increase cortisol levels. Pituitary gland releases more adrenocorticotropic (ACTH) hormone in pituitary gland tumor. This increase in the adrenocorticotroic horm one is known as Cushings disease. Adrenal gland abnormality or tumor might cuase Cushings syndrome. Even though70 80 % cases of the Cushing's syndrome occur due to excessive secretion of ACTH from the pituitary adenomas, it is evident that only 10 15 % pituitary adenomas secret excessive ACTH. Even though approximately 10 % cases of the Cushing's syndrome occur due to excessive secretion of cortisol from the adrenal adenomas, it is evident that only 6 % adrenal adenomas secret excessive cortisol. However, exact aetiology of excessive secretion of ACTH from pituitary adenomas and cortisol secretion from adrenal adenomas has not been well established. Genetic studies established that mutation in the ubiquitin-specific protease 8 is responsible for Cushing's disease 1,2. Difference between Cushings syndrome and Cushings disease: Tumor in the adrenal gland produces more amount of cortisol. This leads to the development of Cushings syndrome. Cushings syndrome can also be developed due to tumor in the pituitary gland. Cushings syndrome is the group of symptoms in which cortisol levels remains elevated for the longer duration. Tumor in the pituitary gland produces more amount of ACTH. This ACTH stimulates more secretion of cortisol from the adrenal gland. This type of Cushings syndrome is called as Cushings disease. Tumors produced by ACTH can be produced anywhere in the body and these are termed as ectopic tumors. Long term steroid administration is one of the causes of Cushings syndrome. Cushings disease may occur due to the endogenous factors like self-overproduction of cortisol by the body. Endogenous over-production of cortisol may occur due to pituitary tumor (Cushings disease), adrenal tumor and ectopic tumors3. Hypothalamus is the part of brain below which pituitary gland is present. Corticotropin-releasing hormone (CRH) is secreted by paraventricular nucleus (PVN) of the hypothalamus. CRH stimulates pituitary gland to secret ACTH. ACTH gets transported through blood and as result adrenal gland gets stimulated to secret cortisol. Zona fasciculata is the region of cortex of adrenal gland which is responsible for the secretion of cortisol. Corticosteroid hormones are under the control of hypothalamus-pituitary-adrenal axis. Corticosteroids exhibit most prominent metabolic activity during the postprandial period. During this period, these hormones behave as contra-insular hormones. Hence, it provides substrates for oxidative metabolism and stimulate lipolysis and proteolysis. This results in the release of fatty acids and amino acids which induce glucose production by stimulating gluconeogenesis and inhibiting glycogen synthesis. Elevated levels of cortisol are responsible for the negative fee dback which is responsible for the reduced secretion of ACTH. Pathophysiology: In all types of etiologies of Cushing syndrome, there are raised levels of cortisol. Cortisol secreting adenoma in the cortex of adrenal gland occurs in Cushings syndrome. This adenoma of cortex of adrenal gland might be of primary hypercortisolism or hypercorticism types. Cushings syndrome due to elevated levels of ACTH is known as ectopic Cushing syndrome. Patients with severe hypercortisolism are associated with the phenotypes like glucose intolerance, dyslipidaemia, metabolic bone disease, and abnormal weight gain. On the other hand patients with mild or moderate hypercortisolism are rarely associated with glucose intolerance, dyslipidaemia, metabolic bone disease, and abnormal weight gain. Hence, it would be difficult to differentiate these patients from other patients with metabolic syndrome. There is presentation of striae, supraclavicular fat pads, and proximal muscle weakness in patients with increased hypercortisolism6. Elevated levels of corticosteroids results in the augm ented production of glucose at the level of liver and skeletal muscle. In liver corticosteroids increase levels of glucose by stimulating gluconeogenesis and inhibiting insulin sensitivity. Corticosteroids stimulate gluconeogenesis by acting on different genes responsible for glucose metabolism. Corticosteroids reduce insulin sensitivity by exerting antagonistic effect on metabolic action of insulin which is most important hormone required for suppression of glucose production7,8. Corticosteroids decrease expression and phosphorylation of insulin receptor substrate (IRS)-1, phosphatidylinositol-3kinase (PI3K) and protein kinase B (PKB/AKT). As a result, there is decrease in migration of glucose transporter GLUT4 to the cell surface which results in the reduction of glucose uptake. It also leads to decrease of glycogen synthase kinase (GSK)-3 phosphorylation and results in the decrease of glycogen synthesis. In skeletal muscles, corticosteroids increase insulin resistance which results in the decreased glucose uptake and prevention of glycogen synthesis. Corticosteroids exhibit effect on insulin resistance by directly acting on the insulin receptor or alteration in the insulin function by altering lipid and protein metabolism9,10. Corticosteroids also play prominent role in the regulating adipose tissue differentiation, distribution and metabolism. Corticosteroids can stimulate differentiation of pre-adipocytes in adipocytes. Increased adipocytes are associated with raised body fat mass. Corticosteroid specifically act on visceral fat and not on the peripheral fat. Hence, corticosteroids are associated with central obesity in Cushings syndrome. Corticosteroids also play role in the release of hormone like adipokine which is responsible for the development of insulin resistance. Co-occurrence of insulin resistance and increased visceral fat can lead to the development of metabolic syndrome which is associated with impairment in the glucose metabolism. Metabolic syndrome comprises of visceral obesity, diabetes mellitus, and dyslipidemia. Effect of corticosteroids on the pancreatic beta cells result in the decreased insulin secretion. Corticosteroids exhibit effect on insulin secretion in dose dependent and time dependent manner. Corticosteroid exhibit effect on different steps of insulin secretion like glucose uptake, glucose utilization and calcium fluxes and exocytosis of granules containing insulin. Glucose transporter GLUT2 and glucokinase expression gets reduced due to corticosteroids11,12. Corticosteroids can change AMP-activated protein kinase (AMPK) activity in tissue specific manner. Suppression of AMPK is proportional to hypercortisolism. Due to tissue specific activities, AMPK increases appetite, visceral obesity and dyslipidemia. Upon activation, AMPK plays key role in glycolysis and fatty acid synthesis which produces ATP. Due to hormone-sensitive lipase (HSL), there is increased level of lipids form adipose tissue which lead to development of adipocytes. 11 - hydroxysteroid dehydrogenase type 1 (11 H SD1) is responsible for the activation of cortisol from the inactive cortisone. 11 H SD1 overexpressed in mature adipocytes in conditions like hepatic steatosis and there is increased levels of cholesterol and triglycerides. 11 H SD1 is also associated with insulin resistance. Cardiovascular complications associated with corticosteroids include systemic arterial hypertension, atherosclerosis, and thromboembolism. It has been established that elevated levels of corticosteroid can lead to the increase in renin-angiotensin system, stimulated sympathetic nervous system and endothelin system. It also leads to reduced nitric oxide (NO) synthesis and kallikrein-kinin system. Patients of Cushings syndrome are associated with irreversible arterial stiffness. Endothelin, homocysteine, vascular endothelial factor, adrenomedulin, and cell adhesion molecules are the markers of endothelial dysfunction and are responsible for vascular endothelial and smooth muscle proliferation and fibrosis around vessels and consequently development of atherosclerosis plaques. In subclinical Cushings syndrome both systolic and diastolic hypertension can occur. Blood pressure can elevate in patients with Cushings syndrome due to ACTH stimulated cortisol level15,16. Corticosteroids also p roduces immunosuppression and neuropsychiatric complications. Ectopic ACTH production lead to Cushings syndrome and neurocognitive impairment. Neuropsychiatric disorders associated with Cushings syndrome are major depression, mania, anxiety, and cognitive impairment17. Bone complications associated with corticosteroids include osteoporosis and osteoarthritis. Osteoporosis may occur in patients with Cushings syndrome due to increased bone reabsorption, decreased bone formation, reduced intestinal calcium absorption and increased urinary calcium excretion18. Molecular Pathology: Adrenocortical carcinomas are associated with clinical hypercortisolism and androgen overproduction. Elevated levels of urinary metabolites of androgens or glucocorticoid precursors are evident in the adrenocortical carcinomas. It reflects reduced activity of steroidogenic enzymes. Bilateral macronodular adrenal hyperplasia (BMAH) is seldom connected with MEN1, familial adenomatous polyposis, and fumarate hydratase gene mutations. Bilateral adrenal hyperplasias are presented as in the form of nodule diameter greater than 1 cm (macronodular) or less than 1 cm (micronodular). Patients with Cushings syndrome possesses ARMC5 gene mutations and associated with subclinical BMAH. In addition to the ARMC5 gene mutation, there is occurrence of mutations in histone H3 lysine 79 methyltransferase gene (DOTL1), in a histone deacetylase gene (HDAC9), or in a prune homologue 2 gene (PRUNE2) in BMAH19,20. Molecular genetic abnormalities are helpful in the identifying causes of the Cushings syndrome. Glucocorticoid receptor gene mutation, dysfunction of proteins related to glucocorticoid-receptor function (Brg1 and HDAC2), and TP53-inactivating defects are responsible for the occurrence of Cushings syndrome. Overexpression of testicular orphan receptor 4 (TR4),30 a nuclear receptor with unknown ligand, the pituitary transforming gene (PTTG),31 and epidermal growth factor receptor are responsible for occurrence of Cushings syndrome. Overexpression of these genes are useful in identifying causal relationship and establishing therapeutic roles. Somatic mutations in the ubiquitin speci?c peptidase 8 gene (USP8) established role of epidermal growth factor receptor in Cushings syndrome. USP8 inactivation produces augmented epidermal growth factor receptor deubiquitination which leads to impairment in its down regulation and increased growth factor signalling and pro-opiomelanocortin (POMC) a nd ACTH synthesis. Mutations in the cAMP-dependent or -catenin signalling pathways are expresses in the adrenal adenomas. Mutations of GNAS (encoding Gs, which activates adenylate cyclase) are reported in cortisol secreting adenomas and -catenin (CTNNB1) mutations in cortisol-secreting adenomas. Protein kinase A (PRKACA) mutations are reported in adenomas of Cushings syndrome. Phosphodiesterase 11A (PDE11A) or phosphodiesterase 8B (PDE8B) genetic variants are responsible for adrenal adenomas21. Most of the clinical features of Cushings syndrome like body weight gain and blood pressure are common. Hence, it would be difficult to make exact diagnosis of Cushings syndrome. Hence, laboratory tests need to be performed for the diagnosis of Cushings syndrome. These tests would also be helpful in identifying Cushing disease which mainly occurs due to tumor of pituitary gland. Dexamethasone suppression test and 24-hour urinary and salivary measurement for cortisol are useful for the confirmation of Cushings syndrome. Dexamethasone suppression test involves frequent administration of dexamethasone and continuous monitoring of cortisol and ACTH levels. In this test, if body is monitoring cortisol, there would be decrease in the cortisol level. However, in cases of Cushings syndrome, there would be increase in the cortisol level. This test is not always useful because other illness or condition may produce high level of cortisol. This condition is called as pseudo-Cushings states. Doc tors need to treat pseudo-Cushings states like depression. Post treatment, if there is no reduction in cortisol along with other physical worsening, Cushings syndrome would be confirmed. ACTH measurement in the blood can be useful in differentiating Cushings syndrome and Cushings disease. Blood ACTH levels would be less in cases of Cushings syndrome, however it would be normal or higher in cases of Cushings disease. This is because, blood ACTH levels would be less in patients with adrenal origin Cushings syndrome as compared to the other origin of Cushings syndrome. ACTH producing tumor from the pituitary origin can be differentiated from the other parts of origin by using inferior petrosal sinus sampling, or IPSS. In this test, small plastic tube need to be inserted in the right and left veins in the groin and attach them to the veins near the pituitary gland. Blood should be collected form these veins and other locations far from the pituitary. During this procedure, medications which increase ACTH levels from the pituitary need to be injected. ACTH levels produced near pituitary and far from the pituitary need to be measured to assess tumors produced by pituitary origin. Inferior petrosal sinus sampling (IPSS) is more reliable as compared to the dexamethasone suppression test. Magnetic resonance imaging (MRI) can also be used as a diagnostic tool for Cushings syndrome. In this test, contrast is useful for showing up tumor in the MRI scan. Identification of the definitive tumor along with positive dexamethasone suppression test would be useful in diagnosis of Cushings disease. In such cases, there is no requirement of IPSS test. In few healthy people, there may be abnormal area on the pituitary, which might resemble tumor in MRI, hence abnormality doesnt reflect occurrence of Cushings disease. In few cases, tumor may be too small to detect using MRI. Hence, absence of tumor should not exclude Cushings syndrome. Sodium and potassium levels can be increased in patients with Cushings syndrome, hence assessment of electrolyte balance can be used as a diagnostic tool23. Treatment and management: Main aim of the treatment of Cushings syndrome should be reduction in the level of cortisol. Treatment of Cushings syndrome may vary based on the cause of the disease. Corticosteroid medication use should be reduced. Dose of the corticosteroid should be reduced. However, reduced dose of corticosteroid should be useful in the management of chronic inflammatory disease. Non-corticosteroids drugs can be administered along with corticosteroids to reduce dose of corticosteroids. Use of corticosteroids should not be stopped abruptly because it may lead to decrease in cortisol levels. In patients with existence of tumor, surgery should be performed to remove tumor. Pituitary tumors can be removed by performing surgery through nose and neurosurgeon can perform this surgery. Adrenal gland tumors can be removed by standard surgical procedure and using minimally invasive surgical technique. After the completion of the surgery, cortisol replacement medications should be provided to the patients to maintain normal levels of cortisol. Cortisol replacement medications usually takes long duration to maintain normal level of cortisol. Radiation therapy should be provided to the patients, in whom surgeon cant remove tumor completely. Hence, in such cases radiation therapy should be used as an adjuvant therapy along with surgery. Radiation therapy should be used in patients in whom surgery can not be performed. Radiation should be given in little doses for a duration of 6 weeks. Stereotactic radiosurgery, which is also called as Gamma Knife surgery can also be used, in which large single dose of radiation should be given to tumor part with minimal exposure to the surrounding area. Medications to control cortisol levels should be administered to patients, whom are very sick and surgery can not be performed in such patients24. Ketoconazole, mitotane and metyrapone can be used to reduce excessive production of cortisol from the adrenal gland. It is evident that, Ketoconazole can reduce plasma cortisone, however it can not reduce plasma ACTH. Metyrapone exhibits its action by inhibiting 11-hydroxylase. Due to use of metyrapone, there may be increase in ACTH levels relative to the decrease in the cortisol levels. This may result in the stimulation of the adrenal androgen and increased mineralocorticoid production. Mifepristone is useful in the Cushings syndrome patients with diabetes and glucose intolerance. Mitotane exhibits its action by inhibiting 11-hydroxylase, 18-hydroxylase, 3-hydroxy-lase, hydroxysteroid dehydrogenase, and several cholesterol side chain cleavage enzymes. Mitotane exhibits adrenolytic action by binding its metabolite to the macromolecules in adrenal cortical cell mitochondria. This results in the cell destruction and cellular necrosis. Mifepristone does not reduce cortisol level; howev er it blocks action of cortisol on tissues. Pasireotide is useful in the Cushings disease because it reduces the ACTH secretion from pituitary tumor. This medication should be administered twice daily, if surgery can not be performed or in cases of unsuccessful surgery. If none of the treatment works, bilateral adrenalectomy should be performed. In bilateral adrenalectomy, there would be surgical removal of adrenal gland. This surgical intervention is useful in reducing excess levels of cortisol, however such patients require life-long cortisol replacement medications. Newer compounds like CDK2/cyclin inhibitor R-roscovitin (targeting PTTG overexpression) or ge?tinib, the epidermal growth factor receptor-tyrosine kinase inhibitor are responsible for the inhibition of corticotroph tumour growth. Hence, these compounds are helpful in the alleviate clinical and biochemical features of Cushings syndrome. Ge?tinib exhibits effect in Cushings syndrome by decreasing ACTH secretion in USP8-mutated human corticotroph cells26. Patients with Cushings syndrome should take care of their general health. They should take healthy diet and exercise on regular basis. High impact or heavy weight exercise should be avoided by patients with Cushings syndrome because bones might weaken in these patients. More amount of calcium and vitamin D should be administered to strengthen the bones. Patients with Cushings syndrome should quit smoking and avoid consumption of large quantity alcohol. Nurse should advise MV to follow-up regular basis. MV should inform doctor about adverse effects of medications. Nurse should advise MV to keep adequate supply of corticosteroids to avoid shortage. MV and her family members should be aware of evaluating and measuring blood pressure, blood glucose and body weight. Safe environment should be provided to MV because there is possibility of fall due to weak bones. Fall prevention strategies should be provided to MV. MV should wear identification mark for Cushings syndrome, hence other docto rs can identify her as patient. Nurse should encourage MV to verbalize feelings and concerns. MV and family members should adapt to the emotional instability and should cope with mood swings, irritability, and depression. Assurance should be given to MV that, physical changes occurred due to Cushings syndrome can be disappeared if cause of the disease treated. Weight gain and edema can be managed by consuming low carbohydrate and low sodium diet. Conclusion: Excessive exposure to glucorticoids results in mortality and morbidity due to Cushing's syndrome. Genetic and molecular studies established that primary adrenal lesions and ACTH secretion are responsible for the excessive secretion of cortisol. Biochemical and imaging diagnostic studies proved useful in differentiating Cushing's syndrome from Cushing's disease. Radiotherapy, drug therapy and surgical treatment improved management of patients with Cushing's syndrome. Management goals for the patients with Cushing's syndrome should be normal functioning of the hypothalamic-pituitary-adrenal axis, normal functioning of the pituitary gland, and evading of tumour recurrence. References: Duan K, Gomez Hernandez K, Mete O. 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