Leadership In The Small Business

Leadership In The Small Business Leadership is one of the important factors for the survival and success of entrepreneurial ventures. During the second half of the 20th century, there were a lot of literatures about leadership emanating from the United States. However, these researches mainly focused on the leadership in large companies and organizations. How relevant is the picture for small and medium business? Does the experience or lessons of large companies and organizations on management adapt to the small and medium business? These questions have attracted more attentions due to the development of the small and medium business. The definition of the small business varies in different countries and even in different industries. But the small business holds an important position for the development of domestic economy and even the global economy. Therefore, it is essential for scholars on management to study the leadership in the small business. The purpose of this essay is to analyze the importance of leadership in the small business in order to provide some suggestions for the small business on leadership. There are six parts in this essay. The first part is a brief introduction consisting of the writing significance, the writing purpose and the structure of this essay. The second part of this essay will introduce the leadership and its functions. The essay will introduce the small business and its features in the third part. The main part of this essay is the fourth part, where the importance of leadership in the small business will be analyzed, including the leadership in small business and the significance of leadership in the small business. And the fifth part will provide some recommendations to leaders in small business for bringing a success to their own companies in the future. And a conclusion will be made in the end. 2. Leadership and Its Functions This essay will represent some relevant knowledge about leadership and its function in this part. 2.1 The definition of Leadership Leadership is one of the most important factors for the development of each company and organization. Lots of researchers on entrepreneurship use the terms management and leadership interchangeably. However, the leaders and managers are not necessarily the same (Johnson, 2013). And according to Johnson (2013), the main distinction between leaders and managers are that the leaders have some followers they can inspire to action, but the managers have some resources that they can allocate. Therefore, the leadership can be regarded as a process by which the leaders take some measures to influence the thoughts, attitudes and behaviors of others (Mills, 2005). 2.2 The Types of leadership style Different types of leadership styles exist in the work environments. And each leadership style has the advantages and disadvantages. And the culture and goals of an organization are the two important factors to determine which leadership style is appropriate for the company or organization best (Johnson, 2013). In the following, this essay will introduce the leadership styles in a vague and general way. The leadership styles include the laissez-faire leadership style, the autocratic leadership style, the participative leadership style, the transactional leadership style, the transformational leadership style, etc (Goleman, 2000). The laissez-faire leaders often allow their employees to work by themselves. And sometimes the managers do not have enough control over their work and their people (Taleghani, Salmani and Taatian, 2010). The laissez-faire leaders will give complete freedom to their employees to do the work. However, in the autocratic leadership style, the leaders have complete power over their employees and the employees have few opportunities to make suggestions (Travis, 2013). In the transactional leadership, the employees will follow their leaders when their leaders distribute tasks to them, and therefore, the transactional leadership focuses on the short-term tasks (Taleghani, Salmani and Taatian, 2010). Whats more, a transformational leader pays more attention to the employees higher needs, such as fulfillment or justice (Travis, 2013). 2.3 The functions Significance of leadership Since leadership plays an important role on the success of companies and organizations, the functions cannot be belittled. The leadership functions are related with the functions of leaders management. The leaders have to set the goals for companies, motivate and inspire their subordinates, make plans for companies for more profits, and this essay will analyze the functions of leadership from these perspectives. 2.3.1 To develop company culture One of the functions of leadership is to create and develop company culture. The employees may perform as a team or perform as individuals. If the companys tasks need cooperation between employees, the leaders should implement some measures and adopt relevant policies to make employees to cooperate with each other, under which circumstance, the cooperation will become one key aspect of company culture. 2.3.2 To ensure the effectiveness of group-effort By management, the leaders should delegate the authority to take measures to make employees to contribute the maximum energy and time to jobs and the achievement of objectives of the companies (HubPages, 2013). Meanwhile, by management, the leaders can ensure the availability of resources and make sure that the resources can be used to the largest extent. 2.3.3 To make plans for the companies The leaders and employees need to aware of the schedule and their own responsibilities to complete the achievement, and then the leaders make plans for the company to ensure that the company can gain more achievement. 3. Small Business and Its features This essay has introduced the definition and functions of leadership in the second part. Simultaneously, the previous studies on leadership mainly focus on the large enterprises. Therefore, it is very important for researchers to analyze the leadership in the small business. Before this, this essay will mainly introduce the small business and its features in a vague and general way. 3.1 The definition of small business In accordance with the United States Small Business Administration Office of Advocacy, more than 99.5% of all U.S. firms are small business (Cooper, 2013). Although the definition varies from industry to industry and is different in different countries, the small business refers to that the firms are with less than 500 employees in general issued by the United States Small Business Administration Office of Advocacy (Cooper, 2013). In Australia, the small businesses always refer to the companies with less than 100 employees (Gray, Densten Sarros, 2003). 3.2 The history of small business It is reasonable to gain the conclusion that the small business holds an important position for the development of gross economy from the statistics issued by the United States Small Business Administration Office of Advocacy. And since the definition of small business varies from country to country, and therefore, the history of small business is also different in different countries. For example, the origin of small business can date back to the 17th century in the USA (U.S. Department of State, 2013). And in China, the origin of small business can date back to the 14th-15th century. In one word, the small business has a long history. 3.3 What are the features of small business? In order to analyze the importance of leadership in the business small business, the researchers should make acquaintance with the features of small business. Firstly, generally, the business owners always are the leaders of the companies or organizations (Vitez, 2013). The business owners have to make plans and set goals for the companies and organizations (Vitez, 2013). Secondly, due to its size and investment capitals, the small business always have limited resources and low-end technology, so it is difficult for the small business to compete with large enterprises and even the medium business. According to Vitez (2013), the operational management is one the most important parts for the small business management and due to the size, the small businesses are easier to operate. 3.4 The current issues on management faced by small business Small businesses always are confronted with lots of problems related to their size and limited investment technology. This essay will mainly analyze the current issues on management faced by small businesses. Firstly, because the small business owners must be the leaders of companies or organizations, the business owners have to pay more attention to the needs of their company on talents, the establishments of companies goals and other works, and due to the limitation of energy, the management of small businesses may be into chaos. Secondly, because of the limited capitals, it is difficult for small business to adopt the newest technology, so they may adopt lower-end management technology. The above-mentioned contents also can illustrate the necessity to update the leadership in the small businesses. 4. The Importance of Leadership in the Small Business This essay has introduced the functions of leadership and the features and the current management issues of small business. In this part, this essay will analyze the importance of leadership in the small business. And at first, this essay will represent the leadership in the small business, where the features of leadership in the small businesses compared with big and medium size enterprises. 4.1 Leadership in Small Business Due to its size of small business, the owners of the small business must be the leaders of the companies or organizations and the small business is easier to operate. There are some distinctive features of the leadership in small business. Firstly, the owners of the small business always provide the mission, values and goals for the small business (Vitez, 2013). And the owners should run the company and lead other employees to achieve the goals of company. Therefore, the leadership in small business demands the owners of small business to work through employees, not around them (Vitez, 2013). Secondly, the owners of small business also should attach importance on the human resource needs of their own companies or organizations. The recruitment of employees holds a key position for the development and expansion of every company and organization. Therefore, the leadership in the small business also requires the owners of the small business to lead the employees. Different from the human resource management, the owner of the small business should directly understand the current job market and the salary standard for different job positions (Dalglish, 2003). Meanwhile, the owner also should train new employees directly (Dalglish, 2003). Thirdly, the owners of the small business often are the leaders, and therefore, there are few other leaders in the small business. As a result, unlike the leaders in the large companies or organizations, the leaders in the small business should make decisions on the development and expansion on their own (Dalglish, 2003). Whats more, unlike th e large companies or organizations, the owners of the small business should pay attention to the cash flow, paying bills, collecting money from customers. Simultaneously, the owners of the small business should make decision in accordance with the accounting information. All in all, the owners of the small business are also the leaders in the small business. Unlike the leaders of the large companies and organizations, the leaders in the small business should make themselves acquaintance with business knowledge in various fields. 4.2 Significance of leadership in the Small Business It is reasonable to gain the conclusion that the leadership in the small business is very important and significant from the analysis in the prior parts. In this part, this essay will mainly analyze the significance of leadership in the small business from some perspectives. 4.2.1 To Help the Small Business to Win the Competition in the Market When researchers analyze the development and survival of the small business, they often attach importance on the entrepreneurial activity as a strategy to offset economic deterioration brought about by globalization. Under the circumstance of globalization, the small businesses are in an increasingly competitive market (Bolden and Terry, 2000). For example, in the study made by Centre for Leadership Studies, all the interviewed small businesses held the opinion that when they operate in the global market, they must gain competitive threats in every direction (2000). However, good leadership can help the small business to win the competition in the market because they the good leadership can make appropriate strategies to develop and attract more talents to work for them. On the contrary, if the leaders in the small businesses make inappropriate or wrong strategies to develop their business, they may fail the competition in the market and even go bankruptcy (Ingram, 2013). For example , the Apple Inc was a small business, and even just a workshop at the beginning and now has become a well-known high-tech company due to the management of Jobs Stevens. In one word, the leadership can enhance the small businesses to win the competition in the market. 4.2.2 To Manage Changes Because continuous organizational change is essential to guarantee the development and survival of the small businesses (Bolden and Terry, 2000), if there is no change happening to the small businesses, they may go backwards. Simultaneously, the organizational culture of change can be considered as one of the most important factors to the development and survival of the small businesses (Abbas and Asghar, 2010). As a result, the main task for the leaders is to develop an organizational culture of change within the organization. Whats more, if the leaders do not have the ability to develop the culture of change within the organizations and companies, the small businesses cannot adapt to the changeable environment. Due to the development of the globalization, there are more changes happening to the market for the small businesses, for example, the introduction of technologies, the competition from the international companies and the increase of comprehensive talents, etc. Therefore, th e leadership is very important for the small businesses to manage changes within the organizations and outside the organizations. 4.2.3 To Overcome the Current Restriction, Barriers and Weaknesses According to the study made by the Centre for Leadership Studies (2000), the increasing level of legislation and regulation are the main barriers to growth and competitiveness by the leaders in the small businesses, especially the leaders in the manufacturing industry (p.14). Due to the increase of the small businesses in the market, the governments issued some policies and regulations to specify the development of the small businesses, which can be regarded as one of the main current restrictions. Meanwhile, due to its size and scale, there are some their own defects for the small businesses. For example, the location of the small businesses may be more distant from the markets compared to the large companies or organizations, and the small businesses cannot attract more talents like the large enterprises because the small businesses may have better reputations. Therefore, the leaders in the small businesses should take some measures to overcome the current restrictions, barriers an d weaknesses. 4.2.4 To Deal with the Potential Threats and Challenges There is a wide agreement that the small businesses are confronted with some potential threats and challenges, such as that it is difficult for the small businesses to acquire more advanced technologies and more qualified staffs to work for them (Chen, 2006). Meanwhile, because the small businesses may not have better reputations and cannot provide higher salaries to the employees, the small businesses can not retain existing employees (Bolden and Terry, 2000). Meanwhile, the financial factor is also one of the main threats and challenges for the small businesses due to the shortage of cash flow and the threats of bad debtors (Gartenstein, 2013). Whats more, due to the limitation of capitals and staffs, the small businesses may have no money and energy to spend on innovation, which may cause them to fail the competition in the market. As a result, one of the main tasks for the leaders in the small businesses is to deal with the potential threats and challenges. Thus, the good entrepreneurial activities can help the small businesses to transfer the potential challenges as the strengths for the small businesses. 4.2.5 To Strengthen Company Advantages Although there are some limitations and challenges of the small businesses, the small businesses also have some advantages, such as that the small businesses are easier to operate (Vitez, 2013). Moreover, the owners of the small businesses attach importance on the relationships between customers and make every effort to understand the supply and demands in the market. The other perceived strengths of the small businesses include that the small businesses is flexible to response the change in the market and have the ability to make their own decisions. Whats more, the staffs in the small businesses can interact with the senior directors and managers directly (Bolden and Terry, 2000). Simultaneously, all the employees in the small businesses know one another, which makes it easier to cooperate with each other. All of the above-mentioned contents are the advantages of the small businesses, and therefore, the good entrepreneurial activities can strengthen the company advantages. 4.2.6 To make correct development strategies and the ways forward Nearly all the companies and organizations should make development strategies and plans aiming at company growth. And most of the companies always achieve the growth of companies through building the company and increasing the profitability (Williams, 2013). As a result, the companies should implement some measures to build the company and increase the profitability. Under this circumstance, the leaders in the small businesses should make correct development strategies and the ways forward. However, some small companies do not have any correct development strategies. For example, in the study made by the Centre for Leadership Studies (2000), among the 12 interviewed companies, the leaders in the company 9 stated that this company did not have a documented strategy although they would like to become the most profitable company in the UK. Therefore, if the company wants to grow, it should maintain correct development strategies. On the contrary, the company 2 took a conscious decision on the commercial side and then gained more markets in the competition from other small businesses (Bolden and Terry, 2000). This essay has introduced that there are some challenges faced by the small businesses in the part 4.2.4. Some small businesses make strategies to deal with the challenges, such as that a number of companies make every effort to keep up-to-date technology (Taleghani, Salmani and Taatian, 2010). For example, the famous high-tech company in the USA, Apple Inc, was a small company at the beginning and now its products have been used all of the world due to the correct development strategies made by Jobs Stevens. Therefore, the leadership can enhance the small business to own correct development strategies and ways forward. 4.2.7 To make appropriate HRM policies to attract more talents Almost all the companies considered that the staff as one of the most important resource although the small business generally employ less than a hundred people (BusinessBlogs, 2010). The number of employees in the small businesses is not insignificant but the appropriate human resources management policies and activities can help in streamlining the function of human resource of the small businesses (BusinessBlogs, 2010). Human resource can be the vital assets of each company. Therefore, human resource management can benefit every small business. Generally speaking, a company in the small business mainly consists of less than 1000 employees, and the operation of the small business should obey the rules and regulations established by the authorities. The appropriate human resource management policies may grant equal rights to employees (Buzzle, 2013). Simultaneously, the appropriate human resource management policies also can help in recruitment and motivation of best talents in the industry (Buzzle, 2013). Whats more, the appropriate human resource management policies can act as a guide for the small businesses to establish professional relationships with employees (Buzzle, 2013). On the contrary, the inappropriate human resource management policies may make employees disappointed. For example, a Chinese small company, Ganzhou JB Magneto-Electricity Limited Liability Company has attached importance on the establishment of human resource management policies, for example, the leaders of this company adopts the differentiation salary incentive mechanism to attract more talents (Yang, 2008). Therefore, the leadership is very important because the leaders can make appropriate HRM policies to attract more talents and employees. 5. Recommendations to leaders in the Small Business The prior part of this essay has introduced the significance of the leadership in the small businesses, and therefore it is essential for the leaders to improve the management strategies. Under this circumstance, in this part, this essay will provide some recommendations to leaders in the small businesses. 5.1 To Communicate with Employees The leaders in the small businesses should communicate with employees in order to implement leadership. The leaders should communicate exactly what they are doing and what they will do in the future (Wictor, 2012). The leaders can take email and written announcement to notice the employees. Meanwhile, the leaders in the small business can prepare and hold some meetings to make clear agenda items and clear next steps to employees. For example, the Zappos Company always provides open letters to staffs. Whats more, the leaders should explain to staff about companys tasks and business and the people should not be managed without notice. 5.2 To Believe in the Employees However, before communicating with employees, the leaders in the small businesses should believe in the employees because the employees in the small business should be noticed about the goals of companies. Whats more, if the leaders believe in the employees, the employees will have the opinions that they are serving for themselves. If the leaders believe in the employees, the employees will actively understand and fulfill the specific roles of their own (Smith, 2013). 5.3 To Promote Innovation During the current society, the technology is very important for the development and survival of the small businesses, and therefore, the leaders in the small businesses should promote innovation. Firstly, the leaders in the small businesses should hire people smarter than themselves (Smith, 2013). Secondly, the leaders should spend more time, energy and money promoting innovation. For example, the leaders can learn about the advanced technologies from large enterprises and even go aboard to introduce higher technologies into their own companies and organizations. 5.4 To Try to Predict the Obstacles Nowadays, due to the development of the small businesses and the appearance of more small businesses, some authorities have issued some regulations and laws to slow the development of the small businesses. Meanwhile, the small businesses have some limitations and deficiencies, and therefore, the small businesses are confronted with some challenges and threats. Under this circumstance, the leaders should try to predict the obstacles and then to deal with these threats and challenges. 5.5 To Make Plans The leaders should make plans through taking time for a regular evaluation and analyzing the general and exact situation inside and outside the small businesses. The leaders should be good in crises so that they should not sit around to let crises develop (Dowell, 2013). The leaders should involve identifying potential problems and solving them before the crises develop further and deep (McQuerrey, 2013). Meanwhile, the good leaders should analyze the plans and adapt the plans to new circumstances and opportunities (Dowell, 2013). 6. Conclusion The small businesses have different definitions in different countries and industries but in general, the small businesses have less than 500 employees in the USA. The small business has a long history and plays an important role in the development of domestic and international economy. However, the small business has some deficiencies and due to its size and investment capitals, the small business always have limited resources and low-end technology, so it is difficult for the small business to compete with large enterprises and even the medium business. And leadership is one of the most important factors in the survival and success of entrepreneurial ventures. Thus, if the small business wants to achieve development, the leaders should pay more attention to the establish leadership and take more and better entrepreneurial activities because the leadership can enhance the small companies and organizations to win the competition in the market, to overcome the deficiencies, to strengthen the advantages and even help small businesses to make correct strategies. In conclusion, the leaders in the small business should believe in the employees and communicate with them in order to establish leadership in the small businesses.

Why the Korean War Broke Out

Why did the Korean War break out? Reasons as to why war broke out in Korea can be debated due to the fact that a number of factors contributed towards the war. The viewpoint of North Korea starting the war can be seen as Kim ill sung had the intention of reuniting Korea under communism, however there was hostility within South Korea as Syngman Rhee also aimed to reunite Korea under his nationalist views. The two superpowers of the time can be seen as responsible for the outbreak of war because the Korean War can be viewed as a product of the cold war as the USSR backed the north and the USA helped fight with the south.The view of war breaking out as a result internal conflict within Korea can be seen due to both Kim’s and Rhee’s intent on reuniting Korea under their leadership. North Korea’s aggression towards starting the war is due to the fact that Kim aimed on bringing communism to the south and unite the whole of Korea; Kim’s intent on starting war can be seen in the fact that he had multiple visits to Stalin in order to receive both permission and support for invading the south.Kim was able to persuade Stalin to let him invade by stating there would be no US intervention and that he would have control over the South within a few weeks. North Korea’s actions can also be seen as to why war broke out because they did pass the 38th parallel and invade the south, therefore acting as the aggressor as they had had military equipment supplied by the USSR with an army 135,000 men who believed in what they were fighting for as supposed to South Korea’s unprepared smaller army made up of conscripted men.Regardless of the fact that the north was first to invade the south, blame can still be put on Rhee for the outbreak of war. This is due to the fact that South Korea did launch small scale attacks on the north prior to the invasion and this can be seen as a form of instigation for war. The outbreak of war can also be seen as t he result of internal Korean conflict as Rhee had the same intentions as Kim to reunite Korea by invading past the 38th parallel, only Kim was able to do it first as he had soviet support making him the dominate power whereas Rhee had no US support at the start of the North’s invasion.The war between North and south Korea was regarded as a civil war by the British yet when we look closer into why the war broke out we can see that the superpowers were behind it and that the Korean civil war can be seen as a product of the cold war occurring between the USA and USSR at the time. The USSR can be seen to have responsibility for the outbreak of war as it can be argued that Kim would have not invaded the south without Stalin’s support and permission because without Stalin’s military support Kim would not have been powerful enough to achieve his goal of gaining total control of Korea within a few weeks after his invasion.The USSR can also accept responsibility for the war because of fact that Stalin aimed to spread his communist sphere of influence across the world. Stalin had initially rejected Kim’s request of invading the south but in 1950 he granted Kim support and permission to invade, this was most likely due to the fact that communism was established in china at the time giving him incentive to spread his communist support throughout Asia and also he had successfully detonated the atom bomb giving him more reason to believe that the US would not repeat their use of the atom bomb on Stalin out of fear of retaliation.China’s contribution towards the outbreak war is slim as their only initial contribution to the start of the war was to allow for soviet supplies to pass through china and reach the North Koreans. The involvement of the USA can be seen as the reason why the conflict within Korea transformed from a civil war into a fully recognised war. US aims during the cold war was to contain the spread of communism so that the à ¢â‚¬Å"domino theory† would not occur therefore when they were alerted that the North Koreans invaded the south they went to the United Nations in order to get involved in the war.Other reasons for US involvement include the fact that elections were coming up and Truman believed that taking action in Korea would boost his support. Although the US originally intended to help prevent the north spreading communism to the south McArthur found that he was having great success in fighting the north Korans within South Korea gave him reason to pass the 38th parallel and attempt to take completely remove communism from Korea.The US doing this created outbreak of war in Korea as china decided to get involved out of fear of the US approaching the Yalu River, therefore Turing a civil war into the Korean War Overall the outbreak of war can be blamed all factors that contributed the war. The war breakout can be seen as the result of aggression with Korea with both Kim and Rhee launching sma ll scale attack on each other and sharing the intent of uniting Korea however the superpowers are responsible for the actual outbreak of the Koran war.This is because both sides of Korea would not have been strong enough to start a war without the influence of the superpowers. The USSR gave permission and supplies to Kim allowing him to invade the south and America got involved in Korea creating a war as it caused a form of retaliation from the south that would have lost against a soviet fueled invasion from the north. Therefore the Korean War was a product of the cold war between America and the USSR.

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The CDC consists of multiple component agencies. The CDC is mostly responsible for: investigating factors that contribute to the communicable diseases, monitoring of the occurrence of the communicable diseases, developing standards of practice and policies on disease control. The mission of the CDC is supporting communities and protecting US citizens in regards to health, safety and security by collecting and circulating health information, as well as responding to health threats, both internal and external.Show MoreRelatedRegulatory Agency Paper 4301485 Words   |  6 Pagesï » ¿Regulatory Agency Paper HCS/430 April 20, 2015, 2015 Katrina Sullivan Regulatory Agency Paper Option 1: Health Care Segment When people think of health care, they often think up images from their own experiences in doctors offices, clinics, and hospitals. 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Walt Disney Company’s Yen Financing Case Essay - 4601 Words

Introduction: The Walt Disney Company is the largest media conglomerate in the world and is headquartered in Burbank, California, USA. It was established by Walt and Roy Disney in 1923. Since its inception, Disney has grown vastly so that operational areas now include theme parks, motion pictures, television dramas and consumer products. In 1955, the most charming place in the world was ‘Disneyland’ was open for the public. The idea was to create a magical place for the whole family. Ever since then, Disneyland theme parks have been growing and today Walt Disney Company owns 14 theme parks in the world. In Film Industry, Disney mainly focused on children; however the films produced by Disney under touchstone label were focused†¦show more content†¦And the ratio of debt to total capitalization jumped from 20% to 43%. Japanese Royalties Situation With the opening of Tokyo Disneyland in April 1983 and the inflow of yen royalty receipts, the Walt Disney want to increase the assets and decrease debt, they realized they had an opportunity to use the yen royalties from Japan to pay down some of their debt: * In 1984 the average exchange rate is 347.30 JPY/US$ * The royalties of Disneyland Tokyo of JPY 8 billion was equivalent to US $ 33,712,600 * This represents 11.58% (=33,712,600 / 291,033,000) of 1984 operating income before corporate expenses, a percentage which is more common to grow, since Disney itself will probably not grow as rapidly as its JPY royalties * In Figure 5, only 21.47% of all debts has a maturity greater than 2 years * The JPY has also depreciated to disrupt Disney’s financial plan for its large, long-term construction, expansion, production, and development. * Disney transferred Yen to USD from the 2nd quarter of 1984 through the first quarter of 1985, because the JPY recei pts are a huge amount of money. * However, it has appreciated in the quarter since then. Issues: TheShow MoreRelatedThe Walt Disney Companys Yen Financing, Harvard Case Study1352 Words   |  6 Pagesthat it becomes more expensive to buy  ¥ and more expensive to buy the foreign import. Risk can work both ways: if the ex-rate is 125 ¥ / $ (dollar appreciates, Yen depreciates) in 6 months, the cost is only $800. In this case, the dollar got stronger, so it became cheaper to buy Yen, and the foreign product (priced in a fixed amount of Yen) became cheaper. Ex-rate volatility (currency risk) means the cost of parts could range between $800-1250 over the next 6 months for the U.S. manufacturer. ImagineRead MoreWalt disney companys yen financing1838 Words   |  8 PagesCASE STUDY THE WALT DISNEY COMPANYS YEN FINANCING Alexandra Molnà ¡r Laure Vigneron Manuel Aguilee Pimprapai Lertamornkitti Pranav Goyal EXECUTIVE SUMMARY Walt Disney, an American leisure and entertainment company, receives royalty payment from Tokyo Disneyland every year. The royalties were denominated in yen and were constantly growing and becoming significant for the company (8 billion Yen in 1984, with 10-20% projected growth). However, the depreciation of the yen against the dollar couldRead MoreWalt Disney Case2290 Words   |  10 PagesThe Walt Disney Company’s Yen Financing International Financial Economics Universiteit van Amsterdam Question 1 Should Walt Disney Company hedge its yen exposure? Why? On April 1983 Tokyo Disneyland started to operate. The Japanese company that operated this park paid royalties on certain revenues to Walt Disney Productions. The Yen royalties receipts in 1984 already reached a height of 8 billion Yen. The director of finance of the Walt Disney Company expected a further growth of 10% toRead MoreAccounting 1-4 Chapter100452 Words   |  402 Pagesknow how to read financial statements, you can’t really know your business. Many companies spend significant resources teaching their employees basic accounting so that they can read financial statements and understand how their actions affect the company’s financial results. One such company is Springfield ReManufacturing Corporation (SRC). When Jack Stack and 11 other managers purchased SRC for 10 cents a share, it was a failing division of International Harvester. Jack’s 119 employees were countingRead MoreCase Study on Ebay18810 Words   |  76 PagesQuestion Paper Integrated Case Studies - I (MB3J1): January 2009 Case Studyâˆâ€" (100 Marks) †¢ This section consists of questions with serial number 1 - 5. †¢ Answer all questions. †¢ Marks are indicated against each question. Read the case carefully and answer the following questions: 1.Till 2005, eBay EachNet was the leader in the Chinese e-commerce market, controlling more than half of it. But eBay EachNet soon lost its market leadership position to Taobao.com (Taobao). In this context, analyze theRead MoreSolutions: Income Statement and Pearson Education121412 Words   |  486 PagesCapital Structure in a Perfect Market Debt and Taxes Financial Distress, Managerial Incentives, and Information Payout Policy Capital Budgeting and Valuation with Leverage Valuation and Financial Modeling: A Case Study Financial Options Option Valuation Real Options Raising Equity Capital Debt Financing Leasing Working Capital Management Short-Term Financial Planning Mergers and Acquisitions Corporate Governance Risk Management International Corporate Finance 1 4 16 26 50 69 89 106 123 134 148 166 175Read MoreInvestment Bodie Kane Notes30163 Words   |  121 Pageseasily sell the stocks of the firm if they don’t li ke the incumbent management team or â€Å"police† the managers through board of directors (â€Å"stick†) or use compensation plans tie the income of managers to the success of the firm (â€Å"carrot†). In some cases, other firms may acquire the firm if they observe the firm is underperforming (market discipline). III. Clients of the financial system 1. Household sector: a. Tax concerns: people in different tax brackets need different financial assets with Read MoreContemporary Issues in Management Accounting211377 Words   |  846 Pagesfrom a UK perspective Robert W. Scapens 16. Strategic cost management: upsizing, downsizing, and right(?) sizing John K. Shank 17. Environmental management accounting Kazbi Soonawalla 18. Organization control and management accounting in context: a case study of the US motion picture industry S. Mark Young, Wim A. Van der Stede, and James J. 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Dementia Free Essays

string(132) " potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours\." Dementia Dementia  has become an all-important  disease  because the population is aging rapidly and the cost of health care associated with  dementia  is ever increasing. In addition to cognitive function impairment, associated behavioral and psychological symptoms of  dementia  (BPSD) worsen patient’s quality of life and increase caregiver’s burden. Alzheimer’s  disease  is the most common type of  dementia  and both behavioral disturbance and cognitive impairment of  Alzheimer’s  disease  are thought to be associated with the N-methyl-D-aspartate (NMDA) dysfunction as increasing evidence of dysfunctional glutamatergic neurotransmission had been reported in behavioral changes and cognitive decline in  Alzheimer’s  disease. We will write a custom essay sample on Dementia or any similar topic only for you Order Now We  reviewthe literature regarding  dementia  (especially  Alzheimer’s  disease), BPSD and relevant findings on glutamatergic and NMDA neurotransmission, including the effects of memantine, a NMDA receptor antagonist, and NMDA-enhancing agents, such as D-serine and D-cycloserine. Literatures suggest that behavioral disturbance and cognitive impairment of  Alzheimer’s  disease  may be associated with excitatory neurotoxic effects which result in impairment of neuronal plasticity and degenerative processes. Memantine shows benefits in improving cognition, function, agitation/aggression and delusion in  Alzheimer’s  disease. On the other hand, some NMDA modulators which enhance NMDA function through the co-agonist binding site can also improve cognitive function and psychotic symptoms. We propose that modulating NMDA neurotransmission is effective in treating behavioral and psychological symptoms of  Alzheimer’s  disease. Prospective study using NMDA enhancers in patients with  Alzheimer’sdisease  and associated behavioral disturbance is needed to verify this hypothesis. Mental disorders constitute a huge social and economic burden for health care systems worldwide [1], raising the question of effective and lasting treatments. Physical activity (PA) and exercise (EX) continue to gain the attention of practitioners and researchers with regard to prevention and treatment of different psychopathological abnormalities. In the general population, several epidemiological studies have found significant cross-sectional correlations between mental health and PA levels. In an adult US population, regular PA is associated with a significantly decreased prevalence of current major depression, panic disorder, agoraphobia, social phobia, and specific phobia [2]. A study from Norway confirmed this negative cross-sectional association between depression and leisure-time PA of any intensity (not work-related PA), and pointed out that social factors such as social support, rather than biological markers, play an important role [3]. Recently, a Dutch study replicated this finding, reporting lower rates of any affective, anxiety, or substance use disorder in subjects who exercised at least 1 h/wk, without finding a linear dose-response relationship [4]. Prospectively, the overall incidence of mental disorders and co-morbid mental disorders, as well as the incidence of anxiety, somatoform, and dysthymic disorder, decreases by PA [5]. Furthermore, a four-year prospective study revealed that PA decreases the incidence rates of depressive and anxiety disorders in older adults [6]. Finally, ten Have et al. reported in their epidemiological study that patients engaging in regular PA were more likely to recover from their mental illness at a three-year follow-up In psychiatric patients, different mechanisms of action for PA and EX have been discussed: On a neurochemical and physiological level, a number of acute changes occur during and following bouts of EX, and several long-term adaptations are related to regular EX training. For instance, EX has been found to normalize reduced levels of brain-derived neurotrophic factor (BDNF) and therefore has neuroprotective or even neurotrophic effects [7-9]. Animal studies found EX-induced changes in different neurotransmitters such as serotonin and endorphins [10,11], which relate to mood, and positive effects of EX on stress reactivity (e. g. , the hypothalamus-pituitary-adrenal axis [12,13]). Finally, anxiolytic effects of EX mediated by atrial natriuretic peptide have been reported [14]. Potential psychological mechanisms of action include learning and extinction, changes in body scheme and health attitudes/behaviors, social reinforcement, experience of mastery, shift of external to more internal locus of control, improved coping strategies, or simple distraction Several prospective studies have found that a high level of PA seems to delay the onset of dementia (see [74] for a review). Since improvements in strength and endurance after training were found in cognitively impaired patients as well as healthy controls [75], PA interventions are generally feasible in this population. For Alzheimer’s disease (AD), preliminary evidence suggests that EX interventions may improve communication performance [78], Mini Mental State Examination scores and verbal fluency [79], and disruptive behavior [80]. Four studies [81-84] found that PA slowed down and partially reversed the decline in performance of activities of daily living and progression of the cognitive symptoms related to dementia, in contrast to an older study, which did not find improvements in functional ability [85]. Zschucke , E. and Gaudlitz, K. Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence Zschucke , E. and Gaudlitz, K. (2013) Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence. Journal of Preventative Medicine and Public Health  , 46 (1), p. 12-21. Available at: http://www. ncbi. nlm. nih. gov/pmc/articles/PMC3567313/ [Accessed: 6th Mar 13]. Leptin, an adipocytokine produced in the peripheral system as well as in the brain, is implicated in obesity, food intake, glucose homeostasis, and energy expenditure. Leptin expression levels and signaling pathways may also be linked to the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. Epidemiological studies have demonstrated that higher circulating leptin levels are associated with lower risk of dementia including Alzheimer’s disease, and lower circulating levels of leptin have been reported in patients with Alzheimer’s disease. Leptin receptors are highly expressed in the hippocampus, a brain area involved in learning and memory and severely affected during the course of Alzheimer’s disease. In laboratory studies, several in vivo and in vitro studies have shown that leptin supplementation decreases amyloid-? (A? ) production and tau phosphorylation, two major biochemical events that play a key role in the pathogenesis of Alzheimer’s disease. In this review, we will review the structure of leptin, the type of receptors of leptin in the brain, the various biological functions attributed to this adipocytokine, the signaling pathways that govern leptin actions, and the potential role of leptin in the pathophysiology of Alzheimer’s disease. Leptin exerts its functions by binding to the leptin receptor (ObR). This binding can involve several signaling pathways including JAK/STAT pathway, ERK pathway and the PI3K/Akt/mTOR Pathway. Modulation of these pathways leads to the regulation of a multitude of functions that define the intricate involvement of leptin in various physiological tasks. In this review, we will specifically relate the potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours. You read "Dementia" in category "Papers" All this work points to leptin as a possible target for developing supplementation therapies for reducing the progression of Alzheimer’s disease. Leptin is a 146 amino acid protein with a molecular weight of 16 kDa encoded by the  ob  gene and primarily, but not exclusively, expressed by the white adipose tissue (WAT) and is implicated in obesity, food intake, and energy homeostasis. Leptin protein was discovered by the molecular geneticist Jeffrey Friedman in 1994 at Rockefeller University and the work was published in a landmark  Nature  paper in December 1994 [1]. The human  ob  gene has been mapped to chromosome 7q31. 3 [2] and encodes a 4. 5 kb mRNA transcript that is translated into a 167 amino acid peptide and subsequently processed in the ER into the 146 amino acid mature leptin protein [1]. Antecedent to the discovery of the leptin protein and positional cloning of the  ob  gene in 1994, the  ob/ob  mouse characterized by hyperphagia and a marked obese phenotype was serendipitously discovered by animal caretakers in 1950 at Jackson Laboratories [3]. It was the general consensus that the  ob/ob  mouse possessed a mutation in the  obgene, but this was not elucidated and unequivocally established until the discovery of the leptin protein and mapping of the  ob  gene by Friedman and colleagues in 1994 who showed that the mutation resulted in the loss of leptin production. In 1966, the  db/db  mouse was discovered, again at Jackson Laboratories, which not only exhibited a similar hyperphagic, obese phenotype, but also hyperglycemia [4]. Tartaglia and colleagues in 1995 showed that the  db/db  mouse phenotype can be attributed to the mutation in the  db  gene that codes for the long-form of the leptin receptor obRb [5]. However, it was the seminal work of Doug Coleman and colleagues who demonstrated by a series of parabiosis experiments using  ob/ob  mice and  db/db  mice pairs and established that the  ob/ob  mice lacked a circulating factor whereas the  db/db  mice produced the circulating factor but were not able to respond to it [6,7]. The validity of these breakthroughs was affirmed by subsequent discovery of the leptin protein and cloning of the  ob  gene [1] as well as the cloning of the  db  gene which coded for the long-form leptin receptor obRb [5]. Further corroboration emanated from the finding that the  db  mice produced the truncated form of obRb that was incapable of transducing leptin-mediated intracellular signal transduction [8-12] and administration of exogenous leptin obviated the obese, hyperphagic, hypothermic, and hypometabolic phenotype in  ob/ob  mice [13-15]. Go to: ————————————————- Leptin – structure, expression, and secretion The crystal structure of leptin has revealed the secondary and tertiary structure of the leptin molecule. The three dimensional crystal structure of leptin depicts the presence of four antiparallel ? -helices (A, B, C, and D) [16]. Two long crossover loops connect the A-B and C-D ? -helices, while a short loop connects the B-C ? -helices [16]. The entire leptin molecule is oblong shaped with the dimensions of 20x25x45 A0[16]. The entire molecule comprising of the bundle of four ? -helical loops adopts a bilayered stratified structure with ? helices A-D in one layer contiguous with ? -helices B-C in the other layer [16]. The conformation adopted by the leptin molecule results in the surface emergence of a few key hydrophobic residues like Phe41, Phe92, Trp100, Trp138, and Leu142  which not only play an indispensable role in the regulation of solubility and aggregation kinetics of the leptin protein, but are also critically requisi te for as well as modulate the binding of leptin to the leptin receptor and determine the binding kinetics of the leptin-leptin receptor interaction [16]. The three dimensional four-helical bundle crystal structure of leptin exhibits an overt, conspicuous congruence with other cytokines such as growth hormone (GH) [17], leukemia inhibitory factor (LIF) [18], and G-CSF (G-colony stimulating factor) [19], despite lack of primary sequence homology with these proteins or other proteins [1]. Leptin is expressed primarily by the white adipose tissue [1,20] and circulating leptin levels are proportional to the white adipose tissue mass [21,22]. In humans, leptin expression in the subcutaneous adipose tissue is significantly more in magnitude than omental adipose tissue [23-26]. Other studies have demonstrated no difference in leptin expression between the subcutaneous and omental adipose tissue [27]. Leptin expression in humans also exhibits sexual dimorphism with circulating leptin levels about 3-fold greater in females than males [25,28,29]. It is now certain that other tissues also produce leptin, including stomach [30,31], mammary gland [32], human placenta [33], ovaries [34], heart [35], skeletal muscle [36], pituitary gland [37], and the brain [37-39]. In the brain leptin mRNA expression and immunoreactivity has been seen in the hypothalamus, cortex, dentate gyrus and the hippocampus of the rat [38,39]. Leptin immunoreactivity has also been reported in the mouse and hamster brain [40]. Leptin expression and circulating leptin levels are primarily contingent on the white adipose tissue mass [21,22] and are significantly elevated in obesity [21,22,41,42]. Consistent with this observation, weight loss is associated with a decrease in leptin levels in the plasma [22]. Leptin levels in the plasma also fluctuate in an ultradian manner and exhibit diurnal rhythm [43,44]. Leptin secretion occurs in a pulsatile rhythm with ~30 pulses of leptin secretion in a 24-hour cycle [43,45]. Acute caloric restriction reduces leptin levels by ~30% within 24 hours [46-48] whereas caloric excess elevates leptin levels in the plasma by ~35% within 5-8 hours [47]. Therefore, nutritional intake regulates leptin expression in an acute as well as chronic fashion. The physiological and hormonal parameters that increase leptin expression include obesity [21,22,41], overfeeding or excess caloric intake [49,50], insulin [51-55], glucocorticoids [51,52,56,57], glucose [58], tumor necrosis factor ? (TNF? ) [54,59], estradiol [60-62], and IL1 [63,64] among others. The physiological and hormonal factors that decrease leptin expression include androgens [61,65], acute caloric restriction [49,50], growth hormone [66-69], somatostatin [68,70], exposure to cold temperatures [50,71,72], ? 3  adrenergic agonists [70,73-76], long-term exercise [77,78], cAMP (51, 57), PPAR? agonists such as thizolidinediones Pioglitazone, Troglitazone, and Rosiglitazone [79], and free fatty acids [80] among others. Go to: ————————————————- Leptin receptors Leptin receptors (obR) are encoded by the  db  gene [5]. The obR are transmembrane spanning proteins that transduce and mediate leptin signaling. The obR exhibit structural and functional homology to the class I cytokine receptors [81,82]. The obR along with other class I cytokine receptors are typified by the characteristic presence of four cysteine residues and a â€Å"WSXWS† motif [81,83] which are a part of multiple fibronectin Type III subdomains in their extracellular domains [84]. The obR transcript undergoes alternate splicing to generate six different receptor isoforms (obRa – ob-Rf) [11]. The six isoforms of obR are distinguished by and exhibit very little homology in their intracellular domain [85]. However, all the six isoforms have the same extracellular domain of over 800 amino acids and a transmembrane domain that spans 34 amino acid residues [85]. The six isoforms of obR are pigeonholed into three different groups, namely – short form, long form, and secreted obR [85]. The short-form of obR subsuming obRa (894 amino acids), obRc (892 amino acids), obRd (901 amino acids), and obRf (896 amino acids) possess a short 30-40 amino acid residue intracellular domain [85]. bRb (1162 amino acids) is the only functionally active leptin receptor isoform capable of transducing leptin signaling as it contains an intracellular domain that spans ~280 amino acid residues [5]. The obRe isoform (805 amino acids) lacks the intracellular domain and is therefore classified as a secreted soluble receptor and functions as a buffering system involved in the transport of leptin an d bioavailibility of free circulating leptin [86,87]. The short isoforms obRa, obRc, obRd, and obRf are abundantly expressed in the choroid plexus and endothelial cells of the brain microvasculature that form the BBB and may therefore regulate the flux of leptin across the BBB [88,89]. obRb is pervasively expressed in the human and rodent brain with the highest density in the ventromedial, arcuate, and dorsomedial hypothalamic nuclei [90-93]. obRb is termed the long-form leptin receptor and is solely responsible for propagating signal transduction mechanisms initiated by leptin [5,94]. The short forms of the leptin receptor ob-Ra, ob-Rc, obRd, and obRf are devoid of intracellular signaling motifs that are obligatory for signal transduction [5]. However the short form receptors obRa and obRc are highly expressed in the choroid plexus and it is speculated that they mediate the uptake of leptin across the BBB (88, 89). obRb expression has been reported in several regions of the rodent and human brain including the hypothalamus [90,92,93], hippocampus, brain stem (nucleus of the solitary tract and the dorsal motor nucleus of the vagus), amygdala and the substantia nigra [92,93,95,96]. In the hippocampus leptin receptor immunoreactivity is observed in the CA1/ CA3 region and the dentate gyrus [95,97]. Furthermore, axonal and somato-dendritic regions and hippocampal synapses exhibit leptin receptor immunolabeling in primary hippocampal cultures [97]. Go to: ————————————————- Biological and physiological functions Leptin was discovered as the endogenous hormone that precludes obesity and regulates energy homeostasis [1]. Antecedent to the discovery of leptin in 1994, about two decades ago, Doug Coleman had posited the role of a circulating hormone that thwarted obesity via its action in the brain to regulate food intake and energy homeostasis and in the peripheral tissues to regulate energy catabolism, thermogenesis as well as basal metabolism [7]. This was corroborated in the mid 1990s after the discovery of leptin by studies that demonstrated in rodents that administration of exogenous leptin decreased food intake and augmented energy expenditure [13-15,98,99]. Leptin administration augments energy expenditure by actuating the ? -oxidation of fatty acids in the mitochondria and also inducing the expression of enzymes involved in ? -oxidation [100]. However, the notion that high levels of leptin augment weight loss and circumvent obesity must be tempered with the fact that high endogenous leptin levels have been effete in thwarting obesity in humans and other mammals [21,22,41]. This can be ascribed to a phenomenon termed â€Å"leptin resistance† [101-103]. Leptin plays a pivotal role in the induction of puberty and fertility. Leptin reinstates puberty, restores fertility in  ob/ob  mice, escalates puberty and fosters reproductive behavior in wildtype rodents [104-107]. Leptin directly regulates the hypothalamic-pituitary-gonadal (HPG) axis by inducing gonadotropin release and modulating estradiol production in the ovarian follicles [108,109]. Leptin also regulates the hypothalamic-pituitary-adrenal (HPA) axis by attenuating corticotrophin releasing hormone (CRH) production and release [110,111] as well as directly inhibiting ACTH (adrenocorticotropic hormone)-induced glucocorticoid release from the adrenal cortex [111-113]. Leptin is also integrally involved in the physiological homeostasis of the circulatory system. Emerging evidence implicates leptin in hematopoeisis as leptin is involved in proliferation and differentiation hematopoietic precursors [114-116]. Higher plasma levels of leptin (~100ng/mL), suchas those observed in obese individuals, foster and promote platelet aggregation [117]. Leptin is also one of the most potent inducers of vascular epithelial cell growth and angiogenesis and the short forms and the long-form of the leptin receptor is abundantly expressed in the vasculature [117-119]. Go to: ————————————————- Leptin function in the brain Hypothalamus Leptin signaling in the hypothalamus regulates food intake and energy homeostasis in mammals. The arcuate nucleus (ARC), dorsomedial nucleus (DMH), and the ventromedial nucleus (VMH) of the hypothalamus express the obRb in the greatest density. In the ARC, the obRb is abundantly expressed in two disparate neuronal cell types, ones that express neuropeptide Y (NPY) and agouti-related peptide (AgRP) and the others that express pro-opiomelanocortin (POMC) [92,120-122]. Leptin induced activation of the obRb in the POMC neurons results in depolarization and increased biosynthesis of ? -melanocyte-stimulating hormone (? -MSH) which signals downstream by actuating the melanocortin system comprising of melanocortin-3-receptors (MC3R) and melanocortin-4-receptors (MC4R) expressed by the second order neurons downstream to evoke an anorexiogenic (decreased appetite) response [122-127]. Activation of the melanocortin pathway not only suppresses appetite but also increases energy expenditure by increasing sympathetic tone resulting in ? oxidation of fatty acids in skeletal and adipose tissue. While leptin activates the POMC-expressing neurons, the actuation of obRb by leptin in the NPY/AgRP neurons results in the decreased genesis of NPY and AgRP peptides which are orexiogenic (increase appetite) in nature [122,128]. Therefore, in conspectus, leptin signaling in the hypothalamus results in the decreased expression of orexiogenic peptides (NPY, AgRP) and incr eased expression of anorexiogenic peptides (? -MSH) as well as increased energy expenditure in the adipose tissue and skeletal muscle tissue. Hippocampus Leptin receptors are abundantly expressed in the CA1 and CA3 regions of the hippocampus as well as the dentate gyrus [95,97]. Leptin regulates the excitability and firing of hippocampal neurons via the modulation of BK potassium channels [97]. Leptin also improves memory processing and retention when administered directly into the CA1 region in mice [129] and rodents that are deficient in the leptin receptor (db/db  mice and  fa/fa  rats) exhibit profound deficits in spatial learning and memory [129-131]. Treatment of acute hippocampal slices with leptin results in the conversion of short-term potentiation (STP) to long term potentiation (LTP) by enhancing Ca2+  influx through NMDA receptors [132]. Leptin increases synaptogenesis and aids in memory formation in the hippocampus and is purported to be a cognitive enhancer [133]. Leptin also increases neurogenesis in the dentate gyrus of adult mice [134]. Leptin also plays a critical role in hippocampal neuronal survival by activating the PI3K-Akt and JAK2/STAT3 signal transduction pathways [135]. Leptin upregulates the expression of potent endogenous antioxidant enzyme Mn-SOD (manganese superoxide dismutase) and the anti-apoptotic protein Bcl-xL (B-cell lymphoma xL) in a STAT3-dependent manner in the hippocampus [135]. Leptin stabilizes mitochondrial membrane potential and attenuates the glutamate-induced mitigation in mitochondrial membrane potential and also extenuates the free iron-induced augmentation in mitochondrial ROS [135]. Go to: ————————————————- Leptin signaling Leptin binding to its long-form receptor obRb actuates four major signal transduction pathways that are coupled to obRb – JAK/STAT pathway, ERK pathway, PI3K/Akt/mTOR pathway, as well as the AMPK/SIRT1 signal transduction pathways. JAK/STAT pathway Leptin signaling via the obRb is integrally coupled to the JAK2/STAT3, JAK2/STAT5 and JAK2/STAT6 pathways [10]. The long-form of the leptin receptor obRb is constitutively coupled to Janus kinase 2 (JAK2) via the evolutionary conserved domains proximal to the membrane [136]. The binding of leptin to obRb evokes a conformational change in the receptor that actuates JAK2 by phosphorylation at Tyr1007/1008  residues [136]. Activated phosphorylated JAK2 subsequently phosphorylates evolutionary conserved tyrosine residues of obRb [94] at Tyr985, Tyr1077  and Tyr1138  [137,138]. The obRb phosphorylated at Tyr1077  and Tyr1138  serves as a docking site and recruits Srchomology 2 (SH2)- and Src-homology 3 (SH3)-domain comprising roteins that subsume proteins such as Signal Transducer and Activator of Transcription 3 (STAT3), Signal Transducer and Activator of Transcription 5 (STAT5), and Src homology region 2 domain-containing phosphatase 2 (SHP2) [139]. The phosphorylated Tyr1138  residue of obRb recruits STAT3 and STAT5 which are subsequently phosphorylated by JAK2 at Tyr705  and Tyr694  respectively. The phosphorylation STAT3 and STAT5 causes their disengagement from the leptin receptor, results in the dimerization of STAT proteins via their p hosphotyrosine residues in the SH2 domains [140-142], and culminates in their nuclear translocation [142]. In the nucleus, STAT dimers bind to distinct motifs or elements in the DNA called ? -IFN-activated site (GAS) in the enhancer regions of target genes and thereby modulate and regulate gene expression of target genes [142-146]. In the nucleus, the STAT signaling is abrogated by dephosphorylation and subsequent export of STAT proteins from the nucleus to the cytosol [142,144,147] or by targeted degradation of the STAT proteins via the Ubiquitin Proteasomal System (UPS) [148]. The JAK/STAT pathway is negatively regulated by three classes of proteins, namely – suppressors of cytokine signaling (SOCS), protein inhibitors of activated STATs (PIAS), and protein tyrosine phosphatases (PTP) [149]. There are eight members of the SOCS family and their expression is induced by JAK/STAT signaling (STAT3 in particular) thereby suggesting the existence of a negative feedback loop that abrogates JAK/STAT signaling [150]. The SOCS proteins negatively regulate the JAK/STAT pathway by competitively engaging and occupying the phosphotyrosine residues in obRb via their SH2 domains and obviating the recruitment of STAT proteins to obRb, thereby precluding STAT activation [150,151]. SOCS proteins via their SH2 domains also directly bind to JAK2 and extenuate the kinase activity of JAK2 [150,151]. The PIAS proteins negatively regulate the JAK/STAT signaling pathway by impeding the binding of STAT proteins to the response elements in the DNA by physically interacting and binding with STAT proteins via their zinc-binding RING-finger domains [151]. SHP1 and SHP2 are most well characterized protein tyrosine phosphatases implicated in the negative regulation of the JAK/STAT pathway [149]. SHP1 and SHP2 possess two SH2 domains and therefore bind to phosphotyrosines of JAK2 and obRb and effectuate the dephosphorylation of JAK2 and obRb thereby terminating the JAK/STAT signaling [149]. ERK pathway The extracellular regulated kinase (ERK) pathway is an integral part of a larger signaling network called mitogen activated protein kinase (MAPK) pathway that is activated by leptin signaling via the leptin receptor (obRb). While phosphorylation of Tyr1138  and Tyr1077  are both requisite and mediate the activation of STAT3 and STAT5 respectively, the phosphorylation of Tyr985  of obRb mediates the activation of ERK pathway [138]. Leptin signaling via the obRb evokes the actuation of ERK pathway, both centrally and peripherally, as well as in  in vivo  and  in vitro  experimental paradigms [85]. Leptin evokes the activation of ERK pathway by both JAK2-mediated and JAK2-independent signaling effects [94,152]. Contemporary evidence has implicated the protein tyrosine phosphatase SHP2 and the adaptor protein Grb2 (growth receptor bound 2) as the requisite mediators in the leptin-induced activation of ERK signaling pathway [153]. Leptin signaling also activates other members and signaling cascades subsumed under the MAPK signaling pathway, namely p38 [154-157] and JNK pathways [156]. PI3K/Akt/mTOR pathway Leptin signaling also induces the activation of the ubiquitous, pervasive, nutrient-sensitive anabolic, and the broad spectrum PI3K/Akt/mTOR pathway [152,158-161]. Empirical evidence has demonstrated that the adaptor proteins IRS1 (insulin receptor substrate 1) and IRS2 (insulin receptor substrate 2) mediate the leptin-obRb induced activation of PI3K-Akt pathway [94,158,162]. A multitude of studies have demonstrated that leptin induces the activation of Akt via phosphorylation of Akt at Ser473[163,164]. As a consequence, Akt activation is ensued upon leptin signaling which results in inhibition of GSK3? through phosphorylation at Ser9  residue [165-167]. Evidently leptin also activates the serine/threonine kinase mammalian target of Rapamycin (mTOR) in the hypothalamus and macrophages [168,169] through the PI3K-Akt pathway [170]. mTOR is an evolutionary conserved kinase that modulates translation of several mRNA transcripts involved in cell growth and proliferation. mTOR regulates translation by phosphorylation and attenuation of the inhibitor of mRNA translation, eukaryotic initiation factor 4E-binding protein (4E-BP) [171-175], as well as through the phosphorylation and activation of S6 kinase (p70S6K1) [176,177]. TOR is autophosphorylated at Ser2481  and exhibits spontaneous intrinsic kinase activity under the activation of Akt [178,179]. mTOR phosphorylation and activation is negatively regulated by the TSC1/TSC2 protein complex [170]. Akt phosphorylates TSC2 causing disintegration of the TSC1/TSC2 complex which consequently results in mTOR activation [180]. Furthermore, Akt has been shown to directly phosphorylate mTOR at Ser2 448residues and consequently activate mTOR [181,182]. Therefore, Akt positively regulates mTOR activation by direct phosphorylation at Ser2448  as well as by indirect means which involves relieving the repressive effects of the upstream inhibitor TSC1/2 complex. Thus leptin, by virtue of its inherent ability to activate Akt, is expected to increase mTOR phosphorylation and activity. AMPK-SIRT1 pathway The 5’AMP activated protein kinase (AMPK) is the master regulatory kinase termed the â€Å"fuel gauge† that integrates signals from upstream mediators and effectors of hormones and cytokines to maintain metabolic homeostasis [183]. AMPK activation leads to increase ? -oxidation of fatty acids in the mitochondria and inhibition of lipogenesis [184,185]. Multiple lines of evidence have cogently demonstrated that leptin activates AMPK and consequently increases fatty acid oxidation [186-188]. One exception to this is the hypothalamic neurons, where leptin inhibits AMPK activation to evoke satiety and other hypothalamic effects of leptin [189-191]. In general, AMPK plays a catabolic role and engenders energy production via effects on glucose and lipid metabolism. AMPK activation also effectuates the induction of the NAD+  Ã¢â‚¬â€œ dependent deacetylase SIRT1 (silent mating type information regulation 2 homolog) [192,193], a metabolic master regulator unequivocally implicated in ageing and the regulation of lifespan [194-198] as well as regulating metabolism [199,200]. The anorexic effect of leptin mediated by the activation of POMC neurons in the hypothalamus is contingent on SIRT1 expression and activation in the neurons of the arcuate nucleus of the hypothalamus [201]. Go to: ————————————————- Role of leptin in Alzheimer disease Alzheimer Disease (AD) is a progressive, debilitating and the most prevalent neurodegenerative disorder typified by memory impairment and cognitive dysfunction eventually leading to fatality. The gross pathologic hallmarks of autopsied brains of patients with AD include atrophy with widened sulci and narrowed gyri in the temporal, parietal, and frontal lobes as well as the neocortex and cingulated gyrus areas of the cerebral cortex. The entorhinal cortex, amygdala, hippocampus and the para-hippocampal gyrus also exhibit pronounced atrophy due to neuronal loss [202,203]. There is a decrease in gross weight of brain by 10-15% in AD patients [202]. The thickness of the six cortical layers (cortical ribbon) is usually reduced by 10-20% in AD [202] and ventricular dilation is apparent prominently in the temporal horn as a consequence of the atrophy of the amygdala and the hippocampus. Furthermore, there is a propensity for the loss of larger neurons than the loss of smaller neurons or glial cells in AD [202]. Microscopically, AD is characterized by two most common and distinct â€Å"hallmark† microscopic lesions namely senile plaques and neurofibrillary tangles (NFT). Senile plaques are extraneuronal deposits of accumulated and aggregated amyloid-? (A? ) protein in the brain parenchyma, while the NFT are intraneuronal aggregates of protein tau in the hyperphosphorylated state. Other pathological features of the AD brain include synaptic loss, neuronal and dendritic loss, neuropil threads, granulovacuolar degeneration, dystrophic neurites, Hirano bodies, and cerebrovascular amyloid deposition. There is substantial evidence that leptin modulates A? production and metabolism. Chronic peripheral leptin administration in Tg2576 mice has been reported to reduce the brain A? evels [204]. Moreover leptin also decreases the BACE1 activity in SH-SY5Y cell line [204]. Leptin decreases tau phosphorylation explicitly at residues Ser202, Ser396, and Ser404  in retinoic acidinduced differentiated SH-SY5Y cells, differentiated human NT2 cells (NT2N), and rat primary cortical neurons [205-207]. Leptin also increases synaptogenesis and aids in memory formation in the hippocampus and is purported to be a cognitive enhancer [133]. Leptin has been shown to convert STP into LTP in hippocampal cultures and hippocampal slices [132]. Recent evidence suggests that leptin facilitates spatial learning and memory [130] and also increases neurogenesis in the dentate gyrus of adult mice [134]. Recent epidemiological studies have also unequivocally implicated decreased leptin levels in the pathogenesis of AD. In the Framingham prospective study, 785 subjects were followed between 1990 and 1994 from the original Framingham cohort [208]. The study concluded that leptin levels were inversely related to the risk of developing dementia of the Alzheimer type [208]. A year preceding the findings of Lieb and colleagues, a morphometric study in Japan conducted by Narita and group found higher leptin levels were positively correlated with higher hippocampal volumes [209]. Leptin decreases Amyloid-? (A? ) levels by attenuating the genesis and augmenting the clearance of the peptide The A? peptide is derived from a two-step successive proteolytic cleavage of Amyloid-? precursor protein (A? PP) [210]. In the first step, A? PP is cleaved by the membrane-bound protease BACE1 (? -site APP cleaving enzyme 1) (also called ? secretase) to generate CTF? (carboxy terminal fragment ? ) (also known as C99 fragment) [211-215] which in the second step is subsequently cleaved by the ? -secretase complex to generate A? peptide [216-218]. According to the â€Å"amyloid cascade hypothesis†, A? is considered as the culpable factor in the instigation and progression of all the neurodegenerative events that characterize AD [219]. A plethora of studies have demons trated that leptin decreases A? levels in several  in vivo  and  in vitro  paradigms [204,220-223]. Leptin has been shown to mitigate A? roduction by extenuating BACE1 activity in neural cultures [204]. Recent studies have implicated the AMPK/SIRT1 pathway in the leptin-induced modulation of A? levels [222]. Emerging data from our unpublished work has not only corroborated the finding that leptin regulates A? metabolism via SIRT1, but also implicated the ubiquitous transcription factor NF-? B as a SIRT1 target downstream in the modulation of A? genesis (unpublished). Leptin decreases A? levels by targeting all facets of A? metabolism, namely – production, clearance, and degradation. We have shown that leptin increases the expression levels of insulin degrading enzyme (IDE) putatively by activating the Akt pathway [223], thus augmenting the degradation of A?. Furthermore, leptin also increases the expression levels of LRP1 [223], suggesting that leptin may foster the uptake of A? by astrocytes and microglia or reuptake of A? by neurons and therefore target A? for intracellular degradation or for clearance across the blood-brain-barrier (BBB). Leptin also effectuates the ApoE-mediated clearance of A? [204]. Specifically, leptin dose-dependently increased the LRP1-mediated uptake of ApoE-bound A? , therefore committing A? toward the endosomal/lysosomal degradation pathway [204]. Leptin attenuates BACE1 expression and activity The first line of evidence linking leptin signaling dyshomeostasis in the pathogenesis of Alzheimer disease emanated from the work of Tezapsidis and colleagues [204], who demonstrated in neural cultures from transgenic mice that leptin mitigates BACE1 activity by evoking changes in lipid composition of lipid rafts of cell membranes. Furthermore, the study also demonstrated that the lipolytic ability of leptin as a consequence of increased ? -oxidation of fatty acids and decrease  de novo  synthesis of fatty acids and triglycerides underlies the mechanistic link between the effects of leptin on lipid composition of membranes and BACE1 activity. Recent data from our studies [223] and other laboratories [221] cogently demonstrate that leptin negatively regulates BACE1 expression, both  in vitroand  in vitro  paradigms. Moreover, Greco and colleagues have attributed this effect of reduced BACE1 expression on the ability of leptin to induce PPAR? expression and activation [221]. Indeed, leptin is a well characterized inducer of PPAR? expression and activity [220,224]. In light of this, it is important to reiterate that multiple lines of evidence exist in current literature demonstrating the role of PPAR? as a negative regulator of BACE1 expression [225]. Another mediator of leptin induced modulation of BACE1 expression may be the transcription factor STAT3. The BACE1 promoter contains a multitude of STAT3 binding sites [226]. Multiple lines of evidence have implicated STAT3 in the regulation of BACE1 expression [226-228]. Leptin may also modulate BACE1 activity via the activation of the PI3K/Akt and ERK signaling pathways [229]. BACE1 expression is also modulated by the master transcription factor NF-? B [230]. We have found that leptin represses NF-? B transcriptional activity via induction of SIRT1 expression and activity and thereby attenuates BACE1 expression (unpublished). Furthermore, inhibition of SIRT1 activity significantly compromised the mitigating effect of leptin on BACE1 expression (unpublished). Therefore, the entire range of discrete signal transduction pathways activated by leptin may be implicated in the modulation of BACE1 expression. Leptin mitigates tau phosphorylation It is now the consensus that tau hyperphosphorylation precedes and leads to PHF formation in NFT [231] and aberrant tau hyperphosphorylation is implicated in neurodegeneration in AD [232-236]. Recent studies by Tezapsidis and colleagues as well as our work has cogently demonstrated that leptin decreases hyperphosphorylation of tau, primarily by the activation of known canonical signal transduction pathway coupled to leptin receptors. Firstly, Greco  et al. demonstrated  in vitro, in SH-SY5Y and NTera-2 human neuronal cell lines, that leptin reduces the phosphorylation of tau at Ser202, Ser396, and Ser404  residues [205]. In the same study, it was shown that leptin was ~300-fold more potent than insulin at mitigating tau phosphorylation and the activation of AMPK pathway was implicated in mediating this effect [205]. The following year, the same group systematically investigated the involvement of other signal transduction pathways activated by leptin that may contribute to the attenuation of tau phosphorylation and concluded that leptin-induced activation of Akt, p38 MAPK, as well as AMPK were all intricately involved [206]. Notably, of great mechanistic importance, was the revelation that all the three aforementioned pathways activated by leptin, culminated in the phosphorylation of the tau kinase GSK3? at Ser9  residue leading to the inhibition of its kinase activity. Therefore, leptin-induced activation of Akt, p38 MAPK, and AMPK signal transduction pathways converged at the focal point – GSK3? , a bona fide tau kinase [206,207]. Data from our studies carried out in organotypic slices from the hippocampi of adult rabbits has also cogently demonstrated that leptin inhibits GSK3? -induced tau phosphorylation at AT8 (Ser202, Thr205) and PHF1 (Ser396, Ser404) epitopes via the activation of Akt [223,237]. Of greater importance and relevance, was the finding that 8-weeks of leptin treatment in CRND8 transgenic mice resulted in a ~2-fold decrease in tau phosphorylation at AT8 and PHF1 epitopes [221]. Leptin fosters synaptogenesis and synaptic plasticity Several studies have shown that synaptic dysfunction and synaptic loss are the cardinal hallmarks of incipient AD [238-244]. Electron microscopy [238,241,245-248], immunohistochemical and biochemical studies [240,249-251] have demonstrated that synaptic loss in the neocortex and the hippocampus is an early episode in Alzheimer’s disease [252,253]. Synaptic loss is also the most important structural correlate of cognitive impairment in AD [250,254-260]. Synaptic dysfunction can be detected in patients diagnosed ith mild cognitive impairment (MCI), a condition which may or may not progress to AD and characterized by many as a prodromal state of AD [247,261]. Leptin plays an indispensable role in learning, memory, and maintenance of synaptic plasticity [262]. Leptin receptor mutant  db/db  mice and  fa/fa  rats have deficits in spatial memory and inadequate short term memory processing as assessed by the Morris water m aze [130] and T-maze footshock avoidance test paradigms [129]. In the CA1 region of the hippocampus, leptin exclusively enhances the NMDA receptor-mediated synaptic transmission [132]. Leptin facilitates the trafficking of NMDA receptors to the plasma membrane and this may contribute to the effect of leptin on enhancing the NMDA receptor-mediated current [133]. This was also corroborated in a  Xenopus  oocyte model system expressing recombinant NMDA receptors [132]. Leptin evokes the conversion of STP to LTP in acute hippocampal slices. Further delving into the molecular mechanism underlying this effect has implicated the PI3K/Akt and ERK signaling cascades at the nexus as the inhibitors of these signaling pathways mitigated this effect of leptin [132]. Furthermore, in the CA1 region of the hippocampus, leptin also fosters the induction of a novel form of LTD and this effect was attributed to NMDA receptor activation [263]. The study by Durakoglugil also examined the signal transduction cascades involved in the induction of this novel LTD by leptin and concluded that this effect was contingent on the PI3K signaling cascade, but independent of the ERK signaling pathway [263]. In addition to regulating synaptic strength by modulation of LTP and LTD, leptin also fosters synaptogenesis. The leptin deficient  ob/ob  mice have decreased synapse density and exogenous leptin corrects this deficit in these mice [264,265]. Leptin also induces the expression of a multitude of pre- and postsynaptic proteins such as synapsin2A and synaptophysin in the hippocampus [266]. Leptin also has a profound effect on dendritic morphology. Leptin augments filopodial stabilization, fosters mobility and boosts their density, thus promoting synapse formation [267]. Interestingly, this effect of leptin on filopodial stability and density is contingent on ERK signaling pathway and not on the PI3K signaling pathway [267]. Leptin increases neuronal survival and mitigates cell death There is growing consensus that leptin is a growth and survival factor in the CNS. Leptin increases the viability of SH-SY5Y cells and suppresses apoptosis by down-regulation of caspase-10 and TRAIL and this effect is contingent on the ability of leptin to activate the JAK-STAT, PI3K-Akt, as well as ERK signaling pathways [268]. Leptin has been shown to exert neuroprotective properties in cultured MN9D rat dopaminergic cells against 6-OHDA. Leptin also averted the 6-OHDA-induced dopaminergic cell loss in the substantia nigra of mice when administered intracranially [269]. This pro-survival effect of leptin on dopaminergic neurons was attributed to the JAK2-dependent activation of the ERK signaling pathway resulting in increased levels of survival factors p-CREB and BDNF [269]. Our recent work has unequivocally demonstrated that leptin upregulates the expression of Insulin-like Growth Factor – 1 (IGF-1), a known neurotrophic and survival factor in the brain [270]. Leptin has also been shown to attenuate apoptotic cell death of cultured cortical neurons in an  in vitro  oxygen-glucose deprivation model of global ischemia [271]. Furthermore, the study by Zhang  et al. , also cogently showed that intraperitoneal administration of leptin in mice reduced the infarct volume and significantly improved behavioral parameters in a middle cerebral artery occlusion (MCAO) model of global ischemia [271]. This effect of leptin was attributed to the activation of ERK signaling pathway as the general inhibitor of ERK signaling abolished this effect of leptin, both  in vitro  and  in vivo  [271]. Another study employing hippocampal cultures has demonstrated that leptin inhibits neuronal cell loss in response to growth factor withdrawal and oxidative insult by evoking JAK-STAT activation leading to enhanced expression Mn-SOD and Bcl-xL and stabilizing the mitochondrial membrane potential [135]. Leptin also mitigated neuronal loss in response to excitotoxic insult evoked by glutamate in hippocampal cultures by the aforementioned molecular mechanism [135]. Leptin also protected the hippocampal neurons from kainite-induced damage in response to excitotoxicity evoked seizures in a mice model of temporal lobe epilepsy [135]. A recent study found that leptin also attenuates MPP+-induced cell death in neuronal cultures via the activation of STAT3 and inducing the expression of UCP-2 that culminates in the obviation of mitochondrial dysfunction by MPP+  [272]. Of particular interest is the finding that cultured cortical neurons secrete prodigious amounts of leptin in response to oxygen-glucose-serum deprivation that results in enhanced expression of IL-1? and increased intransigence to apoptotic cell death [273]. Moreover, neutralization of this endogenous leptin with an antibody resulted in increased susceptibility of these cultured cortical neurons to oxygen-glucose-serum deprivation – induced cell death [273]. The salutary effects of leptin on neuronal viability and function have also been corroborated by electrophysiological studies. One such study has cogently demonstrated that leptin combats the hypoxia-induced inhibition of spontaneously firing hippocampal neurons by activating the BK channels (large conductance Ca2+  activated K+  channels) [274]. Leptin induces proliferation of neuronal progenitors – evokes neurogenesis As Alzheimer disease is typified with selective neuronal loss in the hippocampus and other regions of the brain, the debunking of the dogma that neurogenesis occurs exclusively prenatally and the revelation that neurogenesis persists in the adult mammalian brain has opened novel therapeutic avenues to combat the neuronal loss in AD. Chronic leptin treatment increases hippocampal neurogenesis in mice and induces proliferation of adult hippocampal progenitor cultures [134]. This effect of leptin on adult hippocampal neurogenesis is attributed to increased cell proliferation in the dentate gyrus and not enhanced cell differentiation or cell survival [134]. The study by Garza and colleagues unequivocally implicated the JAK2-STAT3 and PI3K-Akt signal transduction pathways in the leptin induced enhancement of hippocampal neurogenesis [134]. Furthermore, leptin rescues the attenuation in adult hippocampal neurogenesis in a mouse model of chronic unpredictable stress-evoked depression via the inhibition of GSK3? nd subsequent stabilization of ? -catenin [275]. Leptin has also been documented to evoke neurogenesis and angiogenesis in a mouse stroke model (Avraham  et al. , 2011). Go to: ————————————————- Conclusion Here we have reviewed the contemporary knowledge on the protective role of the adipokine leptin and its signaling in Alzheimer’s disease. In conspectus, leptin impinges on all facets of Alzheimer’s disease pathophysiology (Figure 1). These attributes of leptin such as the decrease in A? production and increase of A? learance, reduction in tau hyperphosphorylation as well as increased synaptogenesis, increased memory, increased spatial learning, and increased neurogenesis catapult leptin treatment as a unique therapeutic intervention and an indispensable tool in the elucidation of biochemical mechanisms involved in the etiology of the sporadic form of Alzheimer’s disease. Marwarha , G. and Ghribi, O. Leptin signaling and Alzheimer’s disease Marwarha , G. and Ghribi, O. (2012) Leptin signaling and Alzheimer’s disease. American Journal of Neurodegenerative Disease, 1 (3), p. 45-265. Lifestyle nonpharmacological interventions can have a deep effect on cognitive aging. We have reviewed the available literature on the effectiveness of physical activity, intellectual stimulation, and soc ialization on the incidence of dementia and on the course of dementia itself. Even though physical activity appears to be beneficial in both delaying dementia onset and in the course of the disease, more research is needed before intellectual stimulation and socialization can be considered as treatments and prevention of the disease. Through our paper, we found that all three nonpharmacological treatments provide benefits to cognition and overall well-being in patients with age-related cognitive impairments. These interventions may be beneficial in the management of dementia. Alzheimer’s disease (AD) is a neurodegenerative disorder with devastating consequences [1]. Despite being the most common cause of dementia, affecting approximately 5. 4 million Americans [2] and almost 50% of people over the age 85 [3], no cure has yet been discovered. Efforts are also focusing on the development of more effective strategies to slow the progression of AD to increase the quality of life of those affected. Even a two-year delay in disease onset would reduce the prevalence of AD among Americans by two million people within fifty years [4]. If an intervention that delayed the onset of AD by five years had been applied back in 1997, we would have seen a 50% reduction in AD incidence [4]. Research on strategies to slow the development and progression of AD is arguably more important now than ever before, since the number of people with AD is expected to nearly triple over he next forty years [4], and dementia is the most important contributor to disability in the elderly [5]. Among others, three nonpharmacological interventions are particularly relevant as they might positively influence cognition, general functioning, and overall quality of life. These three strategies arephysical exercise,  intellectual stimulation,  and  social interaction. While there are studies that evaluate the role of individual and multimodal interventions on AD, there is a lack of literature on the combination of all three. The purpose of this paper is to review key areas of the literature that focus on the effects of physical exercise, intellectual stimulation, and socialization strategies on AD evolution, as they collectively play an important role in the management of Alzheimer’s disease. Physical exercise encapsulates both aerobic exercises (e. g. , walking and cycling) and nonaerobic exercises (e. g. , strength and resistance training; flexibility and balance exercises). For intellectual stimulation, we examine studies that have evaluated the prognostic effects of either cognitive hobbies (e. g. reading, word puzzles, and card games) or cognitive training (e. g. , computer training games/paradigms that target specific cognitive domains such as memory and attention). Social interaction is defined as the participation of an AD patient in group-related activities, such as mealtime conversations, support groups, or other forms of social engagement. The health benefits attributed to physical acti vity are numerous and well known. Exercise has been associated with a lower incidence in many chronic diseases, such as coronary heart disease [6], type 2 diabetes [7], obesity [8], cancer [9], bone loss [10], and high blood pressure [11]. We have reviewed the effects of physical exercise on cognition. Higher cardiorespiratory fitness has been related to higher scores on tests of cognitive function [12]. A meta-analysis of randomized controlled trials examining the relationship between exercise and cognition showed modest improvements in attention, processing speed, executive function, and memory among older adults in the treatment arms [13]. This is highly relevant for the elderly population, as it suggests that physical activity can serve as a preventative measure against age-related cognitive decline [14]. Several large longitudinal studies followed older adults without cognitive impairments at baseline and measured rate of incident dementia to clarify the relationship between physical activity and incident cognitive loss. A large prospective study by Podewils et al. identified an inverse relationship between physical activity and dementia risk [15]. Compared to no exercise, physical activity has been linked with reduced risks of developing cognitive impairment and dementia [16] with the risk for dementia being further reduced with increasing levels of physical activity. Larson and colleagues found that persons who exercised three or more times per week had a reduced risk of developing dementia compared to those who exercised less, and the reduction was more marked among those with the poorest physical function at baseline [17]. These results were corroborated by Buchman et al. who found that participants in the lowest percentiles of physical activity had more than twice the risk of developing dementia than those in the highest percentiles of physical activity [18]. Furthermore, Lautenschlager et al. demonstrated that these results might be transferable to adults with mild cognitive impairment (MCI), and, thus, at high risk for dementia; participants who underwent exercise training showed modest improvements in cognition after six months [19]. Physical exercise has, therefore, been recommended as a preventative measure of mild cognitive impairment and dementia [20,  21]. There is much less research focusing on the effect of physical activity in AD patients. This may be due to the challenges of implementing an exercise regime while managing the behavioral and emotional disturbances in AD patients, particularly in the later stages of the disease. However, the results in the available literature are promising. Early research involving AD patients in nonrandomized controlled trials showed significant cognitive improvements among participants who underwent cycling training and somatic and isotonic-relaxation exercises [22,  23]. Physical exercise may have beneficial effects in AD patients beyond cognition as well. A meta-analysis on 30 randomized controlled trials that employed exercise, behavioral and environmental manipulations in patients with cognitive impairment found exercise had positive effects on strength and cardiovascular fitness in addition to improvements in behavior and cognition [24–26]. Further evidence supporting multifaceted positive effects of exercise on AD can be traced to recent randomized controlled trials of physical exercise regimes on AD patients (Table 1). Compared to controls, patients in the intervention programs showed better physical functioning (functional reach, walking, and mobility). After treatment, these patients also showed improved performance of activities of daily living (ADLs), and less cognitive decline and cognitive improvement in some cases. Physical exercise, therefore, appears to be beneficial for AD patients. While the majority of the studies did not find any differences in depression, one study by Steinberg found increased depression and decreased quality of life in patients who underwent the exercise intervention [31]. Further research into the effect of physical exercise on mood and quality of life in AD patients is, therefore, required. When considering the role of exercise on AD, it is important to note that any positive results may be due to a placebo effect, even in randomized controlled trials. However, due to the varied nature of the outcome measures used in these studies, it is unlikely that every intervention group demonstrated significant gains over the controls due to a placebo effect alone. Furthermore, control group members never appeared to show any improvement and often showed higher rates of functional and cognitive decline. Enhanced neuroplasticity might be underlying the improvements seen. Colcombe and colleagues demonstrated that older adults without dementia who performed aerobic exercises had greater grey and white matter volumes compared to adults who engaged in stretching and toning exercises [38]. Exercise has also been associated with functional connectivity between brain networks often affected by age, such as the default mode, frontal parietal, and frontal executive networks, in older adults without dementia [39]. While randomized controlled trials in AD patients examining the relationship between neuroplasticity and exercise are underway, correlational studies examining brain volumes and cardiorespiratory fitness have been done. In AD patients, cardiorespiratory fitness has been associated with brain volume. VO2peak, peak oxygen consumption, has been positively correlated with greater whole brain volume and white matter volume [40], notably in the inferior parietal lobule, hippocampal, and parahippocampal regions [41]. Future results of randomized controlled trials will improve our knowledge in this field of research. Overall, physical activity offers promising outcomes for cognition and physical health in the elderly population and AD patients. Engagement in intellectually stimulating activities has been linked with reduced risk of developing AD and intellectual stimulation has been widely explored as a nonpharmacological treatment option for dementia [42]. Among cognitively ormal older persons, randomized control trials employing intellectual training concluded that cognitive interventions produce protective and potentially long lasting positive effects in various cognitive domains as well as activities of daily living [43]. There is also evidence that frequent engagement in hobbies, including reading, puzzles, and games, for at least six hours per week reduces the risk of incident dementia [44]. The concept of intellectual stimulation as a preventative measure for dementia in healthy older adult s can be parallel to the notion of building a â€Å"compensatory mechanism† or â€Å"cognitive reserve† [45–48]. Cognitive reserve refers to the hypothesis that individual differences shaped by inherent characteristics and external sources including intelligence, years of education, occupation, and intellectual activities, may provide neural protective support against dementia [45–47]. It has been argued that these collective life experiences may contribute to building cognitive reserve and, thus, provide skills to compensate for AD pathology [45–47]. In other words, a greater cognitive reserve might delay the appearance of dementia despite the presence of neuropathology, after which a rapid progression of cognitive decline may ensue once pathology is significant enough to result in AD diagnosis. Thus, AD patients with higher education and occupation accomplishments suffer more rapid decline in cognitive abilities when compared to AD patients with less education and occupational attainment following diagnosis [49]. Another study by Helzner and colleagues [50] investigated the relationship between premorbid leisure activity and rate of cognitive decline in AD patients. Leisure activities were classified into four categories: intellectual, social, physical, and other. Higher-frequency participation in intellectual leisure activities prior to AD diagnosis was associated with delayed AD onset followed by faster cognitive decline. The study by Helzner and colleagues [50] provides evidence for the benefits of intellectual stimulation on slowing down AD development. Besides reducing the risk of dementia, cognitive interventions later in life may affect functional decline in AD. Treiber and colleagues [51] explored the association between engaging in cognitively stimulating activities in late life and the rate of cognitive decline in incident AD. This study included a wide range of intellectual activities that required varying levels of cognitive demand, for example, completing puzzles, reading, watching television, listening to music, and cooking. The results suggested that higher-frequency participation in stimulating activities in early stages of dementia resulted in slower cognitive decline. However, as time progressed there was an overall decrease in participation in activities, which might reflect the nature of AD in terms of functional abilities. Intellectual stimulation can be divided into several categories including cognitive stimulation, cognitive t How to cite Dementia, Papers

Supervision Concepts and Skill Building †Free Samples to Students

Question: Discuss about the Supervision Concepts and Skill Building. Answer: Introduction: Before applying any strategy, it is important to look at the issue from different perspectives and to know who was wrong and who was right(Johnson, R, Clark, G, 2008). One of the most important questions to ask is, was the receptionist honest with the customers? If she was not, then the burden is on her. The most effective strategies, in this case, are the following. In any business environment, it is important to make sure that there is an understanding before making any judgment. In this case, the person who is in the middle of the issue is the receptionist. Therefore, as a manager, I must be just, and fear and that calls for me to hear her side of the story. I would ask her if she tried to call the landscaper herself(Helo, P, Gunasekaran, A, Rymaszewska, 2017). The reason for asking the question is because if she knew that the landscaper was not available on the phone, why did she refer the customer to a person who is not reachable? As a manager, it is important to know more about stakeholders. Though the problem here revolves around the receptionist, the landscaper has his fair share of the blame. Reliability of an employee is crucial to an employer(Dabholkar, 2015). An employee who cannot be found when he or she is needed ought not to work for an organization. With this in mind, it is important to make sure that I get to know about the behaviors of the landscaper. Knowing the behaviors of the landscaper would help me to deal with the issue with all fairness. Though it would be important to know about the landscaper from himself, I would make sure that I get information from different people in the Association as well as look for more information about him from his past customers. The best way to make sure that a tree never grows again is but digging out its roots. The same strategy would be very effective in this case.(Cummings, T, Christopher, G, 2014) To make sure that the problem does not emerge again, I would make sure to deal with the person who is at the center of the issue, and that is the landscaper. He ought to give his side of the story if the problem is to be dealt with once and for all. The most appropriate way of doing so is by inviting the landscaper and having a one on one session with him. During the session, there are some questions that I would ask him. One of them is if the allegations of him not picking the phone are true, second is why does he not get back to the customers, and the third and most harsh but must be asked if he is tired of working(Mitra, 2016). The receptionist cannot be followed up if there is no way to prove if she is doing her job well. The only way to do so is by having the contacts of the customer. This is to make sure that the information provided by the receptionist can be verified(Coghlan, D, Teresa, B, 2014). Asking for the landscapers number The number of the landscaper will be used in proving if he is on voicemail as the customer claims. At the same time, I would be taking the number so as to make sure that it is a genuine number which is owned by one of the landscapers from the Association(Certo, 2015). The customer might have been provided with the wrong number mistakenly. The receptionist must be given a chance to give her side of the story. I would ask her if the services she provided to the customer are of good quality. To prove if the information provided by the receptionist is true, I would make a call to the customer. The customer has the right to good services, and for this reason, I must hear her side of the story. The whole case must be followed up in a way that every party that is affecting the work of the receptionist must be consulted. The landscaper must give reasons why his phone is on voicemail and why he does not receive or answer the calls of the customers. If it is true he does that; then the receptionist is suffering because of his negligence and unreliability. Therefore, the landscaper ought to make things clear so as the whole issue can be dealt with. Enquiring if there are more available landscapers The receptionist stated that there were no other landscapers and that the customer had no choice than to keep on waiting on the unreliable landscaper(Zurich, 2017). Therefore, to make sure that the information provided to the customer is true and reliable, I would take the initiative of finding out if it is true that there are no more free landscapers. The truth about the issue will dictate the type of action that should be taken(Woodside, R Tricia, M, 2016). The last and most important step would be taking action. If it is true that the landscaper has been ignoring the customers, I believe he is of no use to the association and that he should reform or be fired(Moore, 2014). If it is a lie that there are no freer landscapers, the receptionist will face a disciplinary action because she failed in providing quality services to the customer. Steps to determine how LNA Masters Landscapers Association could deliver better service to the customers seeking referrals The following flow chart looks at all aspects of how the Association can take its services to a higher level. Bibliography Certo, S., 2015. Supervision: Concepts and Skill-Building. New York: McGraw-Hill Higher Education. Coghlan, D, Teresa, B, 2014. Doing Action Research in your Organization. Boston: SAGE. Cummings, T, Christopher, G, 2014. Organization Development and Change. Boston: Cencage Learning. Dabholkar, P., 2015. How to Improve Perceived Service Quality by Increasing Customer Participation. Proceedings of the 1990 Academy of Marketing Science (AMS) Annual Conference. Berlin: Springer International. Helo, P, Gunasekaran, A, Rymaszewska, 2017. Managing Service Delivery. In Designing and Managing Industrial Product-Service Systems (pp. 49-56). New York: Springer International Publishing. Johnson, R, Clark, G, 2008. Service Operations Management: Improving Service Delivery. New York: Pearson. Mitra, A., 2016. Fundamentals of Quality Control and Improvement. New York: John Wiley and Sons. Moore, S., 2014. The Mediation Process: Practical Strategies for Resolving Conflict. New York: John Wiley and Sons. Woodside, R Tricia, M, 2016. Generalist Case Management: A Method of Human Delivery. Boston: Cencage Learning. Zurich, L., 2017. Service Operations and Management.