Friday, September 6, 2019
Disease Trends and the Delivery of Health Care Servies Essay Example for Free
Disease Trends and the Delivery of Health Care Servies Essay INTRODUCTION Americans use health care services every day, and they use them for a number of different reasons. Whether it is for preventing or curing illness, mending broken bones, delivering infants, or perhaps long term care in a nursing home there has been and will always continue to be a consistent need for the health care industry. According to an article published by the National Center for Health Care Statistics, there are a number of different factors that determine how much health care people use, the various types of care that they use, and the timing of care that they seek (Bernstein, Hing, Moss, Allen, Siller and Tiggle, 2003). These factors could include many different variables; however, for the purpose of this paper we will discuss how trends such as the aging population, and the growing rate of obesity in America are likely to influence the delivery of health care services in the future. THE AGINING POPULATION The population of the United States on April 1, 2010 was 308.7 million people. This is according to an article regarding the 2010 Census report (Howden Meyer, 2011). In the same article the age composition of the population is broken down. It shows that those aged infant to 18 accounted for 24.0 percent of the countryââ¬â¢s population. In addition citizens between the ages of 18 and 44 represented 36.5 percent, and those 45 to 64 made up 26.4 percent of the population. Finally, individuals aged 65 or older accounted for 13.0 percent of the United States population (Howden Meyer, 2011). These numbers are expected to change significantly over the next few decades. More specifically, the older population which consists ofà individuals 65 or older is expected to grow rapidly. This expected growth is largely in part due to the generation known as the baby boomers. This concept is supported in another article published by the U.S. Census Bureau. It states, Between 2010 and 2050, the United States is projected to experience rapid growth in its older population. In 2050, the number of Americans aged 65 and older is projected to be 88.5 million, more than double its projected population of 40.2 million in 2010. The baby boomers are largely responsible for this increase in the older population, as they will begin crossing into this category in 2011. (Vincent Velkoff, 2010, para 2). In addition, there are other factors that support the population growing older. These factors include a decline in fertility rates, and an increase in the age of average life expectancy. It goes without saying that older generations have different medical needs then do younger generation. Furthermore, as the populations grows older there will be a greater demand for health care services. According to a summary report published by the University of Albany it is estimated that 84 percent of people 65 or older are likely to suffer from at least one chronic medical condition. Such conditions include cancer, heart disease and diabetes to name a few (2006). Along with rising health care needs there will be a greater demand for prescription medications as well. In conjunction with these factors the need for long term care facilities will grow also. As we know already when there is a demand for something there must also be an adequate supply. There is great concern that as the population ages it is probable that the supply of health care services may not be enough. In the same summary published by the University of Albany it states, The expected growth of the older adult pop ulation in the U.S. over the next 50 years will have an unprecedented impact on the U.S. health care system, especially in terms of supply and demand for health care workers. The supply of health care workers may decrease as they age and large numbers retire and/or reduce their working hours. At the same time, older adults consume a disproportionately large share of American health care services, so the demand for health services will grow. The aging population will also affect the nature of the skills and services the health care workforce must be equipped to provide, and the settings in which this care is provided.à (2006, page 2) In addition, there will not just be a greater need for health care professionals such as psycians, nurses, lab technicians and more. There will also be a large necessity for advancements in health care technologies and facilities. We know that there is nothing that can be done to stop the process of aging itself; however, there are measures that can be taken to reduce the health complications that are related to aging. According to the Centers for Disease Control and Prevention, a few opportunities to improve health and quality of life in older generations include promoting healthy lifestyle choices such as quitting smoking, and increasing the use of preventative services (2011). THE GROWING RATE OF OBESITY Obesity is a disease that is associated with having an excess amount of body fat. It is condition that has been linked to a number of different medical issues including diabetes, high blood pressure, high cholesterol, and stroke to name a few. As reported by the Centers for Disease Control and Prevention, over one-third of the population is considered obese costing the United States an estimated $147 billion in 2008 (2013). Although the numbers are already astonishing they are only expected to grow in the future. An article featured in the American Medical News predicts that if the obesity trends continue to rise by 2030 an estimated 50 percent of Americaââ¬â¢s men and 45 to 52 percent of its women will be obese (Henry, 2011). There are many factors that contribute to the growing trend of obesity. According to the U.S. Department of Health and Human Services, the environment around us does not support healthy lifestyle habits (2012). This is because we live in a world with advance d technologies and conveniences. With busy schedules it is often easy for people to give in to fast food or microwave dinners because they are quick and easy. It can also be difficult for people to get physical exercise because many neighborhoods around the country lack safe places for recreation, or affordable gyms (The U.S. Department of Health and Human Services, 2012). A few different demographic factors linked to the obesity trend include age, sex, and race. As mentioned previously, Americans spent as estimated $147 billion for health care services in 2008. This number is expected to grow substantiallyà over time. One author wrote that the cost of obesity is expected to reach $344 billion by the year 2018 (Thorpe, n.d.). These numbers are outrages. In addition to the rising health care cost that stems from obesity we have to be concerned about the health complications that can come with the disease. Obesity has been linked to an insane number of health conditions including type II diabetes, high blood pressure, heart disease, stroke, osteoarthritis, some forms of cancer, sleep apnea and many more. There are steps that can be taken to prevent obesity, and the health issues that are associated with it. Eating healthy is vital, and not always as easy as it sounds. It can be so very easy to fall into food traps but we should focus our time and energ y towards foods that are rich in nutrients and low in calories. These foods include lean meats and proteins, fruits and vegetables, and whole grains. It is also important to exercise on a regular basis. Exercises such as walking, swimming, or running are excellent. In addition, reversing the obesity epidemic in America is going to require a community effort. Schools, places of business, and government agencies should all be involved in this mission. CONCLUSION As our population ages, and obesity rates rise in America there is no doubt that the health care industry will need to adapt. These issues will require many advancements is medical technology, as well as a larger supplies of health care professionals including doctors, nurses, mental health providers, lab technicians, long term care providers, and administrators. The list could go on and on. Therefore, in the next few decades it will be important for the industry to recruit, and adequately train new health care professionals as the baby boomer population nears retirement. Moving forward, it will also be important for the community, and not just the health care world, to implement new ways to encourage preventative care. This will require many different organizations to become involved, most especially schools because the key to prevention is education. If the younger generations are taught the healthy way to live, and if more parents lead by example the future of this country would i n turn be much more healthy. The world of health care is ever changing, and there are many differentà trends that affect it. As the future rolls forward it will be most interesting to see how health care professionals adapt to each trend. REFERNCES Bernstein, A. B., Hing, E., Moss, A. J., Allen K. F., Siller A.B. Tiggle R. B. (2003). Health Care in America: Trends in Utilization. Hyattsville, MD: National Center for Health Statistics. Retrieved from: http://www.cdc.gov/nchs/data/misc/healthcare.pdf Centers for Disease Control and Prevention. (2011). Chronic Disease Prevention and Health Promotion. Retrieved from http://www.cdc.gov/chronicdisease/resources/publications/aag/aging.htm Centers for Disease Control and Prevention. (2013). Obesity and Overweight. Retrieved from http://www.cdc.gov/obesity/data/adult.html Henry, T. A. (2011). U.S. Obesity Rate Expected to Reach 50% by 2030. Retrieved from http://www.amednews.com/article/20110912/health/309129951/4/ Howden, L. M., Meyer, J. M. (2011). Age and Sex Composition: 2010. 2010 Census Briefs. U.S. Census Bureau. Retrieved from http://www.census.gov/prod/cen2010/briefs/c2010br-03.pdf Thorpe, K. (n.d.). New Data Shows Obesity Costs Will Grow to $344 Billion by 2018. Retrieved fr om http://www.fightchronicdisease.org/media-center/releases/new-data-shows-obesity-costs-will-grow-344-billion-2018 University of Albany. (2006). The Impact of the Aging Population on the Health Workforce in the United States: Summary of Key Findings. Retrieved from http://www.albany.edu/news/pdf_files/impact_of_aging_excerpt.pdf U.S. Department of Health and Human Services. (2012). What Causes Overweight and Obesity?. Retrieved from http://www.nhlbi.nih.gov/health/health-topics/topics/obe/causes.html Vincet, G. K., Velkoff, Victoria A. (2010). The Next Four Day Decades the Older Population in the United States: 2010 to 2050: U.S. Census Bureau. Retrieved from http://www.census.gov/prod/2010pubs/p25-1138.pdf
How the Town of Maycomb Strongly Demonstrates Social Iniquity Essay Example for Free
How the Town of Maycomb Strongly Demonstrates Social Iniquity Essay People can be unfair, unjust, and downright cruel. In the novel ââ¬Å"To Kill a Mockingbirdâ⬠, there is a good demonstration by the members of Maycombââ¬â¢s society of the theme of social iniquity that has very strong supporting evidence towards this opinion. Many different acts are shown to price the county of Maycomb is biased and unfair to its members. It proves things are not as they seem considering the fact that the county of Maycomb is a very proper and ââ¬Ëclassyââ¬â¢ group of people, to some extent. But, as many people read, they notice there are hidden things involved in this ââ¬Ënot so properââ¬â¢ place. People in Maycomb are biased towards others based on their colour, job, age, gender, age or family. In more than one way are people discriminated and treated differently due to these aspects of them. Examples that are shown in the novel of social inequity the difference in treatment from a white man compared to a black man, the missionary circle or the different age groups in Maycomb. In the county, there are a group of ladies that like to get together and ââ¬Ëtalkââ¬â¢ about situations that go on in Maycomb and get each otherââ¬â¢s input on each of the situations that are brought up. They like to call themselves the missionary circle. Some people think that this group is just a group built to gossip. ââ¬Å"I heard Mrs. Grace Merriweather giving her report in the living room on the equalled lives of the mrunas, it sounded to me. They put the women out in huts when their time came, whatever that was; they had no sense of family- I knew thatââ¬â¢d distress Aunty.â⬠(Lee, 121). This quote is simply just an example of what the missionary circle talks about. They find different topics and news about the county and gather around at different locations to talk about it, acting as if they are a club. They all haveà different opinions, sometimes belittling different figures or characters in the novel. Some of the opinions given from the members reflect upon other members opinions of situations or characters making some opinions bias. Some of the things said by the missionary circleââ¬â¢s members can be untrue. Since the characters or figures that are being spoken about are not there to defend or give their point of view, this makes the judgement unfair. ââ¬Å"I tell you there are some good but misguided people in the town. Good but misguided.â⬠(124). This quote is in reference to Atticus. Some people could say this quote has a significant impact on this novel because it opens the discussion of the group up to different people in the town and the judgement, sometimes false, that they get from people. Everyone has their own opinions of others, sometimes their opinion is part of someone elseââ¬â¢s. The missionary circleââ¬â¢s members are socially high in the rankings from the opinions of others. They tend to be the ââ¬Ëpopularââ¬â¢ group in Maycomb which is why Alexandra wanted to join the group in the first place. The members of the missionary circle consider themselves fine upstanding Christian women of Maycomb. The missionary circle talks about different people in Maycomb and where they are ranked in the social standards to their perspective. The black people of Maycomb tend to be a topic the group talks about and most of the rest of the county. In the novel, people tend to make it seem as though black people are treated very poorly compared to white people. White people think they are better than them and consider it a crime if a black man beats a white man in any way shape or form. This is when Tom Robinson comes into play. He is a huge aspect of the book. He is put into trial for supposedly raping Mayella Ewell. When the court date comes, the information gathered from both sides point to Tom as being innocent. Many people suspect Mr. Bob Ewell was the man that beat Mayella for coming to a black man. Evidence suggest that Tom Robinson only losses his case because of his colour. Even in the courtroom, people are divided by their colour and class. The black people of the crowd have to sit on the balcony while the white folk sit on the floor. This isà discrimination against the black race. They are treated differently than the white people because of false and prejudice judgement and opinions of others. ââ¬Å"A white manââ¬â¢s word against a black manââ¬â¢s word, the white man always wins.â⬠(Lee, 243) This quote is a significant piece of evidence that represents the injustice and biased treatment against black people in Maycomb. This can also demonstrate the fact of how Maycomb tends to be bias towards characteristics of people or families that are out of their control such as age, gender, wealth, race or even your family. Everything the people in Maycomb are is based upon these factors that are out of their control. Atticus tells Scout ââ¬Å"Itââ¬â¢s not okay to hate anybody.â⬠(pg. 246). This quote is significant because Atticus is trying to tell Scout that you canââ¬â¢t not like anyone for no reason. He is telling her not to judge a book by its cover. He could be suggesting giving everyone a chance before you give them a negative judgement. In a way, Atticus is trying to navigate Scout away from the common disease in Maycomb of false judgement unlike the rest of Maycomb. Not many people see how they are unfair to each other but it tends to stand out to Atticus which is why he tries to treat people fairly. Atticus also tries teaching Jem and Scout to be respectful to elders and the adults in Maycomb. There are different cases for different people that are older that the kids donââ¬â¢t understand and Atticus is trying to make them appreciate them without telling them their situations. In the novel ââ¬Å"To Kill a Mockingbirdâ⬠, the role of adults is huge. When Scout first goes to school, her first teacher, Mrs. Caroline Fisher, doesnââ¬â¢t know the customs of the county so she à assumes something about the Cunninghamââ¬â¢s family. She doesnââ¬â¢t know that the Cunninghamââ¬â¢s donââ¬â¢t take anything they couldnââ¬â¢t pay back so it seemed as though she got offended when Walter didnââ¬â¢t take the quarter. Everyone in the class knows what the Cunninghamââ¬â¢s are like so when this happens, the class reacted surprised. Mrs. Fisher did not show an act of false judgement which shows that things change in Maycomb. Over time, people begin to look at different situations a bias way due to the perspectives of others. She alsoà doesnââ¬â¢t like the fact that Scout can read. It seems as though she was discouraged by a childââ¬â¢s knowledge and didnââ¬â¢t know how to react towards it. ââ¬Å"Jem and I hated her. If she was on the porch when we passed, we would be raked by her wrathful gaze, subjected to ruthless interrogation regarding our behavior, and given a melancholy prediction on what we would amount to when we grew up, which was always nothing.â⬠(Lee, 13). This quote shows the false judgement on Mrs. Henry Lafayette Dubose on the children. Most of the adults in Maycomb do not fully respect Jem and Scout. This is because of their age; something they cannot control. People treat them differently based on this because nobody stands up for them except themselves. The adults have no reason to follow along in someone elseââ¬â¢s footsteps in this aspect because no one is making the footsteps for anyone to follow in. Stephanie Crawford even told me once she woke up in the middle of the night and found him looking in the window at her. I said what did you do, Stephanie, move over in the bed and make room for him? That shut her up a while. (48). The meaning of this quote could be interpreted many different ways. Mrs. Maudie is saying this about Boo Radley. He is a very mysterious man. Many people in the town have made false accusations about him, not knowing who he truly is, not even what he looks like. Boo is considered a complete outcast to Maycomb. It is as though he doesnââ¬â¢t exist. People donââ¬â¢t even put the initiative to get to know Boo Radley because if they did, they would be considered weird. Mrs. Maudie is, in a way, sticking up for Boo because she doesnââ¬â¢t believe in false judgement. This is Mrs. Maudie showing the opposite of what most adults in Maycomb. People in Maycomb tend to follow other people. This is when a movement happens. The movement in the novel, ââ¬Å"To Kill a Mockingbirdâ⬠is social iniquity because of the decisions made upon the citizens in Maycomb. In a way, the missionary circle is a group of people looking for followers in order to continue their ââ¬Ëclubââ¬â¢ and stream of gossip. People in Maycomb discriminate different people due to their race. This is why black man is considered to be less than a white man in Maycombââ¬â¢s social standards. It is a cruel judgement which is why everyone should be given a fair chance before they are given a label. People also judge people by their age. All of theseà discriminating factors are things you cannot control. It is downright cruel and unfair. Social inequity is something quite simple that should be fixed. Many crucial factors in the novel end up being decided by discrimination. Most people in Maycomb donââ¬â¢t want to break the trend of discrimination and start a new movement by standing up for what is right. It could be very easy to fix. Why carry it on? There isnââ¬â¢t a point. People just end up being punished or judged due to these factors which isnââ¬â¢t right. People shouldnââ¬â¢t be judged on aspects of themselves that they canââ¬â¢t control. Donââ¬â¢t be a follower, be a leader.
Thursday, September 5, 2019
Electron Transport Chain in Respiratory Complex I
Electron Transport Chain in Respiratory Complex I Introduction Every organism depends on energy to survive, in order to maintain an organized state, homeostasis, through metabolism and other biochemical reactions. Energy is generated in a number of different ways depending on the organism. Mammals create energy through the breakdown of organic molecules, such as carbohydrates, proteins and lipids, that yields other compounds that drives cellular processes. One such compound is ATP (Adenosine triphosphate) an essential energy-carrying molecule that is synthesised by respiration through a series of enzyme protein complexes found in the mitochondria. Complex I (NADH:ubiquinone oxidoreductase) is one of those essential protein complex embedded in mammalian mitochondria. NADH produced by the Krebs tricarboxylic acid cycle and ÃŽà ²-oxidation of fatty acids, is oxidised to initiate the mechanistic pathway of Complex I, ultimately reducing ubiquinone and establish proton-motive force across the inner membrane of the mitochondria. It is this proton g radient that will support the generation of ATP from ATP synthase and other core processes. Significant research has been conducted on Complex I, particularly from Bovine heart mitochondria, however to date many aspects of this enzyme is still poorly understood due to its complex structural arrangement and pathways undertaken. To decipher its mechanism, will eventually lead to a greater understanding in the role of Complex I in many diseases and dysfunctions. Mitochondria Mitochondria are small sub-cellular organelles involved in a series of processes primarily with its role in the respiratory system. Occupying almost 10% to 30% of cell volumes of sizes ranging between 0.75 and 3ÃŽà ¼m, the unique shape of a mitochondrion allows the process to take place, with its key structural feature being a double membrane.1 These two membranes are separated by the intermembrane space and overall enclose the central matrix. Whereas the outer membrane is inundated by porins to facilitate the movement of solutes of about 12 kDa or less; the inner membrane is impermeable to solutes but presents the ideal environment for the establishment of an electrochemical proton gradient, by the presence of numerous protein complexes. Additional compartments of the organelle include the cristae and the mitochondrial matrix, which comprises a plethora of enzymes involved in ATP metabolism. Additionally, a range of studies have also indicated the ability of mitochondria to form dynamic networks of interconnected tubules that regulates the cell structure to adapt to its specific function when required. As a result, during disruption of such networks, cellular dysfunction can occur, leading to a number of neural related syndromes such as Parkinsons and Alzheimers.2,3 Aside from the primary role of energy metabolism, the mitochondria also power other core cellular functions such as apoptosis, calcium handling and the formation of iron sulphur clusters. The following sections discuss the main enzymes involved in the electron transport chain that lead to the generation of ATP, particularly respiratory complex I, which will be the main focus of this thesis. Respiratory Complexes Complex II Also known as succinate: ubiquinone oxidoreductase, complex II is a 120 kDa enzyme consisting of four nuclear-encoded subunits which are arranged in two domains.4 It is this distinctive arrangement which allows this enzyme to oxidise succinate to fumarate which is coupled to the production of ubiquinol through the reduction of ubiquinone in the mitochondrial inner membrane. While it is involved with cofactors, this enzyme complex does not directly contribute to the proton motive force in order to establish a chemical gradient.4,5 Succinate+ Q à ¢Ã¢â¬ ââ¬â¢ Fumarate + QH2 Equation 1: Two of the enzymes subunits SdhA and SdhB form a hydrophilic, succinate dehydrogenase subcomplex and forms the succinate/fumarate binding site whereas SdhB contains three iron-sulphur clusters which are embedded to the mitochondrial membrane by the remaining SdhC and SdhD subunits.4 These latter subunits contain a heam group and ubiqionone binding sites. When a flavin dinucleotide, which is ligated to SdhA, it oxidises succinate, the electrons produced in this process are passed down through the iron-sulphur clusters. The electrons subsequently allow the reduction of ubiquinone to ubiquinol.6,7 Complex III Complex III or ubiquinol:cytochrome c oxidoreductase is an 240 kDa enzyme which is made up of 11 subunits. Its structure comprises of two ubiquinone binding sites; Qo, present towards the mitochondrial membrane, catalyses the oxidation of ubiquinol to ubiquinone and Qi, present towards the matrix, catalyses the reduction of ubiquinone to ubiquinol.8,9 Complexes I and II produces ubiquinol from the reduction of ubiquinone, which binds to the Qo site on complex III. During this process, an electron is passed along the iron-sulfur cluster reducing it and moving it towards cytochrome c1 and cytochrome c resulting in a conformational change. The change causes a second electron to be transferred through another pathway formed of cytochromes bL and bH towards to Qi binding site, in where it allows the formation of a semiquinone anion through the reduction of an already bound ubiquinone. Parallel to this, a second quinol is oxidised at Qo allowing the electron to be transferred through the first pathway of Rieske iron-sulphur cluster and cytochrome c1 and the second electron follows the second pathway mentioned above to Qi, reducing the semiquinone anion to ubiquinol.10 The oxidation at Qo releases four protons into the inter-membrane space of the mitochondria and the reduction at Qi results in the uptake of two protons from the matrix wh ich are transferred into the inter-membrane space during ubiquinol oxidation. This complete cycle allows the reduction of two cytochrome c molecules.9 QH2 + 2 cyt c3+ + 2H+in à ¢Ã¢â¬ ââ¬â¢ Q + 2 cyt c2+ + 4H+out Equation 2: Oxidation and reduction cycles in Complex III results in the movement of four protons into the inter-membrane space maintains the proton motive force used by ATP synthase to synthesise ATP.8 Complex IV Complex IV, also known as cytochrome c oxidase, is an enzyme, which comprises of 13 subunits, of which three are encoded by the mitochondrial genome. The enzyme catalyses the oxidation of cytochrome c which leads to the reduction of oxygen to water allowing the translocation of four protons across the mitochondrial inner membrane.11,12 The oxidation of cytochrome c produces electrons that are transferred to an active site where molecular oxygen is reduced. This reduction producing water releases free energy required for the pumping of four protons from the matrix of the mitochondria into its inner-membrane space. This movement of protons is facilitated through two known proton channels: the K-channel passes two protons for the reduction of oxygen and the D-channel allows the movement of newly translocated protons.13 O2 + 4 cyt c2+ + 8H+in à ¢Ã¢â¬ ââ¬â¢ 2 H2O + 4 cyt c3+ + 4H+out Equation 3: The translocated protons and the reduction of oxygen to water allows ATP synthase to generate ATP as this contributes to the proton motive force similar to Complex III. Complex V Primarily known as ATP Synthase, this enzyme complex operates by utilising the proton chemical gradient established in the intermembrane space by the preceding complexes, to drive the synthesis of ATP from ADP and inorganic Phosphate. With an average size of 580 kDa, the enzyme is composed of 16 subunits organised in two hydrophobic and hydrophilic domains; the hydrophobic domain forms a proton conductive pore through the inner membrane while the hydrophilic domain, containing three copies of ÃŽà ± and ÃŽà ² subunits, spreads into the matrix. The two domains are linked by an asymmetric central stalk and a peripheral stalk, which acts as a stator to prevent the F1 domain rotating freely during catalysis. The interfaces between the two subunits forms the binding sites for ADP and inorganic Phosphate. 14,15 ADP + P+ nH+in à ¢Ã¢â¬ ââ¬â¢ ATP + nH+out Equation 4 Complex I Complex I, is the first and largest enzyme involved the electron transfer chain of the mitochondrion. Alternatively known as NADH:ubiquinone oxidoreductase, its primary role is to oxidise NADH and ultimately reduce ubiquinone.16 NADH + H+ + Q + 4H+in à ¢Ã¢â¬ ââ¬â¢ NAD+ + QH2 + 4H+out Equation 5: Just like the other protein complexes, the potential energy released from the redox reaction within the complex, translocates four protons across the inner membrane for every molecule of oxidized NADH and removes two additional protons from the matrix for the reduction of quinone. The processes contribute to the overall electrochemical gradient which is to be used by ATP synthase to synthesise ATP.17 Structure To date, complex I has been found in a variety of species, including many prokaryotes. The complex I from bovine heart mitochondria is primarily used in studies due to its close sequential identity with the human complex I enzyme. The mammalian complex I is one of the most complex and largest enzymes known, with a combined mass of 980 kDA and composed of at least 45 different polypeptide subunits; with 14 strictly conserved core subunits that are necessary for function and also common across the among all known complex I.16 The significance of the additional subunits in complex I among different species still remain a mystery. It is known some be involved in protection against reactive oxygen species generation and some are required needed for proper assembly and stability of the enzyme.16,18 As observed by single-particle electron microscopy (EM) for both bacterial and mitochondrial enzymes, the determined structure of the enzyme closely resembles to an L shape, with seven hydrophobic core subunits that constitutes the membrane tail domain and seven hydrophilic core subunits that constitutes peripheral (hydrophilic) arm domain protruding into the mitochondrial matrix; which is known as the catalytic domain as it includes all redox centres and binding site while the membrane domain consists mostly of hydrophobic subunits. 16 While the full structure of the eukaryotic complex is not still well characterised, in 2006, Sazanov group successfully reported structure of the hydrophilic domain of complex I from Thermus thermophiles bacteria.20 The Peripheral Arm of complex I The peripheral arm of the complex is composed of seven individual subunits, that together, houses the NADH-oxidizing dehydrogenase module, which provides electron input into a noncovalently-bound flavin mononucleotide (FMN) molecule. The molecule sequentially transfers the electron to a chain of nine iron-sulphur (Fe-S) clusters, eight of which are found in the bovine enzyme. Additionally, the hydrophilic arm also comprises of a Q-module, which conducts electrons to the quinone-binding site for quinol production. 16,20 All of these Within the respiratory chain complexes, there are three different types of Fe-S clusters, two of which, are found in complex I; Two binuclear [2Fe-2S] and six tetranuclear [4Fe-4S] clusters. As the name suggests, the binuclear clusters are composed of two iron atoms that function as bridged by two acid-labile sulphur atoms. Each iron atom is also coordinated by an additional two sulphur atoms found on the surrounding cysteine residues from the protein complex. In the tetranuclear Fe-S clusters, four iron atoms and four sulphur atoms are arranged in a cube with each iron atom also ligated to sulphur cysteine-residue on the surrounding protein, similar to binuclear Fe-S.22 Due to their conformational arrangements and redox capabilities provided by the iron atom, these clusters act as electron transfer agents or also known as ferrodoxins. The detection of these clusters can be achieved by EPR (electron paramagnetic resonance) which is successfully achieved in many studies. However, out of the two binuclear and six tetranuclear iron-sulfur clusters found in complex I, only two binuclear and four tetranuclear clusters are EPR active.22 Figure 1.: structures of the iron-sulphur clusters found in complex I. As previously mentioned, seven of the eight clusters, form a 95 Ãâ¦-long extensive chain directly from the flavin site to the quinone binding site on the interface of the membrane domain. Even though the distances between these chains may seem far apart, as much as 14 Ãâ¦, distances are close enough to allow electron transfer to occur.23,24 However, the presence of the eight cluster is still not well understood. Cluster 2Fe[24] found on the opposite side of the Flavin site, is believed not to be involved in electron transfer pathway. While it was just a theory with no evidence, it has been proposed that this additional cluster functions as an electron store that accepts an electron from the flavosemiquinone species preventing the generation of reactive oxygen species during enzyme turnover.24 Membrane Domain of complex I The membrane domain comprises the proton-translocating module which catalyses proton transport. With the exception of subunit ND1 and the quinone binding site, found on the interface of the peripheral arm, the membrane domain functions totally independently from the two arms of complex I. Within the membrane domain, there are four structural subunits that have been identified to be possibly involved with proton translocation; these include subunits ND2, ND4 and ND5. There is also an additional transporter which believed to be either ND1, ND6 or ND4L. Each believed to be transporting one proton per catalytic cycle. Each individual subunits are composed of charged residues and helices that creates half-channels that allow the passage of proton to occur. The membrane structure is also held together by a long ÃŽà ±-helix chain that spans across its entire length. Its feature is to maintain and support the integrity of the membrane domain.26 Overall Mechanism of complex I The mammalian complex I includes 45 known proteins, out of which 14 core subunits comprises of both hydrophilic and hydrophobic domains as explained above.16 The mechanism through the electron transfer chain starts with a Flavin mononucleotide (FMN) molecule which is non-covalently bound to the 51kDa subunit through hydrogen bonds at the top of the hydrophilic domain. FMN molecule oxidises NADH leading to the reduction of iron-sulphur clusters (Fe-S) which transfers electrons from Flavin to the quinone-binding site {51}. This electron transfer distorts the conformation of the protein through changes in its redox state leading to alterations in pKa values of its side chains; these alterations allows four hydrogen ions being pumped out of the mitochondrial matrix.24 It is believed NADH gets oxidised to NAD+ through a hydride transfer avoiding the formation of the unstable NAD. Radical.24 This oxidation process occurs when the nicotinamide ring of the NADH lies above the flavin isoalloxazine system, allowing the electron donor hydride (C4 of the 27 nicotinamide ring) and acceptor (N5 of the flavin) to come within 3.5 Ã⦠of each other and transfer electrons.28 As explained above, NADH oxidation leads to transfer of electrons through seven iron-sulphur clusters chain between Flavin and quinone reduction binding site in the membrane.20 It is the final Fe-S cluster that donates the electrons to the bound ubiquinone substrate which is believed to be accessed through an entry point in the membrane to the binding site.21 These iron-sulphur clusters are best detected using a technique called electron paramagnetic resonance (EPR). Previous studies have observed five reduced Fe-S clusters through EPR from Bovine compliex I reduced by NADH, and their spectra are represented N1b, N2, N3, N4 and N5.25 This technique will be further explained throughout this thesis. A much recent study by Roessler et al. (2010) used EPR to understand the tunnelling electron transfer pathway through these clusters. Previous studies have already established EPR signals N1b, N2 and N3 are detected from 2Fe cluster in the 75 kDa subunit (position 2), and from 4Fe clusters in the PSST (position7) and 51 kDa subunits (position 1) respectively along the clusters chain due to interactions with ubisemiquinones and flavosemiquinone. As the other EPR signals have yet failed to be assigned to a particular cluster, Roessler et al. (2010) went on to use double electron-electron resonance (DEER) spectroscopy to detect N4 and N5. Their results demonstrate that N4 is assigned to the first 4Fe cluster in the TYKY subunit (position 5), and N5 to the all-cysteine ligated 4Fe cluster in the 75 kDa subunit (position 3).25 The study propose an alternating energy potential profile for electron transfer along the chain between the actives sites, in B.taurus, which enhances the rate of a single electron travelling through the empty chain subsequently leading to more efficient energy conversion in complex I.25 Followed by the iron-sulfur cluster is the site of quinone reduction. A study performed by Sazanov and Hinchliffe has identified a supposed binding site for the quinone head group from T. thermophilus complex I hydrophilic domain between the 49 kDa and PSST subunits.20 This alleged site is close to the cluster where the ubiquinone substrate accepts electrons from the chain and it has also been acknowledged the 49 kDa and PSST subunits play an important role in quinone binding and catalysis.29 Nevertheless, it is believed that additional hydrophobic subunits may also be involved in quinone binding and these are still being investigated. Even though the mechanism of NADH oxidation and ubiquinone reduction is relatively well understood, how this oxidoreduction leads to quinone reduction and subsequent protons pumping across the mitochondrial membrane from complex I still remain a mystery. A number of theories for complex I mechanism have been proposed based on the proton-pumping systems of the other mitochondrial respiratory complexes. These theories have been outlined below: A direct coupling mechanism as demonstrated by complex IV through cytochrome c oxidase where the proton transfer is determined by a gating reaction occurring at the same time as the electron transfer reaction that started it.30 An indirect coupling mechanism as seen in complex V (ATP synthase) explained previously. A study performed by Efremov et al., suggests that within complex I, one proton is translocated by a directly coupled mechanism at the Fe-S clusters and the rest are moved when quinone reduction drives conformational changes to the four-helix bundle of Nqo4 and of Nqo6 in complex I, subsequently affecting the C-terminal helix of Nqo12. The C-terminal has been identified by the authors running parallel to the membrane. The effect on this helix consequently leads to the other three helices to tilt which results in proton translocation.31 A Q-cycle-like mechanism as represented by complex III where quinol is used as a carrier to transport protons across the mitochondrial membrane. A study completed by Dutton and co-workers suggested the complete reverse of this mechanism for complex I featuring the presence of two ubiquinone binding sites; one facing the inter-membrane space, Qo, and the other facing the mitochondrial matrix, Qi. The quinone substrate would bind at Qi, and be reduced by one electron from a quinol already bound at Qo and another electron from the Fe-S cluster; subsequently leading to two protons being taken up from the matrix while the formed semiquinone specie is still bound at Qo. Following the uptake of the protons, semiquinone is oxidised to ubiquinone.32 Nevertheless, further studies conducted have found no evidence of ubiquinol oxidation signifying complex I do not work through this mechanism.30,33 While the first isolation of complex I from bovine heart mitochondria by Joe Hatefi et al occurred 40 years ago, information on its overall mechanism of action is still very limited particularly the mechanism of redox-proton coupling occurring in the membrane domain. To further understand this, new studies are being conducted to trap radical intermediates formed at the interface of the peripheral and membrane arm to establish the pathway that initiates proton translocation. Semiquinone radicals Semiquinones are catalytic intermediates formed within complex I during the reduction of quinones at the quinone binding site and can exist in neutral or anionic form. Due to the presence of the unpaired electron, semiquinone intermediates can be studied using EPR spectroscopy. There are numerous pathways in which the formation of semiquinones can occur from quinone. The scheme below, proposed by Roessler and Hirst, illustrates the three main possible routes taken to obtain quinol. Pathways A and B involves with the generation of a neutral semiquinone radical specie based on the transferring of a proton and electron. On the other hand, pathway C which follows through pathway B involve with the generation of an anionic radical specie generated from an electron transfer. All pathways lead to formation of quinol by series of electron transfer and protons. The pathway shown in grey which occurs from the protonation of the neutral semiquinone radical specie will result in a 1-electron-2-centre bond which are energetically unstable.27 Aside from one study, majority of the studies till date, have proved the existence of semiquinones by observing EPR signals using submitochondrial particles (SMPs). As the name suggests, these are inverted membrane vesicles housing the entire electron transport chain containing all enzyme complexes.34 However, since quinone cofactors are used by majority of the other complexes, distinguishing the semiquinone signals with each complex, has been far from successful. More recently, there has been a wave of research focusing on the identification of semiquinone radicals exclusively from complex I, however these have proved even more challenging as the organic intermediates produced very low intensity signals. Within complex I, there are two species of semiquinone that have been identified; SQNf and SQNs.35,36 Based on their EPR properties, SQNf or fast relaxing semiquinones has been reported only during the presence of an established proton gradient across the membrane. On the other hand, SQNs or slow relaxing semiquinones, are not effected by proton gradient. The presence of two semiquinones has also lead to the possibility of complex I to contain two separate quinone binding sites; Due to SQNf having a spin-spin interaction with Fe-S cluster N2, it is theorised that SQNf binding site is located close to the cluster at around 12 Ã⦠estimated distance, in contrast, SQNs binding site is suggested to be located around 30 Ã⦠from N2 cluster.22,25,37 Within the complex, the SQNf is believed to be involved in proton pumping and its site aids the system by acting as bound co-factor site that facilitates the transfer of one electron from one site to another allowing the formation of a binding pocket for the SQNs in equilibrium with the ubiquinone pool of the membrane.22,25,32,35,38 The presence of two separate quinone binding sites still remains a mystery and cannot be totally ruled out even though it has been suggested that SQNf and SQNs signals are detected from the same semiquinone species located from different sites or present in catalysis states.39 A recent potential way of observing semiquinone intermediates via EPR is through the use of liposomes. Liposomes containing just Complex I or proteoliposomes, will facilitate the capture of semiqinone within its native environment and hopefully provide an insight in the mechanism of Complex I and the binding of Q10. Liposomes Liposomes are spherical nanovesicles used in a variety of applications. Composed of a phospholipid bilayer, these small vesicles have an aqueous solution core surrounded by a hydrophobic membrane. Hydrophobic chemicals associate with the bilayer while the hydrophilic solutes dissolved in the core cannot readily pass through the bilayer; essentially mimicking the cellular phospholipid bilayer. Due to these features, liposomes can be loaded both with hydrophobic or hydrophilic molecules and are excellent drug carriers or in this case house protein complexes. Liposomes are also not naturally occurring and must be artificially generated using lipid extracts by aggregating them.40 As liposomes are formed from naturally occurring lipids of low intrinsic toxicity, they are biodegradable and non-toxic. The functionality of liposomes is dependent based on three main factors. These include: size, bilayer composition and liposome surface properties.40 Phospholipids are one the essential components in the formations of liposomes and can be divided into synthetic and natural phospholipids. They consist of two fatty acids hydrophobic chains linked to a hydrophilic (polar) head group, and they have either glycerol or sphingomyeline as the back bone. Having both hydrophobic and hydrophilic components, make phospholipids having amphipathic molecules.41 The diversity of the hydrophilic head group molecules and hydrophobic chains length allows the formation of different phospholipids which affects the surface charge and bilayer permeability of the liposomes.40 The length and degree of saturation of the hydrocarbon acyl chains determines the stability of the liposomal membrane, by affecting the temperature at which the membrane changes from a closely packed gel phase to a fluid phase. The surface charge of the liposomes is determined by the charge of the lipid forming it which can be altered by modifying lipids with hydrophilic moieties to membrane bilayers.40 Liposomes can be composed of naturally-derived phospholipids such as cholesterol, one of the commonly used lipids in liposome formation. It enhances the stability of the lipid bilayer and form highly ordered and rigid membrane with fluid like characteristics. Other phospholipids, synthetic and non-synthetic, can also be used for the formation of the liposomes such as pure surfactant components like DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine).42 Classifications of liposomes Liposomes are classified according to their morphological sizes and lamellarity, depending on their composition and method of formation.40 Multilamellar vesicles (MLVs) consists several concentric phospholipid bilayers or lamellar ranging between 100nm to 20 Ãâà µm in size depending on the method of preparation. These large bilayers allow the integration of lipophilic molecules and proteins. Small unilamellar vesicles (SUVs) single phospholipid bilayer and sized between 20 nm to 100nm. Ideal for encapsulation small compounds and proteins. Large unilamellar vesicles (LUVs) single phospholipid bilayer with size ranging from 100 nm to 1 Ãâà µm. They are known to have larger aqueous core compared with or MLVs, making them suitable to useful to load with numerous compounds. Oligolamellar vesicles (OLVs) vesicles similarly structured to MLVs but consists of anywhere between two and five phospholipid bilayers. Multivesicular liposomes (MVLs) When a large liposome vesicle similar in size to an MLV, enclose a group of liposomes, then the subsequent vesicle is known as multivesicular liposome (MVL). Figure 1.40 The current state of research on liposomes have primarily been focusing on the administration of drugs and other compounds to biological systems since it overcome challenges associated with reaching the target, making them very useful in the cosmetic and pharmaceutical industries.40 Furthermore, it should be noted, some surfactant based phospholipids can mimic the biological systems helping construct important model systems for the research on enzymes and membranes. Many recent publications concerning liposomes have been focused on using this mimetic chemistry, which deals with models, mimicking cellular membrane to facilitate the research into their structures as well as the mechanisms both in vivo and in vitro.40 Aims of Project The current state of research on complex I remain largely focused on the determination of the mechanism since only a fraction has been found. Fully understanding will help solve many diseases and other complication caused by complex I. Whereas the mechanism of the reactions between NADH and iron sulphur clusters have been established, little is known about the mechanism of proton translocation as well as the role and existence of semiquinones that will lead into revealing more information into the function of the enzyme. The work described in the following records, using the best technique available, EPR, will aim to be using current studies of using liposomes to mimic cellular conditions, similar to the mitochondrial membrane, for complex I in order to obtain data regarding reduction of Q10 and proton translocation. Materials Preparation of Complex I from Bovine Mitochondria Preparation of Complex I proteoliposomes Stock solutions of 25 mgmL-1 of POPC in chloroform was transferred to a glass homogeniser with the required amount of ubiquinone-10 contained in chloroform. The chloroform was removed under Argon. An alternative approach is to remove under vacuum using rotary evaporator. The resulting phospholipid film was resuspended in 675 ÃŽà ¼L of buffer (10 mM Tris-SO4 (pH 7.5) and 50 mM KCl), and extruded 25 times through a Whatman 0.1 ÃŽà ¼m pore membrane. The liposome mixture was solubilised with the addition of 160 ÃŽà ¼L of octyl-glucoside from an aqueous 10% stock solution, sonicated for 10 min, and further incubated on ice for 10 min. The following steps were carried out at 4 Ãâà °C. 0.2 mg of AOX (50 ÃŽà ¼L of 7.8 mgmL-1) and 0.2 mg of complex I (10 ÃŽà ¼L of 20 mgmL-1) were added to the solubilised lipids and incubated for a further 10 min, followed by the addition of 100 ÃŽà ¼L of SM2 Biobeads. The mixture wa
Wednesday, September 4, 2019
Essay on John Miltonââ¬â¢s Paradise Lost and the War in Heaven
Paradise Lost and the War in Heavenà à à à From the beginning of book 1 the war in heaven seems more than a simple, finished event. In reality, we have the authorized formal side presented: the war was ambitious, impious, proud, vain, and resulting in ruin. Satanââ¬â¢s first speech implies that there was another side-even after we have partly discounted the personal tones of the defeated leader who speaks of the good old lost cause, ââ¬Å"hazard in the Glorious Enterprise.â⬠That too is a formal side, presented by the losing actor in the drama. Then Satan goes on, to reveal, before he can pull himself together in defiance, something more: à Into what Pit thou seest From what highth falââ¬â¢n, so much the stronger provd He with his thunder: and then who knew The force of these dire Arms? (I, 91, ff) à A little later the surprise has been bolstered with a kind of indignation: à But still his strength concealââ¬â¢d Which tempted our attempt, and wrought our fall. (I, 641 f.) à We soon learn that we cannot get answers in hell, but we begin to see certain questions, and the possibility that their answers may appear when we see the actual dramatic presentation of the rebellion. For one thing, Satanââ¬â¢s ââ¬Å"innumerable forceâ⬠receives a definite tally later- it is only one third of the angels. And this fact will look different when we learn that God opposes the enemy force with an equal number only, and then puts a fixed limit on the individual strength of the contestants, and then sends only the Son against the rebels, and with His strength limited too. Satan puts so much concentration on having shaken the throne of god, against ââ¬Å"His utmost powerâ⬠-ââ¬Å"Who from the terrour of this Arm so late/... ...s; and then the gigantic niceness of the detail that pictures the mountains, pulled up by the tops, coming bottom side up toward them. In between we are forced to look away, to separate ourselves from the action, and see it as a spectator, not as a participator. In the grand finale of physical ridicule the rebels are again left exposed to laughter by the interrupted point of view. Never do they appear so ridiculous, not even as a timorous flock, as when they are caught isolated between the before and the behind. à This is to be understood metaphorically, as the climax of their physical humiliation. It does not last, any more than their later mass metamorphosis into serpents, with which this is parallel. But it is a punishment, on the material level, for the material nature of their sin. If they regain their form in hell, that is because they regain free will.
Tuesday, September 3, 2019
Osteomyelitis Essay -- Health, Diseases
Osteomyelitis: Osteomyelitis is a common bone infection caused by bacteria or in some cases, fungus [1]. Osteomyelitis generally occurs by infection of bacteria in several different ways, including via the bloodstream, from neighboring areas of infection, or due to non-sterile joint replacements and internal fixations such as fractures [2]. In 90% of cases, an S. aereus bacterium is the microbial culprit responsible for osteomyelitis [3]. In the cases of open would fractures, osteomyelitis can interfere with normal bone healing and regeneration [4]. Symptoms of osteomyelitis include bone pain, fever, malaise, swelling, redness, chills, excessive sweating, and joint pains [5]. It is reported that in 20% of the cases, the infection is hematogenous, or spread by the blood [6]. The incidence of spinal osteomyelitis was reported to be 1 in 450,000 in 2001 [7]. The incidence of vertebral osteomyelitis is reported to be 24 cases per 1,000,000 and the incidence in children is approximately 1 in 5,00 0 [8]. Approximately 10-15% of people with vertebral osteomyelitis develop spinal-cord compression and approximately 30% of patients with long bone osteomyelitis develop deep vein thrombosis (DVT) [9]. Mortality rates are generally low unless sepsis occurs [10]. The overall incidence of osteomyelitis was found to be higher in developing countries compared to developed nations [11]. Current Clinical Standard of Care: The current gold standard treatment for osteomyelitis is gentamycin or vancomycin impregnated poly methyl methacrylate (PMMA) beads [12]. These beads are surgically implanted at the site of bacterial infection, and the antibiotic will diffuse from these beads [12]. Both vancomycin and gentamycin inhibit bacterial g... ..., the in vivo studies show that the effectiveness of the delivery system in terms of bacterial growth inhibition is comparable to the clinical standard of care, the PMMA beads. Further studies would include determining the compressive strengths of the PUR scaffolds to decide where they could be placed in a load-bearing setting, systemic toxicity studies to ensure that neither the vancomycin nor PUR is present in toxically high concentrations in the serum after implantation, and a prolonged study to show that the PUR scaffold is in fact biodegradable, thereby by-passing the second surgical step which is required for the PMMA beads. Li et al [21] also did not do any studies comparing the PUR-LTI and PUR-HDIt scaffolds under the same experimental conditions. These studies would also be critical to determine which scaffold formulation should be pursued long-term.
Monday, September 2, 2019
Hate Crimes and The Mitchell v. Wisconsin Decision Essay -- Hate Crime
Hate Crimes and The Mitchell v. Wisconsin Decision The American Heritage Dictionary defines hate as intense dislike or animosity. However, defining hate as the basis for a crime is not as easy without possibly jeopardizing constitutional rights in the process. Hate crime laws generally add enhanced punishments to existing statues. A hate crime law seeks to treat a crime, if it can be demonstrated that the offense was a hate crime differently from the way it would be treated under ordinary criminal law. Since the 1980s, the problem of hate crimes has attracted increasing research attention, especially from criminologists and law enforcement personnel who have focused primarily on documenting the prevalence of the problem and formulation criminal justice responses to it. Lawmakers have passed legislation to encourage data collection and attach enhanced penalties to hate crimes at both state and federal levels. à à à à à When Americans are assaulted merely because of their real or perceived sexual orientation, gender, or disability, the law should be as tough on their assailants as it currently is tough on criminals who attack based on racial, religious, or ethnic bias. Yet only in rare circumstances can the federal government investigate and prosecute hate violence against gays, lesbians, or bisexuals. Attempts have been made to reach a definition of hate crime, including that it is a crime, most commonly violence, motivated by prejudice, bias or hatred towards a particular group of which the victim is rarely significant to the offender and is most commonly a stranger to him or her. The current law (18 U.S.C. 245) permits federal prosecution of a hate crime only if the crime was motivated by bias based on race, religion, national origin, or color, and the assailant intended to prevent the victim from exercising a "federally protected right" (e.g. voting, attending school, etc.) T his dual requirement substantially limits the potential for federal assistance in investigating or prosecuting hate crimes, even when the crime is particularly heinous. à à à à à Hate crimes demand a priority response because of their special emotional and psychological impact on the victim and the victimsââ¬â¢ community. The damage done by hate crimes cannot be measured solely in terms of physical injury or dollars and cents. Hate crimes may effectively intimidate other members of the vi... ...à à à à Law." Human Rights 22 (1995): 32-33 Dennis, Valerie. MTV remembers Matthew Shepard with 17-hour program on hate à à à à à crimes, University Wire, 01-10-2001 Feingold, Stanley. "Hate Crime Legislation Muzzles Free Speech." The National Lawà à à à à à à à à à Journal 15 (July 1, 1993): 6, 16 Franke-Folstad, Kim. Denver Rocky Mountain News Staff Writer, HATE-CRIME à à à à à LAWS NOT A BLACK-WHITE ISSUE. Denver Rocky Mountain News, 01-18-à à à à à 1999, pp 6A Gellman, Susan. "Sticks And Stones." UCLA Law Review 39 (December, 1991):à à à à à à à à à à 333-396 Patrick, Robert F. Cops find hate often has broad definition, The Washington Times, 04-à à à à à 02-01, pp C1 R.A.V. v. St. Paul (505 U.S. 377) Texas v. Johnson (491 U.S. 397) The Associated Press, Reno Fights Hate Crimes, Newsday, 01-09-1998, pp A21 The Christian Science Publishing Society 30 Brad Knickerbockers, Staff writing of The à à à à à Christian Science Monitor, Hate Crimes: Should they receive special attention? à à à à à The Christian Science Monitor, 06-23-200, pp 22 U.S. v. O'Brien (391 U.S. 367) Wisconsin v. Mitchell (508 U.S. 476) Wooley v. Maynard (430 U.S. 705) W.V. State Board of Education v. Barnette (319 U.S. 624)
Sunday, September 1, 2019
Effects of Having a Schizophrenic Family Member Essay
A. What is Schizophrenia? Schizophrenia is a complex brain disorder that makes it hard for people affected to think clearly, have normal emotional responses, act normally in social situations and tell the difference between what is real and what is not. It makes people withdraw from the outside world and always act out in fear. People suffering from schizophrenia may see or hear things that donââ¬â¢t exist, speak in strange ways, think that people are trying to harm them, and always feel as if they are being watched. They have difficulty in doing activities of daily life. This disease is caused either by oneââ¬â¢s genetic make-up or abnormal brain structure. But the environment can be a cause too, as for the environmental factors, more and more research is pointing to stress. Like any other disease, schizophrenia has its own symptoms like strange ways of speaking, inability to express emotion and irrational statements. It is in these symptoms that we can detect persons with schizophrenia. And it is important that we diagnose them for medical treatment for schizophrenia may lead to violent behavior. B. Statement of the Problem People with schizophrenia donââ¬â¢t relate with people well and therefore makes it hard for the people who care for them to maintain a healthy relationship with them, the people they are related to, for example. For Schizophrenic people, it is hard to hold a stable job or even care for themselves. This makes them dependent on others and who else is best to care for them than their own family. However, schizophrenia sometimes results to violent behavior due to their inability to think clearly and belief that people are always trying to harm them. That is why many of their family members donââ¬â¢t know how to deal with them and this causes stress within the family. C. Thesis Statement Effects of Having a Schizophrenic Family Member D. Significance of the Study Schizophrenia is not a rare condition. The lifetime risk of developing schizophrenia is widely accepted to be 1 in a 100. It therefore affects thousands of families. The love and support of a family is vital in treating Schizophrenia but it is difficult to cope with its symptoms. A family member deals with extreme reactions, deterioration from personal hygiene, inability to concentrate and social withdrawal. It is seen that families only put up with the patients for a short period of time because of their frustration in what seems to be lack of progress in treatments. In their inability to understand a person with schizophrenia, a familyââ¬â¢s emotional support may wane and some even cut off all contact with their schizophrenic son, daughter, or sibling.
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