Theory Paper Research Example | Topics and Well Written Essays - 1000 words

Theory - Research Paper Example Over the years, the model has been adopted to examine a wide range of long-and-short-term health behaviours among people of all ages and nationalities such as the spread of cancer due to the failure by people to go for free cancer screening clinics (Rejeski, Brawley, McAuley, & Rapp, 2006). The Health Belief Model was developed out of the realization that humans possess positive, negative and neutral values and their response to various issues is based on these three regions. The Health Belief Model often has two dimensions namely the threats and net threats. These two areas are categorized into susceptibility, severity, benefits and barriers and it is believed that these four constructs explain people’s willingness to react to situations. While these four concepts are usually constant, an addition of cues to action usually triggers the willingness and motivates clear behaviour. In recent days, there has been an addition of self-efficacy, which is the focus on one’s self-belief in the capacity to successfully complete an action (Rejeski, Brawley, McAuley & Rapp, 2006). Ideally, the Health Belief Model is founded on the hypothesis that if the end result is desirable, there is a higher likelihood for individuals to be more motivated to alter their behaviour. For this model to work, psychologists believe that certain behaviours are pointers to certain results. The self-efficacy expectancy concept posits that individuals have within them what it takes to bring about certain results. If a particular incentive is added to the environment within which an individual lives, then the chances of getting a certain outcome is amplified (Rejeski, Brawley, McAuley, & Rapp, 2006). Perceived Susceptibility; this is usually defined as an individual’s opinion of the probabilities of acquiring a certain condition. In the Health Belief Model, this is often used to define the threatened people as well as in defining the risk levels. This concept

History of Oklahoma Research Paper Example | Topics and Well Written Essays - 750 words

History of Oklahoma - Research Paper Example The west side of state experienced extensive drought and winds to generate storms as the east side of the region experienced a tropical climate. Hunting and gathering was a perverse activity in the west side of the state. The people that lived on the eastern side of the state practiced farming since the climate was favorable. According to the evidence of anthropologists humanity exists in the region prior to 1500 A.D. Researchers find oldest form of Paleo cultures, clovis cultures and folsom. Indigenous people populate the area that symbolically represents a pan-shaped figure. The eastern side of Oklahoma represented the Caddoan Mississippian culture that practiced agrarian activities. Natives living in the area established their houses on mounds and Chiefdoms controlled different communities. The Caddoan Mississippian culture emerged from earlier culture in 1000 A. D. Geographical-location of Caddoan was on Woodland penetrating the Red River. Other communities believed to live in the eastern side of Oklahoma included Wichita people that survived on the Great Plains. The difference between Mississippian cultures and Wichita plains culture is that the latter practiced agrarian activities while the former practiced hunting and gathering. Farming activity appeared in the South Canadian Rivers at 900 AD. . Native Americans at this period that practiced farming grew different types of crops such as legumes. The people practiced fishing, hunting of rabbits, deer, and gathered mussels. Indigenous people constructed rectangular thatched dwellings mostly near the river basins. Apache groups appeared at around 1500 and collaborated with Wichita cultures. Archeologist evidence suggests that Kiowa-Apache culture were hunter and gatherers. The only difference between Wichita culture and Apache culture is that the latter used dogs in their hunting spree. Both cultures are similar in that they

Critical Thinking Essay Example | Topics and Well Written Essays - 1000 words - 1

Critical Thinking - Essay Example When organizations use effective critical thinking skills and processes, they draw legitimate conclusions based on perfect evidence and well-supported claims. In an organization employees are expected to make good decisions. And these decisions need to be based on a methodical and careful examination of all existing information. In order to take a good decision it is important to ask relevant questions, listen to the each and every one, compile complex information, and involve others and make use of their expertise in critical decision making. Recently, I got promoted as the regional sales manager for a pharmaceutical company. This promotion came to me as a reward for helping my company achieve the set target and also by getting involved in the companies’ decision making that will determine the future growth of my company. Until the last year the sales target was only 3 crores but the company put forward a proposal to achieve 50 crores in the next 10 years. Though it looked challenging, I took up the challenge and initiated the planning process. I made a through market survey to find out if such a huge target could be achieved in the next 10 years. I also took the feed back from my subordinates and also suggestions my superiors. Before I put forth the final plan in front of my company, I had to make sure the all my team members were with me and supported my plan. Once I finished with my planning I presented it. I was confident about the success of my plan because each and every step to be taken was planned out critically.

Successful Implementation of Electronic Health Information Technology Research Paper

Successful Implementation of Electronic Health Information Technology - Research Paper Example In case of these, the system is destroyed, replaced, and a new life cycle begins (McGonigle and Mastrian 201-202). There are various risks involved in the purchasing and implementing of the HIT system. An organization therefore, needs to follow particular steps to avoid the risks. According to McGonigle and Mastrian, a waterfall model is necessary in guiding the steps involved in purchasing and implementing of a new HIT system (205). This model mainly includes feasibility, analysis, design, implementation, testing, and maintenance. In New York’s Bezalel Rehabilitation and Nursing Center, before the purchase of a HIT system, the management, in collaboration with the concerned staff ensure that the previous system is analysed, including its effectiveness and failures. This way, it becomes easy to identify the needs of the organization, as well as the capacity, and type of the specific system to be purchased. This is because a new system is capable of either solving problems or creating new problems in an organization. Therefore, the main step is to identify, and analyse the workflow of the previous system, and its strengths and weaknesses, which need improvement. This ensures the purchase of the right technology that will serve the needs of the organization (McGonigle and Mastrian 206). Implementing of the new technology in this company involves the selection of programming codes, which best suit the new technology. This includes the right language of programming for the new technology, and other programming codes, based on the requirements of the new acquisition. Testing involves the programming units of the system, its integration level, data capacity, and testing of the whole system. Of great importance is the volume of data the system can accommodate. Beta testing by a team of employees ensures that the system works according to commands in its task execution. Finally, the staff is briefly trained on

Critical Thinking Essay Example | Topics and Well Written Essays - 1000 words - 1

Critical Thinking - Essay Example When organizations use effective critical thinking skills and processes, they draw legitimate conclusions based on perfect evidence and well-supported claims. In an organization employees are expected to make good decisions. And these decisions need to be based on a methodical and careful examination of all existing information. In order to take a good decision it is important to ask relevant questions, listen to the each and every one, compile complex information, and involve others and make use of their expertise in critical decision making. Recently, I got promoted as the regional sales manager for a pharmaceutical company. This promotion came to me as a reward for helping my company achieve the set target and also by getting involved in the companies’ decision making that will determine the future growth of my company. Until the last year the sales target was only 3 crores but the company put forward a proposal to achieve 50 crores in the next 10 years. Though it looked challenging, I took up the challenge and initiated the planning process. I made a through market survey to find out if such a huge target could be achieved in the next 10 years. I also took the feed back from my subordinates and also suggestions my superiors. Before I put forth the final plan in front of my company, I had to make sure the all my team members were with me and supported my plan. Once I finished with my planning I presented it. I was confident about the success of my plan because each and every step to be taken was planned out critically.

What Mary Didn’t Know Essay Example for Free

What Mary Didn’t Know Essay The knowledge argument aims to refute physicalism, the belief that the world is entirely physical. Physicalism, also known as materialism, is the view that an individual’s experiences are subjective as it follows the strain of the conscious mind. It plays with the idea that an individual’s understanding of the world could be fulfilled through physical means. In the text What Mary Didnt Know, Jackson relays the hypothetical story of a scientist named Mary who was said to have developed a grasping knowledge about every physical aspect of the world. She was also kept away from being exposed to colors and only sees and learns things in black and white. When it was decided that she should be released her from her self-contained room, she was able to see a myriad of colors for the first time (Jackson, 1986). Out of this scenario, Jackson posits a question that challenges the principles of physicalism: If Mary has knowledge of all physical facts about the world and has learned something new once outside, it must be something that is not physical, and therefore it would dispute that everything in reality can be explained through physical means (Jackson, 1986). The central statement of the argument flows in this manner: P1: Prior to Mary’s release, it is a known fact that she is knowledgeable about the physical aspect about the world and other people. P2 After releasing Mary from her confined space and out into the world of color, Mary realizes that she does not know everything there is to know about other people and the world as she has obtained additional information about them. Therefore, it is postulated that Mary has not exhausted all physical information regarding other people and the world as she has learned something new outside her confinement. Clearly, this conclusion states that the notions about physicalism are false since there are certain truths that are not encompassed in the physicalist aspect of things (Jackson, 1986). The main conviction against physicalism is said to be the idea of qualia. According to Jackson, Qualia is said to be something that which is felt from experience. It is the notion that connects experiences to an idea or knowledge of a subject in a distinct way. Not everyone’s experience is the same as individuals are inherently different so one could denote that there are different ways to experience and interpret qualia. Neverthelss, Qualia poses problems of its own such as the assimilation of consciousness, introspection, comprehension and familiarity. However, the thought that will be focused on here is the existing conflict between qualia and physicalism (Jackson, 1986). If a physicalist claims that Mary knows what it’s like to see colors while confined in her room, the physicalist must be able to explain why Mary appears to acquire that knowledge when she leaves. The physicalist may deny the claim of knowledge intuition but then it would have to disregard the postulates that follow it (Jackson, 1986). There are many possible responses to support Jackson’s argument. One of which is the ability hypothesis from Ryle (1949) which illustrates a definite distinction between the proposed knowledge-that and knowledge-how. Knowledge-that is simply information which clarifies a statement based on the knowledge that has been obtained. Knowledge-how refers to a statement or information that is concerned with the process of how one obtains new knowledge. The knowledge argument only reinforces that Mary gains knowledge-how. On the other hand, the second postulate in the knowledge argument would only be true if Mary gained propositional knowledge (O’Hear, 2003). Secondly, there is the notion of metaphysically necessary truths. A metaphysical necessary truth is something that which could have failed to be the case. Logical truths could provide clear examples of this. For instance, an argument which states that a hippopotamus cannot fly like birds is a necessary truth. However, if laws the laws of nature were different then a hippopotamus would be able to fly like birds in a metaphysical sense (O’Hear, 2003). A metaphysically necessary truth is a truth that is narrowed down to the basics which does not simply rely on the existing nature of laws. Saul Kripke (1972) was notable for his argument regarding metaphysically necessary truths that disregards pure logic. For example, his view, that water is H2O is metaphysically necessary but he also recognizes that there are substances that resemble water or shares similar superficial qualities like its taste and visual appearance. However, he argues that such substances are not really water because it has a different molecular composition (O’Hear, 2003). In connection with the metaphysical necessary truths argument, a third approach introduces the distinction between a priori and a posteriori physicalism. It assumes that if physicalism is true then the complete truth about a subject matter is a priori that is extracted from the complete physical truth (O’Hear, 2003). A Priori is the initial statement taken out of the context of the complete physical truth, which is the posteriori. As was mentioned, the crucial claim of a posteriori physicalism is that it asserts that in order to be aware of the knowledge or change, one must be able to experience it. However, it is argued that Mary does not have relevant experience with regard to human color vision therefore she does not know. This argument would only be valid if the posteriori is not physically conceivable (O’Hear, 2003). A fourth draws from the conceivability argument of Descartes. The main argument emphasizes the dual properties of the mind and body. Descartes believes that if an individual can clearly and definitively visualize his or her mind without the body and his or her body without the mind, then both can exist without each other, which emphasizes the dichotomy between the two. Contemporary versions of this argument is said to carry out the inversion of qualia wherein one’s view of a subject matter may be different to the view of another (O’Hear, 2003). The fifth anti-physicalist argument is derived from the explanatory thought. The contention begins with the premise that physicalist descriptions of consciousness justify only the structure of the thought and function or role of the experience, which is not enough to explain the consciousness at work. For instance, if an individual learns about the Eiffel tower from a book, he or she envisions it through the descriptions in the book that describes its history and structure and its impact on the society. The knowledge the individual acquires from the book is limited since the actual experience of being in Paris to witness the structure has not been experienced (O’Hear, 2003). The sixth and final argument asserts the distinction of various conceptions of the physical. The argument stresses that the properties which define information by the conception of physical theory differs from the attributes that define those which rely on the conception of objects. It suggests that the first premise is open to either of the two interpretations. The notions about inverted qualia definitely support this argument since it makes use of the special attributes that is missing in observations that is purely physical (O’Hear, 2003). Conclusion The knowledge argument of Jackson assess that there is a difference in the type of fact being presented and that it may not be entirely physical. The succeeding anti-physicalist arguments and its derivative all question the essential assertions of physicalism that creates an abstract notion of reality. Jackson’s efforts in creating a stir on the drawbacks of physicalism have contributed a great deal of knowledge into exploring the depths of the subconscious mind. The arguments presented in the paper were long and confusing but it was very interesting to see different sides of the anti-physicalists streams of thought since collectively, the main premise of Jackson made much more sense. However, it seems that supporters of physicalists are coming up with their own responses to such arguments which create a much more complex understanding of just how a human’s consciousness works to define the physical world. References Jackson, F. (1986). What Mary Didn’t Know. The Journal of Philosophy, 83(5), 291-295. Retrieved March 11, 2009 from JSTOR database. O’Hear, A. (2003). Minds and persons. New York: Cambridge University Press.

Tuberculosis: Prevention and Treatment

Tuberculosis: Prevention and Treatment Tuberculosis (TB) is an airborne infectious disease which is caused by strains of mycobacteria, mainly Mycobacterium tuberculosis1. There are roughly one third of the worlds population are infected with tuberculosis where nine millions of new cases reported annually2. Although tuberculosis can be prevented and treated, it continues to cause millions of deaths every year2. When infected individual coughs, sneezes or spits, M. tuberculosis is propelled into the air and infected those who breathed in the bacteria that existed in droplets of saliva3. Primarily, tuberculosis will affect the lungs, known as pulmonary tuberculosis3. It will also affect other parts of body, for instance lymph nodes, bones, brain and kidneys3. Once a person is infected with tuberculosis, there are basically three possible ways may occur. Firstly, the immune system plays a vital role and strong enough to kill the bacteria3. Secondly, immune system is not strong enough to fight off the bacteria but is able to b uild a defensive barrier against the bacteria3. Individuals who are latently infected with M. tuberculosis show asymptomatic where these bacteria lie dormant in the lungs and able to reactivate after years1. The disease is often reactivated in those who are immunocompromised or generally weakened. Lastly, the immune system fails to kill bacteria causing the bacteria to grow and spread towards other parts of body which is called active tuberculosis3. In the fight of tuberculosis, World Health Organisation (WHO) recommends universal Bacille Calmette-Guà ©rin (BCG) vaccination in the countries with high TB burdens4. BCG vaccine contains weakened form of M. tuberculosis which will induce human antibodies to fight against this type of bacteria. The efficacy of BCG vaccination can be ranging from 0% to 84%5. This may be due to the frequency of TB exposure and quality of vaccine used, leading to arguments on BCG vaccination efficacies4. One of the greatest arguments is that BCG vaccination causing positive reactions to tuberculin skin testing and hence interfere with the diagnosis of latent TB4. Existence of evidences showing the rates of efficacy also depends on geographical location, age at vaccination and form of TB further complicate the situation. Currently, TB chemotherapy is made up of combination of a list of first-line drugs isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) 6. If the treatment fails d ue to bacterial drug resistance, or patient unable to tolerate, second-line drugs for instance para-aminosalicylate (PAS), fluoroquinolones, ethionamide and cycloserine are introduced6. These are considered as second line drugs generally either less potent with larger doses regimen or more toxic with serious side effects6. Tuberculosis is presently treated in two phases, namely initial phase and continuous phase7. In initial phase, the patient will be treated with concurrent use of four first line drugs, with the aim to eradicate or control bacteria population to replicate in rapid motion and also avoid the emergence of bacteria resistance7. The treatment choices available for initial treatment include isoniazid, rifampicin, pyrazinamide and ethambutol7. Streptomycin is used rarely but can be used in patients who infected with bacteria that are resistant to isoniazid before the therapy is commenced7. The duration for initial phase is 2 months whereas the continuous phase takes 4 months7. During the four months of continuous phase, patients are treated with isoniazid and rifampicin at same doses7. Most of the TB treatment is supervised where drug administration needs to be fully supervised by healthcare professions since lengthy duration of treatment causing incompliance in patients7. These patients who are unlikely to be compliance will be given the drugs three times a week until the course is completed while patients who able to comply with the treatment will not be supervised7. Despite the chemotherapy treatment and BCG vaccine, TB remains as a significant infectious disease due to increasing emergence of drug resistant TB and co-infection with Human Immunodeficiency Virus (HIV) 6. Since the host defense in HIV patients is suppressed, they are more susceptible to TB infections. Moreover, drug- drug interactions between antiviral therapy and anti-TB also causing complications in treating co-infected patients6. Drug resistant TB has evolved mainly because of improper treatment or incompliance in patients who stop taking their medications before the bacteria is being fully eradicated since the duration of treatment is lengthy which takes 6-9 months8, 9. The mechanism involved includes chromosomal mutations in genes that responsible for drug targets encoding9. When there is a sequential accumulation of mutations, multi-drug resistant tuberculosis (MDR-TB) emerges where the M. tuberculosis strains will resistant to two of the most commonly used drugs, Isoniazid and Rifampicin9. Patients with MDR-TB are then relying on the second-line drug classes, fluoroquinolones and the three injectable agents namely amikacin, capreomycin, and kanamycin10, 11. The chances to cure would dramatically be reduced for patients who infected with extensively drug-resistant tuberculosis (XDR-TB), a situation where the isolated strains are resistant against any one of fluoroquinolones and at least one of three injectable drugs6. In order to combat with the MDR-TB or XDR-TB and optimize the tuberculosis drug regimen, it is crucial to understand the mechanism of action of current using first-line drugs and how resistance is developed against these drugs. Isoniazid (INH) or isonicotinic acid hydrazide is discovered in 1952, a bactericidal agent which active against organism of the genus Mycobacterium, especially M. tuberculosis, M. bovis and M. kansassi6, 12. In vivo, INH has shown to be bactericidal in culture over the first 48 hours which become bacteriostatic after this particular time frame12. This indicates that INH is bacteriostatic for slow replicating bacilli but is bactericidal against rapidly dividing mycobacterium. The minimal tuberculostatic concentration is 0.025 to 0.05ug/ml13. INH is a prodrug that needs to be activated by catalaseperoxide hemoporotein, KatG before acts by inhibiting mycolic acid synthesis and cell wall disruption in susceptible mycobacterium13, 14. This inhibitory action is only targeted to mycobacteria since other bacteria do not contain mycolic acid in the cell wall13. INH acts by inhibit enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA that are crucial in fatt y acid synthesis system for mycolic acid15. Resistance to INH is believed due to mutations in gene encoding catalaseperoxidase katG or InhA or lacking KatG 9, 14. Isoniazid is metabolised in the liver, mainly by acetylation and dehydrazination where slow acetylator may experience higher concentration leads to potential toxicity before excreted in the urine within 24 hours13. Rifampicin (RIF), discovered in 1963, is a lipophilic semisynthetic derivative of rifamycin antibiotic which is produced by the fermentation of a strain of Amycolatopsis mediterranei6, 9, 16. RIF has bactericidal activities against a broad spectrum of microorganisms including gram-positive and gram-negative. RIF will inhibit the action of DNA-dependent RNA polymerase of mycobacteria that is encoded by rpoB through formation of a stable drug-enzyme complex9. This will suppress the initiation chain formation in RNA synthesis and hence prohibit protein synthesis in M. tuberculosis9. Development of resistance to RIF is mostly due to mutation in 81 base pair region of rpoB gene thus facilitate a straightforward approach to detect MDR-TB since 85-90% RIF-resistant strains are also resistant to INH9. RIF produces peak plasma concentration of 7ug/mL in 2 to 4 hours after ingestion of 600mg17. It also distributed well to most of the body tissues and fluids, including cerebrospinal fluid since it is lipophilic17. Following absorption from the gastrointestinal tract, RIF is eliminated rapidly in the bile with fewer amounts excreted through urine17. Pyrazinamde (PZA) is discovered in 1954 and it produces excellent sterility effects against semidormant tubercle bacilli at slightly acidic pH6, 9. The antimicrobial activity of PZA is through interference with mycolic acid synthesis in M. tuberculosis by pyrazinoic acid, an active moiety of PZA9. Conversion of PZA to pyrazinoic acid is mediated by pyrazinamidase enzyme that is encoded by pncA gene in M. tuberculosis, thus indicating that these bacilli are sensitive to PZA9. Resistance against PZA evolved when mutation occur at pncA gene that is responsible for pyrazinamidase, hence affecting the activity of this enzyme9. PZA is well absorbed from gastrointestinal tract and is widely distributed to most tissues and fluid too17. The oral administration of 500 mg PZA produces plasma concentrations of 9-12ug/ml after two hours and 7ug/ml after 8 hours17. PZA is metabolized in liver whereas the metabolites are excreted through renal glomerular filtration17. Ethambutol (EMB) is discovered in 1962, acts as bacteriostatic agent and is active against undergoing cell division6, 18. EMB primarily targets on impairment of cell wall polymerization by inhibits arabinosy transferase, a vital enzyme responsible for mycobacteria cell wall biosynthesis9, 18. Since arabinosy transferase enzyme is encoded by embC-embA-embB genes, resistance against EMB evolved is believed due to mutation of these genes9. EMB is currently used as one of the first-line treatment for tuberculosis mainly because of its synergistic effect with other front-line drugs and its low toxicity property18. There is roughly 75-80% of an oral dose of EMB is rapidly absorbed in gastrointestinal tract with absorption unaffected when administered with foods19. In addition, EMB is distributed widely to body tissues and fluid, including cerebrospinal fluid before being metabolized in the liver and excreted in urine19. Streptomycin (SM) is an aminoglycoside antibiotic, used as first line treatment for TB when it first discovered in 19441, 6. Streptomycin is isolated from the bacteria Streptomyces griseus and its antimicrobial effects against M. tuberculosis is highly effective when use in combination with other first line agents20. However, SM is no longer considered as first line treatment as resistance against it has developed rapidly1. The optimum pH for SM is at pH8 where its bacteriostatic activity will reduce with increasingly acidic environment20. SM acts by binding tightly to A site of 16S ribosomal RNA subunit, interferes with mRNA translation, causing faulty protein being produced1, 9. Resistant emergence when the mutation occurs at gene rpsL and rrs that encoded for 16S and S12 ribosomal protein1, 9. Upon administration, SM is poorly absorbed from gastrointestinal tract and mostly administered parentally1. SM is mostly excreted in urine and patients with low renal profile might experienc e toxicity such as neurotoxic reactions1. When the first line treatment is no longer suitable for patients or patients develop multi-drug resistance TB, second line drugs will then be introduced in combating the TB. Second line drugs that are mostly used include Ethionamide (ETH), Cycloserine (CS), Para-Aminosalicylic Acid (PAS) and Fluoroquinolones (FQ). ETH has been in use since 1960s, is a structural analogue of INH and it targets at inhibition of mycolic acid biosynthesis in tubercle bacilli9, 21. INH however is much more potent than ETH since the minimal inhibitory concentration for ETH is 0.5-5.0ug/mL21. Resistance evolved due to mutation at gene InhA and ethA which encode for oxygenase enzyme in activation of ETH 9. In vitro, CS has inhibitory effect on M. tuberculosis at 5-200ug/mL and there is no cross resistance occurred between CS and other drugs13. CS acts by interfereing the biosynthesis of bacterial cell wall13. CS is well absorbed in gastrointestinal tract and also widely distributed to body tissues and fluid including cerebrospinal fluid13. PAS was first introduced as first line drug but being replaced by Ethambutol in 1960s1. It acts bacteriostatically with possessing inhibitory effect at concentration less than 1mg/ml by interfere with folic acid metabolism in bacteria1. PAS is readily absorbed from gastrointestinal tract and distributed well throughout the body. Approximately 80% of the drugs will be excreted via kidney after being metabolized to acetylated form1. Moxifloxacin and Gatifloxacin are both been synthesized and evaluated as excellent bactericidal agents through inhibiting DNA gyrase, an ATP-dependent enzymes topoisomerase II which is responsible in bacteria DNA transcription9. DNA gyrase is consisted of two subunits that is arranged in a complex, is encoded by two different genes, gyrA and gyrB where mutations at gyrA will normally cause bacteria resistance to these new generation of flouroquinolones9. Due to the increasing incidence of multidrug resistance TB, it is highly desirable to develop new drugs that are not only potent and effective against current resistant strains of M. tuberculosis but also possess shorter treatment duration since most of the incompliance of patients is brought up by lengthy TB treatment. Most of the mechanisms of action of current treatments are involved in interfering the bacterial DNA synthesis, protein and mycolic cell wall biosynthesis. The enzymes that participate in these pathways could also be the target of newly designed drugs such as TMC207, one of the new drugs which are currently under investigations and clinical trials. TMC207 is a member of diarylquinoline class of compound which target at adenosine triphosphate (ATP) synthase by binding to subunit C of the synthase, blocking the energy pathway of mycobacteria22, 23. In vitro, TMC207 not only possesses ability to inhibit both drug sensitive and resistant M. tuberculosis isolates, but also able to sterilize the patient through killing the dormant bacilli bactericidally22. TMC207 showed a minimum inhibitory concentration of 0.03ug/mL against M. tuberculosis, suggesting a more potent agent compared to current first- line treatments such as isoniazid and rifampicin23. Apart from that, its synergistic effect with pyrazinamide could promise as effective drug combination for sterilizing the patients against TB22. A phase I clinical trials which involved short terms administration of TMC207 in healthy individuals showing no adverse effects and the subjects are well tolerated with it23. However, it is essential to investigate the selectivity of TMC207 again st mammalian ATP synthase with longer periods to ensure the patients safety when administered with TMC207. Thiacetazone (TAC) is widely used as second line anti-TB agent against multiresistant tuberculosis at present24. TAC acts by interferes the biosynthesis pathway of mycolic acid in tubercle bacilli24. The fact that M. tuberculosis has been difficult to eradicate and remains persistent is due to its cell wall that composed of mycolic acid which is resistant against chemical injury, dehydration and also has low permeability to antibiotics24. Mycolic acid contains cyclopropane rings that is activated through cyclopropane mycolic acid synthase (CMASs), has a significant contribution to tuberculosis24. By inhibiting the cyclopropanation, the cell wall biosynthesis will then be interrupted, introducing the bactericidal effects24. The aim of this research is to synthesis and evaluates the analogues of Thiacetazone which might be potential anti tuberculosis agents. The analogues will be tested against different strains of mycobacteria in lab. The target actions of these analogues will also be identified based on the structure of the analogues. The above analogue is synthesized when a benzylaldehyde reacts with a primary amine. This is a condensation process and an imine is produced. The changes at position R1 to R3 with different electron withdrawing groups are first planned to be evaluated. However, the plan is prohibited since the corresponding structures are either unavailable or too expensive that falling outside the budget. After revised on the previous analogues that were discovered and their respective MIC values obtained from lab, the structures of new analogues that are going to be evaluated are finally sorted out. The R1 to R3 positions would be replaced by either a -chloro or a -methoxy with R8 position would either be an amine, a methyl or a benzene ring. A chloro is used at position R1 to R3 since it is electron withdrawing, big and lipophilic molecule whereas the methoxy group is electron donating, small and quite lipophilic. For R8 position, an amine is selected because it is electron withdrawing and small. A methyl is also selected since it is quite lipophilic, small and electron donating. On the other hand, benzene ring which is highly lipophilic, neither electron donating nor withdrawing group might have a different effect on the analogue synthesized. References: Patrick Brennan, Douglas Young (2008). Tuberculosis. 88(2), 85-86, 137-138, 162-163. Health Protection Agency. http://www.hpa.org.uk/HPA/ National Health Services. http://www.nhs.uk/Pages/HomePage.aspx Zaida Araujoa, Jacobus Henri de Waard, Carlos Fernà ¡ndez de Larrea, Rafael Borges, Jacinto Convit (2008). The effect of Bacille Calmette-Guà ©rin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis. Vaccine 26, 5575-5581. Hart and Sutherland (1977). BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Br Med J2(6082), 293-295. Global Alliance for TB Drug Development. http://www.tballiance.org/home/home.php 57th edition of British National Formulary: Section on Tuberculosis drugs, 316-317. Blumberg, H. M. et al. (2003). American Thoracic Society/ Centers for Disease and Prevention/ Infectious Disease Society of American: treatment of TB. Am.J.Respir.CareMed.167, 603-662. Suhail Ahmad and Eiman Mokaddas (2009). Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis. Respiratory Medicine 103(12), 1777-1790. Frieden TR, Sherman LF, Maw KL, et al. (1996). A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA 276, 1229-1235. Mukherjee JS, Rich ML, Socci AR, et al. (2004). Program and principles in treatment od multi-drug resistant tuberculosis. Lancet 363, 474-481. Zhang Y. et al. (2003). Isoniazid. Tuberculosis 2, 739-758. Hardmn, J.G., L.E. Limbird, P.B Molinoff, R.W. Ruddon, A.G. Goodman (2006). Goodman and Gilmans The Pharmacological Basis of Therapeutics. 9, 1164-1165. Zhang Y, Heym B, Allen B, Young D, Cole S (1992). The catalase-peroxidase gene and isoniazid resistance by Mycobacterium Tuberculosis. Nature 358, 591-593. Richard A. Slayden, Richard E. Lee and Clifton E. Barry (2002). Molecular Microbiology 38(3), 514-525. Rup Lal, Sukanya Lal (2005). Recent trends in rifamycin research. BioEssays 16(3), 211-216. Hardmn, J.G., L.E. Limbird, P.B Molinoff, A.G Gilman (2001). Goodman and Gilmans The Pharmacological Basis of Therapeutics. 10, 1278-1281. Raghunandan Yendapally and Richard E. Lee (2008). Design, synthesis and evaluation of novel ethambutol analogues. Bioorganic and Medical chemistry Letters 18(5), 1607-1611. McEvoy, G.K. (2007). Admerican Hospital Formulary Service. Besthesda, 551. Selman A. Waksman (1953). Streptomycin: Background, Isolation, Properties and Utilisation. Science, 118(3062), 259-266. Sampson AE, Barry CE (1999). Abstract General Meeting American Society Microbiology. 99, 635. Andreas H.D., Alexander Pym, Martin Grobusch et al. (2009). The Diarylquinoline TMC207 for Multidrug- Resistant Tuberculosis. 360(23), 2397-2405. Anna C. Haagsma, Rooda Abdillahi-Ibrahim, Marijke J. Wagner, Klaas Krab, Karen Vergauwen, Jerome Guillemont, Koen Andries, Holger Lill, Anil Koul, and Dirk Bald (2009). Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towardsthe Eukaryotic homologue. Antimicrobial Agents and Chemotherapy, 53(3), 1290-1292. Anuradha Alahari, Xavier Trivelli, Yann Guà ©rardel, Lynn G. Dover, Gurdyal S. Besra, James C. Sacchettini, Robert C. Reynolds, Geoffrey D. Coxon, Laurent Kremer (2007). Thiacetazone, an Antitubercular Drug that Inhibits Cyclopropanation of Cell Wall Mycolic Acids in mycobacteria. PloS ONE, 2(12): e1343. Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets. We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC), and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strain Mycobacterium bovis BCG, as well as in the related pathogenic species Mycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses of mycolic acids purified from drug-treated mycobacteria showed a significant loss of cyclopropanation in both the ?- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclop ropanation, suggesting that the drugs act directly on CMASs. This is a first report on the mechanism of action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria. The implications of this study may be important for the design of alternative strategies for tuberculosis treatment.