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Because Rodriguez does not dispute that Officer Struble had probable cause to medicine vs dentistry cheap diamox 250 mg without prescription stop him medicinenetcom diamox 250 mg, the only question is whether the stop was otherwise executed in a reasonable manner treatment mononucleosis buy diamox 250 mg overnight delivery. Approximately 29 minutes passed from the time Officer Struble stopped Rodriguez until his narcotics-detection dog alerted to medicine quotes doctor cheap diamox 250mg on-line the presence of drugs. That amount of time is hardly out of the ordinary for a traffic stop by a single officer of a vehi Cite as: 575 U. During that time, Officer Struble conducted the ordinary activities of a traffic stop—he approached the vehicle, questioned Rodriguez about the observed violation, asked Pollman about their travel plans, ran serial warrant checks on Rodriguez and Pollman, and issued a written warning to Rodriguez. And when he decided to conduct a dog sniff, he took the precaution of calling for backup out of concern for his safety. As Caballes makes clear, the fact that Officer Struble waited until after he gave Rodriguez the warning to con duct the dog sniff does not alter this analysis. The stop here was “lawful at its inception and other wise executed in a reasonable manner. As in Ca balles, “conducting a dog sniff [did] not change the charac ter of [the] traffic stop,” ibid. The majority’s rule thus imposes a one way ratchet for constitutional protection linked to the characteristics of the individual officer conducting the stop: If a driver is stopped by a particularly efficient of ficer, then he will be entitled to be released from the traf fic stop after a shorter period of time than a driver stopped by a less efficient officer. Similarly, if a driver is stopped by an officer with access to technology that can shorten a records check, then he will be entitled to be released from the stop after a shorter period of time than an individual stopped by an officer without access to such technology. I “cannot accept that the search and seizure protections of the Fourth Amendment are so variable and can be made to turn upon such trivialities. We have repeatedly explained that the reasonableness inquiry must not hinge on the characteris tics of the individual officer conducting the seizure. We have held, for example, that an officer’s state of mind “does not invalidate [an] action taken as long as the cir cumstances, viewed objectively, justify that action. We have spurned theories that would make the Fourth Amendment “change with local law enforcement practices. And we have rejected a rule that would require the offense establishing probable cause to be “closely related to” the offense identified by the arresting officer, as such a rule would make “the constitutionality of an arrest. In Devenpeck, a unanimous Court explained: “An arrest made by a knowl edgeable, veteran officer would be valid, whereas an arrest made by a rookie in precisely the same circumstances would not. We see no reason to ascribe to the Fourth Amendment such arbitrarily variable protection. Under its reasoning, a traffic stop made by a rookie could be executed in a reasonable manner, whereas the same traffic stop made by a knowledgeable, veteran officer in precisely the same circumstances might not, if in fact his knowledge and experience made him capable of completing the stop faster. We have long rejected inter pretations of the Fourth Amendment that would produce such haphazard results, and I see no reason to depart from our consistent practice today. B As if that were not enough, the majority also limits the duration of the stop to the time it takes the officer to complete a narrow category of “traffic-based inquiries. According to the majority, these inquiries include those that “serve the same objective as enforce ment of the traffic code: ensuring that vehicles on the road are operated safely and responsibly. Inquiries directed to “detecting evidence of ordinary criminal wrongdoing” are not traffic-related inquiries and thus cannot count toward the overall duration of the stop. Caballes expressly anticipated that a traffic stop could be reasonably prolonged for officers to engage in a dog sniff. We explained that no Fourth Amendment violation had occurred in Caballes, where the “duration of the stop. The dividing line was whether the overall duration of the stop exceeded “the time reasonably required to complete th[e] mission,” id. The majority’s approach draws an artificial line between dog sniffs and other common police practices. The lower courts have routinely confirmed that warrant checks are a constitutionally permissible part of a traffic stop, see. Such warrant checks look more like they are directed to “detecting evidence of ordinary crimi nal wrongdoing” than to “ensuring that vehicles on the road are operated safely and responsibly. Per haps one could argue that the existence of an outstanding warrant might make a driver less likely to operate his vehicle safely and responsibly on the road, but the same could be said about a driver in possession of contraband. A driver confronted by the police in either case might try to flee or become violent toward the officer. But under the majority’s analysis, a dog sniff, which is directed at uncov Cite as: 575 U. The majority suggests that a warrant check is an ordinary inquiry incident to a traffic stop because it can be used “‘to determine whether the apparent traffic violator is wanted for one or more previous traffic offenses. But as the very treatise on which the majority relies notes, such checks are a “manifest[ation of] the ‘war on drugs’ motivation so often underlying [routine traffic] stops,” and thus are very much like the dog sniff in this case. And the lower courts have routinely upheld such questioning dur ing routine traffic stops. The majority’s rea soning appears to allow officers to engage in some ques tioning aimed at detecting evidence of ordinary criminal wrongdoing. But it is hard to see how such inquiries fall within the “seizure’s ‘mission’ [of] ad dress[ing] the traffic violation that warranted the stop,” or “attend[ing] to related safety concerns. C On a more fundamental level, the majority’s inquiry elides the distinction between traffic stops based on prob able cause and those based on reasonable suspicion. Although the Court has commented that a routine traffic stop is “more analogous to a so-called ‘Terry stop’ than to a formal arrest,” it has rejected the notion “that a traffic stop supported by probable cause may not exceed the bounds set by the Fourth Amendment on the scope of a Terry stop. Although all traffic stops must be executed reasonably, our precedents make clear that traffic stops justified by reasonable suspicion are subject to additional limitations that those justified by probable cause are not. A traffic stop based on reasonable suspicion, like all Terry stops, must be “justified at its inception” and “reasonably related in scope to the circumstances which justified the interfer ence in the first place. It also “cannot continue for an excessive period of time or resemble a traditional arrest. By contrast, a stop based on probable cause affords an officer considerably more leeway. In such seizures, an officer may engage in a warrantless arrest of the driver, Atwater, 532 U. It asserts that the traffic stop in this case, which was undis putedly initiated on the basis of probable cause, can last no longer than is in fact necessary to effectuate the mis sion of the stop. And, it assumes that the mission of the stop was merely to write a traffic ticket, rather than to consider making a custodial arrest. In support of that durational requirement, it relies primarily on cases involving Terry stops. The only case involving a traffic stop based on probable cause that the majority cites for its rule is Caballes. But, that decision provides no support for today’s restructuring of our Fourth Amendment jurisprudence. In Caballes, the Court made clear that, in the context of a traffic stop supported by probable cause, “a dog sniff would not change the character of a traffic stop that is lawful at its inception and otherwise executed in a reasonable manner. To be sure, the dissent in Caballes would have “appl[ied] Terry’s reasonable-relation test. But even it conceded that the Caballes majority had “implicitly [rejected] the application of Terry to a traffic stop converted, by calling in a dog, to a drug search. In doing so, it renders the difference between probable cause and reasonable suspicion virtually meaningless in this context. That shift is supported nei ther by the Fourth Amendment nor by our precedents interpreting it. Had Officer Struble ar rested, handcuffed, and taken Rodriguez to the police station for his traffic violation, he would have complied with the Fourth Amendment. But because he made Rodriguez wait for seven or eight extra minutes until a dog arrived, he evidently committed a constitutional violation. Rodriguez suffered no Fourth Amendment violation here for an entirely inde pendent reason: Officer Struble had reasonable suspicion to continue to hold him for investigative purposes. Our precedents make clear that the Fourth Amendment per mits an officer to conduct an investigative traffic stop when that officer has “a particularized and objective basis for suspecting the particular person stopped of criminal activity. Officer Struble testified that he first became suspicious that Rodriguez was engaged in criminal activity for a number of reasons.

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Jennifer wanted disabilities may want to treatment with cold medical term generic diamox 250mg fast delivery partici • Civic involvement and leadership to treatment wasp stings cheap diamox 250 mg line increase community aware pate in the same opportunities as opportunities ness about this challenge and their peers medicine escitalopram generic 250 mg diamox. In addition medicine vending machine generic 250mg diamox otc, Jennifer Perhaps you already have a focus to brainstorm possible solutions thought students and community in mind. If not, here are some and strategies to overcome the members needed to feel more questions to consider. What would it look daughter without needing per with a disability, what experiences like While ability can more efectively adults with disabilities making her list, she realized that participate in and contribute • Informing an anti-bullying and social inclusion often becomes to all aspects of life in the autism awareness campaign more challenging in middle and community at the middle school level high school than during elemen • Determining the status and • Exploring what the tary school, when children are direction inclusive youth community and school district sometimes more accepting and programming is headed in the can do to make sure all their parents more involved community children are and feel included in their social and academic lives. Jennifer observed that as students age, they become more independent and interested in being around peers who have things in common. For this reason, and because her daughter was in middle school, Jennifer Is a community conversation always decided to focus her event on in the best approach For ad this approach is designed strategies that any local group ditional examples of focus areas, to identify the existing or organization could adopt see the sidebar on this page listing resources, opportunities, and to do strategic planning. The identifed promising decides to hold a community organizer frequently plays the solutions to the challenge. In this case, a learning circle planning group plans the • Table hosts: the table hosts or community of practice event by choosing the venue, are people who are asked to to keep momentum and inviting participants, and sit and stay at one table. This person encouraging everyone to share, of people, rather than welcomes the group, explains and keeping the conversation soliciting their insights and the process, keeps track of time, on topic and focused on ideas. During are the individuals who attend • Fewer than 12 people are the harvest, the facilitator may the event and participate in gathered. Friends Tanya and Emily worked tical ideas and doable strategies for together to organize and host expanding inclusive opportunities their community conversation. Solution hesitant about the community focused conversations enable conversation format. After all, participants to focus primarily they were tired of people talking on generating strategies, gaining and not doing anything. How could a series planning next steps instead of of guided conversations lead spending valuable time discuss people to action Conversations more about the World Cafe that only focus on challenges and process, they realized that asking barriers to inclusion can reinforce the right questions really could inaction and result in hopelessness make all the diference. Community conversa tions should instead focus time and energy on generating solu tions and possibilities. Ask questions that push people Figure 2: Checking your questions strategies to keep conversations to think about what they can do positively framed. Think about your questions are encouraged to structure their questions with “what” and “how” as you consider the following events around 1-2 questions that helps facilitate conversations ideas: move people toward solutions and about possibilities. Consider • Do your questions action (see page 13, Possible com the difference between these simultaneously address munity conversation questions). Meaningful including youth with disabilities encourage responses from questions lead people to think in after-school activities at everyone who will be creatively and innovatively. We will talk about that keep people focused on input and to see if you get the role and responsibilities of problems. It may take the Event and Art of Facilitating the value behind your topic, some tweaking to get the sections (see page 15). Right now, such as “Why is inclusion question just the way you we address how to frame your essential for all people You may think of not help people see their many questions that could be role in nding solutions and asked, but to fully explore and committing to action. Because discuss the topic and generate people chose to come to solutions, we suggest posing your event, you can assume only two questions. Help them take the next step by posing questions that tap into participants’ personal experiences and connections, such as “What can our community do to meaningfully employ more people with disabilities Make a list of several questions about inclusion that are Possible community conversation questions important to and will resonate Below is a list of possible questions that could be used with the community. Write these questions in a way Topic: Inclusion of high school students that encourages action and Question 1: What can we do to ensure that all high school students commitment. While looking over the questions posed by parents as part of Question 2: What can I do in the next 6 months to ensure that all our project, we noticed two high school students are and feel included These pronouns make people consider Topic: Collaboration between community, schools, and families their personal role, rather than Question 1: What can we do as a community to better support focusing on what other people collaboration between the community, schools, and families For example, “What Question 2: What can I do in the next 3 months to improve can we as a community do to collaboration between my community, schools, and families For example, Topic: Community inclusion “What can I do in the next six Question 1: How do we build upon the strength of our months to increase the inclusive communities to ensure that all citizens are included Think about the questions you Are the questions phrased Are the questions relevant to have drafted and consider the broadly enough to encourage re your participants A few parents took to help include your child in ac particular care in developing For example, if your topic is related tivities of his/her choosing For opportunities, a question that or may not have a child who feels example, one parent focused her asks for defnition, such as “What excluded. Or, consider this consider hiring people with dis tions that change the community. She broad cross-section of your com wondered what employers would munity to the event, some people have to gain by hiring people with will not consider themselves disabilities and altered one of her members of your school commu questions to read: “What can I do nity and may not have many ideas to diversify my workplace Changing the wording— most event participants, especially such as “How can we as a com to employers. Another parent munity increase inclusive school decided to focus on inclusion more opportunities for all students By asking a more question and helps participants general question—not specifc consider what their role could to the inclusion of people with be as a community member for disabilities—more participants making schools more inclusive. She re worded her question to state: “How do we build upon the strength of our communities to ensure that all citizens are included This is a great way to receive feedback and to get the types of re sponses you anticipated. Because for youth with disabilities, she and were integral in inviting the brewery was typically rst sought some partners to and getting business leaders closed on Mondays, her event help her. The team invited would not compete with local Arc and an adult service a local professional with business. Parents in the group agency in her town, both of facilitation experience to brought potluck dishes, which were happy to help introduce the event, conduct limiting the expense. They the large-group harvest publicity was also free as met as a “planning team” discussion at the end, and Kristen emailed most of the three or four times before oat among tables to spur invitations. While most support of the parents in our project parents reported being pleasantly decided to handle all of the surprised at the enthusiasm and planning and logistics themselves. Keep this in mind ing, choose questions However, other parents decided when forming your team. This enhanced the people will be very ready and planning process and expanded able to assist while others may 6 weeks before the number of different people not be as available. Try not to be Invite participants through inviting community members to disheartened or lose energy on personal invitations and attend, leading to a potentially those who are not willing or able to by distributing fyers, more diverse participant group. Focus posters, news releases, these parents also shared with on nding the people who are e-invitations, and social us that involving a team led to excited and available. In the end, media announcements deeper consideration of how to the parents in our project found pose questions that would lead to it best to combine their energy real change in their communities. Be Tthe event are that the space Clocation and set up are both creative and consider alternatives. Make sure If the tables are too small, push comfortable for participants, and your room is easy to locate. The not be clear where people should are too big, limit the number of term “World Cafe” was developed go when they arrive at the venue, chairs set at the table. If a venue because the events sought to post signs that give directions to only ofers chairs, borrow card create the intimate, pleasant the room or have a greeter present tables from friends and neighbors.

The selection of the patient characteristics to symptoms 7 days past ovulation discount diamox 250 mg amex be used medications like lyrica diamox 250 mg without prescription, and the order in which they would be used treatment for vertigo generic diamox 250 mg without a prescription, was a complex task with many factors examined and weighed simultaneously medications 101 250mg diamox for sale. Neonates were defined as newborns and all other patients of age less than 29 days at admission. In addition, there are normal new born categories for the 2,000–2,499 gram and over 2,500 gram birth weight ranges. Based on New York hospital data, a neonate under 750 grams dis charged alive costs over 159 times more than a normal newborn. The state of New York had collected birthweight as a standard variable in its statewide hospital database. However, most hospital databases have not historically collected birthweight as a stan dard variable. Unfortunately, some diagnoses usually associated with neonates can also be used as principal diagnosis for non-neonate patients. Patients with age over 28 days with a principal diagnosis that is strictly a neonatal diag nosis. A patient was considered to have a multiple major infection when a diagnosis was present from two or more different major infection categories. In addition to length of stay, the database con tained patient cost computed using departmental cost-to-charge ratios. All trauma diagnoses were reviewed and divided into eight body site categories (head, chest, abdomen, kidney, urinary, pelvis and spine, lower limb, and upper limb). Within each body site, the traumas that were considered significant were identified. Patients were differentiated based on the sub stance being abused: 13 Opioid abuse Alcohol abuse Cocaine and other drug abuse Each category of substance abuse was then further subdivided based on whether the patient left against medical advice, and the presence of complications and comorbidities. Patients with certain mouth, larynx, or pharynx diseases are not patients on long-term ventilation support, but are patients who are having the tracheostomy performed for therapeutic reasons as treatment for the mouth, larynx, or pharynx problem. Major Diagnostic Categories 1 Diseases and Disorders of the Nervous System 2 Diseases and Disorders of the Eye 3 Ear, Nose, Mouth, Throat, and Craniofacial Diseases and Disorders 4 Diseases and Disorders of the Respiratory System 5 Diseases and Disorders of the Circulatory System 6 Diseases and Disorders of the Digestive System 7 Diseases and Disorders of the Hepatobiliary System and Pancreas 8 Diseases and Disorders of the Musculoskeletal System and Connective Tissue 9 Diseases and Disorders of the Skin, Subcutaneous Tissue and Breast 10 Endocrine, Nutritional and Metabolic Diseases and Disorders 11 Diseases and Disorders of the Kidney and Urinary Tract 12 Diseases and Disorders of the Male Reproductive System 13 Diseases and Disorders of the Female Reproductive System 14 Pregnancy, Childbirth and the Puerperium 15 Newborns and Other Neonates with Conditions Originating in the Perinatal Period 16 Diseases and Disorders of Blood, Blood Forming Organs and Immunological Disorders 17 Lymphatic, Hematopoietic, Other Malignancies, Chemotherapy and Radiotherapy 18 Infectious and Parasitic Diseases, Systemic or Unspecified Sites 19 Mental Diseases and Disorders 20 Alcohol/Drug Use and Alcohol/Drug Induced Organic Mental Disorders 21 Poisonings, Toxic Effects, Other Injuries and Other Complications of Treatment 22 Burns 14 Table 1–1. Some of these primarily affect pediatric patients while others affect patients of all ages. The number of secondary diagnoses has no effect on the subclass assigned to the patient. As the health care industry has evolved there has been increased demand for a patient classification system that can be used for applications beyond resource use, cost, and payment. In particular, a patient classification system is needed for: the comparison of hospitals across a wide range of resource and outcome measures. As previ ously defined, these patient attributes have the following meaning: Severity of illness. The relative volume and types of diagnostic, therapeutic, and bed services used in the management of a particular disease. The addition of the four subclasses addresses patient differences relating to severity of illness and risk of mortality. For exam ple, a patient with acute choledocholithiasis (acute gallstone attack) as the highest secondary diagnosis may be considered a major severity of illness but only a minor risk of mortality. The severity of illness is major since there is significant organ system dysfunction associated with acute choledocholithiasis. However, it is unlikely that the acute episode alone will result in patient mortality and thus, the risk of mortality for this patient is minor. If additional, more serious diag noses are also present, patient severity of illness and risk of mortality may increase. For example, if peritonitis is present along with the acute choledocholithiasis, the patient may be considered an extreme severity of illness and a major risk of mortality. Since severity of illness and risk of mortal ity are distinct patient attributes, separate subclasses are assigned to a patient for severity of illness and risk of mortality. Although the subclasses are numbered 1–4, the numeric values represent categories and not scores. For example, severity subclass 4 congestive heart failure patients are not comparable to severity subclass 4 patients with a fractured leg. In other words, the deter mination of the severity of illness and risk of mortality is disease-specific. Thus, the significance attributed to complicating or comorbid conditions is dependent on the underlying problem. For example, certain types of infections are considered a more significant problem in a patient who is immunosuppressed than in a patient with a fractured arm. Patients with multiple comorbid conditions involving multiple organ systems represent difficult-to-treat patients who tend to have poor outcomes. Other examples of this kind of consolidation include vaginal deliv ery with complicating diagnoses and other antepartum diagnoses with complicating diagnoses. Examples of surgical category consolidations are cholecystectomy with common duct exploration versus chole cystectomy without common duct exploration, and total mastectomy versus subtotal mastectomy. For example, carpal tunnel releases are now rarely performed on an inpatient basis. For example, scoliosis (curvature of the back) is one of the primary reasons spinal fusions are performed on pediatric patients. Spinal fusions for scoliosis tend to be more complex than spinal fusions for other clinical reasons such as a herniated disk. A medical hierarchy is necessary because newborns do not have a principal diagnosis in the usual sense. Gestational age is used as part of the severity of illness and risk of mortality subclass assignment for newborns. The end goal is to create categories that are clinically coherent and have sufficient case volume to be useful. Next most common is endoscopic lung biopsy followed by certain other biopsies of bone, soft tissue, blood vessel, cervix, uterus, and bladder. Other reclassified procedures with volume are interruption of vena cava and linear repair eyelid laceration. Another situation occurs when the principal diag nosis is overly broad, or the sequencing of principal diagnosis and secondary diagnosis is unclear, or a surgical procedure provides clarification of the principal diagnosis. The chest pain diagnosis is a symptom of the angina or coronary atherosclerosis and should have been recorded as a secondary diagnosis. There is some ambigu ity in the sequencing of principal and secondary diagnosis, while the patient fundamentally is a gastroenteritis patient who has some level of dehydration. The end result is that clinically similar amputation patients are grouped together rather than dispersed into separate lower volume amputation groups. The sequencing of principal diagnosis and secondary diagnosis on the patient discharge records is not altered by any of these resequencing processes. The term “level” is used when referring to the categorization of a secondary diagnosis. For secondary diagnoses, there are four dis tinct severity of illness levels and four distinct risk of mortality levels. The four levels are numbered sequentially from 1 to 4 indicating, respectively, minor, moderate, major or extreme severity of ill ness or risk of mortality. Each secondary diagnosis is assigned to one of the four severity of illness levels and one of the four risk of mortality levels. The severity of illness level and risk of mortality level associated with a patient’s secondary diagnoses is just one factor in the determina tion of a patient’s overall severity of illness subclass and risk of mortality subclass. The process of determining the severity of illness or risk of mortality subclass of a patient consists of three phases. A detailed description of the determination of the severity of illness subclass and the risk of mortality subclass will be presented separately. The three-phase process of determining the severity of illness subclass is summarized in figure 2–1. Three-phase process for determining patient severity of illness subclass 30 Phase I—Determining the severity of illness level of each secondary diagnosis 1. Eliminate secondary diagnoses associated with the principal diagnosis If a secondary diagnosis is closely related to the principal diagnosis and does not add any distin guishing information, the secondary diagnosis is excluded from the determination of the severity of illness subclass.

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In California these disorders are most common among Laotian (1 in every 1 medications safe during breastfeeding buy 250 mg diamox,300 live births) and Cambodian populations (1 in every 2 treatment table diamox 250mg for sale,800 live births) medicine used for pink eye generic diamox 250 mg line, but are seen in other Asian (including East Indian) medicine technology generic diamox 250 mg on-line, Black/African American, Middle Eastern and Mediterranean populations as well. Genetic testing of partner(s) is recommended for anyone with beta thalassemia or beta thalassemia trait. Persons with trait may have mild microcytic anemia which, in the absence of other indications of iron deficiency, should not be treated with iron supplements. Persons with beta thalassemia trait are at risk for having a child with a more severe form of thalassemia or sickle cell disease if the other parent also has beta thalassemia or sickle cell trait or disease. However, individuals with this thalassemia may require intermittent transfusions and may have moderate to severe complications. These individuals must be followed by a hematologist in conjunction with a primary care provider. Hemoglobin E is a variant of normal (A) hemoglobin screened for at birth since 2005 in California. In conjunction with certain genetic globin mutations, Hemoglobin E may cause serious disease. Individuals born outside of California or born prior to 2005 may be unaware that they carry one or more genes for making hemoglobin E. Hb E is very common in Southeast Asian populations in California; benign (Hb E/E) and significant forms (Hb E/beta thalassemia) are seen in 1 of every 80 Laotian live births, 1 in every 100 Cambodian live births and 1 in every 700 other Southeast Asian live births, less frequently in other Asian populations, and occasionally in people of other races or ethnicities. Genetic testing of partners of anyone with Hb E trait or condition who is considering having children is recommended. These individuals do not have any symptoms other than mild microcytic anemia in some cases. The microcytic anemia can be misdiagnosed as iron deficiency; however, iron supplementation should be avoided. Consequently, individuals of Southeast Asian origin with this form of anemia should be tested for a hemoglobinopathy. Persons with Hb E/beta thalassemia should be followed by a hematologist along with a primary care provider. Mild to moderate anemia, brittle bones or other bone problems, and/or an enlarged spleen are characteristic of milder forms of thalassemia, and a pale and listless appearance, dark urine, jaundice or slowed growth can be indicative of a more severe form. Many forms of thalassemia can cause chronic iron overload even in non-transfused patients. The symptoms of iron overload (such as liver or heart disease, hypogonadism, hypothyroidism, diabetes or metabolic syndrome, osteoarthritis, and osteoporosis) are insidious and can result in serious problems later in life that are preventable with early diagnosis and treatment. People born in or with ancestry in Asia (especially Southeast Asia, India and China), the Middle East, Northern Africa, or Mediterranean regions are more likely to have thalassemia, but anyone of any race can have one of these disorders. Thalassemias are most common in the most densely populated parts of the state and those with the largest populations of people from affected regions. Patients with undiagnosed milder forms of thalassemia may present with microcytic anemia that can be mistaken for iron deficiency anemia, however, treatment with iron supplements is harmful to such patients. These patients and suspected patients with severe symptoms should be referred to a hematologist for diagnosis and care. Children 51 to 100 cases born to two parents with these traits may inherit severe forms of thalassemia or sickle cell/ 101 to 175 cases thalassemia and may have significant health problems and shortened life expectancy. What steps should I take if I suspect thalassemia or thalassemia trait in a patient Patients with unexplained microcytic red cell indices should be referred to a hematologist experienced with thalassemia for diagnosis. If there is a history of thalassemia in the extended family or if the patient is from one of the highly affected ethnic groups, advice on genetic testing prior to pregnancy or birth should be provided and testing for all related family members should be recommended. Domann the Fine Print: Because this is a paper written by a beginning student as an assignment, there are no guarantees that everything is absolutely correct and accurate. In view of the possibility of human error or changes in our knowledge due to continued research, neither the author nor the University of Iowa nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from the use of such information. All material contained in this paper is copyright of the author, or the owner of the source that the material was taken from. Genetic and molecular basis for the thalassemia 7 Globin synthesis in beta thalassemia 7 Globin synthesis in alpha thalassemia 8 7. Experiment design to test the hypothesis 18 Experiments using animal model 18 Experiment using human model 19 15. Jetawattana Thalassemias, disorders of hemoglobin synthesis 3 Abstract Thalassemias are a group of hereditary diseases of abnormal hemoglobin synthesis where the normal hemoglobin protein is produced in lower amounts than usual. These conditions cause varying degrees of anemia, which can range from insignificant to life threatening. Thalassemia can be classified according to the deficient globin chain, alpha or beta thalassemia. Patients with severe anemia who receive regular blood transfusions become iron overloaded, which increases damaging free radical activity and lowers antioxidant levels in their bodies. Several investigators have provided evidence supporting the hypothesis that oxidative stress plays an important role in development of clinical complications in thalassemia. Increasing antioxidant activity is then expected to bring oxidative stress down to minimal level. Therefore, it is important to understand the mechanisms of free radical-induced oxidative stress damage in thalassemia before using it as a potential tool in diagnosis and treatment of the disease. Jetawattana Thalassemias, disorders of hemoglobin synthesis 4 Introduction Thalassemia is described as a heterogenous group of inherited anemias characterized by a reduced or absent amount of hemoglobin. Many studies have shown that reactive oxygen species are generated in increased amounts in thalassaemic red cells. Conditions such as rupture of erythrocytes, iron overload, and depletion of antioxidants in tissues. This implies the possible alteration of redox status in thalassaemic patients, which may adversely affect their health. Specific treatments for thalassemia are employed based on many factors such as age of the patients and severity of the disease. Currently, studies on the correlation between lipid peroxidation and plasma levels of antioxidants such as vitamin A, C, and E as well as correlations with antioxidant enzymes to hemoglobin disorders have been reported (5, 12, 13). An effective form of gene therapy and stem cell transplantation are now being used to improve conventional treatment and enhanced the prognosis of thalassaemia (20, 22,23). The goal of this paper is to provide information about thalassemia and will focus on its correlation with oxidative stress. Normal structure and expression of globin gene clusters Human hemoblobin is a heterotetramer protein, compose of two alpha and two beta subunits as shown in Figure 1. Each subunit contains a heme group, an iron containing compound that binds to oxygen. The synthesis of hemoglobin is controlled by two developmentally regulated multigene clusters: the alpha-like globin cluster on chromosome 16 and the beta-like globin cluster on chromosome 11 as demonstrated in Figure 2. Jetawattana Thalassemias, disorders of hemoglobin synthesis 5 persons, the synthesis of alpha and beta globin chains is finely balanced during terminal erythroid differentiation but the mechanism of balanced expression is unknown [2]. Pseudogenes and the globin gene, whose functional significance is unknown, are not represented. To make visualization of them easier, the globinlike genes are represented over a larger space of genome than they actually span [2]. Jetawattana Thalassemias, disorders of hemoglobin synthesis 6 Normal Hemoglobins [1] A normal human hemoglobin pattern is expressed as A2A. Hemoglobin A is the designation for the major hemoglobin protein that exists after birth that is a tetramer with two alpha chains and two beta chains (2 2). Hemoglobin A2 is a minor component (less than 3%) of the hemoglobin found in red cells after birth and consists of two alpha chains and two delta chains (2 2). The beta protein is not expressed before birth and the gamma hemoglobin (HbF) is the predominant hemoglobin protein found only during fetal development. Hemoglobin F is a tetramer molecule of two alpha chains and two gamma chains (2 2). The genes for HbF and HbA are closely related and exist in the same gene cluster on chromosome 11.

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