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By D. Kaelin. Morehead State University.

Associate Professor Department of Biochemistry and Molecular Biology Kathlyn McGreevy Marshall University School of Medicine Huntington buy discount zoloft 25mg online, wv Production Manager Michael Wolff Mary Ruebush generic zoloft 25 mg overnight delivery, Ph purchase zoloft australia. Cover Design Joanna Myllo Cover Art Christine Schaar Rich LaRocco • Contents Preface. Medical Genetics Chapter 1: Single-Gene Disorders 289 Chapter 2: Population Genetics. The Notes were designed to be accompanied by faculty lectures-live, on video, or on the web. To maximize the effectiveness of these Notes, annotate them as you listen to lectures. Many students find that previewing the Notes prior to the lecture is a very effective way to prepare for class. It also affords you the opportunity to map out how the information is going to be presented and what sort of study aids (charts, diagrams, etc. The major steps involved in handling genetic information are illustrated by the central dogma of molecular biology (Figure I-1-1). Ultimately, during the process of gene expression, this information is used to synthesize all the proteins made by an organism. Although this definition is now complicated by our increased appreciation of the ways in which genes may be expressed, it is still useful as a general, working definition. When cells divide, each daughter cell must receive an accurate copy of the genetic information. The M phase (mitosis) is the time in which the cell divides to form two daughter cells. Interphase is the term used to describe the time between two cell divisions or mitoses. Five-Carbon Sugars Nucleic acids (as well as nucleosides and nucleotides) are classified according to the pentose they contain. Bases Commonly Found in Nucleic Acids • Purines contain two rings in their structure. Other purine metabolites, not usually found in nucleic acids, include xanthine, hypo- xanthine, and uric acid. Nucleosides and Nucleotides Nucleosides are formed by covalently linking a base to the number 1 carbon of a sugar (Figure 1-1-4). The numbers identifying the carbons of the sugar are labeled with "primes" in nucleo- sides and nucleotides to distinguish them from the carbons of the purine or pyrimidine base. Nucleoside di- and triphosphates are high-energy compounds because of the hydrolytic energy associated with the acid anhydride bonds (Figure 1-1-6). Examples of Nucleotides The nomenclature for the commonly found bases, nucleosides, and nucleotides is shown in Table 1-1-2. A always pairs with T (two hydrogen bonds), and G always pairs with C (three hydrogen bonds). Thus, the base sequence on one strand 0/0 A = % T (% U) defines the base sequence on the other strand. The hydrophilic sugar-phosphate backbone of each strand is on 10% G + 10% C = 20% the outside of the double helix. The hydrogen-bonded base pairs are stacked in the center of therefore, % A + % T the molecule. These molecules may exist as relaxed circles or as snpercoiled structures in which the helix is twisted around itself in three-dimensional space. The basic packaging unit of chromatin is the nucleosome (Figure 1-1-10): Histones are rich in lysine and arginine, which confer a positive charge on the proteins. Heterochromatin is more highly condensed, producing interphase heterochromatin as well as chromatin characteristic of mitotic chromosomes. Figure I-1-12 shows an electron micrograph of an interphase nucleus containing euchromatin, hetero- chromatin, and a nucleolus. The nucleolus is a nuclear region specialized for ribosome assembly (discussed in Chapter 3). I 12 meulCa • Nucleic Acid Structure and Organization Euchromatin Heterochromatin Nucleolus Figure 1-1-12. Chromosome abnormalities may be assessed on mitotic chromosomes by karyotype analysis (metaphase chromosomes) and by banding techniques (prophase or prometaphase), which identify aneu- ploidy, translocations, deletions, inversions, and duplications. Cytosine arabinoside (araC) is used as an effective chemotherapeutic agent for cancer, although resistance to this drug may eventually develop. In certain cases, resistance is related to an increase in the enzyme cytidine deaminase in the tumor cells. Endonuclease activation and chromatin fragmentation are characteristic features of eukaryotic cell death by apoptosis. Which of the following chromosome structures would most likely be degraded first in an apoptotic cell? The figure shows the nucleoside adenosine, which is the base adenine attached to ribose. Each of these parental strands is then used as a template for the synthe- sis of a new complementary strand (semiconservative replication). Completion of the process results in the production of two identical linear mol- bonds. The two identical sister chromatids are separated from each other when the cell divides Exonucleases remove during mitosis. The individual (metaphase) chromatids and centromere are difficult to visualize in the photograph Figure 1-2-2. The newly synthesized strand is complementary and antiparallel to the parental strand used as a template. Note The mechanism of replication in eukaryotes is believed to be very similar to this. With each round of replication in most normal cells, the telomeres are shortened because unlimited replication. This contributes to the aging of cells, because eventually the telomeres become so short that the chromosomes cannot function properly and the cells die. Telomerase is thus able to replace telomere sequences that would Quinolones and otherwise be lost during replication. Normally telomerase activity is present only in embryonic fluoroquinolones inhibit cells, germ (reproductive) cells, and stem cells, but not in somatic cells. Mismatch inactivated through mutation repair occurs in the G2 phase to correct replication errors. Xeroderma pigmentosum is an autosomal recessive disorder, characterized by extreme sensitivity to sunlight, skin freckling and ulcerations, and skin cancer.

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Care must be taken Many patients who complete tapering from to initiate naltrexone well after tapering is opioid medication continue to need support completed to avoid precipitating withdrawal and assistance purchase zoloft with paypal, especially during the first 3 to symptoms zoloft 100 mg low price. Other patients might benefit from 12 months discount 100 mg zoloft free shipping, to readjust to a lifestyle that is continued counseling to strengthen relapse free of both maintenance medication and prevention skills. During this period, treat- support of continued drug testing helpful after ment providers should focus on reinforcing tapering. The treat- Continuing-Care Phase ment system should be flexible enough to allow Continuing care is the phase that follows suc- for transition according to a patientís progress cessful tapering and readjustment. The program should modify at this stage comprises ongoing medical fol- treatment based on the best interests of patients, lowup by a primary care physician, occasional rather than infractions of program rules. Ongoing treatment, require that a patient return to the acute phase although less intense, often is necessary but instead that he or she receive intensified because the chronic nature of opioid addiction counseling, lose take-home privileges, or can mean continuous potential for relapse to receive a dosage adjustment. Significant co-occurring disorders evidence that problems are under control, the should be well under control. People in this patient might be able to return to the phase should continue to participate regularly supportive-care or medical maintenance phase. Positive, sustained addressing these problems are important to outcomes are more attainable in a therapeutic facilitate recovery from addiction. Various environment with readily available, supportive, strategies have been developed, including psy- qualified caregivers. It is difficult to provide chosocial and biomedical interventions and high-quality care and facilitate favorable treat- peer-support approaches. Infected the most important indicator of treatment out- injection sites, cellulitis, and abscesses are comes (e. Bacterial endocarditis Patients who stayed in treatment a year or remains a concern. Long-term tobacco use con- longer abused substances less and were more tributes to other diseases. Program administrators need to develop comprehensive patient population profiles for planning, staffing, and resource allocation. Treatment providers should explain program Factors affecting patient goals and treatment plans to every patient. Another factor found to affect retention be individualized and happened during was motivation or readiness for treatment (Joe respectful of patientís et al. Some patients patients want to taper from maintenance medi- require several attempts at treatment before cation more quickly than seems advisable. Staff becoming stabilized for extended periods should work with these patients to achieve their (Koester et al. Patients have cited individualized medication dosages are probably other factors that discourage retention, such as the most important factor in patient retention staff insensitivity, lack of treatment skills and (Joseph et al. Shortening more attention to other concerns (reviewed in intake results in better program retention (see Leavitt et al. Some treatment providers offering prospective patients either cost-free have found that patients are more likely to treatment or moderate fee rates significantly remain in treatment when they are involved in increased treatment entry and retention for the its planning and management. Patients were more likely to stay in treatment when they were motivated strongly M anagem ent, and engaged earlier in useful activities Behavioral Treatm ents, (Simpson, D. In the critical first 90 days of treatment, higher service inten- and Psychotherapy sities, especially for practical services that helped patients achieve basic goals, have been Counseling and Case associated with higher retention. Examples M anagem ent include attentive case management, psychiatric services, introduction to peer groups, and Patient counseling in individual, family, or assistance with insurance, transportation, and group sessions offers a venue for many treat- housing (Grella and W ugalter 1997). Good staff lifestyle and abstinence from substances of attitudes and interactions with patients have abuse. Usually, individual concluded that good counseling rapport was sessions during the acute phase (see chapter 7) related to improved abstinence and reductions are more intensive than those that follow, in criminality (e. In some States, Medicaid ï Identifying problems that need extended ser- regulations and contracts require or limit coun- vices and referring patients for these services seling frequency. Counselors should convey ï Support groups, which buoy members and observations to medical staff about patientsí provide a forum to share pragmatic informa- conditions and information about other aspects tion about maintaining abstinence and man- of patientsí lives that might clarify health prob- aging a day-to-day substance-free lifestyle. Neither type of conditions can interact with addiction treat- group needs a predetermined end point or set ment medications. Using a manual with a structured cope with hepatitis C and adhere to its treat- curriculum enables counselors and other staff ment regimens. It can reduce patientsí sense of Some patients resist group counseling and isolation and help them cope with addiction avoid sessions. Offering smaller groups might and other life problems by providing feedback ease their concerns while therapists explore the from peers, social skill training and practice, reasons for their resistance (e. Some State agencies do better in groups with members who have offer courses in group process and dynamics. Some women are uncomfortable in patients learn skills to attain and maintain male-dominated groups and do better in abstinence women-only groups. Others feel embarrassed about personal subjects related to their addic- ï Cognitive behavioral groups, in which tion. Gay men, lesbians, and bisexuals might patients learn to alter pervasive thoughts and feel isolated in predominantly heterosexual actions groups. In such cases, the consensus panel ï Interpersonal-process groups, which delve recommends individual, women-only, or into developmental issues contributing to sexual-orientation-specific groups. The authors concluded that social service-focused case management m anagem ent was an important and effective adjunct to Some researchers have investigated the useful- addiction treatment. McLellan and coworkers (1999) described a Cognitive and Behavioral system with an active case management compo- Therapies nent to help patients access services for hous- Other interventions, both in use and under ing, medical care, and legal and parenting study, include cognitive-enhanced techniques to assistance. Six months after the systemís imple- increase treatment participation, modify mentation, patients receiving these services behavior, and address patientsí social, emo- showed greater reduction in alcohol use and tional, and behavioral problems, as well as any improvement in medical conditions, family co-occurring disorders. The consensus panel aspects of their lives that reinforce abstinence believes that substance abuse and addiction and to understand how these reinforcers can involve major learning elements and are influ- serve as alternatives to substance use. This approach is useful for thoughts, actions, and feelings and their sub- treatment planning because it sets concrete stance use and to increase patient participation goals and emphasizes positive behavioral in counseling (Czuchry and Dansereau 2003). Patients with poor attention more effective than negative, punishing contin- stamina were found to have greater success in gencies or threats (Gruber et al. In one study, a balance of posi- Less educated patients exposed to mapping- tive and negative reinforcements, as part of a enhanced counseling also had better 12-month well-constructed contingency management followups than those in standard counseling plan, helped patients reduce their drug use (Pitre et al. Tangible rewards, such as colleagues, ìThe use of node-link mapping take-home medication privileges, should be appears to reduce cultural, racial, and class paired with social reinforcements, such as barriers by providing a visual supplement and praise from the counselor or other patients, to a common language that enhances counselorñ optimize their value. For example, a nega- tive drug test result might earn one take-home medication dose (other treatment and program variables must be taken into account, including Federal and State regulations). Other incentives may include special gressive muscle relaxation and desensitization, scheduling for medication administration, meal contingency management had a demonstrated vouchers, gift certificates, entertainment tick- record of effectiveness, whereas systematic ets, or toys for patientsí children. Designing desensitization alone was less effective in such programs requires significant effort, yet eliminating opioid use but reduced fear of with- the rewards can add an important dimension to drawal and general anxiety (Piane 2000). They used gram of motivational stepped-care levels in take-home medication privileges to increase which clear contingencies were matched with the involvement of significant others and treatment responses.

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It is notewor- Carroll and colleagues (1995) compared the thy that interventions treatment zoloft 100mg online. The group receiving enhanced treatment had better neonatal outcomes generic zoloft 25 mg amex, but the two groups did not differ in percentages of Nutrition Assessm ent zoloft 100 mg line, positive drug tests. The authors attributed these results primarily to more frequent prena- Counseling, and tal care in the contingency management group. Assistance However, results of the study were limited by the small sample size (seven women in each People with substance use disorders often are group), the inability to discern which compo- poorly nourished. Substances themselves may nents contributed to improved outcomes, and impair usersí metabolism, interfere with nutri- use of a demanding contingency procedure that ent availability, and affect appetite. Their school-age have wholesome, well-balanced diets consistent children also might qualify for school breakfast with their ethnic or cultural backgrounds and and lunch programs, as well as summer food financial situations. Information about the members who facilitate a nutrition education Federal W omen, Infants, and Children pro- program. Managers are responsible for keeping staff members focused Medication on patient care and improved treatment outcomes. Managers should set clear staff guidelines, supply the needed resources, and create a culture that nurtures professional growth The Community and staff retention. In ment should recruit employees who reflect [A]dministrators addition, staff mem- patient demographics and should consider bers should main- hiring people who are recovering from addic- should recruit tain appropriate tion (see below). People working with diverse groups should remember that diversity also exists within cul- Transference and tures. It is important to be sensitive to cultural ally competent countertransfer- differences but to avoid acting on cultural ence. Understanding both a patientís people; offer with addictions cultural influences and his or her individuality project feelings or requires taking time to know the patient. Correctly identifying such factors Countertransference requires an effort to see the world through each supervision and occurs when treat- patientís eyes. Information on cultural compe- ment providers pro- tence and diversity is available at W eb sites of ongoing training. Sterling and col- urineî to describe an unsatisfactory urine drug leagues (2001) noted the existence of ìequivocal test (ìpositive testî is less judgmental). Staff findings of the effect that therapist and patient should avoid terms suggesting the criminal similarity plays in treatment outcomeî (p. The consen- Federal and State resources are available for sus panel believes that employing treatment programs seeking literature in languages other professionals and support staff who are in than English. Community colleges, universities, recovery also adds valuable perspectives to and other institutions or agencies might assist treatment and provides role models for in translating forms and pamphlets. State regulations may estab- lish a minimum abstinence period before an Flexibility in thinking, behavior, and attitudes. Staff biases, are not judgmental, and do not have members who are in recovery and their col- punitive attitudes toward patients (Bell 2000). At least Staff Retention one study has associated such attitudes with Retaining staff is important for several reasons: lower rates of patient retention and poorer patient outcomes (Caplehorn et al. Staff members can experience permitting staff members to attend offsite burnout when they work in isolation with training during work hours. Managers should take concrete steps ï Encourage professional development by to retain staff, including the following: supporting staff certifications. Even the most ï Offer routine praise and recognition for staff professional, committed counselor struggles contributions and achievements. Staff members usually feel less isolated and overwhelmed Training when a team makes treatment decisions. W hen a lack of cohesion exists, staff members Training should be offered for all staff mem- risk burnout, disillusionment, or cynicism. A bers, including secretaries, nurses, counselors, well-coordinated team also reduces the level supervisors, and managers, to ensure a strong of intrastaff disagreements about patient care knowledge base so that staff members do their and decreases the likelihood of ìstaff split- best and to affirm that all staff members are ting,î when patients pit staff members against valued members of the treatment team. Managers should sional staff members acquire education credits hold regular staff meetings. Staff cooperation to maintain their licensure by offering onsite also can be fostered through training and training, collaborating with other agencies for retreats. The program director or manager reciprocal training, or paying for educational should mediate disputes among staff members. One way to address negative staff Federal and State attitudes is to include successful patients in agencies and profes- training (Bell 2000). Training should ensure that staff events and resource dards require members are knowledgeable about drug materials abuse trends in the community. Staff members should have allow staff from access to generic skills training such as crisis smaller programs to attend their sessions. The importance ing organizations, such as the Association for of emphasizing sensitivity to patient needs Addiction Professionals, and professional should be reviewed periodically. A program physician might members, often the first to speak with patients, educate staff members about the etiology play an important role. A random-callback policy Control Plans avoids patient complaints of being unfairly Federal opioid treatment standards state that ìpicked onî by staff members. All scheduled that patients can substances should be accounted for rigorously the possibility of store medications and inventoried continuously. All from receipt through dispensing and measured take-home medica- at the beginning and end of each workday. W ithin the dispensary, remains misunderstood even among some employees should open the safe or work with health care professionals. Some treatment Transition in Federal oversight of substance providers have overcome community opposi- abuse treatment from the U. Having ade- Children and Family Services, Joint quate onsite staff is equally important in avoid- Commission on Accreditation of Healthcare ing and resolving community problems. Glezen Organizations, National Commission for and Lowery (1999) provide other practical Correctional Health Care, State of Missouri guidelines for addressing community concerns Department of Mental Health Division of about substance abuse treatment facilities. Alcohol and Drug Abuse, and W ashington Community opposition can be triggered when State Department of Social and Health Services community groups believe that they have been Division of Alcohol and Substance Abuseó informed or consulted insufficiently. The relations with the payer community (Edmunds availability of public transportation is impor- et al. Adding designed, and operated in accordance with alternative care models and longer acting accreditation standards, Federal guidelines, pharmacotherapies to the services continuum and State and local licensing, approval, and can decrease loitering, illicit transactions, ille- operating requirements. Staff and patients from the parent organizationís community should be part of a multifaceted, proactive effort relations department. Although program contacts w ith com m unity activities differ in specificity and scope, a Personal contact with community leaders per- community relations plan should address the mits open dialog, information sharing, and dis- following: cussion of community developments, needs, and problems. Occasional becoming increasingly instrumental in empow- press releases can ering patients as active participants in public community notify the public relations, community outreach, and program about specific support initiatives and in local, State, and services demon- services, activities, national community education efforts. Staff members with community improvement and and the general development expertise can support other public. A program organizations in advocacy, promotional, and counter negative support efforts.