Condet

Arthur Wakefield Baker, MD

• Assistant Professor of Medicine

https://medicine.duke.edu/faculty/arthur-wakefield-baker-md

Examples are the insulin receptor erectile dysfunction young living purchase extra super cialis 100mg with visa, elastin erectile dysfunction treatment himalaya order 100 mg extra super cialis with mastercard, thyroid peroxidase can erectile dysfunction cause low sperm count cheap 100mg extra super cialis with mastercard, and tyrosine hydroxylase erectile dysfunction doctor omaha generic extra super cialis 100 mg amex. Organ specificity and subcellular localization for evolutionarily conserved genes also occur through post-translational modification of their encoded proteins. Glycosylation of proteins directed to the plasma membrane receptors or for secretion is an example of this post-translational mechanism for normal protein diversity in the human organism. The relatively rare circumstance in which a change in a protein impairs function is called a mutation and may produce an inborn error of metabolism. True mutations provide insight into the functional role of the normal protein in human metabolism. Inborn errors of metabolism are classified here in accordance with the organ, cell, and subcellular location of normal protein function (Table 32-1) and the abnormal mechanisms that interfere with the normal metabolic flow resulting from impaired proteins (Table 32-2). By understanding the pathophysiologic mechanisms producing disease, the normal function and cellular location were defined for these proteins. As science progresses in protein and gene replacement therapy, this approach to disease classification provides a practical working model for clinical intervention. Accumulation to toxic concentrations of substrates in a blocked catabolic reaction. Examples: maple syrup urine disease, glucose-galactose malabsorption, galactosemia 2. Examples: congenital adrenal hyperplasia, intermittent porphyria, familial hypercholesterolemia of a metabolic disease, as well as the environmental causes, is that one can predict, intervene in, and prevent the disease by a variety of stratagems. In general, the severity of an inborn error of metabolism depends on the degree of protein impairment rendered by the genetic mutation. Thus, a "leaky" mutation may not be expressed until adulthood, whereas a complete block in the same metabolic pathway is lethal in infancy. The pathophysiologic mechanisms outlined in Table 32-2 may occur individually or combine to produce loss in homeostasis and a disease state. The extent of disease and the clinical outcome in the complex human organism involve not only a specific genetic block but also alternate metabolic pathways (epigenetic phenomena) and the environment. Clinical outcome depends on (1) the ability to engineer the environment and to accommodate for impaired protein function through alternate pathways and (2) the timeliness of environmental and medical intervention in preventing irreversible organ damage. Many disorders are produced by mutant proteins that impair the transport of nutrients into cells (Table 32-3). Familial glucose-galactose malabsorption syndrome exemplifies defective transporter protein, resulting in specific accumulation of non-transported glucose to toxic concentrations in the intestinal lumen. Direct evidence for the genetic control of intestinal glucose transport in humans was obtained by in vitro studies of jejunal biopsy material from families in which the affected members express refractory diarrhea on ingesting D-galactose or D-glucose. Biopsy material from asymptomatic first-degree relatives demonstrated partial impairment of this transport function and defined autosomal recessive inheritance. These physiologic data suggested that a single mutant gene affected sodium-dependent, active glucose transport by human jejunal (and proximal renal tubular) microvilli. Expression cloning of active glucose transport has now confirmed the presence of energyand sodium-dependent glucose transporter genes, their deduced amino acid sequences, and specific codon changes producing syndromes of familial glucose-galactose malabsorption and renal glycosuria. Now a family of active and facilitative glucose transporter genes is known to be differentially expressed by specific organs and there are a large number of inherited defects involving the plasma membrane transport of glucose. Glucose transporters represent a family of proteins whose definitions of function evolved after their cloning and molecular genetic analyses (Table 32-4). Comparing the data from families with renal glycosuria and glucose-galactose malabsorption, it became evident that different Na+ -dependent active glucose transporters were present in kidney and gut epithelium. Many diseases characterized by "hormone resistance" are caused by another family of proteins that function in the plasma membrane. The concept of failure to respond to hormone stimulation originated in the early 1940s with a description of pseudohypoparathyroidism (see Chapter 264). Heritability of resistance to parathormone was suggested before the existence of parathormone receptors, hormone-sensitive adenylate cyclases, or guanine nucleotide-binding proteins was known.

For the minority of hypertensive patients without co-morbid conditions erectile dysfunction doctors tucson az purchase 100 mg extra super cialis with amex, target organ damage impotence reasons generic extra super cialis 100 mg visa, or concomitant cardiovascular risk factors discussing erectile dysfunction doctor purchase 100 mg extra super cialis, drug therapy should begin with a diuretic or a beta-blocker (see erectile dysfunction young cure buy extra super cialis 100mg lowest price. For most patients, however, co-morbid conditions may dictate the choice of another class of drug and/or avoidance of diuretics and beta-blockers for initial therapy (see. For patients with coexistent diabetes mellitus or cardiovascular disease, randomized controlled trials have provided compelling indications for initial drug choices from specific drug classes. When monotherapy is unsuccessful, a second agent, usually of a different class, should be added. In contrast, traditional fixed-dose combinations, which contain full conventional doses of each component, should be reserved for patients who do not respond adequately to monotherapy. Recommended dose ranges for individual drugs are listed in Table 55-8 (see Table 55-7 for dose ranges for combination agents); common adverse effects are summarized in Table 55-9. The most common treatable cause of resistant hypertension is volume overload, and these patients frequently benefit from the addition of a diuretic-a loop diuretic if they have concomitant renal dysfunction. Re-evaluation for secondary causes of hypertension and possible referral to a hypertension specialist are indicated. Doses should be titrated slowly downward and medications discontinued one at a time, if possible. Step-down therapy is generally most effective for patients who are also making lifestyle modifications. Clues from the medical history, physical examination, initial laboratory evaluation and clinical course help identify the 5% of hypertensive patients with specific causes for the disorder (see Table 55-3. Patients with the more common and treatable forms of secondary hypertension share the characteristics outlined in Figure 55-6. The signs, symptoms, and physical and laboratory findings that point to a specific secondary etiology for hypertension may appear as part of the initial evaluation or may emerge in the course of follow-up, especially in conjunction with a disappointing response to usual medical therapy. Because some of these conditions can be superimposed on underlying chronic essential hypertension, it is particularly important to remain alert for these diagnoses in patients who have been treated for prolonged periods but whose hypertension is progressively more difficult to control. Renovascular disease is the most common (1 to 2%) cause of curable/treatable secondary hypertension. Any lesion that obstructs either large or small renal arteries can cause renovascular hypertension. The most common and clinically important of these are intrinsic lesions of the large vessels (see Chapter 112) because they can be physically treated and the hypertension either cured or ameliorated. Of patients with renovascular hypertension, atherosclerotic disease is found in 75% overall and in nearly all elderly patients, whereas fibrous or fibromuscular disease is found in 25%, including the vast majority of younger patients. The usefulness of screening tests for renovascular hypertension is highly variable, so patients should be referred to high-volume centers for testing. Patients most likely to have renovascular hypertension include those with hypertension of abrupt onset, especially in the young or in late middle-aged or elderly patients; those with malignant hypertension or sudden acceleration of benign hypertension; and those who fail to respond to medical therapy. An upper abdominal bruit, particularly one that is systolic-diastolic or continuous in timing, is high pitched, and radiates laterally from the midepigastrium, occurs in one half to two thirds of patients with surgically proven renovascular hypertension. A definitive diagnosis of renal artery stenosis is made by selective renal angiography, which defines the anatomy of the stenotic renal artery and hence provides information needed to plan the approach to revascularization. The natural history of renal artery stenosis is progressive arterial occlusion with loss of renal function. For patients with obstruction of renal blood flow caused by an ostial stenosis at the origin of the renal artery and those who have unsuccessfully undergone balloon angioplasty, renal artery stents are useful in maintaining renal artery patency. Renal function and serum potassium levels must be monitored closely, particularly when therapy is initiated. Normal autoregulation of the glomerular filtration rate, which depends on an intact intrarenal renin-angiotensin system, is lost when the renin-angiotensin system is interrupted with these drugs. Renal function can deteriorate and renal mass can be lost very rapidly in patients with atherosclerotic disease who are treated medically. Significant reduction in renal size is the most sensitive index of loss of renal mass.

In Newfoundland doctor for erectile dysfunction in dubai order extra super cialis 100mg otc, Labrador erectile dysfunction normal testosterone 100mg extra super cialis with amex, Quebec erectile dysfunction diabetes qof purchase 100 mg extra super cialis visa, and the Yukon erectile dysfunction 35 year old male discount extra super cialis 100mg with visa, modern treaties have resulted in the transfer of more than 6 million ha to First Nation people. In Ontario, a 2014 to 2015 forest tenure modernization project provided funding to support sustainable forest licenses for Indigenous communities (Natural Resources Canada 2016a). For environmental reasons, some First Nation groups oppose the pipeline while others support it for the economic benefits it will bring their First Nation communities (Jang 2016). Today, geothermal energy produced on the Peguis First Nation and Fisher River Cree Nation Reserve in Manitoba heats reserve homes, and First Nation people are trained and certified in geothermal trades (Paul 2015). Western Canada: British Columbia Along the Pacific Coast, First Nation people traditionally settled in permanent villages and subsisted on food resources from the ocean such as salmon, shellfish, sea lions, otters, whales, and seaweed. Today, fisheries are an important industry for First Nations located in western Canada, where salmon, halibut, herring, and other fish are caught and processed in canneries (Notzke 1994). The First Nations Forestry Council of British Columbia works to support First Nation forestry activities through training programs, business support, policy development, mountain pine beetle action plans, ecosystem stewardship planning, and more (B. Today, the Yukon and Northwest territories are used for renewable and nonrenewable energy projects such as crude oil, natural gas, thermal electrical facilities, hydroelectric plants, and wind energy projects. Several pipelines carry crude oil and natural gas through the region (Canada National Energy Board 2011). For example, in the Yukon Territory, members of the Vuntut Gwitchin First Nation live along the migration route of the Porcupine caribou herd and rely on resources provided by the herd for food, clothing, and crafts. Their traditional way of life is being threatened by oil and gas companies that want to develop the Arctic National Wildlife Refuge (Vuntut Gwitchin First Nation, N. Here, Mixteca Indian farmers are reviving pre-Hispanic farming practices to restore and farm the land. Actions taken by these farmers include terracing hillsides, plowing with oxen, and farming via a technique called "milpa," where corn, squash, and beans grow together and increase soil nutrients (Malkin 2008). In the 1970s, the Maya and members of local Ejidos (communally farmed lands) began to harvest trees for railroad ties. In the 1980s, a forestry pilot program helped members of the Ejidos learn timber marketing strategies and sustainable management techniques. The Ejidos of central Quintana Roo occupy more than 400,000 ha of forest, much of which is permanent forest reserve (Bray et al. Land-tenure issues create challenges for tribal communities managing natural resources on reservation lands. Some reservations consist entirely of trust land, but, as a result of the General Allotment Act of 1887, many reservations also include other types of land, such as land owned by individual Indian families or land owned by non-Indigenous people who acquired the land from tribal families (Frantz 1999). The resulting checkerboard pattern of land ownership on many reservations is problematic for farming, ranching, and other activities-including developing and implementing carbon management plans-that require access to or management of large land tracts (Indian Land Tenure Foundation 2016). In addition to land-tenure issues, Native American tribes in the United States have historically faced challenges in obtaining water for their reservations (Colby et al. In arid regions of the West, early settlers began a tradition of removing water from rivers via dams, diversions, and canals for agriculture, mining, and other purposes. Native American reservations downstream from western civilizations had no guarantee of sufficient water delivery during much of the 1800s. A 1908 Supreme Court decision known as the Winters Doctrine set the priority use date for water rights on tribal reservations as the same date that each reservation was established regardless of whether the tribe was using water for irrigation or other purposes at that time (Frantz 1999). The Winters Doctrine means that, today, tribes hold some of the most senior (highest-priority) water rights (referred to as "paper water") on river systems in the West. However, gaining access to actual water allocations ("wet water") can still be a long and arduous process for tribes that involves legal settlements November 2018 Sierra Madre Occidental (Jalisco, Nayarit, Zacatecas, and Durango) In the Sierra Madre Occidental Mountains, Huichol people live as subsistence farmers, using slash-andburn practices to convert forest into agricultural land. The quality of Huichol land is harmed by the slash-and-burn farming, and cattle grazing further damaged soil quality (Cultural Survival 1992). Central Highlands, Sierra Norte de Puebla, and the Gulf Coast the Nahua, speakers of the Nahuatl language, live near what was once the center of the Aztec empire. Most Nahua farm, growing maize, beans, chili peppers, squash, camotes, onions, tomatoes, and other cash crops such as sugarcane and coffee. While tribal governments have the authority to manage their land base, the complexities of overlapping jurisdictions and land-use customs can delay crucial resource management decisions.

Hence viagra causes erectile dysfunction buy 100mg extra super cialis free shipping, cardiac transplantation should be considered only for patients with refractory symptoms erectile dysfunction pills wiki cheap 100mg extra super cialis otc. The Digitalis Investigation Group: the effect of digoxin on mortality and morbidity in patients with heart failure erectile dysfunction pump canada buy extra super cialis 100mg without a prescription. Heart Failure Guideline Panel: Heart Failure: Evaluation and Care of Patients with Left Ventricular Systolic Dysfunction erectile dysfunction caused by lack of sleep discount 100 mg extra super cialis with visa. Lechat P, Packer M, Chalon S, et al: Clinical effects of beta-adrenergic blockade in chronic heart failure: A meta-analysis of double-blind, placebo-controlled, randomized trials. Carvedilol Heart Failure Study Group: the effect of carvedilol on morbidity and mortality in patients with chronic heart failure. Opening and closing of these channels, resulting from changes in the configuration of protein subunits, regulates ionic flow into and out of the cell. These conformational changes in protein subunits occur in response to changes in transmembrane voltage, in which case the channel is termed voltage gated, or in response to various neurotransmitters, enzymes, metabolic products, or ions, in which case the channel is termed ligand gated. The transmembrane movement of ions generates the transmembrane action potential, which has five phases. Phase 0, the upstroke, is caused by the movement of sodium and/or calcium ions into the cell and reaches a level of close to +30 mV (the inside of the cell is positive with respect to the extracellular space). Phase 1, the spike of the action potential, is attributed to rapid inactivation of the sodium current and activation of a short-lived, transient outward current referred to as Ito. The magnitude of this potassium outward current increases with time, and its increase, coupled with eventual deactivation of the calcium inward current, leads to the end of the plateau and the onset of phase 3, the phase of rapid repolarization. Phase 4, the phase between action potentials, represents electrical diastole, during which most cells have no change in transmembrane voltage, which remains close to -85 mV (the inside of the cell is negative with respect to the extracellular space). However, some cells may depolarize spontaneously during diastole and consequently reach the threshold for activation of the inward current and produce a spontaneous action potential (see. These cells are the pacemaker cells and are responsible for spontaneous impulse formation. The ionic currents responsible for spontaneous diastolic depolarization include a decaying outward current and an inward current activated by hyperpolarization, which is carried by sodium ions and is referred to as If. The cells in the sinoatrial or sinus node, which is the primary pacemaker region, lack the rapid sodium inward current system; their upstroke is generated by the slow inward calcium current. Thus the rate of rise of their action potentials is slower than that of cells having the rapid sodium inward current. The action potential configuration of cardiac cells varies with the location, size, and function of the various cell types. The sinus node is a spindle-like structure located near the junction of the superior vena cava and the right atrium. Modulation of the rate of spontaneous diastolic depolarization in the sinus node by sympathetic and parasympathetic stimulation results in either speeding or slowing. However, the sinus node spontaneously depolarizes even when denervated, a capability that permits transplanted hearts to beat spontaneously. These bypass tracts, referred to as Kent bundles, offer alternative pathways from the atria to the ventricles. These pathways also permit the development of re-entry circuits between the atria and the ventricles and are an important cause of tachyarrhythmias in patients with otherwise normal hearts. The bundle branches give rise to the terminal Purkinje fiber network, which lines the endocardial surface of both ventricles and carries the impulse to the ventricular myocardial cells. The cells of the His-Purkinje system are larger in diameter, depolarize and conduct more rapidly, and have a longer action potential duration than do the working cells in either the atria or the ventricles. Depolarization of the ventricles is initiated by depolarization of the interventricular septum from the left ventricular to the right ventricular side. The right and left ventricles then depolarize simultaneously and sequentially from apex to base and from endocardium to epicardium. This sequential depolarization of the ventricular Figure 49-1 (Figure Not Available) the major ionic currents responsible for the atrial and ventricular action potentials (A) and the sinoatrial node action potential (B). The numbers 0 to 4 beside the action potential demonstrate its five phases, and +30 and -85 mV refer to transmembrane voltage difference.

Prerequisite(s): Completion of all course requirements for engineer degree in information technology erectile dysfunction is caused by buy 100 mg extra super cialis fast delivery, or permission of instructor erectile dysfunction 2014 order 100 mg extra super cialis amex. Notes: May be repeated with change in topic can you get erectile dysfunction pills over the counter effective 100 mg extra super cialis, but degree credit is only given once trimix erectile dysfunction treatment generic 100mg extra super cialis visa. Prerequisite(s): Completion of all course requirements for the Engineer degree in Information Technology and permission of Project Director. Students must submit a Project Proegree Report form to the Graduate Student Service Office. George Mason University 2016-2017 Official University Catalog 3131 Prerequisite(s): Admission to candidacy. Investigates culture and language as primary shapers of relationships and identities. Investigates student achievement in relationship to classroom experiences and the language and cultural knowledge students bring to school. Examines vernacular discourses, including those in cyberspace and popular culture, while considering pedagogical implications. Teams engage in collaborative inquiry as they form and frame salient questions, take actions to improve teaching and learning, gather, analyze and interpret multiple forms of data, and share their experience in communities George Mason University 2016-2017 Official University Catalog 3133 of practice. Illustrates how learning technologies can be applied in a variety of teaching and training contexts including elearning, educational software, instructional design, corporate training, and curriculum development. Emphasis will be placed on the ways in which technological and social changes influence and shape the goals and outcomes of the K-12 educational process. Section 508 web accessibility standards and assistive technologies to access the computer will be explored. Explores curriculum integration of technology, and focuses on learning and using commercially available applications software. Students apply this understanding by designing and developing accessible web site using web authoring tools. Students explore basic authoring capabilities, and learn to apply those capabilities by designing and producing materials using commands, procedures, and functions of scripting language. Focuses on strategies for searching, sorting, creating, and communicating with information, much of which is structured by variety of online and offline databases. Addresses draw and paint programs, scanning and George Mason University 2016-2017 Official University Catalog 3137 editing images, and using visual communication to support K-12 learning. Covers the ways integration of tools in K-12 curriculum support learning, and difference between hypermedia and multimedia. Covers design and layout principles, appropriate use of images to facilitate communication, and ways K-12 teachers can design opportunities for students to learn concepts. Students learn to cultivate effective visual design practices for creating instructional products. Students learn to cultivate effective audio and video design practices for creating instructional products. Students learn to integrate the latest information and communication technologies into the creation of instructional products. Students learn to create instructional products using the latest e-learning design applications. Students learn pedagogical approaches to mobile learning as well as investigate various mobile platforms and applications. Students develop expertise in action research methodology, design, and implementation. Notes: To be taken at mid-degree program point with minimum 12 and maximum 15 credits. Hands-on activities focus on technology planning, selection, implementation, and evaluation utilizing instructional design best practices. Examines history and trends of online learning, and characteristics of K-12 virtual learners. Focuses on design model with attention to representative problems, performances of understanding, communities of practice, and mentors.

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