Modes of Natural Selection Whereas the previous section discussed several mechanisms for microevolution youtube gastritis diet buy cheap pantoprazole 40mg online, which deals with changes in a population over a short period of time (tens to hundreds of years) gastritis symptoms bloating purchase pantoprazole 40mg on-line, natural selection is the only method capable of generating stable evolutionary changes over long periods of time (thousands to millions of years) gastritis diet àâèòî buy discount pantoprazole 40mg on-line. It may occur as stabilizing selection lymphocytic gastritis diet purchase 20 mg pantoprazole free shipping, directional selection atrophic gastritis symptoms treatment pantoprazole 40 mg with visa, or disruptive selection (see Figure 16 gastritis diet uk buy generic pantoprazole 40 mg. For instance gastritis high fat diet buy 20mg pantoprazole amex, human birth weight is maintained within a narrow band by stabilizing selection chronic gastritis symptoms uk 20 mg pantoprazole with mastercard. Fetuses that weigh too little may not be healthy enough to survive, and fetuses that weigh too much can experience trauma during delivery through the relatively narrow birth canal. In addition, the larger the fetus, the more resources it requires from the mother. For all of these reasons, it is advantageous to keep birth weights within a narrow range. Each of these forms of selection would be pressured for by a different environment. If we have a heterogeneous plate of bacteria, very few may have resistance to antibiotics. If we then treat the plate with ampicillin (a type of antibiotic), only those colonies that exhibit resistance will survive. When Darwin studied finches on the Galapagos islands, he noted that although there were many species, they arguably all had a common ancestor. Seeds were either quite large or fairly small, requiring a large or small beak, respectively. Thus, if the original ancestor had a medium-size beak, over time, the animals with slightly larger or smaller beaks would be selected for. It has been observed in several species, including many insect species such as bees and ants, that certain individuals will endure sacrifices to benefit others. These social insects have large castes of workers that are sterile but work for the benefit of the whole colony, including the sexually reproducing insects. Some attempted to explain this phenomenon by proposing group selection, suggesting that there was a gene that led certain individuals within the population not to reproduce. A related theory to group selection is kin selection, which suggests that organisms will behave altruistically if they are closely related to successfully reproducing organisms. This would explain our social insect example above, because the workers are related to the fertile queen of the colony. Inclusive fitness refers to the number of alleles that an individual passes on to the next generation, even if only indirectly through altruistic behavior. Speciation Speciation is defined as the emergence of new species, a group of individuals who can interbreed freely with each other but not with members of other species. If we took two groups of the same species and separated them geographically for a long period of time, different evolutionary pressures would lead to different adaptive selections. If enough time passed, the changes would be sufficient to lead to reproductive isolation. Prezygotic mechanisms prevent formation of the zygote completely; postzygotic mechanisms allow for gamete fusion but yield either inviable or sterile offspring. Although a horse and donkey can produce a viable mule, the mule will be sterile and thus unable to contribute to a self-perpetuating mule lineage. Ecological Isolation Two species living in the same territory but in different habitats. Behavioral Isolation Members of two species are not sexually attracted to each other because of differences in such things as pheromones (chemical signals) and courtship displays. Reproductive Isolation the genitalia of two species are incompatible, so interbreeding cannot occur. Hybrid Sterility Hybrid offspring are sterile and thus incapable of producing functional gametes. Hybrid Breakdown First-generation hybrids are viable and fertile, but second-generation hybrid offspring are inviable and/or infertile. The potential for hybrid breakdown exists whenever closely related but reproductively isolated species are introduced to each other, and it occurs more in plants than in animals. Adaptive Radiation When a single ancestral species gives rise to a number of different species, adaptive radiation has occurred. Each species diverges to the point that it is able to occupy a unique ecological niche. Going back to the finches we mentioned previously, they exhibit adaptive radiation because the single ancestor led to 13 distinct species, each of which has a specific environmental role that is not filled by another species. Patterns of Evolution When we look at similarities between two species, we must be careful to determine whether those similarities are due to sharing a common ancestor or sharing a common environment with the same evolutionary pressures. When analyzing species this way, three patterns of evolution emerge: convergent evolution, divergent evolution, and parallel evolution (see Figure 16. For example, fish and dolphins have come to resemble one another physically, although they belong to different classes of vertebrates. They evolved certain similar features in adapting to the conditions of aquatic life. For example, seals and cats are both mammals belonging to the order Carnivora, yet they differ markedly in general appearance. These two species live in very different environments and adapted to different selection pressures while evolving. Origin of Life Although we have discussed some very simple organisms, we have not suggested how life began. The earliest evidence of life appears in stromatolites, the trace evidence of photosynthetic bacteria, which have been dated to about 3. In the 1920s, Oparin and Haldane proposed a mechanism for the origin of life, which was tested in the 1950s by Stanley Miller. Oparin and Haldane suggested that the conditions of early earth favored the creation of organic molecules, such as simple amino acids. The very early planet contained high amounts of carbon, hydrogen, and nitrogen along with lesser amounts of oxygen. It was hypothesized that with massive energy input from many sources, including the sun, lightning, radioactive decay, and volcanic activity, bonds formed between these atoms. Miller carried out an experiment in which he mixed these gases and exposed them to an electrical discharge. At the end of a week, many simple amino acids were found in the reaction apparatus. These microspheres had a selectively permeable membrane that separated them from their surroundings and maintained an independent internal environment. They are capable of carrying out enzymatic activity within their membrane if enzymes and substrate are present. Although microspheres and coacervates have some properties characteristic of life, they are not living cells. The collection of organic polymers that are believed to have been the primitive ancestors of living cells are called protobionts. Once this hereditary mechanism developed, protobionts would have been able to grow, split, and transmit important genetic information to their progeny. Self-replicating molecules eventually evolved to code for many of the molecules needed by primitive cells. We noted the vast body of evidence supporting evolution, including findings in paleontology, biogeography, comparative anatomy, comparative embryology, and molecular biology. The genetic basis of evolution explains both macro- and microevolutionary development, which can result in speciation and sub-speciation, respectively. Although our time together has been brief, we would like to congratulate you on a job well done completing these review notes. We hope that we have accomplished our goal of reviewing the biology content clearly and concisely. Biology-and physics and chemistry-is the foundation upon which your future medical practice is built. What could be more fun and more rewarding than the opportunity to prove yourself intellectually capable of success in your passionate pursuit of excellence in the medical sciences? Lamarck wrongly suggested that evolution occurred by increased or decreased use of a structure. Natural selection states that those organisms with more favorable traits will have greater reproductive success, thereby leading to those traits being expressed to a greater degree in the next generation. Punctuated equilibrium is an alternative theory of evolution stating that evolution occurs in rapid bursts rather than gradually over time. Hardy-Weinberg equilibrium can be used to predict phenotypic and allelic frequencies in a nonevolving population. Whereas microevolution may occur by many mechanisms, long-term evolutionary changes may be carried out only by natural selection. Natural selection may be classified as stabilizing, directional, or disruptive selection based on the new species deviation from the original normative standard. Altruistic behavior benefits one individual at the direct reproductive expense of another. Experimental evidence from Stanley Miller demonstrates that the primordial environment of the earth was sufficient to create the organic molecules necessary for life. A mutation due to excessive amounts of ultraviolet light occurs in an unfertilized egg; this will affect the child who is born from that egg. The muscular strength gained by a weight lifter during his lifetime is inherited by his children. A green-feathered bird that survived all of the predators in the forest will pass on the green feather genes to its offspring. A flower with tasty nectar that is eaten by a butterfly is more likely to pass on its delicious genes through the pollen spread by the butterfly than one that is not tasty. Favorable genetic variations become more and more common in individuals throughout their lives. Natural selection drives organisms to live in groups and ultimately become distinct species. As the climate got colder during the Ice Age, a particular species of mammal evolved a thicker layer of fur. At what point are two populations descending from the same ancestral stock considered separate species? When their habitats are separated by a significantly large distance so that they cannot meet 6. In a nonevolving population, there are two alleles, R and r, which code for the same trait. As the ocean became saltier, whales and fish independently evolved mechanisms to maintain the concentration of salt in their bodies; this can be explained by A. In a particular Hardy-Weinberg population, there are only two eye colors: brown and blue. Adaptive radiation results when an ancestral species gives rise to many descendants, which are adapted to different parts of the environment. How would scenarios for adaptive radiation differ if speciation occurred allopatrically (different ranges) versus sympatrically (overlapping ranges)? Typically, r-selected species produce many offspring, each of which has a relatively low probability of surviving to adulthood. On the other hand, k-selected species invest more heavily in fewer offspring, each of which has a relatively high probability of surviving to adulthood. In the scientific literature, r-selected species are occasionally referred to as "opportunistic," whereas k-selected species are described as in "equilibrium. B To find the correct answer, we have to read each choice in part and eliminate the ones that fit with the modern-day theories of inheritance. Basically, any statement that will argue that acquired characteristics are passed on to the offspring will be incorrect. Based on this, we can tell right away that (B) is incorrect because the muscular strength is an acquired characteristic and thus cannot be transmitted to the offspring. Lamarck argued that a giraffe that stretches its neck to reach for high trees will produce offspring with longer necks, but modern evolutionary theories proved this argument to be incorrect. The survival of the fittest leads to an increase of those favorable genes in the gene pool. Basically, Darwin strongly believed that, as (A) states, natural selection is the driving force of evolution and that the fitness of an individual is measured in terms of reproductive success, as (D) states. Through natural selection, organisms become separated in groups, depending on how adapted they are to a particular environment, and these groups eventually separate to the point of becoming distinct species. The theory of natural selection applies to a population of organisms, not to a particular individual. As such, favorable genetic variations become more and more common from generation to generation, not during the lifetime of an individual. In fact, the chance mutations an individual organism accumulates over its life span are more likely to be harmful than helpful. C the Hardy-Weinberg equilibrium exists in certain ideal conditions that, when satisfied, allow one to calculate the gene frequencies within a population. The Hardy-Weinberg equation can be applied only under these five conditions: (1) the population is very large; (2) there are no mutations that affect the gene pool; (3) mating between individuals in the population is random; (4) there is no net migration of individuals into or out of the population; (5) the genes in the population are all equally successful at reproduction. Monogamy is not a necessary condition for the Hardy-Weinberg equilibrium to be applied, making (C) the correct answer. B the situation described in the question stem is an example of directional selection. In directional selection, the phenotypic norm of a particular species shifts toward an extreme to adapt to a selective pressure, such as an increasingly colder environment. Only those individuals with a thicker layer of fur were able to survive during the Ice Age, thus shifting the phenotypic norm. A Two populations are considered separate species when they can no longer interbreed and produce viable, fertile offspring. C When two or more lineages not sharing a recent common ancestor independently developed similar characteristics, a convergent evolution is said to have taken place. Whales and fish do not share a recent common ancestor; whales are mammals, but fish are not. Since they independently developed a similar mechanism to maintain the concentration of salt in their bodies, convergent evolution must have occurred. B Using the information given to use in the question stem, we can determine that the percentage of the population with blue eyes (genotype = bb) = 36% = q2 = 0. Since this is a Hardy-Weinberg population, we can assume that p + q = 1, so p = 1Â0. So 48% of the population is heterozygous for brown eyes, making (B) the correct answer. D We can assume that this is a Hardy-Weinberg population since we are not told otherwise. Let us denote P the frequency of the dominant allele (C) and q the frequency of the recessive allele (c). If the variation is selected for by the environment, that individual will be more fit and more likely to survive to reproductive age. Survival of the fittest leads to an increase of those favorable genes in the gene pool. Carbon, hydrogen, nitrogen, and small amounts of oxygen present in the atmosphere and seas bonded together in various ways and accumulated, forming a primordial soup. Thus, out of the answer choices, the molecule that did not participate in the formation of the precursor molecules was helium, (B). B In laboratory experiments, abiotically produced polymers in an aqueous solution can spontaneously assemble into tiny proteinaceous droplets called microspheres. These microspheres have selectively permeable membranes and their internal chemical environment is distinct from that of their surroundings. Thus, from the given choices, the one that does not describe microspheres is (B), the correct answer. At the end of each topic, you will find a "Takeaways" box, which gives a concise summary of the problem-solving approach, and a "Things to Watch Out For" box, which points out any caveats to the approach discussed above that usually lead to wrong answer choices. Finally, there is a "Similar Questions" box at the end so you can test your ability to apply the stepwise technique to analogous questions. A hypertonic environment means that the environment is more concentrated than the cell is. Note that you can similarly express this condition by stating that the cell is hypotonic to the environment. A hypotonic solution is one that is less concentrated than the solution to which it is being compared. The cell is being moved into a hypertonic environment, which means that the environment is more concentrated with solutes than the interior of the cell. Takeaways Questions that involve osmosis are usually combined with other biology topics (particularly kidney function) to create a multistep solution. The key is to have a solid understanding of what hypertonic and hypotonic mean and how the terms can be used interchangeably to describe the same state. The sodium potassium pump moves in two potassium ions as it moves out three sodium ions. The net effect is to decrease cell solute concentration as the cell loses one ion per each pump. Using the terms hypertonic and hypo-osmotic, describe the relationship between the interstitial fluid and the filtrate as well as the relationship between the filtrate and the interstitial fluid. An individual drinks a large coffee in the morning, and when he goes to the restroom finds that his urine is nearly colorless. Fetal Circulation Key Concepts Chapter 5 Fetal circulation Fetal structures Fetal lungs are supplied with only enough blood to nourish the lung tissue itself because fetal lungs do not function prior to birth. Obstruction of which fetal structure would cause an increase in blood supply to fetal lungs? The major difference is that in fetal circulation, blood is oxygenated in the placenta because, as the question states, fetal lungs are nonfunctional before birth. The fetal circulatory route contains three shunts that divert blood flow away from the developing fetal liver and lungs.
First gastritis symptoms treatment effective 40mg pantoprazole, if there are medical conditions that make Alzheimer symptoms worse that illness needs to be managed gastritis or gerd buy pantoprazole 40 mg overnight delivery. Experts within this field recognize that caregivers are at a high risk for depression and medical illness gastritis diet journals 40 mg pantoprazole sale. As a result gastritis diet 50 cheap 20mg pantoprazole with amex, recommendations and guidance about community resources and support is integrated into the overall management of the disease syarat diet gastritis buy pantoprazole 20 mg without a prescription. Cholinesterase inhibitors Cholinesterase inhibitors are a class of medicines that block cholinesterase-an enzyme that breaks down the neurotransmitter acetylcholine antral gastritis diet plan best 20mg pantoprazole. However gastritis chronic diet cheap pantoprazole 40 mg without a prescription, the disease eventually continues to progress despite treatment and the average effect is often modest gastritis diet 5 small buy pantoprazole 40mg fast delivery. However, global changes in cognition, behavior and functioning have been detected by both physicians and caregivers, indicating that even small measurable differences may be clinically significant. These drugs are similar yet have distinct pharmacology profiles such as onset of action, side effect profile, potential drug interactions, ease of administration. However, no published results are available for severe dementia, though open-label follow up from trials suggests that these drugs continue working as the cholinergic deficit increases. Positive changes in cognition, behavior and function were demonstrated, however, the disease continues to progress and the treatment effect is modest and short lived. Improvements in cognitive functions for the first two years were significantly better than placebo. However, no benefits were seen in the long term endpoints of institutionalization, and the experts state that improvements in cognition does not reduce institutionalization as reported by pharmaceutical companies. Also, a therapy that is beneficial but results in longer life expectancy may actually increase health care costs compared to not treating due to the longer life expectancy. An over stimulation of these receptors could lead to neuronal loss which could affect the pathophysiology of Alzheimer disease. The medication is still being studied and is approved in the United States and several European countries. For example, among the behavioural disturbances common in Alzheimer disease, depression is more common early in the illness, while delusions and hallucinations are more common in the middle and later stages. Behavioural issues to be addressed include major depression and other depressive syndromes, suicidal ideation or behaviour, hallucinations, delusions, agitation, aggressive behaviour, disinhibition, anxiety, apathy, and sleep disturbances. Behaviour Agitation/aggression Anxiety Apathy Disturbed effect/mood Altered ideation/perception Vegetative features Agent Antipsychotics,anticonvulsants, antidepressants, anxiolytics Antidepressants, anxiolytics, anticonvulsants Antidepressants, stimulants Antidepressants, anticonvulsants Antispsychotics Antidepressants, anxiolytics, stimulants Source: American Psychiatric Association. There is sufficient evidence from randomized controlled trials to support the use of both traditional and atypical antipsychotics for the management of agitation and psychosis in dementia. Of the two classes atypical antipsychotics appear to be better tolerated compared to traditional antipsychotics. The American Academy of Neurology practice guidelines conducted an in-depth review of pharmacological therapies for non-cognitive symptoms in dementia. The expert panel conclude that most studies in this area focus on mixed populations with dementia. Major Problem and Challenges for Disease Control: Why Does the Disease Burden Persist? While a cure is desirable, the likely first step may be an intervention that reduces the risk of future disease, similar to the approach to cardiovascular disease. Clinicians and caregivers are challenged with caring for an increasing aging population affected by dementia. Increased life expectancy has seen a rise in chronic medical disease and associated illnesses, including dementia. For example, there will be an estimated 400% increase in population of North Americans aged 85 and older by 2050, 40% of whom will develop dementia. Psychiatric and behavioural problems are present in up to 90% of patients with dementia. Some of these treatment options include employing unique social and environmental interventions; knowledge and use of increasingly sophisticated medications, and providing individualized therapy to patients, working with care givers or varying systems providing care. Management of dementia is also complex since it requires differentiating and managing various changing neuropsychiatric and behavioural problems. A balance also has to be reached between aggressive intervention and palliative care continued treatment versus withdrawal of medicines, and patient benefit versus caregiver burden. Managing dementia is complex and presents a major public health concern for the today and the future. A broad public health approach is needed to improve the care and quality of life of people with dementia and family caregivers. The aims and objectives of the approach should either be articulated in a stand-alone dementia policy or plan or be integrated into existing health, mental health or old-age policies and plans. Some high-income countries have launched policies, plans, strategies or frameworks to respond to the impact of dementia. There are several key issues that are common to many national dementia policies and plans, and these may be necessary to ensure that needs are addressed in an effective and sustainable manner. These include: scoping the problem; involving all the relevant stakeholders, including civil society groups; identifying priority areas for action; implementing the policy and plan; committing resources; having intersectoral collaboration; developing a time frame and monitoring and evaluation. The priority areas of action that need to be addressed within the policy and plan include raising awareness, timely diagnosis, commitment to good quality continuing care and services, caregiver support, workforce training, prevention and research. Universal social support through pensions and insurance schemes could provide protection to this vulnerable group. Formal recognition of the rights of people with dementia and their caregivers through legislation and regulatory processes will help reduce discriminatory practices. Where capacity is impaired due to dementia, legal provisions should recognize and protect the right to appropriate autonomy and selfdetermination including substitute or supported decision-making and procedures for implementing advance directives. Education and support relating to ethical decision-making and human rights should be an essential part of capacity-building for all involved in providing dementia care, including policy-makers, professionals and families. This challenges governments to develop and improve services for people with dementia, focusing on earlier diagnosis, provision of support in the community, and a responsive health and social care sector. Integrated and coordinated health and social pathways and services will be needed to cater for the changing needs of people with dementia and their caregivers. Such pathways should ensure that the needs of specific or minority population groups are taken into account. Improved community support will assist families to provide care for longer and to delay or reduce reliance on high-cost residential care. Capacity-building of the workforce is essential to improve knowledge and awareness of the benefits of a coordinated response to care. Dementia care, long-term care and chronic disease management incorporating a multidisciplinary team should form part of professional education and should be supported by the development of appropriate practice guidelines. In a world with an increasingly mobile population, the migrant workforce brings its own set of challenges that need to be understood and addressed. Most care is provided by family and other informal support systems in the community and most caregivers are women. However, changing population demographics may reduce the availability of informal caregivers in the future. The provision of care to a person with dementia can result in significant strain for those who provide most of that care. The beneficial effects of caregiver interventions in decreasing the institutionalization of the care recipient have been clearly demonstrated. Despite evidence of effectiveness, there have been no successful examples of scale-up in any of the health systems in which the evaluative research has been conducted. Further research should focus on implementation in order to inform the process of scale-up. Despite the availability of services in some countries or parts of countries, there are barriers to uptake. Lack of understanding of services, lack of understanding or stigma attached to the syndrome, previous poor experience with services, and cultural, language and financial barriers creates obstacles to service utilization. Information and education campaigns for the public - including people with dementia, their caregivers and families  can improve service utilization by raising awareness, improving understanding and decreasing stigmatizing attitudes. Support is needed to enable informal caregivers to be able to continue in their role for as long as possible. Support includes information to aid understanding, skills to assist in caring, respite to enable engagement in other activities, and financial support. For those who are living with dementia (both the person and their family), the stigma contributes to social isolation and to delays in seeking diagnosis and help. There is an urgent need to improve the awareness and understanding of dementia across all levels of society as a step towards improving the quality of life of people with dementia and their caregivers. Governments have a role to play in resourcing public awareness campaigns and in ensuring that key stakeholders are involved in such campaigns. They should be accurate, effective and informative and should be developed in consultation with people with dementia, their families and other stakeholders, including civil society. A range of actions is required to improve care and services for people with dementia and their caregivers. These actions include advocacy and awareness-raising, developing and implementing dementia policies and plans, health system strengthening, capacity-building, supporting caregivers and research. On Alzheimer disease these proposed therapies target a variety of proteins such as circulating A protein, A plaques, protein tau, P-tau. A significant percentage of patients developed antibodies to A, although at different titers, and no adverse events were reported. This trial was stopped after the report of serious adverse events from 18/298 patients (6%), who developed meningoencephalitis. Indeed, there was a marked reduction in A deposition in some patients, as well as significant reduction of plaques deposition in different cortical regions. Residual plaques showed a particular appearance suggesting phagocytosis from microglia. Passive immunotherapy Passive immunization has also been investigated ultimately, in two major clinical trials. The North American studies 301 and 302 completed as planned; the two complementary studies in Europe were early terminated in August 2012. Other trials, targeting the midregion of the A -A monoclonal antibody directed against the midregion of the A peptide, was shown to neutralize soluble A species, prone to be toxic. Although it missed its primary outcome, the trials showed some signs of slowing cognitive decline perhaps more evident in milder subjects. Statistics found a 34% less mental decline in mild Alzheimer patients compared to those on a placebo treatment for 18 months according the Eli Lilly & Co. Researchers and medical doctors have suggested that treatment must be given earlier on, at the prodromal stage, or even earlier. The study will involve about 300 participants from Colombia and the United States. They all share a rare genetic dominant mutation that typically triggers Alzheimer symptoms around the age of 45. This trial is unique and has great expectations from the scientific and medical communities as it will help determine if the amyloid hypothesis is correct. By targeting tau, the medicine aims to stabilize microtubules, which help support and transport of essential nutrients and information between cells. This discovery has prompted new therapies directed at blocking these enzymes, thus preventing or slowing the progression of the disease. Result of significant clinical trial data demonstrated that the use of secretase inhibitors is non-specific, worsens cognitive decline and is associated with serious safety issues. As mentioned above, brain damage in Alzheimer disease is caused by amyloid, but metal ions, such as zinc and copper, both of which accumulate in the brain with old age, are also neurotoxic. Research has shown that these metals cause amyloid aggregation, and the mixture of the two. These drugs, do not attack the underlying disease pathology, instead they compensate for the loss of neurons that communicate via this enzyme. Cholinesterase inhibitors appear to slow down cognitive decline, however the improvements are very modest. Most of these studies show some improvement in cognition, however there is very little evidence to support global improvements in cognition, functional ability and behavior. However, at present there is insufficient evidence to recommend its use in practice. Gingko biloba, a plant extract that contains numerous pharmacological properties, some of which are thought to be antioxidative, anti-inflammatory or neurotransmitter modulators. Current research suggests that the use of gingko biloba provides smaller effects that that of cholinergics. Also, it is currently unknown which of the active components of this alternative compound contributes to cognitive enhancing effects. Furthermore, the compound is a non-regulated supplement in several countries and standardized preparations are not available. One is a surrogate for the disease, which demands nearly perfect sensitivity and specificity. The other is a supporting measure in the diagnosis, which again, requires a fairly high sensitivity and specificity. Still, as of 2013 a definite diagnostic is only possible after death of the patient with brain histopathology. New biomarkers will allow the identification of individuals at risks and help in characterizing subpopulations for disease onset, progression and outcome. These specific markers could potentially facilitate the development of personalized treatments for each stage of the disease. Again most promising expectations of these new biomarkers would be to target molecules that researchers will use to develop medicines vaccines for individuals at risks. Biomarkers are also important monitoring tools for high throughput screening of candidate molecules such as active compounds, antibodies or genes which can modulate a particular biomolecular pathway involved in Alzheimer disease. However, recent data suggest extremely limited utility of biomarkers for Go/NoGo decisions in early stages of clinical development as there are still have no evidence linking them to clinical outcome. There are numerous technical issues and challenges to measuring brain amyloid: 1) limit of detection, 2) not possible to distinguish vascular deposition from cerebral deposition, 3) the measure is continuous but often treated as a binary, positive or negative, 4) the amyloid burden is reported relative to a reference region, the cerebellum. These imaging techniques remain extremely costly and therefore cannot be used in routine in all countries to monitor disease progression. Moreover as has happened in other areas of imaging and diagnostics modified and cheaper could potentially be developed and may be worth researching. It is produced by the choroid plexus and serves as a protection for shocks and transport waste from the central nervous system. While these two proteins represent the two key pathological mediators of disease, other aspects of this multifaceted disease such as oxidative stress, calciummediated toxicity, and neuroinflammation are being unraveled, giving rise to possible new biomarkers for diagnostic or disease progression. There are different assays that provide different results, which while correlated, are not directly interpretable. The key issue is that a clinical standard has yet to be developed, which make comparison of results across studies a challenge. Also, the ability to identify what is an optimal cutpoint is a challenge given the variation in assays and assay results. Blood-based biomarkers represent a considerable challenge because blood is not in direct contact with brain. Therefore brain derived proteins and metabolites that passes through the blood-brain barrier become markedly diluted into blood and plasma which are other complex mediums. Also the size of the particles may affect the rate of exchange across the blood brain barrier. The advantages of using markers in blood and plasma are obvious as they can easily be collected from patients at an 6. Blood is a complex fluid, composed of proteins, lipids and metabolites as well as different cell types eg red cells, platelets and lymphocytes, which composition can fluctuate depending on internal and external environment. This makes it more challenging to target specific assay for disease but also offers a large palette of possible targets. Search for a protein assay Measuring proteins in blood is complex due to the wide dynamic range of proteins, isoforms, complexes as well as activities, and post-translational modifications. Despite these challenges, developments in both bioinformatics and mass spectrometry have led to substantial advances in proteomic analysis in blood and plasma. Among these proteins are the apolipoprotein-E (ApoE) and several proteins with established roles in A clearance. These collaborations are essential as they provide larger and cross validation between studies. With technical improvements of the proteome analysis, it is very likely that specific and reproducible markers will become available in the near future. We can also envisage that these markers could be used to help differentiate different sets of patients with distinct disease progression rates and adapt treatment in consequence. The European Union is also involved to find new therapies for neurodegenerative diseases and enable early diagnosis for early targeted treatment. Pharmacog for "Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development" is a partnership of 32 academic and industry actors from seven countries, coordinated by GlaxoSmithKline R&D and the Universitй de la Mйditerranйe. This ambitious European project aims at providing the tools needed to define more precisely the potential of a drug candidate, reduce the development time of new medicines and thus accelerate the approvals of promising new medicines. It is also unclear whether patients who do not respond to one anticholinesterase inhibitor will respond to another. Furthermore, ways of measuring, determining response, and assessing when medications need to be stopped remain unclear and need to be addressed. There may also be a need for more comparative clinical trials of these agents to determine which agent offers the greatest benefit and causes least resistance. The effective and appropriate administration of cholinergic and other medicines requires good baseline assessment with validated scales for objective measurement. Important factors other than cognitive functions and activities of daily living need to be studied. These data are extremely difficult to capture as Alzheimer disease is also prone to external environmental and social factors. Gaps Between Current Research and Potential Research Issues that Could Make a Difference A review of currently available treatments suggests a number of areas for further study. Some of these recommendations are within the realm of improved evaluation and assessment.
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Looking at (A) gastritis symptoms fatigue discount 40 mg pantoprazole with amex, we can decide right away that it is a correct association gastritis lower back pain cheap pantoprazole 40 mg on-line, because trypsin does indeed hydrolyze specific peptide bonds gastritis diet ìòñ cheap pantoprazole 20 mg with amex. Next gastritis diet how long buy pantoprazole 20 mg free shipping, we can eliminate (C) gastritis diet in pregnancy pantoprazole 20mg low cost, because it is true that pancreatic amylase hydrolyzes starch to maltose gastritis symptoms empty stomach order 20mg pantoprazole free shipping. C Protein digestion begins in the stomach gastritis tylenol cheap 40 mg pantoprazole with visa, where pepsin (secreted as pepsinogen) hydrolyzes specific peptide bonds gastritis treatment dogs buy cheap pantoprazole 40mg online. Protein digestion continues in the small intestine as trypsin (secreted as trypsinogen), chymotrypsin (secreted as chymotrypsinogen), carboxypeptidase, aminopeptidase, and dipeptidase hydrolyze specific parts of the peptide. Glancing at the other choices, we confirm once more that (A) is the correct answer. B the question is basically asking us to identify the structure that would prevent food from reaching the small intestine. Because the child presents with projectile vomiting, we can assume that food reached the stomach but cannot continue its course to the intestine. D the mouth has an important role in digestion, because it is the first part of the digestive tract to interact with food. First, the mouth (the teeth and tongue, specifically) churns the food into small pieces, a process called mechanical digestion. With the help of the tongue, a bolus is formed, which will then be swallowed and sent through the esophagus to the stomach. Primarily one type of chemical digestion occurs in the mouth: the chemical digestion of starch to maltose, a process initiated by salivary amylase (ptyalin). Although lingual lipases are present, very little fat digestion actually takes place. Looking at the first graph, we notice that the enzyme has maximal activity at a relatively low pH (3Â4). It must be an enzyme that functions in an acidic environment, most likely in the stomach. The second graph portrays an enzyme whose optimal activity occurs at a high pH (9. It must correlate to an enzyme that works in a basic environment, such as the small intestine. Our task now is to select the answer choice that pairs the first graph to a gastric enzyme, and the second graph to a small intestinal enzyme. Pepsin is secreted in the stomach and works best in an acidic pH, whereas chymotrypsin acts in the small intestine at a basic pH. B In the mouth, teeth chew the bread into smaller particles, and salivary amylase digests some of the starch (the major component of bread) into maltose. The bread bolus is then propelled through the pharynx and esophagus, entering the stomach through the cardiac sphincter. There is no chemical digestion of starch in the stomach, so after a couple of hours, the chyme will pass through the pyloric sphincter and enter the small intestine. In the small intestine, pancreatic amylase hydrolyzes starch into maltose, whereas maltase, sucrase, and lactase hydrolyze various disaccharides into their respective monosaccharides. Finally, the piece of bread will finish its course through the large intestine and the rectum and will eventually be expelled through the anus. The only choice that correctly identifies all of the segments of the digestive tract is (B). A the epiglottis is a small flap that covers the trachea during swallowing; in a way, it is a switch that ensures food and air travel through different passageways. The lower esophageal (cardiac) sphincter controls the passage of food into the stomach and prevents anything from getting out of the stomach. A Glancing at each choice, we realize that only chylomicrons are correctly paired with their site of absorption. Large fatty acids and glycerol, which combine to form triglycerides, along with phosphoglycerides and cholesterol, are packaged into protein-coated droplets called chylomicrons. The chylomicrons are then absorbed into tiny lymph vessels within the villi called lacteals, which lead to the lymphatic system. D Starch is hydrolyzed to maltose by two enzymes: salivary amylase (secreted by the salivary glands) in the mouth and pancreatic amylase (secreted by the pancreas) in the small intestine. B the intestinal capillaries transport nutrients from the intestines to the liver, where they get processed, repackaged, and distributed. It is true that both enterokinase and maltase are secreted by the intestinal glands, so (C) and (D) can be eliminated. Sucrase does indeed hydrolyze sucrose to glucose and fructose, a process that occurs in the small intestine; we can eliminate (A). Carboxypeptidase, on the other hand, is an enzyme that hydrolyzes a terminal peptide bond at the carboxy terminal, as the name indicates. Glancing at the other two answers, we confirm that (C) and (D) are indeed true associations. The first two names refer to alveolar inflammation caused by the inhalation of some substance that was not properly filtered out by nasal hairs and mucus. Including those at 102°F; that is, the temperature at which most hot tubs are set. The happy, relaxed bathers who breathe these bacteria might be in for a long road of respiratory troubles. As mentioned earlier, hot tub lung falls in a category of hypersensitivities, which can potentially go away by themselves. The best way to avoid hot tub lung is to make sure that the tub is being cleaned properly and routinely before entering it. Many types of stressors (pathogens, particles, or chemicals) can irritate them and cause respiratory distress. They allow for dirt and particulate matter to be removed from the air in addition to warming and humidifying the air before it reaches the lungs. Air enters the respiratory tract through the external nares of the nose and then passes through the nasal cavity, where it is filtered through mucous membranes and nasal hairs. The pharynx serves as a tunnel between the mouth and esophagus through which food travels (Chapter 7), whereas the larynx is only a pathway for air. To keep food out of the respiratory tract, the opening of the larynx (glottis) is covered by the epiglottis during swallowing. From the larynx, air passes into the cartilaginous trachea and then into the mainstem bronchi (one per side). These bronchi continue to divide into smaller structures known a s bronchioles until they are tiny structures in which gas exchange occurs (the alveoli). Real World the left lung has a small indentation that makes it slightly smaller than the right lung. The bronchi and trachea also contain ciliated epithelial cells to catch material that may have made it past the initial check in the nose. Each alveolus is coated with surfactant, a detergent that lowers surface tension and prevents the alveolus from collapsing on itself. A network of capillaries surrounds each alveolus to carry oxygen and carbon dioxide. The branching and minute size of the alveoli allow for an exceptionally large surface area for gas exchange-approximately 100 m2. Ventilation the lungs themselves are contained in the thoracic cavity, which, as we will see in the next chapter, also contains the heart. They are separated from the organs of digestion by a muscle known as the diaphragm, which is necessary for inspiration. Although breathing is controlled autonomically, the diaphragm is actually composed of skeletal muscle and is, therefore, under somatic control. The surface adjacent to the lung is visceral, and all other parts of the sac are parietal (see Figure 8. The side directly touching our fist is the visceral pleura, and the outer layer is the parietal pleura, which is associated with the chest wall in real life. The space within the sac is referred to as the intrapleural space, which in our bodies contains a thin layer of fluid (imagine pouring a bit of water into the balloon before blowing it up). In addition, there is a pressure differential between the intrapleural space and the lungs. Air enters the intrapleural space, thereby increasing the intrapleural pressure and collapsing the lung. Pneumothorax is treated by inserting a needle and withdrawing air from the intrapleural space. This might sound a lot like physics, and the process of ventilation is, in fact, grounded in physics. Here, we are going to use pressure differentials between the lungs and intrapleural space to drive air into the lungs. We use our diaphragm as well as the external intercostal muscles (layer of muscles between the ribs) to expand the thoracic cavity. As the cavity enlarges, the diaphragm flattens down, and the chest wall moves out (see Figure 8. The gas in the lungs is at atmospheric pressure, which is now higher than the pressure in the intrapleural space. We can see, then, that the lungs will expand as air is sucked in from a higher-pressure environment. This mechanism is referred to as negative-pressure breathing, because the driving force is the lower (relatively negative) pressure in the intrapleural space compared with the lungs (alveoli). Real World Emphysema is a disease characterized by the destruction of alveolar walls. This results in reduced elastic recoil of the lungs, making the process of exhalation extremely difficult. Simple relaxation will reverse the processes we discussed in the last paragraph (see Figure 8. As the diaphragm and external intercostals relax, the chest cavity decreases in size (volume). Now, pressure in the intrapleural space is higher than in the lungs, which is still at atmospheric level. During highly active tasks, we can speed this process up by using the internal intercostal muscles, which oppose the externals and pull the rib cage down, actively decreasing the volume of the thoracic cavity. Finally, we should recall that surfactant prevents the complete collapse of our alveoli during exhalation by reducing surface tension at the alveolar surface. Our ventilation is primarily regulated by neurons (ventilation centers) in the medulla oblongata that rhythmically fire to cause regular contraction of respiratory muscles. As the partial pressure of carbon dioxide rises, the respiratory rate will increase to counter it. Key Concept Inhalation and exhalation are different processes in terms of energy expenditure. Muscle contraction is required to create the negative pressure in the thoracic cavity that forces air in during inspiration. Expiration during calm states is entirely due to elastic recoil of the lungs and musculature. Of course, during more active states, the muscles can be used to force air out and speed the process of ventilation. We can choose to breathe more rapidly or slowly; however, extended periods of hypoventilation would lead to increased carbon dioxide levels and an override by the medulla oblongata (which would jump-start breathing). The opposite process (hyperventilation) would blow off too much carbon dioxide and inhibit ventilation (hopefully before we pass out! Not until oxygen falls to a very low level does hypoxia drive the ventilatory response. One instrument used is a spirometer, which can measure the amount of air normally present in the lungs and the rate at which ventilation occurs. Note that we do not breathe all that rapidly when oxygen is abundant; a normal respiration rate is around 12 breaths per minute. On top of Mount Everest, where there is only one third as much oxygen as at sea level, ventilation may increase to 80 to 90 times per minute! There will always be some air left over, because expelling it all would require lung collapse, which we definitely want to avoid. Instead, we shallowly breathe only what we need, which may be a liter or so with each breath. Gas Exchange Our last item for this chapter is the actual movement of gas in the lungs, which is, after all, their primary function. As we already mentioned, a network of pulmonary capillaries surrounds each alveolus. The capillaries bring deoxygenated blood from the pulmonary arteries, which stem from the right ventricle. As they approach, the single-celled alveolar layers allow for diffusion of carbon dioxide from the blood into the lungs and oxygen in the opposite direction. Since blood is deoxygenated as it enters, it has a relatively low partial pressure of oxygen and a relatively high pressure of carbon dioxide, facilitating the transfer of each down its respective concentration gradient. Since the gradient between the blood and air in the lungs is already present as the blood enters the lungs, no energy is required for gas transfer. Key Concept O2 in the alveoli flows down its partial pressure gradient from the alveoli into the pulmonary capillaries, where it can bind to hemoglobin for transport. How would our respiratory systems adjust on the slopes as we move to higher altitudes where less oxygen is available? First, we can breathe more rapidly to try and increase gas exchange; second, we could make more red cells to carry the oxygen (polycythemia; see Chapter 9). In the long term, we could develop more blood vessels (vascularization), which would facilitate the distribution of a lower amount of oxygen to tissues. Conclusion the functional unit of the lung is the alveolus, just as the basic unit of muscle was the sarcomere. We learned that gas exchange across the lungs is a result of passive diffusion of carbon dioxide and oxygen down their concentration gradients. This diffusion is accomplished in the alveoli, which, when laid out, have an area of 100 m2! The actual process of breathing in and out is controlled by chemoreceptors in the ventilatory centers of the brain stem. Although we can voluntarily influence our breathing rate to a certain degree, our nervous system takes care of ventilation and gas concentrations in the body. Pressure gradients between the intrapleural space and lung provide the physical basis for ventilation. We literally suck air in from the atmosphere, because the pressure in the thoracic cavity during inspiration is lower than that in the outside world. The binding of oxygen to hemoglobin in the lungs is a concept that will be expanded on in the next chapter, as well as how altitude, pH, and chemicals may affect this binding. The external nares and nasal cavity provide a method to both remove contaminants from air as well as humidify it before it reaches the lungs. The epiglottis provides a mechanism to prevent large material from entering the larynx and bronchi. The diaphragm and intercostal muscles are responsible for generating the negative pressure differential between each intrapleural space and its associated lung. Vital capacity is the sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume. Gas exchange in the lungs is a passive process resulting from the large, pre-existing concentration gradients of oxygen and carbon dioxide. Which of the following associations between the two stages of respiration and the contraction of muscles is correct? The maximum amount of air that can be forcibly inhaled and exhaled from the lungs C. The volume of air that can still be forcibly exhaled following a normal exhalation D. Which of the following mechanisms exists in the respiratory system to ensure that inhalation occurs rapidly and safely? The epiglottis covers the glottis to ensure that food does not enter the trachea during swallowing. Which is the correct sequence of passageways through which air travels during inhalation? Would you expect the vital capacity of mountain dwellers to be greater or less than the vital capacity of people residing at sea level? What other physiological adaptations would you expect to observe in mountain dwellers? D Gas exchange in the lungs relies on passive diffusion of oxygen and carbon dioxide. This is accomplished easily because there is always a difference in the partial pressures of these two gases. In addition, the thin and moist alveolar surfaces allow for fast diffusion and gas exchange across their membranes. D the muscles involved in ventilation are the diaphragm (which separates the thoracic cavity from the abdominal cavity) and the intercostal muscles of the rib cage. During inhalation, the diaphragm contracts and flattens, while the external intercostal muscles contract, pushing the rib cage up and out. During exhalation, both the diaphragm and the external intercostals relax, causing a decrease in the size of the thoracic cavity. C During inhalation, as the diaphragm and external intercostal muscles contract, the rib cage and chest wall are pushed up and out, and the thoracic cavity increases in volume. This volume increase, in turn, reduces the intrapleural pressure, causing the lungs to expand and fill with air. This process is referred to as negative-pressure breathing because air is drawn into the lungs by a vacuum. In contrast, positive-pressure breathing, as in a patient on a ventilator, occurs when air is forced into the lungs because the pressure is greater in the ventilator than in the lungs.
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Temporo-mandibular joint condylectomy and its effect over occlusion in cats: a cadaveric study. Classic Brainstem Lesion · Cranial nerve deficits  Usually unilateral  Often occur in clusters. Non-contagious Non-progressive Ataxia & spastic gait associated with cerebellar disease 236 6 1/25/2019 Department of Veterinary Clinical Sciences Using Exam, Try to determine: Brain Spinal Cord Neuromuscular Clinical Divisions of the Spinal Cord 1. High Cervical Low Cervical Thoracolumbar Lumbosacral Coccygeal (C1-C5) (C6-T2) (T3-L3) (L4-S3) (Cd) Neurologic Exam Tip: Simplify your exam: Pay attention to 3 spinal reflexes. Cats that do not become continent in 1 month usually fail to regain urinary function. Neuromuscular Diseases · Tick Paralysis · Coon Hound Paralysis · Myasthenia gravis · Botulism, others. Types of Nystagmus · Peripheral Lesions  Horizontal  Rotary · Central Lesions  Horizontal  Rotary  Vertical General Rules for Suspecting a Central Vestibular Lesion 1. Outside Assets: Assets owned by different legal entities (or outside a legal entity) 5. A legal entity has legal capacity to enter into agreements or contracts, assume obligations, incur and pay debts, sue and be sued in its own right, and is held responsible for its actions Administrative Entities: 1. How it works General Partner Total Control/Liability 1% Ownership Limited Partner(s) No Control/Liability 99% Ownership c. Can help the elderly to maintain independence when long term care is needed the Charging Order: 1. If the distributions are made on a Pro-Rata basis the judge may force the distribution 3. Uses the charging order as the remedy to get assets out of the entity (States vary in enforcement 3. Asset protective entities will protect from an outside lawsuit and cannot be pierced if the entity is created properly. The same protection does not apply to an individual who owns assets in their own name 4. High risk assets must be placed in separate asset protective entities in order to shield them from lawsuits Rock Solid Asset Protection Implementation 1. Many attorneys will create entities without the proper knowledge of how they work and how they protect assets. This often creates difficulties for defendants who think their assets are protected, but do not realize they are almost always vulnerable. The cost of entity structuring is inconsistent with both the knowledge of the legal professional and the amount of work they have to do. When the mystery is matched with the surrounding anatomy, clues to how stimulation with dry needle, electroacupuncture or aquapuncture work may provide answers. This article is designed to cover some very commonly used points in and around the head and their anatomically-related structures beneath the skin. Some of the points are classical acupoints, while some are transpositional acupoints as defined by Dr. It is used as a sedation point, Shen disturbances, epilepsy, sleep disorders and prolapse of the anus. While the acupuncture needle has been directed in a cranial or caudal direction by various acupuncturists, the needle often can be popped out with over-zealous petting during a treatment. This midline depression is on the interparietal bone as it connects the two parietal bones. It makes its appearance about the forty-fifth day of the canine gestation and can either fuse or remain a separate bone. It is from this interparietal bone that the external sagittal crest arises in mesocephalic and dolichocephalic breeds. As seen in the attached figure, there is a slight dip in the bone in line with the external auditory meatus. The sensory area is innervated by the greater occipital nerve (dorsal branch of cervical nerve 2). The projection neurons will then travel in the spinocervicothalamic tract ipsilaterally to the lateral cuneate nucleus. After synapsing, the information from the second projection neuron decussates and travels through the medial lemniscus to the contralateral midbrain and thalamic neurons (the ventral caudal lateral nucleus) and then project to the somesthetic area of the cerebral cortex. The somesthetic area in the canine brain is described classically as being located in the parietal lobe of the cerebrum caudal to the cruciate sulcus. It overlaps with the motor cortex because it is localized in the caudal part of the postcruciate gyrus and the rostral suprasylvian gyrus and is somatotopically organized. The pathway is unusual because it has two spinal projection neurons (and four neurons involved instead of the typical three neurons for conscious pathways). Ascending tracts within in the medial lemniscus may influence scattered nuclei in the midbrain to release acetylcholine on the thalamic and affect the sleep and wakefulness cycle. The suprachiasmatic nucleus (located dorsal and lateral to the optic chiasm) in the hypothalamus controls circadian rhythm including wakefulness and sleep. This very commonly used point is found in the philtrum at the level of the ventral limits of the nares. Veterinarians have used a perpendicular insertion with a dry needle (or a 20-22 g needle) to a depth of 0. Anatomically, at this midline junction of hair and ventral philtrum, there is not many remarkable anatomical structures. Sensory information travels along the infraorbital nerve and then the maxillary nerve into the rostral alar foramen and then into the round foramen. The information is transported to the trigeminal ganglion (the sensory ganglion for all the three divisions of the trigeminal nerve). The sensory axons enter the brain and synapse on the pontine sensory nucleus of the trigeminal nerve. From this pontine nucleus, fibers travel in the trigeminal lemniscus also known as the trigeminothalamic tract to the ventral caudal nucleus of the thalamus and then on to the primary and secondary somesthetic areas of the cerebral cortex. Some the kinesthetic fibers have unipolar cell bodies in the midbrain (nucleus of the mesencephalic tract of V) instead of in the trigeminal ganglion. This is an exception to the rule that primary afferent cell bodies are outside the central nervous system (as a ganglion). If any of these fibers from the trigeminal lemniscus travel rostrally and connect into the mesencephalic reticular formation, axons are stimulated in the reticular alerting system in the ipsilateral cerebral cortex. Axons also travel to intralaminar thalamic neurons via the central tegmental tract. It has been recommended by experienced veterinarians that the animal be approached from behind as the acupuncture needed is placed vertically in this point. The point has been very successfully used for pets that need assistance with shock, coma, Wind-Cold (pale tongue, respiratory infection) deficiencies, Wind-Heat (red tongue, respiratory infection) deficiencies. This is very successful as an appetite stimulant, so it is recommended to have food handy. The lateral hypothalamic nucleus is the center for appetite stimulation with a suggested hypocretin-orexin neuropeptide secretion. Input to the lateral hypothalamic nucleus comes from the hippocampus via the fornix, the periventricular system transmitting impulses from the thalamus and from the retina via the optic tract. The ventral caudal thalamic nucleus receiving inputs from the 258 trigeminothalamic tract are very close. Could neurons from this thalamic region project to the lateral hypothalamic nucleus? Interestingly, outputs form the lateral hypothalamic nucleus are many, but the projections to the nucleus ambiguus and the dorsal vagal nucleus provide a more detailed completion of the activity of using Shan-Jen. The effect of this is stimulation of gastrointestinal motility and gastrointestinal function by increasing the activity of the vagus nerve by influencing the parasympathetic nucleus of the X (vagus nerve). It is used for dental pain, mandibular pain, facial paralysis, headache, and head shaking. The needle is placed on the side of the face, in a depression in the middle of the masseter muscle just rostral to angle of the mandible. The muscles of mastication include the temporalis, lateral pterygoid, medial pterygoid and masseter. All of these muscles are innervated by the mandibular division of the trigeminal nerve. Developmentally, these four muscles are derivatives of the first branchial (pharyngeal) arches where it receives its initial innervation from the trigeminal nerve and its arterial supply. The masseteric fossa, located just rostral to the temporomandibular joint, becomes a deeper depression in a direct relationship with the amount of masseter muscle present. The angle of the mandible is created by the hooked process in the dog, the angular process, which serves for the attachment of the both pterygoids medially and the masseter laterally. The trigeminal nerve is primarily sensory, but the motor (masticatory) nucleus of the trigeminal nerve supplying these muscles resides in the pons medial to the pontine sensory nucleus of V. Synapses for sensory information from the trigeminal nerve resides from the substantia gelatinosa of the spinal cord to the spinal nucleus of V in the medulla to the pontine sensory nucleus in the pons and extends to the mesencephalic nucleus of V to the midbrain. Research on this extensive nucleus in humans has demonstrated that facial pain and temperature sensation is received by the spinal tract and nucleus of V and touch and point discrimination interacts with the pontine sensory nucleus of V. Proprioceptive neurons from the muscles of mastication migrated into the brain tissue during development and uniquely located themselves as the mesencephalic nucleus of V. The nerves that reside deep to the skin within the masseteric fascia and superficial to the masseter muscle are the dorsal and ventral buccal branches of the facial nerve as well as the auriculotemporal branch of the mandibular branch of the trigeminal nerve. The parotid salivary duct wrapped in its buccopharyngeal fascia travels straight across the muscle to empty in the buccal mucosa at the level of the upper premolar 4s (108, 208). This welldeveloped muscle sheet begins at the tendinous raphe of the neck (as the cutaneous colli m. The auricotemporal nerve leaves the mandibular nerve at the oval foramen and passes medial and caudal to the retroarticular process of the temporal bone and emerges between the base of the auricular cartilage caudally and the masseter muscle rostrally. Many branches are given off, but key to this discussion is that, as the nerve turns dorsorostrally, a transverse facial branch is given off to the tactile hairs and the skin extending dorsal and ventral to the zygomatic arch. Communicating branches to the facial nerve join the dorsal branch of the facial nerve to innervate the skin over the surface of the masseter muscle ventral to the zygomatic arch. At this bend is the geniculate ganglion, cell bodies of the visceral and special visceral afferent fibers of the facial nerve. Interestingly, the facial nerve sends multiple efferents to the face (including the caudal belly of the digastricus, ear canal and stylohyoid nerve and concave surface of the ear (via the trigeminal nerve) as the nerve exits the stylomastoid foramen caudal to the external acoustic meatus. First, the nerve must course rostrally and ventrally to the cartilage of the ear canal and travel dorsal and rostral and exits toward its destinations very close to (and sharing fibers with) the trigeminal nerve. This complicated pathway of the facial nerve and trigeminal nerve with their interconnections may be responsible for the multiple results when acupuncture needles are placed. While the facial nerve is primarily considered a motor nerve, the sensory components triggered by the facial nerve have the cell body in the geniculate ganglion and axons that travel into various regions of the brain. This muscular region is also derived from branchial arches should send afferents to the solitary nucleus via the solitary tract. This is a poorly dissected area by anatomists for the afferents from the platysma. If it does go to the solitary nucleus, other neurons are entering from the auditory tube, pharynx, larynx, esophagus, thoracic and abdominal viscera. Efferents from the solitary nucleus have numerous terminals including the hypothalamus and amygdala. For example, the masseteric fascia with its collagen fibers surround nerves which travel down to the different masseteric muscle fibers and eventually blend into the periosteum of the bone. Importantly, where there is connective tissue, there is blood vessels to the capillary level and, with them, motor and sensory nerves. This acupuncture point is ventral to the ear in the depression between the mandible and the cranial to the mastoid process of the temporal bone. It is used for otitis, cervical stiffness, facial paralysis and swelling in the face. Before the facial nerve exits, it sends motor branches to the stapedius muscle and carries sensory fibers in chorda tympani from the mechanoreceptors and taste receptors from fungiform papillae on the rostral two thirds of the tongue. There are also preganglionic parasympathetic axons to salivary glands and glands of the tongue. Anatomically, this very large facial nerve exits the skull from the stylomastoid foramen. It gains axons from the auricular branches from the vagus nerve (which supplies the external ear canal). The facial nerve will send branches to the caudal auricular muscles as it courses caudally close to the dorsal midline of the neck. The facial nerve curves ventrally and then rostrally around the annular cartilage and gives off branches to the caudal belly of the digastricus m. Sensory information enters the facial nerve at this point from the skin of the medial and lateral parts of the rostral (concave) surface of the ear. As the facial nerve curves near the caudal border of the mandible, it divides into several branches. Another divides into dorsal and ventral buccal branches and distributes to muscles of facial expression. The dorsal branch receives sensory inputs from the area ventral to the zygomatic arch on the caudal aspect of the check from cranial nerve V. The last branch distributes motor input to several superficial facial muscles like the orbicularis oculi, rostral auricularis, and levator nasolabialis mm. It is important to remember that the ear canal is surrounded by the parotid (para, "by"; otic, "ear") salivary gland. Pain from otitis externa, otitis media as well as dental problems are quickly and easily diagnosed, and treatment options augmented by acupuncture increase sensory input into the brain and should trigger some relief. The pathways into the brain from the triggered nerve to find a relief for pain makes it easy to understand why this is a commonly used point. Sensory input from the maxillary division (V2) of the trigeminal nerve enters the rostral alar foramen and then through the round foramen. Other branches enter the brain cavity at the orbital fissure 261 (ophthalmic division, V1) and oval foramen (mandibular division, V3). The trigeminal ganglion is present immediately inside this area of the round foramen with its pseudounipolar neurons and axons that leave to travel to the extensive spinal tract of the trigeminal nerve. Nociceptive (painful stimuli) and thermoreceptive neurons turn caudally as they enter the pons along the caudal surface of the middle cerebellar peduncle and enter the spinal tract of the trigeminal nerve and turn medially to synapse in the nucleus of the spinal tract of V. While some axons from this nucleus go to other cranial nerves, the axons can decussate and travel to the opposite ventral caudal nucleus of the thalamus by way of the trigeminothalamic tract, medial lemnicus and spinal lemnicus. The medial part of this nucleus relays primary information from cutaneous and proprioceptive receptors to the primary and secondary somesthetic (somatosensory) areas of the cerebral cortex. These areas in the cerebral cortex can regulate sensory input to the brain by sending axons to primary afferent axons (presynaptic inhibition). After pain is realized, the response to pain probably triggers the amygdala, which in turn drives the hypothalamus to release corticotropin releasing hormone. Adrenocorticotrophin, released from the pars distalis of the adenohypophysis travels via the bloodstream to the zona fasciculata of the adrenal cortex and stimulates the release of cortisol. Further progression of this goes on to stimulate P450scc in mitochondria to further the progress of steroidogenesis. The hypothalamus also stimulates the sympathetic nervous system for the release of epinephrine and norepinephrine from the adrenal medulla. One should mention that the zygomaticotemporal nerve of the mandibular division of cranial nerve V collects sensory information over the lateral and rostral areas from the tragus, as well as other areas such as the dorsomedial edge of the ear, over the zygomatic arch, and over the skin over the mandible. Mandibular teeth send sensory information into the brain with the mandibular nerve. This wide distribution travels ventrally, rostral to the auricular cartilage, then curves medially and then dorsally around the retroarticular process of the temporal bone to enter into the oval foramen. After the mandibular nerve enters the cranial vault, the cell bodies in the trigeminal ganglion project axons to the spinal tract of the trigeminal nerve and its nucleus. It is found over the temporalis muscle about a third of the way between the rostral 262 and basal portion of the vertical ear canal to the lateral canthus of the eye. The sensory supply to this region is supplied by the zygomaticotemporal nerve which as a wide distribution from the zygomatic arch to midline. The pathway of the zygomaticotemporal nerve is a little different than the average sensory nerve.
