Hoodia

Jon M. Braverman, M.D.

• Denver Health Medical Center
• University of Colorado School of Medicine
• Denver, CO

Anthracotic pigmentation of the lung is secondary to the inhalation of carbon dust ii herbals teas safe during pregnancy buy 400mg hoodia fast delivery. Hemosiderin Golden yellow-brown granular pigment Found in areas of hemorrhage or bruises Systemic iron overload -7 hemosiderosis -7 hemochromatosis Prussian blue stain 2 herbals dario order cheap hoodia online. Causes Hyperparathyroidism Parathyroid adenomas Renal failure Paraneoplastic syndrome Vitamin D intoxication Milk-alkali syndrome Sarcoidosis Paget disease Multiple myeloma Metastatic cancer to the bone iii herbs pregnancy 400 mg hoodia with visa. I Chemical agents herbs used in cooking discount hoodia uk, physical agents kan herbals buy cheap hoodia 400mg line, and nutritional imbalances can also injure cells aasha herbals - purchase hoodia 400mg without prescription. I I Apoptosis is a specialized form of programmed cell death that can be regulated genetically or by i cellular or tissuetriggers. He says he has noticed that he has had difficulty walking over the past few months. Supplementation with which of the following vitamins/nutrients would most likely have prevented this conditionfi Physical examination shows epigastric tenderness and a periumbilical discoloration. Adhesion is mediated by complementary molecules on the surface of neutrophils Integrins: stable binding and and endothelium adhesion I. Step 1: at sites of inflammation, the endothelial cells have increased expression of Esselectin and P-selectin ll. Step 2: neutrophils weakly bind to the endothelial selectins and roll along the surface iii. Step 4: binding of the integrins firmly adheres the neutrophil to the endothelial cell Table 3-1. Redistribution to the surface: P-selectin is normally present in the WeibelPalade bodies of endothelial cells and ca~ be redistributed to the cell surface with exposure to inflammatory mediators such as histamine ll. They then move between the endothelial cells, migrating through the basement membrane toward the inflammatory stimulus 4. Chemotaxis is the attraction of cellstoward a chemical mediator that is released in the area of inflammation b. During inflammation macrophages are mainly recruited from the blood (circulating monocytes) iv. Definition: specialized form of chronic inflammation characterized by small aggregates of modified macrophages (epithelioid cells and multinucleated giant Bilobed Nucleus, cells) usually surrounded by a rim of lymphocytes Large Granules (Blue) b. Neutrophils are important white blood cells in acute inflammation that contain granules with many degradative enzymes. Chediak-Higashi syndrome is an example of a genetic diseasewith defective neutrophil phagocytosis. Once a bacterium has been phagocytized, both oxygen-requiring and oxygen-independent enzymes can contribute to the killing of the bacteria. Chronic granulomatous disease of childhood and myeloperoxidase deficiency are genetic immunodeficiencies related to a deficiency of oxygendependent killing. Chemical mediators of inflammation include vasoactiveamines, the kinin system, arachidonic acid products, the complement cascade,and cytokines. A wide variety of diseasescan cause chronic granulomatous inflammation, most notably tuberculosis, syphilis, leprosy, and fungal infections. Gram stain analysisof cerebrospinal fluid obtained by a lumbar puncture shows Gram-negative intracellular diplococci. She says that her sputum was initially a rust color, but it has been more yellowish over the past few days. Examples: surface epithelial cells (skin and mucosal lining cells), hematopoietic cells, stem cells, etc. Definition: occurs with clean wounds when there has been little tissue damage and the wound edges are closely approximated b. Definition: occurs in wounds that have large tissue defects and when the two skin edges are not in contact b. Labile cell populations that regenerate throughout life include surface epithelial cells, hematopoietic cells, and stem cells. Stable cells that replicate at a low level through life, but can divide if stimulated, include hepatocytes, proximal tubule cells, and endothelial cells. Permanent cellsthat cannot replicate in adult life include neurons and cardiac muscle. Tissuerepair with replacement of a damaged area bya connective tissue scar is mediated by I many growth factors and cytokines. Initially granulation tissue forms, which later undergoes wound I contraction mediated by myofibroblasts, eventually resulting in true scar formation. A 16-year-old girl comes to the physician because of a "large growth" on her earlobe. Physical exarni~ation shows a 3-cm, firm tumor hanging from her left earlobe: Excessive production of which of the following types of collagen is associated with this conditionfi Her cook passed away 6 months ago, and she has been eating "tea and toast" ever since. Definition: an excessive amount of blood in a tissue or organ secondary to vasodilatation (active) or diminished venous outflow (passive) Table 5-1. Hemostasis involves interactions between the vascular wall, platelets, and the favoring the formation of a coagulation system stable thrombus versus those 2. Membrane expression of the phospholipid complex, which is an important In a Nutshell platform for the coagulation cascade d. Peripheral blood smear shows thrombocytopenia with enlarged immature platelets (megathrombocytes) iv. Bone marrow biopsy shows increased numbers of megakaryocytes with immature forms d. Splenectomy, which removes the site of platelet destruction and antibody, production 5. Definition: inherited bleeding disorder characterized by either a deficiency or qualitative defect in von Willebrand factor b. Definition: any intravascular mass that has been carried down the bloodstream from its site of origin, resulting in the occlusion of a vessel 2. Common sites of infarction include the lower extremities, brain, intestine, kidney, and spleen d. General sequence of tissue changes after infarction: i ischemia -7 coagulative necrosis -7 inflammation -7 granulation tissue -7 fibrous scar, I I I F. If the hypoxia persists, the cellular injury becomes irreversible, leading to the death of cells and the patient " 2. Stage I: compensation, in which perfusion to vital organs is maintained by reflex mechanisms 1. Acute adrenal insufficiency 42 mtlClical Circulatory Pathology Chapter Summary Edema is the presence of excess fluid in the intercellular space. Vascularwall injury triggers transient vasoconstriction, facilitation of platelet adhesion, and activation of both the extrinsic and intrinsic clotting pathways. Causes of thrombocytopenia due to decreased platelet production include aplastic anemia and tumor. Causes of qualitative platelet defects include von Willebrand disease, Bernard-Soulier syndrome, Glanzmann thrombasthenia, aspirin, and uremia. Von Willebrand disease is an inherited bleeding disorder characterized by a deficiency or qualitative defect in von Willebrand factor, which facilitatesformation of platelet clots. Factors involved in thrombus formation include endothelial injury, alterations in laminar blood flow, and hypercoagulability of blood. Thrombi can lead to a spectrum of outcomes, including vascular occlusion and infarction, embolism, thrombolysis, and organization and recanalization. Ninety-eight percent of emboli are thromboembolia, but many other materials have also formed emboli. Pulmonary emboli are a common form of emboli that are often clinicallysilent but can cause infarction orsudden death. Systemic arterial emboli usually arise in the heart and may cause infarction in a I variety of sites, depending upon where they lodge. Ninety-nine percent of infarcts result from thrombotic occlusion of an artery or vein. The general sequence of tissue changes after infarction is: ischemia leads to coagulative necrosis, which leads to inflammation, which leads to granulation tissue, which leads to fibrous scar. Shock is characterized by vascular collapse and widespread hypoperfusion of cells and tissues due to reduced blood volume, cardiac output, or vascular tone. A bone marrow biopsy shows increased number of megakaryocytes with immature forms. Which of the following groups of laboratory studies is most consistent with this disorderfi Allof a sudden, the woman develops shortness of breath and oozing from the intravenous site on her right arm. Mongoloid facial features (flat face, low-bridged nose, and epicanthal folds) involvingtwo acrocentric chromosomes with the break ill. Broad short neck extremely large chromosome vr, Palmar (simian) crease and a tiny one, which is vu, Congenital heart defects typically lost. Lab: Down syndrome can be screened by assaying maternal serum levels of cc-fetoprotein, chorionic gonadotropin, and unconjugated estriol. Karyotypic (genetic) sex: presence of a Y chromosome results in testicular development ~ b. Ductal sex: presence of Miillerian (female) or Wolffian (male) duct adult derivatives d. Phenotypic sex: ambiguous or female genitalia do Testicular feminization (complete androgen insensitivity syndrome) I. Point mutation: single nucleotide base substitution Synonymous mutation (silent mutation): a base substitution resulting in a codon that codes for the same amino acid Missense mutation: a base substitution resulting in a new codon and a change in amino acids -. Nonsense mutation: a base substitution producing a stop codon and therefore producing a truncated protein ii. Mutations of promoter or enhancer regions: interfere with transcription factors, resulting in decreased transcription of the gene. Cystic fibrosis (mucoviscidosis) the majority of cysticfibrosis cases result from deletion of a. Most common mutation is a deletion of the amino acid phenylalanine at posiside chains. Pathogenesis: defective chloride channel protein leads to abnormally thick viscous degraded by the cytosolic mucous, which obstructs the ducts of exocrine organs proteasome complex rather. Normal at birth but develop profound mental retardation by 6 months of age u, Lack of tyrosine: light-colored skin and hair iii. May have a mousy or musty odor to the sweat and urine (secondary to metabolite [phenylacetate] accumulation) c. Enzyme defect: deficiency of homogentisic acid oxidase resulting in the accumulation of homogentisic acid b. Homogentisic acid has an affinity for connective tissues (especially cartilage), resulting in a black discoloration (ochronosis) c. Definition: a group of rare diseases that have in common a deficiency in an enzyme necessary for the metabolism of glycogen, which results in the accumulation of glycogen in the liver, heart, and skeletal muscle b. Reticuloendothelial system Hepatosplenomegaly Lymphadenopathy Bone marrow involvement J. Definition: group of inherited connective tissue diseases that have in common a defect in collagen structure or synthesis Disorders of collagen b. Definition: differential expression of genes based on chromosomal inheritance from maternal versus paternal origin. May playa role in Huntington disease, neurofibromatosis, and myotonic dystrophy Deletion t Normal Normal r t Deletion Chromosome r Chromosome Chromosome:J Chromosome 15 I 15 15 I 15 r Prader-Willi Syndrome Angelman Syndrome the inheritance of a deletion on chromosome 15. Serious complications of Down syndrome include congenital heart disease (endocardial I cushion defects), duodenal atresia, Hirschsprung disease,acute lymphoblastic leukemia, and early onset of Alzheimer disease. Klinefelter syndrome and Turner syndrome are important disorders of sex chrornosornes. Cysticfibrosis now has mean survival of 30 years and is I characterized clinically by recurrent severe pulmonary infections and pancreatic insufficiency. I Albinism is an autosomal deficiency of melanin pigmentation in the skin, hair follicles, and eyes that I occurs secondary to tyrosinase deficiency and is associated with an increased risk of basal cell and I squamous cell skin cancers. I Glycogen storage diseasesare rare diseasesdue to abnormalities of glycogen metabolism that result in accumulation of glycogen in liver, heart, and skeletal muscle. Important subtypes include von Gierke disease, Pompe disease, and McArdle syndrome. I Niemann-Pick disease is an autosomal recessive deficiency of sphingomyelinase, leading to accumulation of sphingomyelin with hepatosplenomegaly, mental deterioration, and death by age two. Gaucher disease is an autosomal recessivedeficiency of glucocerebrosidase, leading to accumulation of glucocerebroside, with hepatosplenomegaly and bone marrow involvement.

Diseases

• Maghazaji syndrome
• Triple A syndrome
• Precocious epileptic encephalopathy
• Pertussis
• Bacterial vaginosis
• Mesomelic dysplasia Thai type
• Braddock Jones Superneau syndrome

In the classic transperitoneal approach herbs pictures buy genuine hoodia online, the kidney is harvested through a midline or through a left or right subcostal incision xena herbals purchase hoodia in india, whereby the peritoneum is opened gayatri herbals buy hoodia cheap online. The sub or supra costal approach can also be performed without opening the peritoneal space ayur xaqti herbals best order hoodia. In the dorsal lumbar technique herbs you can smoke cheap hoodia 400mg amex, an incision is performed underneath the 12th rib herbs to lower cholesterol purchase hoodia 400mg with mastercard, and the 12th rib is resected. As an alternative, the incision goes above the 12th rib; in both cases, the approach is extraperitoneal, and care should be taken not to open the pleural space. On the right side, the liver may make dissection difficult in a transperitoneal approach. A Cochrane review comparing open surgery (different approaches) to laparoscopy (different approaches) for harvesting living donor kidneys has been published in 2011 [321]. Six studies were identified that randomised 596 live kidney donors to either laparoscopic donor nephrectomy or open donor nephrectomy arms. All studies were assessed as having low or unclear risk for selection bias, allocation bias, incomplete outcome data and selective reporting bias. As various different combinations of techniques were used in each 116 study, there was substantial heterogeneity in the results. Laparoscopic donor nephrectomy was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. The authors conclude that laparoscopic donor nephrectomy is associated with less pain compared with open surgery. However, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using laparoscopic vs open donor nephrectomy procedures were exposed to longer warm ischaemia periods, although this has not been reported as being associated with short-term consequences. Based on this Cochrane review, it can be concluded that laparoscopic and open approach to harvesting living donor kidney have comparable outcomes with regard to donor safety and graft function. The laparoscopic approach seems to have some advantage in terms of comfort for the donor. It should however be stressed that, as for most surgical techniques, local experience might play an important role. The European Association of Urology describes the possible surgical approaches in more detail. They state that laparoscopic techniques have equal outcomes to open surgery techniques, but result in shorter recovery and less post-operative morbidity, although they add the recommendation that this procedure should only be performed by surgeons with experience with this technique. They do recommend to use the flank costal approach with retroperitoneal dissection over the transperitoneal approach. Suggestions for future research fi More large scale, multicentre randomised controlled trials are needed to establish the safety of the laparoscopic approach when applied in a generalised context, and to better quantify the gain in donor comfort of this approach. What are the indications for an additional haemodialysis session in the recipient immediately before the transplantation procedurefi We recommend to not routinely perform a haemodialysis session immediately before the actual transplantation procedure unless there are specific clinical indications. In some dialysis centres, a routine haemodialysis session immediately before the transplantation procedure is carried out to improve the metabolic status of the patient. However this is not routinely done in other centres where dialysis is performed only in case of some clinical indications (hyperkalaemia, fluid overload). Performing an additional dialysis before transplantation may increase cold ischemia time and activate inflammation. Ultrafiltration during pre-transplant dialysis is avoided in some centres, while some argue for ultrafiltration to improve cardiac function before surgery; it is unclear whether dehydration might jeopardize graft perfusion and diuresis in the perioperative phase. The negative effect of a haemodialysis session immediately before transplantation, especially when ultrafiltration was performed, on immediate graft function was also pointed out by Schmidt et al. The logistical organisation of such a dialysis session may result in a delay of the surgery and hence increase cold ischaemia time. There is evidence that ultrafiltration just prior to transplantation is associated with more delayed graft function after transplantation. As a consequence, the guideline development group recommends to perform an additional dialysis session immediately before the transplantation procedure only when there is a clear clinical or biochemical indication, that cannot be resolved by conservative measures alone. Effect of hemodialysis before transplant surgery on renal allograft function-a pair of randomized controlled trials. We suggest that central venous pressure is measured and corrected in the early post-operative period to prevent hypovolemia and delayed graft function. Assessment of adequate hydration status during first hours and days in kidney transplant patients is important for proper patient management. Dehydration might cause delayed graft function due to decreased renal perfusion; on the other hand, fluid overload might result if fluid loading is done in patients who remain anuric in the post-operative period. It is not clear whether measurement of central venous pressure measurement provides additional information to guide fluid management on top of clinical assessment of the patient. It was unclear whether this manoeuvre was associated with decreased incidence of delayed graft function or better graft survival. However, there was general consensus in the guideline development group that good hydration is crucial to avoid delayed graft function. The influence of intraoperative central venous pressure on delayed graft function in renal transplantation: a single-center experience. Factors influencing serum creatinine level in kidney recipients in a multivariate analysis. Perioperative fluid management in kidney transplantation: is volume overload still mandatory for graft functionfi There is no evidence to prefer one type of solution (crystalloids versus colloids, normal saline versus Ringer) for intravenous volume management of the recipient during kidney transplant surgery. Patients receiving kidney grafts should be properly hydrated to allow immediate kidney graft function. Postoperative management differs in various centres and it is unclear whether crystalloid or colloid solutions are the first choice of volume replacement. In a randomized controlled double blind trial, OfiMalley et al compared normal saline versus lactated Ringerfis solution for intraoperative intravenous fluid therapy in predominantly living donor kidney transplantation [330]. The study was prematurely stopped since patients treated with normal saline experienced significantly more acidosis and hyperkalaemia. There was no difference between the two solutions on postoperative graft function. Five (19%) patients in the normal saline group versus none in the lactate Ringer group had potassium concentrations >6 mmol/L (P < 0. Another randomised controlled trial compared normal saline, lactated Ringerfis solution and Plasmalyte at comparable infusion rates (20-30ml/kg/hour) in 90 living donor kidney transplant recipients [331]. Although the best metabolic profile was associated with Plasmalyte, renal function at first postoperative week was similar. There is evidence that maintenance of adequate perfusion pressure during the perioperative phase is of importance to avoid delayed graft function. There is no evidence comparing crystalloid versus colloid solutions during kidney transplantation. In other areas of medicine, all evidence seems to point towards no difference in survival between crystalloid versus colloid solutions in patients thought to need volume replacement [333, 334]. If anything, high doses of starches might even be associated with increased mortality [334]. The type of crystalloid solution seems to have no impact on graft outcome; however, the use of normal saline can result in metabolic acidosis, and associated with that, increase in potassium. They have no specific recommendation in the perioperative setting of kidney transplantation[335]. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Such a benefit would decrease the risk of delayed graft function and therefore improve the long-term graft function and survival. In patients with acute kidney injury in the non-renal transplant population, there is compiling evidence for the lack of effect of the use of "renal dose dopamine" [336]fi During low dose dopamine infusion, urine flow rate, effective renal plasma flow, creatinine clearance and total urinary sodium excretion were enhanced; however, no data on delayed graft function, or later graft function were available. Three small randomised controlled trials showed better short-term graft function and reduced risk of delayed graft function with low-dose dopamine in comparison with no dopamine, but all were at high risk of bias (multiple testing, potentially selective outcome reporting, patient selection, immunosuppression era, adjustment from confounding factors, limited information due to congress abstract source, number of patients) [339-341]. When it comes to outcomes at three months to one year after transplantation, four small retrospective cohort studies also failed to show evidence suggesting benefit for patients treated with low-dose dopamine, both in terms of patient and graft [343-346]. There is no evidence to support that low dose dopamine can improve graft outcome in terms of relevant outcomes as delayed graft function, or serum creatinine levels in the midand long term. As such, the guideline development group 126 judged that the use of low dose dopamine cannot be recommended. No other guideline body provides a statement on this topic Suggestions for future research No suggestions References 336. Dopamine treatment of human cadaver kidney graft recipients: a prospectively randomized trial. The effect of dopamine on graft function in patients undergoing renal transplantation. We do not recommend routinely using low molecular weight heparin, unfractionated heparin or aspirin before transplantation to prevent graft thrombosis. Patients treated with dialysis might be at higher risk for thromboembolic events, especially arteriovenous fistula thrombosis, deep vein thrombosis and embolism for reasons poorly understood. In some of those patients graft vein thrombosis or other thromboembolic events may occur after kidney transplantation. Prophylactic use of antithrombotic agents potentially reduces that risk at the cost of increased bleeding in the immediate post-operative period, with the potential need for reintervention and damage to the transplanted organ. In a randomised trial in 75 living donor kidney transplant recipients, there was no event of thromboembolism in either the treatment arm (difference between low molecular weight heparin or unfractionated heparin) or the placebo arm during the first week post-transplantation, while there was a small comparable risk for bleeding complications in both arms [347]. In a small moderate quality randomised control trial in deceased donor kidney transplantation, Horvath et al evaluated preoperative injection of 2500 units of heparin or placebo followed by 17 days of therapy [348]. Three-month graft survival and the number of thrombotic events were similar in both arms. Lundin et al conducted a retrospective study in 120 kidney transplant recipients [349]. Bleeding events were similar in both arms, and although there were numerically more graft nephrectomies in the control arm (4/64 control versus 0/56), the result was not statistically significant and reasons for this observation were not reported. We found one retrospective cohort study (N= 200) in which low dose heparin given just before vascular clamping was compared with no prophylaxis [350]. Although both the number of patients experiencing graft thrombosis and the number needing blood transfusions were numerically higher in control group, results were not statistically significant and confidence intervals wide. We found one study in which 105 patients treated with aspirin during the first three months along with low molecular weight heparin for first 5 days after transplantation were compared with 121 historical controls [351]. They found numerically fewer events of graft thrombosis and biopsy proven chronic allograft nephropathy at one year. None of these results were adjusted for confounding or statistically significant and confidence intervals were very wide. In another retrospective cohort study, Nagra et al found similar numbers of graft thrombosis leading to graft loss after heparin prophylaxis compared with no prophylactic anticoagulation. Amongst the 254 patients, there was one bleeding incident leading to graft loss [352]. Finally we found two retrospective cohort studies comparing low-dose aspirin with no prophylaxis during the first moth after transplantation. Both found fewer cases of graft thrombosis but used a historical control group and did not attempt adjustment for potential confounding in their analysis [353, 354]. There is no consistent and convincing evidence for routine antithrombotic therapy by unfractionated or low molecular weight heparin. There is no study dealing with low dose heparin or low molecular weight heparin prophylaxis in patients with obvious risk of thrombosis such as genetic mutation of factor V Leiden, prothrombin mutation or those already on anticoagulation therapy. As these patients do have an indication for anticoagulation anyway, and as there is no convincing consistent evidence for an increased bleeding risk, we suggest such patients to receive low molecular weight heparin prophylaxis for 4 weeks as recommended by the Haematological society. In patients who have an indication for chronic antiplatelet drugs, aspirin should not be stopped, as the pharmacodynamic action on platelet activity lasts more than 7 days. Necessity of routine postoperative heparinization in non-risky live-donor renal transplantation: results of a prospective randomized trial. The role of intraoperative heparin in cyclosporine treated cadaveric renal transplant recipients. Influence of aspirin on early allograft thrombosis and chronic allograft nephropathy following renal transplantation. Low dose aspirin as prophylaxis against renalvein thrombosis in renal-transplant recipients. However, the authors pointed out that the result was dependent on whether the same surgeon performed or attended the operations, so there might be a decreased effect in surgeons with high experience. The incidence of major urological complications in the non-stented group differed widely between the different studies (between 0 and 17. Two patients lost their grafts to infective urinary tract complications in the stented group. Stent use was 131 independently associated with reduction in ureteral complications (incidence rate ratio 0. There is no evidence for such a benefit in children and there is no consensus among paediatric transplant surgeons for using prophylactic ureteral stenting. In view of the published evidence, prophylactic placement of a stent should be recommended.

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In 2009, a crowd-source database of dollar bill traffic was created by marking a large number of dollar bills and soliciting individuals to log in their locations and the serial numbers of the marked dollar bills if they received any. The database has been used to track and predict an influenza epidemic, based on the ability to analyze the migration data of hand-to-hand transactions, 218 as modeled by the dollar exchange database. In 2012, astronomers discovered numerous planets revolving around stars in the Milky Way galaxy by reanalyzing sets of previously collected spectral data. The scientists 219 looked for blue-shift/red-shift spectral wobbles produced by planets orbiting stars. These new, exciting findings were made possible because the old data was stored and made available for reanalysis. National Academy of Sciences has called for scientists to provide publishers with the 220 primary data that supports the conclusions contained in their manuscripts. The idea behind this requirement is that modern research is complex, data-intensive, expensive, and collaborative, with data contributed by multiple laboratories. Without access to the primary data sets, there is no way to verify the experimental results or the final conclusions claimed in journal articles. Furthermore, without the primary data, colleagues cannot extend the research beyond the questions contained in the original manuscript. Sometimes, the most important purpose of a publication is to provide scientists with data for other studies (vida supra). In a recent scientific conference in Lyon, France, scientists from Google and the University of Cambridge refused to share the primary data for their analysis of YouTube video prefer211 ences. The chairman of the conference took the position that the conference should not accept papers for which the primary data was withheld. How do we know if it is because 211 they are not universal or the authors made a mistakefi In the realm of Big Data, scientific credibility is based on public access to the primary data and to all the protocols accounting for the collection, annotation, extraction, and analysis of the data. The important topic of deidentification is often shoved aside in data-sharing discussions. About a decade ago, I attended a conference in which an information officer was lecturing a group on the topic of medical data warehousing. He boasted that his medical center had put terabytes of well-annotated data at his disposal. I asked if his institution had plans for deidentifying and sharing the data with the public, thus giving everyone a chance to use the data. He indicated, quite diplomatically, that deidentification was a long-term goal, but other projects took priority. There are many reasons for institutions and corporations to equivocate on the topic of deidentification. When forced to share against their will, such entities often resort to the following four disingenuous diversions. There is no need to show tangible progress; they only need to show a credible effort. It never ceases to amaze me that institutions will typically assign deidentification projects to the same computer scientists who insist that deidentification is impractical or impossible. The data manager uses his or her imagination and skill to produce a selected set of deidentified records for user access. Big Data should promote discovery by providing users with large, complex, and heterogeneous data that can be freely explored. Because employees are often required to restrict their research to activities that benefit their employer, the intellectual output from closed Big Data resources has limited scope and utility. Furthermore, primary data that supports published scientific conclusions must be 220 made available to the public. Assertions based on proprietary and undisclosed data have no scientific credibility. The license stipulates the purposes to which the resource can be used and encumbers the licensee with various restraints,obligations, andfees. Much has been written about the importance of distributing deidentified records to the public, but very little deidentified data has actually been publicly released. Office of Civil Rights held a workshop on deidentification in the health care industry. Data used in research and in public policy analysis will ultimately need to be disclosed to the public; otherwise, the quality of the data and the validity of research results, cannot be evaluated. Currently, some of the methods used to deidentify health data are held by patent or are otherwise encumbered as intellectual property. Healthcare workers and scientists who would like to deidentify records often do not know the methods that are freely available to them, and cannot assess whether any particular method is encumbered. These would include free-text scrubbing algorithms, methods to identify and remove safe harbor identifiers, statistically valid ambiguation and obfuscation methods, relevant encryption protocols, and methods to safely reconcile patient identifiers within and across institutions. Reliable methods for creating and assigning unique patient codes involve humans and software. It is easy to see how instant access to industry catalogs, inventory data, transaction logs, and communication records can improve the efficiency of businesses. It is less easy to see how Big Data can speed up scientific research, an endeavor customarily based on labor-intensive and tedious experiments conducted by scientists and technicians in research laboratories. For many fields of science, the traditional approach to experimentation has reached its fiscal and temporal limits; the world lacks the money and the time to do research the old-fashioned way. Everyone is hoping for something to spark the next wave of scientific progress, and that spark may be Big Data. Scientific experiments have increased in scale, cost, and time, but the incremental progress resulting from each experiment is no greater today than it was in the early 1960s. In the field of medicine, the 50-year progress between 1910 and 1960 greatly outpaced progress between 1960 and 2010. Nearly all the engineering and scientific advances that shape the world today were discovered prior to 1960. These engineering and scientific advancements pale in comparison to the advances in medicine that occurred between 1910 and 1960. Civil engineers prevented a wide range of common diseases using a clean water supply and improved waste management. Safe methods to preserve food, such as canning, refrigeration, and freezing, saved countless lives. In 1941, Papanicolaou introduced the smear technique to screen for precancerous cervical lesions, resulting in a 70% drop in the death rate from uterine cervical cancer, one of the leading causes of cancer deaths in women. By 1947, we had overwhelming epidemiologic evidence that cigarettes caused lung cancer. By the mid1950s, the sterile surgical technique was widely practiced, bringing a precipitous drop in postsurgical and postpartum deaths. If the rate of scientific accomplishment is dependent upon the number of scientists on the job, you would expect that progress would be accelerating, not decelerating. According to the National Science Foundation, 18,052 science and engineering doctoral degrees were awarded in the United States in 1970. By 1997, that number had risen to 26,847, nearly a 223 50% increase in the annual production of the highest level scientists. The growing work force of scientists failed to advance science at rates achieved in an earlier era, with fewer workers, but not for lack of funding. The beginning of the end of high-speed progress may have come in the late 1960s and early 1970s with the advent of successful clinical trials for highly effective chemotherapeutic agents effective against a wide range of childhood cancers. Subjects in these trials would be followed for years to determine survival rates in the control population. The prospective, randomized control trial, performed on children with cancer, was so very successful that it served as the required standard for drug testing over the next half century. The problem has been that very few of the drugs tested on adults with cancer have had the kind of curative successes that we see with the childhood tumors. Larger, longer, and increasingly expensive studies were conducted to demonstrate incremental improvements in chemotherapeutic regimens. Over the decades, it became evident that tumors occurring in adults had different responses to therapeutic agents depending on the stage of the tumor. These observations inspired additional clinical trials for the different subtypes of cancers. The relative inefficiency of clinical trials has contributed to the high cost of developing new treatments; at least $1 billion per drug. The shift toward testing drugs on populations of subjects has drastically increased the number of potential clinical trials. Funders of medical research are slowly learning that there simply is not enough money or time to conduct all of the clinical trials that are needed 210 14. Despite all the wonderful scientific discoveries that are reported in the popular press, the benefits will be slow to arrive. Big Data provides a way to accelerate scientific progress by giving researchers data that can expand or bypass the clinical trial process. In fact, much of what we know about public health is based on the analysis of large data collections. By reviewing millions of medical records and billions of medical tests, researchers can find subpopulations of patients with a key set of clinical features that would qualify them for inclusion in customized trials. The biological effects of drugs, and the long-term clinical outcomes, can be assessed retrospectively on medical records in Big Data resources. Perhaps the most important scientific application of Big Data will be as a validation tool for small data experiments. Like any human endeavor, experiments must be validated, and the validation of an experiment, if repeated in several labs, will cost more than the original study. Using Big Data, it may be feasible to confirm that experimental findings based on small, prospective studies are consistent with observations made on very large 227 populations. In some cases, confirmatory Big Data observations, though not conclusive in themselves, may enhance our ability to select the most promising experimental studies for further analysis. Moreover, in the case of drug trials, observations of potential side effects, nonresponsive subpopulations,and serendipitousbeneficial drugactivitiesmay be uncovered in a Big Data resource. In the past, statisticians have criticized using retrospective data in drug evaluations. There are just too many biases and opportunities to reach valueless or misleading conclusions. Today, there is a growing feeling that we just do not have the luxury of abandoning Big Data. Using these large resources may be worth a try if we use the best available data and the best analytical methods and if our results are interpreted by objective, competent experts. Today, statisticians are finding opportunities afforded by retrospective studies for establishing 158,159,228 causality, once considered the exclusive domain of prospective experiments. One of the most promising areas of Big Data study, over the next decade or longer, will be in the area of retrospective experimental design. Funding agencies and corporations should ask themselves, before financing any large research initiative, whether the study can be 229 performed using existing data held in Big Data resources. Few of us would choose to have our medical records, financial transactions, and the details of our personal lives examined by the public. When the identifying information that links a record to a named individual is removed, then the residual data becomes disembodied values and descriptors. Deidentified data poses no threat to humans, but it has great value for scientific research. This data is used to monitor the incidence and the distribution of cancer, detect emerging infectious diseases, plan public health initiatives, appropriate public assistance funds, manage public resources, and monitor industrial hazards. Deidentified data collected from individuals provides objective data that describes us to ourselves. Without this data, society is less safe, less healthy, less smart, and less civilized. Those of us who value our privacy and our personal freedom have a legitimate interest in restraining Big Data. Individuals who receive the benefits of Big Data should expect to pay something back. In return for contributing private records to Big Data resources, the public should expect resources to apply the strictest privacy protocols to their data. Leaks should be monitored, and resources that leak private data should be disciplined and rehabilitated. There are about a billion people who have Facebook accounts wherein they describe the intimate details of their lives. This private information is hanging in the cloud, to be aggregated, analyzed, and put to all manner of commercial purposes.

Class I malocclusions can result from lip/cheek/tongue pressure (or lack thereof) herbals for cholesterol best order hoodia, significant systemic or endocrine issues herbs mac and cheese purchase hoodia overnight, and less commonly neoplastic or cystic formation may also result in tooth deviation vaadi herbals products review order cheap hoodia online. Displacement in some situations was previously believed to result from persistence of the deciduous teeth herbs cooking buy genuine hoodia on line. However herbals vaginal dryness buy hoodia without a prescription, research shows that deciduous tooth persistence is caused by improper eruption of the permanent teeth herbals on demand coupon code buy genuine hoodia online. The major issue is that the mandibular canines typically cause significant occlusal trauma to the palate, gingiva, and/or maxillary canine teeth. This condition is often caused by line breeding for a specific size and shape of the head. Further evaluation of these findings supports the theory that malocclusions likely occur secondary to the degree to which achondroplasia is expressed within the patient. However, as in all malocclusions, it is rare to have the patient show clinical signs. Nevertheless, therapy of the traumatic malocclusion is recommended (Yelland R 2013). An asymmetry can occur in one of three directions: rostrocaudal, dorsoventral or side to side. In general, this malocclusion causes palatine or gingival (+/tooth) trauma and if this is occurring, therapy is recommended. Surgical which generally consists of extraction of teeth causing occlusal trauma. This should be the treatment of choice for traumatic malocclusions in tier 1 & 2 countries. Orthodontic: this is where the maloccluded teeth are moved into the correct or a nontraumatic position via the use of various appliances. Coronal amputation and endodontic/restorative where the offending teeth are shortened and undergo endodontic therapy (vital pulp therapy or root canal treatment) or their shape is changed by odontoplasty and a restoration/sealant placed. The latter two are challenging techniques and should only be attempted by dental specialists (and potentially veterinarians with advanced training). Key Points: fi Malocclusions in veterinary patients often cause trauma which can result in significant morbidity and therefore require treatment, regardless of lack of clinical signs. In: the American Anatomical Memoirs, number 19, Wistar Institute of Anatomy and Biology, Philadelphia. Quality and regular dental care is necessary to provide optimum health and quality of life in veterinary patients. Unand undertreated dental disease has a serious impact on the welfare of the patient, and as such is an unacceptable condition for any veterinarian to leave purposefully unadressed. Dental disease is common Historically, it was a commonly held belief that companion animals required little if any dental care; however, we now know that dental disease is the most common medical condition in companion animals. Over 80% of dogs and 70% of cats have evidence of periodontitis by the age of 3 (Kortegaard et al, 2008). Further, 10% of dogs have a fractured tooth with painful direct pulp exposure (termed complicated crown fractures) (Golden 1982, Chidiac 2002) and Bellows (2009) found 20-75% of mature cats are clinically affected with oral resorptive lesions, depending on the population examined. It is estimated that 50% of large breed dogs have small fractures (termed uncomplicated crown fractures) with painful dentin exposure (Hirvonen et al. Therefore, the clear majority of veterinary patients are dealing with significant pain, infection, or both daily. Dental disease causes pain and suffering It is well documented in humans that dental pain can be extreme (Bender 2000; Hargreaves et al. Multiple published articles link dental pain to decreased productivity sleep disturbance, and significant social and psychological impacts (Reisine et al, 1989; Anil et al, 2002, Heaivilin et al, 2011, Choi et al, 2015). Pain is an experience unique to each individual, and behavioural demonstrations of pain, especially dental pain, may be missed by owners and veterinarians. Nociception research is becoming less common as animal care committees at academic institutions around the world become stricter in their guidelines for responsible animal use in research settings. However, non-human mammals have been found to be excellent models for dental pain in the human world (le Bars 2001). Research into excruciating human pulpitis has found small rodents to be an excellent model. Notable and repeatable changes due to pulpal pain include decreased weight gain, increased time to complete meals, shaking, yawning, freezing and decreased activity (Chidiac 2002, Chudler et al. Additional research is strongly recommended into better understanding oral pain and how it should best be assessed in companion animal species. As in other areas of the body, unchecked infection is an ethically unacceptable condition, once suspected, to leave without appropriate therapy. Dental disease can alter behaviour Behavioural scoring systems to evaluate pain exist for a variety of systems and species (Matthews et al, 2015) and are described in more depth in the Anaesthesia Section. However, it is important to note that dental pain indicators are often vague and non-specific. There are many conditions which cause pain for our patients, including, but not limited to periodontal disease, tooth and jaw fractures, tooth resorption, caries, traumatic malocclusions, feline oralfacial pain syndrome, and some oral neoplasias. It is important for practitioners to understand that the absence of noting a behavioural change due to chronic dental pain does not mean that the pain is not there, nor does it imply any lack of severity. When pain is noted behaviorally, behaviours such as pawing, mutation of the mouth, and decreased appetite appear prevalent (Rusbridge et al. As veterinarians, it is our absolute responsibility as veterinarians to diagnose, treat, and relieve pain and suffering for our animal patients. To allow untreated dental disease to cause continuous pain without therapy is a significant animal welfare issue. It is our duty as veterinarians to proactively diagnose these painful conditions, offer appropriate therapy, and educate our owners about the welfare issues of not treating these conditions. Interpreting behavioural signals of oral pain can be complex, however it is a simple fact that animals will continue to eat despite debilitating and extreme dental pain. Animals require nourishment to survive, and the instinct to survive is stronger than the desire to avoid pain. It is important to remember that while the majority of animals will demonstrate normal oral behaviours, such as playing with toys, marking with facial glands, or using their mouth to explore their environment despite experiencing dental pain, others may be prevented from expressing these natural and essential behaviours due to chronic discomfort. Additionally, clients report that they are happier to know their pets are not in pain (McElhenny J, 2005). Whether or not behavior changes are observed, the underlying pain should not be a condition which the animal is expected to endure, either by the veterinary community or by owners. While a definitive behavioural guide for assessing behavioural changes due to oral disease and discomfort is not available at this time, the authors strongly suggest this is an area that deserves further research. Dental pain and infection cause physiological signs of stress Infectious aetiologies such as endodontic and especially periodontal disease bring with them a significant bacterial disease burden, which the patient must cope with on a daily basis. While these may be appropriate in the short term, chronic stressors negatively affect multiple body systems. Immune function impacts may be first noted with the development of an acute stress leukogram, progressing to leukopenia and immunosuppressive inflammatory cytokine changes with chronicity (Henkman et al, 2014). Several publications have linked chronic stress responses to decreased ability to eliminate bacterial infection and increased susceptibility to disease in humans and mice (Biondi et al, 1997; Karin et al, 2006; Kjank et al, 2006). Equally important is following up on these, or any additional changes the owner has noted since professional dental therapy has been completed. Follow-up at 2 as well as 8-10 weeks would be advised, to get a full picture of the improvements noted following therapy. Veterinary handling techniques have welfare implications the welfare needs of our patients begin from the time they enter our practices. The human-animal bond is tenuous, and fear experienced during handling for veterinary procedures can disrupt this bond quickly (Knesl et al, 2016). Education on, and commitment to reducing stress involved with handling for oral exams and procedures related to dental therapy needs to be considered when addressing dental disease in our patients. All procedures in the oral cavity (including professional teeth cleaning) must be performed under general anaesthesia with a secured airway (endotracheal intubation). All precautions, safety measures, monitoring rules and standards apply, as referenced in the Anaesthesia section (Hyperlink to Anaesthesia). Gentle, efficient and thoughtful tissue handling (minimally invasive surgery) is recommended to prevent excessive pain and swelling post-procedure. In addition, appropriate choice of, or avoidance of mouth gag use altogether may help to prevent trauma (Hyperlink to Anaesthesia). Local and regional anaesthetic blocks, and adequate preand postoperative pain management are necessary for controlling the pain that may be experienced from proper dental therapy. The person conducting the dental procedure cannot possibly evaluate the pathology, nor conduct any meaningful subgingival treatment without proper anaesthesia. This may lead to a cosmetically improved oral cavity with persistent infection, inflammation, and pain. Therefore, not only is the procedure ineffective, it often results in masking the pathology present, which delays appropriate care. This directly opposes the welfare benefits, and improvements to quality of life, that are at the centre of these guidelines. Additionally, the stress or discomfort incurred during this time consuming cosmetic procedure is wholly avoidable and indefensible from a medical and ethical standpoint. As such, the World Small Animal Veterinary Association strongly objects to the practice of veterinary dentistry without appropriate anaesthesia is inadequate, and provides a substandard level of care which may be misleading to the pet owner. Education in dental care will increase animal welfare: Veterinary dental care is an essential component of a preventive healthcare plan, and yet it is largely ignored in the veterinary educational system. As otherwise noted in these Guidelines more thoroughly (see Universities section), the universities role in the education and promotion of educational opportunities for not only diagnosis and therapeutic techniques for dental disease, but oral pain detection and behavioural changes associated with its pathology, must be addressed by veterinary curriculum internationally. Without educational reform and prioritization, welfare and quality of life improvements achievable from increased quantity and quality of dental care will be impeded. As welfare advocates, the veterinary profession needs to change their messaging regarding the need for dental care for companion animals, begin to advocate for proper dental care for our patients, and educate our clients on the importance of quality dental care to the welfare of their pets. By utilizing the five tenets of animal welfare as our guide, regular dental examination and proper therapy will help to address infection, control pain, and allow return to regular behavior. Keeping these goals central to our thought processes while recommending and performing procedures in the oral cavity is essential to the practice of humane veterinary medicine. Key Points fi Modern animal welfare science looks to veterinarians to care for animals in ways that minimize fear, suffering, and pain, and allows them to express natural behaviours. References Brambell, Roger (1965), Report of the Technical Committee to Enquire Into the Welfare of Animals Kept Under Intensive Livestock Husbandry Systems, Cmd. Oliveira (2017) Pain assessment in cats with dental pathology: the accuracy of a behavioral observation-based scale. Animal welfare 6, 187-205 Hirvonen T, Ngassapa D, Narhi M (1992) Relation of dentin sensitivity to histological changes in dog teeth with exposed and stimulated dentin. Psychogenic Stress in Hospitalized Dogs: Cross Species Comparisons, Implications for Health Care, and the Challenges of Evaluation. Psychological stress, neuroimmunomodulation, and susceptibility to infectious diseases in animals and man: a review. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Opportunities for incorporating the human-animal bond in companion animal practice. Pettersson A, Mannerfelt T (2003) Prevalence of dental resorptive lesions in Swedish cats. Section 3: Anesthesia and Pain management Introduction the vast majority of dogs and cats have some form of dental and/or oral disease. However, outward clinical signs of distress are not always noted, and thus most pets suffer in silence. Professional oral care, including dental cleanings, is generally associated with mild pain. More invasive dental procedures, such as advanced periodontal therapy, tooth extractions, root canal therapy, and oral surgeries such as mandibulectomy/maxillectomy and jaw fracture repair, are typically associated with moderate to severe pain. This section provides recommendations and suggests the best practices in anesthesia and pain management for canine and feline patients with oral/dental diseases. The American College of Veterinary Anesthesia and Analgesia has published a position statement on this issue acvaa. From an anaesthesia perceptive, some other reasons are discussed below: fi the risks of anesthesia in healthy or even mildly compromised pets is low especially when performed by trained individuals, and avoiding anesthesia is not a valid concern. Some sedatives that are required for chemical restraint are often contra-indicated in particular cases. Most important, cardiopulmonary monitoring may not be easily achieved during sedation. Patient preparation and assessment Adequate handling and restraint will minimize stress and facilitate sedation.

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