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STUDENT DIGITAL NEWSLETTER ALAGAPPA INSTITUTIONS |
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Emer M. Smyth PhD
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Figure 10-2 shows a timeline of key events associated with the grant; important developments relating to the wider research field are shown above the line muscle relaxant drugs flexeril purchase rumalaya gel 30gr amex, while grantspecific events are shown below it xanax muscle relaxer discount rumalaya gel 30gr on line. Indeed muscle relaxer 93 order rumalaya gel 30 gr online, one of the co-investigators felt that a key constraint on maximising the impact of the grant had been finding time to take forward some of the insights gained at this time muscle relaxant lotion cheap rumalaya gel 30gr overnight delivery. Although it is difficult to distinguish clearly between the impacts of this grant and the first one received from the Stroke Association zyprexa spasms cheap rumalaya gel 30 gr with amex, the two grants provided the basis for recruiting a viable patient cohort for long-term study and vital preliminary data without which it would have been very difficult to secure follow-on funding muscle relaxant for bruxism buy rumalaya gel 30 gr line. A co-applicant on the original application wrote his PhD theses using data obtained from the research; one of the researchers involved was subsequently inspired to complete a PhD part-time, and the grant provided 50% of the data for her research. However, for the practising medics who were part of the original study team, the long-term impact has been less certain. Most have left research to pursue clinical practice full-time; one of the co-applicants, for example, is now a hospital Director of Geriatrics. More broadly, however, there is some suggestion that the grant may have had an important role in building capacity in this research area within Leeds University as a whole. The aim of the centre is to `perform internationally competitive translational research. In combination with the 1993 Stroke Association grant, the investigators were able to assemble a large patient group and control cohort as the basis for a long-term and comprehensive mapping exercise, during which they have examined a range of linkages between genotypes, intermediate phenotypes and the risk of stroke. This ongoing stream of research continues to produce publications, including a paper in Stroke in 2007 that brought together many of the findings from the preceding 15 years in single discussion of predictive variables for mortality (Carter et al. A co-investigator suggested that within 10 days of a stroke, there are often so many potential confounding factors that could be influencing results that there were always questions about what might be being missed. For the department as a whole, however, the implications of the grant in terms of research targeting (as opposed to capacity building) have been less clear. Typically, though, symptoms last for only a few minutes to a couple of hours and may disappear altogether within 24 hours. Although clinicians continue to work as part of the unit, the co-investigator felt that the historical focus on large-scale clinical studies had arguably been lost since the completion of the grant. However, the investigators we spoke to admitted that dissemination attempts had not been as successful as they had hoped. He suggested that a possible explanation for this might have been the difficulty the research group had in communicating its findings to a community to which he was not directly linked (since his own specialisation was diabetes research). One of the co-applicants was able to present some of the findings of the research in stroke-specific events, but the impact of this campaign overall was uncertain, partly because research addressed risk factors and its clinical implications were still uncertain. The co-investigator we spoke to also highlighted difficulties the group had had in achieving recognition in the United States. In fact, the focus had been on establishing a viable cohort and conducting basic mapping experiments to explore potential linkages and identify biomarkers for stroke. Recent discussions with a pharmaceutical company based in Cambridge suggest that the research stream as a whole may contribute to therapeutic developments in the future. This observation had spurred a stream of in-vitro research, which now seemed likely to yield therapeutic applications. She found that beyond provision of aspirin for some patients, follow-up seemed to have been negligible. Much of his work has focused on characterising risk factors in a field that was new and untested when he began his research career. Table 10-2 shows, in point form and by impact category, some of the impacts, described more fully above, that have emerged from this grant. The team found that infarcts were observed only in regions showing persistent elevation of nimodipine binding, as determined by histology performed in a separate group of rats (n=8) after 24 hours of reperfusion. The team concluded in separate studies that increased nimodipine binding to ischaemic tissue, which is an index of tissue vulnerability to ischaemic cell death, is initially reversible. The conclusion, therefore, was that nimodipine binding was a sensitive indicator of early and reversible ischaemia-induced cerebral dysfunction. The results of this study, together with findings from many others at the time, led to recognition that the negative effects of ischaemic stroke could be attenuated if the brain is given back its blood supply rapidly. The possibility that brain function may be salvaged after infarction if the brain is reperfused rapidly was subsequently proven in human studies with tissue plasminogen activator. Through the creation of various networks, campaigns designed to educate the public and healthcare practitioners about the way strokes are treated and managed have led to improved lives for many patients and millions of dollars saved for the healthcare system. It was then discovered that when the brain is deprived of its 1 Nimodipine is a dihydropyridine calcium channel blocker originally developed for the treatment of high blood pressure. Thus, although stroke was recognised as a frequently devastating disease, these findings meant that when stroke does occur, a region of the brain adjacent to the most damaged area remains viable (alive) even if it does not function for a while. This meant that at least part of the deficit experienced by a patient after stroke may be reversible if doctors could identify these viable regions and were able to maintain and prolong the viable state of the tissue. By measuring the activity of the calcium channels that allow the passage of harmful calcium ion into cells, the research team believed that they could identify the regions of the brain affected by the stroke that were still salvageable. The study proposed to explore the potential use of a previously developed nimodipine model to distinguish among the ischaemic regions of rat brains those regions that will recover and those that will die due to a lack of oxygen. This was achieved by exposing rat brain to short periods of ischaemia followed by reperfusion (restoration of blood flow). This model allowed the research team to test the overarching hypothesis that measurement of the binding capacity of the calcium channels would indicate the severity and duration of the ischaemia and predict whether the region had been reversibly or irreversibly injured. In previous studies in their rat model, the team had found that when they restored previously restricted blood flow to the area around the middle cerebral artery, it recovered more quickly. Nimodipine binding was high in areas with restricted blood supply and declined when the blood flow was restored. Nimodipine binding persisted in areas where tissue death due to lack of oxygen had occurred, and so nimodipine was thought to be a sensitive indicator of early and reversible brain dysfunction caused by restricted blood flow (Berger and Hakim, 1989, and Vogel and Hakim, 1988). Hakim had completed a postdoctoral fellowship in cerebral metabolism at the Montreal Neurological Institute and Hospital in 1980. In 1984, Hakim became a certified fellow of the American Board of Psychiatry and Neurology. In this section, we further examine how the research topic was identified based on the two critical factors: 1. During his neurology residency at the Montreal Neurological Institute and Hospital he was intrigued by patients with Wernicke-Korsakoff syndrome, who exhibit severe memory deficits in association with alcoholism and thiamine deficiency but show only very limited brain lesions. Hakim then began to study how systemic conditions result in focal brain damage, which led to an interest in stroke because of the selective nature of the damage caused by ischaemic stroke. The idea for this research initially arose from clinical and scientific curiosity and dissatisfaction with current practice. As previously discussed, research was beginning to indicate that some of the cerebral deficit following an ischaemic stroke could be prevented or reversed if the viable regions could be identified and if it was understood how to maintain and prolong the viable state of the tissue. This paper also indicated that brain tissue facing potential death could recover if blood flow resumed to the affected areas. Up until this time, the general belief was that once an individual had a stroke there would be no return of function. At the time of this grant proposal, when using the permanent occlusion model, it was found that all the brain regions exposed to ischaemia eventually infarct but at different rates. Thus it had not then been possible to test the ability of the nimodipine binding model to distinguish the ischaemic regions that could be salvaged and those that could not. Cell death occurs when there is an unregulated and excessive passage of calcium ions into cells. By measuring the activity of the calcium channels, it was believed that the regions of the brain affected by the stroke that are still salvageable could be detected. Thus it was believed that damaged cells could be saved with timely re-supply of oxygen and glucose to the ischaemic areas through restitution of blood flow. This model involves occluding the middle cerebral artery, thereby creating damage similar to that seen in patients with stroke. Hakim described it as a well-accepted model of global ischaemia that allows for reperfusion. He also indicated that it correlated well with the varying degrees of neuronal injury. Using this model, the team could insert radioactive nimodipine through calcium channels into neuronal cells. The model presented several advantages, which included ease of preparation, a high rate of predictable ischaemic neuronal damage, a low incidence of seizures and the absence of prolonged anaesthesia (Pulsinelli et al. In-vitro binding with this ligand has proved to be extremely insensitive to pathological change, whereas in-vivo binding had shown marked sensitivity to ischaemic insult. Specifically, the team had shown that in-vivo binding of [3H]-nimodipine (a radiolabelled dihydropyridine) was initially increased in areas of severe ischaemia but this was followed by a complete absence of binding capability (Hakim and Hogan, 1991). In areas of more moderate ischaemia, a less pronounced and delayed increase in nimodipine binding occurs. It was thought that the appearance and disappearance of dihydropyridine binding was a reflection of the severity and duration of cerebral ischaemia and thus a potential marker for cell death (Hogan and Hakim, 1992). Administering radiolabelled nimodipine molecules after stroke would allow radiographic imaging to be used to determine which brain cells had been affected. Knowing which part or parts of the brain are infarcted could allow doctors to identify and target these areas for treatment, thus preventing further cell death. The study also intended to test the following hypotheses: Oxygen consumption of cortical regions of the brain in vivo fails to increase during activation because the functional density of capillaries in the brain tissue is close to the maximum achievable density of perfused capillaries. In patients recovering from cerebral ischaemic stroke, the oxygen consumption of post-ischaemic brain tissue will remain low until the functional density of capillaries has returned to the normal average. The team injected nimodipine into the bloodstream of a rat and then measured its concentrations in the bloodstream and brain tissue. By comparing the concentration of the molecule in the bloodstream with the concentration in the brain tissue, the team estimated how many more molecules would be found in brain tissue compared with what would be expected if uptake was completely passive. That is, did the brain seem to hold on to more of this drug than would be predicted with passive distribution between the bloodstream and the brain tissue This difference, this excess of the molecule in the brain at given times, is known as the binding potential. Using autoradiography, [3H]-nimodipine binding was measured regionally in the brains of rats exposed to 10, 20 or 30 minutes of carotid clamping. The interval that would maximise binding to [3H]-nimodipine in the regions not committed to histologic infarction was to be chosen for subsequent experiments. The effect of varying the duration of reperfusion following a set interval of carotid clamping on nimodipine binding and subsequent histologic outcome was determined. Experiments were planned to determine the degree of non-specific binding to nimodipine in normal and ischaemic rats. The regional maximum number of binding sites and an index of binding affinity following two ischaemic intervals were measured. The feedback from the review committee was predominantly positive and the proposal received a strong score. Some concern was voiced by the committee with respect to the terminology used in the proposal. This was important, because although nimodipine binds to infarcted regions in focal models of rodent ischaemia, this may not occur in the restricted and less severe damage of a global ischaemic model. One reviewer expressed concern that the binding may not be restricted to voltagesensitive calcium channels or strictly active ones. However, this did not deter reviewers from recognising and acknowledging the potential of the anticipated findings. Others wanted to know about the dynamics of the receptor binding, how it opens and closes, and how the calcium influx could be measured. It was decided, however, that this grant was sufficiently different from his other funded grants and represented a new research direction. Ultimately, the reviewers and the funding organisation were excited by this research proposal. The funding requested was intended to pay for a technician, a summer student, experimental animals (rats), radioactive supplies and other consumables. The methods for this work were already established in the laboratory, so there was no request for additional equipment. Dr Hakim also held a grant from the National Institute of Health in the United States to study calcium channel activity in focal ischaemia. Thus, the amount of Can$60,000 may be a conservative figure and could be as high as Can$75,387. Doing so required the work of 12 individuals and thus was a very expensive process. When the team initially began to conduct studies using nimodipine, they found they suddenly needed different kinds of equipment, as systems had to be developed to detect nimodipine in the brain and analyse the results. For instance, the team needed access to video equipment, cassettes and a dark room. Dr Hogan was a fellow at the time and now specialises in neurology and stroke research at the Ottawa Hospital Research Institute. Dr Hakim described the laboratory technician, Jocelyn Barthe, as someone who understood what the research team was trying to accomplish and helped them greatly.
As we have seen spasms 1982 cheap rumalaya gel 30 gr line, there is considerable evidence for such maternal control in both phytoseiid mites and scale insects muscle relaxant injections trusted rumalaya gel 30 gr. Scale insects are mixed: adult males are winged unlike the usual case for sib-mating (Hamilton 1967) spasms left upper quadrant buy cheap rumalaya gel 30gr line, yet they have very short lives muscle relaxant drug names rumalaya gel 30gr cheap, are poor fliers spasms near ribs buy rumalaya gel 30 gr low cost, and appear often to mate near their place of birth spasms in legs 30gr rumalaya gel mastercard. This is not impossible: maternally transmitted Wolbachia endosymbionts are well known to affect the chromosome dynamics of their hosts (see Box 5. Alternatively, in an outcrossed population, bacteria that caused males to be functionally haploid would, at least initially, often kill the males. Bacterial endosymbionts have been reported from phytoseiid mites and are common in scale insects. Larvae from both taxa are often gregarious, as are those of the coffee borer beetle. After crossing-over and forming chiasmata, each daughter chromosome is a mixture of paternal and maternal parts. These occur more or less at random and after this time there is no possibility of whole-genome drive based on parental origin, unless we imagine "reverse recombination," a highly unlikely achievement. Achiasmatic meiosis is almost always found in one sex only and usually in the heterogametic sex. Thus, many flies (Diptera) are male heterogametic and male achiasmatic, while butterflies and moths (Lepidoptera) are female heterogametic and female achiasmatic. Similarly, the Wolbachia bacteria that cause cytoplasmic incompatibility in Drosophila do so by interfering with the separation of paternal chromosomes and act from the first mitotic division onward (Tram and Sullivan 2002). In Drosophila both maternally 394 Genomic Exclusion active and paternally active nuclear mutations are known that interfere with the paternally derived chromosomes in the fertilized egg (Loppin et al. And in gynogenetic or pseudogamous asexuality, the paternal genome is excluded from the beginning. The timing may be linked to when the progeny begins to express its own genes (rather than relying on transcripts and proteins inherited from the mother) and may be linked to the fact that silencing occurs only in males rather than in all progeny (so that sex identification may be necessary), but otherwise the significance of the delay is obscure. It is natural to wonder whether the two systems tend to evolve under the same circumstances. Certainly, they are often found together in the same groups: thus, both kinds of inheritance are frequently found in mites and coccoids. There are several reasons to expect this coincidence, including the possibility that parahaplodiploidy may provide one route to the evolution of haplodiploidy (Schrader and HughesSchrader 1931). Sciarid Chromosome System Fungus gnats of the genus Sciara have a chromosomal system among the most complicated of any animal, one so complex as easily to deter further study (but reviewed in Gerbi 1986). Haig (1993d) has provided a hypothetical account of how the complex sciarid system we see today may have resulted from a long history of intragenomic conflict centering on sex determination and the sex ratio. We begin our account with as simple an overview of the sciarid chromosomal system as we can muster, based primarily on Sciara coprophila. Finally, we review the cytogenetic basis for the various aberrant chromosomal behaviors. Notable Features of the Sciarid System the sciarid chromosome system has 3 separate elements: the autosomes; the X chromosome, which has an unusually complicated lifecycle in the 2 sexes; and the germline-limited chromosomes, which may vary in number within species. Germline transmission of these elements is entirely normal in adult females, with each autosome, X, and L having a one-half chance of transmission. Autosomes show paternal loss, as does the X chromosome, while all L chromosomes are transmitted. An added complexity is that the maternal X shows nondisjunction and each sperm cell has 2 identical maternal Xs. Thus, the zygote has 3 X chromosomes, it has 2n autosomes, and it has a varying number of L chromosomes, typically 3. By the seventh round of cell divisions, 1 of the 2 paternal X chromosomes is eliminated from the germ and soma of both sexes, as is 1 of the 2 Ls (parental origin uncertain). The second paternal X is eliminated in the soma of individuals destined to become males. In spermatogenesis, the maternal X fails to disjoin and 2 copies are retained in each sperm, yet this temporary gain is almost immediately reversed in the embryo when 1 of the 2 paternal Xs is eliminated in both sexes. This temporary gain, fol396 Genomic Exclusion lowed by reversal, with no net gain, suggests a possible history of intragenomic conflict. Note that the second paternal X is eliminated from the soma of individuals who become males. This suggests conflict over the sex ratio and leaves the maternal X with a possibly controlling influence over later loss in transmission of the paternal X. Note also that, in spite of paternal genome loss among the regular chromosomes of males, the L chromosomes are all transmitted, although 1 paternal L is promptly eliminated from the embryo. This trait is controlled by a large paracentric inversion on the X chromosome such that those females who are heterozygous for the inversion produce only daughters while homozygous wildtype (no inversion) produce only sons. The evolutionary trajectory is imagined to begin with a driving X chromosome, like those found in other dipterans (see Chap. But instead of the autosomes evolving to suppress the driving X, they evolve to drive with the X. The arriving paternal chromosomes can be marked or "imprinted" for later preferential treatment. The only surprise perhaps is that the imprint should be retained throughout life, despite robust paternal genome expression. But, as we shall see, there is also a genetic bias that could bridge this gap: in males the soma contains only a maternal X. It would be interesting if X chromosomes were especially likely to harbor genes biasing the cytoplasm toward maternal interests. With X drive now accompanied by autosomal drive and no Y standing in the way, the sex ratio is expected to become female biased. Mothers are then selected to control the sex ratio, or at least to increase the number of males they produce. A plausible means is suggested by the current X chromosome constitution of somatic cells: females have both Xs and males only the maternal. It is easy to imagine a gene that converts females into males by engineering the elimination of the paternal X in somatic cells. The doubling of the maternal X by nondisjunction in spermatogenesis, followed by its early elimination in the embryo, is puzzling even if we imagine their system to be a vestige of an earlier sex ratio conflict. In eggs that would normally develop into males, by eliminating 1 X from the soma, the trick might just work, if the rule was "eliminate 1 paternal X" (rather than "eliminate all paternal Xs"). Once paternal genome loss is in place, a paternal chromosome that resisted exclusion from the germline would normally generate an individual with 3 homologous chromosomes instead of 2. X chromosomes, however, will tolerate aneuploidy whenever there is a process in place in which all but a set number of Xs (1 or 2) is eliminated from the soma-for example, as in the rule "delete all paternal Xs" (assuming meiosis is normal in females). Because Sciara tolerates germline aneuploidy, offspring inherit a paternal X* and maternal X, with the paternal X marked for elimination. X* now acts as a sperm-borne pathogen that kills daughters and is transmitted from father to son. But if it manages to lose whatever functions cause female aneuploid inviability before its disappearance, it could persist. And it will be selected for exclusion from the female soma, with all elements agreeing on the benefit of such action. In short, an X has now evolved into an L, showing drive in males, normal segregation in females, and elimination from the soma in both sexes. But the evolution of L chromosomes brings new selection pressures on the sex ratio. Because they drive more in males than in females, they are expected to bias the sex ratio toward sons. This is the first time in the evolution of the system in which an element favors a male-biased sex ratio and, unimpeded, the sex ratio is expected to reach equilibrium at 2:1, assuming twice the propagation of Ls through males as through females. Imagine a mutant X chromosome, X, which resists the action of the Ls and causes itself to produce only female-determining eggs. Such an X will spread because females enjoy higher reproductive success when the sex ratio is male biased. The key assumption is that the L chromosome evolves to control the sex ratio, thus favoring the monogenic counterstrategy. L chromosomes may more easily evolve control of the sex ratio because, being germline-limited, there is no negative pleiotropic covariation with other phenotypic traits. An entire chromosome is free to evolve narrow genetic functions with little or no constraint from pleiotropic phenotypic effects. That Ls came from Xs is consistent with the fact that in the first spermatocyte the L remains condensed and heteropycnotic (Metz 1938), just as do the sex chromosomes in many species. Likewise, the mechanism of L elimination-failure of sister chromatids to separate-appears to be the same as for somatic X elimination. Sex ratios in ocellaris are digenic, while those of reynoldsi appear to be a mixture of di- and monogenic. As Haig (1993d) is the first to admit, his story is a post-hoc attempt to fit theory to the facts that goes well beyond the available facts and permits many alternative scenarios not yet explored. Yet it is the first argument of any sort to explain the evolution of an extremely aberrant genetic system, itself apparently made up of a variety of selfish genetic elements. Especially striking are arguments that link the evolution of one subsystem to another, as in: X drive L chromosomes monogenic eggs. For example, it is not obvious how, mechanistically, a driving X chromosome can be "joined" by the maternal autosomes. Also, Ls 400 Genomic Exclusion could easily have evolved from standard B chromosomes rather than from Xs, a possibility that removes the difficulties of aneuploidy. It is also easy to imagine that bacterial endosymbionts played a leading role in the evolution of the system (Normark 2004). Bacterial endosymbionts are associated with monogeny in wood lice (Armadillidium spp. Further progress will clearly require much more empirical work, both evolutionary and mechanistic, on the species concerned. It is also worth emphasizing that, regardless of how exactly the system evolved, there are abundant opportunities for conflict in the extant species. Autosomes, Xs, and Ls all have different patterns of inheritance, and so different optima regarding sex ratios and behavior toward kin. Mechanisms Little is known about the mechanisms underlying the sciarid chromosomal system. We provide a review of the major findings for each of the genetic elements in this section. In most cases of chromosome elimination (certainly paternal genome loss), elimination is achieved by a failure to pair at the metaphase plate or the pulling into a dead-end corner by filaments attached to a nongenerative pole. By contrast, the disappearance of 1 of the 2 paternal Xs from the primordial germ cells of both sexes occurs in a most unusual way, with 1 X moving quickly toward the nuclear membrane; becoming attached, engulfed, and evaginated; and reappearing as a vesicle in the cytoplasm, a lone chromosome surrounded by a double membrane (Perondini and Ribeiro 1997 and references cited therein). Instead, there is clear evidence that the membrane is primed for regenerating itself: ribosomes on the membrane become numerous near the point of attachment, and endoplasmic reticulum and mitochondria are frequent in the nearby cytoplasm. The transformation from independent nuclear chromosome to cytoplasmic vesicle takes about 3 hours, and higher temperature leads to quicker transformation. Elimination of paternal Xs from somatic tissue (1 lost in females, 2 in males) proceeds by a different mechanism than elimination in the germline (de Saint Phalle and Sullivan 1996). The first abnormality shown by a soon-to-be-eliminated X is a failure of sister chromatids to separate. The chromatids separate at the centromeres and the telomeres but remain attached along a region of the long arm of the X. The centromeres remain attached to the spindle apparatus and under tension at the metaphase plate, stretched in opposite directions so, if one centromere should become detached, the entire complex would migrate to the opposite pole. This work also confirmed classic findings that the process requires a cis-acting region of the X chromosome, near the centromere, known as the "controlling element" (Crouse 1960). If this region is translocated to an autosome, the autosome is eliminated in embryos when it is of paternal origin. As in regular X-elimination, this elimination is due to the failure of the long arms of the autosome to separate. The controlling element is in the region of the proximal X heterochromatin that contains most of S. The elimination occurs in cycles 7, 8, and 9 in males and almost exclusively in cycle 9 in females. Sanchez and Perondini (1999) have developed a model for sex determination in sciarids based on control of X chromosome elimination. They argue that the evidence is best accommodated by assuming a 2-factor system in which a chromosomal factor interacts with the X chromosomes causing their elimination. A maternal factor, in turn, regulates the chromosomal factor and maternal imprint of chromosomes makes them impervious to the chromosomal factor. Virtually nothing is known about the process except that, as in X elimination, L sister chromatids fail to separate on the metaphase plate (de Saint Phalle and Sullivan 1996). It would not be surprising if this failure were controlled by an element on the L, because the L would benefit from its own somatic exclusion. A monopolar spindle is formed in meiosis I (that is, spindles radiate out from a single centrosome), the chromosomes remain scattered and fail to pair, and they are not oriented in a metaphase-like array. Maternal chromosomes move toward the single pole while paternal chromosomes attach to the spindle and move in the opposite direction into a cytoplasmic bud to be eliminated (Kubai 1982). Because the spindles from the pole extend all the way to the nongenerative side and because they attach to the paternal chromatin cluster and their microtubules interact with kinetochores of paternal chromosomes, it has been speculated that they are involved as much in taking the paternal chromosomes away as they are in drawing the maternal chromosomes to the pole (Kubai 1982, Esteban et al. While maternal chromosomes are drawn to the pole, with the centromeres leading, the reverse is the case with paternal chromosomes, which often move as if the ends are being pulled toward the nongenerative side-in other words, their centromeres lag (Abbott et al.
Quality 30gr rumalaya gel. Non steroidal anti-inflammatory drugs (NSAIDs): Mayo Clinic Radio.
The technique involved preparing a groove on the lingual surfaces of the teeth and adapting an annealed spasms of the bladder order rumalaya gel 30gr with visa, multi-strand (flexible) orthodontic wire muscle relaxant m 58 59 order rumalaya gel 30 gr on line. The wire was secured to the teeth with composite muscle relaxant pills cheap 30gr rumalaya gel mastercard, ensuring that the interproximal areas remained unbonded muscle relaxant in pediatrics order rumalaya gel 30 gr without a prescription. Gerstein and King (1975) reviewed the use of removable partial denture splints for the treatment of mobility muscle relaxant at walgreens discount 30 gr rumalaya gel. The appliance referenced was designed by Kratochvil and used specific design criteria to promote maximum stability and cleansability muscle relaxant 1 rumalaya gel 30gr generic. Occlusal rests should extend completely through the center of the occlusal surface in a mesio-distal direction at a depth of 1. Interproximal guide planes provide bracing and help eliminate tooth-prosthesis voids. Major connectors should be kept as far away from gingival margins as anatomically possible. The "I" bar clasp is recommended because it engages a more physiologic degree of undercut, is a cleaner clasp arrangement, and places less unfavorable forces on the abutment when torquing forces are produced by the partial denture. Removable splints were promoted due to better access for plaque removal when compared to fixed splints. Other advantages of the removable splints include less tooth preparation, pulpal trauma, chairside time, clinical effort, and expense. Such partial dentures require extremely meticulous preparation and technical expertise for "precision" design. Although the time periods for the study were short, the authors concluded that precision designed partial dentures may be effective in stabilizing mobile teeth. The authors observed that forces applied to 1 tooth in a splint were transmitted to all teeth within the splint. The direction of the initial force was maintained and comparable areas of the splinted periodontium were affected. Forces applied to non-splinted teeth were not transmitted to adjacent teeth and force sufficient to cause necrosis did not cause pocketing. Mandel and Viidik (1989) used Vervet monkeys to study the effects of rigidly splinting anterior teeth that had been extruded 3 mm and replaced into the socket. Rateitschak (1963) studied the effect of initial preparation and occlusal adjustment on tooth mobility in 80 patients using the Muhlemann periodontometer with a deflective force of 500 gm. Orthodontics or removable splints caused an initial increase in the mobility which returned to baseline by 2 years. Extensive fixed bridgework was placed following periodontal therapy and the patients monitored for 2 to 6 years. No further bone loss was observed between the insertion of the fixed bridgework and the final examination. The authors noted that the telescoping bridges reduced mobility during an initial 4-week period when they were not removed and for an additional 6 weeks, when the bridges were removed daily. The mobility of non-splinted control teeth was also reduced at the 4- and 10-week periods. The authors suggest that the reductions in mobility may have been due to the establishment of a harmonious occlusion and not necessarily due to splinting. The use of removable partial denture splints in the treatment of post-surgical tooth mobility. The role of occlusion in periodontal disease and the biological rationale for splinting in treatment of periodontitis. Effect of splinting on the mechanical and histological properties of the healing periodontal ligament in the Vervet monkey (Cercopithecus aethiops). The role of occlusion for the stability of fixed bridges in patients with reduced periodontal support. The therapeutic effect of local treatment on periodontal disease assessed upon evaluation of different diagnostic criteria. Stabilizing periodontally weakened teeth by using guide plane removable partial dentures: A preliminary report. The authors found no significant difference between splinted and nonsplinted segments with regard to tooth mobility, gingival bleeding, attachment level, or radiographic bone scores. Teeth that were initially more mobile received no significant benefit from splinting when compared to initially lessmobile teeth. Using maxillary teeth in a group of 10 patients, 1 quadrant was splinted following osseous surgery and the other was not. During a follow-up period of 24 weeks, it was noted that splinting had no effect on mobility at any time. Also, postoperative mobility seemed more dependent upon preoperative mobility than on the treatment method. Internal Derangement: An abnormal relationship of the articular disk to the mandibular condyle, fossa, and/or articular eminence. Meniscal Displacement with Reduction: the condition wherein the articular disk is located anterior or anteromedial to the condylar head when the jaw is closed. When the jaw is open the disk assumes the normal relationship to the condylar head and articular eminence. Meniscal Displacement without Reduction: the condition wherein the articular disk is always located anterior or antero-medial to the condylar head regardless of whether the jaw is open or closed. The condyle is elliptical in shape with its mediolateral diameter being greater than its anteroposterior diameter. The joint is divided into upper and lower compartments by the disk which is attaches to the medial and lateral aspect of the condyle. The sphenomandibular ligament attaches to the lingula on the medial aspect of the mandible and the stylomandibular ligament attaches to the posterior border of the ramus (Figure 1). The joint is innervated by the auriculotemporal nerve and masseteric branches of the trigeminal nerve (V. The blood supply derives from the superficial temporal, middle meningeal, and other associated branches of the internal maxillary artery. These zones consist of a moderately thick anterior band, a thin narrow intermediate band, a posterior band which is the thickest area of the disk, and a retrodiskal zone (bilaminar zone) (Rees, 1954). The posterior attachment of the disk, sometimes referred to as the retrodiskal pad, contains numerous large vascular spaces and elastic tissue. The disk appears to have limited capacity for repair and the pathologic changes are usually degenerative (Blackwood, 1969). Medially and laterally, the articular disk blends with the capsule (which surrounds the disk) and attaches to the condyle. Anteriorly, it attaches to the articular eminence, condyle, and superior head of the lateral pterygoid. Posteriorly, there are firm retrodiskal tissue attachments to the glenoid Figure 1. Basic anatomy (articulation and capsule) Posterior Roof of Glenoid Fossa Bilaminar Region, Posterior temporal attachment-. Anteriorly, the capsule is reinforced by the temporomandibular ligament, a dense, collagenous ligament without elastic fibers, which functions to maintain contact between articular surfaces and limit extreme movement. Mandibular Condyle Histology There are 3 distinct cell zones in the cartilage of the mandibular condyle during growth: articular zone, proliferative zone, and hypertrophic zone. The proliferative and hypertrophic zones manifest cartilage replacement by mineralized bone, similar to other growing bones. The surface of the articular zone is renewed independent of the proliferative zone, and this difference is reflected in the response of this zone to some of the pathologic processes occurring in this area. With age, the articular zone becomes increasingly fibrous, the proliferative zone is reduced to a narrow band of cells, and the hypertrophic zone is replaced by fibrocartilage (Blackwood, 1969). Articular Remodeling Joint remodeling may be progressive, regressive, and peripheral. Progressive and peripheral remodeling constitutes the addition of tissue to the joint surfaces. Peripheral remodeling occurs primarily at the edges of the articular surfaces and occasionally involves the periosteum. Progressive and peripheral remodeling accompanies cellular activity in the proliferative zone, resulting in new cartilage formation and increasing vertical dimension. Regressive remodeling results from osteoclastic resorption of the subarticular bone and replacement with new cartilage and bone, lowering the vertical dimension. During remodeling, the articular surfaces of the joint remain intact and play a relatively passive role by adapting to the changes taking place in the tissues beneath (Blackwood, 1969). As the condyle moves forward, the meniscus is displaced downward and forward, with forward movement due to pull of the lateral pterygoid muscle and attachments to the condyle. The disk is allowed to move forward 7 to 10 mm due to fibro-elastic connective tissue in the posterior attachment which "recoils" on closing (Rees, 1954). Movement between the lower joint structures is rotational while translation occurs between the structures of the upper joint (Okeson, 1991). In 1955, Schwartz identified a more definitive subgroup of patients who presented with painful, limited mandibular movement. He attributed this to spasms of the musculature and termed it "temporomandibular joint pain-dysfunction syndrome. Treatment principles included reduction of stress, pain and spasm, therapeutic exercise, and possible judicious occlusal alteration. The workshop seemed to approve a classification established by the International Headache Society and the American Academy of Craniomandibular Disorders. Currently, however, the masticatory muscle disorders (myofascial pain, myositis, spasm, reflex splinting, hypertrophy, etc. Internal derangements or disk-interference disorders, as classified by Okeson in 1991, include: disk displacement or dislocation with reduction; disk dislocation without reduction; adhesions; and alterations in form. Joint sounds are often caused by internal derangements but also may be present in "normal" joints as well Section 1. Clicking is the most common joint sound and is caused by the posterior movement of an anteriorly positioned disk or the passage of the condyle against the posterior aspect of the disk during reduction of the disk during jaw opening. Reciprocal clicking produces a similar sound near maximum intercuspation when the disk recoils anteriorly. Crepirus is a grating sound caused by rubbing of irregular articular surfaces or dry synovial surfaces of the joint often associated with degenerative joint disease. Clinically, there was limitation of opening (24 to 32 mm) with deviation toward the affected side. He felt transcranial radiographs were beneficial in assessing condylar position and joint spaces and thus useful in diagnosis. Although technological advances allow imaging using tomography, computed tomography, and magnetic resonance imaging, none of these techniques can predictably differentiate between adaptation and pathologic changes. Prior to the expense and radiation of most imaging techniques, a high probability should exist that the findings of the examination will aid significantly in diagnosis and treatment selection (Dixon, 1991). If the displacement was painful or had existed for days or weeks, a flat, hard, acrylic bite plane was worn for a few days and then an anterior repositioning splint to move the mandible forward until the disk returned to its normal position (recapturing the disk). Anterior repositioning appliances are still being used, although not without controversy. Only 25 to 36% of the patients had long-term reductions of pain and dysfunction. Posterior open bites were found to be a problem and occlusal equilibration or rehabilitation was costly, time consuming, and difficult. For these reasons, anterior repositioning appliances should be used with discretion and only if initial treatment with a stabilization appliance (splint) proves unsuccessful (Okeson, 1991). DeBoever (1980) included ear symptoms, noting their presence in 25 to 37% of the patients, with jaw deviation to the affected side upon opening. The controversy over the importance of occlusion versus the impact of psychosocial stress persists; however, most authorities have discounted the role of occlusal discrepancies. Increased masticatory muscle activity, tension, and pain have been related to periods of subjective stress. During sleep, it is termed nocturnal bruxism and during waking hours is called diurnal parafunction. Diurnal parafunction also includes oral habits such as nail biting, finger sucking, tongue thrusting, and chewing on various objects. Most individuals demonstrate signs of bruxism but only 5 to 20% are aware of their parafunctional activity. The occlusal wear pattern in a bruxer will result in facets that align while wear facets associated with mastication do not. Nocturnal bruxism has been related to periods of daytime emotional and physical stress and is currently, considered a stressrelated sleep disorder. Evidence indicates there is no direct relationship with occlusal interferences, although the etiology is probably multi-factorial and occlusion could play a minor role in certain cases (Attanasio, 1991). Tooth wear, fractured cusps, injury to the periodontium with hypermobility of teeth, hypercementosis, and pulpitis may result from bruxism. Initial therapy should rely on reversible procedures including interocclusal appliances, stress management, physical therapy, pharmacological muscle relaxants, and/or occlusal adjustment (Attanasio, 1991). Early treatment may include patient education and counseling, habit management, physical therapy, bio-feedback, bite-splint appliances, short-term analgesics, and/or muscle relaxants. Greene and Laskin (1983) compared the initial and longterm results of conservative, reversible therapy to 10 previously published papers, regarding irreversible procedures. Treatment modalities were variable (oral appliance, biofeedback, psychological counseling, medication, transcutaneous nerve stimulation, placebo), but all were reversible and required some degree of patient cooperation and participation. Immediately following treatment, 74% had been greatly improved, 25% had minor or no improvement, and 1% worsened. When phoned, 90% of the patients were doing well (53% asymptomatic, 37% minor symptoms), 8% were no better than before treatment, and 2% were worse.
It is clear that the Party will have to be a partner both in the National Front as well as in its relations to the opposition (Civic Forum) infantile spasms 2012 rumalaya gel 30gr. Should the corresponding measures and clearly formulated party lines fail to be adopted spasms pelvic floor buy generic rumalaya gel 30 gr on-line, there is danger that the party may disintegrate and will have diminished hopes of gaining a significant portion of the vote in the next elections back spasms 20 weeks pregnant 30 gr rumalaya gel visa. The political directive for the plan of action of the entire party over the next few days is laid out in the speech of the Secretary General at the Nation-wide Party Caucus muscle relaxant reversal agents cheap rumalaya gel 30 gr visa. To acquaint every communist with the discussions of the Caucus spasms sleep order rumalaya gel 30 gr mastercard, and explain the conclusions of its discussion and seek their fulfillment by communists and other workers spasms pelvic area generic 30 gr rumalaya gel fast delivery. Trust in the party must be supported by well thought-out cadre decisions and not by lack of control and certainly not by pressure. Engage in an active dialogue and cooperate with all who want to build a socialist Czechoslovakia. This [includes] those individuals and groups who are concentrated in the Civic Forum and uphold these positions. It is necessary, however, to immediately initiate the preparations and to responsibly choose delegates who will carry the responsibility for the ensuing fate of our party and this country. We refuse the demands for the liquidation of the People=s Militia, basic organizations in the workplace and the transfer of party property. The People=s Militia are not aimed against our nation, but are necessary to prevent sabotage and revolutionary attempts. The main goal at the present is to secure the fulfillment of all the tasks in the national economy. To ensure the continuation of production, supply, operation of services and healthcare. The caucus repudiated the random attacks of the Civic Forum against the president of the republic, for this function must be protected in accordance with our Constitution. The Civic Forum feels itself competent to negotiate immediately with the government about the critical situation in our country, to express the actual demands of the public and to discuss the solutions. The Civic Forum wishes to begin such negotiations, which should be the beginning of a universal discussion on the future of Czechoslovakia, by a negotiation of these urgent and ever more openly formulated demands: 1. The pernicious politics of people, who for years refused any kind of democratic dialog with the society, completely legally resulted in the terrible events of the last days. That a committee be set up which would concretely investigate these measures, find the culprits and propose punishments for them. That all the criminals of conscience, including those who have been detained in connection with the last demonstration, be immediately released. The Civic Forum demands that this proclamation be published in the official Czechoslovak media. The Civic Forum stakes its authority behind the plan for a general strike on 27 November from 12:00 p. The Civic Forum believes that its creation and task corresponds with the will of the 40,000 current signatories of the petition Several Sentences, and is open to all the constituents and forces of society whose concern is that our country should begin peacefully finding the way to a democratic social order, and through it to economic prosperity. This crisis is the result of the inactivity of the current political and economic system. Almost all the mechanisms necessary for society to properly react to the changing internal and external conditions have been eliminated. For interminable decades the self-evident principle has not been respected: who has the power must also carry the responsibility. The people are thus sentenced to play the role of mere executors of the orders of the powerful. The directive system of the central leadership of the national economy has plainly failed. The promised reconstruction of the economic mechanism is slow, ineffective and is not carried out by the necessary political changes. These problems will not be resolved by a substitution of persons in positions of power or by the departure of a few politicians from public life. Rights the Czechoslovak Republic must be a legal, democratic state in the spirit of the traditions of Czechoslovak statehood and in the spirit of the internationally accepted principles, expressed above all in the Universal General Declaration of Human Rights and in the International Pact on Civic and Political Rights. A new constitution must be worked out in this spirit, in which the relationship between the citizens and the state in particular will be revised in detail. This constitution must, of course, be only accepted by a newly elected constitutional assembly. The enforcement of civic rights and freedoms will be reliably ensured by a developed system of legal guarantees. An independent judiciary must also constitute a constitutional and fair judiciary. We insist on righting the wrongs done in the past as a result of politically motivated persecutions. The Political System We demand fundamental, effective and lasting changes in the political system of our society. We must create anew or renew the democratic institutions and mechanisms, which will enable the real participation of all citizens in public affairs and at the same time will become an instrumental barrier against the abuse of political and economic power. All existing and newly created political parties and other political and social groups must have the same opportunities to partake in the free elections of all the representational bodies. Czechoslovakia will be an equal union of both nations and all nationalities, observing the principles of a federative state order. Foreign Policy We are striving for our country to once again occupy a worthy place in Europe and in the world. We are a part of Central Europe and we want to therefore maintain good relations with all of our neighbors. Meanwhile, we want to revise the agreements motivated by the excessive ambitions of the leading representatives of the state. It takes away the desire to work and wastes its results, plunders the natural resources, destroys the environment and increases the total backwardness of Czechoslovakia. We are convinced that this economic system is impossible to improve through partial improvements. Its successful functioning is contingent on the breaking of the monopoly on the positions in today=s big businesses, and the creation of true competition. The latter can only be created on the basis of a parallel, equal existence of different types of ownership and the gradual opening of our economy to the world. The state will, of course, retain in the future a series of irreplaceable functions. It will ensure universal economic conditions equal for all, and undertake macro-economic regulatory policies with the intent to contain inflation, the growth of foreign debt and impending unemployment. Only the state can guarantee the indispensable minimum of public and social services and the protection of the environment. Social Justice Decisive for us, is that conditions be created in the society for the development and the assertion of everyone=s ability. Czechoslovakia must be a socially just country in which people receive aid in old age, sickness and difficult situations. An important precondition for such a society, however, is a prosperous national economy. Churches, communities, businesses and various state volunteer organizations can contribute to the creation of a vivid network of social services. Thus the possibilities for the assertion of a rare sense of human solidarity, responsibility and love for one=s neighbor will be expanded. The Environment We must all look for a way to renew the harmony between the people and the environment. We will strive for a progressive repair of the damages which we have inflicted upon nature for the last several decades. We will try to restore our countryside and our dwellings to their original beauty, to ensure better protection of nature and natural resources. We will accomplish in the shortest possible time a significant amelioration in the basic conditions of human life: we will try to ensure quality drinking water, clean air and uncontaminated food. We will press for a fundamental amelioration in the system of environmental care which will be aimed not only at liquidating the current sources of pollution, but first of all at preventing further damages. We will, at the same time, change the composition and objective of the national economy, and thus decrease in particular the consumption of energy and raw materials. Culture Culture can not be only something for the artists, scholars and teachers, but a way of life for the entire civic society. It must be extricated from the chains of any ideology and must overcome the artificial separation from world culture. Art and literature can not be limited and must be provided many opportunities for publication and contact with the public. We will rule out its naive and demagogic overestimation, as well as its degraded position which makes it a tool of the ruling party. A democratic school system should be organized on humanist principles, without a state monopoly on education. It is true that the news they issued played an important role in informing and mobilizing of the public. Society must respect teachers in any type of school and must provide them with a space where they can assert their personality. It is necessary to return to the universities the rights, which ensure their independence and the freedom of the academic soil, and this for professors and students alike. Upbringing and education must lead to independent thought and morally responsible discussion. Our program today is concise, we are working, however, on making it more concrete. We have been led to it through impartial analysis of the objective processes of our time. The increasing varieties of social development in different countries are becoming in ever more perceptible feature of these processes. The variety of sociopolitical structures which has grown over the last decades from national liberation movements also demonstrates this. This objective fact presupposes respect for other peoples views and stands, tolerance, a preparedness to see phenomena that are different as not necessarily bad or hostile, and an ability to learn to live side by side while remaining different and not agreeing with one another on every issue. The de-ideologization of interstate relations has become a demand of the new stage. That would lead to spiritual impoverishment, for it would mean renouncing so powerful a source of development as sharing all the original things created independently by each nation. In the course of such sharing, each should prove the advantages of his own system, his own way of life and values, but not through words or propaganda alone, but through real deeds as well. That is, indeed, an honest struggle of ideology, but it must not be carried over into mutual relations between states. Otherwise we simply will not be able to solve a single world problem; arrange broad, mutually advantageous and equitable cooperation between peoples; manage rationally the achievements of the scientific and technical revolution; transform world economic relations; protect the environment; overcome underdevelopment; or put an end to hunger, disease, illiteracy, and other mass ills. Finally, in that case, we will not manage to eliminate the nuclear threat and militarism. This has led to a renewed interest in the manufacturing of consent and the role of covert action in the promotion of ideas on social and political organization and freedom of expression. This conference aims at a multi-disciplinary evaluation of the lasting significance and consequences of the cultural activities of the Cold War in Western Europe as a battle-ground for the shaping of democratic societies. It also seeks to reassess the critical interpretations of the Cold War that were developed in the 1960s and 1970s and take a fresh look at the complex mix of public and private organizations that were engaged in this struggle. The journal Intelligence and National Security is keen to publish the conference papers with the idea of bringing out a Special Issue. In connection with this, the material is also likely to appear as both a hard-back and soft-back book. How did memories of and traditions of resistance in the Second World War affect the conceptualization of the Cold War How were labor and business relations shaped under the influence of Cold War thinking, and what were the consequences for democratic society What use was made of intellectuals and their ideas in the (covert) politics of the cultural cold war How does one assess the linkages between intellectual activities and clandestine networks The actions of the 20-21 August should, according to the expectations of the adversary, accelerate the fall and development of events in the country with the aim of achieving their purpose. Legal proceedings were taken against the criminal act of sedition according to paragraph 100 of the criminal code. With the agreement of the municipal prosecutor in Prague, house searches of the main organizers S. Documentation was obtained on the criminal activity of the main organizers of the enemy campaign. It is necessary to consider the leveling of accusations and imprisonment through the perspective of the developing security situation and decide whether to proceed to trial immediately on the 21 August 1989. In total 211 interrogations were carried out, 10 people were charged with crimes according to paragraph 100 of the criminal code, 76 people were charged with felonies according to paragraph 6 of law #150/69 Sb. The plan of the antagonist was nipped in the bud and its spread was successfully stopped. The original letter along with copying equipment was confiscated and house searches of main organizers M. Several dozen people are participating in these marches, and their numbers increase daily. Besides provoking the state powers, the antagonist wants to activate the public, confirm his own ability to act and disclose eventual counter-measures.
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