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Patient preparation in pediatric surgery.

This article has outlined the developmental concerns which make pediatric preparation for surgery a necessity. The goals, methodology, and essential elements of programming have been presented, along with a review of the supporting literature. Some of the major concerns expressed by children have been illustrated. In summary, the following are the essential points to keep in mind when planning pediatric patient care: Honesty. There is no substitute for the trust developed between an honest physician and the patient. Awareness of developmental concerns. The timing, wording, and presentation of preparation materials must be based on an accurate assessment of the child's cognitive and emotional readiness. Involvement of the patient and parent in decision making, treatments, and procedures whenever possible. Patients and families who feel in control are much more trusting and receptive to the physician's plan. Follow-up. Make certain the patient and family are aware of your continued concern for their well-being. In addition, ask what they feel helped them and their child the most, and what could have been done to be more helpful. This helps continued refinement of a program designed to meet client needs.

Adolescent↗

Vaccinia virus intermediate and late promoter elements are targeted by the TATA-binding protein.

Vaccinia virus replicates in the cytoplasm of the host cell and encodes its own RNA polymerase and transcription factors. The proteins that target the poxvirus RNA polymerase to intermediate- and late-class promoters have not been identified. In this study, representatives of the intermediate and late promoters were characterized at the nucleotide level to identify essential motifs. Both intermediate and late viral promoters are shown to have an essential element suggestive of TATA boxes, which are potential targets for the TATA-binding protein (TBP). Several approaches were used to test for TBP requirement in vaccinia virus transcription, including overexpression of TBP, expression of a dominant negative mutant of TBP, RNA interference, and expression of adenovirus E1A protein, which inactivates TBP. In each case, the results support an essential role for TBP in vaccinia virus intermediate- and late-gene transcription. These findings indicate that poxviruses have integrated TBP as a central feature into an otherwise heterologous transcription system. A model for transcriptional switching, in which both intermediate and late promoter elements are targeted by TBP that recruits viral transcription factors to assemble a functional complex on their cognate promoters and a dysfunctional, repressed complex on the other class, is proposed.

Adenovirus E1A Proteins↗

Unique structural determinants in the signal peptides of "spontaneously" inserting thylakoid membrane proteins.

A series of thylakoid membrane proteins, including PsbX, PsbY and PsbW, are synthesized with cleavable signal peptides yet inserted using none of the known Sec/SRP/Tat/Oxa1-type insertion machineries. Here, we show that, although superficially similar to Sec-type signal peptides, these thylakoidal signal peptides contain very different determinants. First, we show that basic residues in the N-terminal domain are not important, ruling out electrostatic interactions as an essential element of the insertion mechanism, and implying a fundamentally different targeting mechanism when compared with the structurally similar M13 procoat. Second, we show that acidic residues in the C-domain are essential for the efficient maturation of the PsbX and PsbY-A1 peptides, and that even a single substitution of the -5 Glu by Val in the PsbX signal peptide abolishes maturation in the thylakoid. Processing efficiency is restored to an extent, but not completely, by the highly hydrophilic Asn, implying that this domain is required to be hydrophilic, but preferably negatively charged, in order to present the cleavage site in an optimal manner. We show that substitution of the PsbX C-domain Glu residues by Val leads to a burial of the cleavage site within the bilayer although insertion is unaffected. Finally, we show that substitution of the Glu residues in the lumenal A2 loop of the PsbY polyprotein leads to a block in cleavage on the stromal side of the membrane, and present evidence that the PsbY-A2 signal peptide is required to be relatively hydrophilic and unable to adopt a transmembrane conformation on its own. These data indicate that, rather than being merely additional hydrophobic regions to promote insertion, the signal peptides of these thylakoid proteins are complex domains with uniquely stringent requirements in the C-domain and/or translocated loop regions.

Amino Acid Sequence↗

A chronic disease outreach program for Aboriginal communities.

BACKGROUND: Our objective is to describe a program to improve awareness and management of hypertension, renal disease, and diabetes in 3 remote Australian Aboriginal communities. METHODS: The program espouses that regular integrated checks for chronic disease and their risk factors are essential elements of regular adult health care. Programs should be run by local health workers, following algorithms for testing and treatment, with backup, usually from a distance, from nurse coordinators. Constant evaluation is essential to develop community health profiles and adapt program structure. RESULTS: Participation ranged from 65% to 100% of adults. Forty-one percent of women and 72% of men were current smokers. Body weight varied markedly by community. Although excessive in all, rates of chronic diseases also differed markedly among communities. Rates increased with age, but the greatest numbers of people with morbidities were middle age and young adults. Multiple morbidities were common by middle age. Hypertension and renal disease were early features, whereas diabetes was a variable and later manifestation of this integrated chronic disease syndrome. Adherence to testing and treatment protocols improved markedly over time. Substantial numbers of new diagnoses were made. Blood pressure improved in people in whom antihypertensive agents were started or increased. Components of a systematic activity plan became more clearly defined with time. Treatment of people in the community with the greatest disease burden posed a large additional workload. Lack of health workers and absenteeism were major impediments to productivity. CONCLUSION: We cannot generalize about body habitus, and chronic disease rates among Aboriginal adults. Pilot data are needed to plan resources based on the chronic disease burden in each community. Systematic screening is useful in identifying high-risk individuals, most at an early treatable stage. Community-based health profiles provide critical information for the development of rational health policy and needs-based health services.

Adult↗

Dealing with a shifting paradigm.

In 1970, T. S. Kuhn, in The Structure of Scientific Revolutions argued that scientists work by creating a comprehensive model--a model he called "a paradigm." A paradigm, Kuhn said, is an encompassing world view that tells us what facts to pay attention to and what to ignore. He contended that, although we may think that we consider all the facts and ask all the questions, there is always some ordering and selection going on, and we must first be prepared by our paradigm to make sense of what we see. He stated that one of the first signs that a paradigm is shifting is the discovery of facts that seem significant and indisputably true but cannot be explained by the current model. The essential elements, according to Kuhn, that are required for a paradigm to shift are a strong stimulus, a rapidly changing environment, and the realization that whether the change is good or bad is essentially of no significance. The parties most closely involved are frequently the last to appreciate that the shift has occurred.

Economics, Hospital↗

Interactions between metallothionein and trace elements.

Metallothionein is an important metal-binding protein which occurs in varying amounts in a wide range of tissues but particularly in liver, kidneys, intestine and pancreas. Synthesis of the protein is induced by zinc and copper and also by cadmium and many other non-essential elements. The concentration of the protein in tissues depend on zinc and copper status and on patho-physiological state. A variety of stress factors stimulate metallothionein synthesis, particularly in liver. The turnover rate of metallothionein in tissues is relatively high but depends to a large extent on its metal content. There has been much speculation as to the function of the protein and one important role appears to lie in the cellular detoxification of copper, zinc and other metals. Metallothionein also appears to participate in metabolic interactions between zinc and copper. The protein occurs in small amounts in blood and urine and assay of these concentrations may be used in the assessment of trace element status.

Amino Acid Sequence↗

Nickel.

Nickel is an essential element for at least several animal species. These animal studies associate nickel deprivation with depressed growth, reduced reproductive rates, and alterations of serum lipids and glucose. Although there is substantial evidence of an essential status for nickel in animals, a deficiency state in humans has not been clearly defined. Nickel is a silver-white metal with siderophilic properties that facilitate the formation of nickel-iron alloys. In contrast to the soluble nickel salts (chloride, nitrate, sulfate), metallic nickel, nickel sulfides, and nickel oxides are poorly water-soluble. Nickel carbonyl is a volatile liquid at room temperature that decomposes rapidly into carbon monoxide and nickel. Drinking water and food are the main sources of exposure for the general population with the average American diet containing about 300 micrograms Ni/d. Nickel is highly mobile in soil, particularly in acid soils. There is little evidence that nickel compounds accumulate in the food chain. Nickel is not a cumulative toxin in animals or in humans. Almost all cases of acute nickel toxicity result from exposure to nickel carbonyl. The initial effects involve irritation of the respiratory tract and nonspecific symptoms. Patients with severe poisoning develop intense pulmonary and gastrointestinal toxicity. Diffuse interstitial pneumonitis and cerebral edema are the main cause of death. Sodium diethyldithiocarbamate is an investigational drug used to chelate nickel following exposure to nickel carbonyl. Nickel is a common sensitizing agent with a high prevalence of allergic contact dermatitis. Nickel and nickel compounds are well-recognized carcinogens. However, the identity of the nickel compound or compounds, which cause the increased risk of cancer, remains unclear. Currently, there are little epidemiological data to indicate that exposure to metallic nickel increases the risk of cancer, or that exposure to the carcinogenic forms of nickel causes cancer outside the lung and the nasal cavity.

Animals↗

A multidomain TIGR/olfactomedin protein family with conserved structural similarity in the N-terminal region and conserved motifs in the C-terminal region.

Based on the similarity between the TIGR (trabecular-meshwork inducible glucocorticoid response) (also known as myocilin) and olfactomedin protein families identified throughout the length of the TIGR protein, we have identified more distantly related proteins to determine the elements essential to the function/structure of the TIGR and olfactomedin proteins. Using a sequence walk method and the Shotgun program, we have identified a family including 31 olfactomedin domain-containing sequences. Multiple sequence alignments and secondary structure analyses were used to identify conserved sequence elements. Pairwise identity in the olfactomedin domain ranges from 8 to 64%, with an average pairwise identity of 24%. The N-terminal regions of the proteins fall into two subgroups, one including the TIGR and olfactomedin families and another group of apparently unrelated domains. The TIGR and olfactomedin sequences display conserved motifs including a residual leucine zipper region and maintain a similar secondary structure throughout the N-terminal region. The correlation between conserved elements and disease-associated mutations and apparent polymorphisms in human TIGR was also examined to evaluate the apparent importance of conserved residues to the function/structure of TIGR. Several residues have been identified as essential to the function and/or structure of the human TIGR protein based on their degree of conservation across the family and their implication in the pathogenesis of primary open-angle glaucoma. Additionally, we have identified a group of chitinase sequences containing several of the highly conserved motifs present in the C-terminal region of the olfactomedin domain-containing sequences.

Algorithms↗

A novel muscle-specific enhancer identified within the deletion overlap region of two XLDC patients lacking muscle exon 1 of the human dystrophin gene.

Previous studies point to the involvement of several discrete transcriptional enhancers in the modulation of dystrophin gene expression in skeletal and cardiac muscle. Analysis of deletion breakpoints in two X-linked dilated cardiomyopathy patients with mutations that remove muscle exon 1 identified a 3.2-kb deletion overlap region (XLDC3.2) between -1199 and +2057 bp predicted to contain regulatory elements essential for dystrophin gene expression in cardiac muscle. A novel-sequence-based search strategy was used to identify a 543-bp region downstream of muscle exon 1 rich in cardiac-specific transcriptional elements. Designated dystrophin muscle enhancer 2 (DME2), this candidate enhancer was seen to function in a position- and orientation-independent manner in muscle cell lines but not in fibroblasts. As only modest activity was observed in primary neonatal rat cardiomyocytes, DME2 is thought to play a role in dystrophin gene regulation at later stages of cardiac muscle development.

3T3 Cells↗

Establishment of uteroplacental circulation.

Haemochorial placentation, as it occurs in the human and other primate and rodent species, requires a connection of the placenta with supplying maternal (uteroplacental) arteries. Very little is known of the initial stages but endovascular trophoblast invasion seems to represent an essential element for further elaboration of an adequate uteroplacental circulation. In the human, endovascular trophoblast arrives in myometrial segments of spiral arteries only from about 15 weeks of pregnancy. This is preceded by an interstitial type of cytotrophoblast invasion which seems to be associated with regressive changes in spiral artery walls. It is possible that the latter forms an essential priming factor to allow subsequent endovascular migration. Endovascular trophoblast invasion has been documented in different laboratory animals, including the rat and the golden hamster. Especially in the latter case a sequence of changes in the maternal component, i.e. the maternal cellular elements in the spiral artery walls, precede the arrival of trophoblast. Besides, there is also some evidence of haemodynamical factor(s) influencing trophoblast migration. Because of the importance of this phenomenon in the establishment of an adequate uteroplacental circulation, it is essential to develop further experimental models for studying pathological situations as exist in human pregnancy.

Animals↗

Functional effects of domain deletions in a multidomain serine protease, C1r.

The C1r subcomponent of the first component of complement is a complex, multidomain glycoprotein containing five regulatory or binding modules in addition to the serine protease domain. To reveal the functional role of the N-terminal regulatory domains, two deletion mutants of C1r were constructed. One mutant comprises the N-terminal half of domain I joined to the second half of the highly homologous domain III, resulting in one chimeric domain in the N-terminal region, instead of domains I-III. In the second mutant most of the N-terminal portion of domain I was deleted. Both deletion mutants were expressed in the baculovirus-insect cell expression system with yields typical of wild type C1r. Both mutants maintained the ability of the wild type C1r to dimerize. The folding and secretion of the recombinant proteins was not affected by these deletions, and C1-inhibitor binding was not impaired. The stability of the zymogen was significantly decreased however, indicating that the N-terminal region of the C1r molecule contains essential elements involved in the control of activation of the serine protease module. Tetramer formation with C1s in the presence of Ca2+ was abolished by both deletions. We suggest that the first domain of C1r is essential for tetramer formation, since the deletion of domain I from C1r impairs this interaction.

Amino Acid Sequence↗

Clinical judgment, expert programs, and cognitive style: a counter-essay in the logic of diagnosis.

The question of the extent to which one can rationally reconstruct the process of medical diagnosis and reduce it to an algorithm is explored. The act of diagnostic insight is such that a computational program cannot 'catch on' in the way that a competent diagnostician can. Clinical diagnostic reasoning in a particular case requires as a necessary condition an extraordinarily complex and rich structure of background knowledge as well as an intuitive element, such as is manifest when one 'catches on' to a joke. Computers cannot 'catch on' due to their limitations in the computational mode. As a consequence, there can be no computer simulation of an essential element in diagnostic procedures.

Artificial Intelligence↗

Pharmacologically induced elements of the hunting and feeding behavior in the pteropod mollusk Clione limacina. I. Effects of GABA.

1. The pteropod mollusk Clione limacina is a predator, feeding on the small pteropod mollusk Limacina helicina. Injection of gamma-aminobutyric acid (GABA) into the hemocoel of the intact Clione evoked some essential elements of the hunting and feeding behavior, i.e., protracting the tentacles, opening the mouth, and triggering the rhythmic movements of the buccal mass. This pattern resembled that evoked by presentation of the prey: Clione grasped the Limacina by its tentacles, extracted the prey's body from the shell and then swallowed it. 2. In electrophysiological experiments, several targets of GABA action have been found: 1) direct application of GABA to isolated cerebral motor neurons projecting to the protractor muscles of tentacles resulted in their excitation; 2) GABA activated the feeding rhythm generator located in the buccal ganglia; 3) GABA exerted excitatory or inhibitory effects on the receptor cells of statocysts, the effects being mediated by the efferent input to these cells; 4) GABA suppressed the defense reaction, which is an inhibition of the locomotor activity and of tentacle motor neurons, arising in response to stimulation of the head afferents; and 5) GABA potentiated an excitatory action of the serotoninergic metacerebral cells on the feeding rhythm generator. 3. Effects of GABA on the tentacle motor neurons and the feeding rhythm generator are pharmacologically distinguishable. The action of GABA on the feeding rhythm generator was mimicked by baclofen (which activates the GABAB receptors in mammalian neurons) and was not sensitive to bicuculline (the GABAA receptor antagonist in mammals). On the other hand, bicuculline competitively inhibited the GABA-induced excitation of the tentacle motor neurons. 4. GABAergic neurons have been located in the cerebral, pedal, and buccal ganglia by means of immunohistochemical methods.

Animals↗

Diving accident management, with special emphasis on the situation in the Red Sea.

Accident management is a concept commonly misunderstood, frequently confused with accident treatment. The situation in the Sinai and the Red Sea makes a broad definition of the term "management" necessary. Management encompasses the whole spectrum: from recognition of the need for a hyperbaric facility, establishing one, education of dive center management, instructors, boat skippers and deck hands, to actual contingency plans set according to the different geographical sites. The essential elements of communication, oxygen first aid, transportation, and actual recompression therapy or other treatments and follow-up must be included. Furthermore, a link to the international organisations involved with diving accident management is an essential and desired backup.

Accident Prevention↗

Changes in spectral reflectance of wheat leaves in response to specific macronutrient deficiency.

In wheat (Triticum aestivum L.) plants, deficiency of an essential element may drastically affect growth, appearance, and most importantly yield. Wheat, the focus of this study, is one of the crops studied in the CELSS program. Information about nutrient deficiencies in crops grown in controlled environment is essential to optimize food productivity. The main objective of this study was to determine whether deficiency of Nitrogen (N), Phosphorus (P), Potassium (K), Calcium (Ca) and Magnesium (M) alters spectral reflectance properties of wheat leaves. Plants were grown in the greenhouse and growth chamber, in a modified Hoagland's nutrient solution. Spectral reflectance of fully expanded wheat leaves from 280 to 1100 nm, nutrient concentrations (N, P, K, and Ca) and chlorophyll (Chl) were determined when deficiency symptoms were first evident (approximately 6-7 weeks). Chlorophyll content and fresh and dry weight, were used to assess the severity of the nutrient stress. All nutrient deficiencies affected chlorophyll content and generally increased reflectance in the visible (VIS) 400-700 nm and infrared (IR) 700-1100 nm ranges. Magnesium and nitrogen deficiencies had the most pronounced effect on chlorophyll concentration height, and reflectance. All macronutrient deficiencies tested reduced chlorophyll concentration, increase reflectance in the visible range and caused a shift in the position of the red edge (the point of maximum slope on the reflectance spectrum of vegetation between red and near-infrared wavelengths) toward shorter or longer wavelengths; depending upon the element. In the greenhouse, N and Mg induced the greatest increase in reflectance of 33% and 25% in the VI range and 86% and 53% in the IR range, respectively. However, in the growth chamber, an increase of 97% and 25% occurred in the VI range, and 20% and 33% in the IR range, respectively. In the IR range in the growth chamber, P, K, and Ca deficiency caused a reduction in reflectance (412-770 nm). This research indicates that mineral deficiencies and reflectance are not specific to one environment and could have important implications for the design of CELSS in space, and perhaps the future of terrestrial agriculture.

Biomass↗

Sp1 is essential for estrogen receptor alpha gene transcription.

The exact molecular mechanisms regulating estrogen receptor (ER)alpha expression in breast tumors are unclear, but studies suggest that the regulation is at least partly transcriptional. We therefore undertook a detailed analysis of ERalpha promoter activity in a number of breast cancer cell lines. We find that the majority of ERalpha promoter activity lies within the first 245bp of the 5'-flanking region of the gene. Three elements essential for full ERalpha promoter transcriptional activity were identified within the -245 to -192bp region in transient transactivation assays using linker-scanner mutation analysis. These three elements include two binding sites for the Sp1 family of transcription factors as well as a non-consensus E box. We show that both Sp1 and Sp3 bind to this region using electrophoretic mobility shift assays. Exogenous expression of Sp1 or Sp3 in Sp1/3-negative Drosophila Schneider SL2 cells results in transactivation of the -245 to +212bp fragment of the ERalpha promoter. These data demonstrate that transcription of ERalpha is dependent upon the expression of members of the Sp1 family.

Animals↗

Genetic analysis of the minimal replicon of the Lactococcus lactis subsp. lactis biovar diacetylactis citrate plasmid.

Using a combination of mutagenesis with the transposon gamma delta and polymerase chain reaction subcloning, the essential elements of the replication region of the Lactococcus lactis subsp. lactis biovar diacetylactis citrate plasmid have been identified. An open reading frame, coding for a protein with homology to Rep proteins from other Lactococcus plasmids, is essential. This protein is trans-acting and could not be replaced by the Rep protein from another Lactococcus plasmid. A second open reading frame immediately downstream from the first could be removed or inactivated with no apparent effect on plasmid replication. A region containing two 10 bp direct repeats and three tandem repeats of a 22 bp sequence, immediately upstream of the essential open reading frame, is also essential and probably includes the origin of replication. A 181-bp DNA fragment containing this region was sufficient to allow replication in Lactococcus if the trans-acting protein was provided on another replicon. Single-stranded replication intermediates could not be detected, suggesting that the citrate plasmid uses theta replication rather than rolling-circle replication.

Amino Acid Sequence↗

Chromium, lead and cadmium in Danish milk products and cheese determined by Zeeman graphite furnace atomic absorption spectrometry after direct injection or pressurized ashing.

A method for the direct determination of chromium in homogeneous samples of milk and milk products is described. Minimum sample handling and prevention of contamination was given priority. After injection of the sample into the graphite furnace, the sample was ashed in a stream of oxygen at 650 degrees C and then further ashed at 1,100 degrees C with argon as the purge gas. Zeeman background correction was used in the atomisation step at 2,300 degrees C. The detection limit was 0.7 ng/g. Direct detection of chromium in milk, using only argon as purge gas, was inferior. Non-homogeneous and solid samples, e.g. yoghurt with fruit jam and cheese, were ashed under pressure with nitric acid before analysis. The same analytical principle as used for chromium was also used for the analysis of lead and cadmium in the samples. Analytical quality control was performed for both methods and the results are reported. The results for lead, cadmium and chromium in Danish milk and milk products were in the parts per billion or parts per trillion range and compare well with literature data. The intake of lead, cadmium and chromium from milk and milk products is less than 4% of the total Danish dietary intake of these elements. It is concluded that the contribution from milk and milk products to the total intake of lead and cadmium is toxicologically insignificant and that milk and milk products are only a minor source of the essential element chromium.

Animals↗