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Current and evolving strategies for colorectal cancer screening.

BACKGROUND: Colorectal cancer is a major cause of cancer mortality and morbidity. Screening can potentially prevent most colorectal cancers by detection and removal of precursor adenomas. METHODS: The literature and clinical practice guidelines are reviewed, with an emphasis on advances of the last 10 years and evolving screening methods. RESULTS: Colonoscopy has come to be used for screening in persons at average risk for colorectal cancer because of the comparative ineffectiveness of other methods, although these methods continue to be recommended. Virtual colonoscopy and fecal DNA testing are emerging technologies with promise to be more effective than fecal occult blood testing or sigmoidoscopy in selecting those persons who should undergo colonoscopy. Next to age, family history is the most common risk factor for colorectal cancer and one that warrants more aggressive screening and, in some instances, genetic counseling and testing. Hereditary nonpolyposis colorectal cancer accounts for as many as 1 in 20 colorectal cancers, but to take advantage of recent advances in genetic testing for this disorder, a high level of clinical suspicion must be maintained. CONCLUSIONS: If we are to reduce mortality and morbidity from colorectal cancer, practicing clinicians need to be aware of current and evolving strategies for colorectal screening, and assertively recommend the appropriate strategy to their patients.

Colonography, Computed Tomographic↗

No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly.

BACKGROUND: It has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function. In agreement with this hypothesis, recent work has shown a negative correlation between evolutionary rates and the number of protein-protein interactions. However, the extent to which the number of protein-protein interactions influences evolutionary rates remains unclear. Here, we address this question at several different levels of evolutionary relatedness. RESULTS: Manually curated data on the number of protein-protein interactions among Saccharomyces cerevisiae proteins was examined for possible correlation with evolutionary rates between S. cerevisiae and Schizosaccharomyces pombe orthologs. Only a very weak negative correlation between the number of interactions and evolutionary rate of a protein was observed. Furthermore, no relationship was found between a more general measure of the evolutionary conservation of S. cerevisiae proteins, based on the taxonomic distribution of their homologs, and the number of protein-protein interactions. However, when the proteins from yeast were assorted into discrete bins according to the number of interactions, it turned out that 6.5% of the proteins with the greatest number of interactions evolved, on average, significantly slower than the rest of the proteins. Comparisons were also performed using protein-protein interaction data obtained with high-throughput analysis of Helicobacter pylori proteins. No convincing relationship between the number of protein-protein interactions and evolutionary rates was detected, either for comparisons of orthologs from two completely sequenced H. pylori strains or for comparisons of H. pylori and Campylobacter jejuni orthologs, even when the proteins were classified into bins by the number of interactions. CONCLUSION: The currently available comparative-genomic data do not support the hypothesis that the evolutionary rates of the majority of proteins substantially depend on the number of protein-protein interactions they are involved in. However, a small fraction of yeast proteins with the largest number of interactions (the hubs of the interaction network) tend to evolve slower than the bulk of the proteins.

Bacterial Proteins↗

Evolving principles of surgical management and prognostic factors for outcome in renal cell carcinoma.

The generally accepted principles for the surgical management of renal cell carcinoma (RCC) were first described more than 30 years ago. Since then, much has changed in the understanding of the basic biology and genetics of kidney cancer. Improvements in cross-sectional imaging has allowed for more accurate preoperative clinical staging of renal tumors, and the necessity of completing all the components of the radical nephrectomy have been questioned. Surgical techniques have also evolved, and technology has advanced to make possible new methods of managing renal tumors. The TNM staging system is currently the most extensively used system to provide prognostic information for RCC. However, data published in the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors. Furthermore, the recent discovery of molecular tumor markers are expected to revolutionize the staging of RCC and lead to the development of new therapies based on molecular targeting. This review will examine the evolving principles in the surgical management of RCC as well as provide an update on current staging modalities and prognostic factors.

Carcinoma, Renal Cell↗

Complementarity theory: why human social capacities evolved to require cultural complements.

This article introduces complementarity theory, which explains the psychology of cultural diversity as a product of evolved social proclivities that enable-and require-people to coordinate action in culture-specific ways. The theory presents evolutionary processes and psychological mechanisms that may account for the cultural variability of social coordination devices such as language, relational models, rituals, moral interpretations of misfortune, taboos, religion, marriage, and descent systems. Human fitness and well-being depend on social coordination characterized by complementarity among the participants' actions. This complementarity is based primarily on coordination devices derived from the conjunction of cultural paradigms and specific, highly structured, evolved proclivities. The proclivities have no adaptive value without the paradigms, and the paradigms have no meaning without the proclivities. They are coadapted to function together. Operating in conjunction with each other, proclivities and paradigms jointly define the generative structures for meaningful coordination of social interaction in each particular culture.

Journal Article↗

Reconsidering evolved sex differences in jealousy: comment on Harris (2003).

In a recent article, Harris (2003) concluded that the data do not support the existence of evolved sex differences in jealousy. Harris' review correctly identifies fatal flaws in three lines of evidence (spousal abuse, homicide, morbid jealousy), but her criticism of two other lines of evidence (self-report responses, psychophysiological measures) is based, in part, on a mischaracterization of the evolutionary psychological theory and a misunderstanding of the empirical implications of the theory. When interpreted according to the correct criterion (i.e., an interaction between sex and infidelity type), self-report studies (both forced-choice and non-forced choice) offer strong support for the existence of sex differences in jealousy. Psychophysiological data also offer some support, although these data are weakened by validity-related concerns. In addition, some refutational evidence cited by Harris (responses to real infidelity, responses under cognitive load) actually does not refute the theory. An integrative model that describes how jealousy might result from the interaction of sociocultural variables and evolved sex differences and suggestions for future research directions are discussed.

Arousal↗

Evolving neural models of path integration.

We use a genetic algorithm to evolve neural models of path integration, with particular emphasis on reproducing the homing behaviour of Cataglyphis fortis ants. This is done within the context of a complete model system, including an explicit representation of the animal's movements within its environment. We show that it is possible to produce a neural network without imposing a priori any particular system for the internal representation of the animal's home vector. The best evolved network obtained is analysed in detail and is found to resemble the bicomponent model of Mittelstaedt. Because of the presence of leaky integration, the model can reproduce the systematic navigation errors found in desert ants. The model also naturally mimics the searching behaviour that ants perform once they have reached their estimate of the nest location. The results support possible roles for leaky integration and cosine-shaped compass response functions in path integration.

Algorithms↗

Physiological mechanisms of evolved desiccation resistance in Drosophila melanogaster.

We investigated physiological characters associated with water balance in laboratory populations of Drosophila melanogaster selected for resistance to desiccating conditions for over 100 generations. Five replicate, outbred, desiccation-selected (D) populations were compared with their control (C) populations. Water loss rates of female D flies were approximately 40% lower than those of C females. Although excretory water loss was reduced in desiccation-selected flies, it comprised less than 10% of total water loss, indicating that the D populations have evolved reduced cuticular and/or respiratory water loss rates. Total surface lipid amounts did not differ between the C and D flies. Cuticular hydrocarbons from D flies were longer than those from C flies and melted at slightly higher temperatures, possibly contributing to reduced water loss rates. Desiccation-selected flies contained approximately 30% more bulk water than controls, as well as more glycogen. However, total metabolic water stores did not differ between the stocks owing to higher lipid levels in the C populations. The ability to tolerate water loss, as measured by water content at the time of death, did not differ between D and C flies. Thus, evolution of increased desiccation resistance has occurred by multiple physiological mechanisms, but some potential adaptive differences have not evolved.

Animals↗

Evolvability of the mode of peptide binding by an RNA.

The HIV Rev-response element (RRE) RNA binds strongly to two unrelated peptides, the HIV Rev peptide and an RRE-binding aptamer, the RSG-1.2 peptide, at a similar site, but using distinct sets of interactions. In this study, the nucleotide base requirements for the binding of the RRE to the Rev and RSG-1.2 peptides were determined by selection of Rev- and RSG-1.2-binding RRE variants using a bacterial reporter system. As a result, distinct differences in the bases necessary for binding the two peptides were found in the upper stem of the RRE. Strikingly, single nucleotide changes in this region were found to switch the peptide-binding specificity of the RRE from a bifunctional Rev- and RSG-1.2-binding mode to either a Rev-specific or a RSG-1.2- specific mode, demonstrating how an RNA can evolve alternative binding strategies in discrete steps without intermediate loss of function. This evolvability of the mode of peptide binding by an RNA presumably reflects the multidimensionality of conformational space that a given RNA has available for ligand recognition, which may have been utilized in the evolution of RNA-polypeptide complexes.

Electrophoresis, Polyacrylamide Gel↗

Steady-state kinetic characterization of evolved biphenyl dioxygenase, which acquired novel degradation ability for benzene and toluene.

Biphenyl dioxygenase (Bph Dox) catalyzes initial oxygenation in the bacterial biphenyl degradation pathway. Bph Dox in Pseudomonas pseudoalcaligenes KF707 is a Rieske type three-component enzyme in which a large subunit (encoded by the bphA1 gene) plays an important role in the substrate specificity of Bph Dox. Steady-state kinetic assays using purified enzyme components demonstrated that KF707 Bph Dox had a kcat/Km of 33.1 x 10(3) (M(-1) s(-1)) for biphenyl. Evolved 1072 Bph Dox generated by the process of DNA shuffling (Suenaga, H. et al., J. Bacteriol., 184, 3682-3688 (2002)) exhibited enhanced degradation activity not only for biphenyl (kcat/Km of 62.2 x 10(3) [M(-1) s(-1)]) but also for benzene and toluene, compounds that are rarely attacked by KF707 Bph Dox. These results suggest that evolved 1072 Bph Dox acquires higher affinities and catalytic efficiencies for various substrates than the original KF707 enzyme.

Benzene↗

Let regionalization continue to evolve.

This commentary provides a practical perspective on the benefits of regionalization within the context of the lead paper by Lewis and Kouri. Discussion of the best structure of health systems needs to take into account the reality that constitutional and funding responsibility--and therefore accountability--for our healthcare system lies with provincial governments. Accountability at the provincial government level is simply a part of regionalization and should be expected by health system managers. Regionalization of healthcare is in its infancy. Systems necessary to support regionalization, which can only be established under a regionalized structure (e.g., information technology, procurement, human resources and service planning), are evolving. Given the size and complexity of the healthcare system, as we gain more experience with regionalization the systems we need to support it will attain their potential, as will the managers of the system. Regionalization was the most appropriate option for healthcare in the 1990s given the objectives of provincial governments to achieve efficiencies, better utilize resources and improve patient care. We must allow regionalization to evolve in order to see long-term improvements in the healthcare system.

Canada↗

"Religion is the finding thing": an evolving spirituality in late life.

This paper discusses some important dimensions of faith and of the social contexts surrounding faith that are illustrative of continuity and growth in spirituality in the lives of older adults. Examples of an evolving spirituality emerge in the analysis of a recent qualitative research study that probed the nature of religious experience among thirty-one community-dwelling elders and fifteen elders residing in long-term care facilities. Face-to-face interviews with these forty-six older adults and with seven people who directed or assisted with formal and informal programs of faith comprise the empirical base for this paper. The seven people, I refer to them mnemonically as faithreps, worked in various ways in the long-term care settings to provide programs involving faith to older adults. The faithreps came from a range of educational and religious backgrounds and are not accurately or handily categorized. An evolving spirituality is shaped by the older person's links to the structural and the socio-relational contexts that have been created through interaction in the past as well as through interaction in the present. Moreover, the interaction of older adults and faithreps encourages spiritual growth because as social actors engaged with one another over a sustained period of time in an institutional setting, questions and dialogue about life and its meaning are regularly evoked. The social interactions that foster spiritual evolution may be an admixture of the secular and the sacred. Such socio-relational contexts were once part of the naturalistic settings of daily life among the old, but now must emerge through the efforts and planning of others. The salience of faith among present cohorts of older adults sensitizes us to the necessity of devoting more consideration to optimal ways of strengthening and building contexts that are conducive to the evolution of spirituality.

Aged↗

Integrated perspective of evolving intrapsychic and person-environment functions: implications for deaf and hard of hearing individuals.

The authors review and integrate certain diverse theories to explain and suggest appropriate interventions for difficulties in socioemotional functioning experienced by many deaf persons. These diverse perspectives include a hierarchical circular systems approach, psychosocial stage theory, social learning theory, and representational models, or evolving expectancies of others. These perspectives, which can facilitate understanding of social behaviors and development and lead to improved interventions, provide background for a 3-level model proposed in the article. The model focuses on the relationship between the deaf person and the proximal social environment. The model's first level takes into account intrapsychic processes such as self-concept; the second highlights reciprocal interactions between the person and the social environment. The third describes the resulting memories and expectancies that develop and evolve and that influence the person's previous intrapsychic thoughts, feelings, and perceptions. These, in turn, affect social interactions, in a recurrent, spiraling fashion. This hierarchical model can be used as a framework for concurrent or sequential interventions with Deaf people.

Affect↗

Bordetella pertussis, the causative agent of whooping cough, evolved from a distinct, human-associated lineage of B. bronchiseptica.

Bordetella pertussis, B. bronchiseptica, B. parapertussis(hu), and B. parapertussis(ov) are closely related respiratory pathogens that infect mammalian species. B. pertussis and B. parapertussis(hu) are exclusively human pathogens and cause whooping cough, or pertussis, a disease that has resurged despite vaccination. Although it most often infects animals, infrequently B. bronchiseptica is isolated from humans, and these infections are thought to be zoonotic. B. pertussis and B. parapertussis(hu) are assumed to have evolved from a B. bronchiseptica-like ancestor independently. To determine the phylogenetic relationships among these species, housekeeping and virulence genes were sequenced, comparative genomic hybridizations were performed using DNA microarrays, and the distribution of insertion sequence elements was determined, using a collection of 132 strains. This multifaceted approach distinguished four complexes, representing B. pertussis, B. parapertussis(hu), and two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Of the two B. bronchiseptica complexes, complex IV was more closely related to B. pertussis. Of interest, while only 32% of the complex I strains were isolated from humans, 80% of the complex IV strains were human isolates. Comparative genomic hybridization analysis identified the absence of the pertussis toxin locus and dermonecrotic toxin gene, as well as a polymorphic lipopolysaccharide biosynthesis locus, as associated with adaptation of complex IV strains to the human host. Lipopolysaccharide structural diversity among these strains was confirmed by gel electrophoresis. Thus, complex IV strains may comprise a human-associated lineage of B. bronchiseptica from which B. pertussis evolved. These findings will facilitate the study of pathogen host-adaptation. Our results shed light on the origins of the disease pertussis and suggest that the association of B. pertussis with humans may be more ancient than previously assumed.

Journal Article↗

Inflammatory mediators in BAL fluid as markers of evolving pneumonia in leukocytopenic patients.

STUDY OBJECTIVES: Pneumonia during chemotherapy-induced leukocytopenia is a major cause of overall treatment failure in patients with hematologic malignancies. To improve outcome in these high-risk patients, early diagnosis of pulmonary infiltrates and institution of adequate antimicrobial treatment are mandatory. To identify patients with evolving pneumonia, we have prospectively studied the prognostic value of cytokine and complement measurements in early BAL samples from febrile leukocytopenic patients. DESIGN: Prospective, comparative study. SETTING: Hematology/oncology section of a university hospital. PATIENTS: Twenty-one patients with leukocytopenia (WBC count < 1.000/microL) following cytoreductive chemotherapy for malignant disorders. INTERVENTION: Early BAL sampling primarily for microbiologic diagnostic purposes. MEASUREMENTS AND RESULTS: Proinflammatory cytokines and activated complement components were measured in the BAL aspirates and the results were related to the prevalence or subsequent evolution of overt pneumonia. Of the 21 patients studied, 10 patients presented with overt pneumonia at BAL sampling (group A), 5 patients developed objective signs of pneumonia 3 to 5 days after BAL (group B), and 6 patients remained free of pneumonia during follow-up (group C). In comparison with group C, patients in groups A and B both had distinctly elevated bronchoalveolar levels of tumor necrosis factor-alpha, interleukin-6, granulocyte colony-stimulating factor, C3a, and C5a. CONCLUSIONS: Cytokine and complement determinations in early BAL samples may aid in the identification of febrile leukocytopenic patients with evolving pneumonia 3 to 5 days prior to the manifestation of diagnostic clinical and radiographic signs.

Adult↗

Isolation of photosystem II-enriched membranes and the oxygen-evolving complex subunit proteins from higher plants.

Methods for the isolation of highly active oxygen-evolving photosystem (PS)II membranes from higher plants and the purification of the oxygen-evolving complex (OEC) subunits are described. Membrane samples used as the material for various in vitro studies of PSII are prepared by solubilization of thylakoid membranes with the non-ionic detergent Triton X-100. The OEC subunit proteins are dissociated from the PSII-enriched membranes by alkaline treatment or salt treatment, and then purified by ion-exchange chromatography using an automated high-performance liquid chromatography system.

Buffers↗

Evolving eyes.

Despite the incredible diversity among extant eyes, laws of physics constrain how light can be collected resulting in only eight known optical systems in animal eyes. Surprisingly, all animal eyes share a common molecular strategy using opsin for catching photons, but there are a diverse collection of mechanisms with proteins unrelated to each other used to focus light for vision. However, opsin is expressed in either one of two types of photoreceptor that differ fundamentally in their structure and tissue of origin. Taken together, this collection of observations strongly suggests that eyes have had multiple origins with remarkable convergence due to physics and molecular conservation of the opsin protein. Yet recent work has shown that a family of conserved genes are involved in eye formation despite substantial differences in their structure and origin, leading to a controversy over whether eyes evolved once or repeatedly. A likely resolution of this discussion is that particular genes and genetic programs have become associated with specific features needed for eyes and such suites of genes have been recruited as new eyes evolve. Since specific genes and their products are used repeatedly, it is somewhat difficult to conceptualize their causal relationships relative to evolutionary processes. However, detailed comparison of developmental programs may offer clues about multiple origins.

Animals↗

Evolving treatment strategies for chronic refractory angina.

Chronic refractory angina is a term used to describe patients who, despite optimal medical therapy, have both angina and objective evidence of ischaemia. It is estimated that 5-15% of the 12 million patients with chronic angina in the US meet the criteria for having refractory angina. This review focuses on the following evolving pharmacological therapies for chronic refractory angina: L-arginine, ivabradine, ranolazine, nicorandil and trimetazidine. Evolving devices and invasive procedures including enhanced external counterpulsation, spinal cord stimulation, and transmyocardial revascularisation are also briefly discussed.

Acetanilides↗

Calcium exchange and structural changes during the photosynthetic oxygen evolving cycle.

PSII catalyzes the oxidation of water and reduction of plastoquinone in oxygenic photosynthesis. PSII contains an oxygen-evolving complex, which is located on the lumenal side of the PSII reaction center and which contains manganese, calcium, and chloride. Four sequential photooxidation reactions are required to generate oxygen. This process produces five Sn-states, where n refers to the number of oxidizing equivalents stored. Calcium is required for oxygen production. Strontium is the only divalent cation that replaces calcium and maintains activity. In our previous FT-IR work, we assessed the effect of strontium substitution on substrate-limited PSII preparations, which were inhibited at the S3 to S0 transition. In this work, we report reaction-induced FT-IR studies of hydrated PSII preparations, which undergo the full S-state cycle. The observed difference FT-IR spectra reflect long-lived photoinduced conformational changes in the oxygen-evolving complex; strontium exchange identifies vibrational bands sensitive to substitutions at the calcium site. During the S1' to S2' transition, the data are consistent with an electrostatic or structural perturbation of the calcium site. During the S3' to S0' and S0' to S1' transitions, the data are consistent with a perturbation of a hydrogen bonding network, which contains calcium, water, and peptide carbonyl groups. To explain our data, persistent shifts in divalent cation coordination must occur when strontium is substituted for calcium. A modified S-state model is proposed to explain these results and results in the literature.

Calcium↗