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PubMed2005

Mitotic-exit control as an evolved complex system.

The exit from mitosis is the last critical decision during a cell-division cycle. A complex regulatory system has evolved to evaluate the success of mitotic events and control this decision. Whereas outstanding genetic work in yeast has led to rapid discovery of a large number of interacting genes involved in the control of mitotic exit, it has also become increasingly difficult to comprehend the logic and mechanistic features embedded in the complex molecular network. Our view is that this difficulty stems in part from the attempt to explain mitotic-exit control using concepts from traditional top-down engineering design, and that exciting new results from evolutionary engineering design applied to networks and electronic circuits may lend better insights. We focus on four particularly intriguing features of the mitotic-exit control system and attempt to examine these features from the perspective of evolutionary design and complex system engineering.

Biological Evolution↗

PubMed2004

The evolving role of genomics in shaping care for persons with dementia.

Alzheimer's disease and other chronic dementing conditions remain formidable challenges for individuals, their families, and health care providers. In addition to the challenges inherent in the sheer numbers affected, the complex and relatively unpredictable progression of these disorders complicates the delivery of interventions for health care providers. Identifying genetic and environmental etiologic factors and understanding their relationship to the natural history of dementia brings health care providers closer to more effective pharmacologic treatments and perhaps cure. In the meantime, genomics research brings professional nurses closer to providing more specific, perhaps individualized, anticipatory guidance and to providing nonpharmacologic interventions in a genotype-directed way to patients with chronic dementing conditions. The emergence of a genomics-based health care environment presents an opportunity and a challenge for gerontological nurse clinicians, educators, and researchers--an opportunity to evolve practice toward a higher level of specificity and effectiveness and a challenge to do so in a equitable and sensitive manner that improves health and quality of life for all served.

Aged↗

PubMed2006

Sex determination: ways to evolve a hermaphrodite.

Most species of the nematode genus Caenorhabditis reproduce through males and females; C. elegans and C. briggsae, however, produce self-fertile hermaphrodites instead of females. These transitions to hermaphroditism evolved convergently through distinct modifications of germline sex determination mechanisms.

Animals↗

PubMed2006

Ephemeral profiles of prescription drug and formulation tampering: evolving pseudoscience on the Internet.

The magnitude of non-therapeutic use, or misuse of prescription pharmaceuticals now rivals that of illicit drug abuse. Drug and formulation tampering enables misusers to administer higher doses by intended and non-intended routes. Perceived motives appear to be a combination of interests in achieving a faster onset and enhancing psychoactive effects. Narcotic analgesics, stimulants, and depressants are widely sought, examined, and tampered with for recreational use. This review examines tampering methods reported on the Internet for selected pharmaceutical products. The Internet provides broad and varied guidance on tampering methods that are specific to drug classes and unique formulations. Instructions are available on crushing, separating, purifying and chemically altering specific formulations to allow changes in dosage, route of administration, and time course of effects. Many pharmaceutical formulations contain features that serve as "barriers" to tampering. The nature and effectiveness of formulation barriers vary widely with many being overcome by adventurous misusers. Examples of successes and failures in tampering attempts are frequently described on Internet sites that support recreational drug use. Successful tampering methods that have widespread appeal evolve into recipes and become archived on multiple websites. Examples of tampering methods include: (1) how to separate narcotic drugs (codeine, hydrocodone, oxycodone) from excipients and non-desirable actives (aspirin, acetaminophen, ibuprofen); (2) overcoming time-release formulations (beads, layers, matrices); (3) removal of active drug from high-dose formulations (patches, pills); (4) alteration of dosage forms for alternate routes of administration. The development of successful formulations that inhibit or prevent drug/formulation tampering with drugs of abuse should take into consideration the scope and practice of tampering methods available to recreational drug users on the Internet.

Chemistry, Pharmaceutical↗

PubMed2026

Policy pathways and historical insights: Canada's evolving approach to psychedelic access for end-of-life distress.

Canada's evolving attitudes toward psychedelic interventions in palliative and end-of-life care reflect a departure from historically prohibitionist policies and an emerging recognition of their therapeutic potential for individuals facing end-of-life distress. This shift parallels international regulatory developments in jurisdictions such as the United States, Australia and parts of Europe, where cautious policy liberalization has signaled growing acceptance of psychedelics within clinical contexts. Canada is also a relevant case because of its formative role in the development of modern palliative care, its contemporary frameworks emphasizing holistic approaches to suffering at the end of life, and its experience with medical assistance in dying, all of which have shaped national conversations about suffering, autonomy, and end-of-life care. Additionally, Canada's distinctive historical approach to drug regulation-marked by federal flexibility, mechanisms for compassionate access, and responsiveness to patient advocacy-combined with rising public demand and incremental provincial changes, may uniquely position the country along a transitional pathway toward clinical integration of psychedelics in palliative care. At the same time, Canadian drug policy remains heterogeneous across substances and provinces, underscoring the political contingency of reform. Within this dynamic landscape, Canada's psychedelic drug policy trajectory aligns with broader international trends toward cautious medicalization and regulated access to psychedelic therapies, while also offering an instructive case for how end-of-life frameworks and federal-provincial governance shape policy development.

Humans↗

PubMed2005

Prospective randomised study of endovenous radiofrequency obliteration (closure) versus ligation and vein stripping (EVOLVeS): two-year follow-up.

PURPOSE: To study intermediate clinical outcomes, rates of recurrent varicosities and neovascularisation, ultrasound changes of the GSV, and the quality of life changes in patients from EVOLVeS trial. METHODS: Forty five patients were re-examined 1 year and 65 two years after treatment. Follow-up visits included clinical examination with CEAP classification and calculation of venous clinical severity score (VCSS), ultrasound examination, and a quality of life questionnaire. RESULTS: The clinical course of the disease (CEAP, VCSS) was similar in the two treatment groups. 51% of the GSV trunks occluded by RFO underwent progressive shrinkage with the external diameter decreased from 6.3 SD 1.4 mm at 72 h after treatment to 2.9 SD 1.5 mm at 2 years. An additional 41% of the GSV became undetectable by ultrasound at 2-year follow up. In two patients we observed re-opening of an initially closed GSV lumen. Neovascularisation was found in one RFO case and in four S and L cases. Cumulative rates of recurrent varicose veins at combined 1 and 2 years follow-up were 14% for RFO and 21% for S and L (NS). The difference in global QOL score in favour of RFO re-appeared at 1 year and remained significant at 2 years after treatment. CONCLUSION: The 2-year clinical results of radiofrequency obliteration are at least equal to those after high ligation and stripping of the GSV. In the vast majority of RFO patients the GSV remained permanently closed, and underwent progressive shrinkage to eventual sonographic disappearance. Recurrence and neovascularisation rates were similar in the two groups although limited patient numbers prevent reliable statistical analysis. Improved quality of life scores persisted through the 2-year observations in the RFO group compared to the S and L group.

Angioplasty↗

PubMed2005

Robustness, evolvability, and neutrality.

Biological systems, from macromolecules to whole organisms, are robust if they continue to function, survive, or reproduce when faced with mutations, environmental change, and internal noise. I focus here on biological systems that are robust to mutations and ask whether such systems are more or less evolvable, in the sense that they can acquire novel properties. The more robust a system is, the more mutations in it are neutral, that is, without phenotypic effect. I argue here that such neutral change--and thus robustness--can be a key to future evolutionary innovation, if one accepts that neutrality is not an essential feature of a mutation. That is, a once neutral mutation may cause phenotypic effects in a changed environment or genetic background. I argue that most, if not all, neutral mutations are of this sort, and that the essentialist notion of neutrality should be abandoned. This perspective reconciles two opposing views on the forces dominating organismal evolution, natural selection and random drift: neutral mutations occur and are especially abundant in robust systems, but they do not remain neutral indefinitely, and eventually become visible to natural selection, where some of them lead to evolutionary innovations.

Animals↗

PubMed2006

How do obligate parasites evolve? A multi-gene phylogenetic analysis of downy mildews.

Plant parasitism has independently evolved as a nutrition strategy in both true fungi and Oomycetes (stramenopiles). A large number of species within phytopathogenic Oomycetes, the so-called downy mildews, are defined as obligate biotrophs since they have not, to date, been cultured on any artificial medium. Other genera like Phytophthora and Pythium can in general be cultured on standard or non-standard agar media. Within all three groups there are many important plant pathogens responsible for severe economic losses as well as damage to natural ecosystems. Although they are important model systems to elucidate the evolution of obligate parasites, the phylogenetic relationships between these genera have not been clearly resolved. Based on the most comprehensive sampling of downy mildew genera to date and a representative sample of Phytophthora subgroups, we inferred the phylogenetic relationships from a multi-gene dataset containing both coding and non-coding nuclear and mitochondrial loci. Phylogenetic analyses were conducted under several optimality criteria and the results were largely consistent between all the methods applied. Strong support is achieved for monophyly of a clade comprising both the genus Phytophthora and the obligate biotrophic species. The facultatively parasitic genus Phytophthora is shown to be at least partly paraphyletic. Monophyly of a cluster nested within Phytophthora containing all obligate parasites is strongly supported. Within the obligate biotrophic downy mildews, four morphologically or ecologically well-defined subgroups receive statistical support: (1) A cluster containing all species with brownish-violet conidiosporangia, i.e., the genera Peronospora and Pseudoperonospora; (2) a clade comprising the genera with vesicular to pyriform haustoria (Basidiophora, Benua, Bremia, Paraperonospora, Plasmopara, Plasmoverna, Protobremia); (3) a group containing species included in Hyaloperonospora and Perofascia which almost exclusively infect Brassicaceae; (4) a clade including the grass parasites Viennotia oplismeni and Graminivora graminicola. Phylogenetic relationships between these four clades are not clearly resolved, and neither is the position of Sclerospora graminicola within the downy mildews. Character analysis indicates an evolutionary scenario of gradually increasing adaptation to plant parasitism in Peronosporales and that at least the most important of these adaptive steps occurred only once, including major host shifts within downy mildews.

Animals↗

PubMedDate not supplied

Evolving models of Geriatric Nursing care.

Outcomes of care improve when older patients are cared for by nurses with demonstrated competence in geriatrics and in environments that structure nursing care around the needs of older adults. The past twenty years has seen the development of a number of exciting new nursing models in the delivery of care for older adults. This article highlights some of these evolving models of nursing practice in assisted living, home care, hospitals, and nursing homes.

Aged↗

PubMed2007

Evolving role of self-expanding metal stents in the treatment of malignant dysphagia and fistulas.

BACKGROUND: Self-expanding metal stents (SEMS) are touted as the cornerstone of endoscopic palliation of unresectable esophageal cancer. However, usage at MD Anderson has fallen in recent years, despite a greater volume of patients with esophageal cancer. OBJECTIVE: To compare our more recent experience with that of earlier reported institutional experience and to assess how esophageal stent use has evolved. DESIGN: A retrospective chart review. SETTING: A tertiary referral cancer center. PATIENTS: Ninety-seven patients with malignant dysphagia who had SEMS placed from 2000 to 2003. INTERVENTIONS: Placement of SEMS for malignant disease. MAIN OUTCOMES MEASUREMENTS: Dysphagia scores, overall survival, and complication rates. RESULTS: Dysphagia scores improved in 86%, and tracheoesophageal fistula symptoms improved in 90%. Complications were seen in a majority of the patients and major complications in 37%. Ten patients had hematemesis, migrations occurred in 5, and early unexpected deaths in 2. Adenocarcinoma and female sex were factors associated with increased odds of a major complication. Prior chemoradiation, age, stricture location, and length were not associated with complications. Median survival was 77 days. LIMITATIONS: Noncomparative retrospective single-center study. CONCLUSIONS: SEMS fall short of an ideal palliative method, because complications that require additional intervention are frequent. Usage has declined despite higher numbers of patients with esophageal cancer. However, for patients with tracheoesophageal fistulas, SEMS are the treatment of choice. For patients who are not candidates for chemoradiation or who failed to achieve adequate palliation with such therapy, SEMS offer a viable, albeit imperfect, endoscopic approach.

Adenocarcinoma↗

PubMed2004

China's evolving health care market: how doctors feel and what they think.

This paper reports on a questionnaire survey and 12 focus groups conducted among doctors in three provinces of China, namely Guangdong, Shanxi, and Sichuan. The survey (N = 720) and focus group participants were drawn from both rural and urban areas, as well as public and private sectors, in equal numbers The aim was to gauge how Chinese doctors feel about themselves and what they think of the Chinese health care system. We found low satisfaction levels with own income (8%), job (27%), skill (30%), and other important aspects of their professional life. The health care system received only 32% approval rating. Quality of care and patient safety issues were major concerns, especially in the growing but poorly regulated private sector. The public sector came under criticism for its high fees and bad service quality. The feedback point to the need for an appropriate regulatory framework to guide the development of China's evolving health care market. A revitalized medical profession that is fully engaged in the reform process could also significantly impact the success of ongoing health care reform efforts.

Attitude of Health Personnel↗

PubMed2004

Metachronous squamous cell carcinomas evolving from independent oropharyngeal and pulmonary squamous papillomas: association with human papillomavirus 11 and lack of aberrant p53, Rb, and p16 protein expression.

Squamous cell carcinoma evolving from squamous papilloma in both the upper and lower respiratory tract in the same patient is uncommon. The molecular mechanisms underlying the progression have not been well investigated. We herein describe a case of squamous cell carcinoma arising from respiratory papilloma in two independent occasions. The patient initially had oropharyngeal squamous cell carcinoma arising in a squamous papilloma at the age of 25 years. He subsequently developed squamous cell carcinoma in the left lower lobe of the lung, which was also associated with squamous papilloma, 8 years after the complete excision of the oropharyngeal lesion. Polymerase chain reaction-based broad-spectrum human papillomavirus DNA amplification and typing showed the presence of human papillomavirus type 11 DNA in both oropharyngeal and pulmonary tumors. Immunohistochemical studies showed that the expression status of p53, Rb, and p16 proteins was unaltered during tumor progression. These observations indicate that human papillomavirus 11-associated neoplastic transformation and tumor progression in the respiratory tract may not involve aberrant regulation of the p53 and Rb signaling pathways.

Adult↗

PubMed2004

Pemphigus foliaceus with neutrophilic spongiosis evolving to an atypical pemphigus phenotype.

A 46-year-old Brazilian man, with initial pustular lesions, neutrophilic spongiosis and subcorneal cleavage evolved to an atypical pemphigus phenotype, with suprabasal acantholysis. Interestingly, his autoantibody profile, tested by immunofluorescence, immunoblotting, enzyme-linked immunosorbent assay, and immunoprecipitation revealed exclusive IgG anti-desmoglein 1 antibodies in all phases of the disease.

Acantholysis↗

PubMed2004

The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure.

OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in atrial chamber remodeling was studied in a canine model of heart failure (HF). BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF. Studies of the structural mechanisms of cardiac remodeling have been limited to the left ventricle. The structural alterations associated with atrial chamber remodeling in evolving HF have not been studied. METHODS: Age- and weight-matched dogs were subjected to right ventricular pacing (240 beats/min) for one and three weeks to produce early and severe HF, respectively. Atrial tissues were assessed for myocyte and ECM changes. RESULTS: Right atrial and left atrial (LA) pressures were significantly increased in early and severe HF. The LA wall tension index was significantly increased at both HF stages by 116% and 443%, respectively. Atrial collagen synthesis and degradation were significantly increased in severe HF. Gelatinase activity was significantly increased at both early and severe stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)-9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was significantly correlated with gelatinase activity and collagen synthesis. Although total atrial collagen content was not changed, disarray of collagen fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was also present in severe HF. CONCLUSIONS: There is marked atrial chamber remodeling in canine pacing-induced HF, which is characterized by myocyte hypertrophy and dynamic collagen turnover. Atrial remodeling may contribute to the development of atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic target.

Animals↗

PubMed2006

Myocardial contrast echocardiography evolving as a clinically feasible technique for accurate, rapid, and safe assessment of myocardial perfusion: the evidence so far.

Intravenous myocardial contrast echocardiography (MCE) is a recently developed technique for assessment of myocardial perfusion. Up to now, many studies have demonstrated that the sensitivity and specificity of qualitative assessment of myocardial perfusion by MCE in patients with acute and chronic ischemic heart disease are comparable with other techniques such as cardiac scintigraphy and dobutamine stress echocardiography. Furthermore, quantitative parameters of myocardial perfusion derived from MCE correlate well with the current clinical standard for this purpose, positron emission tomography. Myocardial contrast echocardiography provides a promising and valuable tool for assessment of myocardial perfusion. Although MCE has been primarily performed for medical research, its implementation in routine clinical care is evolving. This article is intended to give an overview of the current status of MCE.

Acute Disease↗

PubMed2006

Evolving practice patterns in colon and rectal surgery.

BACKGROUND: Minimum numbers of cases required for certification by the American Board of Colon and Rectal Surgery (ABCRS) have been determined from a prospective database of all applicants applying for examination since 1989. These data represent the longitudinal evolution of practice patterns in tertiary colorectal training programs. STUDY DESIGN: After obtaining permission from the ABCRS, access to the database was obtained and data from the 12-year period 1994 to 2005 were analyzed. RESULTS: The database contains the operative and endoscopic case numbers of 673 residents. The number of training programs increased from 28 to 39 (28%) and the number of residency positions from 50 to 66 (24%). Median numbers of anorectal patients per resident remained remarkably constant over the period of study. Both rigid sigmoidoscopy (67 to 44 per resident) and flexible sigmoidoscopy (135.5 to 39 per resident) decreased substantially; colonoscopy volume increased (209 to 264 per resident). Perineal procedures for rectal prolapse consistently comprise 50% to 60% of the total procedures for prolapse. Low anterior resection for rectal cancer outnumber abdominoperineal resections by a 3/1 ratio. Coloanal anastomoses have steadily increased. Laparoscopic approaches for all abdominal operations have increased substantially, with the greatest increase being in diverticular resections (6.5% to 44.7%). CONCLUSIONS: Prospective data collection by ABCRS has permitted calculation of minimum numbers of operative cases for training colorectal surgeons, with the advantage of a rolling average that reflects evolving practice patterns in teaching programs. Analysis of these data allows planning of needs-based educational programs and may ultimately be involved in designing the maintenance of certification process.

Anal Canal↗

PubMed2004

Using the Surface Evolver to model droplet formation processes in membrane emulsification.

A model was developed to describe the droplet formation mechanism in membrane emulsification from the point of view of Gibbs free energy with the help of the Surface Evolver, which is an interactive finite element program for the study of interfaces shaped by surface tension. A program to test the model was written and run which allows the user to track the droplet shape as it grows, to identify the point of instability due to free energy, and thus predict droplet size. The inputs of the program are pore geometry, oil-aqueous phase interfacial tension, and contact angle. The model reasonably predicted droplet sizes for oblong-shaped pores under quiescent conditions where the force balance approach is not applicable. The model was validated against experimental conditions from the literature where the average error of the predictions compared to the mean droplet sizes was 8%.

Journal Article↗

PubMed2005

A troubled beginning: evolving concepts of an old arrhythmia.

The development of the sphygmograph in the nineteenth century marked the beginning of graphic registration of the arterial and venous pulse. Mackenzie, among other investigators, used this technique to study cardiac rhythm. In the early 20th century, Einthoven developed the electrocardiogram, which replaced the less sophisticated arterial and venous registrations of cardiac events and allowed for more detailed arrhythmia analysis. Interestingly, the early study of cardiac arrhythmias was obscured by misinterpretation. Specifically, atrial fibrillation stands out as a rhythm that was extensively studied though misconstrued in its early history. What follows is an in-depth consideration of the original investigations and evolving theories of this important arrhythmia.

Atrial Fibrillation↗