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PubMed2003

A computationally derived structural model of doxorubicin interacting with oligomeric polyalkylcyanoacrylate in nanoparticles.

We report a molecular simulation study of doxorubicin interacting within a frame of n-butyl polycyanoacrylate, one of the most commonly encountered polymers in the production of nanoparticles. Emphasis is put on the tetrameric, hexameric and octameric oligomers (PACA's). Log P was calculated for all interacting species. Molecular dynamics along with energy minimization processes (molecular mechanics MM2, semi-empirical quantum mechanics PM3) were employed to probe the conformational behavior of doxorubicin and polyalkylcyanoacrylate both as isolated species and interacting with each other. A docked structure of protonated doxorubicin with two octamers of n-butyl polycyanoacrylate is described. Among the main stability factors of the assembly was the charge-dipole interaction representing a stabilizing contribution of -33 kcal/mol. The mechanism of aggregation and desegregation (doxorubicin release) can be summarized as follows: oligomeric PACA's are lipophilic entities that scavenge amphiphilic doxorubicin already during the polymerization process by extraction of the protonated species from the aqueous environment to the increasingly lipophilic phase of the growing PACA's. The establishment of hydrogen bonds between the ammonium N-H function and the cyano groups is noteworthy. The cohesion in PACA nanoparticle comes therefore from a blend of dipole-charge interaction, H bonds, and hydrophobic forces,

Cyanoacrylates↗
PubMed2001

[The future of urology in Europe: a perspective from the European Urology Association].

INTRODUCTION: In order to be able to influence and monitor future developments for urologists, strategies should be promoted in advance to guarantee the future of the speciality and to accommodate the inevitable changes. Faced with this challenge, the EAU, through its Strategy Planning Office (SPO), has prepared a document which is offered, here, in abbreviated form, to the European and international urological communities for general consideration. MATERIAL AND METHODS: A group of subjects, related to the domains and internal consistency of urology as a speciality, were selected and discussed among the members of the SPO and later submitted to open consultation among distinguished members of the urological community. The topics selected for discussion included: what is urology; urology in the university; sub-specialization in urology; training in urology; does kidney transplantation belong to urology, and others. RESULTS: It is shown that urology is going through an exciting and hazardous transition period. Urology has conflicting problems in its traditional domains due to changes in health care policy, and internal identification problems due to its permanent expansion and sub-specialization options. Weaker points are its relation with primary care medicine (shared care options), the presence and role of urology in institutions such as the university, department of surgery, children's hospitals, administration, etc.; the desegregating effect of the sub-specialities; the increasing encroachment of other specialities, and the increasing outpatient effect of technological progress. CONCLUSIONS: An action plan is proposed to confront these changes without losing manpower, internal consistency or social image and improving patient care quality, excellence of training and scientific progress.

Europe↗
PubMed2000

Mealiness assessment in apples and peaches using MRI techniques.

Mealiness (woolliness in peaches) is a negative attribute of sensory texture that combines the sensation of a desegregated tissue with the sensation of lack of juiciness. In this study, 24 apples cv. Top Red and 8 peaches cv. Maycrest, submitted to 3 and 2 different storage conditions respectively have been tested by mechanical and MRI techniques to assess mealiness. With this study, the results obtained on apples in a previous work have been validated using mathematical features from the histograms of the T2 maps: more skewed and the presence of a tail in mealy apples, similar to internal breakdown. In peaches, MRI techniques can also be used to identify woolly fruits. Not all the changes found in the histograms of woolly peaches are similar from those observed in mealy apples pointing to a different underlying physiological change in both disorders.

Food Technology↗
PubMed1999

Mealiness assessment in apples using MRI techniques.

Small samples of Top Red apples stored 6 months under controlled atmosphere (expected to be non-mealy) and 2 degrees C (expected to be mealy) have been used for MRI imaging. Multi-slice-multi-echo magnetic resonance images (64*64 pixels) have been recorded with a 8 ms echo time. Three out of four apples corresponding to the sample maintained under controlled atmosphere did not developed mealiness while three out of four fruits corresponding to the sample stored at 2 degrees C became mealy after 6 months of storage. The minimum T2 values obtained for the mealy apples show to be significantly lower (F = 13.21) when compared with non-mealy apples pointing that a more desegregated structure and a lower juiciness content leads to lower T2 signal. Also, there is a significant linear correlation (r = -0.76) between the number of pixels with a T2 value below 35 ms within a fruit image and the deformation parameter registered during the Magness-Taylor firmness test. Finally, all T2 maps of mealy apples show a regional variation of contrast which is not shown for non-mealy apples. Significant differences (F = 19.43) between mealy and non-mealy apples are found in the histograms of the T2 maps as mealy apples show a skew histogram combined with a "tail" in their high T2 extreme which is not shown in the histograms of non-mealy apples. These histogram features are also shown for an apple showing internal breakdown indicating that in mealy apples there is a differential water movement that may precede internal breakdown.

Food Technology↗
PubMed2003

(Dis)abling children in primary school micro-spaces: geographies of inclusion and exclusion.

The geography of disabled children's schooling in the United Kingdom (UK) is changing, and this is underpinned by a growing international consensus that disabled children should be educated within mainstream school settings (UNESCO, The Salamanca statement and framework for action on special educational needs. World Conference on Special Needs Equality and Quality, Salamanca, Spain, 1994). As a result, new geographies of desegregation in disabled children's education are emerging, with disabled children being increasingly educated within mainstream rather than 'special' schools. This paper explores this issue, focusing on the (re)production of discourses of 'inclusion' and 'disability' in two mainstream primary schools in England. Empirical findings demonstrate that school actors reproduce meanings of inclusion and disability in different ways within and between school settings. It is shown that discourses of inclusion are frequently based on educational-medical models of disability, and can serve to exclude some children from mainstream schools. With this in mind, the paper highlights the value of a spatially sensitive evaluation of inclusion, that emphasises the importance of schools as unique moments in space and time to everyday practices of inclusion and disability.

Architectural Accessibility↗
PubMed2002

Women's experiences of hospital admission.

The primary aim of this study was to examine women's experiences of inpatient psychiatric services. A secondary aim was to use the emerging themes in service planning and to develop an evaluation tool. Focus groups and individual interviews with women in receipt of psychiatric services in Croydon were used. The findings suggest continuity with both negative and positive aspects of institutional care described before the policy of community care was introduced. The attempts to 'normalize' institutional care by desegregating wards appear rather to have compounded problems faced by women. Women were clear about what they felt they wanted and needed. Women are dissatisfied about many aspects of care aside from the problems associated specifically with mixed sex wards. This suggests that sexual segregation of wards alone is a necessary but an insufficient measure to improve inpatient care. The findings can inform development of a women-only service in Croydon and of a tool to evaluate it.

Female↗
PubMed2005

Did life begin on the beach?

Water is one of the prerequisites of life. Further requirements are the existence of a system of interacting organic molecules capable of capturing and converting the supply of external energy and elaborating the replicating function that is needed for propagation. None of this would be possible without the existence of some means of concentrating, selecting, and then containing these mutually interacting substances in proximity to one another, i.e., a primitive cell. Starting from this hypothesis we propose a model for the development of life on Earth. Our model embodies the following new features: (1) rapid cycles of catalysis and transport of material, (2) desegregation (separation by tidal action and degradation by catalysis) as well as segregation (by chromatography on tidal beaches), (3) cross-catalysis instead of auto-catalysis, as well as (4) compartmentalization, although the latter idea is of course not new. But our "lipid first" model, in contrast to earlier "peptide first" or "RNA first" models, provides for the compartments needed to act as a cradle for the subsequent development of information- rich molecules like peptides and RNA. If anything, the earliest information-rich molecules were probably membrane-spanning peptides/proteins.

Catalysis↗
PubMed2002

Nucleolar changes in bovine nucleotransferred embryos.

This study focused on nucleolar changes in bovine embryos reconstructed from enucleated mature oocytes fused with blastomeres of morulae or with cultured, serum unstarved bovine fetal skin fibroblasts (embryonic vs. somatic cloning). The nucleotransferred (NT) embryos were collected and fixed at time intervals of 1-2 h (early 1-cell stage), 10-15 h (late 1-cell stage), 22-24 h (2-cell stage), 37-38 h (4-cell stage), 40-41 h (early 8-cell stage), 47-48 h (late 8-cell stage), and 55 h (16-cell stage) after fusion. Immunocytochemistry by light and electron microscopy was used for structure-function characterization of nucleolar components. Antibodies against RNA, protein B23, protein C23, and fibrillarin were applied. In addition, DNA was localized by the terminal deoxynucleotidyl transferase (TdT) technique, and the functional organization of chromatin was determined with the nick-translation immunogold approach. The results show that fully reticulated (active) nucleoli observed in donor cells immediately before fusion as well as in the early 1-cell stage after fusion were progressively transformed into nucleolar bodies displaying decreasing numbers of vacuoles from the 2- to 4-cell stage in both types of reconstructed embryos. At the late 8-cell stage, morphological signs of resuming nucleolar activity were detected. Numerous new small vacuoles appeared, and chromatin blocks reassociated with the nucleolar body. During this period, nick-translation technique revealed numerous active DNA sites in the periphery of chromatin blocks associated with the nucleolar body. Fully reticulated nucleoli were again observed as early as the 16-cell stage of embryonic cloned embryos. In comparison, the embryos obtained by fetal cloning displayed a lower tendency to develop, mainly during the first cell cycle and during the period of presumed reactivation. Correlatively, the changes in nucleolar morphology (desegregation and rebuilding) were at least delayed in many somatic NT embryos in comparison with the embryonic NT group. It is concluded that complete reprogramming of rRNA gene expression is part of the general nuclear reprogramming necessary for development after NT.

Animals↗
PubMed2002

Simulational studies of axial granular segregation in a rotating cylinder.

Discrete particle simulation methods have been used to study axial segregation in a horizontal rotating cylinder that is partially filled with a mixture of two different kinds of granular particles. Under suitable conditions segregation was found to occur, with the particles separating into a series of bands perpendicular to the axis. In certain cases the band structure exhibited time-dependent behavior, including band formation, merging and motion along the axis, all corresponding to phenomena that arise experimentally. In order to examine how the many parameters specifying the problem affect the segregation process, simulation runs were carried out using a variety of parameter settings, including combinations of friction coefficients not realizable experimentally. Both segregation and desegregation (mixing) were investigated, and cylinders with both explicit end caps and periodic ends were used to help isolate the causes of segregation.

Journal Article↗
PubMed2000

Necessity for afferent activity to maintain eye-specific segregation in ferret lateral geniculate nucleus.

In the adult mammal, retinal ganglion cell axon arbors are restricted to eye-specific layers in the lateral geniculate nucleus. Blocking neuronal activity early in development prevents this segregation from occurring. To test whether activity is also required to maintain eye-specific segregation, ganglion cell activity was blocked after segregation was established. This caused desegregation, so that both eyes' axons became concentrated in lamina A, normally occupied only by contralateral afferents. These results show that an activity-dependent process is necessary for maintaining eye-specific segregation and suggest that activity-independent cues may favor lamina A as the target for arborization of afferents from both eyes.

Aminobutyrates↗
PubMed1993

Health professionals and South Africa: supporting change in the health sector.

Now that political change is on the way in South Africa, what should be the position of doctors who are invited to visit the country? Does the "academic boycott" still have relevance? Waterston and Zwi review the case for and against an academic boycott policy, using evidence collected during the recent visit by Physicians for Human Rights (UK) and the Johannes Wier Foundation. The health system in South Africa is still inequitable, and despite progress towards desegregation in hospitals there is little momentum towards universal provision of primary health care, especially in the rapidly growing townships around big cities. The authors consider that pressure on the government should be maintained by outside organisations but that support directed towards appropriate health care should be encouraged, particularly in public health and primary health care.

Attitude↗
PubMed2001

The future of urology in Europe: an overview from the European association of urology.

INTRODUCTION: In order to be able to influence and monitor future developments for urologists, strategies should be promoted in advance to guarantee the future of the speciality and to accommodate the inevitable changes. Faced with this challenge, the EAU, through its Strategy Planning Office (SPO), has prepared a document which is offered, here, in abbreviated form, to the European and international urological communities for general consideration. MATERIAL AND METHODS: A group of subjects, related to the domains and internal consistency of urology as a speciality, were selected and discussed among the members of the SPO and later submitted to open consultation among distinguished members of the urological community. The topics selected for discussion included: what is urology; urology in the university; sub-specialization in urology; training in urology; does kidney transplantation belong to urology, and others. RESULTS: It is shown that urology is going through an exciting and hazardous transition period. Urology has conflicting problems in its traditional domains due to changes in health care policy, and internal identification problems due to its permanent expansion and sub-specialization options. Weaker points are its relation with primary care medicine (shared care options), the presence and role of urology in institutions such as the university, department of surgery, children's hospitals, administration, etc.; the desegregating effect of the sub-specialities; the increasing encroachment of other specialities, and the increasing outpatient effect of technological progress. CONCLUSION: An action plan is proposed to confront these changes without loosing manpower, internal consistency or social image and improving patient care quality, excellence of training and scientific progress.

Europe↗
PubMed2005

Screening for asthma in Cantonese-speaking immigrant children.

BACKGROUND: Asthma prevalence among Chinese immigrant children is poorly understood and attempts to screen these children have produced varied outcomes. We sought to learn how to improve screening for asthma in Chinese immigrant children. METHODS: Children (n = 152) were administered the Brief Pediatric Asthma Screen in either Cantonese or English, they then viewed and reacted to a video showing people wheezing and subsequently took a pulmonary function test. RESULTS: The diagnosed asthma prevalence for our study population was 27.0%, with another 5.3% having possible undiagnosed asthma. Very few children had spirometry findings below normal. In multivariate analysis, being native born (p = 0.002) and having a family history of asthma (p = 0.003) were statistically associated with diagnosis of asthma. After viewing the video, 35.6% of respondents indicated that the images differed from their conception of wheezing. Of four translations of the word "wheeze" no single word was chosen by a majority. CONCLUSION: Our findings suggest that asthma diagnoses are higher for Chinese children who were born in the US suggesting that desegregation of data might reveal at risk subpopulations. Care needs to be taken when diagnosing asthma for Cantonese speakers because of the centrality of the word wheeze and the challenges of translation.

Adolescent↗
PubMedDate not supplied

Medicare as a catalyst for reducing health disparities.

As the nation's largest purchaser and regulator of health care, Medicare is positioned to be a leader in reducing racial and ethnic health disparities. Its leverage was demonstrated in 1966-the year of Medicare's inception-when hospitals desegregated as a condition for receiving Medicare reimbursement. Since then, Medicare has contributed to dramatic improvement in the health of the elderly and disabled minority population, although disparities between minority and white beneficiaries remain. A National Academy of Social Insurance study panel is exploring how Medicare could use its leverage to reduce disparities, for both its beneficiaries and the rest of the nation.

Cultural Diversity↗
PubMedDate not supplied

"The Civil Rights Movement of the 1990s?": The anti-abortion movement and the struggle for racial justice.

In 1964, Claude and Jeanne Nolen, who were white, joined an interracial NAACP team intent on desegregating local restaurants in Austin, Texas as a test of the recently passed Civil Rights ACt. Twenty-five years later, the Nolens pleaded "no contest" in a courtroom for their continued social activism. This time the issue was not racial segregation, but rather criminal trespassing for blockading abortion clinics with Operation Rescue. The Nolens served prison sentences for direct action protests that they believe stemmed from the same commitment to Christianity and social justice as the civil rights movements. Despite its relationship to political and cultural conservatism, the anti-abortion movement since Roe v. Wade (1973) was also a product of the progressive social movements of the turbulent sixties. Utilizing oral history interviews and organizational literature, the article explores the historical context of the anti-abortion movement, specifically how the lengthy struggle for racial justice shaped the rhetoric, tactics, and ideology of the anti-abortion activists. Even after political conservatives dominated the movement in the 1980s, the successes and failures of the sixties provided a cultural lens through which grassroots anti-abortion activists forged what was arguably the largest movement of civil disobedience in American history.

Abortion, Induced↗
PubMed2004

Cultured nestin-positive cells from postnatal mouse small bowel differentiate ex vivo into neurons, glia, and smooth muscle.

Little is known about postnatal enteric nervous system (ENS) development, but some reports suggest that the postnatal bowel may contain neural stem cells. Therefore, we created an in vitro model of desegregation using an enzymatic and mechanical tissue technique. This approach yielded a group of cells from the small intestine of lactating and adult mice, which ex vivo attach to the culture dish; actively proliferate; and express nestin, vimentin, and the pro-neural transcription factors neurogenin-2 (ngn-2), Sox-10, and Mash-1. In the conditions grown, double immunostains suggest that they differentiate into various cell types, particularly neurons, smooth muscle, and glia including 04 protein-positive cells. They also express the neurotrophic-protein tyrosine kinase (Trk) receptors TrkA, TrkB, and TrkC; the low-affinity neurotrophin receptor p75NTR; and the glial-derived neurotrophic factor receptors (GFR)alpha-1, GFRalpha-2, and GFRalpha-3. The neurons expressed several sensory and motor neurotransmitters present in the central and enteric nervous systems, including calcitonin gene-related peptide, neuropeptideY, peptideYY, substance P, vasoactive intestinal polypeptide, and galanin; along with glia, these neurons formed elaborate intercellular connections. They also express c-KIT, CD34, CD20, and CD45RO, suggesting they either have a hematogenous origin or may differentiate toward hematogenous lines. These findings suggest that these cells may be enteric neural stem cells (ENSCs); may normally be present in the small intestine; and may have the capacity to proliferate and differentiate into neurons, glia, and smooth muscle. Further identification and purification of intestinal ENSCs will provide a means to study the regulation of their differentiation and should give insight into the mechanisms involved in development and remodeling of the ENS. The possible therapeutic application of postnatal stem cells such as ENSCs needs to be evaluated, including their use for transplantation in the central nervous system.

Animals↗
PubMed1998

Vinculin and cell-cell adhesion.

Vinculin, a 117-kDa protein, is a constituent of adhesion plaques and adherence junctions in non-muscle cells. We investigated the role of vinculin on the physical strength of cell-cell adhesion by conducting disaggregation assays on aggregates of parental wild-type F9 mouse embryonal carcinoma cells (clone BIM), two vinculin-depleted F9 cell lines, gamma 227 and gamma 229, and a reconstituted gamma 229 cell line (R3) that re-express vinculin. Immunoblotting demonstrated that the four cell lines used in the study had similar expressions of the cell-cell adhesion molecule E-cadherin and associated membrane proteins alpha- and beta-catenin. Double immunofluorescence analysis showed that, in contrast to the vinculin-null cell lines. BIM and R3 cells expressed abundant vinculin at the cell margins in adhesion plaques and in cell-cell margins that also contained actin. Laminar flow assays showed that both the vinculin-positive and vinculin-negative cell aggregates that were formed in culture in the course of 24 to 48 hours largely remained intact despite the imposition of shear flow at high shear rates. Since laminar flow imposed on cell aggregates act to separate cells from each other, our data indicate that F9 cells that were adherent to a substrate formed strong cell-cell adhesion bonds independent of vinculin expression. On the other hand, aggregates of vinculin-depleted gamma 229 and gamma 227 cells that were formed in suspension during a two-hour static incubation at 37 degrees C were desegregated more easily with the imposition of shear flow than the BIM and R3 cell aggregates formed under identical conditions. Loss of vinculin was associated with a reduction in cell-cell adhesion strength only among those cells lacking contact to a substrate. Overall, the results indicate that vinculin is not needed for forming strong cell-cell adhesion bonds between neighboring carcinoma cells which are adherent to the basal lamina.

Actins↗
PubMed1992

The troubled profession: is medicine's glass half full or half empty?

Abundant evidence that medicine is in trouble includes serious career dissatisfaction among practicing and would-be physicians as well as steeply declining interest in generalist careers, especially internal medicine. Medicine is threatened by ever-rising health care expenditures and ineffectual but vexing administrative efforts to contain them. Additional problems challenge internal medicine in particular: the clinical complexity of practice, lower income potential, and incomplete clinical experiences for medical students. Yet, in the past 25 years, spectacular advances in science and technology enabled improved patient care and outcomes; more women and minorities entering the profession brought it into better demographic balance; relative physician incomes rose; and access to physician services improved with Medicare and Medicaid and the desegregation of southern hospitals. Despite an unfinished agenda, never before has medicine held so much promise for improving the health of the public. Despite various professional problems, no other career offers the unique blend of state-of-the-art science and humanism that epitomizes internal medicine--medicine's integrating specialty.

Attitude of Health Personnel↗