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PubMed1998

Synthesis of 7-arylmorphinans. Probing the "address" requirements for selectivity at opioid delta receptors.

Through arylation of 6-keto opiates with diaryliodonium iodide, a series of 7-aryl opiates (3-8) have been prepared in an effort to investigate the effect of conformational mobility of the delta "address" moiety on opioid agonist and antagonist potencies. Evaluation of the ligands in the mouse vas deferens and guinea pig ileum preparations revealed that they were less potent and less selective than the conformationally constrained ligands, naltrindole (1, NTI) and 7-(spiroindanyl)oxymorphone (2, SIOM), at delta opioid receptors. It is concluded that the coplanarity of the address moiety with the C ring of the morphinan structure enhances delta antagonist potency and selectivity.

Animals↗
PubMed2006

Chemoselectively addressable template: a valuable tool for the engineering of molecular conjugates.

We herein report the modular design and the synthesis of new molecular conjugates, which can combine a cell targeting function (ligand domain) with potential cytotoxic molecules (effector domain). The present approach utilizes a cyclic peptide template, Chemoselectively Addressable Template (CAT) as a key intermediate. These CAT molecules exhibit two independent and chemically addressable domains which permits the sequential and regioselective assembly of different ligand and/or effector domains. The attachment of various units to the template was achieved by the formation of iterative oxime bonds. The chemoselective oxime bonds were produced by the reaction of glyoxylyl aldehyde groups obtained from serine precursors. The process was further developed to prevent transoximation reactions. RAFT(c[-RGDfK-])4, a synthetic vector targeting the tumor-associated a alpha(V)beta3 integrin was prepared and coupled to either a cytotoxic peptide or oligonucleotide as an illustration of present approach. The potential application of this approach has been further demonstrated by the synthesis of high molecular weight compounds such as RAFT(c[-RGDfK-])16, a alpha(V)beta3-targeting ligand of high valency index.

Aldehydes↗
PubMed2000

Sentence comprehension is mediated by content-addressable memory structures.

Studies of working memory demonstrate that some forms of information are retrieved by a content-addressable mechanism (McElree & Dosher, 1989; McElree, 1996, 1998), whereas others require a slower search-based mechanism (McElree & Dosher, 1993). Measures of the speed and accuracy of processing sentences with filler-gap dependencies demonstrate that the probability of maintaining a representation of a filler item decreases as additional material is processed, but that the speed with which a preserved representation is accessed is unaffected by the amount of interpolated material. These results suggest that basic binding operations in sentence comprehension are mediated by a content-addressable memory system.

Cognition↗
PubMed2002

A survey of genetic counselors' strategies for addressing ethical and professional challenges in practice.

There is limited research about ethical and professional dilemmas that genetic counselors encounter in their practice and their strategies for addressing them. In this study, 454 genetic counselors rated the frequency with which they encounter each of 16 ethical/professional challenges identified and categorized previously (McCarthy Veach P., Bartels DM, LeRoy BS (2001) J Genet Couns 10(2):97-119). Over 40% indicated these issues occurred frequently: patient emotions, diversity, financial constraints, uncertainty, and colleague error. Two hundred and fifty-five respondents provided personal anecdotes describing exceptionally challenging situations and recommended strategies for addressing them. Most of their anecdotes involved informed consent, value conflicts, confidentiality, colleague error, withholding information, and resource allocation. The most frequently recommended strategies were further discussion with patients, consultation with other professionals, and referral to other health sources. Thirty-five respondents were unable to/did not offer strategies. Respondent demographics were not related to frequency of issues, type of anecdote, or recommended strategies. Practice, policy, and research implications are discussed.

Attitude of Health Personnel↗
PubMed2004

[The problems of the form of address Du vs. Sie between nurses and patients in Germany].

This article is an overview of selected nursing and linguistic literature examining the use of the pronoun Du vs. Sie in Germany. The aim of this literature review is to show the difficulties faced when one is choosing a form of address and relate these difficulties to the daily nursing routine. This overview will show clearly that the choice of pronoun can "form social reality". Linguistic literature distinguishes two dimensions: One is the vertical dimension (power semantic) which shows the unequal relationship of the speaker and the listener. The other is the horizontal dimension (solidarity semantic) which shows the equality of the talking partners. The analysis of nursing literature brought to light that the choice of form of address should be considered with regard to the aspects power, familiarity vs. distance, distain vs. respect.

Germany↗
PubMed2002

Individually addressable parallel peptide synthesis on microchips.

Miniaturized, spatially addressable microchips of peptides and peptidomimetics are powerful tools for high-throughput biomedical and pharmaceutical research and the advancement of proteomics. Here we report an efficient and flexible method for the parallel synthesis of peptides on individually addressable microchips, using digital photolithography and photogenerated acid in the deprotection step. We demonstrate that we are able to synthesize thousands of peptides in a 1 cm(2) area on a microchip using 20 natural amino acids as well as synthetic amino acid analogs, with high stepwise yields and short reaction-cycle times. Epitope screening experiments using a p53 antibody (PAb240) produced clearly defined binding patterns. The peptidomimetic sequences on the microchip show specific antibody binding and provide insights into the molecular details responsible for specificity of epitope binding. Our approach requires just a conventional synthesizer and a computer-controllable optical module, thereby allowing potential development of peptide microchips for various pharmaceutical and proteomic applications in routine research laboratories.

Amino Acid Sequence↗
PubMed2006

Addressing parenting concerns of bone marrow transplant patients: opening (and closing) Pandora's box.

Although a significant number of adults undergoing stem cell transplant (SCT) or bone marrow transplantation (BMT) care for dependent children, and these treatments pose significant challenges for families, research has virtually ignored the impact of parenting on patients' quality of life during BMT/SCT and children's responses to having a parent undergo these treatments. Physicians rarely inquire about parenting concerns related to the extended hospitalizations necessitated by these treatments, yet clinical experience suggests that addressing patient concerns about children's reactions to cancer and BMT/SCT can improve the experience of the patient and the patient's family, and help the medical team respond effectively to sources of patients' distress. Parents frequently want to know what reactions to expect from children, thus general developmental information is reviewed, and recommendations given for when professional help for children is warranted. A key way for parents to support their children is with open, honest communication; however, parents often find it extremely difficult to talk about cancer and BMT/SCT with their children. The medical team can assist patients' efforts to communicate with and support their children by asking about a patient's children, providing some targeted information, and discussing the potential impact of treatments on parenting capacity. Inquiring about and addressing parenting concerns may initially seem difficult, but can ultimately facilitate stronger doctor-patient alliances, and more compassionate care.

Adaptation, Psychological↗
PubMed2005

Individually addressable recessed gold microelectrode arrays with monolayers of thio-cyclodextrin nanocavities.

Four, individually addressable 30 microm diameter, e-beam deposited, gold microelectrodes recessed by 6 microm were suitably spaced on a single substrate to avoid diffusional overlap between each microelectrode. The single substrate device was functionalised with thiolated alpha-, beta-, and gamma-cyclodextrin nanocavities without spacer groups to ensure close proximity of the cavities to the electrode surface. The microelectrodes were assessed in two stages. The e-beam deposited micron sized electrodes were characterized using models for recessed and inlaid microdisk electrodes. Subsequently, each individually addressable, atomically flat, micro-patterned gold electrode with thiolated CD ensembles was treated as a nanoporous electrode assembly. Theoretical and experimental results were compared using cyclic voltammetry. Atomic force microscopy was also used to characterise the modified microelectrodes. Comparisons were made with thiolated CDs deposited on macroelectrodes. This is the first report of the behaviour of immobilized CD nanocavities ensembles on atomically flat gold microelectrodes.

Journal Article↗
PubMed1997

Addressing barriers: disabled rights and the implications for nursing of the social construct of disability.

Drawing upon the writings of disabled people, this paper explores some of the issues which nurses working with disabled people are trying to address, in particular the barriers model of disability. Traditionally disability has been regarded as a personal tragedy afflicting the individual, hence the response to disability has been via the charity, health and welfare systems. Disabled people over the past two decades have substantially challenged this view of disability and the responses it prompts, arguing that disability is created by social barriers and barriers in the built environment. This requires a different response. Nurses working with disabled people, such as learning disability nurses, have struggled to develop more appropriate responses to disability, for example by developing working alliances with people with learning difficulties in order to both promote health and address disabling barriers. The issues these nurses face and some of the lessons disabled people have taught them are relevant to the nursing profession's wider struggle to shed its medical and dependency image.

Attitude of Health Personnel↗
PubMed1998

A systematic review of clinical research addressing the prevalence, aetiology, diagnosis, prognosis and therapy of otitis media in Australian Aboriginal children.

The objective of this review was to systemically identify and summarize all the clinically relevant evidence available from studies addressing the prevalence, aetiology, diagnosis, prognosis and therapy of otitis media in Australian Aboriginal children. Electronic searching of Medline, the Australian Medical Index and the Aboriginal and Torres Strait Islander Health Bibliographic Index was performed. This was supplemented by hand searching the Menzies School of Health Research otitis media collection, the Aboriginal and Torres Strait Islander Health Information Bulletin and Aboriginal Health: an annotated bibliography. Data were extracted and placed in a series of evidence tables relevant to clinical practice. There were 59 studies that met the inclusion criteria. The majority were surveys, and only 19 addressed diagnosis, prognosis or therapy. Severe otitis media in rural Aboriginal children does not occur in isolation but as part of a spectrum of chronic bacterial infections of the respiratory tract. Although the aspects of poverty that result in this condition remain to be clarified, exposure to other young children with chronic nasal discharge is likely to be important. Whilst there is a considerable amount of literature on otitis media in Australian Aboriginal children, the number of studies most relevant to improving health outcomes is small. A systematic approach to disease surveillance, diagnosis, and application of medical interventions is required urgently. Future medical research should be concerned with the evaluation of interventions and the generalisabilty of studies from different populations.

Adolescent↗
PubMed2001

Ethics and communication: does students' comfort addressing: ethical issues vary by specialty team?

Ethics education aims to train physicians to identify and resolve ethical issues. To address ethical concerns, physicians may need to confront each other. We surveyed medical students to determine if their comfort challenging members of their ward teams about ethical issues varies by specialty and what attributes of students and their teams contributed to that comfort. Compared to other specialties, students felt significantly less comfortable challenging team members about ethical issues on surgery and obstetrics/gynecology. We suggest that ethics education must address the atmosphere on ward teams and give students skills to help them speak out despite their discomfort.

Adult↗
PubMed2005

Preliminary clinical results of two techniques for addressing graft tunnel mismatch in endoscopic anterior cruciate ligament reconstruction.

This study reports the initial clinical results of 540 degrees of graft rotation or free tibial bone block to address graft tunnel mismatch in endoscopic anterior cruciate ligament (ACL) reconstruction. The operative reports of patients who underwent endoscopic ACL reconstruction between 1999 and 2001 were reviewed. Nine of 11 patients treated with a free tibial bone block and 14 of 17 patients treated with 540 degrees of graft rotation were evaluated. Mean follow-up was 20 months (range: 13-40 months) for the bone block group and 34 months (range: 18-48 months) for the 540 degrees group. There were statistically significant improvements in physical examination test results postoperatively, and only one patient in the 540 degrees group had a grade one positive pivot shift test. KT-1000 arthrometer testing demonstrated a statistically significant decrease in manual maximum and side-to-side differences at final follow-up. Mean Lysholm and Noyes sports function scores were excellent or good for all patients. One patient required reoperation for flexion contracture, one patient required an arthroscopic irrigation and debridement for a minor infection, and one patient required arthroscopic subtotal medial meniscectomy for failed meniscal repair. No difference was noted between these results and previous results of patients undergoing conventional endoscopic ACL reconstruction. These results demonstrate graft rotation and free bone block techniques are effective in addressing graft tunnel mismatch in endoscopic ACL reconstruction.

Adolescent↗
PubMed2006

[Discharge letters addressed to patients--confidence enhancement and psychoeducation].

OBJECTIVE: There are only some reports about discharge letters addressed to patients. By a case report benefits and potential of letters to patients should be shown. METHOD: The presented case report describes the hospital stay of a 19 year old patient suffering from schizophrenia. RESULTS: The case report indicates that letters to patients provide a useful source of information and can help the patient to understand the nature of his illness. Furthermore, letters to patients are important to increase confidence and can lead to an open atmosphere in the therapeutic process. CONCLUSIONS: Letters to patients enhance the role of patients as self-responsible partners in health care. In single cases a personal addressed letter to the patient is feasible in psychiatric hospitals despite shortness of time.

Adult↗
PubMed1981

In vitro synthesis and posttranslational uptake of cytochrome c into isolated mitochondria: role of a specific addressing signal in the apocytochrome.

Administration of the thyroid hormone 3,3,5'-triiodo-L-thyronine (T3) to rats leads to a marked increase in hepatic levels of mRNA for cytochrome c. Messenger RNA prepared from the free polysomes of T3-treated rats directed the in vitro synthesis of a polypeptide which only differed in amino acid sequence from mature cytochrome c in that it contained an NH2-terminal methionine. The in vitro product was incorporated specifically into purified rat liver mitochondria and became inaccessible to added trypsin when the mitochondria were added after translation was completed. Horse heart apocytochrome c, but not the holocytochrome, could compete with the in vitro synthesized polypeptide for its uptake into mitochondria. This suggests that the primary structural features of apocytochrome c, which serve as an addressing signal for mitochondria, are masked after the acquisition of heme and that this process occurs in the mitochondria. The addressing signal seems to be contained in a specific segment of the cytochrome polypeptide because only one fragment generated by CNBr cleavage of horse apocytochrome c, extending from residue 66 to the carboxy end of the molecule, could compete with the in vitro product for its transfer into mitochondria.

Animals↗
PubMed1996

Addressing dependent amphetamine use: a place for prescription.

Amphetamines are among the most widely used of illicit drugs in Australia, and evidence documenting the occurrence of amphetamine-related harms, particularly among chronic regular users, is increasing, A review of contemporary Australian treatment approaches suggests that conventional modalities are unlikely to address the needs of a large proportion of dependent amphetamine users. This has prompted clinicians in Australia and the United Kingdom to commence treatment programmes incorporating substitution therapy. Despite the positive impressions of clinicians involved in these programmes, further research is required to establish the role and efficacy of such treatment approaches. Issues to be addressed in the establishment of a controlled study are examined.

Journal Article↗
PubMed2000

Addressing regulatory barriers to licensing nicotine products for smoking reduction.

This paper examines the current regulatory obstacles to extending the permitted use of NRT, and to include smoking reduction ways of addressing these. There are major differences between different countries in regulations concerning NRT. These differences appear to be due to different attitudes to cigarette smoking as an issue and different preconceptions about nicotine as an addictive and potentially toxic drug. The paper considers how existing WHO and American Psychiatric Association definitions of mental disorders may be used in submitting proposals for use of NRT as an aid to smoking reduction and how concerns over safety and abuse and dependence liability can be addressed. It also examines what new evidence may be needed. Coordinating the efforts of the pharmaceutical industry, clinicians and researchers will probably be important in moving regulatory authorities further in the direction of accepting NRT for widespread use in smoking reduction.

Attitude to Health↗
PubMed2006

Identifying and addressing barriers to the delivery of optimal therapy for primary central nervous system lymphoma in the broader community.

Despite recent advances in the management of primary central nervous system lymphoma (PCNSL), recent population-based studies suggest that prognosis in the broader community has not improved substantially over the last 20 years. It is possible that this difference in outcome reflects a significant selection bias in the clinical series and trials reported. However, there is also preliminary evidence suggesting that patients in the community may not receive optimal management. There are many possible reasons that might account for disparities in care and outcome, but these have not been specifically addressed with regard to PCNSL. We have sought to elaborate some potential causes of these disparities; however, future studies are needed to identify and address specific barriers to care in the community.

Aged↗
PubMed2006

Interventions to address the stigma associated with leprosy: a perspective on the issues.

This paper presents a perspective on stigma as an effect of leprosy. It identifies some of the strengths and weaknesses of current approaches to stigma reduction in leprosy and presents a rationale for considering alternative strategies. It is suggested that models used to explain health behavior in developed societies are inappropriate for explaining leprosy stigma or for developing strategies to address it. The author recommends due consideration of the alternative logic that characterizes cultural belief systems in countries where leprosy is a challenge. Criticism of the common practice of information dissemination as a strategy to address leprosy stigma is defended and the merits and limitations of an integrated health service in India is discussed. The author defends the suggestion that the principal objective of stigma interventions should be "normalization". An example of a Nepalese project based on empowerment theory is given to demonstrate how the transformation of identity from outcast to positive change agent, can effect "normalization".

Health Knowledge, Attitudes, Practice↗