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Aims and Objectives: This study aimed to explore public health nurses' experiences with mental health promotion for adolescent immigrants in lower secondary and high school, aiming to enhance knowledge and insights for effective mental health promotion., Methodological Design and Justification: A qualitative design employing a hermeneutic approach was chosen. Thirteen public health nurses were selected using purposive criterion sampling and snowballing. Thematic analysis was applied, adhering to COREQ guidelines for transparency., Ethical Issues and Approval: The research was approved by the Norwegian Centre for Research Data. The guidelines of the National Committee for Research Ethics in the Social Sciences and the Humanities were followed., Research Methods, Instruments, And/or Interventions: Data were collected through three focus-group interviews (n = 13), using semi-structured interview guides to explore the experiences of public health nurses in promoting mental health among adolescent immigrants., Outcome Measures: This study identified three key themes: (i) Striving to understand adolescent immigrants' mental health aspects, including both positive and negative aspects; (ii) Different strategies for promoting mental health, viewing adolescents as both recipients and contributors to their well-being; and (iii) Barriers to public health nurses' promotion of mental health, including language, cultural, and knowledge-related obstacles and trust issues., Results: Public health nurses noted that language barriers and trust issues often delayed adolescent immigrants from seeking help for mental health concerns. Cultural competence and empathy were deemed crucial. To meet these needs, public health nurses must build rapport with parents, collaborate with professionals, implement follow-up programmes, and advocate for policy changes., Study Limitations: Limitations of this qualitative study include potential bias from the authors' background and non-generalizability of results to other contexts., Conclusions: In conclusion, public health nurses' experiences reveal the need for enhanced cultural competence, language proficiency, and trust-building to better serve adolescent immigrants. Collaborative efforts, follow-up programmes, and policy advocacy are essential to improve mental health promotion in school settings., (© 2024 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Background: Mothers are recommended to breastfeed their children but can find it challenging and experience breastfeeding problems. Qualified breastfeeding counselling from healthcare professionals can help mothers master breastfeeding, but there is a need to explore mothers' lived experiences with receiving breastfeeding counselling. We aimed to reveal breastfeeding mothers' experiences with receiving breastfeeding counselling from midwives and public health nurses (PHNs) to provide a deeper insight into the phenomenon of breastfeeding counselling, which may improve breastfeeding counselling in practice., Methods: A qualitative design with a hermeneutic phenomenological approach was used. Individual interviews of 11 breastfeeding mothers from Norway were conducted from September 2021 to 2022. Van Manen's guided existential inquiry guided the reflective process to provide deeper insights into the phenomenon of breastfeeding counselling., Results: The study captured the meaning of breastfeeding mothers' lived experiences with breastfeeding counselling. Three themes and eight sub-themes were found. Breastfeeding was at stake for the mothers because breastfeeding could be reduced or stopped, and qualified breastfeeding counselling from midwives and PHNs was essential for them to establish and continue breastfeeding. They needed to be perceived as both breastfeeding mothers and as women with their own needs to master everyday life during the breastfeeding period., Conclusions: This study offers insights to midwives, PHNs and others offering breastfeeding counselling by facilitating an understanding of being a breastfeeding mother receiving breastfeeding counselling. Qualified breastfeeding counselling and a trusting relationship with midwives and PHNs are essential for mothers to establish and continue breastfeeding, while deficient counselling may cause breastfeeding difficulties. Mothers need to be treated as whole and competent persons to avoid objectification and fathers/partners need to be included in breastfeeding counselling. The 'Baby-Friendly Hospital Initiative' should be continued, and guidelines should align with the mothers' need to incorporate breastfeeding into their daily lives during the breastfeeding period., (© 2024. The Author(s).)

Aims and Objectives: To explore midwives' and public-health nurses' experiences of breastfeeding counselling in order to provide a deeper insight into breastfeeding counselling., Methodological Design and Justification: A qualitative design was used, and qualitative content analysis was conducted to analyse the data in accordance with the phenomenological hermeneutic tradition., Ethical Issues and Approval: The Norwegian Centre for Research Data approved this study. All participants provided written consent., Research Methods: Four focus-group interviews were conducted on a sample of eight midwives and 13 public-health nurses in Norway., Results: Three interrelated themes describing the meaning of midwives' and public-health nurses' experiences with breastfeeding counselling emerged from the analysis: Breastfeeding Counselling Means Responsibility for Collaboration and Facilitation, Being Confident as a Breastfeeding Counsellor Means Striving for Professional Competence and Supporting the Individual Breastfeeding Family Means Being Sensitive and Adapting to Novel Situations., Study Limitations: The focus groups comprised a mix of midwives and public-health nurses, which may have inhibited honest declaration of these professionals' opinions of each other., Conclusion: Midwives and public-health nurses regard structural factors and prioritising breastfeeding support in society as important for providing good breastfeeding counselling. Midwives and public-health nurses strive to find a balance between relying on their own competence, promoting breastfeeding in accordance with guidelines and respecting mothers' choices. Healthcare professionals require knowledge about breastfeeding, good clinical judgement, a listening attitude and openness to how breastfeeding affects mother's everyday life to provide good breastfeeding care., (© 2023 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Introduction: Primary care placement for nursing and medical students is vital for developing the competence to accommodate the increasing number of patients with multimorbid and complex conditions. Prior studies have suggested that interaction quality in primary care placement empowers learning. However, research mapping interaction quality in primary care placements in municipal emergency care units is lacking. This study aimed to systematically map interaction quality for nursing and medical students in primary care placement in two municipal emergency care units., Materials and Methods: This study adopted a systematic descriptive observational design. Systematic observations ( n  = 201 cycles) of eight nursing students ( n  = 103 cycles) and six medical students ( n  = 98 cycles) were used to map interaction quality across six learning situations between March and May 2019. Observations were coded using the Classroom Assessment Scoring System-Secondary (CLASS-S). Data were analyzed using descriptive statistics and Spearman correlations., Results: Interaction quality is described in three domains: (I) emotional support, (II) framework for learning, and (III) instructional support , and the overall measure, student engagement . The results indicated middle-quality interactions in the emotional and instructional support domains and high quality in the framework for learning domain and student engagement. Correlations exhibited similar patterns and ranged from non-significant to strong correlations., Conclusion: The interaction qualities indicated a generally positive and supportive learning environment contributing to nursing and medical students' learning and active participation in work tasks related to their professional roles. Thus, this new form for primary care placement for nursing and medical students in the municipal emergency care units was found to be a positive learning arena. These results may enhance nursing and medical education programs in countries with similar health services and education. Health education, supervisors, peers, and others contributing to students' learning should recognize which interaction qualities may affect learning and how to improve quality, thus affecting supervisors' approach to training students. While the CLASS-S showed potential for mapping interaction qualities for nursing and medical students in primary care placement in municipal emergency care units, further studies are needed to validate the CLASS-S for use in clinical placement settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giske, Gamlem, Kvangarsnes, Landstad, Hole and Dahl.)

We compared online distributed information provided to patients with cancer in Scandinavian countries through the lens of governmentality. A secondary comparative qualitative analysis was conducted. Discourses in online patient information showed differences in governmentality techniques across the countries: Norway used a paternalist approach, Denmark an educative approach, and Sweden an individualistic approach and expected the patients to make the "right" decisions. Online information for patients with cancer in Denmark and Norway showed high professional and health care system involvement, whereas in Sweden, there was high patient involvement. There was almost no use of the person-centered approach among the online discourses., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore the competence areas of public health nurses in Norway., Design: A qualitative and comparative design was employed., Sample: A purposive sample of 41 public health nurses participated., Measurements: Data were gathered from focus groups and individual interviews. The interviews centered around an open question about public health nurses' knowledge. They also discussed 10 proposed competence areas for public health nursing, developed from the literature. A qualitative content analysis was conducted on the interview transcripts, followed by a synthesis of the data from the interviews and earlier developed competencies. The 10 competence areas for Norwegian public health nursing were then refined. Finally, we compared the affirmed competence areas with earlier developed cornerstones and the new educational guidelines., Results: The interviews revealed 10 competence areas. These 10 competence areas were synthesized with the 10 proposed competencies from literature. Ten affirmed competence areas, which mostly corresponded with the competences from literature, were developed. The affirmed competencies were supported by the previously developed cornerstones and new educational guidelines., Conclusions: The affirmed competencies will help promote and explain the content and focus of PHNs' work in Norway and may have implications for education and international research., (© 2022 The Authors. Public Health Nursing published by Wiley Periodicals LLC.)

Background: Medical education has been criticised for not adapting to changes in society, health care and technology. Internationally, it is necessary to strengthen primary health care services to accommodate the growing number of patients. In Norway, emergency care patients are increasingly treated in municipal emergency care units in the primary health care system. This study explores medical students' learning experience and how they participated in communities of practice at two municipal emergency care units in the primary health care system., Methods: In this qualitative study, we collected data from March to May 2019 using semi-structured individual interviews and systematic observations of six ninth-semester medical students undergoing two-week clerkships at municipal emergency care units. The interview transcripts were thematically analysed with a social constructivist approach. A total of 102 systematic observations were used to triangulate the findings from the thematic analysis., Results: Three themes illuminated what the medical students learned and how they participated in communities of practice: (i) They took responsibility for emergency care patients while participating in the physicians' community of practice and thus received intensive training in the role of a physician. (ii) They learned the physician's role in interprofessional collaboration. Collaborating with nursing students and nurses led to training in clinical procedures and insight into the nurses' role, work tasks, and community of practice. (iii) They gained in-depth knowledge through shared reflections when time was allocated for that purpose. Ethical and medical topics were elucidated from an interprofessional perspective when nursing students, nurses, and physicians participated., Conclusions: Our findings suggest that this was a form of clerkship in which medical students learned the physician's role by taking responsibility for emergency care patients and participating in multiple work tasks and clinical procedures associated with physicians' and nurses' communities of practice. Participating in an interprofessional community of practice for professional reflections contributed to in-depth knowledge of ethical and medical topics from the medical and nursing perspectives., (© 2022. The Author(s).)

Interprofessional collaboration will be one of the main factors in the effort to increase patient safety in the coming years. Research has identified several challenges to interprofessional collaboration between nurses and doctors, where fragmentation of both education and clinical practice contributes to a strong affiliation to one's own profession with little emphasis on collaboration. The aim of this study was to generate more knowledge about how nurses and doctors experience interprofessional collaboration in observation and treatment of patients on a surgical ward. The study was conducted in 2018 and used an explorative qualitative design that was based on four semi-structured focus group interviews. The respondents were 11 nurses and seven doctors with experience from different surgical specialties and employed in three different surgical wards in a Norwegian hospital. The data were analyzed using systematic text-condensation. The following three main categories, each with two subcategories, emerged: 1) Organization and culture: a lack of interprofessional meeting places and experience-based hierarchy; 2) Communication: use of communication tools and little room for professional discussions; and 3) Trust and respect: dependence and recognition and a blurred distribution of responsibility. Both nurses and doctors wished for closer interprofessional collaboration in observation and treatment in the surgical ward; however, organizational limitations with few interprofessional meeting places and time pressure made this difficult.

International migration is a complex phenomenon that touches on a multiplicity of economic, social and security aspects affecting our daily lives. In the Nordic countries' migration is a contentious political topic as the number of migrants has significantly increased in recent decades. The aim of this study is to analyse governmental policy documents on migrants in Denmark, Finland, Norway and Sweden and to identify and compare how they are described within an empowerment perspective. A critical discourse analysis was undertaken of each Nordic country. The findings revealed that all four documents placed migrants in a passive position in regard to decision-making and that an empowerment perspective was lacking. Migrants are similarly treated in each Nordic country as a problem to deal with rather than as a possible resource for the society and the approach seeks to protect the welfare state and the culture of the country. The lack of empowerment perspective may be having a negative impact on the health and well-being of migrants and on their integration in the Nordic society. The article concludes by raising several questions in regard to migration and empowerment in the Nordic context., (© The Author(s) 2020. Published by Oxford University Press.)

Aim: To explore how the patient is constructed and socially positioned in discourses of web-based pathways information available to people with cancer in Norway., Design: Mixed qualitative and quantitative design, using Corpus-Assisted Critical Discourse Analysis., Methods: The study, conducted in January 2020, examined the language of one general and six specific web-based cancer pathways information brochures. The approach combines analysis of word frequencies and concordance lines using corpus analysis software to identify the 'linguistic fingerprint' or 'aboutness' of the text prior to further qualitative critical discourse analysis., Results: The analysis identified three core discourses which constructed the patient differently: (a) a participating active person, in a brief, inclusive discourse; (b) a passive person lacking knowledge or perception of their situation in dominant, medical and interprofessional expert discourse; and (c) reduced to a disease and a code in the pathways discourse., Conclusion: This study offers insight into the construction of patients in online clinical pathways information for cancer treatment. The analysis revealed how governance systems such as New Public Management and its demands on efficiency and productivity influence the cancer pathways. The World Health Organization has promoted a person-centred approach, emphasizing the importance of participation and a partnership of equals. A person-centred approach to care was not evident in the discourse of the online documents. The dominant ideology of these pathways was paternalistic with patients constructed as passive persons who get standardized treatment., Impact: This study gives new insight that can be valuable for nurses, other healthcare professionals and the government. The lack of a person-centred focus in the cancer pathway information could have a negative impact on the patient's health outcomes by promoting a culture of inattention to the patients' needs and wishes among practitioners. The results may provide a stimulus for discussion about the role of patients in cancer treatment., (© 2020 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Since the adoption of the Universal Declaration of Human Rights by the United Nations in 1948, human rights as set out in government documents have gradually changed, with more and more power being transferred to individual., Objectives: The aim of this article is to analyze how the position of the patient in need of care is constructed in Norway's renamed and revised Patients' and Service Users' Rights Act (originally Patients' Rights Act, 1999) and published comments which accompanying this legislation from the Norwegian Ministry of Health and Care Service., Research Design: A constructivist design was used, and Fairclough's critical discourse approach was adopted to analyze the text of the Patients' and Service Users' Rights Act and comments., Findings: The analysis identified three discourses: (a) political discourse, containing ethical discourses about priority and economy, in which patients are constructed as powerless individuals; (b) expert discourse, containing a theme about patients' trust in the healthcare team and its knowledge, in which patients are constructed as helpless individuals lacking knowledge; and (c) patient participation and patient autonomy discourse, containing ethical discourses about decision-making, in which patients are constructed not only as individuals with needs and rights but also as "troublesome.", Conclusion: Dominant paternalistic discourses in the legal text validate the power of medicine, the healthcare system, and heath personnel over the needs, rights, participation, and autonomy of the patient.

In public health nursing interprofessional collaboration has become a goal, however, there is little clarity on the distribution of responsibility or approach to cooperation between the professional groups. The aim of the study was to explore public health nurses' perceptions of their experiences related to interprofessional collaboration. A qualitative content analysis was carried out. An interview study with a purposeful sample of 23 Norwegian public health nurses (PHNs) was conducted. Data were analysed using semi-structured interviews to identify categories and themes of PHNs' working lives. The data were classified into three major themes: institutionality: the institutional understanding of the professional roles; competence: clarifying jurisdictional borders, and recognition: professionals' recognition of different roles. There needs to be a robust strategy in collaborative working that involves public health nurses among other professionals to avoid role overlap, interpersonal and interprofessional conflict and reduce the damaging threat or stress that comes with informal or ad hoc rules of engagement and status claiming by one profession over another.

Aims: Government programs and the Norwegian Directorate of Health give public health nurses in Norway an explicit role in population-based health promotion and disease-prevention work. The aim of this paper is to explore Norwegian public health nurses' experiences with population-based work., Methods: A phenomenological hermeneutic approach was adopted, involving face-to-face interviews with a purposeful sample of 23 public health nurses from urban and rural districts in two counties in Norway., Results: Three themes were identified: the predominance of work at the individual level, a lack of resources, and adherence to administrative directives. The interviews revealed that the public health nurses were mostly occupied with individual problem-solving activities. Population-based work was hardly prioritized, mostly because of a lack of resources and a lack of recognition of the population-based role of public health nurses., Conclusions: The study indicates contradictions between the public health nursing practice related to population-based work and the direction outlined by the government and the public health nursing curriculum, which may mean that the public health nursing role is not sufficiently clarified. The implementation of practice models and administrative directives and resources, as well as an explicit emphasis on population health in public health nursing education, can contribute to increased population-based interventions. Greater knowledge of and emphasis on population-based work in public health nursing are needed.

Background: A changing healthcare system affects the professional identity of nursing groups. Public health nursing has experienced challenges in balancing the paternalistic expert ideology and the empowerment participation ideology. A strong professional identity can legitimate nursing, and possibly influence the quality of nursing work. Narrations from practice can illuminate the nurses' theoretical and practical knowledge and help illustrate their collective professional identity., Aim: To illuminate the meaning of public health nursing knowledge and professional identity in a continuously changing public health nursing practice., Method: A qualitative interview study with a purposeful sample of 23 Norwegian public health nurses was carried out. Data were analysed using phenomenological hermeneutics, a descriptive method inspired by Ricoeur's philosophy of interpretation., Findings: Three themes emerged (i) Being a generalist: emphasising the need for generalised knowledge and using clinical judgement, (ii) Being one who empowers: focusing on resources and coping strategies, (iii) Being occupied with individual problem solving: focusing on individuals with special needs, using standardised techniques and protocols, and lacking specialised knowledge., Conclusion: Interpretation of the nurses' stories illuminated their need for generalised evidence-based knowledge, but also the importance of using sound clinical judgement in a diverse complex practice, where service users need encouragement, support and expert advice. Time pressures can limit the nurses' involvement. Many had an individual problem-focus more than a primary prevention focus, in contrast to governmental regulations stating that Norwegian public health nurses should focus on health promotion and primary prevention. Public health nurses have a broad generalised knowledge of their special target group giving them a 'specialist generalist' role. Clarification of this role, in relation to jurisdictional borders, can create a strong identity at a time when healthcare policy promotes economic values, professional neutrality and increased collaboration., (© 2015 Nordic College of Caring Science.)

Background: In today's health care, new health reforms focus on market values and demands of efficiency influence health workers' professional practice. Norwegian public health nurses work mainly with healthy populations, but the children, families and young people they meet can be in vulnerable and even dependent situations. Strategies in coping with ethically challenging encounters can be important for the identity of the profession., Aim: The aim of the study was to illuminate public health nurses' experiences of being in ethically charged encounters and to reflect upon how these experiences can influence their professional identity., Method: A purposive sample of 23 Norwegian public health nurses with experience ranging from 0.5 to 25 years narrated about their work-related experiences. The interviews were interpreted with a phenomenological hermeneutic method inspired by the philosophy of Paul Ricoeur., Findings: Four themes were identified: feeling responsible, being committed, feeling confident and feeling inadequate. These experiences were related to both work and private life and involved an emotional commitment to the well-being of children, young people and families., Conclusion: On the basis of the findings, it can be estimated that PHNs are committed to their work, and defending children's rights is a strong driving force. Responsibility for service users is a deciding factor that can overshadow institutional demands. It seems as if value conflicts mobilised courage which is essential in maintaining moral strength. This is in turn important for a strong professional identity and can have positive implications for the quality of public health nursing work., (© 2013 Nordic College of Caring Science.)

Aims: Health care is under constant change creating new and demanding tasks for public health nurses. The curriculum for public health nursing students is controlled by governmental directives that decide the structure and content of their education. This paper analyses manifest and latent discourses in the curriculum, in order to reveal underlying governmental principles for how public health nurses should promote health and prevent diseases., Methods: A critical discourse analysis of the Norwegian public health nursing curriculum was conducted., Results: The study indicates i) 'a competing biomedical and social-scientific knowledge-discourse', with biomedical knowledge dominating the content of the curriculum; ii) 'a paternalistic meta-discourse', referring to an underlying paternalistic ideology despite a clear focus on user participation; and iii) 'a hegemonic individual discourse'. Even though the curriculum stipulates that public health nurses should work at both an individual and a societal level, there is very little population focus in the text., Conclusions: Recent political documents concerning public health nursing focus more on health promotion, however, this is not sufficiently explicit in the curriculum. The lack of emphasis on social scientific knowledge, and the blurred empowerment and population perspective in the curriculum, can lead to less emphasis on health promotion work in public health nursing education and practice. The curriculum should be revised in order to meet the recent governmental expectations.

Aims and Objectives: The aims of this study are to develop knowledge about (1) the experiences of next of kin in caring for seriously ill patients with cancer and (2) the effects of strain and support on the next of kin's ability to cope., Background: Better treatment has resulted in patients with cancer normally living longer. Because this treatment is typically administered in a polyclinic or at home, next of kin inherit the largely unknown and demanding role of caregiver., Design: A qualitative, descriptive and interpretive design., Methods: Focus group interviews were used. The sample comprised 16 adults who were the next of kin of patients with cancer. A thematic content analysis was performed, the text coded for meaning units, condensed and interpreted based on the understanding of the next of kin's role and ability to handle the situation., Results: The role of next of kin is multifaceted and challenging. It is important for next of kin to be near and to take care of the sick. Next of kin's acceptance of the situation plays a crucial role in their ability to cope and to look forward. The unpredictability of the situation adds stress and affects the daily routines., Conclusions: Providing next of kin with knowledge, support and guidance is important in helping them to understand and cope with the situation and to reduce the amount of strain that they experience in the caregiving role., Relevance to Clinical Practice: This study emphasises the importance of health workers in possessing the knowledge and competence required to educate, guide and support the next of kin of those with cancer. Health workers should provide care to next of kin, and a support system for next of kin must also be available., (© 2012 Blackwell Publishing Ltd.)

Background: The aim of this study was to evaluate how tissue gas tensions and tissue metabolites measured in situ can detect hypoperfusion and differentiate between aerobic and anaerobic conditions during hemorrhagic shock. We hypothesized that tissue PCO(2) (PtCO(2)) would detect hypoperfusion also under aerobic conditions and detect anaerobic metabolism concomitantly with or earlier than other markers., Methods: Prospective experimental animal study with eight anesthetized pigs subjected to a continuous blood loss ∼8% of total blood volume per hour until death. We measured cardiac index, organ blood flows, and tissue levels of PO(2), PCO(2), glucose, pyruvate, lactate, and glycerol in intestine, liver, kidney, and skeletal muscle., Results: With reduction in blood flow to the organs under aerobic conditions, PtCO(2) increased ∼1-4 kPa from baseline. With the onset of tissue hypoxia there was a pronounced increase of PtCO(2), lactate, lactate-pyruvate (LP) ratio, and glycerol. Tissue pH and bicarbonate decreased significantly, indicating that metabolic acid was buffered by bicarbonate to generate CO(2)., Conclusion: Moderate tissue hypoperfusion under aerobic conditions is associated with increased PtCO(2), in contrast to metabolic parameters of ischemia (lactate, LP ratio, and glycerol) which remain low. From the onset of ischemia there is a much more rapid and pronounced increase in PtCO(2), lactate, and LP ratio. PtCO(2) can be used as a marker of hypoperfusion under both aerobic and anaerobic conditions; it gives an earlier warning of hypoperfusion than metabolic markers and increases concomitantly with or earlier than other markers at the onset of tissue anaerobiosis., (© 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.)

An improved phosphoramidite method is described to prepare oligonucleotides modified with the acyclic, achiral monomers 1. Examination of dimers, prepared on solid support or in solution, showed that phosphortriester dimers containing the allylic unit 1 were unstable towards bases, whereas phosphordiester dimers were stable. Phosphordiester dimers were obtained by replacing cyanoethyl phosphoramidites 2 with phosphoramidites 3, which gave phosphordiesters directly upon oxidation. The phosphordiester dimers were found to be stable towards capping and oxidation, but were somewhat labile towards acids. By reducing the contact time to acids during detritylation it was possible to prepare oligonucleotides containing 4 or 8 modified A, G or T units. The modified oligonucleotides hybridized to complementary DNA and RNA, although with reduced affinity (DeltaT(m) per modification -1 to -5 degrees C).

Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by Tm measurements showing a deltaTm of -2 to -6.5 degrees C per modification. An oligonucleotide with two modifications at the 3'-end showed considerable resistance towards cleavage by a 3'-exonuclease. No antiviral activity against HIV-1 or HSV-1 was found for 1, B = G or T, or for any of the trihydroxy derivatives 5.

We report synthesis and high-affinity hybridization of fully modified home-thymine 2'-deoxy and 2'-deoxy-2'-fluoro xylo nucleic acids.

An achiral, acyclic nucleoside analogue has been incorporated once or twice in oligodeoxyribonucleotides by the phosphoramidite method, and conditions found which allow deprotection of the oligonucleotides containing a sensitive modified allylic unit. The binding affinity of the modified oligonucleotides towards complementary DNA and RNA was reduced compared to unmodified DNA (DeltaT(m) -2 to -6.5 degrees C). An oligonucleotide with two modifications at the 3'-end showed considerable resistance towards cleavage with a 3'-exonuclease.

Synthesis of an oligonucleotide containing one methylphosphonate locked nucleic acid (LNA) thymine monomer using the phosphoramidite approach is described. The binding affinity of this 9-mer methylphosphonate LNA towards complementary DNA and RNA oligonucleotides was increased compared to the reference DNA, but decreased compared to the reference LNA. In the 9-mer sequence context studied, introduction of a single methylphosphonate LNA monomer, contrary to a single LNA monomer, efficiently inhibits 3'-exonucleolytic degradation.

The thymidine monomers of LNA with both alpha- and beta-configuration are incorporated with polarity reversals (i.e., with 3'-3' and 5'-5' junctions) in oligodeoxynucleotides with beta- and alpha-configuration, respectively. A 5'-O-phosphoramidite of the beta-LNA monomer is synthesised. Large destabilisations of duplexes with both complementary DNA and RNA are observed for oligodeoxynucleotides containing the alpha-LNA monomer, whereas a duplex with complementary RNA of an alpha-oligodeoxynucleotide containing the beta-LNA monomer is not destabilised.

To investigate the structural basis of the unique hybridization properties of LNA (locked nucleic acid) three novel LNA derivatives with modified carbohydrate parts were synthesized and evaluated with respect to duplex stabilities. The abasic LNA monomer (X(L), Figure 1) with the rigid carbohydrate moiety of LNA but no nucleobase attached showed no enhanced duplex stabilities compared to its more flexible abasic DNA counterpart (X, Figure 1). These results suggest that the exceptional hybridization properties of LNA primarily originate from improved intrastrand nucleobase stacking and not backbone preorganization. Two monocyclic seco-LNA derivatives, obtained by cleavage of the C1'-O4' bond of an LNA monomer or complete removal of the O4'-furanose oxygen atom (Z(L) and dZ(L), respectively, Figure 1), were compared to their acyclic DNA counterpart (Z, Figure 1). Even though they are more constrained than Z, the seco-LNA derivatives Z(L) and dZ(L) destabilize duplex formation even more than the flexible seco-DNA monomer Z.

We have used 2D NMR spectroscopy to study the sugar conformations of oligonucleotides containing a conformationally restricted nucleotide (LNA) with a 2'-O, 4'-C-methylene bridge. We have investigated a modified 9-mer single stranded oligonucleotide as well as three 9- and 10-mer modified oligonucleotides hybridized to unmodified DNA. The single-stranded LNA contained three modifications whereas the duplexes contained one, three and four modifications, respectively. The LNA:DNA duplexes have normal Watson-Crick base-pairing with all the nucleotides in anti-conformation. By use of selective DQF-COSY spectra we determined the ratio between the N-type (C3'-endo) and S-type (C2'-endo) sugar conformations of the nucleotides. In contrast to the corresponding single-stranded DNA (ssDNA), we found that the sugar conformations of the single-stranded LNA oligonucleotide (ssLNA) cannot be described by a major S-type conformer of all the nucleotides. The nucleotides flanking an LNA nucleotide have sugar conformations with a significant population of the N-type conformer. Similarly, the sugar conformations of the nucleotides in the LNA:DNA duplexes flanking a modification were also shown to have significant contributions from the N-type conformation. In all cases, the sugar conformations of the nucleotides in the complementary DNA strand in the duplex remain in the S-type conformation. We found that the locked conformation of the LNA nucleotides both in ssLNA and in the duplexes organize the phosphate backbone in such a way as to introduce higher population of the N-type conformation. These conformational changes are associated with an improved stacking of the nucleobases. Based on the results reported herein, we propose that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions (preorganization) by the LNA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases., (Copyright 2000 John Wiley & Sons, Ltd.)