Tele-orthodontics and sensor-based technologies: a systematic review of interventions that monitor and improve compliance of orthodontic patients.

BACKGROUND: Recent advances in orthodontics offer appealing tools to monitor compliance and designate protocols to enhance it. OBJECTIVE: This systematic review of systematic reviews (SRs) aimed to assess the effectiveness of digitized communication methods and sensor-based devices that track compliance in orthodontic patients. SEARCH METHODS: Five electronic databases (PubMed, Web of Science, MEDLINE, PsycINFO, and EMBASE) were searched from database inception up to 4 December 2022. SELECTION CRITERIA: SRs using digitized systems and sensor-based technologies to monitor and/or improve compliance with orthodontic treatment or during an active retention phase were included. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, and risk of bias assessment using the AMSTAR 2 tool were performed independently by two review authors. A qualitative synthesis of outcomes from moderate- and high-quality SRs was provided, and evidence was graded in accordance with a scale of statements. RESULTS: A total of 846 unique citations were retrieved. After study selection, 18 SRs met the inclusion criteria, and 9 moderate- and high-quality reviews were further integrated into the qualitative synthesis. Digitized communication methods were found to be effective in improving compliance with oral hygiene practices and adherence to orthodontic appointments. Monitoring removable appliance wear with microsensors revealed sub-optimal levels of compliance with wear instructions of intra-oral and extra-oral appliances. One review discussed the informational value of social media platforms and their importance in guiding the decision-making process to seek orthodontic treatment and compliance-related experiences. LIMITATIONS: The variability in the quality of included SRs and the limited number of primary studies on certain outcomes present as limitations within this overview. CONCLUSIONS: The integration of tele-orthodontics and sensor-based technologies to improve and monitor compliance within orthodontic practices is promising. There is sufficient evidence that establishing communication channels with orthodontic patients through reminders and audiovisual systems positively impact their oral hygiene practices throughout orthodontic treatment. However, understanding the informational value of social media as communication channels between clinicians and their patients, and their overall effect on modulating compliance is still insufficient. REGISTRATION: CRD42022331346.

Dental students' knowledge of and attitudes towards prescribing medication in Western Australia.

INTRODUCTION: Dentists can prescribe medications for prophylactic and therapeutic purposes. In Australia, dental graduates can autonomously practise within the scope of their qualifications without needing to undertake an internship post-graduation. Although previous research has identified knowledge gaps amongst dental students in Australia on pharmacology and pharmacotherapeutic knowledge, there has been no published research that qualitatively highlights dental students' knowledge of medication prescribing in Australia. This study aimed to undertake a qualitative analysis of Western Australian dental students' attitudes towards and knowledge of medication prescribing. METHODS: This qualitative case study design employed semi-structured interviews as means of collecting data. It utilised a purposive sampling in penultimate and final year dental students at the University of Western Australia. RESULTS: Twenty dental students participated in the study. Five key themes were identified in the data: current and previous education, application when delivering pharmacology and pharmacotherapeutics, teaching to ensure patient-centred care, supervision and referral to relevant resources. Participants agreed that having previous knowledge in the area provides students with confidence regarding medication prescribing. Furthermore, students in this study valued having guidance when prescribing medications. CONCLUSIONS: This study highlights the complexity of medication prescribing for dental students. It also highlights their experience with the current pharmacology and pharmacotherapeutics curriculum. All students interviewed valued application-based teaching, making it specific to dentistry. If curriculum were to be redeveloped, considering their perceptions may be a valuable tool.

A qualitative study of orthodontic patients' experiences in quarantine during the COVID-19 pandemic outbreak.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is one of the most formidable challenges that influenced all domains of health care delivery. This research explored the experiences and challenges orthodontic patients faced in quarantine during the COVID-19 outbreak. The goal was to learn from patients about their oral health and general practices during this time to provide optimal delivery of orthodontic treatment care. METHODS: A phenomenographic qualitative design involving semistructured face-to-face interviews. A purposive sampling strategy was deployed to collect qualitative data from 24 orthodontic patients who quarantined during the COVID-19 pandemic. All interviews were digitally recorded, and afterwards, they were transcribed verbatim. RESULTS: Four main themes and associated subthemes were identified. The themes were (1) oral-health-related behavioral changes, (2) impact on treatment progression, (3) psychosocial impact and attitude changes, and (4) areas for future enhancements in health care delivery. Overall findings revealed both positive and negative behavioral changes in orthodontic patients regarding their adjustment during the quarantine and its implications to general health and well-being. CONCLUSIONS: Findings from this study suggest that COVID-19 impacted dental health care delivery to orthodontic patients during the quarantine. Patients reported psychosocial and behavioral changes as a consequence of treatment disruption and pandemic lockdown. The implications of these findings to the clinical dental environment and patient education are pivotal to further target areas in dental health care delivery that require strengthening. As such, clinicians could expect behavioral changes from orthodontic patients and identify better strategies to mitigate clinical challenges resulting from such changes.

A qualitative meta-synthesis of research into patients' past experiences and perceptions of orthodontic treatment outcomes.

BACKGROUND: There is a growing body of evidence emphasizing the importance of research into patient-centred experience in orthodontics. Benefits following orthodontic treatment are mainly related to improved aesthetics and psychosocial outcomes. However, treatment experience from the perspective of orthodontic patients is yet to be fully understood. OBJECTIVE: To understand the past experiences and current perceptions of treatment outcomes of orthodontic patients. STUDY DESIGN: A qualitative meta-ethnography. SELECTION CRITERIA: Qualitative studies and mixed-methods articles with a distinct qualitative component presenting patients' perception of outcomes and overall experiences after an active course of orthodontic treatment were included. SEARCH METHODS: Comprehensive electronic searches were conducted in MEDLINE, Scopus, Web of Science, PsycINFO, and EMBASE up to May 2021, supplemented by grey literature and manual searches. DATA COLLECTION AND ANALYSIS: Two independent reviewers were involved in study selection, data extraction, and quality appraisal. The Critical Appraisal Skills Programme tool for qualitative research was used to assess the quality of included studies. Analysis of data was conducted using meta-ethnographic methods. RESULTS: Out of 801 retrieved search hits, six studies fulfilled the inclusion criteria and were included in the synthesis. The analysis revealed three main themes and associated sub-themes: (1) Reflection on the past treatment experience, (2) Patient satisfaction with treatment outcomes, and (3) Learning to live with retainers. LIMITATIONS: Results express patients' opinions shortly after treatment, and the long-term impact of orthodontic treatment is yet to be understood. CONCLUSIONS: Orthodontic patients mainly viewed their experiences and treatment results positively. Desirable aesthetic outcomes, psychosocial outcomes, and satisfaction with smiles were often reported in the studies reviewed. However, some barriers to optimal experiences were noticed concerning orthodontic retention. REGISTRATION: PROSPERO (CRD42020180121).

Development and Prospective Validation of a Risk Calculator That Predicts a Low Risk Cohort for Atypical Ductal Hyperplasia Upstaging to Malignancy: Evidence for a Watch and Wait Strategy of a High-Risk Lesion.

BACKGROUND: Guidelines recommend surgical excision of atypical ductal hyperplasia (ADH) due to the concern of undersampling a potential malignancy on core needle biopsy (CNB). The purpose of this study was to determine clinical, radiological and pathological variables associated with ADH upstaging to cancer and to develop a predictive risk calculator capable of identifying women who have a low oncological risk of upstaging. METHODS: A prospectively collected database from a tertiary breast referral center was analyzed for women diagnosed with ADH on CNB between January 2013 to December 2017 who underwent surgical excision. CNB and surgical pathology reports were examined to determine rate of upstaging. The association between clinical, radiological and pathological variables were evaluated using regression analysis to determine predictors of ADH upstaging to cancer. Significant variables (p ≤ 0.05) identified on univariate analysis were assigned a score of "1" and were included in the ADH upstaging risk calculator. RESULTS: A total of 1986 patients underwent surgery for a high-risk lesion. We identified 318 (16.0%) patients who had ADH identified on their CNB who underwent surgery-of which 290 were included in our study. The upstage rate was 24.8%. Five variables were associated with upstaging and included in our calculator: (1) lesion > 5 mm on ultrasound; (2) lesion > 5 mm on mammogram; (3) one or more "high-risk" lesion(s) on CNB; (4) pathological suspicion for cancer and; (5) incomplete removal of calcifications on CNB. Patients with a score of 0 had a 2% risk of being upstaged to cancer and were deemed low risk with 17.2% of patients falling within this category. CONCLUSIONS: Patients with ADH on CNB can be stratified into a low oncological cohort who have a 2% risk of being upstaged to carcinoma. In the future, these select patients may be counselled and potentially offered observation as an alternative to surgery.

Is microductectomy still necessary to diagnose breast cancer: a 10-year study on the effectiveness of duct excision and galactography.

PURPOSE: Patients with spontaneous nipple discharge (SND) who have neither clinically palpable masses nor evidence of disease on imaging with mammogram and/or ultrasound are traditionally investigated with galactogram and duct excision. As breast imaging improves, it has raised the question whether galactography and microductectomy are necessary to diagnose breast cancer. The purpose of this study was to determine the incidence of malignancy in patients presenting with SND who underwent microductectomy and to evaluate the utility of duct excision and galactography in patients whose initial clinical and radiological evaluation were negative. METHODS: A 10-year retrospective study was conducted in British Columbia's largest tertiary breast referral center examining the clinical, radiological and pathological results for all patients who underwent a microductectomy procedure for SND between 2008 and 2017. RESULTS: A total of 231 microductectomies were performed and the overall incidence of malignancy was 13% (n = 32). Following initial work up, 155 patients (67%) had only discharge on exam and no radiologically suspicious findings of malignant disease. Of these patients, 14% (n = 21) were diagnosed with cancer by duct excision. Galactography yielded a sensitivity and specificity of 63% and 36%, respectively (PPV 15% and NPV 85%). Lastly, we found that 3% of patients (n = 8) initially diagnosed with benign disease later developed breast cancer. CONCLUSIONS: Patients with SND should continue to be evaluated with microductectomy to prevent missing a breast cancer. Moreover, we do not recommend performing galactography for diagnosing breast cancer due to poor sensitivity and specificity though it may assist in preoperative planning.

Adverse effects of topical corticosteroids in paediatric eczema: Australasian consensus statement.

Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a child's sleep, education, development and self-esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short-term hypothalamic-pituitary-adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children.

Students' experience and perceptions of undergraduate endodontic education in New Zealand.

This study investigated the clinical experience and perceptions of New Zealand graduating dental students (2019 and 2020) towards endodontic teaching and their clinical learning outcomes using an online survey and clinical scenarios. Quantitative data were analysed using SPSS software, and qualitative data were analysed thematically. Responses were similar for both cohorts (response rates 74%, 2019; 73%, 2020). Endodontic teaching was valuable and interesting but difficult compared with other disciplines. Molar endodontics, finding canals and managing posture were challenging. Students felt more confident and less anxious when supervised by clinicians experienced in endodontics. Time management was the most anxiety-inducing factor and significantly related to clinical experience (p < 0.001). Overall, students appropriately applied knowledge in most areas of endodontics while holistic problem-solving in complex scenarios was variable. Maximising clinical experience and supervision from teachers experienced in endodontics are important for learning, improving confidence and reducing anxiety.

A systematic review of the opportunities and challenges of micro-credentials for multiple stakeholders: learners, employers, higher education institutions and government.

Micro-credentials are gaining traction as viable vehicles for rapid upskilling of the workforce in the twenty-first century and potential pathways for gaining employment for some students. The primary purpose of the current systematic review was to understand the current conceptions and discourses of micro-credentials in higher education and to identify the opportunities and challenges in adopting micro-credentials in higher education. The review also aimed to develop a need-driven micro-credentials framework that demonstrates the value of micro-credentials to stakeholders, i.e., learners, higher education institutions, employers, and government agencies. Key findings revealed that there are various stakeholders' needs and expectations. The learner wants short, practical, and up-to-date courses for their chosen career path, education institutions emphasise accreditation for building trust, employers want clarity regarding the competencies gained through micro-credentials, and government bodies expect higher graduate employability with lower tuition fees. Key findings revealed that implementing micro-credentials can be disruptive in the higher education sector and present several challenges. However, these challenges are likely to be mitigated by increased collaboration among stakeholders. The review has revealed several outstanding research questions critical for the success of micro-credentials as significant pathways to supplement traditional degree programmes. The research presented in the article has implications for policy development to guide the implementation of micro-credentials in the higher education sector.

Psychometric properties of the TACT framework-Determining rigor in qualitative research.

Introduction: The credibility of qualitative research has long been debated, with critics emphasizing the lack of rigor and the challenges of demonstrating it. In qualitative research, rigor encompasses explicit, detailed descriptions of various research stages, including problem framing, study design, data collection, analysis, and reporting. The diversity inherent in qualitative research, originating from various beliefs and paradigms, challenges establishing universal guidelines for determining its rigor. Additionally, researchers' often unrecorded thought processes in qualitative studies further complicate the assessment of research quality. Methods: To address these concerns, this article builds on the TACT framework, which was developed to teach postgraduate students and those new to qualitative research to identify and apply rigorous principles and indicators in qualitative research. The research reported in this article focuses on creating a scale designed to evaluate the psychometric properties of the TACT framework. This involves analyzing the stability of its dimensions and understanding its effectiveness as a tool for teaching and research. Results: The study's findings indicate that the TACT framework, when assessed through the newly developed scale, exhibits stable dimensions consistent with rigorous qualitative research principles. The framework effectively guides postgraduate students and new researchers in assessing the rigor of qualitative research processes and outcomes. Discussion: The application of the TACT framework and its evaluation scale reveals several insights. Firstly, it demonstrates the framework's utility in bridging the gap in pedagogical tools for teaching rigor in qualitative research methods. Secondly, it highlights the framework's potential in providing a structured approach to undertaking qualitative research, which is essential given this field's diverse methodologies and paradigms. However, the TACT framework remains a guide to enhancing rigor in qualitative research throughout all the various phases but by no means a measure of rigor. Conclusion: In conclusion, the TACT framework and its accompanying evaluative scale represent significant steps toward standardizing and enhancing the rigor of qualitative research, particularly for postgraduate students and early career researchers. While it does not solve all challenges associated with obtaining and demonstrating rigor in qualitative research, it provides a valuable tool for assessing and ensuring research quality, thereby addressing some of the longstanding criticisms of the quality of research obtained through qualitative methods.

Job prospects and career pathways for human anatomy graduates from the University of Otago: Implications for student support and professional development.

The Department of Anatomy (Anatomy) at the University of Otago delivers programs for students in diverse areas, including clinical anatomy, neuroscience, reproduction and biological anthropology. This study explored the experiences of alumni during their study and career pathways post-graduation through an online questionnaire distributed to department alumni. Most of the 190 participants studied anatomy as undergraduates (74.2%) and graduated in the past decade (56.8%). Reasons for taking anatomy included finding the topic interesting, a pathway into professional programs, or a degree requirement. Current employment differed between undergraduate (44.7% currently employed in clinical settings) and postgraduate alumni (26.4% currently employed in research, 19.5% in clinical settings). The main pathways for finding jobs were by direct search (38.6%), completing tertiary education (29.2%), and through social network connections (16.4%). Women alumni were less likely to feel that Anatomy prepared them for their careers than men. Themes related to positive and negative experiences included staff, course material/resources, social events, and peers. Suggestions to improve the departmental "sense of community" included increasing departmental events and resources. Alumni suggested that Anatomy should provide more potential career information, make available recent alumni profiles, and organize career fairs and networking opportunities. Postgraduate alumni were more likely to feel a "sense of belonging" in Anatomy than undergraduate alumni. Findings from this research provide an essential data point in the international evaluation of career prospects of anatomy graduates and provide a road map for other institutions to survey their alumni to obtain local insights.

Adaptiveness for Online Learning: Conceptualising 'Online Learning Dexterity' from Higher Education Students' Experiences.

Online learning dexterity, or the ability to effortlessly adapt to online learning situations, has become critical since the COVID-19 pandemic, but its processes are not well-understood. Using grounded theory, this study develops a paradigm model of online learning dexterity from semi-structured interviews with 32 undergraduate and postgraduate students from a university in New Zealand. Through students' online learning experiences during the pandemic from 2020 to 2021, online learning dexterity is found to be how students make online learning 'just as good' as face-to-face learning by creating and adjusting five learning manoeuvres according to developing online learning circumstances. Undergraduates and postgraduates re-use familiar study strategies as deep learning manoeuvres, but undergraduates restrict support-seeking manoeuvres to lecturers. Technical problems with online systems and poor course organisation by lecturers affected learning productivity, resulting in the need for more time optimisation manoeuvres. Social support helped students activate persistence manoeuvres to sustain online class attendance. However, undergraduates had more problems sustaining interest and engagement during class as they were not as proficient with using learning presence manoeuvres as postgraduates enrolled in distance learning programmes. The theoretical and practical significance of online learning dexterity for post-pandemic higher education is discussed.

Incorporating Lymphovenous Anastomosis in Clinically Node-Positive Women Receiving Neoadjuvant Chemotherapy: A Shared Decision-Making Model and Nuanced Approached to the Axilla.

INTRODUCTION: Lymphedema remains a risk for 13-34% of breast cancer patients who require an axillary dissection (ALND) and radiation. Immediate lymphovenous anastomosis (LVA) may mitigate lymphedema by up to 30% by restoring the physiologic lymphatic drainage immediately after ALND. Currently, completion of ALND (cALND) versus radiation after neoadjuvant therapy (NAC) is being addressed by the Alliance A11202 trial, leaving a paucity of data to guide practice. Our study describes the implementation process of LVA into clinical practice after NAC for node-positive breast cancer in the current clinical context. METHODS: We reviewed a prospective database of LVA in node-positive patients (cT1-4,Nany) who received NAC followed by axillary surgery ± immediate LVA from October 2021 to 2022. The evolution of the surgical approach is described. Specifically, patients who downstaged to clinically negative nodes post-NAC were offered targeted SLNB with dual-tracer and intraoperative frozen section (FS). Patients were reminded that the standard of care for any node positive is cALND. Immediate cALND with LVA was performed for grossly positive nodes or all positive SLNs; cALND was omitted for those with negative SLNs. For a microscopic disease on a frozen section, a shared decision was made pre-operatively, given each patient's differing valuations of the benefit and risks of cALND ± LVA versus no cALND with planned regional radiation postoperatively. LVA was offered as an option as part of our institutional evaluation of the procedure. RESULTS: A total of 15 patients were included; the mean age was 49.9 (range 32-75) with stage IIA to IIIB breast cancer. Of these, 6 (40%) were triple negative, 5 (33.3%) HER-2 positive, and 4 (26.7%) ER/PR+ HER-2 negative. There were 13 women (86.7%) who had persistent axillary adenopathy based on clinical and/or ultrasound assessment, with 8 patients proceeding directly to ALND with LVA. Among these patients, 3 (37.5%) had pathologic nodal disease, and 5 (62.5%) were node negative, confirming the limitations of pre-operative imaging. As a result, the subsequent 7 (46.7%) underwent targeted SLNB with FS, with 3 patients (42.9%) avoiding an ALND as a result of a negative FS. A total of 4 patients (57.1%) had 1 or more positive lymph nodes on FS: 3 proceeded with a cALND and LVA, and 1 patient (14.2%) opted for no cALND based on a pre-operative discussion and received adjuvant radiation and chemotherapy. Of the 11 patients who underwent ALND and LVA, 1 patient (9.1%) developed lymphedema at 6.9 months following their surgery. The accuracy, sensitivity, and specificity of pre-operative US were 46.7%, 85.7%, and 12.5% and intraoperative FS were 88.0%, 72.7%, and 100%, respectively. CONCLUSIONS: As adjuvant nodal radiation and systemic therapy continue to improve, the benefit of a cALND in patients with the limited residual disease remains unclear as we await the outcomes from clinical trials. In the era of clinical uncertainty, we propose a nuanced approach to the axilla by utilizing a shared decision model with patients, incorporating targeted SLNB with FS and completion node dissection when required and desired by the patient, coupled with LVA in a simple stepwise treatment pathway.

Student Nurse Experiences of Learning from Clinical Practice and Simulations in New Zealand: A Descriptive Qualitative Study.

BACKGROUND: In New Zealand, finding quality learning opportunities in the clinical setting is often challenging. In response, using simulation as an alternate learning environment has been proposed. Literature related to the substitution of clinical experience with simulation is relatively sparse and, in New Zealand, non-existent. PURPOSE: This study sought to answer the foundational issue of how students experience learning in the simulation and clinical environment. The research question was: 'how do nursing students in New Zealand experience simulation and clinical practice as an environment for learning?' METHODS: This research used a descriptive qualitative design based on in-depth semi-structured interviews with twelve nursing students and written reflective stories from students' clinical practice. FINDINGS: Students' experiences in the two learning environments were different. These differences were associated with relational care, predictability, responsibility and managing critical incidents. CONCLUSIONS: Each environment offered nursing students valuable, yet unique learning opportunities. The key to educating nursing students is ensuring that both simulations and clinical practice are appropriately placed in the nursing curriculum while recognising their strengths and weaknesses.

Shifting online during COVID-19: A systematic review of teaching and learning strategies and their outcomes.

This systematic literature review of 36 peer-reviewed empirical articles outlines eight strategies used by higher education lecturers and students to maintain educational continuity during the COVID-19 pandemic since January 2020. The findings show that students' online access and positive coping strategies could not eradicate their infrastructure and home environment challenges. Lecturers' learning access equity strategies made learning resources available asynchronously, but having access did not imply that students could effectively self-direct learning. Lecturers designed classroom replication, online practical skills training, online assessment integrity, and student engagement strategies to boost online learning quality, but students who used ineffective online participation strategies had poor engagement. These findings indicate that lecturers and students need to develop more dexterity for adapting and manoeuvring their online strategies across different online teaching and learning modalities. How these online competencies could be developed in higher education are discussed.

Site-Specific Isopeptide Bond Formation: A Powerful Tool for the Generation of Potent and Nontoxic Antimicrobial Peptides.

Antimicrobial peptides (AMPs) have the potential to treat multidrug-resistant bacterial infections. However, the clinical application of AMPs is prevented by their toxicity and poor proteolytic stability. Here, a site-specific approach is used to generate new AMPs to improve their efficacy against bacterial pathogens while reducing their toxicity. We modified and generated a new series of antimicrobial peptides from the leucine- and lysine-rich antimicrobial peptide Amp1L (LKLLKKLLKKLLKLL) by the site-specific incorporation of an isopeptide bond while retaining the peptide's size, sequence, charge, and molecular weight. This single bond switch provides the peptides with a weak helical conformation, strong antimicrobial activity, resistance to proteolytic degradation, low toxicity, and lower hemolytic activity. This new site-specific approach offers a powerful tool for developing potent and nontoxic antimicrobial drugs.

Conceptual model to analyze the effects caused by technological disaster on the physical-chemical state of the lower Doce River waters, Brazil.

Research has shown the effort to develop conceptual models that relate anthropic stressors to changes in aquatic environment state. Several of these models come from the structure Drivers, Pressures, State, Impact and Response (DPSIR), which has been used since the 1990s. However, there is a lack of conceptual models that consider in its structure the connection between the damages caused in the aquatic environment and technological disasters. This research develops a general conceptual model based on the DPSIR structure incorporating technological disasters. Based on the general conceptual model guidelines and the methodological procedure associated with it, a model was developed to assess the Lower Doce River waters' state, by considering Fundão's iron-ore dam failure scenario, which took place in November 2015, in the municipality of Mariana, state of Minas Gerais, Brazil. The relevant aspects of this adaptation of the DPSIR structure were: I) it considers the combined effect of drivers and pressures that already existed in the study area with those originated from the technological disaster; and II) the causal relationships among elements of the model were explicited through a systemic conceptual map, allowing a more holistic and integrated view of the problem. The application of the conceptual model to Doce River's scenario before the disaster allowed us to verify that a set of environmental pressures was already acting in a way to stress it, making the river vulnerable. For the post-disaster scenario, it was possible to determine that the already existing vulnerability condition, caused by urbanization, agriculture1 and mining, had been intensified by adding new pressures due to the tailings dam failure.

Mutation of conserved tryptophan residues at the dimer interface of Staphylococcus aureus nitric oxide synthase.

Nitric oxide synthases (NOSs) share two invariant tryptophan residues within a conserved helical lariat that is part of the pterin-binding site and dimer interface. We mutated Staphylococcus aureus NOS Trp-314 (to alanine, phenylalanine, tyrosine and histidine) and Trp-316 (to alanine, phenylalanine and tyrosine) and characterized the effects of mutation on heme environment, quaternary structure, enzymatic activity, and substrate affinity. With arginine present, all saNOS variants bound heme with native thiolate ligation, formed high spin ferric complexes and were dimeric. All variants catalyze the peroxide-dependent oxidation of N-hydroxy-l-arginine, at rates from 10% to 55% of wild type activity. Arginine-free proteins are dimeric with the exception of W314A. Arginine affinity for all variants decreases with increasing temperature between 15 and 42 °C but is precipitous for position-314 variants. Previous structural and biophysical characterization of NOS oxygenase domains demonstrated that the protein can exist in either a tight or loose conformation, with the former corresponding to the active state of the protein. In the position-314 variants it is likely that the loose conformation is favoured, owing to the loss of a hydrogen bond between the indole side chain and the polypeptide backbone of the helical lariat.

Distinct DNA exit and packaging portals in the virus Acanthamoeba polyphaga mimivirus.

Icosahedral double-stranded DNA viruses use a single portal for genome delivery and packaging. The extensive structural similarity revealed by such portals in diverse viruses, as well as their invariable positioning at a unique icosahedral vertex, led to the consensus that a particular, highly conserved vertex-portal architecture is essential for viral DNA translocations. Here we present an exception to this paradigm by demonstrating that genome delivery and packaging in the virus Acanthamoeba polyphaga mimivirus occur through two distinct portals. By using high-resolution techniques, including electron tomography and cryo-scanning electron microscopy, we show that Mimivirus genome delivery entails a large-scale conformational change of the capsid, whereby five icosahedral faces open up. This opening, which occurs at a unique vertex of the capsid that we coined the "stargate", allows for the formation of a massive membrane conduit through which the viral DNA is released. A transient aperture centered at an icosahedral face distal to the DNA delivery site acts as a non-vertex DNA packaging portal. In conjunction with comparative genomic studies, our observations imply a viral packaging pathway akin to bacterial DNA segregation, which might be shared by diverse internal membrane-containing viruses.

Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity.

Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface. B7-H1 could be further upregulated by tumor environmental factors. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1. Blockade of B7-H1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-gamma. T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy.