Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

Impact of root canal preparation using two single-file systems on the intra-radicular microbiome of teeth with primary apical periodontitis.

OBJECTIVES: This study aimed to describe the effects of two single-file systems on the diversity of the endodontic microbiome of teeth with primary asymptomatic apical periodontitis. MATERIALS AND METHODS: The root canals from single-rooted teeth with apical periodontitis were prepared using either the Reciproc Blue (RB) or the XP-endo Shaper (XPS) instrument system. The latter was followed by a supplementary step with the XP-endo Finisher (XPF) instrument. For irrigation, 5.25% sodium hypochlorite was used. Root canal samples were taken at the baseline (S1), after preparation (S2), and after the supplementary step (S3). DNA was extracted and subjected to high-throughput sequencing using the MiSeq Illumina platform. RESULTS: Samples from 10 teeth from the RB and 7 from the XPS group were subjected to DNA sequencing. Initial samples differed significantly from post-preparation samples in bacterial diversity, with no significant difference when comparing the two instrument systems. The most dominant phyla in S2 were Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, and Actinobacteria. The same phyla were found to dominate baseline samples and samples taken after using XPF, but with differences in the ranking of the most dominant ones. At the genus level, the most dominant genera identified after RB instrumentation were Bacteroidaceae [G-1], Fusobacterium, and Staphylococcus, while the most dominant genera after XPS instrumentation were Fusobacterium and Porphyromonas. These genera were also dominant in the initial samples. CONCLUSIONS: Both treatment protocols had measurable effects on the root canal microbial diversity, with no significant differences between them. Most of the dominant taxa involved in the primary infection and probably in the aetiology of apical periodontitis were eliminated or substantially reduced. CLINICAL RELEVANCE: The most dominant taxa that persisted after instrumentation were Fusobacterium, Porphyromonas, Staphylococcus, and Bacteroidaceae [G-1].

Simplification and Multidimensional Adaptation of the Stratification Tool for Pharmaceutical Care in People Living With HIV.

BACKGROUND: People living with human immunodeficiency virus (HIV) require specific pharmaceutical care (PC). Although the 2017 Capacity-Motivation-Opportunity (CMO) PC model allows a multidisciplinary approach that focuses on patient needs, it is too complex and presents room for improvement. OBJECTIVE: The aim of this study is to simplify and adapt the previous 2017 PC tool through a multidimensional approach to improve HIV patient care, to prove the validity of the model in real-life patients. METHODS: The new PC tool was generated by keeping some of the variables of the 2017 document and conducting a literature search. Content validity was determined by a 2-round Delphi methodology with an expert panel of 42 pharmacists. Consensus for the first and second rounds was defined as ≥70% agreement. The tool generated was validated in 407 real-life patients. RESULTS: Thirty-seven experts completed the first round of the Delphi survey and 36 the second. No consensus was reached for 3 variables, any of the frequency options and 4 interventions, while the experts agreed not to include 1 intervention in round 1. Consensus to include them was found for all but 1 variable and 1 intervention in round 2. The final tool obtained to select and stratify HIV-positive patients was composed of 9 dimensions divided into 17 variables. The new tool was validated with real-life patients and 3 priority levels were defined. CONCLUSIONS AND RELEVANCE: We created a new pyramid of score thresholds to classify patients into priority levels. The new tool simplifies the 2017 model and improves its utility to help HIV-positive patients, owing to its multidimensional approach.

Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families.

Alazami syndrome is a rare disorder with an autosomal recessive inheritance caused by pathogenic biallelic variants in the LARP7 gene. Clinically, it is mainly characterized by short stature, intellectual disability, and dysmorphic facial features. However, the phenotype is not yet well-defined because less than 50 cases have been described to date. Here, we report three new patients from two unrelated Spanish families who, in addition to the defined features of Alazami syndrome, also exhibit unique features that broaden the phenotypic spectrum of the syndrome. Moreover, we describe the novel frameshift variant c.690_699delins27 in the LARP7 gene, in which loss of function is a known mechanism of Alazami syndrome.

Recurrent and functional regulatory mutations in breast cancer.

Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.

Fine-grained mathematical modeling for cost-effectiveness evaluation of public health policies for cervical cancer, with application to a Colombian case study.

BACKGROUND: Cervical cancer (CC) is globally ranked fourth in terms of incidence and mortality among women. Vaccination against Human Papillomavirus (HPV) and screening programs can significantly reduce CC mortality rates. Hence, executing cost-effective public health policies for prevention and surveillance is crucial. However, defining policies that make the best use of the available resources is not easy, as it requires predicting the long-term costs and results of interventions on a changing population. Since the simpler task of predicting the results of public health policies is difficult, devising those that make the best usage of available resources is an arduous challenge for decision-makers. METHODS: This paper proposes a fine-grained epidemiological simulation model based on differential equations, to effectively predict the costs and effectiveness of CC public health policies that include vaccination and screening. The model represents population dynamics, HPV transmission within the population, likelihood of infection clearance, virus-induced appearance of precancerous lesions and eventually CC, as well as immunity gained with vaccination and early detection with screening. RESULTS: We offer a compartmentalized modeling approach that separates population, epidemics, and intervention concerns. We instantiate models with actual data from a Colombian case study and analyze their results to show how our modeling approach can support CEA studies. Moreover, we implement models in an open-source software tool to simultaneously define and evaluate multiple policies. With the support of the tool, we analyze 54 policies within a 30-year time horizon and use as a comparator the CC policy that has been used until recently. We identify 8 dominant policies, the best one with an ICER of 6.3 million COP (Colombian Pesos) per averted DALY. We also validate the modeling approach against the available population and HPV epidemic data. The effects of uncertainty in the values of key parameters (discount rate, sensitivity of screening tests) is evaluated through one-way sensitivity analysis. CONCLUSIONS: Our modeling approach can provide valuable support for healthcare decision-makers. The implementation into an automated tool allows customizing the analysis with country-specific data, flexibly defining public health policies to be evaluated, and conducting disaggregate analyses of their cost and effectiveness.

The Aryl Hydrocarbon Receptor Ligand 6-Formylindolo(3,2-b)carbazole Promotes Estrogen Receptor Alpha and c-Fos Protein Degradation and Inhibits MCF-7 Cell Proliferation and Migration.

INTRODUCTION: Worldwide, breast cancer is the most common cancer in women and is the main cause of death among all neoplasia in this group. Luminal A breast cancer represents approximately 70% of all breast cancers and is treated with hormone therapies targeting estrogen receptor alpha (ERα). Unfortunately, patients develop drug resistance leading to recurrence of neoplasia due to estrogen-independent ERα reactivation. Therefore, it is crucial to identify new molecular targets downstream ERα signaling pathway that allows the implementation of better treatments to improve the outcome of breast cancer patients. Overexpression of c-Fos, an ERα gene target, has been associated with increased cell motility, malignancy, metastasis, and invasion while its neutralization results in decreased breast cancer tumorigenesis. The aryl hydrocarbon receptor (AHR) ligands halogenated and polycyclic aromatic hydrocarbons, highly toxic compounds, down regulate c-Fos and ERα levels. The present study aimed to evaluate whether 6-formylindolo(3,2-b)carbazole (FICZ), a no toxic AHR agonist, modifies c-Fos levels in MCF-7 mammary carcinoma cells as well as to determine its effects on cell proliferation and migration. In addition, the possible mechanism through which FICZ mediates c-Fos levels in MCF-7 cells was investigated. METHODS: Initially, the effect of FICZ on c-Fos mRNA and protein levels in MCF-7 cells, untreated or treated with estradiol, was evaluated by qPCR and Western blot. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin, an AHR prototype agonist, was used as a positive control. Next, we examined the effect of FICZ on MCF-7 cell proliferation and migration by cell counting, MTT, 3H-thymidine incorporation, and scratch-wound assays. Finally, the involvement of proteasome 26S on ERα and c-Fos protein degradation was investigated by the use of MG132 and Western blot. RESULTS: The data show that FICZ treatment downregulates c-Fos mRNA and protein levels, most likely by promoting ERα proteasome degradation, blocking MCF-7 cell proliferation and migration. The results also demonstrate that liganded ERα was required for FICZ-mediated ERα degradation. CONCLUSIONS: Activation of AHR results in a decreased MCF-7 cell proliferation and migration by ERα and c-Fos down regulation. Targeting AHR might be a promising therapy for breast cancer treatment, particularly when estrogen-independent ERα reactivation presents.

Cyst formation and bony ingrowth inside coil-type open-architecture anchors used for arthroscopic remplissage: a volumetric computed tomographic study of 50 anchors.

BACKGROUND: The use of anchors in the proximal humerus during arthroscopic surgery can cause localized bone loss due to osteolysis and cyst formation. The purpose of this study was to use computed tomography (CT) to evaluate the incidence of implant-related bone loss and cyst formation after implantation of polyetheretherketone (PEEK) coil-type open-architecture anchors during remplissage for the management of Hill-Sachs defects (HSDs) in patients with shoulder instability. METHODS: This was a single-cohort, observational study with a minimum of 12 months of follow-up. Subjects undergoing arthroscopic instability surgery with HSD requiring remplissage were included. The volume of the bone defects and the degree of bony ingrowth into the anchor were measured on CT images. RESULTS: Thirty-one participants (28 males, 3 females; mean age 29.4 years, standard deviation [SD] 10.6) in whom 50 anchors (4.5-mm Healicoil PEEK double-loaded anchors) were used were evaluated with a CT performed at a mean of 14.1 (SD 3.74) months after surgery. Full bony ingrowth inside the anchor was found in 15 anchors (30%, range 17.8%-44.5%); clear ossification with a thin lucent rim was found in 10 anchors (20%, range 10.0%-33.7%); discontinuous ossification was found in 8 anchors (16%, range 7.2%-29.1%); and no ossification was observed inside 17 anchors (34%, range 21.2%-48.7%). Regarding bone defect size, no bone defect was identified in 15 anchors (30%, 95% CI 17.9%-44.6%), a partial bone defect was found in 17 anchors (34%, 95% CI 21.2%-48.7%), hole enlargement was found in 17 anchors (34%, 95% CI 21.2%-48.7%), and 1 anchor caused a cyst larger than twice the size of the hole made for anchor insertion (2%, 95% CI 0.1%-8.6%). At the 1-year evaluation, none of the participants presented recurrence or residual apprehension. CONCLUSION: The use of PEEK coil-type open-architecture anchors for remplissage during instability surgery caused large cystic lesions in less than 10% of anchors. There was full bony ingrowth in one-third of anchors, and partial cancellous bone ingrowth occurred in another third of anchors.

Including audience response systems in debriefing. A mixed study during nursing simulation-based learning.

BACKGROUND: The audience response systems are being implemented to support active learning in nursing degree programs. The benefits of audience response systems have been studied in lecture-based classes and seminars, but their advantages or inconveniences when included in the debriefing phase of a high-fidelity clinical simulation have not been explored. The study aim was to discover student´s experience about using of interactive questions during debriefing, and the self-perceived effects on attention, participation and motivation. METHODS: A Mixed-methods study was used exploratory sequential design in a university. The participants were 4th-year students enrolled in the Nursing Degree in a university in Southern Spain. (1) Qualitative phase: a phenomenological approach was utilized, and focus groups were used for data-collection. (2) Quantitative phase: cross-sectional descriptive study using a questionnaire designed "ad hoc", on the experiences on the use of interactive questions in the debriefing phase and the Debriefing Experience Scale. RESULTS: (1) Qualitative phase: the students highlighted the facilitating role of the interactive questions during the reflection part of the debriefing, and mentioned that the interactive questions helped with stimulating attention, participation, and motivation during the analytical part of the debriefing; (2) Quantitative phase: it was observed that the best evaluated dimension was "Motivation", with a mean of 4.7 (SD = 0.480), followed by the dimension "Participation", with a mean of 4.66 (SD = 0.461), and lastly, the dimension "Attention", with a mean of 4.64 (SD = 0.418). CONCLUSIONS: The use of interactive questions contributed the attention, participation, and motivation of the students during the debriefing, contributing towards a highly satisfactory experience of high-fidelity clinical simulation.

[Evaluation of a community-based intervention to increase influenza vaccination coverage in pregnant women]. / Evaluación de una intervención comunitaria para incrementar la cobertura vacunal de la gripe en mujeres embarazadas.

OBJECTIVE: To know the impact of the educational intervention carried out on the professionals of a basic health area and their community participation group, which make up the intervention group (IG), and to analyze its repercussion on the vaccination coverage achieved for influenza in the risk group (pregnant and puerperal women) comparing it with its neighboring basic zone, which makes up the control group (CG), during the 2019/20 vaccination season. DESIGN: Quasi-experimental study of community intervention. SITE: Two basic health zones belonging to the Elche-Crevillente health department, Spain. PARTICIPANTS: Pregnant and postpartum women from 2 basic health areas and the community participation group. Health professionals directly related to the flu vaccination campaign. INTERVENTIONS: Training session for the IG prior to the 2019/20 flu campaign. MAIN MEASUREMENTS: Attitudes towards influenza vaccination in health professionals through the validated CAPSVA questionnaire and the vaccination coverage of pregnant and postpartum women through the Nominal Vaccine Registry and their acceptance of the vaccine in the midwife's office. RESULTS: The influenza vaccination coverage data recorded in Nominal Vaccine Registry for pregnant and puerperal women was 26.4% (n=207) in the IG and 19.7% (n=144) in the CG (p=0.001), with an incidence ratio of 1.34, thus achieving 34% more vaccination in the IG. Acceptance for vaccination in the midwife's office was also high, with 96.5% immunization in IG vs. 89.0% in CG, with a RR=1.09 (95% CI 1.01-1.62). CONCLUSIONS: Joint training strategies for professionals and community assets improve the results of vaccination coverage.

Autologous stem-cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: a multicenter GELTAMO/FIL study.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare lymphoid malignancies that mostly have poor prognoses with currently available treatments. Upfront consolidation with autologous stem cell transplantation (ASCT) is frequently carried out, but its efficacy has never been investigated in randomized trials. We designed a multicenter, international, retrospective study with the main objective of comparing progression-free survival and overall survival of patients with PTCL who underwent ASCT in complete remission (CR) after first-line chemotherapy with a control group who did not undergo ASCT. From the initial population of 286 registered patients, 174 patients with PTCL other than anaplastic large cell lymphoma, ALK-positive, deemed fit for ASCT at the time of diagnosis, and who were in CR or uncertain CR after induction therapy (CR1) were included in our analysis. one hundred and three patients underwent ASCT, whereas 71 did not, in most cases (n=53) because the physician decided against it. With a median follow-up of 65.5 months, progression-free survival was significantly better in the transplanted patients than in the non-transplanted group: 63% versus 48% at 5 years (P=0.042). Overall survival was significantly longer for ASCT patients in the subgroup with advanced stage at diagnosis (5-year overall survival: 70% vs. 50%, P=0.028). In the multivariate analysis, first-line ASCT was associated with significantly prolonged progression-free survival (HR=0.57, 95% CI: 0.35-0.93) and overall survival (HR=0.57, 95% CI: 0.33-0.99). In conclusion, our study supports the use of ASCT as a consolidation strategy for patients with PTCL in CR1. These results should be confirmed in a prospective randomized study.

Differences in chromatic noise suppression of luminance contrast discrimination in young and elderly people.

Aging causes impairment of contrast sensitivity and chromatic discrimination, leading to changes in the perceptual interactions between color and luminance information. We aimed to investigate the influence of chromatic noise on luminance contrast thresholds in young and older adults. Forty participants were divided equally into Young (29.6 ± 6.3-year-old) and Elderly Groups (57.8 ± 6.6-year-old). They performed a luminance contrast discrimination task in the presence of chromatic noise maskers using a mosaic stimulus in a mosaic background. Four chromatic noise masking protocols were applied (protan, deutan, tritan, and no-noise protocols). We found that luminance contrast thresholds were significantly elevated by the addition of chromatic noise in both age groups (P < 0.05). In the Elderly group, but not the younger group, thresholds obtained in the tritan protocol were lower than those obtained from protan and deutan protocols (P < 0.05). For all protocols, the luminance contrast thresholds of elderly participants were higher than in young people (P < 0.01). Tritan chromatic noise was less effective in inhibiting luminance discrimination in elderly participants.

Influence of preventive sex education programmes in compulsory secondary education students: a descriptive observational study.

BACKGROUND: Sex education programmes conducted by health professionals and educators are essential for young people to adopt healthy habits and attitudes towards their sexuality. The Forma Joven Program, promoted by the Andalusian Regional Government's Ministry of Health and Families and Education, is a good example of this. The aim of the study is to determine if different "degrees of intervention" in the informative consultancies of the Forma Joven Program imply differences in knowledge and attitudes towards sexuality. METHODS: This descriptive observational study analysed 27 Compulsory Secondary Education high schools in Huelva. These were included in the Program and belonged to a Primary Care Health District. Out of the 17 institutes initially selected because they met the inclusion criteria (4.256 students), finally 14 (3.596 students) participated. During the 2018/2019 school year, students from 3rd, 4th year of Secondary Compulsory Education (ESO), 1st, and 2nd Baccalaureate of the selected centres were asked to fill in a questionnaire of knowledge and attitudes towards sexuality. It collected variables such as age, sex, school year, institute, educational level and employment status of the father or mother and profile of the professional who delivers the counselling. RESULTS: A total of 1.237 students completed the questionnaire, which represents a participation rate of 34.4%. The average age was 15.59 years (SD 1.26) and 39.9% were girls. In some evaluated questions, we found statistically significant differences between the groups with different levels of exposure to counselling and the acquisition of knowledge and attitudes towards students' sexuality, although in most of them no such differences were found. The results of this study suggest the importance of the quality of counselling over quantity. Some classic myths persist in relation to sexuality and in some situations, they can be decisive when adopting preventive measures to avoid risks related to pregnancy and contagion of STIs. CONCLUSIONS: A greater number of counselling sessions does not imply acquiring a higher level of knowledge or better attitudes towards sexuality. Perhaps the quality of the education is more important than the quantity of counselling sessions.

Close Related Drug-Resistance Beijing Isolates of Mycobacterium tuberculosis Reveal a Different Transcriptomic Signature in a Murine Disease Progression Model.

Mycobacterium tuberculosis (MTB) lineage 2/Beijing is associated with high virulence and drug resistance worldwide. In Colombia, the Beijing genotype has circulated since 1997, predominantly on the pacific coast, with the Beijing-Like SIT-190 being more prevalent. This genotype conforms to a drug-resistant cluster and shows a fatal outcome in patients. To better understand virulence determinants, we performed a transcriptomic analysis with a Beijing-Like SIT-190 isolate (BL-323), and Beijing-Classic SIT-1 isolate (BC-391) in progressive tuberculosis (TB) murine model. Bacterial RNA was extracted from mice lungs on days 3, 14, 28, and 60. On average, 0.6% of the total reads mapped against MTB genomes and of those, 90% against coding genes. The strains were independently associated as determined by hierarchical cluster and multidimensional scaling analysis. Gene ontology showed that in strain BL-323 enriched functions were related to host immune response and hypoxia, while proteolysis and protein folding were enriched in the BC-391 strain. Altogether, our results suggested a differential bacterial transcriptional program when evaluating these two closely related strains. The data presented here could potentially impact the control of this emerging, highly virulent, and drug-resistant genotype.

Enhancing monitoring and transboundary collaboration for conserving migratory species under global change: The priority case of the red kite.

Calls for urgent action to conserve biodiversity under global change are increasing, and conservation of migratory species in this context poses special challenges. In the last two decades the Convention on the Conservation of Migratory Species of Wild Animals (CMS) has provided a framework for several subsidiary instruments including action plans for migratory bird species, but the effectiveness and transferability of these plans remain unclear. Such laws and policies have been credited with positive outcomes for the conservation of migratory species, but the lack of international coordination and on-ground implementation pose major challenges. While research on migratory populations has received growing attention, considerably less emphasis has been given to integrating ecological information throughout the annual cycle for examining strategies to conserve migratory species at multiple scales in the face of global change. We fill this gap through a case study examining the ecological status and conservation of a migratory raptor and facultative scavenger, the red kite (Milvus milvus), whose current breeding range is limited to Europe and is associated with agricultural landscapes and restricted to the temperate zone. Based on our review, conservation actions have been successful at recovering red kite populations within certain regions. Populations however remain depleted along the southern-most edge of the geographic range where many migratory red kites from northern strongholds overwinter. This led us to a forward-looking and integrated strategy that emphasizes international coordination involving researchers and conservation practitioners to enhance the science-policy-action interface. We identify and explore key issues for conserving the red kite under global change, including enhancing conservation actions within and outside protected areas, recovering depleted populations, accounting for climate change, and transboundary coordination in adaptive conservation and management actions. The integrated conservation strategy is sufficiently general such that it can be adapted to inform conservation of other highly mobile species subject to global change.

Expanding the Toolbox of Octahedral Molybdenum Clusters and Nanocomposites Made Thereof: Evidence of Two-Photon Absorption Induced NIR Emission and Singlet Oxygen Production.

Bright NIR phosphorescence from octahedral molybdenum clusters has been known since the 1980s. However, their behavior toward NIR excitation has never been investigated. Here we report their abilities to emit NIR light and produce singlet oxygen upon two-photon absorption. This behavior is observed in solution, in the solid state, and when clusters are embedded homogeneously in a poly(dimethylsiloxane) matrix. Such discoveries open new perspectives in several fields like optoelectronics, photodynamic therapy, or bioimaging.

Pulp healing in immature replanted permanent teeth: A competing risk analysis.

BACKGROUND/AIM: Tooth displacement during avulsion causes total rupture of the pulp's neurovascular supply. Revascularization and pulp healing may occur in immature teeth, which gives rise to the recommendation that root canal treatment may not be required. The aim of this study was to evaluate the prognostic factors for the pulp's response after replantation of young permanent teeth. METHODS: Records from 117 patients with 133 replanted permanent immature teeth were reviewed, and pulp outcomes were classified as healing (hard tissue deposition on the dentinal walls followed by narrowing of the pulp lumen or ingrowth of bone-like tissue inside the pulp canal) or non-healing (pulp necrosis with infection). The effect of clinical and demographic co-variates on the hazards of both outcomes was assessed performing a competing risk model. RESULTS: Pulp necrosis with infection was diagnosed in 78.2% of the teeth, and healing was observed in 12.8% of the teeth. A total of 12 teeth (9.0%) were censored due to prophylactic removal of the pulp or severe external root resorption caused by eruption of adjacent canines. The cs-Cox model demonstrated that the hazards of pulp healing increased in teeth with extra-alveolar periods <15 min (csHR: 7.83, 95% CI 1.76-34.80, p = .01), while the hazards of pulp necrosis with infection decreased (csHR: 0.31, 95% CI: 0.10-0.92, p = .04). Teeth replanted with Moorrees' stages 4 and 5 of root development had higher hazards of pulp necrosis with infection than teeth with stage 2 of root development (csHR: 2.23, 95% CI 1.11-4.50, p = .03; csHR: 2.89, 95% CI: 1.40-5.95; p = .01). CONCLUSIONS: Pulp healing rarely occurred after replantation of young permanent teeth being associated with short extra-alveolar periods <15 min. Early stages of root development decreased the hazards of pulp necrosis with infection.

Novice nurse's transitioning to emergency nurse during COVID-19 pandemic: A qualitative study.

AIM: To explore the experiences and perceptions of recent nursing graduates working in emergency departments during the COVID-19 outbreak. BACKGROUND: Overcrowding in emergency departments has been one of the most prominent issues arising in these units for more than 20 years. However, it has become even more problematic due to the novelty of the coronavirus pandemic, which has forced hospitals to recruit larger numbers of beginner nursing staff as the number of quarantined health professionals increases. METHODS: Sixteen semi-structured interviews were conducted in Spanish emergency departments, which were analysed and synthesized using content analysis. RESULTS: Three major themes emerged from the data analysis: (a) Fears and concerns, (b) Organisational issues and (c) Support for novice nurses. CONCLUSIONS: Our findings may help to understand how shadowing periods as a learning programme for nurses, continuing professional development, evidence-based apps and better planning are needed to ensure both novice nurses' confidence in emergency departments and expert emergency room nurses' ability to cope with complications in critical situations. IMPLICATIONS FOR NURSING MANAGEMENT: Training periods that include shadowing expert emergency room nurses, along with evidence-based technology, provide an opportunity to support novice nurses' transition into the workplace. These measures would provide a safety net and would increase novice nurses' confidence as well as high-quality care.

Use of technology in endodontics by undergraduate dental students in a south-eastern state of Brazil.

INTRODUCTION: This study aimed to determine the level of incorporation of current technologies for endodontic treatment in undergraduate dentistry courses in a south-eastern state of Brazil. METHODS: For data collection, a self-assessment-based online questionnaire was created using the "Google Forms" platform, consisting of 12 multiple-choice and a few open-ended questions. The questions were related to the use of current technologies for diagnosis, imaging, use of ultrasonics in endodontics, instrumentation, use of apex locator, microscopy, photodynamic therapy and thermoplastic techniques during endodontic treatment. The questionnaire was sent to 54 dental schools in Minas Gerais. RESULTS: The results show low technological incorporation during the various stages of endodontic treatment by undergraduate students in dentistry courses in Minas Gerais. CONCLUSION: Despite the availability of several technologies to help perform different stages of endodontic treatment, it was observed that most universities do not teach the use of these technologies. Additional studies are needed to correlate how the lack of incorporation of these technologies could impact on the quality of the endodontic learning for undergraduate students.

Immediate impact of COVID-19 pandemic on farming systems in Central America and Mexico.

CONTEXT: The COVID-19 pandemic has affected all sectors and human activities around the World. OBJECTIVE: In this article we present a first attempt to understand the immediate impact of COVID-19 and the sanitary measures taken by governments on farming systems in Central America and Mexico (CAM). METHODS: Through a review of information generated in these initial months of the COVID-19 pandemic (webinars, blogs, electronic publications, media) and 44 interviews with key informants across the region, we have identified the main impacts felt by different types of farming systems in the region. RESULTS AND CONCLUSIONS: From corporate agricultural production systems, to small and medium scale entrepreneurs and smallholder subsistence farm households, all types of farming systems were impacted, more or less severely, by the different measures implemented by governments such as reduced mobility, closure of public and private venues and restrictions in borders. Larger corporate farming systems with vertical market integration and high level of control or coordination within the supply chain, and smallholder or subsistence farming systems with important focus on production for self-consumption and little external input use, were both relatively less impacted and showed greater adaptive capacity than the medium and small entrepreneurial farming systems dependent on agriculture as their primary income and with less control over the upstream and downstream parts of their supply chain. All types of farming systems implemented a series of mechanisms to cope with the COVID-19 pandemic including the development of alternative value chains, food and agricultural products delivery systems and the exponential use of digital means to communicate and maintain the viability of the different agricultural systems. Collective action and organization of farmers also proved to be an important coping mechanism that allowed some farmers to acquire inputs and deliver outputs in the context of restricted mobility, price volatility, and general uncertainty. Some features of the CAM region played an important role in mediating the impact of COVID-19 and associated sanitary measures. We identify as particularly relevant the nature of agricultural exports, the current structure of the agricultural sector, the diversified livelihood strategies of rural households, and the importance of mobility for rural livelihoods. SIGNIFICANCE: The results presented focus only in the immediate effect of COVID-19 pandemic and the mechanisms implemented by farmers in the first months. Whether these impacts and response mechanisms will result in a transformation of the farming systems towards greater resilience and sustainability is still an open question.