Nucleus downscaling in mouse embryos is regulated by cooperative developmental and geometric programs

Maintaining appropriate nucleus size is important for cell health, but the mechanisms by which this is achieved are poorly understood. Controlling nucleus size is a particular challenge in early development, where the nucleus must downscale in size with progressive reductive cell divisions. Here we use live and fixed imaging, micromanipulation approaches, and small molecule analyses during preimplantation mouse development to probe the mechanisms by which nucleus size is determined. We find a close correlation between cell and nuclear size at any given developmental stage, and show that experimental cytoplasmic reduction can alter nuclear size, together indicating that cell size helps dictate nuclear proportions. Additionally, however, by creating embryos with over-sized blastomeres we present evidence of a developmental program that drives nuclear downscaling independently of cell size. We show that this developmental program does not correspond with nuclear import rates, but provide evidence that PKC activity may contribute to this mechanism. We propose a model in which nuclear size regulation during early development is a multi-mode process wherein nucleus size is set by cytoplasmic factors, and fine-tuned on a cell-by-cell basis according to cell size

How long does treatment with fixed orthodontic appliances last? A systematic review

INTRODUCTION There is little agreement on the expected duration of a course of orthodontic treatment; however, a consensus appears to have emerged that fixed appliance treatment is overly lengthy. This has spawned numerous novel approaches directed at reducing the duration of treatment, occasionally with an acceptance that occlusal outcomes may be compromised. The aim of this study was to determine the mean duration and the number of visits required for comprehensive orthodontic treatment involving fixed appliances. METHODS Multiple electronic databases were searched with no language restrictions, authors were contacted as required, and reference lists of potentially relevant studies were screened. Randomized controlled trials and nonrandomized prospective studies concerning fixed appliance treatment with treatment duration as an outcome measure were included. Data extraction and quality assessment were performed independently and in duplicate. RESULTS Twenty-five studies were included after screening: 20 randomized controlled trials and 5 controlled clinical trials. Twenty-two studies were eligible for meta-analysis after quality assessment. The mean treatment duration derived from the 22 included studies involving 1089 participants was 19.9 months (95% confidence interval, 19.58, 20.22 months). Sensitivity analyses were carried out including 3 additional studies, resulting in average duration of treatment of 20.02 months (95% confidence interval, 19.71, 20.32 months) based on data from 1211 participants. The mean number of required visits derived from 5 studies was 17.81 (95% confidence interval, 15.47, 20.15 visits). CONCLUSIONS Based on prospective studies carried out in university settings, comprehensive orthodontic treatment on average requires less than 2 years to complete

Ca2+ dynamics in oocytes from naturally-aged mice

The ability of human metaphase-II arrested eggs to activate following fertilisation declines with advancing maternal age. Egg activation is triggered by repetitive increases in intracellular Ca2+ concentration ([Ca2+]i) in the ooplasm as a result of sperm-egg fusion. We therefore hypothesised that eggs from older females feature a reduced ability to mount appropriate Ca2+ responses at fertilisation. To test this hypothesis we performed the first examination of Ca2+ dynamics in eggs from young and naturally-aged mice. Strikingly, we find that Ca2+ stores and resting [Ca2+]i are unchanged with age. Although eggs from aged mice feature a reduced ability to replenish intracellular Ca2+ stores following depletion, this difference had no effect on the duration, number, or amplitude of Ca2+ oscillations following intracytoplasmic sperm injection or expression of phospholipase C zeta. In contrast, we describe a substantial reduction in the frequency and duration of oscillations in aged eggs upon parthenogenetic activation with SrCl2. We conclude that the ability to mount and respond to an appropriate Ca2+ signal at fertilisation is largely unchanged by advancing maternal age, but subtle changes in Ca2+ handling occur that may have more substantial impacts upon commonly used means of parthenogenetic activation

Orthodontic trial outcomes: Plentiful, inconsistent, and in need of uniformity? A scoping review.

INTRODUCTION: The selection of appropriate outcomes that matter to both patients and operators is increasingly appreciated, with core outcome sets in clinical trials gaining in popularity. The first step in core outcome set development is the generation of a list of possible important outcomes based on a scoping literature review. Moreover, outcome heterogeneity is known to detract from the findings of systematic reviews and meta-analyses. The aim of this study was to identify the range of outcome domains and specific outcome measures in contemporary orthodontic research. METHODS: Multiple electronic databases were searched from December 31, 2012, to December 31, 2016, to identify clinical trials of orthodontic interventions, with no language restrictions. Abstracts, eligible full texts, and reference lists were screened, and all reported primary and nonprimary outcomes and methods of measurement were recorded. RESULTS: The search identified 1267 abstracts, of which 189 full-text articles were retrieved, and 164 studies were included in the analysis. A total of 54 outcomes were identified and categorized into 14 outcome domains. The most frequently measured outcomes were patient-reported pain, periodontal health, tooth angulation/inclination changes, and treatment duration, followed by rate of tooth movement and skeletal changes. Outcomes that followed the overall course of treatment were assessed in only 14 studies. CONCLUSIONS: Patient perspectives are increasingly being accounted for in orthodontic trials; however, there is little consistency in outcome selection among them. The identified list of outcomes will be used to inform a ranking exercise with service users and providers to establish an agreed core outcome set for future orthodontic clinical trials.Royal College of Surgeons of England and the British Orthodontic Society, which provided funding through a fellowship for Aliki Tsichlaki (grant number OGDF1A1R)

Collaboration in orthodontic clinical trials: prevalence and association with sample size and funding

Abstract Background To assess patterns of research collaboration in orthodontics and possible relationships with sample size and funding status. Methods Orthodontic randomised and non-randomised controlled clinical trials published between 2013 and 2017 were identified through electronic searching. The nature of collaboration, author institutions, study setting, sample size, and funding status were assessed. Linear and logistic regression analyses were applied. Results Of 1153 studies, 217 met the selection criteria. The majority of studies were authored by university academics (86%), were conducted in a single centre (71.9%) and in at least one university hospital (68.2%). The number of practice-based trials (10.1%), as well as the involvement of specialist practitioners (5.2%) in co-authorship, was limited. Multi-centred studies within a single country were associated with a significantly larger sample size compared to single-centred trials (P = 0.00; 95% confidence interval [CI] 33.59, 106.93). However, authorship collaboration either nationally (odds ratio [OR] 2.37; 95% CI 0.85, 6.57) or internationally across different continents (OR 5.54; 95% CI 0.62, 49.52) did not translate into increased funding. Conclusions Most orthodontic studies were undertaken in university hospital settings within a single country. Collaboration is common in orthodontics but involvement of practice settings remains limited, suggesting a need for stimulation of practice-based research and research partnerships

"Over-reviewing" of research? An analysis of orthodontic reviews

INTRODUCTION: Research overviews may be undertaken to identify gaps in the literature, evaluate existing systematic reviews (SRs), and summarize evidence. This paper aims to profile overviews that have been conducted in orthodontics and related interventions since 2012 and to evaluate the degree of overlap among these overviews. METHODS: Overviews published between January 1, 2012 and June 20, 2023 were identified using an electronic search involving Google Scholar and PubMed. A descriptive summary was produced, and citation matrices were used to evaluate the percentage of overlap between overviews using corrected covered area and covered area. This was classified as slight, moderate, high, or very high. RESULTS: A total of 35 overviews were identified across a wide range of topics. Eight overviews included 20 SRs (median no. of SRs per overview, 15; range, 3-62). Meta-analysis was conducted in only 5 overviews. Overlap between overviews on the same topic ranged from slight (2.7%) to very high (53.8%). CONCLUSIONS: Almost all overview topics address treatments and their effects, with a wide variation in the number and quality of SRs included. There is considerable overlap in some orthodontic overviews, suggesting unnecessary duplication and research waste. Researchers should be encouraged to focus on primary data collection to add more high-quality data to SRs, which will ultimately enhance the yield from secondary and tertiary orthodontic research

Epidemiology of maxillofacial trauma in elderly patients receiving oral anticoagulant or antithrombotic medication; a Swiss retrospective study.

BACKGROUND The percentage of elderly trauma patients under anticoagulation and antiplatelet agents has been rising lately. As newer agents are introduced, each comes with its own advantages and precautions. Our study covered elderly patients admitted to the ED with maxillofacial trauma while on anticoagulation (AC) or antiplatelet therapy (APT). We aimed to investigate the demographic characteristics, causes, and types of maxillofacial trauma, along with concomitant injuries, duration of hospitalisation, haemorrhagic complications, and the overall costs of care in the emergency department (ED). METHODS Data were gathered from the ED of Bern University Hospital. In this retrospective analysis, patients over 65 of age were included, who presented at our ED with maxillofacial trauma between 2013 and 2019 while undergoing treatment with therapeutic AC/APT. RESULTS The study involved 188 patients with a median age of 81 years (IQR: 81 [74; 87]), of whom 55.3% (n=104) were male. More than half (54.8%, n=103) were aged 80 years or older. Cardiovascular diseases were present in 69.7% (n=131) of the patients, with the most common indications for AC/APT use being previous thromboembolic events (41.5%, n=78) and atrial fibrillation (25.5%, n=48). The predominant cause of facial injury was falls, accounting for 83.5% (n=157) of cases, followed by bicycle accidents (6.9%, n=13) and road-traffic accidents (5.3%, n=10). The most common primary injuries were fractures of the orbital floor and/or medial/lateral wall (60.1%, n=113), zygomatic bone (30.3%, n=57), followed by isolated orbital floor fractures (23.4%, n=44) and nasal bone fractures (19.1%, n=36). Fractures of the mandible occurred in 14.9% (n=28). Facial hematomas occurred in 68.6% of patients (129 cases), primarily in the midface area. Relevant facial bleeding complications were intracerebral haemorrhage being the most frequent (28.2%, n=53), followed by epistaxis (12.2%, n=23) and retrobulbar/intraorbital hematoma (9%, n=17). Sixteen patients (8.5%) experienced heavy bleeding that required emergency treatment. The in-hospital mortality rate was 2.1% (4 cases). CONCLUSIONS This study indicates that falls are the leading cause of maxillofacial trauma in the elderly, with the most common diagnoses being orbital, zygomatic, and nasal fractures. Haemorrhagic complications primarily involve facial hematomas, especially in the middle third of the face, with intracerebral haemorrhage being the second most frequent. Surgical intervention for bleeding was required in 8.5% of cases. Given the aging population, it is essential to improve prevention strategies and update safety protocols, particularly for patients on anticoagulant/antiplatelet therapy (AC/APT). This can ensure rapid diagnostic imaging and prompt treatment in emergencies

“Over-reviewing” of research? An analysis of orthodontic reviews

Introduction: Research overviews may be undertaken to identify gaps in the literature, evaluate existing systematic reviews (SRs), and summarize evidence. This paper aims to profile overviews that have been conducted in orthodontics and related interventions since 2012 and to evaluate the degree of overlap among these overviews. Methods: Overviews published between January 1, 2012 and June 20, 2023 were identified using an electronic search involving Google Scholar and PubMed. A descriptive summary was produced, and citation matrices were used to evaluate the percentage of overlap between overviews using corrected covered area and covered area. This was classified as slight, moderate, high, or very high. Results: A total of 35 overviews were identified across a wide range of topics. Eight overviews included 20 SRs (median no. of SRs per overview, 15; range, 3-62). Meta-analysis was conducted in only 5 overviews. Overlap between overviews on the same topic ranged from slight (2.7%) to very high (53.8%). Conclusions: Almost all overview topics address treatments and their effects, with a wide variation in the number and quality of SRs included. There is considerable overlap in some orthodontic overviews, suggesting unnecessary duplication and research waste. Researchers should be encouraged to focus on primary data collection to add more high-quality data to SRs, which will ultimately enhance the yield from secondary and tertiary orthodontic research

Development of a core outcome set for orthodontic trials using a mixed-methods approach: Protocol for a multicentre study

© 2017 The Author(s). Background: Orthodontic treatment is commonly undertaken in young people, with over 40% of children in the UK needing treatment and currently one third having treatment, at a cost to the National Health Service in England and Wales of £273 million each year. Most current research about orthodontic care does not consider what patients truly feel about, or want, from treatment, and a diverse range of outcomes is being used with little consistency between studies. This study aims to address these problems, using established methodology to develop a core outcome set for use in future clinical trials of orthodontic interventions in children and young people. Methods/design: This is a mixed-methods study incorporating four distinct stages. The first stage will include a scoping review of the scientific literature to identify primary and secondary outcome measures that have been used in previous orthodontic clinical trials. The second stage will involve qualitative interviews and focus groups with orthodontic patients aged 10 to 16 years to determine what outcomes are important to them. The outcomes elicited from these two stages will inform the third stage of the study in which a long-list of outcomes will be ranked in terms of importance using electronic Delphi surveys involving clinicians and patients. The final stage of the study will involve face-to-face consensus meetings with all stakeholders to discuss and agree on the outcome measures that should be included in the final core outcome set. Discussion: This research will help to inform patients, parents, clinicians and commissioners about outcomes that are important to young people undergoing orthodontic treatment. Adoption of the core outcome set in future clinical trials of orthodontic treatment will make it easier for results to be compared, contrasted and combined. This should translate into improved decision-making by all stakeholders involved. Trial registration: The project has been registered on the Core Outcome Measures in Effectiveness Trials (COMET) website, January 2016

Αξιολόγηση Υπηρεσιών Βιβλιοθηκών μέσω Τεχνικού Νευρωνικού Δικτύου

Περιέχει το πλήρες κείμενοΣκοπός της επικείμενης εργασίας είναι η δημιουργία ενός συστήματος αξιολόγησης βιβλιοθηκών, το οποίο χρησιμοποιείται με σκοπό τη μέτρηση/κατάταξη της αποδοτικότητας των λειτουργιών μιας βιβλιοθήκης. Οι παρακάτω μετρήσεις έγιναν με βάση τους καθιερωμένους δείκτες της ΜΟΠΑΒ. Καταλήξαμε στους εν λόγω δείκτες, τους οποίους θα εξετάσουμε και στους οποίους θα βασίσουμε την έρευνα λόγω των χαρακτηριστικών που παρουσιάζουν. Αρχικά, πρόκειται για τους πιο αντιπροσω- πευτικούς δείκτες για την αξιολόγηση μιας βιβλιοθήκης, καθώς οι δείκτες αυτοί αφορούν όλα τα είδη των βιβλιοθηκών και όχι μόνο τις ειδικές ή κάποιο συγκεκριμένο είδος. Πέρα από τη συχνότητα με την οποία τους συναντάμε, σημαντικός λόγος για την επιλογή τους ήταν πως αφορούν δείκτες υπηρεσιών που σχεδόν όλες οι βιβλιοθήκες έχουν· επίσης, αφορούν τις δύο από τις τρεις κύριες λειτουργίες μιας βιβλιοθήκης (πρόσκτηση και δανεισμό) και επιπλέον είναι ευκατανόητοι και εύκολα επε- ξεργάσιμοι για την εξαγωγή αποτελεσμάτων. Τα αποτελέσματα από την εκάστοτε επεξεργασία και κρίση είναι έγκυρα και αξι- όλογα, ενώ αυτονόητο είναι ότι δεν υπάρχει κόστος για την εξαγωγή τους και δεν απαιτείται κάποιο συγκεκριμένο εργαλείο. Τα κριτήρια είναι καταρχήν υποκειμενικά, αλλά η ανάλυση και η αξιολόγηση γίνεται με αντικειμενικότητα. Για τη δημιουργία του συστήματος αξιολόγησης βιβλιοθηκών βασιστήκαμε στη μάθηση με επίβλεψη με τη βοήθεια ενός νευρωνικού δικτύου