Orthopaedic surgeons display a positive outlook towards artificial intelligence: A survey among members of the AGA Society for Arthroscopy and Joint Surgery.

Purpose: The purpose of this study was to evaluate the perspective of orthopaedic surgeons on the impact of artificial intelligence (AI) and to evaluate the influence of experience, workplace setting and familiarity with digital solutions on views on AI. Methods: Orthopaedic surgeons of the AGA Society for Arthroscopy and Joint Surgery were invited to participate in an online, cross-sectional survey designed to gather information on professional background, subjective AI knowledge, opinion on the future impact of AI, openness towards different applications of AI, and perceived advantages and disadvantages of AI. Subgroup analyses were performed to examine the influence of experience, workplace setting and openness towards digital solutions on perspectives towards AI. Results: Overall, 360 orthopaedic surgeons participated. The majority indicated average (43.6%) or rudimentary (38.1%) AI knowledge. Most (54.5%) expected AI to substantially influence orthopaedics within 5-10 years, predominantly as a complementary tool (91.1%). Preoperative planning (83.8%) was identified as the most likely clinical use case. A lack of consensus was observed regarding acceptable error levels. Time savings in preoperative planning (62.5%) and improved documentation (81%) were identified as notable advantages while declining skills of the next generation (64.5%) were rated as the most substantial drawback. There were significant differences in subjective AI knowledge depending on participants' experience (p = 0.021) and familiarity with digital solutions (p < 0.001), acceptable error levels depending on workplace setting (p = 0.004), and prediction of AI impact depending on familiarity with digital solutions (p < 0.001). Conclusion: The majority of orthopaedic surgeons in this survey anticipated a notable positive impact of AI on their field, primarily as an assistive technology. A lack of consensus on acceptable error levels of AI and concerns about declining skills among future surgeons were observed. Level of Evidence: Level IV, cross-sectional study.

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Children and young people's consultation rates for psychosocial problems between 2016 and 2021 in the Netherlands.

BACKGROUND: Worldwide, there are concerns about declining mental health of children and young people (CYP). OBJECTIVES: To examine trends in GP consultation rates for psychosocial problems and the impact of the COVID-19 pandemic. METHODS: We performed a population-based cohort study using electronic GP records of CYP (0-24 years) living in the Rotterdam metropolitan area between 2016 and 2021. We calculated monthly consultation rates for psychosocial problems, stratified by age group and sex. We used negative binomial models to model the pre-COVID-19 trend, and estimate expected rates post-COVID-19 onset. We modelled the effect of COVID-19 infection rate and school closure on consultation rates per sex and age group. RESULTS: The cohort increased from 64801 to 92093 CYP between January 2016 and December 2021. Median age was 12.5 years and 49.3% was female. Monthly consultation rates increased from 2,443 to 4,542 consultations per 100,000 patient months over the six years. This trend (RR 1.009, 95%CI 1.008-1.011) started well before the COVID-19 pandemic. Consultation rates of adolescent girls and young women increased most strongly. Between March and May 2020, there was a temporary reduction in consultation rates, whereupon these returned to expected levels. COVID-19 infection rate and school closures showed small but significant associations with consultation rates for psychosocial problems but this did not affect the overall trend. Although consultation rates for psychosocial problems increased, this increment was stable over the entire study period. CONCLUSION: The COVID-19 pandemic did not significantly increase consultation rates for psychosocial problems in CYP. The consultation rates increased, especially in adolescent girls and young women.

CYP' consultation rates for psychosocial problems within general practice almost doubled between 2016 and 2021 in the Rotterdam metropolitan area, the Netherlands.This increase was steady over time and was not affected by the COVID-19 pandemic.Consultation rates in general practice for psychosocial problems increased most strongly in adolescent girls and young women.

Influence of a Concomitant Medial Meniscus Injury on Knee Joint Function and Osteoarthritis Presence after Anterior Cruciate Ligament Reconstruction.

(1) Background: The aim of this study was to investigate how a medial meniscus injury accompanying an anterior cruciate ligament rupture affects the clinical outcome 10 years after ACL reconstruction. (2) Methods: A total of 37 patients who received anterior cruciate ligament reconstruction (ACLR) were included in this retrospective study. Two groups were analyzed at a single follow-up of 10 years: (i) "isolated (ACLR)" (n = 20) and (ii) "ACLR with medial meniscal injury" (n = 17). The following clinical scores were recorded: International Knee Documentation Committee (IKDC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm Score and Tegner Activity Score. To determine the degree of osteoarthritis the Kellgren-Lawrence score was used. (3) Results: The "isolated ACLR" study group scored significantly higher (p < 0.05) on the IKDC subjective questionnaire (mean: 88.4) than the "ACLR with medial meniscus injury" group (mean: 81). The KOOS category "activities of daily living" showed significantly better results in the isolated ACLR group (p < 0.05). The "ACLR with medial meniscus injury" group had significantly higher degree of osteoarthritis (p < 0.05). No significant differences were found in all the other clinical scores. (4) Conclusions: The results of this study further indicate that patients with a concomitant medial meniscus injury have slightly more discomfort in everyday life and increased risk of developing osteoarthritis 10 years after surgery.

Evaluation of practice nurses' management of paediatric psychosocial problems in general practice.

BACKGROUND: Child mental health services are under major pressure worldwide. In the Netherlands, Youth Mental Health Practice Nurses (YMHPNs) have been introduced in general practice to improve access to care. In this study, we evaluated care delivered by YMHPNs. METHODS: We used medical records of a population-based cohort (21 717 children, 0-17 years). Characteristics of children consulting a YMHPN, type of problem, care delivered by YMHPNs and referrals were assessed using quantitative content analysis. RESULTS: Records of 375 children (mean age 12.9 years, 59.2% girl) were analysed. These children were often in their adolescence (57.3% was between 13 and 17 years), and more often female than male (59.2% vs 40.8%). YMHPNs had a median of four consultations (IQR 2-7) with the child. YMHPNs managed a variety of psychosocial problems. YMHPNs managed 22.4% of children without need of referral, 52.0% were eventually referred for additional care. 13.3% of children dropped out during the treatment trajectory. In the remaining 12.3% of children, the treatment trajectory was stopped because the child was already attending specialized services, the treatment trajectory was still ongoing or the medical record was inconclusive. CONCLUSIONS: YMHPNs successfully managed one in four children with psychosocial problems without need for referral. Nevertheless, most children were eventually referred for additional care.

Somnotate: A probabilistic sleep stage classifier for studying vigilance state transitions.

Electrophysiological recordings from freely behaving animals are a widespread and powerful mode of investigation in sleep research. These recordings generate large amounts of data that require sleep stage annotation (polysomnography), in which the data is parcellated according to three vigilance states: awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. Manual and current computational annotation methods ignore intermediate states because the classification features become ambiguous, even though intermediate states contain important information regarding vigilance state dynamics. To address this problem, we have developed "Somnotate"-a probabilistic classifier based on a combination of linear discriminant analysis (LDA) with a hidden Markov model (HMM). First we demonstrate that Somnotate sets new standards in polysomnography, exhibiting annotation accuracies that exceed human experts on mouse electrophysiological data, remarkable robustness to errors in the training data, compatibility with different recording configurations, and an ability to maintain high accuracy during experimental interventions. However, the key feature of Somnotate is that it quantifies and reports the certainty of its annotations. We leverage this feature to reveal that many intermediate vigilance states cluster around state transitions, whereas others correspond to failed attempts to transition. This enables us to show for the first time that the success rates of different types of transition are differentially affected by experimental manipulations and can explain previously observed sleep patterns. Somnotate is open-source and has the potential to both facilitate the study of sleep stage transitions and offer new insights into the mechanisms underlying sleep-wake dynamics.

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning: Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study.

First Insights into Population Structure and Genetic Diversity Versus Host Specificity in Trypanorhynch Tapeworms Using Multiplexed Shotgun Genotyping.

Theory predicts relaxed host specificity and high host vagility should contribute to reduced genetic structure in parasites while strict host specificity and low host vagility should increase genetic structure. Though these predictions are intuitive, they have never been explicitly tested in a population genomic framework. Trypanorhynch tapeworms, which parasitize sharks and rays (elasmobranchs) as definitive hosts, are the only order of elasmobranch tapeworms that exhibit considerable variability in their definitive host specificity. This allows for unique combinations of host use and geographic range, making trypanorhynchs ideal candidates for studying how these traits influence population-level structure and genetic diversity. Multiplexed shotgun genotyping (MSG) data sets were generated to characterize component population structure and infrapopulation diversity for a representative of each trypanorhynch suborder: the ray-hosted Rhinoptericola megacantha (Trypanobatoida) and the shark-hosted Callitetrarhynchus gracilis (Trypanoselachoida). Adults of R. megacantha are more host-specific and less broadly distributed than adults of C. gracilis, allowing correlation between these factors and genetic structure. Replicate tapeworm specimens were sequenced from the same host individual, from multiple conspecific hosts within and across geographic regions, and from multiple definitive host species. For R. megacantha, population structure coincided with geography rather than host species. For C. gracilis, limited population structure was found, suggesting a potential link between degree of host specificity and structure. Conspecific trypanorhynchs from the same host individual were found to be as, or more, genetically divergent from one another as from conspecifics from different host individuals. For both species, high levels of homozygosity and positive FIS values were documented.

Imaging Reactive Oxygen Radicals in Excised Mouse Lung Trapped by Reaction with Hydroxylamine Probes Using 1 GHz Rapid Scan Electron Paramagnetic Resonance.

PURPOSE: Oxidative stress is proposed to be critical in acute lung disease, but methods to monitor radicals in lungs are lacking. Our goal is to develop low-frequency electron paramagnetic resonance (EPR) methods to monitor radicals that contribute to the disease. PROCEDURES: Free radicals generated in a lipopolysaccharide-induced mouse model of acute respiratory distress syndrome reacted with cyclic hydroxylamines CPH (1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride) and DCP-AM-H (4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid), which were converted into the corresponding nitroxide radicals, CP• and DCP•. The EPR signals of the nitroxide radicals in excised lungs were imaged with a 1 GHz EPR spectrometer/imager that employs rapid scan technology. RESULTS: The small numbers of nitroxides formed by reaction of the hydroxylamine with superoxide result in low signal-to-noise in the spectra and images. However, since the spectral properties of the nitroxides are known, we can use prior knowledge of the line shape and hyperfine splitting to fit the noisy data, yielding well-defined spectra and images. Two-dimensional spectral-spatial images are shown for lung samples containing (4.5 ± 0.5) ×1014 CP• and (9.9 ± 1.0) ×1014 DCP• nitroxide spins. These results suggest that a probe that accumulates in cells gives a stronger nitroxide signal than a probe that is more easily washed out of cells. CONCLUSION: The nitroxide radicals in excised mouse lungs formed by reaction with hydroxylamine probes CPH and DCP-AM-H can be imaged at 1 GHz.

Cyclic Disulfide-Bridged Dinitroxide Biradical for Measuring Thiol Redox Status by Electron Paramagnetic Resonance.

Among low-molecular-weight thiols, glutathione (GSH) is the main antioxidant in the cell, and its concentration is an indicator of the redox status. A cyclic disulfide-linked dinitroxide was designed for monitoring GSH by electron-paramagnetic resonance (EPR) spectroscopy. Reaction of the disulfide with GSH and three other thiols was measured at 9.6 GHz (X-band) and shown to be of first order in thiols. It is proposed that the reaction of the disulfide with 1 equiv of thiolate produced a short-lived intermediate that reacts with 1 equiv of thiolate to produce the cleavage product. The equilibrium ratio of the cleaved and intact disulfide is a measure of the redox state. Since the long-term goal is to use the disulfide to probe physiology in vivo, the feasibility of EPR spectroscopy and imaging of the disulfide and its cleavage product was demonstrated at 1 GHz (L-band).

The Combination of Glucocorticoids and Hyaluronic Acid Enhances Efficacy in IL-1ß/IL-17-Treated Bovine Osteochondral Grafts Compared with Individual Application.

Patients with knee osteoarthritis often receive glucocorticoid (GC) or hyaluronic acid (HA) injections to alleviate symptoms. This study evaluated the impact of Triamcinolone Hexacetonide (a GC), HA, and a combination of both on bovine osteochondral grafts exposed to IL-1ß and IL-17 in an ex vivo culture. Metabolic activity increased with GC treatment. GCs and GCs/HA counteracted cytokine effects, with gene expressions similar to untreated controls, while HA alone did not. However, HA improved the coefficient of friction after two weeks. The highest friction values were observed in GC-containing and cytokine-treated groups. Cytokine treatment reduced tissue proteoglycan content, which HA could mitigate, especially in the GC/HA combination. This combo also effectively controlled proteoglycan release, supported by reduced sGAG release. Cytokine treatment led to surface cell death, while GCs, HA, or their combination showed protective effects against inflammation. The GC/HA combination had the best overall results, suggesting its potential as a superior treatment option for osteoarthritis.

Mincing bovine articular cartilage with commercially available shavers reduces the viability of chondrocytes compared to scalpel mincing.

PURPOSE: The study aimed to compare the effect of mincing bovine articular cartilage with different shaver blades on chondrocyte viability. METHODS: Bovine articular cartilage was harvested either with a scalpel or with three different shaver blades (2.5 mm, 3.5 mm, or 4.2 mm) from a commercially available shaver. The cartilage harvested with a scalpel was then minced into fragments smaller than 1 mm3 with a scalpel. All four conditions were cultivated in a culture medium for seven days. After Day 1 and Day 7, the following measurements were performed: metabolic activity, RNA isolation, and gene expression of anabolic (COL2A1 and ACAN) and catabolic genes (MMP1 and MMP13), live/dead staining and visualization using confocal microscopy, and flow cytometric characterization of minced cartilage chondrocytes. RESULTS: Mincing the cartilage with shavers significantly reduced metabolic activity after one and seven days compared to scalpel mincing (p < 0.001). Gene expression of anabolic genes (COL2A1 and ACAN) was reduced, while catabolic genes (MMP1 and MMP13) were increased after day 7 in all shaver conditions. Confocal microscopy showed a thin line of dead cells at the lesion side with viable cells beneath for the scalpel mincing and a higher number of dead cells diffusely distributed in the shaver conditions. After seven days, there was a significant decrease in viable cells in the shaver conditions compared to scalpel mincing (p < 0.05). Flow cytometric characterization revealed fewer intact cells and proportionally more dead cells in all shaver conditions compared to the scalpel mincing. CONCLUSION: Mincing bovine articular cartilage with commercially available shavers reduces the viability of chondrocytes compared to scalpel mincing immediately after harvest and after seven days in culture. This suggests that mincing cartilage with a shaver should be considered a matrix rather than a cell therapy. LEVEL OF EVIDENCE: Level II therapeutic study.

Unicompartmental Knee Arthroplasty Provides Superior Clinical and Radiological Outcomes Compared to High Tibial Osteotomy at a Follow-Up of 5-8 Years.

BACKGROUND: Knee Osteoarthritis (OA) is a debilitating disease. Initially, the medial compartments are affected in most cases. For this pathology, joint preservation is preferable. Two surgical procedures aim to meet this goal: high-tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA). The aim was to compare clinical and radiological outcomes of HTO versus UKA in patients with unicompartmental, medial OA. METHOD: Retrospective case series. A total of 86 (61 UKA, 25 HTO) patients that received either treatment at a single, specialized center were assessed pre-operatively and at a single follow-up examination at 77.13 months (±8.170). The Knee Society Score (KSS), range of motion (ROM), SF36 questionnaire and the Tegner score were used. The Kellgren-Lawrence score was assessed pre- and post-surgically. Survivorship with the endpoint "revision" was assessed. RESULTS: The UKA group showed significantly better improvements in KSS scores for pain (p < 0.006) and function (p < 0.001). OA progression (p < 0.02) and survivorship (p < 0.018) differed, significantly favoring UKA. ROM, SF36 and Tegner score did not differ significantly. CONCLUSIONS: The presented mid-to long-term data suggest that UKA provides superior results in selected outcomes. Nevertheless, significant differences in the demographics of treatments indicate the challenge of comparing these two treatments.

Brain stimulation techniques as novel treatment options for insomnia: A systematic review.

Despite the success of cognitive behavioural therapy for insomnia and recent advances in pharmacotherapy, many patients with insomnia do not sufficiently respond to available treatments. This systematic review aims to present the state of science regarding the use of brain stimulation approaches in treating insomnia. To this end, we searched MEDLINE, Embase and PsycINFO from inception to 24 March 2023. We evaluated studies that compared conditions of active stimulation with a control condition or group. Outcome measures included standardized insomnia questionnaires and/or polysomnography in adults with a clinical diagnosis of insomnia. Our search identified 17 controlled trials that met inclusion criteria, and assessed a total of 967 participants using repetitive transcranial magnetic stimulation, transcranial electric stimulation, transcutaneous auricular vagus nerve stimulation or forehead cooling. No trials using other techniques such as deep brain stimulation, vestibular stimulation or auditory stimulation met the inclusion criteria. While several studies report improvements of subjective and objective sleep parameters for different repetitive transcranial magnetic stimulation and transcranial electric stimulation protocols, important methodological limitations and risk of bias limit their interpretability. A forehead cooling study found no significant group differences in the primary endpoints, but better sleep initiation in the active condition. Two transcutaneous auricular vagus nerve stimulation trials found no superiority of active stimulation for most outcome measures. Although modulating sleep through brain stimulation appears feasible, gaps in the prevailing models of sleep physiology and insomnia pathophysiology remain to be filled. Optimized stimulation protocols and proof of superiority over reliable sham conditions are indispensable before brain stimulation becomes a viable treatment option for insomnia.

Local treatment in metastatic GIST patients: A multicentre analysis from the Dutch GIST Registry.

BACKGROUND: The added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of a survey study and retrospective analyses in a clinical database. METHODS: A survey study was conducted among clinical specialists to select most relevant characteristics of metastatic GIST patients considered for local treatment, defined as elective surgery or ablation. Patients were selected from the Dutch GIST Registry. A multivariate Cox-regression model for overall survival since time of diagnosis of metastatic disease was estimated with local treatment as a time-dependent variable. An additional model was estimated to assess prognostic factors since local treatment. RESULTS: The survey's response rate was 14/16. Performance status, response to TKIs, location of active disease, number of lesions, mutation status, and time between primary diagnosis and metastases, were regarded the 6 most important characteristics. Of 457 included patients, 123 underwent local treatment, which was associated with better survival after diagnosis of metastases (HR = 0.558, 95%CI = 0.336-0.928). Progressive disease during systemic treatment (HR = 3.885, 95%CI = 1.195-12.627) and disease confined to the liver (HR = 0.269, 95%CI = 0.082-0.880) were associated with worse and better survival after local treatment, respectively. CONCLUSION: Local treatment is associated with better survival in selected patients with metastatic GIST. Locally treated patients with response to TKIs and disease confined to the liver have good clinical outcome. These results might be considered for tailoring treatment, but should be interpreted with care because only specific patients are provided with local treatment in this retrospective study.

The relationship between mental health, sleep quality and the immunogenicity of COVID-19 vaccinations.

Sleep modulates the immune response, and sleep loss can reduce vaccine immunogenicity; vice versa, immune responses impact sleep. We aimed to investigate the influence of mental health and sleep quality on the immunogenicity of COVID-19 vaccinations and, conversely, of COVID-19 vaccinations on sleep quality. The prospective CoVacSer study monitored mental health, sleep quality and Anti-SARS-CoV-2-Spike IgG titres in a cohort of 1082 healthcare workers from 29 September 2021 to 19 December 2022. Questionnaires and blood samples were collected before, 14 days, and 3 months after the third COVID-19 vaccination, as well as in 154 participants before and 14 days after the fourth COVID-19 vaccination. Healthcare workers with psychiatric disorders had slightly lower Anti-SARS-CoV-2-Spike IgG levels before the third COVID-19 vaccination. However, this effect was mediated by higher median age and body mass index in this subgroup. Antibody titres following the third and fourth COVID-19 vaccinations ("booster vaccinations") were not significantly different between subgroups with and without psychiatric disorders. Sleep quality did not affect the humoral immunogenicity of the COVID-19 vaccinations. Moreover, the COVID-19 vaccinations did not impact self-reported sleep quality. Our data suggest that in a working population neither mental health nor sleep quality relevantly impact the immunogenicity of COVID-19 vaccinations, and that COVID-19 vaccinations do not cause a sustained deterioration of sleep, suggesting that they are not a precipitating factor for insomnia. The findings from this large-scale real-life cohort study will inform clinical practice regarding the recommendation of COVID-19 booster vaccinations for individuals with mental health and sleep problems.

#OMFSurgery: analyzing the use of social media applications in oral and maxillofacial surgery resident training.

BACKGROUND: Despite its increasing popularity, to our knowledge the use of social media applications (SM) for residents' training in Oral and Maxillofacial Surgery (OMFS) has not been investigated yet. The aim of this study was to evaluate the use of SM applications by OMFS residents for post-graduate training in Germany. METHODS: For explorative assessment, an online questionnaire containing 27 questions about the current use of SM for resident training was sent to OMFS residents in Germany. RESULTS: Sixty-four colleagues participated to the study. Thirty-four participants (54%) responded to regularly use those platforms mainly for OMFS-related content. YouTube (65%, n = 37), Instagram (48%, n = 27), ResearchGate (25%, n = 14) and WhatsApp (16%, n = 9) were the most popular platforms. (Surgical) videos (97%, n = 59), pictures and graphics (82%, n = 50) were the mainly accessed contents. Forty-four participants (69%) stated that SM substantially contributed to their OMFS training. Dentoalveolar surgery and implantology (66%, n = 35) and aesthetic facial surgery (55%, n = 29) content contributed most to OMFS resident training. Fifty-one participants (80%) recommended an official SM account of the DGMKG. CONCLUSIONS: SM is frequently used by OMFS residents for the consumption of training-related content. There is an imbalance toward dentoalveolar and facial aesthetic surgery regarding the presented content. Academic institutions and societies should complement their educational activities to not miss this emerging educational innovation. Official SM content by academic institutions and societies could contribute to the existing educational activities.

Effects of clozapine-N-oxide and compound 21 on sleep in laboratory mice.

Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remote control of targeted cell populations using chemical actuators that bind to modified receptors. Despite the popularity of DREADDs in neuroscience and sleep research, potential effects of the DREADD actuator clozapine-N-oxide (CNO) on sleep have never been systematically tested. Here, we show that intraperitoneal injections of commonly used CNO doses (1, 5, and 10 mg/kg) alter sleep in wild-type male laboratory mice. Using electroencephalography (EEG) and electromyography (EMG) to analyse sleep, we found a dose-dependent suppression of rapid eye movement (REM) sleep, changes in EEG spectral power during non-REM (NREM) sleep, and altered sleep architecture in a pattern previously reported for clozapine. Effects of CNO on sleep could arise from back-metabolism to clozapine or binding to endogenous neurotransmitter receptors. Interestingly, we found that the novel DREADD actuator, compound 21 (C21, 3 mg/kg), similarly modulates sleep despite a lack of back-metabolism to clozapine. Our results demonstrate that both CNO and C21 can modulate sleep of mice not expressing DREADD receptors. This implies that back-metabolism to clozapine is not the sole mechanism underlying side effects of chemogenetic actuators. Therefore, any chemogenetic experiment should include a DREADD-free control group injected with the same CNO, C21, or newly developed actuator. We suggest that electrophysiological sleep assessment could serve as a sensitive tool to test the biological inertness of novel chemogenetic actuators.

Scientists have developed ways to remotely turn on and off populations of neurons in the brain to test the role they play in behaviour. One technique that is frequently used is chemogenetics. In this approach, specific neurons are genetically modified to contain a special 'designer receptor' which switches cells on or off when its corresponding 'designer drug' is present. Recent studies have shown that the drug most commonly used in these experiments, clozapine-N-oxide (CNO), is broken down into small amounts of clozapine, an antipsychotic drug that binds to many natural receptors in the brain and modulates sleep. Nevertheless, CNO is still widely believed to not affect animals' sleep-wake patterns which in turn could influence a range of other brain activities and behaviours. However, there have been reports of animals lacking designer receptors still displaying unusual behaviours when administered CNO. This suggests that the breakdown of CNO to clozapine may cause off-target effects which could be skewing the results of chemogenetic studies. To investigate this possibility, Traut, Mengual et al. treated laboratory mice that do not have a designer receptor with three doses of CNO, and one dose of a new designer drug called compound-21 (C21) that is not broken down to clozapine. They found that high and medium doses of CNO, but also C21 altered the sleep-wake patterns of the mice and their brain activity during sleep. These findings show that CNO and C21 both have sleep-modulating effects on the brain and suggest that these effects are not only due to the production of clozapine, but the drugs binding to off-target natural receptors. To counteract this, Traut, Mengual et al. recommend optimizing the dose of drugs given to mice, and repeating the experiment on a control group which do not have the designer receptor. This will allow researchers to determine which behavioural changes are the result of turning on or off the neuron population of interest, and which are artefacts caused by the drug itself. They also suggest testing how newly developed designer drugs impact sleep before using them in behavioural experiments. Refining chemogenetic studies in these ways may yield more reliable insights about the role specific groups of cells have in the brain.