Survey of National Health Service (NHS) orthodontic practitioners in Wales, UK. Part 2: job satisfaction perceptions of the workforce 2021-2022.

OBJECTIVE: To ascertain the perceptions of the Welsh NHS orthodontic workforce regarding their job satisfaction and work life balance. DESIGN: Descriptive cross-sectional survey. PARTICIPANTS AND SETTING: Clinicians providing NHS orthodontic treatment in Wales. METHODS: An anonymised, email-distributed, electronic, two-part survey (onlinesurveys.ac.uk) of the Welsh NHS orthodontic workforce working within Wales was undertaken. The survey consisted of three sections: (1) demographic information (part 1); (2) respondents' working pattern (part 1); and (3) perceptions of professional job satisfaction and work/life balance (part 2). The responses received were exported into an Excel spreadsheet for descriptive analysis. The free-text comments were collated for each question and subsequently underwent a content analysis to identify any common themes. RESULTS: Part 2 of the survey yielded an overall response rate of 69.6% (n = 78). Over 96% (n = 75) of respondents felt that they had 'made the right career choice, including 100% of orthodontic trainees, orthodontic specialists and orthodontic consultants. Of the respondents, 88.5% (n = 69) said they 'enjoyed going to work', with the remaining being mostly neutral in their opinion. Of the respondents, 79.5% (n = 62) felt they were able to 'provide their patients the optimum care' and 64.1% (n = 50) felt that more demands were being placed upon them by patients and parents. Overall, 52.6% (n = 41) of survey respondents believed it was becoming increasingly difficult to achieve an effective work/life balance, and this was more prevalent among male respondents (61.5%, n = 16) than female respondents (48.1%, n = 25), although this difference was not statistically significant (P >0.05). CONCLUSIONS: Over 96% of respondents felt they have chosen the right career and that flexibility and a good working environment are important to job satisfaction. Respondents felt that there are increasing demands being placed upon them by patients/parents, employers, the Regulators, the Government and Health Boards. This is leading to increased difficulty in achieving a satisfactory work/life balance, especially among male respondents.

Survey of National Health Service (NHS) orthodontic practitioners in Wales, UK. Part 1: working patterns 2021-2022.

OBJECTIVE: To ascertain the working patterns of the NHS orthodontic workforce in Wales and any possible future changes. DESIGN: Descriptive cross-sectional survey. PARTICIPANTS: NHS orthodontic practitioners in Wales. METHODS: An anonymised email distributed an electronic two-part survey of the Welsh NHS orthodontic workforce. The survey consisted of three sections: (1) demographic information; (2) respondents' working pattern (part 1); and (3) perceptions of professional satisfaction (part 2). RESULTS: Part 1 of the survey yielded a 70.5% response rate (n = 79); 65.8% of the respondents were women. Of the respondents, 45.6% (n = 36) worked full time (F/T), 39.2% (n = 31) worked less than F/T and 15.2% (n = 12) worked more than F/T. Of the male respondents, 81.5% (n = 22) worked 10 sessions or more compared to 50% (n = 26) of women. The respondents undertook 508.5 orthodontic clinical sessions per week within Wales; of these sessions, 87.6% (n = 445.5) delivered NHS orthodontic care. Of the respondents, 8.4% (n = 7) were planning to increase their orthodontic clinical time within the next 2 years, 24.1% (n = 19) were planning to decrease it and 20.3% (n = 16) were unsure. One-quarter of respondents indicated that they were planning to stop clinical orthodontic activity within the next 5 years, including 53.3% (n = 8) of DwSIs, 37% (n = 10) of primary care specialists and 13.3% (n = 2) of consultants. The pandemic was an influencing factor for 80% of these clinicians. CONCLUSIONS: Part 1 of the survey suggested that the majority of the orthodontic workforce was female, were working full time or more, and spent most sessions delivering NHS care. One-quarter of respondents were planning to cease undertaking orthodontic activity within the next 5 years.

LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function.

Mitochondria-associated RNA-binding proteins (RBPs) have emerged as key contributors to mitochondrial biogenesis and homeostasis. With few examples known, we set out to identify RBPs that regulate nuclear-encoded mitochondrial mRNAs (NEMmRNAs). Our systematic analysis of RNA targets of 150 RBPs identified RBPs with a preference for binding NEMmRNAs, including LARP4, a La RBP family member. We show that LARP4's targets are particularly enriched in mRNAs that encode respiratory chain complex proteins (RCCPs) and mitochondrial ribosome proteins (MRPs) across multiple human cell lines. Through quantitative proteomics, we demonstrate that depletion of LARP4 leads to a significant reduction in RCCP and MRP protein levels. Furthermore, we show that LARP4 depletion reduces mitochondrial function, and that LARP4 re-expression rescues this phenotype. Our findings shed light on a novel function for LARP4 as an RBP that binds to and positively regulates NEMmRNAs to promote mitochondrial respiratory function.

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma.

Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape of HSA may aid in developing therapeutic strategies for dogs and may also inform therapies for the rare and aggressive human cancer angiosarcoma. The objectives of this study were to build a framework for leveraging real-world genomic and clinical data that could provide the foundation for precision medicine in veterinary oncology, and to determine the relationships between genomic and clinical features in canine splenic HSA. One hundred and nine dogs with primary splenic HSA treated by splenectomy that had tumour sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel were enrolled. Patient signalment, weight, metastasis at diagnosis and overall survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables including outcome were assessed. Somatic mutations in TP53 (n = 44), NRAS (n = 20) and PIK3CA (n = 19) were most common. Survival was associated with presence of metastases at diagnosis and germline variants in SETD2 and NOTCH1. Age at diagnosis was associated with somatic NRAS mutations and breed. TP53 and PIK3CA somatic mutations were found in larger dogs, while germline SETD2 variants were found in smaller dogs. We identified both somatic mutations and germline variants associated with clinical variables including age, breed and overall survival. These genetic changes may be useful prognostic factors and provide insight into the genomic landscape of hemangiosarcoma.

The impact of COVID-19 pandemic on orthodontic services and trainees' mental health in India.

Aim: To evaluate the impact of COVID-19 on clinical orthodontic services, orthodontic education, and the emotional well-being of orthodontists and orthodontic trainees in India. Materials and methods: The survey was designed using Survey Monkey™ and distributed to members of the Indian Orthodontic Society via their registered email address and also via social media platforms (WhatsApp and LinkedIn). Results: A total of 610 responses to the survey were received. The majority of respondents agreed on the negative impact of COVID-19 on clinical activity and the associated income of orthodontists. Respondents reported that this was mainly due to national restrictions (70.1%), increased cross infection measures (59.6%), state restrictions (55.9%), and social distancing (39.4%). Ninety one percent of respondents agreed that orthodontic staff should have evidence of vaccination before providing care.COVID-19 was found to have a negative impact on the trainees' perceptions of their clinical dexterity (72.4%), their confidence with respect to academic knowledge (66.5%), their mental health (80.7%), and their stress levels during the pandemic (93.2%). Conclusion: The COVID-19 pandemic has had a negative impact on orthodontic specialists and post-graduate trainees in India. The impact on trainees' mental health was significantly higher compared to trainees from other countries. Decreased clinical activity has reduced the opportunities for learning, and trainers must rise to the challenge of providing additional support to this cohort of trainees who will progress to become the future orthodontic workforce.

A Review of MDMA-Assisted Therapy for Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a common chronic and disabling psychiatric disorder that may develop after exposure to a traumatic life event. There are existing evidence-based psychotherapies and pharmacotherapies for PTSD; however, these treatments have significant limitations. 3,4-methylenedioxymethamphetamine (MDMA) was granted "breakthrough therapy" status by the U.S. Food and Drug Administration (FDA) in 2017 for the treatment of PTSD in conjunction with psychotherapy after preliminary Phase II results. This treatment is currently being investigated in Phase III trials with anticipated FDA approval of MDMA-assisted psychotherapy for PTSD in late 2023. This article reviews the evidence base for MDMA-assisted psychotherapy for PTSD, pharmacology and the proposed causal mechanisms of MDMA, risks and limitations of the current evidence, and challenges and future directions for the field.

Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision therapeutics.

Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.

Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein.

Membrane efflux pumps play a major role in bacterial multidrug resistance. The tripartite multidrug efflux pump system from Escherichia coli, AcrAB-TolC, is a target for inhibition to lessen resistance development and restore antibiotic efficacy, with homologs in other ESKAPE pathogens. Here, we rationalize a mechanism of inhibition against the periplasmic adaptor protein, AcrA, using a combination of hydrogen/deuterium exchange mass spectrometry, cellular efflux assays, and molecular dynamics simulations. We define the structural dynamics of AcrA and find that an inhibitor can inflict long-range stabilisation across all four of its domains, whereas an interacting efflux substrate has minimal effect. Our results support a model where an inhibitor forms a molecular wedge within a cleft between the lipoyl and αß barrel domains of AcrA, diminishing its conformational transmission of drug-evoked signals from AcrB to TolC. This work provides molecular insights into multidrug adaptor protein function which could be valuable for developing antimicrobial therapeutics.

Health Insurance Coverage And Access To Care Among LGBT Adults, 2013-19.

Historically, lesbian, gay, bisexual, and transgender (LGBT) adults have faced barriers to obtaining health insurance coverage, which have contributed to disparities in access to care and health outcomes. The Affordable Care Act (ACA) and the 2015 Supreme Court ruling on marriage equality had the potential to improve access to health insurance for LGBT people. Using data from the nationally representative Health Reform Monitoring Survey, we provide new evidence on trends in coverage and access to care for LGBT and non-LGBT adults between 2013 and 2019. In 2013 LGBT adults were significantly less likely than non-LGBT adults to have insurance coverage and more likely to report difficulty obtaining necessary medical care. Disparities in insurance coverage began to decline in 2014, when the main coverage provisions of the ACA went into effect. By 2017-19, coverage rates for LGBT adults were comparable to those of non-LGBT adults, although significant disparities in access remained.

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer.

CONTEXT/OBJECTIVES: Psilocybin-assisted psychotherapy shows promise in treating depression and existential distress in people with serious medical illness. However, its individual-based methodology poses challenges for scaling and resource availability. The HOPE trial (A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients with Cancer) is an Institutional Review Boards-approved open-label feasibility and safety pilot study examining psilocybin-assisted group therapy in cancer patients with a DSM-5 depressive disorder (including major depressive disorder as well as adjustment disorder with depressed mood). We report here the safety and clinical outcome measures including six-months follow up data. METHODS: Outcome measures were collected at baseline, two-weeks and 26-weeks postintervention. The study involved three group preparatory sessions, one high-dose (25 mg) group psilocybin session, and three group integration sessions with cohorts of four participants over a three-week intervention. RESULTS: Twelve participants completed the trial. no serious adverse events attributed to psilocybin occurred. The primary clinical outcome measures of change in symptoms of depression on the clinician administered 17-item-HAM-D showed clinically substantial decrease in HAM-D scores from baseline to the two-week timepoint (21.5-10.09, P < 0.001) and the 26-week timepoint (21.5-14.83, P = 0.006). Six out of 12 participants met criteria for remission at two weeks, as defined by HAM-D < 7, three out 12 demonstrated a clinically significant change (4-6 points), and eight out of twelve demonstrated a clinically substantial change (7-12 points). CONCLUSION: This pilot study demonstrated the safety, feasibility, and possible efficacy of psilocybin-assisted group therapy for cancer patients dealing with depressive symptoms. Based on demonstrated efficacy and significant reductions in therapist time, future investigations with the group therapy model are warranted.

The COVID-19 experience of orthodontists in Jordan.

OBJECTIVES: To understand the impact of the COVID-19 pandemic on orthodontic clinical services in Jordan. MATERIALS AND METHODS: Google Forms electronic questionnaires were distributed between March and June 2021 using the WhatsApp platform of the Jordanian Orthodontic Society and via direct WhatsApp messages. The survey was identical and contemporaneous to that used in the United Kingdom. RESULTS: The survey yielded 127 unique responses, giving a response rate of 53.1%. The factors that had the greatest impact on service delivery were government guidance (78%), patients' fear of attending (70.1%), and increased cross-infection measures (65.4%). The survey revealed that there had been a perceived deterioration in oral hygiene (60.3%) and levels of compliance (61.9%) in patients in active treatment even though patients in treatment were prioritized during the pandemic. Also, 56.8% of respondents felt clinical staff should be vaccinated and undergo regular testing for COVID-19. Orthodontists within Jordan were optimistic regarding the speed at which clinical services would return to pre-pandemic levels of activity with 32.5% anticipating this would take less than 6 months. CONCLUSIONS: Patients in active orthodontic treatment, during COVID-19, have been prioritized but at the expense of new and review patients. Respondents in Jordan felt COVID-19 would have ongoing effects on clinical care, professional practice, and society. Most respondents supported the vaccination of orthodontic staff and were optimistic about the effect of a vaccination program on restoring clinical services.

Evaluating motion of pancreatic tumors and anatomical surrogates using cine MRI in 0.35T MRgRT under free breathing conditions.

Treatment tolerability is a significant limitation to pancreatic cancer treatment with radiotherapy due to proximity to highly radiosensitive organs and respiratory motion necessitating expanded target margins. Further, pancreatic tumors are difficult to visualize on conventional radiotherapy systems. Surrogates are often used to locate the tumor but are often inconsistent and do not provide strong positional relations throughout the respiratory cycle. This work utilizes a retrospective dataset of 45 pancreatic cancer patients treated on an MR-Linac system with cine MRI acquired for real-time target tracking. We investigated intra-fraction motion of tumors and two abdominal surrogates, leading to prediction models between the tumor and surrogate. Patient specific motion evaluation and prediction models were generated from 225 cine MRI series acquired during treatment. Tumor contours were used to evaluate the pancreatic tumor motion. Linear regression and principal component analysis (PCA) based models were used to predict tumor position from the anterior-posterior (AP) motion of the abdominal surface, the superior-inferior (SI) motion of the diaphragm, or a combination. Models were evaluated using mean squared error (MSE) and mean absolute error (MAE). Contour analysis showed the average pancreatic tumor motion range was 7.4 ± 2.7 mm and 14.9 ± 5.8 mm in the AP and SI directions, respectively. The PCA model had MSE of 1.4 mm2 and 0.6 mm2 , for the SI and AP directions, respectively, with both surrogates as inputs for the models. When only the abdomen surrogate was used, MSE was 1.3 mm2 and 0.4 mm2 in the SI and AP directions, while it was 0.4 mm2 and 1.3 mm2 when only the diaphragm surrogate was used. We evaluated intra-fraction pancreatic tumor motion and demonstrated prediction models between the tumor and surrogate. The models calculated the pancreatic tumor position from diaphragm, abdominal, or both contours within standard pancreatic cancer target margin, and the process could be applied to other disease sites in the abdominothoracic cavity.

Assessment of Various Multimodal Fusion Approaches Using Synthetic Aperture Radar (SAR) and Electro-Optical (EO) Imagery for Vehicle Classification via Neural Networks.

Multimodal fusion approaches that combine data from dissimilar sensors can better exploit human-like reasoning and strategies for situational awareness. The performance of a six-layer convolutional neural network (CNN) and an 18-layer ResNet architecture are compared for a variety of fusion methods using synthetic aperture radar (SAR) and electro-optical (EO) imagery to classify military targets. The dataset used is the Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset, using both original measured SAR data and synthetic EO data. We compare the classification performance of both networks using the data modalities individually, feature level fusion, decision level fusion, and using a novel fusion method based on the three RGB-input channels of a residual neural network (ResNet). In the proposed input channel fusion method, the SAR and the EO imagery are separately fed to each of the three input channels, while the third channel is fed a zero vector. It is found that the input channel fusion method using ResNet was able to consistently perform to a higher classification accuracy in every equivalent scenario.

Analyses of canine cancer mutations and treatment outcomes using real-world clinico-genomics data of 2119 dogs.

Spontaneous tumors in canines share significant genetic and histological similarities with human tumors, positioning them as valuable models to guide drug development. However, current translational studies have limited real world evidence as cancer outcomes are dispersed across veterinary clinics and genomic tests are rarely performed on dogs. In this study, we aim to expand the value of canine models by systematically characterizing genetic mutations in tumors and their response to targeted treatments. In total, we collect and analyze survival outcomes for 2119 tumor-bearing dogs and the prognostic effect of genomic alterations in a subset of 1108 dogs. Our analysis identifies prognostic concordance between canines and humans in several key oncogenes, including TP53 and PIK3CA. We also find that several targeted treatments designed for humans are associated with a positive prognosis when used to treat canine tumors with specific genomic alterations, underscoring the value of canine models in advancing drug discovery for personalized oncology.

Epistemic injustice and the psychiatrist.

BACKGROUND: Psychiatrists depend on their patients for clinical information and are obligated to regard them as trustworthy, except in special circumstances. Nevertheless, some critics of psychiatry have argued that psychiatrists frequently perpetrate epistemic injustice against patients. Epistemic injustice is a moral wrong that involves unfairly discriminating against a person with respect to their ability to know things because of personal characteristics like gender or psychiatric diagnosis. METHODS: We review the concept of epistemic injustice and several claims that psychiatric practice is epistemically unjust. RESULTS: While acknowledging the risk of epistemic injustice in psychiatry and other medical fields, we argue that most concerns that psychiatric practice is epistemically unjust are unfounded. CONCLUSIONS: The concept of epistemic injustice does not add significantly to existing standards of good clinical practice, and that it could produce changes in practice that would be deleterious. Psychiatrists should resist calls for changes to clinical practice based on this type of criticism.

Chromatographic Phospholipid Trapping for Automated H/D Exchange Mass Spectrometry of Membrane Protein-Lipid Assemblies.

Lipid interactions modulate the function, folding, structure, and organization of membrane proteins. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) has emerged as a useful tool to understand the structural dynamics of these proteins within lipid environments. Lipids, however, have proven problematic for HDX-MS analysis of membrane-embedded proteins due to their presence of impairing proteolytic digestion, causing liquid chromatography column fouling, ion suppression, and/or mass spectral overlap. Herein, we describe the integration of a chromatographic phospholipid trap column into the HDX-MS apparatus to enable online sample delipidation prior to protease digestion of deuterium-labeled protein-lipid assemblies. We demonstrate the utility of this method on membrane scaffold protein-lipid nanodisc─both empty and loaded with the ∼115 kDa transmembrane protein AcrB─proving efficient and automated phospholipid capture with minimal D-to-H back-exchange, peptide carry-over, and protein loss. Our results provide insights into the efficiency of phospholipid capture by ZrO2-coated and TiO2 beads and describe how solution conditions can be optimized to maximize not only the performance of our online but also the existing offline, delipidation workflows for HDX-MS. We envision that this HDX-MS method will significantly ease membrane protein analysis, allowing to better interrogate their dynamics in artificial lipid bilayers or even native cell membranes.

Structural mass spectrometry approaches to understand multidrug efflux systems.

Multidrug efflux pumps are ubiquitous across both eukaryotes and prokaryotes, and have major implications in antimicrobial and multidrug resistance. They reside within cellular membranes and have proven difficult to study owing to their hydrophobic character and relationship with their compositionally complex lipid environment. Advances in structural mass spectrometry (MS) techniques have made it possible to study these systems to elucidate critical information on their structure-function relationships. For example, MS techniques can report on protein structural dynamics, stoichiometry, connectivity, solvent accessibility, and binding interactions with ligands, lipids, and other proteins. This information proving powerful when used in conjunction with complementary structural biology methods and molecular dynamics (MD) simulations. In the present review, aimed at those not experts in MS techniques, we report on the current uses of MS in studying multidrug efflux systems, practical considerations to consider, and the future direction of the field. In the first section, we highlight the importance of studying multidrug efflux proteins, and introduce a range of different MS techniques and explain what information they yield. In the second section, we review recent studies that have utilised MS techniques to study and characterise a range of different multidrug efflux systems.

Should we be leery of being Leary? Concerns about psychedelic use by psychedelic researchers.

Psychedelic research is proceeding rapidly, despite ongoing legal and regulatory barriers and lingering questions about study design, such as the difficulty of ensuring adequate blinding, the relative overrepresentation in studies of participants who have previously used psychedelics, and the importance of personal experience with psychedelics for those who provide psychedelic-assisted therapy. Here we wish to explore a distinct concern: whether personal use of psychedelics by researchers could threaten the objectivity and ethical conduct of psychedelic research itself. In 2020, Anderson et al. suggested that psychedelic use could lead even "conservative individuals to become wildly enthusiastic about the potentials of psychedelics to heal and transform". Recent popular press criticisms of psychedelic science, in particular critiques of the MAPS Phase II and Phase III MDMA-Assisted Therapy trials for PTSD, have also raised questions about whether personal use of psychedelic drugs by psychedelic therapists could compromise scientific objectivity, lead to the exploitation of research subjects, or promote biased reporting of results. Here, we elaborate on and attempt to delimit these concerns, with the goal of informing policy related to psychedelic research and the eventual clinical use of psychedelics. In particular, we explore whether the possibility that psychedelic use can directly and positively affect investigators' enthusiasm about psychedelics themselves raises concerns about bias and scientific integrity. We then discuss several practical strategies to reduce perceived conflict of interest.

NHS orthodontic services in Wales: orthodontic workforce distribution and primary care commissioned activity in 2021.

Objectives 1) To ascertain the volume of primary care orthodontic activity commissioned within Wales and compare this to the 12-year-old population; and 2) To ascertain the orthodontic workforce undertaking NHS orthodontic provision within Wales and their distribution.Methods Information was gathered between September and November 2021 from multiple sources within Wales, including: Freedom of Information requests; Welsh Government statistics; orthodontic professional networks; orthodontic provider websites; health boards (HBs); and directors of primary care/contracting/commissioning.Results The HBs had varying levels of orthodontic need and commissioned activity with a significant amount of cross border activity in South Wales. Overall, it indicated that Wales was only commissioning orthodontic activity to meet 76% of the annual orthodontic need. Overall, 97.9% of commissioned primary care orthodontic activity was being used to provide treatment for 9,500 patients per year. Furthermore, 112 GDC-registered clinicians provide NHS orthodontic care within Wales - 52 orthodontic specialists; 32 orthodontic therapists; 24 DwSIs; and 4 orthodontic trainees (StR 1-3). NHS orthodontic care is provided at 47 sites within Wales - 32 sites in the GDS/Specialist Practice, 6 sites within the CDS and 9 secondary care settings.Conclusions NHS commissioned primary care orthodontic activity within Wales is 76% of the potential orthodontic annual need. Primary care orthodontic services are efficient with 97.9% of commissioned activity being used to provide treatment. In total, 112 GDC-registered clinicians provide NHS orthodontic care across 47 sites within Wales, with 29.5% of clinicians working at multiple sites. The distribution of the orthodontic providers is predominately in areas of high population density, resulting in some rural communities being a significant distance from any orthodontic provider.