Evaluating the feasibility of delivering a pain management programme for adults living with sickle cell disease.

Background: Pain is the prominent feature of sickle cell disease (SCD) and negatively affects quality of life. Delivery of pain management programmes (PMPs) has been suggested in clinical guidelines for pain management in SCD; however, further evidence of the feasibility and effectiveness of PMPs in this population is needed. This study explored the feasibility of delivering a sickle cell pain management programme (SCPMP) for adults within a haemoglobinopathies service. Methods: A single arm, repeated-measures observational design was used to determine feasibility of delivering the SCPMP at one study site. Primary feasibility outcomes were recruitment, completion of treatment and outcome measures, satisfaction, credibility and acceptability to participants. Secondary feasibility outcomes were treatment outcomes and processes, frequency of vaso-occlusive crisis (VOC) and healthcare utilisation. Results: Four of five feasibility criteria were met. Annual recruitment of eight participants to a SCPMP was not achieved. Twenty-nine people began a SCPMP during the study period. Twenty-five (86.2%) participants attended ≥5/8 sessions and 21(84%) programme completers provided all end of programme questionnaires. Mean scores of >7 on ten-point scales were seen across satisfaction and credibility questions. At least moderate (Hedges g >0.5) effect sizes were seen in pre-post SCPMP measures of pain interference, anxiety, depression, self-efficacy, pain-related worry and acceptance. A small (Hedges g 0.4) effect size was seen in HRQoL. Following SCPMP attendance, mean frequency of self-reported VOC and hospital admissions reduced. Conclusions: This study suggests that, given an adequate source of referrals, a SCPMP is feasible to deliver and appears acceptable and credible to participants. Exploration of influences on recruitment, such as barriers to group interventions, would be illuminating, prior to investigating feasibility of an adequately powered randomised-controlled trial.

Adolescent OCD Patient and Caregiver Perspectives on Identity, Authenticity, and Normalcy in Potential Deep Brain Stimulation Treatment.

The ongoing debate within neuroethics concerning the degree to which neuromodulation such as deep brain stimulation (DBS) changes the personality, identity, and agency (PIA) of patients has paid relatively little attention to the perspectives of prospective patients. Even less attention has been given to pediatric populations. To understand patients' views about identity changes due to DBS in obsessive-compulsive disorder (OCD), the authors conducted and analyzed semistructured interviews with adolescent patients with OCD and their parents/caregivers. Patients were asked about projected impacts to PIA generally due to DBS. All patient respondents and half of caregivers reported that DBS would impact patient self-identity in significant ways. For example, many patients expressed how DBS could positively impact identity by allowing them to explore their identities free from OCD. Others voiced concerns that DBS-related resolution of OCD might negatively impact patient agency and authenticity. Half of patients expressed that DBS may positively facilitate social access through relieving symptoms, while half indicated that DBS could increase social stigma. These views give insights into how to approach decision-making and informed consent if DBS for OCD becomes available for adolescents. They also offer insights into adolescent experiences of disability identity and "normalcy" in the context of OCD.

Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

Evaluating mental health decision units in acute care pathways (DECISION): a quasi-experimental, qualitative and health economic evaluation.

Background: People experiencing mental health crises in the community often present to emergency departments and are admitted to a psychiatric hospital. Because of the demands on emergency department and inpatient care, psychiatric decision units have emerged to provide a more suitable environment for assessment and signposting to appropriate care. Objectives: The study aimed to ascertain the structure and activities of psychiatric decision units in England and to provide an evidence base for their effectiveness, costs and benefits, and optimal configuration. Design: This was a mixed-methods study comprising survey, systematic review, interrupted time series, synthetic control study, cohort study, qualitative interview study and health economic evaluation, using a critical interpretive synthesis approach. Setting: The study took place in four mental health National Health Service trusts with psychiatric decision units, and six acute hospital National Health Service trusts where emergency departments referred to psychiatric decision units in each mental health trust. Participants: Participants in the cohort study (n = 2110) were first-time referrals to psychiatric decision units for two 5-month periods from 1 October 2018 and 1 October 2019, respectively. Participants in the qualitative study were first-time referrals to psychiatric decision units recruited within 1 month of discharge (n = 39), members of psychiatric decision unit clinical teams (n = 15) and clinicians referring to psychiatric decision units (n = 19). Outcomes: Primary mental health outcome in the interrupted time series and cohort study was informal psychiatric hospital admission, and in the synthetic control any psychiatric hospital admission; primary emergency department outcome in the interrupted time series and synthetic control was mental health attendance at emergency department. Data for the interrupted time series and cohort study were extracted from electronic patient record in mental health and acute trusts; data for the synthetic control study were obtained through NHS Digital from Hospital Episode Statistics admitted patient care for psychiatric admissions and Hospital Episode Statistics Accident and Emergency for emergency department attendances. The health economic evaluation used data from all studies. Relevant databases were searched for controlled or comparison group studies of hospital-based mental health assessments permitting overnight stays of a maximum of 1 week that measured adult acute psychiatric admissions and/or mental health presentations at emergency department. Selection, data extraction and quality rating of studies were double assessed. Narrative synthesis of included studies was undertaken and meta-analyses were performed where sufficient studies reported outcomes. Results: Psychiatric decision units have the potential to reduce informal psychiatric admissions, mental health presentations and wait times at emergency department. Cost savings are largely marginal and do not offset the cost of units. First-time referrals to psychiatric decision units use more inpatient and community care and less emergency department-based liaison psychiatry in the months following the first visit. Psychiatric decision units work best when configured to reduce either informal psychiatric admissions (longer length of stay, higher staff-to-patient ratio, use of psychosocial interventions), resulting in improved quality of crisis care or demand on the emergency department (higher capacity, shorter length of stay). To function well, psychiatric decision units should be integrated into the crisis care pathway alongside a range of community-based support. Limitations: The availability and quality of data imposed limitations on the reliability of some analyses. Future work: Psychiatric decision units should not be commissioned with an expectation of short-term financial return on investment but, if appropriately configured, they can provide better quality of care for people in crisis who would not benefit from acute admission or reduce pressure on emergency department. Study registration: The systematic review was registered on the International Prospective Register of Systematic Reviews as CRD42019151043. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/49/70) and is published in full in Health and Social Care Delivery Research; Vol. 11, No. 25. See the NIHR Funding and Awards website for further award information.

People who experience mental health crises often go to a hospital emergency department and can be admitted to a psychiatric hospital. Emergency departments and psychiatric wards are not always the best environments for supporting people in a crisis. Emergency departments are overcrowded and waits can be very long; psychiatric wards are also very busy. Psychiatric decision units have been introduced to reduce pressure and improve experiences of crisis care. Psychiatric decision units are short-stay hospital-based units where people can be assessed and signposted to the most appropriate care. This study aimed to evaluate the effect of psychiatric decision units on emergency department visits, psychiatric admissions and the cost of mental health care, and to consider the best way for psychiatric decision units to be structured. We looked at research on similar units internationally and identified all psychiatric decision units in England. We evaluated the impact of psychiatric decision units four mental health NHS trusts on emergency department visits and psychiatric admissions by examining electronic patient records in the 2 years before and after units opened, and by comparing records in areas with and without psychiatric decision units using data from NHS Digital. We compared mental health services used by people in the 9 months before and after their first psychiatric decision unit stay. We interviewed people about their experiences of the psychiatric decision unit and crisis care. We also interviewed staff working on and referring people to psychiatric decision units. There were some reductions in psychiatric admissions, emergency department visits and wait times following opening of psychiatric decision units. The resulting cost savings were small and did not outweigh the costs of running psychiatric decision units. People mostly found units safe, calming and supportive, except where they were discharged too quickly. Psychiatric decision units worked best to reduce psychiatric admissions and improve quality of crisis care where stays were longer and staffing levels higher. Psychiatric decision units had more impact on emergency departments where they were larger and stays were shorter.

Prevalence and molecular characterization of Salmonella isolated from wild birds in fresh produce environments.

Wild birds pose a difficult food safety risk to manage because they can avoid traditional wildlife mitigation strategies, such as fences. Birds often use agricultural fields and structures as foraging and nesting areas, which can lead to defecation on crops and subsequent transfer of foodborne pathogens. To assess the food safety risk associated with these events, wild bird feces were collected from produce fields across the southeastern United States during the 2021 and 2022 growing seasons. In total 773 fecal samples were collected from 45 farms across Florida, Georgia, South Carolina, and Tennessee, and 2.1% (n = 16) of samples were Salmonella-positive. Importantly, 75% of Salmonella were isolated from moist feces, showing reduced Salmonella viability when feces dry out. 16S microbiome analysis showed that presence of culturable Salmonella in moist feces correlated to a higher proportion of the Enterobacteriaceae family. From the Salmonella-positive samples, 62.5% (10/16) contained multi-serovar Salmonella populations. Overall, 13 serovars were detected, including six most commonly attributed to human illness (Enteriditis, Newport, Typhimurium, Infantis, Saintpaul, and Muenchen). PCR screening identified an additional 59 Salmonella-positive fecal samples, which were distributed across moist (n = 44) and dried feces (n = 15). On-farm point counts and molecular identification from fecal samples identified 57 bird species, including for 10 Salmonella-positive fecal samples. Overall, there was a low prevalence of Salmonella in fecal samples, especially in dried feces, and we found no evidence of Salmonella transmission to proximal foliage or produce. Fecal samples collected in farms close together shared highly related isolates by whole genome sequencing and also had highly similar Salmonella populations with comparable relative frequencies of the same serovars, suggesting the birds acquired Salmonella from a common source.

Temporomandibular Disorders and Fibromyalgia Prevalence: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the prevalence of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS) in TMD patients and the prevalence of TMDs in patients with FMS. METHOD: A systematic search was performed in electronic databases. Studies published in English examining the prevalence of comorbid TMDs and CWP/FMS were included. The Newcastle-Ottawa Scale was used to assess study quality, and meta-analyses using defined diagnostic criteria were conducted to generate pooled prevalence estimates. RESULTS: Nineteen studies of moderate to high quality met the selection criteria. Meta-analyses yielded a pooled prevalence rate (95% CI) for TMDs in FMS patients of 76.8% (69.5% to 83.3%). Myogenous TMDs were more prevalent in FMS patients (63.1%, 47.7% to 77.3%) than disc displacement disorders (24.2%, 19.4% to 39.5%), while a little over 40% of FMS patients had comorbid inflammatory degenerative TMDs (41.8%, 21.9% to 63.2%). Almost a third of individuals (32.7%, 4.5% to 71.0%) with TMDs had comorbid FMS, while estimates of comorbid CWP across studies ranged from 30% to 76%. CONCLUSIONS: Despite variable prevalence rates among the included studies, the present review suggests that TMDs and CWP/FMS frequently coexist, especially for individuals with painful myogenous TMDs. The clinical, pathophysiologic, and therapeutic aspects of this association are important for tailoring appropriate treatment strategies.

Trust criteria for artificial intelligence in health: normative and epistemic considerations.

Rapid advancements in artificial intelligence and machine learning (AI/ML) in healthcare raise pressing questions about how much users should trust AI/ML systems, particularly for high stakes clinical decision-making. Ensuring that user trust is properly calibrated to a tool's computational capacities and limitations has both practical and ethical implications, given that overtrust or undertrust can influence over-reliance or under-reliance on algorithmic tools, with significant implications for patient safety and health outcomes. It is, thus, important to better understand how variability in trust criteria across stakeholders, settings, tools and use cases may influence approaches to using AI/ML tools in real settings. As part of a 5-year, multi-institutional Agency for Health Care Research and Quality-funded study, we identify trust criteria for a survival prediction algorithm intended to support clinical decision-making for left ventricular assist device therapy, using semistructured interviews (n=40) with patients and physicians, analysed via thematic analysis. Findings suggest that physicians and patients share similar empirical considerations for trust, which were primarily epistemic in nature, focused on accuracy and validity of AI/ML estimates. Trust evaluations considered the nature, integrity and relevance of training data rather than the computational nature of algorithms themselves, suggesting a need to distinguish 'source' from 'functional' explainability. To a lesser extent, trust criteria were also relational (endorsement from others) and sometimes based on personal beliefs and experience. We discuss implications for promoting appropriate and responsible trust calibration for clinical decision-making use AI/ML.

Technique for insertion of a Scheker prosthesis for failed Sauve-Kapandji with a well fixed ulnar stem: A case report.

INTRODUCTION: The Scheker prosthesis is a distal radioulnar joint (DRUJ) arthroplasty used as a salvage option for many DRUJ pathologies. PRESENTATION OF CASE: We report the case of a patient who underwent insertion of a Scheker prosthesis for continued pain and limited motion at the wrist in the setting of a failed Sauve-Kapandji with a well fixed ulnar stem and DRUJ pseudo-arthrosis. DISCUSSION: This report aims to provide a technique for ulnar stem removal without compromising the bone needed for the Scheker prosthesis and for describing the location of a DRUJ osteotomy without compromising radio-lunate stability. CONCLUSION: The Scheker prosthesis is able to be safely inserted for DRUJ salvage after removal of a well fixed ulnar stem if careful removal prevents destruction of the ulna, as described here.

Characterization and biodistribution of under-employed gene therapy vector AAV7.

IMPORTANCE: The use of adeno-associated viruses (AAVs) as gene delivery vectors has vast potential for the treatment of many severe human diseases. Over one hundred naturally existing AAV capsid variants have been described and classified into phylogenetic clades based on their sequences. AAV8, AAV9, AAVrh.10, and other intensively studied capsids have been propelled into pre-clinical and clinical use, and more recently, marketed products; however, less-studied capsids may also have desirable properties (e.g., potency differences, tissue tropism, reduced immunogenicity, etc.) that have yet to be thoroughly described. These data will help build a broader structure-function knowledge base in the field, present capsid engineering opportunities, and enable the use of novel capsids with unique properties.

Propranolol treatment during repetitive mild traumatic brain injuries induces transcriptomic changes in the bone marrow of mice.

Introduction: There are 1.5 million new mild traumatic brain injuries (mTBI) annually in the US, with many of the injured experiencing long-term consequences lasting months after the injury. Although the post injury mechanisms are not well understood, current knowledge indicates peripheral immune system activation as a causal link between mTBI and long-term side effects. Through a variety of mechanisms, peripheral innate immune cells are recruited to the CNS after TBI to repair and heal the injured tissue; however, the recruitment and activation of these cells leads to further inflammation. Emerging evidence suggests sympathetic nervous system (SNS) activity plays a substantial role in the recruitment of immune cells post injury. Methods: We sought to identify the peripheral innate immune response after repeated TBIs in addition to repurposing the nonselective beta blocker propranolol as a novel mTBI therapy to limit SNS activity and mTBI pathophysiology in the mouse. Mice underwent repetitive mTBI or sham injury followed by i.p. saline or propranolol. Isolated mRNA derived from femur bone marrow of mice was assayed for changes in gene expression at one day, one week, and four weeks using Nanostring nCounter® stem cell characterization panel. Results: Differential gene expression analysis for bone marrow uncovered significant changes in many genes following drug alone, mTBI alone and drug combined with mTBI. Discussion: Our data displays changes in mRNA at various timepoints, most pronounced in the mTBI propranolol group, suggesting a single dose propranolol injection as a viable future mTBI therapy in the acute setting.

Bearded or smooth? Awns improve yield when wheat experiences heat stress during grain fill in the southeastern United States.

The presence or absence of awns-whether wheat heads are 'bearded' or 'smooth' - is the most visible phenotype distinguishing wheat cultivars. Previous studies suggest that awns may improve yields in heat or water-stressed environments, but the exact contribution of awns to yield differences remains unclear. Here we leverage historical phenotypic, genotypic, and climate data for wheat (Triticum aestivum) to estimate the yield effects of awns under different environmental conditions over a 12-year period in the southeastern USA. Lines were classified as awned or awnless based on sequence data, and observed heading dates were used to associate grain fill periods of each line in each environment with climatic data and grain yield. In most environments, awn suppression was associated with higher yields, but awns were associated with better performance in heat-stressed environments more common at southern locations. Wheat breeders in environments where awns are only beneficial in some years may consider selection for awned lines to reduce year-to-year yield variability, and with an eye towards future climates.

Repeated closed-head mild traumatic brain injury-induced inflammation is associated with nociceptive sensitization.

BACKGROUND: Individuals who have experienced mild traumatic brain injuries (mTBIs) suffer from several comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation in long-term pain after mTBIs is not fully elucidated. Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes in inflammatory processes following mTBIs and their effects on TBI-related pain. METHODS: We utilized a recently developed transgenic caspase-1 luciferase reporter mouse model to monitor caspase-1 activation through a thinned skull window in the in vivo setting following three closed-head mTBI events. Organotypic coronal brain slice cultures and acutely dissociated dorsal root ganglion (DRG) cells provided tissue-relevant context of inflammation signal. Mechanical allodynia was assessed by mechanical withdrawal threshold to von Frey and thermal hyperalgesia withdrawal latency to radiant heat. Mouse grimace scale (MGS) was used to detect spontaneous or non-evoked pain. In some experiments, mice were prophylactically treated with MCC950, a potent small molecule inhibitor of NLRP3 inflammasome assembly to inhibit injury-induced inflammatory signaling. Bioluminescence spatiotemporal dynamics were quantified in the head and hind paws, and caspase-1 activation was confirmed by immunoblot. Immunofluorescence staining was used to monitor the progression of astrogliosis and microglial activation in ex vivo brain tissue following repetitive closed-head mTBIs. RESULTS: Mice with repetitive closed-head mTBIs exhibited significant increases of the bioluminescence signals within the brain and paws in vivo for at least one week after each injury. Consistently, immunoblotting and immunofluorescence experiments confirmed that mTBIs led to caspase-1 activation, astrogliosis, and microgliosis. Persistent changes in MGS and hind paw withdrawal thresholds, indicative of pain states, were observed post-injury in the same mTBI animals in vivo. We also observed enhanced inflammatory responses in ex vivo brain slice preparations and DRG for at least 3 days following mTBIs. In vivo treatment with MCC950 significantly reduced caspase-1 activation-associated bioluminescent signals in vivo and decreased stimulus-evoked and non-stimulus evoked nociception. CONCLUSIONS: Our findings suggest that the inflammatory states in the brain and peripheral nervous system following repeated mTBIs are coincidental with the development of nociceptive sensitization, and that these events can be significantly reduced by inhibition of NLRP3 inflammasome activation.

MODIFI: protocol for randomised feasibility study of eye-movement desensitisation and reprocessing therapy (EMDR) for functional neurological disorder (FND).

INTRODUCTION: Functional neurological disorder (FND) refers to an involuntary loss of control over and/or aberrant perception of the body. Common presenting symptoms are functional (non-epileptic) seizures, and functional motor disorder, for example, walking difficulties, weakness or tremor. Greater access to effective treatments would lead to reduced distress and disability; and reduce unnecessary healthcare costs.This study will examine eye-movement desensitisation and reprocessing therapy (EMDR) as a treatment for FND. EMDR is an evidence-based treatment for post-traumatic stress disorder (PTSD), but its use for other conditions is growing. An FND-specific EMDR protocol will be tested, and if the intervention proves feasible with promising clinical outcomes, progression to a substantive study could take place. METHODS AND ANALYSIS: Fifty adult patients diagnosed with FND will be recruited. It will be a single-blind randomised controlled trial with two arms: EMDR (plus standard neuropsychiatric care; NPC) and standard NPC. The two groups will be compared at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). Measures of feasibility include safety, recruitment, retention, treatment adherence and acceptability. Clinical outcome measures will assess health-related functioning/quality of life, ratings of FND symptoms and severity, depression, anxiety, PTSD, dissociation, service utilisation and other costs. Improvement and satisfaction ratings will also be assessed. Feasibility outcomes will be summarised using descriptive statistics. Exploratory analyses using (linear/logistic) mixed-effect models will examine the rate of change in the groups' clinical outcome measures across the four time-points.After the intervention period, a sample of participants, and clinicians, will be invited to attend semistructured interviews. The interviews will be analysed using reflexive thematic analysis. ETHICS AND DISSEMINATION: This study has been approved by the NHS West Midlands-Edgbaston Research Ethics Committee. Study findings will be published in open access peer-reviewed journals, presented at conferences, and communicated to participants and other relevant stakeholders. TRIAL REGISTRATION: NCT05455450 (www. CLINICALTRIALS: gov).

GluK2 Is a Target for Gene Therapy in Drug-Resistant Temporal Lobe Epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) crea an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5-containing kainate receptors (KARs). TLE patients are often resistant to anti-seizure medications and suffer significant comorbidities; hence, there is an urgent need for novel therapies. Previously, we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE. METHODS: We combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug-resistant TLE. RESULTS: Here, we confirmed the translational potential of KAR suppression using a non-selective KAR antagonist that markedly attenuated interictal-like epileptiform discharges (IEDs) in TLE patient-derived hippocampal slices. An adeno-associated virus (AAV) serotype-9 vector expressing anti-grik2 miRNA was engineered to specifically downregulate GluK2 expression. Direct delivery of AAV9-anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs. INTERPRETATION: Our gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof-of-concept for a gene therapy approach targeting GluK2 KARs for drug-resistant TLE patients. ANN NEUROL 2023;94:745-761.

Feasibility randomised controlled trial of online group Acceptance and Commitment Therapy for Functional Cognitive Disorder (ACT4FCD).

INTRODUCTION: Functional cognitive disorder (FCD) is seen increasingly in clinics commissioned to assess cognitive disorders. Patients report frequent cognitive, especially memory, failures. The diagnosis can be made clinically, and unnecessary investigations avoided. While there is some evidence that psychological treatments can be helpful, they are not routinely available. Therefore, we have developed a brief psychological intervention using the principles of acceptance and commitment therapy (ACT) that can be delivered in groups and online. We are conducting a feasibility study to assess whether the intervention can be delivered within a randomised controlled trial. We aim to study the feasibility of recruitment, willingness to be randomised to intervention or control condition, adherence to the intervention, completion of outcome measures and acceptability of treatment. METHODS AND ANALYSIS: We aim to recruit 48 participants randomised 50:50 to either the ACT intervention and treatment as usual (TAU), or TAU alone. ACT will be provided to participants in the treatment arm following completion of baseline outcome measures. Completion of these outcome measures will be repeated at 8, 16 and 26 weeks. The measures will assess several domains including psychological flexibility, subjective cognitive symptoms, mood and anxiety, health-related quality of life and functioning, healthcare utilisation, and satisfaction with care and participant-rated improvement. Fifteen participants will be selected for in-depth qualitative interviews about their experiences of living with FCD and of the ACT intervention. ETHICS AND DISSEMINATION: The study received a favourable opinion from the South East Scotland Research Ethics Committee 02 on 30 September 2022 (REC reference: 22/SS/0059). HRA approval was received on 1 November 2022 (IRAS 313730). The results will be published in full in an open-access journal. TRIAL REGISTRATION NUMBER: ISRCTN12939037.

Sleep disturbances are associated with pain intensity and pain-related functional interference in patients experiencing orofacial pain.

BACKGROUND: Sleep and pain have a reciprocal relationship, interacting with psychosocial aspects including depression, anxiety, somatization and significant stressful events. OBJECTIVE: The aim of this study was to assess patients with oro-facial pain (OFP) and related sleep disturbances and determine the strongest psychosocial correlates. METHODS: A cross-sectional study of anonymized data of consecutive patients with OFP {January 2019 and February 2020} were analysed. Diagnostic and Axis-II data were integrated to assess the relationship between sleep disturbances, measured using Chronic Pain Sleep Inventory, and demographic factors, clinical comorbidities, recent stressful events, pain severity and pain- and psychological-related function. RESULTS: Five out of six patients with OFP were presented with pain-related sleep disturbances. Sleep problems were enhanced in patients with primary oro-facial headache compared with other OFP conditions. However, once the level of pain intensity and interference was accounted for, primary headache, was not a significant correlate of pain-related sleep disturbances. Multivariate analysis revealed (average) pain severity and pain interference were both significantly associated with sleep problems. There were also significant independent associations of sleep problems with somatization levels and reported experience of recent stressful events. CONCLUSION: Identifying sleep problems as a part of OFP management may be beneficial and could result in better management outcomes.

Repeated mild traumatic brain injury in mice elicits long term innate immune cell alterations in blood, spleen, and brain.

Mild traumatic brain injury is an insidious event whereby the initial injury leads to ongoing secondary neuro- and systemic inflammation through various cellular pathways lasting days to months after injury. Here, we investigated the impact of repeated mild traumatic brain injury (rmTBI) and the resultant systemic immune response in male C57B6 mice using flow cytometric methodology on white blood cells (WBCs) derived from the blood and spleen. Isolated mRNA derived from spleens and brains of rmTBI mice was assayed for changes in gene expression at one day, one week, and one month following the injury paradigm. We observed increases in Ly6C+, Ly6C-, and total monocyte percentages in both blood and spleen at one month after rmTBI. Differential gene expression analysis for the brain and spleen tissues uncovered significant changes in many genes, including csf1r, itgam, cd99, jak1,cd3ε, tnfaip6, and nfil3. Additional analysis revealed alterations in several immune signaling pathways over the course of one month in the brain and spleen of rmTBI mice. Together, these results indicate that rmTBI produces pronounced gene expression changes in the brain and spleen. Furthermore, our data suggest that monocyte populations may reprogram towards the proinflammatory phenotype over extended periods of time after rmTBI.