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The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0–10. Substantial agreement (range 7.5–10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post COVID-19 illness, for a target population of active individuals, including military personnel and athletes.

Background Mild traumatic brain injury (TBI) can cause temporary disruption to brain function, with up to half of those affected complaining of functional limitations up to 12 months after the initial injury. Mild TBI can cause a range of sequelae, most commonly post-traumatic headache (PTH). The incidence of PTH varies post mild TBI, with up to 80% affected by three months and 60% by one year, with heterogenous phenotypes reported. We aimed to introduce a standardised interview to identify and characterise PTH. The primary outcome was to identify PTH, and the secondary outcome to characterise the phenotype of PTH. Methods Participants were prospectively recruited from a tertiary centre hospital and a military rehabilitation centre in the United Kingdom. Inclusion criteria included a diagnosis of mild TBI or concussion; normal brain imaging; aged 17 years and older; and head injury within the last 12 months at time of screening. We have excluded those with serious underlying pathology; secondary causes of headache (excluding PTH), and non-English speakers. The non-headache specialist phoned the patient primarily to run through the structured headache interview. Following this, the headache specialist conducted a telephone clinical consultation as ‘gold-standard’. Both interviewers defined PTH as headache developing ≤ 7 days as definite, probable (8–30 days) and unlikely (> 30 days). Cohen’s Kappa estimates the inter-rater reliability across categorical variables. We calculated prevalence-adjusted bias-adjusted kappa (PABAK), which adjusts the kappa value for differences in prevalence and bias across variables. Results A total of 194 people were screened and 63 completed paired interviews. The mean age was 26.2 (SD 8.5) years and 19% were female. Most participants displayed a migraine-like phenotype (94%), followed by tension-type-like headache (13%). A very good agreement was demonstrated between the non-specialist and specialist in diagnosing PTH (PABAK 0.90) and differentiating migraine-like versus tension-type-like headache (PABAK 0.83). There was a good agreement for migraine-like versus other headache sub-phenotypes (PABAK 0.75). Conclusions There is currently no standardised interview that aids healthcare professionals with identifying PTH and its sub-phenotype. This structured interview can be used to diagnose PTH and its sub-phenotype. Graphical Abstract

Objective: To investigate validity and reliability of a new measure of case complexity, the Oxford Case Complexity Assessment Measure (OCCAM). Design: Data collection on inpatients and outpatients attending for rehabilitation. In subsets, repeat assessments were undertaken two weeks apart, by clinicians unaware of initial data, and on admission and on discharge from inpatient rehabilitation. Setting: Specialist neurological rehabilitation service. Subjects: Patients receiving rehabilitation after acute onset disability. Interventions: Assessment by clinical staff as part of routine care. Measures: OCCAM, the INTERMED, Rehabilitation Complexity Scale – Extended (RCS-E), clinical judgement of complexity (0–10 numerical rating scale), length of stay and discharge destination (for inpatients). Results: For the OCCAM, the Cronbach’s α coefficient was 0.69 and item-total correlations were moderate to high except for pathology and time. The correlation coefficients with OCCAM were: INTERMED (ρ = 0.694), RCS-E (ρ = 0.736), and team judgement (ρ = 0.796). Inter-rater agreement was excellent (Weighted κ = 0.95). Correlation between admission and discharge scores was ρ = 0.917. Test–retest agreement was good (intraclass correlation coefficient 0.86). Higher mean admission scores were associated with prolonged stays (38.6 ± 12.2 versus 32.9 ± 13.7, P = 0.04) and failure to return home (48.0 ± 13.7 versus mean 32.1 ± 10.7, P < 0.001). The optimal cut-off of OCCAM to detect patients not discharged home was ≥ 34, with corresponding sensitivity and specificity of 84.6% and 62.8%, respectively. Conclusions: This preliminary evidence suggests that the OCCAM may measure case complexity reliably, and may predict rehabilitation resource used and outcome. Further research is warranted.

Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer’s disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah−/−, Rag2−/−, Il2rg−/− mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.

Consumption of high fat, high sugar (western) diets is a major contributor to the current high levels of obesity. Here, we used a multidisciplinary approach to gain insight into the molecular mechanisms underlying susceptibility to diet-induced obesity (DIO). Using positron emission tomography (PET), we identified the dorsal striatum as the brain area most altered in DIO-susceptible rats and molecular studies within this region highlighted regulator of G-protein signaling 4 (Rgs4) within laser-capture micro-dissected striatonigral (SN) and striatopallidal (SP) medium spiny neurons (MSNs) as playing a key role. Rgs4 is a GTPase accelerating enzyme implicated in plasticity mechanisms of SP MSNs, which are known to regulate feeding and disturbances of which are associated with obesity. Compared to DIO-resistant rats, DIO-susceptible rats exhibited increased striatal Rgs4 with mRNA expression levels enriched in SP MSNs. siRNA-mediated knockdown of striatal Rgs4 in DIO-susceptible rats decreased food intake to levels comparable to DIO-resistant animals. Finally, we demonstrated that the human Rgs4 gene locus is associated with increased body weight and obesity susceptibility phenotypes, and that overweight humans exhibit increased striatal Rgs4 protein. Our findings highlight a novel role for involvement of Rgs4 in SP MSNs in feeding and DIO-susceptibility.