Hepatic steatosis estimated by VCTE-derived CAP scores was associated with lower risks of liver-related events and all-cause mortality in patients with chronic liver disease.

INTRODUCTION: The Controlled Attenuated Parameter (CAP) score derived from vibration-controlled transient elastography (VCTE, i.e. Fibroscan®) is a well-validated marker of hepatic steatosis. It is unclear if CAP scores are associated with risks of liver-related outcomes or all-cause mortality. METHODS: In this retrospective cohort study, we identified 7,587 U.S. Veterans (2,689 with cured hepatitis C [HCV], 1,523 with alcohol-associated liver disease [ALD], 3,375 with metabolic dysfunction-associated steatotic liver disease [MASLD]) who underwent VCTE between 5/2015-12/2021. We followed patients for new hepatic decompensation, hepatocellular carcinoma (HCC), and death from the VCTE date until 1/1/2022. Multivariable Cox-proportional hazards regression was used to assess for the associations between CAP measurements and clinical outcomes, adjusting for age, sex, race/ethnicity, body mass index, Charlson Comorbidity Index, diabetes, liver disease etiology, liver stiffness measurements, and FIB-4, and was reported separately by disease etiology and advanced fibrosis status. RESULTS: Over a median follow-up time of ∼1.9 years, hepatic steatosis (grades 1-3 vs. 0) was associated with a lower risk of death (aHR 0.70, 95% CI: 0.57-0.85). Among patients with MASLD, hepatic steatosis was associated with a lower risk of decompensation (aHR 0.54, 95% CI: 0.32-0.90) and death (aHR 0.52, 95% CI: 0.37-0.73). These associations persisted in subgroup analyses of patients with advanced fibrosis and without cirrhosis. DISCUSSION: Among patients who underwent VCTE in clinical practice, the presence of substantial hepatic steatosis estimated by the CAP score was associated with lower all-cause mortality among all patients and lower risk of decompensation and death among those with MASLD.

Postgraduate Medical Ultrasound learner and practice educator perceptions and experiences of academy model clinical ultrasound training in Scotland.

INTRODUCTION: The newly introduced National Ultrasound Training Programme within the NHS Scotland Academy provides an alternative clinical learning environment for postgraduate medical ultrasound learners. Learners during academic year 2022/23 were supported with up to five weeks of clinical education within the NHS Scotland Academy, as an alternative to their local Health Board. This study explores the perceptions and experiences of the first cohort of learners and their practice educators. METHODS: An interview guide was developed comprising questions to explore learners and practice educator experiences and perceptions of the National Ultrasound Training Programme. Ten semi-structured interviews were conducted (Learners n = 5 and Practice Educators n = 5). Thematic analysis was performed by two independent researchers following an established six-stage process. RESULTS: Three themes emerged:1. Importance of the Clinical learning environment, 2. Relationships and 3. Skills and confidence. Organisational challenges within the NHS Health Boards pose barriers to Learners and Practice Educators supporting clinical education. Learners benefitted from both the clinical learning environments while practice educators recognise the advantage of alternative clinical education for their Learner and wider ultrasound services. Further collaboration to capitalise on knowledge exchange was identified for enhancement. CONCLUSION: The NHS Scotland Academy can play a pivotal role in delivering learner-centred, protected clinical education as an adjunct to traditional models of practice education. IMPLICATIONS FOR PRACTICE: Employers and Practice Educators must identify and acknowledge barriers to postgraduate medical ultrasound education. Protected learning time, recognising roles of Learners and Educators and a supportive clinical learning environment are paramount. Learner-centred best practice clinical education can be successfully delivered within the NHS Scotland academy as an adjunct to acute health board clinical education and adopting a collaborative approach will provide enhancements for stakeholders.

You have to work twice as hard as a woman to show that you are competent. Experiences, opportunities and workplace gender harassment for Sport and Exercise Medicine practitioners working in elite sport in Australia.

OBJECTIVE: Our aim was to investigate (1) gender representation, (2) opportunities and training and (3) harassment experiences in Sport and Exercise Medicine (SEM) practitioners working in elite sport in Australia. METHODS: All titled Australian Physiotherapy Association Sport and Exercise Physiotherapists, SEM Physicians and Registrars and doctors and physiotherapists (SEM practitioners) currently/previously/aspiring to work in Australian elite sport were invited to participate in a bespoke online survey and the Gender Experiences Questionnaire. RESULTS: For SEM practitioners currently working in elite sport, men worked more paid hours each week (mean difference (MD) 12.2 (95% CI 5.5 to 19.0)) and more paid weeks each year (MD 6.8 (95% CI 1.2 to 12.5)). Women SEM practitioners (both currently and previously) were more likely than men to work with women, rather than men athletes. All women SEM practitioners experienced significantly more gender harassment, infantilisation, work/family policing and gender policing than men. For SEM practitioners (both current and previous), there were no gender differences in how practitioners found out about or were recruited to their elite sports roles. Women were four times more likely than men to report that their gender or sexual orientation influenced their opportunities in elite sport. Most roles were not advertised with direct approach being the most common method of job recruitment. CONCLUSION: Women SEM practitioners currently working in elite sport worked less paid hours per week and less paid weeks per year. All SEM practitioners were appointed to positions without established procedures, and there were significant challenges for women SEM practitioners in the elite sport workplace with women facing considerably more gender harassment than men.

Tale of quadriceps and hamstring muscle strength after ACL reconstruction: a systematic review with longitudinal and multivariate meta-analysis.

OBJECTIVE: This study aimed to investigate how knee extensor and flexor strength change over time after anterior cruciate ligament reconstruction (ACLR). DESIGN: Systematic review with longitudinal meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023. ELIGIBILITY CRITERIA: Studies of primary ACLR (n≥50), with mean participant age 18-40 years, reporting a quantitative measure of knee extensor or flexor strength were eligible. Muscle strength had to be reported for the ACL limb and compared with: (1) the contralateral limb (within-person); and/or (2) an uninjured control limb (between-person). RESULTS: We included 232 studies of 34 220 participants. Knee extensor and flexor strength showed sharp initial improvement postoperatively before tailing off at approximately 12-18 months post surgery with minimal change thereafter. Knee extensor strength was reduced by more than 10% compared with the contralateral limb and approximately 20% compared with uninjured controls at 1 year for slow concentric, fast concentric and isometric contractions. Knee flexor strength showed smaller deficits but was still 5%-7% lower than the contralateral limb at 1 year for slow concentric, fast concentric and isometric contractions. Between-person comparisons showed larger deficits than within-person comparisons. CONCLUSION: Knee extensor muscle strength is meaningfully reduced (>10%) at 1 year, with limited improvement after this time up to and beyond 5 years post surgery. Many people likely experience persistent and potentially long-term strength deficits after ACLR. Comparison within person (to the contralateral limb) likely underestimates strength deficits in contrast to uninjured controls.

Hop to It! A Systematic Review and Longitudinal Meta-analysis of Hop Performance After ACL Reconstruction.

BACKGROUND: Hop testing is widely used by clinicians to monitor rehabilitation and decide when to return to sport following anterior cruciate ligament reconstruction (ACLR); however, the trajectory of long-term hop performance has not been summarised. OBJECTIVE: To investigate hop performance change over time after ACLR. DESIGN: Systematic review with longitudinal meta-analysis. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023. ELIGIBILITY CRITERIA: Studies with ≥ 50 participants following primary ACLR, with mean participant age of 18-40 years, reporting a quantitative measure of hop performance (e.g. single forward hop distance). Results had to be reported for the ACLR limb and compared with (1) the contralateral limb (within person) and/or (2) an uninjured control limb (between person). RESULTS: We included 136 studies of 23,360 participants. Performance was similar across different hop tests, with steep initial improvements in within-person symmetry, tailing off after 18-24 months. ACLR limb hop performance was 5-10% lower compared with the contralateral limb at 1 year post-surgery, with largest deficits observed for vertical hop [87.0% contralateral limb (95% CI 85.3-88.8) compared with single forward hop 93.8% (95% CI 92.8-94.9)]. By 3-5 years, results were similar between ACLR and contralateral limbs. There were limited data for between-person comparisons (n = 17 studies). Exploratory analyses showed deficits in all forward hopping tests to be very strongly correlated with each other [e.g. single forward and triple hop rho = 0.96 (95% CI 0.90-0.99)], though there was discordance in the relationship between single forward hop and vertical hop performance [rho = 0.27 (95% CI - 0.53 to 0.79)]. CONCLUSIONS: Hop performance is comparable to the uninjured limb by 3-5 years post-ACLR, with the greatest deficits in within-person symmetry present in vertical and side hop tests. Assessment of hopping in multiple planes and comparison with uninjured controls, may provide the most complete evaluation of functional performance.

Applying co-production principles in research: reflections from young people and academics.

Co-production, a form of collaborative working, is guided by principles including valuing all participants, building on individual strengths, blurring distinctions between roles, delivering benefits for all participants, building support networks and supporting people to deliver work themselves. This article explores how co-production is understood by young people and researchers and how co-production principles can be applied within a research context. We identify challenges of implementing existing co-production frameworks in research and key areas to consider for future work.

"I feel more confident": a mixed methods evaluation of the influence of Good Life with osteoarthritis Denmark (GLA:D®) on physical activity participation, capability, barriers, and facilitators in people with knee osteoarthritis.

BACKGROUND: A mixed methods study which aimed to evaluate the influence of Good Life with osteoArthritis Denmark (GLA:D®) on physical activity participation, including perceived capability, barriers, and facilitators in people with knee osteoarthritis. OBJECTIVE: Quantify changes in physical activity participation at 3- and 12-months for people with knee osteoarthritis who participated in an education and exercise-therapy program (GLA:D®). METHODS: A mixed-methods study involving 44 participants with knee osteoarthritis who completed GLA:D®. Guided by the Theoretical Domains Framework, 19 were interviewed, with transcripts analysed using reflexive thematic analysis. University of California Los Angeles physical activity scores were dichotomised as 'more' (≥7) or 'less' active (≤6), and compared between baseline and 3- and 12-months using McNemar's test. Motivation and confidence to exercise (0-10 scale); fear of knee joint damage with exercise (yes/no); and Knee Osteoarthritis Outcome Scores (KOOS) were evaluated. RESULTS: Four overarching themes were identified: prior to GLA:D® 1) fear of knee joint damage, and scarcity of exercise and physical activity information prior to GLA:D®; and following GLA:D® 2) varied exercise-therapy and physical activity participation; 3) facilitators including reduced fear of knee damage, increased confidence, routine, strategies, and support; and 4) ongoing barriers including persistent knee pain, comorbidities, cost, and lack of opportunity and motivation. There was no difference in the proportion of 'more' active participants between baseline (41%) and at 3-months (37%, p = 0.774) or 12-months (35%, p = 0.375). The proportion with fear of damage reduced from baseline (50%) to 3-months (5%) and 12-months (21%). Self-reported motivation (9.1/10) and confidence (9.1/10) to exercise at 3-months were high, and all KOOS subscales improved from baseline to 3-months (effect sizes = 0.41-0.58) and 12-months (effect sizes = 0.29-0.66). CONCLUSION: Varied and often inadequate physical activity participation following GLA:D® indicates more targeted interventions to address ongoing barriers may be required.

Perioperative Liver and Kidney Diseases.

Perioperative risks associated with acute hepatitis, cirrhosis, and chronic kidney disease are substantial and prevalence of underlying chronic kidney or liver disease is rising; surgeries in these populations have accordingly become more common. Optimal perioperative management in both cases is paramount; this article focuses on understanding disease pathophysiology, a targeted preoperative evaluation, accurate estimation of perioperative risk, and anticipation and management of common postoperative complications.

Muscle Fat and Volume Differences in People With Hip-Related Pain Compared With Controls: A Machine Learning Approach.

BACKGROUND: Hip-related pain (HRP) affects young to middle-aged active adults and impacts physical activity, finances and quality of life. HRP includes conditions like femoroacetabular impingement syndrome and labral tears. Lateral hip muscle dysfunction and atrophy in HRP are more pronounced in advanced hip pathology, with limited evidence in younger populations. While MRI use for assessing hip muscle morphology is increasing, with automated deep-learning techniques showing promise, studies assessing their accuracy are limited. Therefore, we aimed to compare hip intramuscular fat infiltrate (MFI) and muscle volume, in individuals with and without HRP as well as assess the reliability and accuracy of automated machine-learning segmentations compared with human-generated segmentation. METHODS: This cross-sectional study included sub-elite/amateur football players (Australian football and soccer) with a greater than 6-month history of HRP [n = 180, average age 28.32, (standard deviation 5.88) years, 19% female] and a control group of sub-elite/amateur football players without pain [n = 48, 28.89 (6.22) years, 29% female]. Muscle volume and MFI of gluteus maximus, medius, minimis and tensor fascia latae were assessed using MRI. Associations between muscle volume and group were explored using linear regression models, controlling for body mass index, age, sport and sex. A convolutional neural network (CNN) machine-learning approach was compared with human-performed muscle segmentations in a subset of participants (n = 52) using intraclass correlation coefficients and Sorensen-Dice index. RESULTS: When considering adjusted estimates of muscle volume, there were significant differences observed between groups for gluteus medius (adjusted mean difference 23 858 mm3 [95% confidence interval 7563, 40 137]; p = 0.004) and tensor fascia latae (6660 mm3 [2440, 13 075]; p = 0.042). No differences were observed between groups for gluteus maximus (18 265 mm3 [-21 209, 50 782]; p = 0.419) or minimus (3893 mm3 [-2209, 9996]; p = 0.21). The CNN was trained for 30 000 iterations and assessed its accuracy and reliability on an independent testing dataset, achieving high segmentation accuracy (mean Sorenson-Dice index >0.900) and excellent muscle volume and MFI reliability (ICC2,1 > 0.900). The CNN outperformed manual raters, who had slightly lower interrater accuracy (Sorensen-Dice index >0.800) and reliability (ICC2,1 > 0.800). CONCLUSIONS: The increased muscle volumes in the symptomatic group compared with controls could be associated with increased myofibrillar size, sarcoplasmic hypertrophy or both. These changes may facilitate greater muscular efficiency for a given load, enabling the athlete to maintain their normal level of function. In addition, the CNNs for muscle segmentation was more efficient and demonstrated excellent reliability in comparison to manual segmentations.

People Are More Variable Than Their Hop Test Would Suggest: Hop Performance and Self-Reported Outcomes Over 11 Years Following ACL Reconstruction.

We aimed to report the trajectory of self-reported outcomes up to 11 years post-ACLR. We also explored the relationship between hop performance at 1 year and: (i) future self-reported knee outcomes; and (ii) risk of subsequent knee events. 124 participants (43 women, mean age 31 ± 8 years) were recruited at 1 year following hamstring-autograft ACLR. Hop performance was assessed with single-forward and side-hop tests. Follow-up was completed at 3 (n = 114), 5 (n = 89) and 11 years (n = 72) post-ACLR. Self-reported outcomes were assessed at each follow-up with the Knee injury Osteoarthritis Outcome Score (KOOS) pain and quality of life (QOL) subscales. Generalized linear mixed models estimated the relationship between hop performance and self-reported outcomes. Subsequent knee events (new injury/surgery) to either knee were recorded, with the relationship between hop performance and risk of subsequent knee events analyzed with Cox proportional hazards. Self-reported knee outcomes were stable (mean change < 10 points) across all timepoints but with major within-sample variability. There was a modest relationship between greater hop performance at 1 year and better future KOOS-pain (average marginal effect [AME] % improvement with + 1 cm single forward hop = 0.06% [95% CI 0.02-0.10]). A nonlinear spline relationship showed better single-forward hop performance was associated with better KOOS-QOL for scores < 108 cm, not present for higher hop scores > 108 cm. There were 21 index and 11 contralateral subsequent knee events. Hop performance was not related to risk of a subsequent knee event (hazard ratio index knee 0.99 [95% CI 0.98-1.02]). In conclusion, self-reported knee pain and quality of life were generally stable across the 11-year follow-up period. Greater hop performance at 1-year post-ACLR was related to better self-reported knee outcomes up to 11-year follow-up (of questionable clinical importance), but not associated with the risk of subsequent knee injury/surgery.

Immersive Photorealistic Three-Dimensional Neurosurgical Anatomy of the Cerebral Arteries: A Photogrammetry-Based Anatomic Study.

BACKGROUND AND OBJECTIVES: Neurosurgeons need a profound knowledge of the surgical anatomy of the cerebral arteries to safely treat patients. This is a challenge because of numerous branches, segments, and tortuosity of the main blood vessels that supply the brain. The objective of this study was to create high-quality three-dimensional (3D) anatomic photorealistic models based on dissections of the brain arterial anatomy and to incorporate this data into a virtual reality (VR) environment. METHODS: Two formaldehyde-fixed heads were used. The vessels were injected with radiopaque material and colored silicone and latex. Before the dissections, the specimens were computed tomography scanned. Stratigraphical anatomic dissection of the neck and brain was performed to present the relevant vascular anatomy. A simplified surface scanning method using a mobile phone-based photogrammetry application was used, and the data were incorporated into a VR 3D modeling software for post-processing and presentation. RESULTS: Fifteen detailed layered photorealistic and two computed tomography angiography-based 3D models were generated. The models allow manipulation in VR environment with sufficient photographic detail to present the structures of interest. Topographical relevant anatomic structures and landmarks were annotated and uploaded for web-viewing and in VR. Despite that the VR application is a dedicated 3D modeling platform, it provided all necessary tools to be suitable for self-VR study and multiplayer scenarios with several participants in one immersive environment. CONCLUSION: Cerebral vascular anatomy presented with photogrammetry surface scanning method allows sufficient detail to present individual vessel's course and even small perforating arteries in photorealistic 3D models. These features, including VR visualization, provide new teaching prospects. The whole study was done with simplified algorithms and free or open-source software platforms allowing creation of 3D databases especially useful in cases with limited body donor-based dissection training availability.

Are hip joint imaging findings associated with symptoms and early hip osteoarthritis features in elite male Australian Football League draftees?

1) describe intra-articular features (prevalence and severity) and bony hip morphology (prevalence and size) in elite male Australia Football League (AFL) draftees; 2) examine the relationship between bony hip morphology (cam and pincer morphology) and intra-articular features (cartilage defects and labral tears); and 3) examine the relationship between intra-articular features, bony hip morphology, and the Copenhagen Hip and Groin Outcome Score (HAGOS). Cross-sectional study. 58 male AFL draftees underwent 3-tesla hip MRI. Alpha angle determined cam morphology and acetabular depth defined pincer morphology. For each hip, intra-articular features were scored semi-quantitatively. All players completed the HAGOS to determine hip/groin symptoms and sports function. Logistic regression determined whether bony hip morphology was associated with labral tears and cartilage defects. Mann-Whitney U tests evaluated the difference in HAGOS subscale scores between football players with and without intra-articular features and bony hip morphology. Cam and pincer morphology were evident in 20% and 19% of hips, respectively. Nearly half of hips (41%) had a labral tear, with only 14% having a cartilage defect. Greater alpha angle was associated with the presence of labral tears (OR 1.14, 95%CI 1.07 to 1.21, p < 0.001) but not cartilage defects. Hip imaging findings were not associated with lower (worse) HAGOS scores. Hip joint imaging findings were common in elite male AFL draftees but not associated with worse pain, symptoms, or sport function. Cam morphology may contribute to the development of labral tears in male AFL draftees.

Control of innate olfactory valence by segregated cortical amygdala circuits.

Animals perform innate behaviors that are stereotyped responses to specific evolutionarily relevant stimuli in the absence of prior learning or experience. These behaviors can be reduced to an axis of valence, whereby specific odors evoke approach or avoidance. The cortical amygdala (plCoA) mediates innate attraction and aversion to odor. However, little is known about how this brain area gives rise to behaviors of opposing motivational valence. Here, we sought to define the circuit features of plCoA that give rise to innate olfactory behaviors of valence. We characterized the physiology, gene expression, and projections of this structure, identifying a divergent, topographic organization that selectively controls innate attraction and avoidance to odor. First, we examined odor-evoked responses in these areas and found sparse encoding of odor identity, but not valence. We next considered a topographic organization and found that optogenetic stimulation of the anterior and posterior domains of plCoA elicits attraction and avoidance, respectively, suggesting a functional axis for valence. Using single cell and spatial RNA sequencing, we identified the molecular cell types in plCoA, revealing an anteroposterior gradient in cell types, whereby anterior glutamatergic neurons preferentially express Slc17a6 and posterior neurons express Slc17a7. Activation of these respective cell types recapitulates appetitive and aversive valence behaviors, and chemogenetic inhibition reveals partial necessity for valence responses to innate appetitive or aversive odors. Finally, we identified topographically organized circuits defined by projections, whereby anterior neurons preferentially project to medial amygdala, and posterior neurons preferentially project to nucleus accumbens, which are respectively sufficient and necessary for innate negative and positive olfactory valence. Together, these data advance our understanding of how the olfactory system generates stereotypic, hardwired attraction and avoidance, and supports a model whereby distinct, topographically distributed plCoA populations direct innate olfactory valence responses by signaling to divergent valence-specific targets, linking upstream olfactory identity to downstream valence behaviors, through a population code. This represents a novel circuit motif in which valence encoding is represented not by the firing properties of individual neurons, but by population level identity encoding that is routed through divergent targets to mediate distinct valence.

Mixed selectivity: Cellular computations for complexity.

The property of mixed selectivity has been discussed at a computational level and offers a strategy to maximize computational power by adding versatility to the functional role of each neuron. Here, we offer a biologically grounded implementational-level mechanistic explanation for mixed selectivity in neural circuits. We define pure, linear, and nonlinear mixed selectivity and discuss how these response properties can be obtained in simple neural circuits. Neurons that respond to multiple, statistically independent variables display mixed selectivity. If their activity can be expressed as a weighted sum, then they exhibit linear mixed selectivity; otherwise, they exhibit nonlinear mixed selectivity. Neural representations based on diverse nonlinear mixed selectivity are high dimensional; hence, they confer enormous flexibility to a simple downstream readout neural circuit. However, a simple neural circuit cannot possibly encode all possible mixtures of variables simultaneously, as this would require a combinatorially large number of mixed selectivity neurons. Gating mechanisms like oscillations and neuromodulation can solve this problem by dynamically selecting which variables are mixed and transmitted to the readout.

Longitudinal changes in adiposity following anterior cruciate ligament reconstruction and associations with knee symptoms and function.

Objective: To evaluate adiposity after anterior cruciate ligament reconstruction (ACLR): i) cross-sectionally (1-year post-ACLR) compared to uninjured controls; ii) longitudinally up to 5 years post-ACLR; and iii) associations with patient-reported symptoms and physical performance. Methods: In 107 individuals post-ACLR and 19 controls, we assessed global (BMI), peripheral (subcutaneous adipose tissue thickness on the posteromedial side of knee MRI), and central (waist circumference in ACLR group) adiposity. Patient-reported symptoms (Knee injury and Osteoarthritis Outcome Score) and physical performance (hop for distance) were evaluated at 1 and 5 years post-ACLR. Linear regression models evaluated adiposity between groups. Paired t-tests evaluated changes in adiposity from 1- to 5 years post-ACLR. Linear regression models analyzed adiposity's associations with patient-reported symptoms and physical performance at 1-year post-ACLR, changes in symptoms and performance over 4 years post-ACLR, and longitudinal changes in adiposity and symptoms and performance, controlling for age, sex, and activity level. Results: Individuals 1-year post-ACLR were associated with higher average global (3 â€‹kg/m2) and peripheral adiposity (2.3 â€‹mm). From 1- to 5 years post-ACLR, higher average global (0.58 â€‹kg/m2) and central (5 â€‹cm) adiposity, and lower average peripheral adiposity (1.3 â€‹mm) were observed. In general, adiposity at one-year post-ACLR was negatively associated with patient-reported symptoms and physical performance, and changes from 1 to 5 years post-ACLR. Increases in adiposity were negatively associated with changes in patient-reported symptoms and physical performance over four years post-ACLR. Conclusion: Greater global and central adiposity is a feature of young adults following ACLR and influences current and future patient-reported symptoms and physical performance.

An unbiased method to partition diverse neuronal responses into functional ensembles reveals interpretable population dynamics during innate social behavior.

In neuroscience, understanding how single-neuron firing contributes to distributed neural ensembles is crucial. Traditional methods of analysis have been limited to descriptions of whole population activity, or, when analyzing individual neurons, criteria for response categorization varied significantly across experiments. Current methods lack scalability for large datasets, fail to capture temporal changes and rely on parametric assumptions. There's a need for a robust, scalable, and non-parametric functional clustering approach to capture interpretable dynamics. To address this challenge, we developed a model-based, statistical framework for unsupervised clustering of multiple time series datasets that exhibit nonlinear dynamics into an a-priori-unknown number of parameterized ensembles called Functional Encoding Units (FEUs). FEU outperforms existing techniques in accuracy and benchmark scores. Here, we apply this FEU formalism to single-unit recordings collected during social behaviors in rodents and primates and demonstrate its hypothesis-generating and testing capacities. This novel pipeline serves as an analytic bridge, translating neural ensemble codes across model systems.

Adiposity and cartilage lesions following ACL reconstruction.

OBJECTIVE: To determine if global, central, or peripheral adiposity is associated with prevalent and worsening cartilage lesions following anterior cruciate ligament reconstruction (ACLR). METHODS: In 107 individuals one-year post-ACLR, adiposity was assessed globally (body mass index), centrally (waist circumference), and peripherally (knee subcutaneous adipose tissue thickness) from magnetic resonance imaging (MRI). Tibiofemoral and patellofemoral cartilage lesions were assessed from knee MRIs at 1- and 5-years post-ACLR. Poisson regression evaluated the relation of adiposity with prevalent and worsening tibiofemoral and patellofemoral cartilage lesions adjusting for age, sex, and activity level. RESULTS: The prevalence ratios of adiposity with tibiofemoral (presence in 49%) and patellofemoral (44%) cartilage lesions ranged from 0.99 to 1.03. Adiposity was more strongly associated with longitudinal changes in tibiofemoral (worsening in 21%) and patellofemoral (44%) cartilage lesions. One-unit increase in global (kg/m2), central (cm), and peripheral (mm) adiposity was associated with a higher risk of worsening tibiofemoral cartilage lesions by 17% (risk ratios [95% confidence interval (CI)]: 1.17 [1.09 to 1.23]), 5% (1.05 [1.02 to 1.08]), and 9% (1.09 [1.03 to 1.16]), and patellofemoral cartilage lesions by 5% (1.05 [1.00 to 1.12]), 2% (1.02 [1.00 to 1.04]) and 2% (1.02 [1.00 to 1.04]), respectively. CONCLUSION: Greater adiposity was a risk factor for worsening cartilage lesions up to 5 years post-ACLR. Clinical interventions aimed at mitigating excess adiposity may be beneficial in preventive approaches for early post-traumatic osteoarthritis.

Recruitment and baseline characteristics of young adults at risk of early-onset knee osteoarthritis after ACL reconstruction in the SUPER-Knee trial.

Objectives: The study aims to (1) report the process of recruiting young adults into a secondary knee osteoarthritis prevention randomised controlled trial (RCT) after anterior cruciate ligament reconstruction (ACLR); (2) determine the number of individuals needed to be screened to include one participant (NNS) and (3) report baseline characteristics of randomised participants. Methods: The SUpervised exercise-therapy and Patient Education Rehabilitation (SUPER)-Knee RCT compares SUPER and minimal intervention for young adults (aged 18-40 years) with ongoing symptoms (ie, mean score of <80/100 from four Knee injury and Osteoarthritis Outcome Score subscales (KOOS4)) 9-36 months post-ACLR. The NNS was calculated as the number of prospective participants screened to enrol one person. At baseline, participants provided medical history, completed questionnaires (demographic, injury/surgery, rehabilitation characteristics) and underwent physical examination. Results: 1044 individuals were screened to identify 567 eligible people, from which 184 participants (63% male) enrolled. The sample of enrolled participants was multicultural (29% born outside Australia; 2% Indigenous Australians). The NNS was 5.7. For randomised participants, mean±SD age was 30±6 years. The mean body mass index was 27.3±5.2 kg/m2, with overweight (43%) and obesity (21%) common. Participants were, on average, 2.3 years post-ACLR. Over half completed <8 months of postoperative rehabilitation, with 56% having concurrent injury/surgery to meniscus and/or cartilage. The most affected KOOS (0=worst, 100=best) subscale was quality of life (mean 43.7±19.1). Conclusion: Young adults post-ACLR were willing to participate in a secondary osteoarthritis prevention trial. Sample size calculations should be multiplied by at least 5.7 to provide an estimate of the NNS. The SUPER-Knee cohort is ideally positioned to monitor and intervene in the early development and trajectory of osteoarthritis. Trial registration number: ACTRN12620001164987.

Social isolation recruits amygdala-cortical circuitry to escalate alcohol drinking.

How do social factors impact the brain and contribute to increased alcohol drinking? We found that social rank predicts alcohol drinking, where subordinates drink more than dominants. Furthermore, social isolation escalates alcohol drinking, particularly impacting subordinates who display a greater increase in alcohol drinking compared to dominants. Using cellular resolution calcium imaging, we show that the basolateral amygdala-medial prefrontal cortex (BLA-mPFC) circuit predicts alcohol drinking in a rank-dependent manner, unlike non-specific BLA activity. The BLA-mPFC circuit becomes hyperexcitable during social isolation, detecting social isolation states. Mimicking the observed increases in BLA-mPFC activity using optogenetics was sufficient to increase alcohol drinking, suggesting the BLA-mPFC circuit may be a neural substrate for the negative impact of social isolation. To test the hypothesis that the BLA-mPFC circuit conveys a signal induced by social isolation to motivate alcohol consumption, we first determined if this circuit detects social information. Leveraging optogenetics in combination with calcium imaging and computer vision pose tracking, we found that BLA-mPFC circuitry governs social behavior and neural representation of social contact. We further show that BLA-mPFC stimulation mimics social isolation-induced mPFC encoding of sucrose and alcohol, and inhibition of the BLA-mPFC circuit decreases alcohol drinking following social isolation. Collectively, these data suggest the amygdala-cortical circuit mirrors a neural encoding state similar to social isolation and underlies social isolation-associated alcohol drinking.