Search

Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the Csf1r ΔFIRE/ΔFIRE mouse model. In juvenile Csf1r ΔFIRE/ΔFIRE mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types. By contrast, with advancing age, pathologies accumulate in Csf1r ΔFIRE/ΔFIRE brains, macroglia become increasingly dysregulated, and white matter integrity declines, mimicking many pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly vulnerable to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular alterations, macroglial dysregulation, and severe tissue calcification. We show that populating Csf1r ΔFIRE/ΔFIRE brains with wild-type microglia protects against many of these pathological changes. Together with the accompanying study by Chadarevian and colleagues 1 , our results indicate that the lifelong absence of microglia results in an age-related neurodegenerative condition that can be counteracted via transplantation of healthy microglia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microglia sculpt developing neural circuits by eliminating excess synapses in a process called synaptic pruning, by removing apoptotic neurons, and by promoting neuronal survival. To elucidate the role of microglia during embryonic and postnatal brain development, we used a mouse model deficient in microglia throughout life by deletion of the fms-intronic regulatory element (FIRE) in the Csf1r locus. Surprisingly, young adult Csf1r ΔFIRE/ΔFIRE mice display no changes in excitatory and inhibitory synapse number and spine density of CA1 hippocampal neurons compared with Csf1r + /+ littermates. However, CA1 neurons are less excitable, receive less CA3 excitatory input and show altered synaptic properties, but this does not affect novel object recognition. Cytokine profiling indicates an anti-inflammatory state along with increases in ApoE levels and reactive astrocytes containing synaptic markers in Csf1r ΔFIRE/ΔFIRE mice. Notably, these changes in Csf1r ΔFIRE/ΔFIRE mice closely resemble the effects of acute microglial depletion in adult mice after normal development. Our findings suggest that microglia are not mandatory for synaptic pruning, and that in their absence pruning can be achieved by other mechanisms., (© 2024. The Author(s).)

The impact of the pandemic on the UK labour market has been extremely heterogeneous across occupations and industries. Using novel data on job search, we document how individuals adjust their job search in response to changing employment patterns across occupations and industries in the UK. We observe that workers changed their search direction in favour of expanding occupations and industries as the pandemic developed. However, non-employed workers are more attached to their previous occupations and workers with low education are more likely to target declining occupations. We also observe workers from declining occupations making fewer transitions to expanding occupations than those who start in expanding occupations, despite targeting these jobs relatively frequently. This suggests those at the margins of the labour market may be least able to escape occupations that declined during the pandemic., (© 2023 The Author(s).)

Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health 1 , it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1-TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease 2,3 ., (© 2022. The Author(s).)

Indepth knowledge of injury and illness epidemiology in circus arts is lacking. Comparing results across studies is difficult due to inconsistent methods and definitions. In 2020, the International Olympic Committee (IOC) consensus group proposed a standard method for recording and reporting epidemiological data on injuries and illnesses in sports and stated that sport-specific extension statements are needed to capture the context of each sport. This is the circus-specific extension to be used with the IOC consensus statement. International circus arts researchers in injury and illness epidemiology and performing arts medicine formed a consensus working group. Consensus statement development included a review of literature, creation of an initial draft by the working group, feedback from external reviewers, integration of feedback into the second draft and a consensus on the final document. This consensus statement contains circus-specific information on (1) injury definitions and characteristics; (2) measures of severity and exposure, with recommendations for calculating the incidence and prevalence; (3) a healthcare practitioner report form ; (4) a self-report form capturing health complaints with training and performance exposure ; and (5) a demographic , health history and circus experience intake questionnaire . This guideline facilitates comparing results across studies and enables combining data sets on injuries in circus arts. This guideline informs circus-specific injury prevention, rehabilitation, and risk management to improve the performance and health of circus artists., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Shorter distance events in track and field are replete with folk tales about which lane assignments on the track are advantageous. Estimating the causal effect of lane assignments on race times is a difficult task as lane assignments are typically non-random. To estimate these effects I exploit a random assignment rule for the first round of races in short distance events. Using twenty years of data from the IAAF world athletic championships and U20 world championships, there is no evidence of lane advantages in the 100m. Contrary to popular belief, the data suggest that outside lanes in the 200m and 400m produce faster race times. In the 800m, which is unique in having a lane break, there is some weak evidence that outside lanes producer slower race times, possibly reflecting the advantage of inside lanes having an established position on the track at the lane break. Given that these results do not support common convictions on lane advantages, they also serve as an interesting case study on false beliefs., Competing Interests: The authors have declared that no competing interests exist.

Background: The Watson Instability Program (WIP1) is current best evidence for conservative management of atraumatic shoulder instability, but it is unknown if this program can be effectively delivered via tele-consultation. The purpose of this longitudinal pre-post intervention study was to determine the effects of the WIP1 on patient-reported outcome measures, scapular position, shoulder strength, and handstand stability in student circus performers with atraumatic shoulder instability when delivered via tele-consultation., Methods: Student circus performers aged between 15 and 35 years from the National Institute of Circus Arts were recruited. A 12-week shoulder exercise program was delivered via tele-consultation during the Melbourne, Australia COVID-19 (coronavirus disease 2019) lockdown. The primary outcome measures were the Western Ontario Shoulder Instability Index score and the Melbourne Instability Shoulder Scale score. Secondary outcomes measures included the Orebro Musculoskeletal Pain Questionnaire, the Tampa Scale for Kinesiophobia, and physical assessment measures including strength via handheld dynamometry, scapular position using an inclinometer, and handstand stability via center-of-pressure fluctuation. Patient-reported outcomes were collected at baseline and 6-week, 12-week, 6-month, and 9-month time points, and physical outcomes were measured at baseline and 9-month time points. A repeated-measures mixed model (with effect sizes [ESs] and 95% confidence intervals [CIs]) was used to analyze patient-reported outcomes, handstand data, strength, and scapular measures. Significance was set at P < .05., Results: Twenty-three student circus arts performers completed the study. Significant improvements were found in both Western Ontario Shoulder Instability Index scores (effect size [ES], 0.79 [95% CI, 0.31-1.33] at 6 weeks; ES, 1.08 [95% CI, 0.55-1.6] at 12 weeks; ES, 1.17 [95% CI, 0.62-1.78] at 6 months; and ES, 1.31 [95% CI, 0.74-1.95] at 9 months; P < .001) and Melbourne Instability Shoulder Scale scores (ES, 0.70 [95% CI, 0.22-1.22] at 6 weeks; ES, 0.83 [95% CI, 0.34-1.37] at 3 months; ES, 0.98 [95% CI, 0.46-1.54] at 6 months; and ES, 0.98 [95% CI, 0.43-1.50] at 9 months; P < .001), as well as Orebro Musculoskeletal Pain Questionnaire scores at all follow-up time points. The Tampa Scale for Kinesiophobia scores reached significance at 6 weeks and 12 weeks. Following rehabilitation, we found statistically significant increases in shoulder strength in all positions tested and increased scapular upward rotation measured at end-of-range abduction, as well as during loaded external rotation. The affected arm showed greater instability than the unaffected arm with a significant intervention effect on the affected arm showing a greater consistent anterior-posterior movement pattern., Conclusion: In a group of circus performers with atraumatic shoulder instability, treatment with the WIP1 via telehealth resulted in clinically and statistically significant improvements in shoulder symptoms and function., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Macrophages reside within the diverse anatomical compartments of the central nervous system (CNS). Within each compartment, these phagocytes are exposed to unique combinations of niche signals and mechanical stimuli that instruct their tissue-specific identities. Whereas most CNS macrophages are tissue-embedded, the macrophages of the cerebrospinal fluid (CSF) system are bathed in an oscillating liquid. Studies using multiomics technologies have recently uncovered the transcriptomic and proteomic profiles of CSF macrophages, enhancing our understanding of their cellular characteristics in both rodents and humans. Here, we review the relationships between CNS macrophage populations, with a focus on the origins, phenotypes, and functions of CSF macrophages in health and disease.

The purpose of this study was to establish the intra-rater and inter-rater reliability of isometric shoulder strength assessment using a hand-held dynamometer (HHD) in functional joint positions in student circus artists with symptomatic atraumatic shoulder instability., Methods: Over two testing sessions, two experienced physiotherapists assessed the shoulder strength of 24 student circus artists with clinically diagnosed atraumatic shoulder instability. Both the symptomatic and asymptomatic shoulder was assessed using a HHD in 10 functional positions. Intra-class correlation coefficients (ICCs) were calculated to determine the reliability of strength measurements., Results: All examined positions showed moderate-high intra-rater and inter-rater reliability. External rotation at 0° and internal rotation in horizontal flexion at 45° revealed the most reliable results, and the shrug position the least reliable. Inter-rater and intra-rater reliability was high and demonstrated similar results in symptomatic and asymptomatic shoulders by both raters., Discussion: This study demonstrated clinical applicability in reliably measuring functional strength in symptomatic atraumatic instability or asymptomatic shoulders when assessed by experienced therapists using an HHD.

The central nervous system hosts parenchymal macrophages, known as microglia, and non-parenchymal macrophages, collectively termed border-associated macrophages (BAMs). Microglia, but not BAMs, were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms -intronic regulatory element (FIRE). However, it is unknown whether FIRE deficiency also impacts BAM arrival and/or maintenance . Here, we show that macrophages in the ventricular system of the brain, including Kolmer's epiplexus macrophages, are absent in Csf1r ΔFIRE/ΔFIRE mice. Stromal choroid plexus BAMs are also considerably reduced. During normal development, we demonstrate that intracerebroventricular macrophages arrive from embryonic day 10.5, and can traverse ventricular walls in embryonic slice cultures. In Csf1r ΔFIRE/ΔFIRE embryos, the arrival of both primitive microglia and intracerebroventricular macrophages was eliminated, whereas the arrival of cephalic mesenchyme and stromal choroid plexus BAMs was only partially restricted. Our results provide new insights into the development and regulation of different CNS macrophage populations., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Study Objective: To evaluate the Essentials in Minimally Invasive Gynecology (EMIG)- Fundamentals of Laparoscopic Surgery Laparoscopic Simulation System and the EMIG Hysteroscopy Simulation System for face validity and functionality in a pilot testing environment., Design: A prospective controlled pilot study., Setting: Three teaching institutions in the US Southwest., Subjects: Twenty-seven residents and gynecologists, with 22 fitting who fit 1 of 4 categories of exposure to hysteroscopic and laparoscopic surgery and surgical simulation. Eleven were postgraduate year 1 and 5 postgraduate year 3, 1 was American Board of Obstetrics & Gynecology certified, and 5 were either fellows in-training or had completed a fellowship in minimally invasive gynecologic surgery., Interventions: After completing a screening survey, each subject was exposed to a structured orientation to the 2 simulation systems and then tested with proctor supervision on the 5 laparoscopic and 2 hysteroscopic exercises. A short 5-point Likert questionnaire designed to determine face validation and question clarity was administered to each subject at sites 2 and 3., Measurements and Main Results: Face validity was high for each of the 7 exercises (means ranged from 4.8 to 4.9 of 5), and subjects considered instructions to be clear (means from 4.7 to 4.9). The recorded exercise times generally reduced with increasing levels of training, although the sample sizes were not designed to determine significance given the pilot design. Similarly, exercise errors were generally less frequent with increasing experience. The systems, including the devices and recording mechanisms, performed well, and proctor evaluation and training were satisfactory., Conclusion: The EMIG laparoscopic and hysteroscopic simulations systems were considered to have good face validity and appear to be suitable for a construct validation trial to confirm their utility in distinguishing among trainees and practitioners with a wide spectrum of endoscopic surgical experience. The recording and specimen storage mechanisms will allow for multiple proctors to rate a candidate's performance, thereby enhancing evaluation consistency and quality., (Copyright © 2019. Published by Elsevier Inc.)

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r ΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r ΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r -/- rodents. Csf1r ΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.

Despite the ever-growing global participation in circus arts, very little research has been conducted into injuries associated with this physical discipline. To date, no studies have examined the incidence of injuries in circus training institutions and schools. In this study, data were collected over an academic year from all student injury presentations to the physiotherapy staff at one Australian circus school. A total of 351 injuries resulting in 1,948 treatments occurred in 33 female and 30 male circus students. The most common mechanisms of injury were acrobatics/tumbling (23%), handstands (12%), adagio (11%), and Chinese pole (10%). The most commonly injured body parts were the ankle (25%), lumbar spine (14%), and shoulder (12%). Interestingly, combined spinal injuries (cervical, thoracic, and lumbar) contributed to 35% of all initial injuries. Females sustained 71% of all hip injuries, but only 33% of all forearm injuries. Males accounted for 59% of all ankle injuries. There were no significant gender-based differences in other body areas. Results indicated that there is no gender-based difference in the overall rate of injury. However, females sustained significantly higher rates of hip injuries and males presented with more forearm and ankle injuries, perhaps reflecting the specific form and style of circus training and contortion undertaken. Spinal injuries had the highest overall rate of initial and follow-up presentations, indicating that both preventative and rehabilitative strategies could be addressed. It is suggested that the most common mechanisms of injury reflect both the amount of time spent training specific disciplines and the extreme physical difficulties and demands placed on the body.