A divergent transcriptional landscape underpins the development and functional branching of MAIT cells.

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.

Predicting post treatment spinal strength and flexibility in work-disabled low back pain patients.

This study examined whether posttreatment trunk strength and flexibility could be predicted from initial trunk strength and flexibility, age, gender, pain severity, diagnosis, length of work disability, return-to-work expectations, anxiety, and fear of reinjury among a group of 96 injured workers with chronic occupational low back pain who completed a multidisciplinary work rehabilitation program. The results indicate that initial average torque in trunk extension, age, gender, and average pain severity contribute significantly to prediction of final average torque in trunk extension. Initial average torque in trunk flexion, age, and gender contributed significantly to prediction of final average torque in trunk flexion, and age and initial range of motion contributed significantly to the prediction of final trunk range of motion. The results indicate that prediction of trunk strength and range of motion can be accomplished from measures of trunk strength and flexibility and pain obtained prior to the onset of rehabilitation. Psychological measures were not predictive of posttreatment trunk strength and flexibility. The ability to predict posttreatment trunk strength should facilitate clinical decision making in these complex cases.

clinical ergonomic job analysis and consultation: Facilitating work reentry in a case with upper extremity cumulative trauma-related disability.

The management of work-related recurrent and chronic upper extremity cumulative trauma disorders (UECTDs) represents a challenge particularly when return to work is a treatment goal. Many of these work-related UECTDs may be the consequence of exposure to such physical stressors as repetition, excessive force, awkward and sustained posture in addition to psychosocial stressors in the workplace. Pain and associated disability can be exacerbated by these ergonomic and psychosocial stressors. The application of ergonomic principles and techniques in the context of clinical management of UECTDs may assist in efforts to return the injured worker to work and reduce the likelihood of increased symptoms, discomfort, and disability. This paper presents a case of a 43-year-old dental hygientist unable to work for a period of 2 months due to recurrent episodes of pain in the neck, right shoulder, and arm radiating to the right thumb experienced episodically over a 10-year duration. The case is presented to illustrate the application of ergonomic principles and techniques in the clinical management of a chronic episodic UECTD. The implementation of an ergonomic job analysis and subsequent ergonomic interventions at the workplace that occurred in conjunction with rehabilitation was associated with anecdotal improvements in pain, function, and comfort levels upon returning to work. While the case highlights the potential utility of ergonomics in the management of an occupational musculoskeletal upper extremity disorder, the need for reliable, valid, cost effective, and time efficient methods to assess ergonomic exposure within a clinical context remain to be developed.

Isokinetic strength testing in monitoring progress in a multidisciplinary work reentry program: A case study.

The purpose of this paper is to present a case study of a patient with a history of low back pain and the use of isokinetic testing in tracking that patient through a work-reentry program. A 44-year-old male with a diagnosis of low back pain underwent a functional capacity evaluation and began a work-reentry program. Initial isokinetic testing revealed low torque outputs in both the trunk and knee flexion and extension tests as well as limited active range of motion. Coefficient of variation appeared to be relatively high and the patient seemed guarded in his movements during the testing. Psychological testing revealed a high fear of reinjury which may have influenced the initial test. Subsequent isokinetic testing performed on the tenth and twenty-fourth days of program and at 1 month post-program exhibited greater than expected increases in torque output. This could be due in part to a reduction in the fear of reinjury, a learning effect with repeated exposure to testing, and the patient's increased confidence in the use of unguarded movements. His trunk range of motion remained essentially the same throughout the serial testing. Pain in the back and left leg was slightly diminished despite an increase in strength and function.