Evidence for the loss and recovery of SLAMF9 during human evolution: implications on Dollo's law.

Signaling lymphocyte activation molecule family member 9 (SLAMF9) is a cell surface protein of the CD2/SLAM family of leukocyte surface receptors. It is conserved throughout mammals and has roles in the initiation of inflammatory responses and regulation of plasmacytoid dendritic cell function. Through comparison of reference sequences encoding SLAMF9 in human, mouse, and primate sequences, we have determined that the SLAMF9 gene underwent successive mutation events, resulting in the loss of the protein and subsequent recovery of a less stable version. The mutations included a single base pair deletion in the second exon and a change in the splice acceptor site of that same exon. These changes would have had the effect of creating and later repairing a frameshift in the coding sequence. These events took place since the divergence of the human lineage from the chimpanzee-human last common ancestor and represent the first known case of the functional loss and recovery of a gene within the human lineage.

Intensive Aerobic Cycling Is Feasible and Elicits Improvements in Gait Velocity in Individuals With Multiple Sclerosis: A Preliminary Study.

BACKGROUND: Aerobic exercise (AEx) has many potential benefits; however, it is unknown whether individuals with multiple sclerosis (MS) can attain the optimal intensity and duration to harness its effects. Forced-rate exercise (FE) is a novel paradigm in which the voluntary pedaling rate during cycling is supplemented to achieve a higher exercise intensity. The aim of this pilot trial was to investigate the feasibility and initial efficacy of a 12-week FE or voluntary exercise (VE) cycling intervention for individuals with MS. METHODS: Twenty-two participants with MS (Expanded Disability Severity Scale [EDSS] 2.0-6.5) were randomly assigned to FE (n = 12) or VE (n = 10), each with twice weekly 45-minute sessions at a prescribed intensity of 60% to 80% of maximum heart rate (HR). RESULTS: Eighteen individuals (FE = 11; VE = 7) completed the intervention, however, adaptations were required in both groups to overcome barriers to cycling. Overall, participants exercised for an average of 42.2 ± 2.3 minutes at an aerobic intensity of 65% ± 7% of maximum HR and a pedaling cadence of 67.3 ± 13.3 RPM. Cycling led to improved treadmill walking speed (0.61 to 0.68 m/sec, P = .010), with somewhat greater improvement with FE compared to VE (increase of 0.09 vs 0.03 m/s, respectively, P = .17) post intervention. Notably, the participant with the highest disability level (EDSS 6.5) tolerated FE but not VE. CONCLUSIONS: Aerobic exercise is feasible for individuals with MS, although those with increased disability may require novel paradigms such as FE to achieve targeted intensity. Further trials are warranted to investigate the effects of FE across the MS disability spectrum.

Reducing inpatient opioid consumption after caesarean delivery: effects of an opioid stewardship programme and racial impact in a community hospital.

Caesarean section is the most common inpatient surgery in the USA, with more than 1.1 million procedures in 2020. Similar to other surgical procedures, healthcare providers rely on opioids for postoperative pain management. However, current evidence shows that postpartum patients usually experience less pain due to pregnancy-related physiological changes. Owing to the current opioid crisis, public health agencies urge providers to provide rational opioid prescriptions. In addition, a personalised postoperative opioid prescription may benefit racial minorities since research shows that this population receives fewer opioids despite greater pain levels. Our project aimed to reduce inpatient opioid consumption after caesarean delivery within 6 months of the implementation of an opioid stewardship programme.A retrospective analysis of inpatient opioid consumption after caesarean delivery was conducted to determine the baseline, design the opioid stewardship programme and set goals. The plan-do-study-act method was used to implement the programme, and the results were analysed using a controlled interrupted time-series method.After implementing the opioid stewardship programme, we observed an average of 80% reduction (ratio of geometric means 0.2; 95% CI 0.2 to 0.3; p<0.001) in inpatient opioid consumption. The institution designated as control did not experience relevant changes in inpatient opioid prescriptions during the study period. In addition, the hospital where the programme was implemented was unable to reduce the difference in inpatient opioid demand between African Americans and Caucasians.Our project showed that an opioid stewardship programme for patients undergoing caesarean delivery can effectively reduce inpatient opioid use. PDSA, as a quality improvement method, is essential to address the problem, measure the results and adjust the programme to achieve goals.

Aerobic cycling reduces fatigue and improves pain in persons with multiple sclerosis: A preliminary study.

Fatigue and pain are prevalent in persons with multiple sclerosis (PwMS), negatively impacting quality of life (QoL). Clinical management is challenging due to their multiple underlying causes. Aerobic exercise elicits central and peripheral effects, which may effectively manage MS-related symptoms. Our aim was to determine the effects of an aerobic cycling intervention on symptoms impacting QoL. Eighteen participants completed a 12-week moderate- to high-intensity aerobic cycling intervention. Participants reported significant improvements in physical fatigue, overall fatigue, pain intensity, and pain interference. Aerobic exercise should be considered as part of a multi-faceted approach to improve fatigue and pain in PwMS.

Patient Versus Clinician Proxy Reliability of the AM-PAC "6-Clicks" Basic Mobility and Daily Activity Short Forms.

OBJECTIVE: The purpose of this study was to test the reliability of the Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" mobility and activity short forms between patients and therapist proxies. As a secondary aim, reliability was examined when patients completed their self-report before versus after the therapist evaluation. METHODS: Patients being seen for an initial physical therapist (N = 70) or occupational therapist (N = 71) evaluation in the acute care hospital completed the "6-Clicks" mobility short form (if a physical therapist evaluation) or activity short form (if an occupational therapist evaluation). Whether patients completed their self-assessment before or after the evaluation was randomized. Patient- and therapist-rated "6-Clicks" raw scores were converted to AM-PAC T-scores for comparison. Reliability was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots, and agreement was assessed with weighted kappa values. RESULTS: The ICCs for the "6-Clicks" mobility and daily activity short forms were 0.57 (95% CI = 0.42-0.69) and 0.45 (95% CI = 0.28-0.59), respectively. For both short forms, reliability was higher when the patient completed the self-assessment after versus before the therapist evaluation (ICC = 0.67, 95% CI = 0.47-0.80 vs ICC = 0.50, 95% CI = 0.26-0.67 for the mobility short form; and ICC = 0.52, 95% CI = 0.29-0.70 vs ICC = 0.34, 95% CI = 0.06-0.56 for the activity short form). CONCLUSION: Reliability of the "6-Clicks" total scores was moderate for both the mobility and activity short forms, though higher for the mobility short form and when patients' self-report occurred after the therapist evaluation. IMPACT: Reliability of the AM-PAC "6-Clicks" short forms is moderate when comparing scores from patients with those of therapists responding as proxies. The short forms are useful for measuring participants' function in the acute care hospital; however, it is critical to recognize limitations in reliability between clinician- and patient-reported AM-PAC scores when evaluating longitudinal change and recovery.

Suspected Septic Sacroiliitis Following Recent Cesarean Section Under Spinal Anesthesia.

Septic sacroiliitis is sacroiliac (SI) joint inflammation secondary to microbial invasion of the synovial space characterized by tenderness over the sacroiliac joint, difficulty walking, and lower back pain that can radiate to the buttocks. Clinicians can easily overlook septic sacroiliitis as a potential diagnosis due to its rare occurrence and non-specific symptoms. A 30-year-old female (G2P2A0) who presented acutely to the ED nine days after an uncomplicated Cesarean section performed under spinal anesthesia. The patient experienced progressive lancinating, electric-shock pain originating from the coccyx radiating to the right buttock and lower back with the inability to bear weight. MRI pelvis demonstrated edematous changes of the right SI joint, indicative of septic sacroiliitis. Patient's condition improved after empiric intravenous antibiotics and was discharged home on the continued intravenous course. Rapid empiric administration of intravenous antibiotics may have prevented the onset of severe complications of an infective SI joint.