Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 exon 1 mutations but not exon 2 mutations have been identified in RTT patients, suggesting that MeCP2-e1 deficiency is sufficient to cause RTT. As expected, genetic deletion of Mecp2 exons 3 and/or 4 recapitulates RTT-like neurologic defects in mice. However, Mecp2 exon 2 knockout mice have normal neurologic function. Here, a naturally occurring MECP2 exon 1 mutation is recapitulated in a mouse model by genetic engineering. A point mutation in the translational start codon of Mecp2 exon 1, transmitted through the germline, ablates MeCP2-e1 translation while preserving MeCP2-e2 production in mouse brain. The resulting MeCP2-e1 deficient mice developed forelimb stereotypy, hindlimb clasping, excessive grooming and hypo-activity prior to death between 7 and 31 weeks. MeCP2-e1 deficient mice also exhibited abnormal anxiety, sociability and ambulation. Despite MeCP2-e1 and MeCP2-e2 sharing, 96% amino acid identity, differences were identified. A fraction of phosphorylated MeCP2-e1 differed from the bulk of MeCP2 in subnuclear localization and co-factor interaction. Furthermore, MeCP2-e1 exhibited enhanced stability compared with MeCP2-e2 in neurons. Therefore, MeCP2-e1 deficient mice implicate MeCP2-e1 as the sole contributor to RTT with non-redundant functions.

Background: Biceps tenotomy and tenodesis are surgical treatments for pathology of the proximal tendon of the long head of the biceps. There is debate over which procedure provides better patient outcomes.Purpose: Compare patient-reported outcomes and satisfaction between biceps tenotomy and tenodesis. Methods: This retrospective cohort study including all patients undergoing arthroscopic biceps tenodesis or tenotomy as part of more extensive shoulder surgery with a single surgeon. Concomitant procedures included rotator cuff repair, subacromial decompression, acromioclavicular joint resection, and debridement. Patients 36-81 years old were contacted by phone at > 2-year post-operatively to complete a biceps-specific outcome questionnaire. Subject decision not to participate was the sole exclusion criterion. Satisfaction scores and frequencies of potential biceps-related downsides (biceps cramping/spasms, biceps pain, shoulder pain, weakness, cosmetic deformity) were analyzed for the effects of procedure, sex, and age.Results: Satisfaction score distributions were similar between patients with tenodesis and patients with tenotomy (χ 2 = 8.34, P = 0.08), although slightly more patients with tenodesis than patients with tenotomy reported being satisfied or very satisfied (96% versus 91%). Perceived downsides occurred more frequently among patients with tenotomy than in patients with tenodesis: 59% of patients with tenotomy reported ≥ 1 downside, versus 37% of patients with tenodesis (P < 0.01). In patients reporting ≥ 1 downside, distributions of total downsides differed between procedures (χ 2 = 10.04, P = 0.04): patients with tenotomy were more likely to report multiple concurrent downsides than were patients with tenodesis (31% versus 16%). Each individual downside tended to be reported as present by a greater proportion of patients with tenotomy than patients with tenodesis. Sex had no effect on satisfaction or downsides, but there was a trend for older patients to report higher satisfaction and fewer downsides.Conclusions: Biceps tenotomy and tenodesis are both viable treatments for proximal biceps tendon pathology, yielding high patient satisfaction. There were trends toward greater satisfaction and fewer problems in patients with tenodesis. Still, younger patients with tenodesis did report perceived downsides. Alternatively, older patients tended to be more satisfied with both procedures overall. Regardless of procedure, most patients receiving either tenotomy or tenodesis would undergo their respective surgery again. Level of Evidence: Level III evidence, retrospective comparative cohort study

Intranasal instillation of vesicular stomatitis virus (VSV) into mice given controllable stress (modeled by escapable foot shock, ES) resulted in enhanced pathogenicity and decreased survival relative to infected mice given uncontrollable stress (modeled by inescapable foot shock, IS) and non-shocked control mice. Survival likely reflected differential cytokine gene expression that may have been regulated by miR146a, a predicted stress-responsive upstream regulator. Controllability also enhanced the accumulation of brain T resident memory cells that persisted long after viral clearance. The unexpected facilitatory effect of ES on antiviral neuroimmune responses and pathogenicity may arise from differential immunoactivating and immunosuppressive effects of uncontrollable and controllable stress.

Stress fractures are highly prevalent in ballet dancers and lead to notable time loss from dancing. Nutritional status, body composition, bone mineral density, and rate of increase in activity are among the components that influence risk for stress fractures. Proper evaluation and management of stress fractures is essential including a review of the causative factors involved in each stress injury. The purpose of this article was to summarize current evidence for risk factors involved in dancers' stress fractures to optimize prevention and treatment. Identified associated factors include low energy availability, low bone mineral density, low fat body composition, abnormal lower extremity biomechanics, genetic factors, and high training loads. Ballet dancers participate in rigorous training and conditioning to achieve seemingly effortless, powerful, aesthetic artistic movements. Caring for these performing artists requires attention to their unique injuries and the remarkable volume of activity undertaken in classes, rehearsals, and performances. Stress-related bone injuries are challenging for both dancers and professional companies because treatment often includes prolonged rest from participation. An understanding of the multifactorial, multisystem nature of these injuries is required to properly diagnose, treat, and prevent the spectrum of these injuries. This review summarizes the current best evidence in dance medicine epidemiology, risk factors, and evaluation and provides a stress fracture management and prevention protocol used in elite ballet. Epidemiology of Stress-related Bone Injury in BalletStress fractures may occur secondary to one of the three mechanisms: (1) abnormal stress on normal bone, (2) normal stress on abnormal bone, or (3) abnormal stress on abnormal bone. Ballet dancers may be especially susceptible to the latter. 1 Recent evidence has described a greater incidence of stress injuries in younger, female dancers. [2][3][4][5] In a systematic review by Smith et al, 2 amateur male and female dancers sustained 0.99 and 1.09 injuries for every 1,000 dance hours, respectively, whereas professional male and female dancers sustained a total of 1.06 and 1.46 injuries, respectively, during the same period. In professional female dancers, 64% of injuries were related to

Cutibacterium (formerly Propionibacterium) acnes (C. acnes) is a commensal bacteria commonly found on the human skin and in the mouth. While the virulence of C. acnes is low in humans, it does produce a biofilm and has been identified as an etiologic agent in a growing number of implant-associated infections. C. acnes infections can prove diagnostically challenging as laboratory cultures can often take greater than 5 days to yield positive results, which are then often disregarded as contaminant. Patients with recurrent bacteremia in the setting of implantable devices warrant further studies to evaluate for an associated valvular or lead endocarditis. The patient in this report demonstrates how cardiac device-related endocarditis secondary to C. acnes can be overlooked due to the indolent nature of this pathogen. This patient presented with an implanted cardiac pacemaker device, as well as retained leads from a prior pacemaker. Transesophageal echocardiography was required to confirm the diagnosis in the setting of multiple positive blood cultures and negative transthoracic echocardiograms over a period of 4 years. The purpose of this report is to highlight the difficulties encountered in diagnosing C. acnes endocarditis in a patient with a cardiac implantable electronic device and persistently positive blood cultures.

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OBJECTIVE There is currently no consensus regarding the appropriate lower instrumented vertebra (LIV) for multilevel posterior cervical fusion (PCF) constructs between C7 and crossing the cervicothoracic junction (CTJ). The goal of the present study was to compare postoperative sagittal alignment and functional outcomes among adult patients presenting with cervical myelopathy undergoing multilevel PCF terminating at C7 versus spanning the CTJ. METHODS A single-institution retrospective analysis (January 2017–December 2018) was performed of patients undergoing multilevel PCF for cervical myelopathy that involved the C6–7 vertebrae. Pre- and postoperative cervical spine radiographs were analyzed for cervical lordosis, cervical sagittal vertical axis (cSVA), and first thoracic (T1) vertebral slope (T1S) in two randomized independent trials. Modified Japanese Orthopaedic Association (mJOA) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores were used to compare functional and patient-reported outcomes at the 12-month postoperative follow-up. RESULTS Sixty-six consecutive patients undergoing PCF and 53 age-matched controls were included in the study. There were 36 patients in the C7 LIV cohort and 30 patients in the LIV spanning the CTJ cohort. Despite significant correction, patients undergoing fusion remained less lordotic than asymptomatic controls, with a C2–7 Cobb angle of 17.7° versus 25.5° (p < 0.001) and a T1S of 25.6° versus 36.3° (p < 0.001). The CTJ cohort had superior alignment corrections in all radiographic parameters at the 12-month postoperative follow-up compared with the C7 cohort: increase in T1S (ΔT1S 14.1° vs 2.0°, p < 0.001), increase in C2–7 lordosis (ΔC2–7 lordosis 11.7° vs 1.5°, p < 0.001), and decrease in cSVA (ΔcSVA 8.9 vs 5.0 mm, p < 0.001). There were no differences in the mJOA motor and sensory scores between cohorts pre- and postoperatively. The C7 cohort reported significantly better PROMIS scores at 6 months (22.0 ± 3.2 vs 11.5 ± 0.5, p = 0.04) and 12 months (27.0 ± 5.2 vs 13.5 ± 0.9, p = 0.01) postoperatively. CONCLUSIONS Crossing the CTJ may provide a greater cervical sagittal alignment correction in multilevel PCF surgeries. However, the improved alignment may not be associated with improved functional outcomes as measured by the mJOA scale. A new finding is that crossing the CTJ may be associated with worse patient-reported outcomes at 6 and 12 months of postoperative follow-up as measured by the PROMIS, which should be considered in surgical decision-making. Future prospective studies evaluating long-term radiographic, patient-reported, and functional outcomes are warranted.