Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome.

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.

Percutaneous Cementation for Improvement of Pain and Function for Osteolytic Pelvic Metastasis: A Systematic Review.

INTRODUCTION: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis. METHODS: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included. RESULTS: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms. CONCLUSIONS: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure. LEVEL OF EVIDENCE: IV, systematic review of level I to IV therapeutic studies.

Alignment options and robotics in total knee arthroplasty.

Total knee arthroplasty is one of the most widely performed surgical procedures today. Its widespread popularity has helped drive innovation and improvement in the field. Different schools of thought have developed regarding the best way to perform this operation. Specifically, there are controversaries regarding the best alignment philosophy for the femoral and tibial components to optimize implant stability and longevity. Traditionally, neutral mechanical alignment has been the preferred alignment target. More recently, some surgeons advocate for alignment matching the patient's pre-arthritic anatomic alignment ("physiologic" varus or valgus), which has been described as kinematic alignment. Functional alignment is a hybrid technique that focuses on the coronal plane minimizing soft tissue releases. To date, there is no evidence demonstrating superiority of one method over another. There is growing popularity of robotic surgical techniques to improve accuracy of implant position and alignment. The choice of alignment philosophy is an important aspect of robotic assisted TKA surgery and has the potential to clarify the optimal alignment technique.

#Scoliosis: an analysis of patient perception of scoliosis on TikTok.

Background: Social media presents an opportunity to analyze popular opinion about patient experiences. Idiopathic scoliosis is a spinal pathology commonly identified in younger patients who are the largest users of social media. Objective: To analyze posts on the social media platform, TikTok, to better understand the scoliotic patient condition. Methods: TikTok posts were searched manually by screening for "#Scoliosis." Variables assessed included number of likes, conveyed tone, gender, activities of daily living, incisional scar, imaging, involved spine level, spinal curvature, pain, formal physical therapy, multiple operations/reoperation, brace use, self-image, mobility, and educational/awareness posts. Number of responses per category were evaluated for the total they represented and the percentage of available posts containing those elements. Odds ratios with 95% confidence intervals were calculated for each collected variable. Results: More posts were positive than negative (P < 0.001) and from female users than male users (P < 0.001). Self-image was the most prevalent subject, with many posts not mentioning activities of daily living, incisional scars, imaging, pain, physical therapy, timing, awareness/education, or involved spine levels. Conclusions: More females post about scoliosis than males, with most posts containing positive self-image-related themes. This may represent a positive public attitude about scoliosis; however, further research is needed.

Management of Stress Fractures in Ballet.

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.

Use of a larger surface area tip on bipolar radiofrequency wands in hip arthroscopy is associated with significantly lower traction and total surgery times.

Clinical outcomes in arthroscopic hip preservation surgery have improved over the past two decades due to many factors, including advancements in technique and instrumentation. Complications following hip arthroscopy are associated with increased traction and overall surgical times. The purpose of this study was to compare traction and surgical times during hip arthroscopy using two different radiofrequency ablation wands produced by the same manufacturer. The authors hypothesized that the wand with a larger surface area would result in significantly less traction and surgical times. This study was a retrospective comparative investigation on patients who underwent arthroscopic surgery of the central, peripheral, peritrochanteric and/or deep gluteal space compartments of the hip. Both wands are 50-degree-angled probes, but the tip and shaft diameters are 3 and 3.75 mm for Wand A (Ambient Super MultiVac 50; tip surface area 7.1 mm2) compared to 4.7 and 4.7 mm for Wand B (Ambient HipVac 50; tip surface area 17.3 mm2), respectively. There was no difference (P = 0.16) in mean age of Wand A patients (30 females, 20 males; 35.2 years) versus Wand B patients (31 females, 19 males; 32.7 years). Traction time was significantly less in the Wand B group (41 ± 6 versus 51 ± 18 min; P < 0.001), as was surgical time (102 ± 13 versus 118 ± 17 min; P < 0.001). There were no significant differences in the number of labral anchors used or Current Procedural Terminology codes performed between groups. In conclusion, it was observed that the use of a larger surface area wand was associated with significantly less traction and surgical times during hip arthroscopy.

Biceps tenotomy versus tenodesis: patient-reported outcomes and satisfaction.

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 (χ2 = 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 (χ2 = 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.

Controllable and uncontrollable stress differentially impact pathogenicity and survival in a mouse model of viral encephalitis.

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.