New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation

Recent studies have shown that topological constraints encoded at the RNA secondary structure level involving basic steric and stereochemical forces can significantly restrict the orientations sampled by helices across two-way RNA junctions. Here, we formulate these topological constraints in greater quantitative detail and use this topological framework to rationalize long-standing but poorly understood observations regarding the basic behavior of RNA two-way junctions. Notably, we show that the asymmetric nature of the A-form helix and the finite length of a bulge provide a physical basis for the experimentally observed directionality and bulge-length amplitude dependence of bulge induced inter-helical bends. We also find that the topologically allowed space can be modulated by variations in sequence, particularly with the addition of non-canonical GU base pairs at the junction, and, surprisingly, by the length of the 5′ and 3′ helices. A survey of two-way RNA junctions in the protein data bank confirms that junction residues have a strong preference to adopt looped-in, non-canonically base-paired conformations, providing a route for extending our bulge-directed framework to internal loop motifs and implying a simplified link between secondary and tertiary structure. Finally, our results uncover a new simple mechanism for coupling junction-induced topological constraints with tertiary interactions

Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment

As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.Peer reviewe

Arthroscopic Posterior Glenoid Reconstruction Using a Fresh Distal Tibia Allograft for Recurrent Posterior Instability

Posterior glenohumeral instability is a relatively uncommon cause of shoulder instability. Recurrent posterior instability with static posterior humeral head subluxation is often associated with critical glenoid bone loss. Unlike anterior instability, the amount of bone loss for posterior instability that requires surgical reconstruction remains a topic of debate. Several techniques have been described to treat critical bony defects in patients with recurrent posterior shoulder instability with the use of both autografts and allografts depending on the amount of bone loss present. Open posterior glenoid bone block procedure is associated with increased risk of complications and morbidity to the patient. As such, all-arthroscopic techniques have emerged with the advantage of allowing for the diagnosis and treatment of concomitant glenohumeral pathology and minimizing soft-tissue dissection through the posterior deltoid and rotator cuff muscles. Reported short-term outcomes of arthroscopic posterior bone block stabilization are promising; however, it remains a technically challenging procedure due to intra-articular graft insertion and subsequent fixation congruent to the posterior glenoid articular margin. We describe an all-arthroscopic technique using a fresh distal tibia allograft fixation using 2 partially threaded screws in conjunction with an arthroscopic Latarjet fixation set for a patient with recurrent posterior shoulder instability and associated glenoid bone loss

The Modified Eden-Lange Tendon Transfer for Lateral Scapular Winging Secondary to Spinal Accessory Nerve Injury

Trapezius paralysis following injury to the spinal accessory nerve can be a debilitating complication resulting from lymph node biopsy, radical neck dissection, or penetrating trauma in the region of the posterior cervical triangle. Disruption of the delicate muscular balance in the shoulder girdle may result in lateral scapular winging, ipsilateral upper extremity radiculopathy, and limited shoulder function and range of motion. Spontaneous recovery with nonoperative management is possible in some patients, and restoration of function after reparative neural procedures has been observed in patients undergoing timely repair. However, extended delays from the time of injury to surgery are common and may necessitate various muscle transfers to reestablish the complex biomechanics and balance of the shoulder girdle. We describe a modification to the classic Eden-Lange procedure with lateral transfer of the levator scapulae and rhomboid minor to the scapula spine and rhomboid major transfer with a small wafer of bone to the scapula body for chronic lateral winging of the scapula following injury to the spinal accessory nerve as the result of a cervical lymph node biopsy

Arthroscopic Subscapularis Repair Using a Clever Hook and Lasso Loop Technique in the Beach Chair Position: A Simple and Reproducible Guide

Addressing subscapularis tendon pathology has garnered increased attention during shoulder arthroscopy in attempt to adequately restore glenohumeral force couples. The appropriate rebalancing of force couples of the rotator cuff musculature by repairing subscapularis tendon tears in patients with large rotator cuff tears has been shown to improve functional outcomes while decreasing retear rates. However, subscapularis tendon tears may be particularly challenging to diagnose and present a significant degree of technical difficulty with the description of multiple arthroscopic and open surgical techniques. In this comprehensive guide, we put forth a simple, concise, and reproducible arthroscopic technique using a Clever Hook and Lasso Loop stitch technique for repairing both high-grade partial and full-thickness tears of the subscapularis tendon

Diagnostic Accuracy of Ultrasonography for Rotator Cuff Tears: A Systematic Review and Meta-analysis

Background: With recent improvements in transducer strength, image resolution, and operator training, ultrasound (US) provides an excellent alternative imaging modality for the diagnosis of rotator cuff tears. Purpose: To evaluate the diagnostic accuracy of US for partial- and full-thickness rotator cuff tears and biceps tendon tears, compare diagnostic values with those of magnetic resonance imaging (MRI) using arthroscopy as the reference standard, assess longitudinal improvements in accuracy, and compare diagnostic values from operators with different training backgrounds. Study Design: Systematic review; Level of evidence, 3. Methods: The PubMed and Cochrane Library databases were systematically searched for full-text journal articles published between January 1, 2010, and April 1, 2020. The inclusion criteria were studies that evaluated the diagnostic accuracy of US for rotator cuff tears or biceps tendon tears utilizing arthroscopy as the reference standard. The exclusion criteria were studies with \u3c10 \u3epatients, studies including massive tears without reporting diagnostic data for specific tendons, and studies lacking diagnostic outcome data. Extracted outcomes included diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value. The mean difference and 95% confidence interval were calculated for both US and MRI diagnostic values, and meta-analysis was conducted using the Mantel-Haenszel random-effects model. Results: In total, 23 eligible studies involving 2054 shoulders were included. US demonstrated a higher median diagnostic accuracy for supraspinatus tendon tears (0.83) and biceps tendon tears (0.93) as compared with subscapularis tendon tears (0.76). US was found to have a higher median accuracy (0.93) for full-thickness supraspinatus tears than partial-thickness tears (0.81). US had superior median sensitivity for partial-thickness supraspinatus tears when performed by radiologists as opposed to surgeons (0.86 vs 0.57). Meta-analysis of the 5 studies comparing US and MRI demonstrated no statistically significant difference in diagnostic sensitivity, specificity, or accuracy for any thickness supraspinatus tears Conclusion: For experienced operators, US is a highly sensitive and specific diagnostic modality for the diagnosis of supraspinatus tears and demonstrates statistically equivalent capability to MRI in the diagnosis of both full- and partial-thickness rotator cuff tears

Statistical Fragility of Single-Row Versus Double-Row Anchoring for Rotator Cuff Repair: A Systematic Review of Comparative Studies.

BackgroundComparative studies and randomized controlled trials (RCTs) often use the P (probability) value to convey the statistical significance of their findings. P values are an imperfect measure, however, and are vulnerable to a small number of outcome reversals to alter statistical significance. The inclusion of a fragility index (FI) and fragility quotient (FQ) may aid in the interpretation of a study's statistical strength.Purpose/hypothesisThe purpose of this study was to examine the statistical stability of studies comparing single-row to double-row rotator cuff repair. It was hypothesized that the findings of these studies would be vulnerable to a small number of outcome event reversals, often fewer than the number of patients lost to follow-up.Study designSystematic review; Level of evidence, 3.MethodsWe analyzed comparative studies and RCTs on primary single-row versus double-row rotator cuff repair that were published between 2000 and 2021 in 10 leading orthopaedic journals. Statistical significance was defined as a P < .05. The FI for each outcome was determined by the number of event reversals necessary to alter significance. The FQ was calculated by dividing the FI by the respective sample size.ResultsOf 4896 studies screened, 22 comparative studies, 10 of which were RCTs, were ultimately included for analysis. A total of 74 outcomes were examined. Overall, the median FI was 2 (interquartile range [IQR], 1-3), and the median FQ was 0.035 (IQR, 0.020-0.057). The mean FI was 2.55 ± 1.29, and the mean FQ was 0.043 ± 0.027. In 64% of outcomes, the FI was less than the number of patients lost to follow-up.) Additionally, 81% of significant outcomes needed just a single outcome reversal to lose their significance.ConclusionOver half of the studies currently used to guide clinical practice have a number of patients lost to follow-up greater than their FI. The results of these studies should be interpreted within the context of these limitations. Future analyses may benefit from the inclusion of the FI and the FQ in their statistical analyses

The Statistical Fragility of Operative vs Nonoperative Management for Achilles Tendon Rupture: A Systematic Review of Comparative Studies.

BackgroundThe statistical significance of randomized controlled trials (RCTs) and comparative studies is often conveyed utilizing the P value. However, P values are an imperfect measure and may be vulnerable to a small number of outcome reversals to alter statistical significance. The interpretation of the statistical strength of these studies may be aided by the inclusion of a Fragility Index (FI) and Fragility Quotient (FQ). This study examines the statistical stability of studies comparing operative vs nonoperative management for Achilles tendon rupture.MethodsA systematic search was performed of 10 orthopaedic journals between 2000 and 2021 for comparative studies focusing on management of Achilles tendon rupture reporting dichotomous outcome measures. FI for each outcome was determined by the number of event reversals necessary to alter significance (P < .05). FQ was calculated by dividing the FI by the respective sample size. Additional subgroup analyses were performed.ResultsOf 8020 studies screened, 1062 met initial search criteria with 17 comparative studies ultimately included for analysis, 10 of which were RCTs. A total of 40 outcomes were examined. Overall, the median FI was 2.5 (interquartile range [IQR] 2-4), the mean FI was 2.90 (±1.58), the median FQ was 0.032 (IQR 0.012-0.069), and the mean FQ was 0.049 (±0.062). The FI was less than the number of patients lost to follow-up for 78% of outcomes.ConclusionStudies examining the efficacy of operative vs nonoperative management of Achilles tendon rupture may not be as statistically stable as previously thought. The average number of outcome reversals needed to alter the significance of a given study was 2.90. Future analyses may benefit from the inclusion of a fragility index and a fragility quotient in their statistical analyses

Humeral Head Morphology Influences Outcomes of Arthroscopic Interposition Glenoid Patch Allograft for Glenohumeral Arthritis.

PURPOSE: To determine short- to midterm patient-reported outcomes of arthroscopic soft-tissue interposition arthroplasty using acellular dermal allograft with a minimum follow-up of 1 year and to assess outcomes in patients with and without flattening of the humeral head. METHODS: Patients with a diagnosis of primary glenohumeral arthritis who underwent arthroscopic soft-tissue interposition arthroplasty with an acellular dermal allograft from July 2010 to November 2019 were retrospectively enrolled. Inclusion criteria were a primary diagnosis of glenohumeral arthritis and Outerbridge 4 full-thickness cartilage loss of ≥50% of the glenoid articular surface. Patients underwent arthroscopic debridement, microfracture, and biological arthroscopic soft-tissue interposition arthroplasty with an acellular dermal matrix. Postoperative outcomes included American Shoulder and Elbow Surgeon (ASES) score, Single Assessment Numeric Evaluation (SANE) score, Penn Shoulder Score (PSS), numeric rating scale (NRS) pain score, analgesic use, and conversion to total shoulder arthroplasty (TSA). Results were stratified according to humeral head morphology on preoperative radiographs. RESULTS: A total of 25 patients were included, with a mean age of 56.0 years (range 19.2 to 74.8) and a mean follow-up of 3.36 years (range 1.03 to 8.98). The mean postoperative ASES score was 64.1 (range 11.7 to 100.0), SANE score was 62% (range 5% to 100%), and PSS was 61.2 (range 10.6 to 97.9). Additionally, 56% of patients rated their shoulder function as improved or much improved, and 36% of patients converted to TSA at a mean of 2.35 years. Patients with and without humeral flattening had similar postoperative ASES scores ( CONCLUSION: Arthroscopic soft-tissue interposition arthroplasty with an acellular dermal allograft resulted in satisfactory short- to mid-term postoperative outcomes for younger patients with glenohumeral arthritis but demonstrated a TSA conversion rate of 36%. Patients with humeral head flattening also had satisfactory shoulder function but were more likely to experience shoulder pain at night. LEVEL OF EVIDENCE: Level IV, therapeutic case series

Quality and Variability of Online Physical Therapy Protocols for Isolated Meniscal Repairs.

The ideal meniscal repair postoperative rehabilitation protocol has yet to be determined. Further, patients are attempting to access health care content online at a precipitously increasing rate given the efficiency of modern search engines. The purpose of this investigation was to assess the quality and variability of meniscal repair rehabilitation protocols published online with the hypothesis that there would be a high degree of variability found across available protocols. To this end, Web-based meniscal repair physical therapy protocols from U.S. academic orthopaedic programs as well as the first 10 protocols identified by the Google search engine for the term meniscal repair physical therapy protocol were reviewed and assessed via a custom scoring rubric. Twenty protocols were identified from 155 U.S. academic orthopaedic programs for a total of 30 protocols. Twenty-six protocols (86.6%) recommended immediate postoperative bracing. Twelve (40.0%) protocols permitted immediate weight-bearing as tolerated (WBAT) postoperatively, while the remaining protocols permitted WBAT at an average of 4.0 (range, 1-7) weeks. There was considerable variation in range of motion (ROM) goals, with most protocols (73.3%) initiating immediate passive ROM to 90°. The types and timing of strength, proprioception, agility, and pivoting exercises advised were extremely diverse. Only five protocols (16.7%) employed functional testing as a marker for return to athletics. The results of this study indicate that only a minority of academic orthopaedic programs publish meniscal repair physical therapy protocols online and that within the most readily available online protocols there are significant disparities in regards to brace use, ROM, weight-bearing, and strengthening and proprioception exercises. These discrepancies reflect the fact that the best rehabilitation practices after a meniscal repair have yet to be elucidated. This represents a significant area for improved patient care through standardization