NeuroPAL: A Multicolor Atlas for Whole-Brain Neuronal Identification in C. elegans.

Comprehensively resolving neuronal identities in whole-brain images is a major challenge. We achieve this in C. elegans by engineering a multicolor transgene called NeuroPAL (a neuronal polychromatic atlas of landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that resolves all neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. We showcase three applications that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding for these stimuli.

Network statistics of the whole-brain connectome of Drosophila.

Brains comprise complex networks of neurons and connections, similar to the nodes and edges of artificial networks. Network analysis applied to the wiring diagrams of brains can offer insights into how they support computations and regulate the flow of information underlying perception and behaviour. The completion of the first whole-brain connectome of an adult fly, containing over 130,000 neurons and millions of synaptic connections1-3, offers an opportunity to analyse the statistical properties and topological features of a complete brain. Here we computed the prevalence of two- and three-node motifs, examined their strengths, related this information to both neurotransmitter composition and cell type annotations4,5, and compared these metrics with wiring diagrams of other animals. We found that the network of the fly brain displays rich-club organization, with a large population (30% of the connectome) of highly connected neurons. We identified subsets of rich-club neurons that may serve as integrators or broadcasters of signals. Finally, we examined subnetworks based on 78 anatomically defined brain regions or neuropils. These data products are shared within the FlyWire Codex ( https://codex.flywire.ai ) and should serve as a foundation for models and experiments exploring the relationship between neural activity and anatomical structure.

Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Arthroscopic Superior Capsular Reconstruction Acts as a Biologic Spacer by Increasing Acromiohumeral Distance.

Massive rotator cuff tears can be successfully treated with a wide variety of surgical procedures depending on many different patient factors. The arthroscopic superior capsular reconstruction (SCR) is a good procedure for a younger patient with pseudoparesis, no lag signs, and a primary complaint of pain. How does the SCR work to achieve a good clinical outcome? One theory is that it restores the force couple and normal kinematics of the shoulder, but more evidence supports the theory that it acts as a biologic spacer. Differences in success of autograft versus allograft is likely due to graft thickness. Recent studies have shown that 6-8mm fascia lata autograft has better outcomes than 2-4mm dermal allograft. Improving the acromiohumeral distance (AHD) and tissue healing to the tuberosity is important, as this may prevent painful impingement. In our experience, when a patient has painful impingement and preserved motion or pseudoparesis, we will routinely offer a soft tissue procedure that can increase the AHD, acting as a spacer to prevent the greater tuberosity from contacting the acromion.

Magnetic Resonance Arthrogram Outperforms Standard Magnetic Resonance Imaging 2 Weeks After First Shoulder Dislocation for Labral Tear Diagnosis.

PURPOSE: To determine the comparative accuracy and precision of routine magnetic resonance imaging (MRI) versus magnetic resonance (MR) arthrogram in measuring labral tear size as a function of time from a shoulder dislocation. METHODS: We retrospectively evaluated consecutive patients who underwent primary arthroscopic stabilization between 2012 and 2021 in a single academic center. All patients completed a preoperative MRI or MR arthrogram of the shoulder within 60 days of injury and subsequently underwent arthroscopic repair within 6 months of imaging. Intraoperative labral tear size and location were used as standards for comparison. Three musculoskeletal radiologists independently interpreted tear extent using a clock-face convention. Accuracy and precision of MR labral tear measurements were defined based on location and size of the tear, respectively. Accuracy and precision were compared between MRI and MR arthrogram as a function of time from dislocation. RESULTS: In total, 32 MRIs and 65 MR arthrograms (total n = 97) were assessed. Multivariate analysis demonstrated that intraoperative tear size, early imaging, and arthrogram status were associated with increased MR accuracy and precision (P < .05). Ordering surgeons preferred arthrogram for delayed imaging (P = .018). For routine MRI, error in accuracy increased by 3.4° per day and error in precision increased by 2.3° per day (P < .001) from time of injury. MR arthrogram, however, was not temporally influenced. Significant loss of accuracy and precision of MRI compared with MR arthrogram occurred at 2 weeks after an acute shoulder dislocation. CONCLUSIONS: Compared with MR arthrogram, conventional MRI demonstrates time-dependent loss of accuracy and precision in determining shoulder labral tear extent after dislocation, with statistical divergence occurring at 2 weeks. LEVEL OF EVIDENCE: Level II, retrospective radiographic diagnostic study.

Posterior Glenoid Bone Block Reconstruction: Indications, Techniques, and Outcomes.

Posterior shoulder instability is of particular therapeutic interest, as it typically affects patients with high functional demands such as young athletes and active adults. Although posterior capsulolabral repair has high return-to-sport rates, it is associated with recurrent instability of up to 11%. Posterior glenoid bone loss and significant glenoid retroversion have been identified as risk factors for recurrent instability and failure after primary arthroscopic soft-tissue repair. Therefore, posterior glenoid bone block reconstruction may be indicated for glenoid bone loss 20% or greater (as measured by the perfect circle technique) or greater than 10% in the setting of pathologic glenoid, failed primary posterior labral repair, incompetent posterior capsular tissue, or significant risk factors for failure of soft-tissue repair. This procedure may be performed arthroscopically or with a posterior open approach using distal tibial allograft, iliac crest autograft, or scapular spine autograft. Although short-term to midterm outcomes have been promising, there remain concerns regarding long-term outcomes, with potentially high rates of late recurrence, revision, and secondary osteoarthritis.

Infection in Shoulder Arthroplasty: Prevention, Diagnosis, and Treatment.

Prosthetic joint infection is a devastating complication following shoulder arthroplasty that can lead to pain, poor function, and poor quality of life. With the increasing number of shoulder arthroplasties performed annually, recognition of prosthetic infection and treatment is necessary. The skin surrounding the shoulder has a unique microbiome, and Cutibacterium acnes is the most commonly encountered bacteria causing prosthetic joint infection. C acnes is a low-virulence organism that resides in the subcutaneous layer of the skin. As a result, the clinical presentation is typically less obvious than prosthetic infections seen in other joints such as the hip and knee. Therefore, diagnosis is not always straightforward, and optimal treatment strategy is unclear. Guidance on prevention, diagnosis, and treatment of shoulder prosthetic joint infection with special emphasis on the consensus definition established at the 2018 International Consensus Meeting is provided.

Reverse total shoulder arthroplasty for primary osteoarthritis with restricted preoperative forward elevation demonstrates similar outcomes but faster range of motion recovery compared to anatomic total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty (RSA) has been increasingly utilized for a variety of shoulder pathologies that are difficult to treat with anatomical total shoulder arthroplasty (TSA). Few studies have compared the outcomes of TSA vs. RSA in patients with cuff intact glenohumeral osteoarthritis and poor preoperative forward elevation. This study aimed to determine whether there is a difference in functional outcomes and postoperative range of motion (ROM) between TSA and RSA in these patients. METHODS: This retrospective cohort study included 116 patients who underwent RSA or TSA between 2013 and 2022 for the treatment of rotator cuff intact primary osteoarthritis with restricted preoperative forward flexion (FF) and a minimum 1-year follow-up. Each arthroplasty group was divided into 2 subgroups: patients with preoperative FF between 91° and 120° or FF lower than or equal to 90°. Patients' clinical outcomes, including active ROM, American Shoulder and Elbow Surgeons score, visual analog scale for pain, and subjective shoulder value were collected. Clinical and radiographic complications were evaluated. RESULTS: There was no significant difference between RSA and TSA in terms of sex (58.3% male vs. 62.2% male, P = .692), or follow-up duration (20.1 months vs. 17.7 months, P = .230). However, the RSA cohort was significantly older (72.0 ± 8.2 vs. 65.4 ± 10.6, P = .012) and weaker in FF and (ER) before surgery (P < .001). There was no difference between RSA (57 patients) and TSA (59 patients) in visual analog scale pain score (1.2 ± 2.3 vs. 1.3 ± 2.3, P = .925), subjective shoulder value score (90 ± 15 vs. 90 ± 15, P = .859), or American Shoulder and Elbow Surgeons score (78.4 ± 20.5 vs. 82.1 ± 23.2, P = .476). Postoperative active ROM was statistically similar between RSA and TSA cohorts in FF (145 ± 26 vs. 146 ± 23, P = .728) and ER (39 ± 15 vs. 41 ± 15, P = .584). However, internal rotation was lower in the RSA cohort (P < .001). This was also true in each subgroup. RSA led to faster postoperative FF and ER achievement at 3 months (P < .001). There was no statistically significant difference in complication rates between cohorts. CONCLUSION: This study demonstrates that patients with glenohumeral osteoarthritis who have a structurally intact rotator cuff but limited preoperative forward elevation can achieve predictable clinical improvement in pain, ROM, and function after either TSA or RSA. Reverse arthroplasty may be a reliable treatment option in patients at risk for developing rotator cuff failure.

Pseudoparesis and pseudoparalysis in the setting of massive irreparable rotator cuff tear: demographic, anatomic, and radiographic risk factors.

BACKGROUND: The primary purpose of this study was to identify demographic, anatomic, and radiographic risk factors for active forward elevation (AFE) <90° in the setting of massive, irreparable rotator cuff tear (miRCT). The secondary purpose was to identify characteristics differentiating between patients with pseudoparalysis (AFE <45°) and pseudoparesis (AFE >45° but <90°). METHODS: This was a retrospective case-control study reviewing patients with miRCTs at a single institution between January 12, 2016 and November 26, 2020. Patients were separated into 2 cohorts based on presence or absence of preoperative AFE <90° with maintained passive range of motion. Demographics, RCT pattern, and radiographic parameters were assessed as risk factors for AFE <90°. A secondary analysis was conducted to compare patients with pseudoparalysis and pseudoparesis. RESULTS: There were 79 patients in the AFE <90° cohort and 50 patients in the control cohort. Univariate analysis confirmed significant differences between the AFE <90° and control cohort in age (71.9 ± 11.0 vs. 65.9 ± 9.1 years), arthritis severity (34.2% vs. 16.0% grade 3 Samilson-Prieto), acromiohumeral distance (AHD; 4.8 ± 2.7 vs. 7.6 ± 2.6 mm), fatty infiltration of the supraspinatus (3.3 ± 0.9 vs. 2.8 ± 0.8) and subscapularis (2.0 ± 1.2 vs. 1.5 ± 1.0), and proportion of subscapularis tears (55.7% vs. 34.0%). On multivariate analysis, age (odds ratio [OR] 1.08, P = .014), decreased AHD (OR 0.67, P < .001), severe arthritis (OR 2.84, P = .041), and subscapularis tear (OR 6.29, P = .015) were independent factors predictive of AFE <90°. Secondary analysis revealed tobacco use (OR 3.54, P = .026) and grade 4 fatty infiltration of the supraspinatus (OR 2.22, P = .015) and subscapularis (OR 3.12, P = .042) as significant predictors for pseudoparalysis compared to pseudoparesis. CONCLUSIONS: In patients with miRCT, increased age, decreased AHD, severe arthritis, and subscapularis tear are associated with AFE <90°. Furthermore, patients with AFE <90° tend to have greater supraspinatus and subscapularis fatty infiltration. Lastly, among patients with AFE <90°, tobacco use and grade 4 fatty infiltration of the supraspinatus and subscapularis are associated with pseudoparalysis compared with pseudoparesis.