Neutrophil immune profile guides spinal cord regeneration in zebrafish.

Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, following rapid recruitment to the injured spinal cord, neutrophils mostly reverse migrate throughout the zebrafish body. In addition, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf-α expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process.

The adaptor protein 2 (AP2) complex modulates habituation and behavioral selection across multiple pathways and time windows.

Animals constantly integrate sensory information with prior experience to select behavioral responses appropriate to the current situation. Genetic factors supporting this behavioral flexibility are often disrupted in neuropsychiatric conditions, such as the autism-linked ap2s1 gene which supports acoustically evoked habituation learning. ap2s1 encodes an AP2 endocytosis adaptor complex subunit, although its behavioral mechanisms and importance have been unclear. Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. Furthermore, ap2s1 biases escape behavior choice in sensory modality-specific manners, and broadly regulates action selection across sensory contexts. We demonstrate that the AP2 complex functions acutely in the nervous system to modulate acoustically evoked habituation, suggesting several spatially and/or temporally distinct mechanisms through which AP2 regulates escape behavior selection and performance. Altogether, we show the AP2 complex coordinates action selection across diverse contexts, providing a vertebrate model for ap2s1's role in human conditions including autism spectrum disorder.

Structural and Functional Organization of Visual Responses in the Inferior Olive of Larval Zebrafish.

The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. Here, we investigate sensory representations in the inferior olive (IO) of larval zebrafish and their spatial organization. Using single-cell labeling of genetically identified IO neurons, we find that they can be divided into at least two distinct groups based on their spatial location, dendritic morphology, and axonal projection patterns. In the same genetically targeted population, we recorded calcium activity in response to a set of visual stimuli using two-photon imaging. We found that most IO neurons showed direction-selective and binocular responses to visual stimuli and that the functional properties were spatially organized within the IO. Light-sheet functional imaging that allowed for simultaneous activity recordings at the soma and axonal level revealed tight coupling between functional properties, soma location, and axonal projection patterns of IO neurons. Taken together, our results suggest that anatomically defined classes of IO neurons correspond to distinct functional types, and that topographic connections between IO and cerebellum contribute to organization of the cerebellum into distinct functional zones.

Dimensionality reduction reveals separate translation and rotation populations in the zebrafish hindbrain.

In many brain areas, neuronal activity is associated with a variety of behavioral and environmental variables. In particular, neuronal responses in the zebrafish hindbrain relate to oculomotor and swimming variables as well as sensory information. However, the precise functional organization of the neurons has been difficult to unravel because neuronal responses are heterogeneous. Here, we used dimensionality reduction methods on neuronal population data to reveal the role of the hindbrain in visually driven oculomotor behavior and swimming. We imaged neuronal activity in zebrafish expressing GCaMP6s in the nucleus of almost all neurons while monitoring the behavioral response to gratings that rotated with different speeds. We then used reduced-rank regression, a method that condenses the sensory and motor variables into a smaller number of "features," to predict the fluorescence traces of all ROIs (regions of interest). Despite the potential complexity of the visuo-motor transformation, our analysis revealed that a large fraction of the population activity can be explained by only two features. Based on the contribution of these features to each ROI's activity, ROIs formed three clusters. One cluster was related to vergent movements and swimming, whereas the other two clusters related to leftward and rightward rotation. Voxels corresponding to these clusters were segregated anatomically, with leftward and rightward rotation clusters located selectively to the left and right hemispheres, respectively. Just as described in many cortical areas, our analysis revealed that single-neuron complexity co-exists with a simpler population-level description, thereby providing insights into the organization of visuo-motor transformations in the hindbrain.

Varus stem positioning does not affect long-term functional outcome in cementless anatomical total hip arthroplasty.

INTRODUCTION: Varus positioning is the most common femoral malposition in total hip arthroplasty (THA). We compared the long-term outcomes of an anatomical cementless femoral stem positioned in varus versus neutral alignment. MATERIALS AND METHODS: Data were retrospectively reviewed for all patients receiving a cementless anatomical femoral stem in THA for osteoarthritis between 1998 and 2008. Exclusion criteria were complex cases, incomplete data or follow-up < 1 year. Primary outcome was survival rate with complications and secondary outcomes were clinical scores, thigh pain, radiological score, cortical hypertrophy and filling rate. RESULTS: Of the 283 included patients, 127 stems were classified as varus and 156 neutral. Mean follow-up was 10 years. Femoral stem size was smaller in the varus group (4.1 vs. 4.4, p = 0.047). A stem-filling rate < 80% was more frequent in the varus group (p < 0.001). The long-term survival rate without any revision procedure was 94.8% ± 2.3% (95%CI 88.4-98.7) in the varus group and 94.1% ± 2.0% (95%CI 91.3-99.1) in the neutral group (p = 0.55). There was no difference in clinical scores, thigh pain or complication occurrence between groups. The Engh-Massin score was lower in the varus group (p < 0.01) and cortical hypertrophy was higher (p < 0.001). CONCLUSIONS: A varus alignment of a cementless anatomic femoral stem does not affect survivorship, clinical outcomes or complication rate on an average follow-up of 10 years, despite increasing stress-shielding rates.

Free-hand distal locking of intramedullary nails: How to quickly achieve perfect circles without specific instrumentation.

INTRODUCTION: Intramedullary locked nails are mainly used for the fixation of mid-shaft fractures in the long bones. But inserting the distal locking screws by the free-hand technique may require high exposure to radiation. Our method achieves perfect circles on radiographs on the first attempt for lower limb fractures without any specific instrumentation. SURGICAL TECHNIQUE: We applied a geometric principle in which two lines perpendicular to another line are parallel to each other. Proximal locking, whether it is done or not, serves as a guide for the first perpendicular line to the nail. The fluoroscopy unit is aligned along the drill sleeve or the screwdriver left in place to achieve perfect circles on the first attempt. DISCUSSION: This technique is simple, reliable, and reproducible. It does not require any specific instrumentation, allows the surgeon to choose any manufacturer's nail and reduces the operating room staff's exposure to radiation.

Does arthroscopic resection of a too-long anterior process improve static disorders of the foot in children and adolescents?

PURPOSE: A too-long anterior process of the calcaneus is a common cause of pain and hind-foot instability. Our goal was to evaluate the early results of arthroscopic resection in terms of static foot disorders in children and adolescents. METHODS: We retrospectively studied 11 ft (10 patients). The inclusion criteria were treatment of TLAP by arthroscopic resection and a minimum follow-up period of six months. Surgery was indicated in cases with persistent symptomatic TLAP resistant to orthopaedic treatment. RESULTS: The mean age at surgery was 11 (range, 7-15) years. The mean follow-up duration was 15 (range, 8-28) months. Pre-operatively, we diagnosed four flat feet, two cavus feet and five feet with normal footprints, but loss of physiological hind-foot valgus. All patients presented with subtalar joint stiffness. At the last follow-up, four feet with no hind-foot valgus were normal, two were unchanged and the other feet had improved. The mean AOFAS increased from 61.9 (range, 47-73) to 89.1 (range, 71-97; P = 0.009). The mean radiological angles were near normal, exhibiting significant improvements in the lateral talo-metatarsal and Djian-Annonier angles. CONCLUSIONS: Arthroscopic resection of a TLAP is safe. In the short term, the restoration of subtalar mobility reduces pain, and improves instability and static disorders. Longer follow-up of a larger patient series is required.