Disruption of neonatal Purkinje cell function underlies injury-related learning deficits

It is hypothesized that perinatal cerebellar injury leads to long-term functional deficits due to circuit dysmaturation. Using a novel integration of GCaMP6f fiber photometry with automated measurement of cerebellar behavior using the ErasmusLadder, we causally link cerebellar injury to altered Purkinje cell responses during maladaptive behavior. Chemogenetic inhibition of neonatal Purkinje cells is sufficient to phenocopy the effects of perinatal cerebellar injury. Our results uncover a direct link between perinatal cerebellar injury and activity-dependent maturation of cerebellar cortex.

Perinatal complications of preterm or term neonates often result in adaptive behavioral deficits. While injury to the developing cerebellum has been correlated to long-term behavioral abnormalities, especially in locomotor function, the specific neural circuits and physiological mechanisms that are disrupted are unknown. Recent work characterized the spatial and temporal components of interlimb coordination in cerebellum-dependent locomotor learning (1). However, the sparsity of techniques available to directly measure neuronal activity during adaptive cerebellar behavior hampers efforts to identify the functional and mechanistic basis of behavioral pathology.We designed a unique method to measure Purkinje cell (PC) activity during an adaptive cerebellum-dependent locomotor learning task. We utilized the ErasmusLadder––an automated behavioral system that can accurately quantify cerebellum-dependent locomotor learning and adaptive behavior. The ErasmusLadder enables the use of an associative conditioned-learning paradigm that is temporally tuned to define cerebellum-specific aspects of motor learning over multiple trials (2, 3). By directly integrating fiber photometry of the genetically encoded Ca²⁺ indicator—GCaMP6f—with the ErasmusLadder, we successfully and simultaneously recorded population responses of PCs in mice in real time during unrestrained behavior on the ErasmusLadder. We used our method to integrate PC activity measurement with adaptive behavioral quantification to identify a mechanistic basis for locomotor learning dysfunction in a clinically relevant mouse model of neonatal brain injury (4).     

The successful management of a Bronchoesophageal fistula after lung transplantation: a case report

We describe an unprecedented, disastrous complication after bilateral lung transplantation (BLT), a bilateral bronchial dehiscence with a right bronchoesophageal fistula leading to life‐threatening septic shock. We also report the successful endoscopic management of this complication by double stenting and stress the efficacy of the multidisciplinary approach to this critical case.     

Temporomandibular disorders due to improper surgical treatment of mandibular fracture: clinical report

A case of mandibular fracture surgically consolidated in a wrong position resulting in craniomandibular disorders is reported. The inadequate surgical alignment of the healed bony segments caused a malocclusion. This changed the original neuromuscular system such that compensatory mechanisms began to change the whole balance of the organism. The patient presented a mandibular crossbite, an asymmetry of the face, and extensive alteration of muscular, articular, and postural function. The bony malunion and malocclusion were treated using an interdisciplinary surgical-orthodontic treatment for correcting functional disorders and aesthetic deformity. Electromyography and computerized mandibular scanning were used to evaluate improvement of the muscular activity, during rest and function, and of the mandibular kinesiology. Timing of surgical treatment and adequate fixation and immobilization of fracture segments are very important to avoid complications such as infection, delayed union, nonunion, malunion, skeletal discrepancies, nerve injury, and (rarely) ankylosis. The surgical approach should be based on the general criteria of traumatologic therapy, restoring the original bone shape and the right occlusal relations as soon as possible.