A Retrospective Single-Center Study of 23 Patients to Compare Gait Before and After Total Hip Arthroplasty Using the S-ROM Modular Hip System.

BACKGROUND This retrospective study used the Harris hip score (HHS) and range of motion (ROM) to compare gait before and after total hip arthroplasty using the modular S-ROM® hip prosthesis in 23 patients treated at a single center. MATERIAL AND METHODS For this study, 23 patients with severe hip deformity, who were treated with a total hip replacement using the S-ROM® modular hip system by DePuy® in the period from 2003 until 2008, underwent a 3-dimensional gait analysis before and after surgery. Values were compared with a validated data set of healthy subjects. Gait analysis took place using 8 infrared cameras (50 Hz), 2 force platforms of Advanced Medical Technology, Inc. (AMTI)®, and the Vicon® 512 system. The HHS and ROM of the hip joint were determined preoperatively and postoperatively. The follow-up period was 16.7±15.2 months. RESULTS A healthy gait pattern is characterized by an even stride length of both legs in relation to body height and relative symmetry of certain gait phases. These characteristics are influenced by the range of motion of the hip joint and by pelvic tilt. Symmetry could be achieved postoperatively in the stance phase and in the single-leg stance phase. However, the gait phases could not normalize. HHS and ROM improved postoperatively. CONCLUSIONS The findings from this retrospective study showed that ROM and HHS significantly improved following THA with the S-ROM® hip prosthesis, but that gait did not completely return to normal.

Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease.

Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling 'high throughput' fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry.

De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed CaV2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.