Standing osteosynthesis of an accessory carpal bone fracture in a Warmblood mare with a 6‐hole 3.5 talonavicular fusion plate and 3.5‐mm screws

A 9-year-old Warmblood, high-level showjumping mare sustained an acute, closed, vertical, comminuted fracture of the left accessory carpal bone (ACB) during a fall. The fracture was repaired under standing sedation and local anaesthesia, using a 6-hole APTUS® 3.5 TFP and 5 × 3.5-mm self-tapping TriLock© screws. The mare recovered from surgery without complications. Upon follow-up examination 9 months post-operatively the mare was sound in all gaits and back to full athletic activity. The ACB fracture had completely healed. The displaced dorsoproximal fracture fragment was in a stationary position and there was evidence of mild nonprogressive osteoarthritis of the antebrachiocarpal joint

Designing allostery-inspired response in mechanical networks

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks

Traffic accident-related injuries in horses

Horses involved in road traffic accidents (RTAs) are commonly presented to veterinarians with varying types of injuries. The aim of this study was describe the pattern and severity of traffic accident-related injuries in horses in a single hospital population. Medical records of horses either hit by a motorized vehicle or involved in RTAs whilst being transported from 1993 to 2015 were retrospectively reviewed and the following data was extracted: Signalement, hospitalisation time, month in which the accident happened, cause of the accident, place of the accident and type of vehicle hitting the horse. Further the different body sites injured (head, neck, breast, fore limb, abdomen, back and spine, pelvis and ileosacral region, hind limb, tail and genital region), the type of injury (wounds, musculoskeletal lesions and internal lesions) and the presence of neurological signs were retrieved from the medical records. 34 horses hit by motorized vehicles and 13 horses involved in RTAs whilst being transported were included in the study. Most of the accidents where horses were hit by motorized vehicles occurred during December (14.7%) and October (14.7%), horses were most commonly hit by cars (85.3%) and the majority of accidents occurred on main roads (26.5%). In 29.4% of the cases, horses had escaped from their paddock and then collided with a motorized vehicle. Most of the accidents with horses involved in RTAs whilst being transported occurred during April (30.8%) and June (23.1%). In 76.9% of the cases the accident happened on a freeway. In the horses hit by motorized vehicles the proximal hind limbs were the body site most commonly affected (44.1%), followed by the proximal front limbs (38.2%) and the head (32.4%). When horses were involved in RTAs whilst being transported the proximal fore limbs (61.5%), the proximal hind limbs (53.8%) and the distal hind limbs, back and head (38.5% each) were the most common injured body sites. Wounds were the most common type of injury in both groups(85.3% hit by motorized vehicle, 76.9% transported ones). In horses hit by a motorized vehicle 35.3% suffered from fractures, in 20.6% a synovial structure was involved and in 5.9% a tendon lesion was present. 14.7% suffered from internal lesions and 14.7% showed neurologic symptoms (40% peripheral, 60% central neurologic deficits). On the other hand, in horses involved in a RTA whilst being transported 30.8% suffered from fractures. There were no synovial structures injured and no tendon injuries were present. Furthermore there were no internal lesions present and only one horse involved in a RTA showed central neurologic symptoms. Injuries of horses being hit by a motorized vehicle were more severe than when horses were protected by a trailer and involved in an RTA whilst being transported. The study has been able to identify the different injury types of traffic accident-related injuries in horses. Awareness of the nature of these injuries is important, to avoid underestimation of their severity

Trans-cellular control of synapse properties by a cell type-specific splicing regulator

The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. ‘Terminal selector’ transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. Focusing on hippocampal pyramidal cells and SST-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner

A cell-type-specific alternative splicing regulator shapes synapse properties in a trans-synaptic manner

The specification of synaptic properties is fundamental for the function of neuronal circuits. "Terminal selector" transcription factors coordinate terminal gene batteries that specify cell-type-specific properties. Moreover, pan-neuronal splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell-type-specific loss-of-function studies to uncover the contribution of the RNA-binding protein SLM2 to hippocampal synapse specification. Focusing on pyramidal cells and somatostatin (SST)-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins. In the absence of SLM2, neuronal populations exhibit normal intrinsic properties, but there are non-cell-autonomous synaptic phenotypes and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner

Trypan Blue Dye Enters Viable Cells Incubated with the Pore-Forming Toxin HlyII of Bacillus cereus

Trypan blue is a dye that has been widely used for selective staining of dead tissues or cells. Here, we show that the pore-forming toxin HlyII of Bacillus cereus allows trypan blue staining of macrophage cells, despite the cells remaining viable and metabolically active. These findings suggest that the dye enters viable cells through the pores. To our knowledge, this is the first demonstration that trypan blue may enter viable cells. Consequently, the use of trypan blue staining as a marker of vital status should be interpreted with caution. The blue coloration does not necessarily indicate cell lysis, but may rather indicate pore formation in the cell membranes and more generally increased membrane permeability

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity