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The use of millions of mice in scientific studies worldwide emphasises the continuing need for a reduction of sample sizes, however, not at the expense of scientific validity. Split-plot designs have been suggested to enhance statistical power while allowing a reduction of animal numbers in comparison to traditional experimental designs. Recently, a promising approach of a split-plot design has been implemented and proven useful using mixed-strain housing of at least three different mouse strains. However, the impact of co-housing different strains of mice in one cage on animal welfare has still to be defined. This study aimed at comparing the effects of mixed-strain and same-strain housing of female C57BL/6J and DBA/2N mice on welfare and behaviour in two experimental phases. In a first phase, mice were housed in either mixed- or same-strain pairs. Home cage behaviour, activity rhythm, body weight, and faecal corticosterone metabolites were assessed. Furthermore, tests for anxiety-like and exploratory behaviour as well as spatial learning were performed. In a second phase, sociability was investigated in newly formed mixed-strain quartets. Mixed-strain housing did not induce alterations in anxiety, locomotion, learning, stereotypic behaviour, and stress hormone levels. However, changes in social behaviours and activity rhythm were observed. Increased agonistic and decreased socio-positive behaviours might point towards mild impacts on welfare in C57BL/6J mice under co-housing conditions. Altogether, scientific research may greatly benefit from co-housing mice of different strains within the same cages (e.g. for the realisation of a split-plot design), provided that strains are carefully selected for compatibility.Myectomy of the four horizontal rectus muscles for infantile nystagmus syndrome without a null point may improve visual acuity and quality of life. Exotropia and adduction loss are complications of this procedure, although abduction is typically preserved. We investigated whether adduction loss may be rescued by reestablishing the attachment of the anterior intermuscular septum (AIMS) to the globe at the medial rectus insertion. We present 2 cases of exotropia and adduction loss following myectomy and transposition surgery, where the nasal AIMS and the medial rectus insertion site were joined with nonabsorbable polyester suture. Both patients experienced improvements in eye alignment and adduction. Based on radiologic observations of the posterior displacement of the pulley, or posterior intermuscular septum (PIMS), with medial rectus contraction, we hypothesize that adduction and alignment were improved by providing an anterior site of action for the posterior movement of the PIMS.

Many chronic illnesses affect bone health, and commonly lead to mineralization abnormalities in young people. As cortical and trabecular bone may be differentially affected in certain diseases, an imaging technique that allows for detailed study of the bone structure is required. Peripheral quantitative computed tomography (pQCT) overcomes the limitations of dual energy X-ray absorptiometry (DXA) and is perhaps more widely available for use in research than bone biopsy. However, in contrast to DXA, where there are large reference datasets, this is not the case for pQCT.

Fifty-five children and young adults aged 7 to 30years had the non-dominant tibia scanned at the 3% & 4% sites for trabecular bone mineral density and the 38% site for cortical bone mineral density and bone mineral content. Image acquisition and analysis was undertaken according to the protocols of two of the largest reference datasets for tibial pQCT. TNG260 The Z-scores generated were compared to examine the differences between protocols an studying trabecular and cortical compartments separately but, there are variations in pQCT scanning protocols, analysis methodology, and a paucity of reference data. Reference datasets may not be generalizable to local study populations, even when analysed using identical analysis protocols.Disrupted bone metabolism can lead to delayed fracture healing or non-union, often requiring intervention to correct. Although the current clinical gold standard bone graft implants and commercial bone graft substitutes are effective, they possess inherent drawbacks and are limited in their therapeutic capacity for delayed union and non-union repair. Research into advanced biomaterials and therapeutic biomolecules has shown great potential for driving bone regeneration, although few have achieved commercial success or clinical translation. There are a number of therapeutics, which influence bone remodelling, currently licensed for clinical use. Providing an alternative local delivery context for these therapies, can enhance their efficacy and is an emerging trend in bone regenerative therapeutic strategies. This review aims to provide an overview of how biomaterial design has advanced from currently available commercial bone graft substitutes to accommodate previously licensed therapeutics that target local bone restoration and healing in a synergistic manner, and the challenges faced in progressing this research towards clinical reality.The discovery and applications of clustered regularly interspaced short palindromic repeat (CRISPR) systems have revolutionized our ability to track and manipulate specific nucleic acid sequences in many cell types of various organisms. The robustness and simplicity of these platforms have rapidly extended their applications from basic research to the development of therapeutics. However, many hurdles remain on the path to translation of the CRISPR systems to therapeutic applications efficient delivery, detectable off-target effects, potential immunogenicity, and others. Chemical modifications provide a variety of protection options for guide RNA, Cas9 mRNA and donor templates. For example, chemically modified gRNA demonstrated enhanced on-target editing efficiency, minimized immune response and decreased off-target genome editing. In this review, we summarize the use of chemically modified nucleotides for CRISPR-mediated genome editing and emphasize open questions that remain to be addressed in clinical applications.