The correlation between altmetric score and traditional measures of article impact for studies pertaining to spine trauma.

PURPOSE: It is becoming increasingly common for researchers to share scientific literature via social media. Traditional bibliometrics have long been utilized to measure a study's academic impact, but they fail to capture the impact generated through social media sharing. Altmetric Attention Score (AAS) is a weighted count of all the online attention garnered by a study, and it is currently unclear whether a relationship with traditional bibliometrics exists. METHODS: We identified the five highest-rated spine-specific and five highest-rated general orthopedic journals by Scopus CiteScore 2020. We then identified all the spine trauma studies across a 5-year span (2016-2020) within these journals and compared AAS with traditional bibliometrics using Independent t-tests and Pearson's correlational analyses. RESULTS: No statistically significant relationships were identified between AAS and traditional bibliometrics for articles pertaining to spine trauma: Level of Evidence (R = - 0.02, p = 0.34), H-Index Primary Author (R = < - 0.01, p = 0.50), H-Index Senior Author (R = - 0.04, p = 0.24), and Number of Citations (R = 0.01, p = 0.40). The top five articles by AAS include those pertaining to motorcycle injuries (AAS = 687), orthosis in thoracolumbar fractures (AAS = 199), golfing injuries (AAS = 166), smartphone-based teleradiology (AAS = 41), and auto racing injuries (AAS = 39). CONCLUSION: The lack of overlap between these types of metrics suggests that AAS or similar alternative metrics should be used to measure an article's social impact. The social impact of an article should likewise be a factor in determining an article's overall impact along with its academic impact as measured by bibliometrics.

Pore-forming bioinks to enable spatio-temporally defined gene delivery in bioprinted tissues.

The regeneration of complex tissues and organs remains a major clinical challenge. With a view towards bioprinting such tissues, we developed a new class of pore-forming bioink to spatially and temporally control the presentation of therapeutic genes within bioprinted tissues. By blending sacrificial and stable hydrogels, we were able to produce bioinks whose porosity increased with time following printing. When combined with amphipathic peptide-based plasmid DNA delivery, these bioinks supported enhanced non-viral gene transfer to stem cells in vitro. By modulating the porosity of these bioinks, it was possible to direct either rapid and transient (pore-forming bioinks), or slower and more sustained (solid bioinks) transfection of host or transplanted cells in vivo. To demonstrate the utility of these bioinks for the bioprinting of spatially complex tissues, they were next used to zonally position stem cells and plasmids encoding for either osteogenic (BMP2) or chondrogenic (combination of TGF-ß3, BMP2 and SOX9) genes within networks of 3D printed thermoplastic fibers to produce mechanically reinforced, gene activated constructs. In vivo, these bioprinted tissues supported the development of a vascularised, bony tissue overlaid by a layer of stable cartilage. When combined with multiple-tool biofabrication strategies, these gene activated bioinks can enable the bioprinting of a wide range of spatially complex tissues.

Mesenchymal stem cell fate following non-viral gene transfection strongly depends on the choice of delivery vector.

Controlling the phenotype of mesenchymal stem cells (MSCs) through the delivery of regulatory genes is a promising strategy in tissue engineering (TE). Essential to effective gene delivery is the choice of gene carrier. Non-viral delivery vectors have been extensively used in TE, however their intrinsic effects on MSC differentiation remain poorly understood. The objective of this study was to investigate the influence of three different classes of non-viral gene delivery vectors: (1) cationic polymers (polyethylenimine, PEI), (2) inorganic nanoparticles (nanohydroxyapatite, nHA) and (3) amphipathic peptides (RALA peptide) on modulating stem cell fate after reporter and therapeutic gene delivery. Despite facilitating similar reporter gene transfection efficiencies, these nanoparticle-based vectors had dramatically different effects on MSC viability, cytoskeletal morphology and differentiation. After reporter gene delivery (pGFP or pLUC), the nHA and RALA vectors supported an elongated MSC morphology, actin stress fibre formation and the development of mature focal adhesions, while cells appeared rounded and less tense following PEI transfection. These changes in MSC morphology correlated with enhanced osteogenesis following nHA and RALA transfection and adipogenesis following PEI transfection. When therapeutic genes encoding for transforming growth factor beta 3 (TGF-ß3) and/or bone morphogenic protein 2 (BMP2) were delivered to MSCs, nHA promoted osteogenesis in 2D culture and the development of an endochondral phenotype in 3D culture, while RALA was less osteogenic and appeared to promote a more stable hyaline cartilage-like phenotype. In contrast, PEI failed to induce robust osteogenesis or chondrogenesis of MSCs, despite effective therapeutic protein production. Taken together, these results demonstrate that the differentiation of MSCs through the application of non-viral gene delivery strategies depends not only on the gene delivered, but also on the gene carrier itself. STATEMENT OF SIGNIFICANCE: Nanoparticle-based non-viral gene delivery vectors have been extensively used in regenerative medicine, however their intrinsic effects on mesenchymal stem cell (MSC) differentiation remain poorly understood. This paper demonstrates that different classes of commonly used non-viral vectors are not inert and they have a strong effect on cell morphology, stress fiber formation and gene transcription in MSCs, which in turn modulates their capacity to differentiate towards osteogenic, adipogenic and chondrogenic lineages. These results also point to the need for careful and tissue-specific selection of nanoparticle-based delivery vectors to prevent undesired phenotypic changes and off-target effects when delivering therapeutic genes to damaged or diseased tissues.

Growth plate extracellular matrix-derived scaffolds for large bone defect healing.

Limitations associated with demineralised bone matrix and other grafting materials have motivated the development of alternative strategies to enhance the repair of large bone defects. The growth plate (GP) of developing limbs contain a plethora of growth factors and matrix cues which contribute to long bone growth, suggesting that biomaterials derived from its extracellular matrix (ECM) may be uniquely suited to promoting bone regeneration. The goal of this study was to generate porous scaffolds from decellularised GP ECM and to evaluate their ability to enhance host mediated bone regeneration following their implantation into critically-sized rat cranial defects. The scaffolds were first assessed by culturing with primary human macrophages, which demonstrated that decellularisation resulted in reduced IL-1ß and IL-8 production. In vitro, GP derived scaffolds were found capable of supporting osteogenesis of mesenchymal stem cells via either an intramembranous or an endochondral pathway, demonstrating the intrinsic osteoinductivity of the biomaterial. Furthermore, upon implantation into cranial defects, GP derived scaffolds were observed to accelerate vessel in-growth, mineralisation and de novo bone formation. These results support the use of decellularised GP ECM as a scaffold for large bone defect regeneration.

Optic neuritis secondary to antiandrogen therapy.

BACKGROUND: Optic neuropathy is a disorder characterised by dysfunction or destruction of the optic nerve tissues. Acquired causes include interruption in the blood supply, nutritional deficiency, compression by a tumour or aneurysm, trauma, and toxic types (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 1). Drug-induced optic neuropathy is of the toxic type and can be defined as a clinical syndrome characterised by papillomacular bundle damage, central, or cecocentral scotoma, and reduced colour vision (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 2011; Sharma and Sharma In Indian J Ophthalmol 59(2):137-141, 2). AIM: To report a case unilateral optic neuritis, secondary to the use of the antiandrogen, cyproterone acetate. CASE REPORT: A 21-year-old female presented with a 4-day history of right brow pain exacerbated by eye movement, and blurring of the right temporal field of vision. She had been taking desogestrel 75 mg and cyproterone acetate 50 mg for the previous 2 months for hormone imbalance. Unaided right visual acuity measured 6/9 and unaided left visual acuity measured 6/6 on Snellen chart. Right red desaturation was present. Goldmann perimetry showed a right enlarged blind spot with predominantly temporal visual field loss. Visually evoked potential (VEP) testing of the right eye showed slightly increased latency, but normal amplitude. Three weeks after discontinuation of the antiandrogen therapy, her symptoms resolved. Repeat Goldmann visual fields showed expansion. CONCLUSION: Known side-effects of cyproterone acetate include retinal vascular disorder and retinal vein thrombosis, but an association with optic neuritis had not been described to date. There was a temporal relationship between cessation of the medication and improvement in visual symptoms. This implies that discontinuation of the offending drug constitutes the basis of treatment in drug-induced optic neuropathy.

Fibrin hydrogels functionalized with cartilage extracellular matrix and incorporating freshly isolated stromal cells as an injectable for cartilage regeneration.

UNLABELLED: Freshly isolated stromal cells can potentially be used as an alternative to in vitro expanded cells in regenerative medicine. Their use requires the development of bioactive hydrogels or scaffolds which provide an environment to enhance their proliferation and tissue-specific differentiation in vivo. The goal of the current study was to develop an injectable fibrin hydrogel functionalized with cartilage ECM microparticles and transforming growth factor (TGF)-ß3 as a putative therapeutic for articular cartilage regeneration. ECM microparticles were produced by cryomilling and freeze-drying porcine articular cartilage. Up to 2% (w/v) ECM could be incorporated into fibrin without detrimentally affecting its capacity to form stable hydrogels. To access the chondroinductivity of cartilage ECM, we compared chondrogenesis of infrapatellar fat pad-derived stem cells in fibrin hydrogels functionalized with either particulated ECM or control gelatin microspheres. Cartilage ECM particles could be used to control the delivery of TGF-ß3 to IFP-derived stem cells within fibrin hydrogels in vitro, and furthermore, led to higher levels of sulphated glycosaminoglycan (sGAG) and collagen accumulation compared to control constructs loaded with gelatin microspheres. In vivo, freshly isolated stromal cells generated a more cartilage-like tissue within fibrin hydrogels functionalized with cartilage ECM particles compared to the control gelatin loaded constructs. These tissues stained strongly for type II collagen and contained higher levels of sGAGs. These results support the use of fibrin hydrogels functionalized with cartilage ECM components in single-stage, cell-based therapies for joint regeneration. STATEMENT OF SIGNIFICANCE: An alternative to the use of in vitro expanded cells in regenerative medicine is the use of freshly isolated stromal cells, where a bioactive scaffold or hydrogel is used to provide an environment that enhances their proliferation and tissue-specific differentiation in vivo. The objective of this study was to develop an injectable fibrin hydrogel functionalized with cartilage ECM micro-particles and the growth factor TGF-ß3 as a therapeutic for articular cartilage regeneration. This study demonstrates that freshly isolated stromal cells generate cartilage tissue in vivo when incorporated into such a fibrin hydrogels functionalized with cartilage ECM particles. These findings open up new possibilities for in-theatre, single-stage, cell-based therapies for joint regeneration.

Angiolymphoid hyperplasia with eosinophilia of the eyelid and orbit: the Western cousin of Kimura's disease?

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon disease most frequently occurring in the head and neck region. It occurs in all races. In spite of a clear distinction between ALHE and Kimura's disease on histological grounds for almost 20 years now, confusion and misdiagnosis still exist to date. Three Spanish patients presented to our institution over a 6 year period with mass lesions in the superior orbit, medial orbito-nasal wall and eyelid, respectively. All patients were of Caucasian extraction and were diagnosed with epithelioid haemangioma on histological tissue analysis. We report on the history and management of these patients which resulted in good functional and cosmetic outcome with no subsequent evidence of disease recurrence.

Attention deficit hyperactivity disorder: diagnosis and treatment masking the ophthalmic clinical presentation of a pineal gland tumour in a teenager.

A 17-year-old male was found to have a fourth cranial nerve palsy and chronic papilloedema following his presentation to our institution with a 6-week history of blurred vision in both eyes and vertical binocular diplopia. A diagnosis of pineal germinoma was made following imaging studies and endoscopic neurosurgical biopsy of the tumour. He was diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) 3 years earlier and treated with amphetamines. Since this diagnosis, he continued to suffer from hyperactive behaviour, poor concentration, worsening headaches and insomnia. Pineal pathology has a known association with sleep disturbance through the disturbance of melatonin synthesis and/or metabolism. This case report serves to highlight how the presence of organic brain disease presenting to an eye department can be masked by a diagnosis of ADHD.