Osseous spicules of the posterior elements causing fast cerebrospinal fluid leaks.

PURPOSE: Dural tears are a common cause of spontaneous spinal CSF leaks. The majority of such leaks occur ventrally along the thecal sac, typically due to ventral osseous spicules that cause a rent in the dura. A minority of dural leaks are posterolateral in location. These leaks usually do not have an identifiable anatomic cause. We have anecdotally observed cases of posterolateral leaks caused by osseous spicules and sought to describe this phenomenon. METHODS: We retrospectively reviewed our imaging database, searching for cases of posterolateral CSF leaks caused by osseous spicules. We identified and included three such patients and reviewed imaging and clinical information from each patient. RESULTS: All three patients had been diagnosed using hyperdynamic CT myelography or conventional CT myelography. Their imaging showed dorsal epidural fluid collections that were related to posterolateral leaks adjacent to dorsal osseous spicules. CONCLUSION: Dorsal osseous spicules have the potential to cause posterolateral CSF leaks.

Insights into the structure and morphogenesis of the giant basal spicule of the glass sponge Monorhaphis chuni.

BACKGROUND: A basal spicule of the hexactinellid sponge Monorhaphis chuni may reach up to 3 m in length and 10 mm in diameter, an extreme case of large spicule size. Generally, sponge spicules are of scales from micrometers to centimeters. Due to its large size many researchers have described its structure and properties and have proposed it as a model of hexactinellid spicule development. Thorough examination of new material of this basal spicule has revealed numerous inconsistencies between our observations and earlier descriptions. In this work, we present the results of detailed examinations with transmitted light and epifluorescence microscopy, SEM, solid state NMR analysis, FTIR and X-ray analysis and staining of Monorhaphis chuni basal spicules of different sizes, collected from a number of deep sea locations, to better understand its structure and function. RESULTS: Three morphologically/structurally different silica layers i.e. plain glassy layer (PG), tuberculate layer (TL) and annular layer (AL), and an axial cylinder (AC) characterize adult spicules. Young, immature spicules display only plain glassy silica layers which dominate the spicule volume. All three layers i.e. PG, TL and AL can substitute for each other along the surface of the spicule, but equally they are superimposed in older parts of the spicules, with AL being the most external and occurring only in the lower part of the spicules and TL being intermediate between AL and PG. The TL, which is composed of several thinner layers, is formed by a progressive folding of its surface but its microstructure is the same as in the PG layer (glassy silica). The AL differs significantly from the PG and TL in being granular and porous in structure. The TL was found to display positive structures (tubercles), not depressions, as earlier suggested. The apparent perforated and non-perforated bands of the AL are an optical artefact. The new layer type that we called the Ripple Mark Layer (RML) was noted, as well as narrow spikes on the AL ridges, both structures not reported earlier. The interface of the TL and AL, where tubercles fit into depressions of the lower surface of the AL, represent tenon and mortise or dovetail joints, making the spicules more stiff/strong and thus less prone to breaking in the lower part. Early stages of the spicule growth are bidirectional, later growth is unidirectional toward the spicule apex. Growth in thickness proceeds by adding new layers. The spicules are composed of well condensed silica, but the outermost AL is characterized by slightly more condensed silica with less water than the rest. Organics permeating the silica are homogeneous and proteinaceous. The external organic net (most probably collagen) enveloping the basal spicule is a structural element that bounds the sponge body together with the spicule, rather than controlling tubercle formation. Growth of various layers may proceed simultaneously in different locations along the spicule and it is sclerosyncytium that controls formation of silica layers. The growth in spicule length is controlled by extension of the top of the axial filament that is not enclosed by silica and is not involved in further silica deposition. No structures that can be related to sclerocytes (as known in Demospongiae) in Monorhaphis were discovered during this study. CONCLUSIONS: Our studies resulted in a new insight into the structure and growth of the basal Monorhaphis spicules that contradicts earlier results, and permitted us to propose a new model of this spicule's formation. Due to its unique structure, associated with its function, the basal spicule of Monorhaphis chuni cannot serve as a general model of growth for all hexactinellid spicules.

Value of gadoxetic acid-enhanced MRI for microvascular invasion of small hepatocellular carcinoma: a retrospective study.

BACKGROUND: The objective of this study was to analyze the accuracy of gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for predicting microvascular invasion (MVI) in patients with small hepatocellular carcinoma (sHCC) preoperatively. METHODS: A total of 60 sHCC patients performed with preoperative Gd-EOB-DTPA-MRI in the Harbin Medical University Cancer Hospital from October 2018 to October 2019 were involved in the study. Univariate and multivariate analyses were performed by chi-square test and logistic regression analysis. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of Gd-EOB-DTPA-MRI were performed by receiver operating characteristic (ROC) curves. RESULTS: Univariate analysis indicated that alanine aminotransferase (≥ 39.00U/L), poorly differentiated pathology, and imaging features including grim enhancement, capsule enhancement, arterial halo sign and hepatobiliary features (tumor highly uptake, halo sign, spicule sign and brush sign) were associated with the occurrence of MVI (p < 0.05). Multivariate analysis revealed that rim enhancement and hepatobiliary spicule sign were independent predictors of MVI (p < 0.05). The area under the ROC curve was 0.917 (95% confidence interval 0.838-0.996), and the sensitivity was 94.74%. CONCLUSIONS: The morphologies of hepatobiliary phase imaging, especially the spicule sign, showed high accuracy in diagnosing MVI of sHCC. Rim enhancement played a significant role in diagnosing MVI of sHCC.

Organic crystal lattices in the axial filament of silica spicules of Demospongiae.

The skeletal system of Demospongiae consists of siliceous spicules, which are composed of an axial channel containing an organic axial filament (AF) surrounded by a compact layer of hydrated amorphous silica. Here we report the ultrastructural investigations of the AF of siliceous spicules from two Demospongiae: Suberites domuncula and Tethya aurantium. Electron microscopy, electron diffraction and elemental mapping analyses on both longitudinal and transversal cross-sections yield that spicules's AF consist of a three-dimensional crystal lattice of six-fold symmetry. Its structure, which is the result of a biological growth process, is a crystalline assembly characterized by a lattice of organic cages (periodicity in the range of 6nm) filled with enzymatically-produced silica. In general, the six-fold lattice symmetry is reflected by the morphology of the AF, which is characterized by six-fold facets. This seems to be the result of a lattice energy minimization process similar to the situation found during the growth of inorganic crystals. Our structural exploitation of three-dimensional organic lattices generated by biological systems is expected to contribute for explaining the relation between axial filament's ultrastructure and spicule's ultimate morphology.

Initial stages of calcium uptake and mineral deposition in sea urchin embryos.

Sea urchin larvae have an endoskeleton consisting of two calcitic spicules. We reconstructed various stages of the formation pathway of calcium carbonate from calcium ions in sea water to mineral deposition and integration into the forming spicules. Monitoring calcium uptake with the fluorescent dye calcein shows that calcium ions first penetrate the embryo and later are deposited intracellularly. Surprisingly, calcium carbonate deposits are distributed widely all over the embryo, including in the primary mesenchyme cells and in the surface epithelial cells. Using cryo-SEM, we show that the intracellular calcium carbonate deposits are contained in vesicles of diameter 0.5-1.5 µm. Using the newly developed airSEM, which allows direct correlation between fluorescence and energy dispersive spectroscopy, we confirmed the presence of solid calcium carbonate in the vesicles. This mineral phase appears as aggregates of 20-30-nm nanospheres, consistent with amorphous calcium carbonate. The aggregates finally are introduced into the spicule compartment, where they integrate into the growing spicule.

Crystallographic orientation and concentric layers in spicules of calcareous sponges.

In this work, the crystallography of calcareous sponges (Porifera) spicules and the organization pattern of the concentric layers present in their inner structure were investigated in 10 species of the subclass Calcaronea and three species of the subclass Calcinea. Polished spicules had specific concentric patterns that varied depending on the plane in which the spicules were sectioned. A 3D model of the concentric layers was created to interpret these patterns and the biomineralization process of the triactine spicules. The morphology of the spicules was compared with the crystallographic orientation of the calcite crystals by analyzing the Kikuchi diffraction patterns using a scanning electron microscope. Triactine spicules from the subclass Calcinea had actines (rays) elongated in the 〈210〉 direction, which is perpendicular to the c-axis. The scale spicules of the hypercalcified species Murrayona phanolepis presented the c-axis perpendicular to the plane of the scale, which is in accordance with the crystallography of all other Calcinea. The triactine spicules of the calcaronean species had approximately the same crystallographic orientation with the unpaired actine elongated in the ∼[211] direction. Only one Calcaronea species, whose triactine was regular, had a different orientation. Three different crystallographic orientations were found in diactines. Spicules with different morphologies, dimensions and positions in the sponge body had similar crystallographic directions suggesting that the crystallographic orientation of spicules in calcareous sponges is conserved through evolution.

Mineral-bearing vesicle transport in sea urchin embryos.

Sea urchin embryos sequester calcium from the sea water. This calcium is deposited in a concentrated form in granule bearing vesicles both in the epithelium and in mesenchymal cells. Here we use in vivo calcein labeling and confocal Raman spectroscopy, as well as cryo-FIB-SEM 3D structural reconstructions, to investigate the processes occurring in the internal cavity of the embryo, the blastocoel. We demonstrate that calcein stained granules are also present in the filopodial network within the blastocoel. Simultaneous fluorescence imaging and Raman spectroscopy show that these granules do contain a calcium mineral. By tracking the movements of these granules, we show that the granules in the epithelium and primary mesenchymal cells barely move, but those in the filopodial network move long distances. We could however not detect any unidirectional movement of the filopodial granules. We also show the presence of mineral containing multivesicular vesicles that also move in the filopodial network. We conclude that the filopodial network is an integral part of the mineral transport process, and possibly also for sequestering calcium and other ions. Although much of the sequestered calcium is deposited in the mineralized skeleton, a significant amount is used for other purposes, and this may be temporarily stored in these membrane-delineated intracellular deposits.

Electron microscope analyses of the bio-silica basal spicule from the Monorhaphis chuni sponge.

We report on a structural analysis of several basal spicules of the deep-sea silica sponge Monorhaphis chuni by electron microscope techniques supported by a precise focused ion beam (FIB) target preparation. To get a deeper understanding of the spicules length growth, we concentrated our investigation onto the apical segments of two selected spicules with apparently different growth states and studied in detail permanent and temporary growth structures in the central compact silica axial cylinder (AC) as well as the structure of the organic axial filament (AF) in its center. The new findings concern the following morphology features: (i) at the tip we could identify thin silica layers, which overgrow as a tongue-like feature the front face of the AC and completely fuse during the subsequent growth state. This basically differs from the radial growth of the surrounding lamellar zone of the spicules made of alternating silica lamellae and organic interlayers. (ii) A newly detected disturbed cylindrical zone in the central region of the AC (diameter about 30 µm) contains vertical and horizontal cavities, channels and agglomerates, which can be interpreted as permanent leftover of a formerly open axial channel, later filled by silica. (iii) The AF consists of a three-dimensional crystal-like arrangement of organic molecules and amorphous silica surrounding these molecules. Similar to an inorganic crystal, this encased protein crystal is typified by crystallographic directions, lattice planes and surface steps. The 〈001〉 growth direction is especially favored, thereby scaffolding the axial cylinders growth and consequently the spicules' morphology.

Prevalence and characterization of small tympanic bone spicules and drumstick-like hyperostotic tympanic bone spicules in the middle ear cavity of dogs.

Rounded, sessile, hyperattenuating structures detected in computed tomography (CT) studies of canine tympanic bullae have been termed "otoliths." These have been proposed to represent dystrophic mineralizations or heterotopic bone formations in the middle ear that are potentially related to chronic otitis media. Aims of the current study were to describe the prevalence, macroscopic, and histological features of structures consistent with "otoliths" in the canine tympanic cavity. Tympanic bullae from 50 routinely necropsied dogs and 139 retrospectively retrieved CT scans of canine clinical cases were examined. Small tympanic bone spicules with pointed or clubbed tips essentially arising from the free margin of the septum bullae were bilaterally present in the tympanic cavities of all 50 of the necropsied dogs. In 48% of the dogs, "otolith"-like CT-detectable bone spicules carrying drumstick-like hyperostoses that were 1-6 mm in diameter were also present. In the retrospective survey of bulla CT scans of 139 cases, the prevalence of hyperostotic tympanic bone spicules (HTBS) was 20%. Findings from the current study indicated that the presence of small tympanic bone spicules in adult dogs is most likely due to physiological bone growth in the septum bullae and that HTBS represent osseous proliferations of small tympanic bone spicules. However, the factors inducing formation of hyperostotic spicules from small tympanic bone spicules remain unknown. The high prevalence of HTBS displaying a similar appearance in bulla CT scans in dogs suggests that these spicules should be included in a differential diagnosis list for "otoliths."

3D-printed bioinspired spicules: Strengthening and toughening via stereolithography.

Recently, the replication of biological microstructures has garnered significant attention due to their superior flexural strength and toughness, coupled with lightweight structures. Among the most intriguing biological microstructures renowned for their flexural strength are those found in the Euplectella Aspergillum (EA) marine sponges. The remarkable strength of this sponge is attributed to its complex microstructure, which consists of concentric cylindrical layers known as spicules with organic interlayers. These features effectively impede large crack propagation, imparting extraordinary mechanical properties. However, there have been limited studies aimed at mimicking the spicule microstructure. In this study, structures inspired by spicules were designed and fabricated using the stereolithography (SLA) 3D printing technique. The mechanical properties of concentric cylindrical structures (CCSs) inspired by the spicule microstructure were evaluated, considering factors such as the wall thickness of the cylinders, the number of layers, and core diameter, all of which significantly affect the mechanical response. These results were compared with those obtained from solid rods used as solid samples. The findings indicated that CCSs with five layers or fewer exhibited a flexural strength close to or higher than that of solid rods. Particularly, samples with 4 and 5 cylindrical layers displayed architecture similar to natural spicules. Moreover, in all CCSs, the absorbed energy was at least 3-4 times higher than solid rods. Conversely, CCSs with a cylinder wall thickness of 0.65 mm exhibited a more brittle behavior under the 3-point bending test than those with 0.35 mm and 0.5 mm wall thicknesses. CCSs demonstrated greater resistance to failure, displaying different crack propagation patterns and shear stress distributions under the bending test compared to solid rods. These results underscore that replicating the structure of spicules and producing structures with concentric cylindrical layers can transform a brittle structure into a more flexible one, particularly in load-bearing applications.

A Bio-Inspired Approach to Improve the Toughness of Brittle Bast Fibre-Reinforced Composites Using Cellulose Acetate Foils.

Bast fibre-reinforced plastics are characterised by good strength and stiffness but are often brittle due to the stiff and less ductile fibres. This study uses a biomimetic approach to improve impact strength. Based on the structure of the spicules of a deep-sea glass sponge, in which hard layers of bioglass alternate with soft layers of proteins, the toughness of kenaf/epoxy composites was significantly improved by a multilayer structure of kenaf and cellulose acetate (CA) foils as impact modifiers. Due to the alternating structure, cracks are deflected, and toughness is improved. One to five CA foils were stacked with kenaf layers and processed to composite plates with bio-based epoxy resin by compression moulding. Results have shown a significant improvement in toughness using CA foils due to increased crack propagation. The unnotched Charpy impact strength increased from 9.0 kJ/m2 of the pure kenaf/epoxy composite to 36.3 kJ/m2 for the sample containing five CA foils. The tensile and flexural strength ranged from 74 to 81 MPa and 112 to 125 MPa, respectively. The tensile modulus reached values between 9100 and 10,600 MPa, and the flexural modulus ranged between 7200 and 8100 MPa. The results demonstrate the successful implementation of an abstract transfer of biological role models to improve the toughness of brittle bast fibre-reinforced plastics.

SM30 protein function during sea urchin larval spicule formation.

A central issue in better understanding the process of biomineralization is to elucidate the function of occluded matrix proteins present in mineralized tissues. A potent approach to addressing this issue utilizes specific inhibitors of expression of known genes. Application of antisense oligonucleotides that specifically suppress translation of a given mRNA are capable of causing aberrant biomineralization, thereby revealing, at least in part, a likely function of the protein and gene under investigation. We have applied this approach to study the possible function(s) of the SM30 family of proteins, which are found in spicules, teeth, spines, and tests of Strongylocentrotus purpuratus as well as other euechinoid sea urchins. It is possible using the anti-SM30 morpholino-oligonucleotides (MO's) to reduce the level of these proteins to very low levels, yet the development of skeletal spicules in the embryo shows little or no aberration. This surprising result requires re-thinking about the role of these, and possibly other occluded matrix proteins.

Roles of larval sea urchin spicule SM50 domains in organic matrix self-assembly and calcium carbonate mineralization.

The larval spicule matrix protein SM50 is the most abundant occluded matrix protein present in the mineralized larval sea urchin spicule. Recent evidence implicates SM50 in the stabilization of amorphous calcium carbonate (ACC). Here, we investigate the molecular interactions of SM50 and CaCO3 by investigating the function of three major domains of SM50 as small ubiquitin-like modifier (SUMO) fusion proteins - a C-type lectin domain (CTL), a glycine rich region (GRR) and a proline rich region (PRR). Under various mineralization conditions, we find that SUMO-CTL is monomeric and influences CaCO3 mineralization, SUMO-GRR aggregates into large protein superstructures and SUMO-PRR modifies the early CaCO3 mineralization stages as well as growth. The combination of these mineralization and self-assembly properties of the major domains synergistically enable the full-length SM50 to fulfill functions of constructing the organic spicule matrix as well as performing necessary mineralization activities such as Ca(2+) ion recruitment and organization to allow for proper growth and development of the mineralized larval sea urchin spicule.

Ontogenetic dynamics of the nudibranch epithelium in Onchidoris muricata (O.F. Müller, 1776).

The integumentary system is the set of organs forming the outermost layer of an animal's body. It comprises the epithelium, muscles, and elements of connective and nerve tissue. The integument acts as a physical barrier between the external environment and the internal environment that serves to protect and maintain the body of the animal. The body of nudibranch mollusks undergo significant changes during ontogenesis, with the subepidermal space changing as the mollusk grows. As the extracellular subepidermal matrix is modified, the number of collagen fibers increases, muscles and nerves develop, and calcite spicules appear and grow. Yet, specific knowledge pertaining to the transformation of the epithelium is absent. In the present work, the ontogenetic dynamics of the surface epithelium of nudibranch mollusks are traced for the first time using Onchidoris muricata (O. F. Müller, 1776) during the postlarval stages of development. Ontogenetic changes in the epithelium of O. muricata were studied using a complex set of morphological methods. According to our data, the degree of modification to the epithelium in ontogenesis depends on individual body parts and is not consistent throughout. First x-cells were recognized as the probable precursors to sclerocytes.

Elemental compositions of sea urchin larval cell vesicles evaluated by cryo-STEM-EDS and cryo-SEM-EDS.

During spicule formation in sea urchin larvae, calcium ions translocate within the primary mesenchymal cells (PMCs) from endocytosed seawater vacuoles to various organelles and vesicles where they accumulate, and subsequently precipitate. During this process, calcium ions are concentrated by more than three orders of magnitude, while other abundant ions (Na, Mg) must be removed. To obtain information about the overall ion composition in the vesicles, we used quantitative cryo-SEM-EDS and cryo-STEM-EDS analyzes. For cryo-STEM-EDS, thin (500 nm) frozen hydrated lamellae of PMCs were fabricated using cryo-focused ion beam-SEM. The lamellae were then loaded into a cryo-TEM, imaged and the ion composition of electron dense bodies was measured. Analyzes performed on 18 Ca-rich particles/particle clusters from 6 cells contained Ca, Na, Mg, S and P in different ratios. Surprisingly, all the Ca-rich particles contained P in amounts up to almost 1:1 of Ca. These cryo-STEM-EDS results were qualitatively confirmed by cryo-SEM-EDS analyzes of 310 vesicles, performed on high pressure frozen and cryo-planed samples. We discuss the advantages and limitations of the two techniques, and their potential applicability, especially to study ion transport pathways and ion trafficking in cells involved in mineralization. STATEMENT OF SIGNIFICANCE: The 'inorganic side of life', encompassing ion trafficking and ion storage in soft tissues of organisms, is a generally overlooked problem. Addressing such a problem becomes possible through the application of innovative techniques, performed in cryogenic conditions, which preserve the tissues in quasi-physiological state. We developed here a set of analytical tools, cryo-SEM-EDS, and cryo-STEM-EDS, which allow reconstructing the ion composition inside vesicles in sea urchin larval cells, on their way to deposit mineral in the skeletons. The techniques are complex, and we evaluate here the advantages and disadvantages of each technique. The methodologies that we are developing here can be applied to other cells and other pathways as well, eventually leading to quantitative elemental analyzes of tissues under cryogenic conditions.

Development and Assessment of Acyclovir Gel Plaster Containing Sponge Spicules.

Acyclovir is an acyclic purine nucleoside analog that is highly effective in inhibiting the herpes simplex virus. However, topical acyclovir has poor efficacy because of its low skin permeability. This study aimed to develop an acyclovir gel plaster containing sponge spicules (AGP-SS) to achieve synergistic improvements in skin absorption and deposition of acyclovir. The process of preparing the gel plaster was optimized by orthogonal experiments, while the composition of the formulation was optimized using the Plackett-Burman and Box-Behnken experimental designs. The selected formula was tested for physical properties, in vitro release, stability, ex vivo permeation, skin irritation, and pharmacokinetics. The optimized formulation exhibited good physical characteristics. In vitro release and ex vivo permeation studies showed that acyclovir release from AGP-SS was dominated by diffusion with significantly higher skin permeation (20.00 ± 1.07 µg/cm2) than that of the controls (p < 0.05). Dermatopharmacokinetic analyses revealed that the maximum concentration (78.74 ± 11.12 µg/g), area under the curve (1091.81 ± 29.05 µg/g/h) and relative bioavailability (197.12) of AGP-SS were higher than those of the controls. Therefore, gel plaster containing sponge spicules show potential for development as transdermal delivery systems to achieve higher skin absorption and deposition of acyclovir, especially in deep skin layers.

The terminology of sponge spicules.

Sponges (Porifera) are a diverse and globally distributed clade of benthic organisms, with an evolutionary history reaching at least the Ediacaran-Cambrian (541 Ma) boundary interval. Throughout their research history, sponges have been subjects of intense studies in many fields, including paleontology, evolutionary biology, and even bioengineering and pharmacology. The skeletons of sponges are mostly characterized by the presence of mineral elements termed spicules, which structurally support the sponge bodies, though they also minimize the metabolic cost of water exchange and deter predators. The description of the spicules' shape and the skeleton organization represents the fundamental basis of sponge taxonomy and systematics. Here, we provide an illustrated catalogue of sponge spicules, which is based on previous works on sponge spicules, for example, and gathers and updates all terms that are currently used in sponge descriptions. Each spicule type is further illustrated through high quality scanning electron microscope micrographs. It is expected to be a valuable source that will facilitate spicule identification and, in certain cases, also enable sponge classification.

Dispersed Bone Spicules as a Cause of Postoperative Headache after Retrosigmoid Vestibular Schwannoma Surgery: A Myth?

Objectives Dispersion of bone dust in the posterior fossa during retrosigmoid craniectomy for vestibular schwannoma (VS) resection could be a source of meningeal irritation and lead to development of persistent postoperative headaches (POH). We aim to determine risk factors, including whether the presence of bone spicules that influence POH after retrosigmoid VS resection. Design Present study is a retrospective case series. Setting The study was conducted at a tertiary skull-base referral center. Participants Adult patients undergoing VS resection via a retrosigmoid approach between November 2017 and February 2020 were included for this study. Main Outcome Measures Development of POH lasting ≥ 3 months is the primary outcome of this study. Results Of 64 patients undergoing surgery, 49 had complete data (mean age, 49 years; 53% female). Mean follow-up time was 2.4 years. At latest follow up, 16 (33%) had no headaches, 14 (29%) experienced headaches lasting <3 months, 19 (39%) reported POH lasting ≥3 months. Twenty-seven (55%) patients had posterior fossa bone spicules detectable on postoperative computed tomography (CT). Age, gender, body mass index, length of stay, tumor diameter, size of craniectomy, the presence of bone spicules, or the amount of posterior petrous temporal bone removed from drilling did not differ significantly between patients with POH and those without. On multivariate logistic regression, patients with POH were less likely to have preoperative brainstem compression by the tumor (odds ratio [OR] = 0.21, p = 0.028) and more likely to have higher opioid requirements during hospitalization (OR = 1.023, p = 0.045). Conclusion The presence of bone spicules in the posterior fossa on postoperative CT did not contribute to headaches following retrosigmoid craniectomy approach for VS resection.

A novel dermal delivery system using natural spicules for cosmetics and therapeutics.

BACKGROUND: Dermal delivery is versatile in therapeutics as well as cosmetics in pursuit of enhancing safety/efficacy and alleviating pain/fear to alternate oral/injective administrations. Natural siliceous spicules offer a potential approach via simple topical medications to circumvent poor penetrations through the skin barrier by loading, carrying, and releasing the active ingredients in a highly efficient and controlled manner. AIMS: The delivery of ingredients loaded on spicules is assessed to improve the dermal efficacy compared to simple topical treatments. METHODS: First, needle-like spicules were isolated from natural freshwater sponges. Then, the active ingredient was loaded via liposome formations. Finally, the dermal efficiency was evaluated. RESULTS: Natural siliceous spicules were purified, sorted, and fully characterized to appear 250 µm of length and 12 µm of diameter on average. A model ingredient, pectolinarin, was efficiently loaded onto the internal space of spicules via lecithin-based liposome formations. The penetration was visualized using a porcine skin sample with a fluorescent dye and assessed quantitatively by a Franz diffusion cell system. Dermal absorption rate was measured 73.4%, while the percutaneous penetration rate was 2.2%. The release pattern turned out a simple diffusion analyzed by Fick's law and Higuchi model. The liposomes loaded onto spicules were further stabilized by a hydrophobic capsulation, which may benefit the overall efficacy of the ingredient. CONCLUSION: A novel dermal delivery system is beneficial to improve the topical efficacy of biologically active ingredients. The outcomes shed a light upon developing skin-protective/improving cosmetics and therapeutics with enhanced performance.

Development of a novel knockout model of retinitis pigmentosa using Pde6b-knockout Long-Evans rats.

Although rats with melanin-pigmentated retinal pigment epithelial (RPE) cells are physiologically more appropriate models for human eye research than their albino counterparts, reliable models from the former strain are not available to study retinal degeneration. Here, we describe the development of a novel Pde6b-knockout Long-Evans (LE Pde6b KO) rat model that recapitulates key features of human retinitis pigmentosa (RP). After the generation of the Pde6b-knockout Sprague-Dawley rats with the CRISPR-Cpf1 system, the LE rat was back-crossed over 5 generations to develop the pigmented LE Pde6b KO strain. Interestingly, LE Pde6b KO displayed well-developed bone-spicule pigmentation; a hallmark of fundus in patients with RP which cannot be observed in non-pigmented albino rats. Moreover, the rat model showed progressive thinning of the retina, which was evident by intravital imaging with optical coherence tomography. Histologically, significant atrophy was observed in the outer nuclear layer. Functionally, LE Pde6b KO presented a marked decrease of amplitude level during electroretinogram testing, demonstrating significant loss of visual function. Therefore, these findings suggest that the LE Pde6b KO model robustly recapitulates the hallmark phenotype of RP. We believe that the LE Pde6b KO model may be used effectively for preclinical translational research to further study retinal degeneration.