Structural and Functional Characterization of Four Novel Fibrinogen Mutations in FGB Causing Congenital Fibrinogen Disorder

Congenital fibrinogen disorders are caused by mutations in genes coding for fibrinogen and may lead to various clinical phenotypes. Here, we present a functional and structural analysis of 4 novel variants located in the FGB gene coding for fibrinogen Bβ chain-heterozygous missense BβY416C and BβA68S, homozygous nonsense BβY345*, and heterozygous nonsense BβW403* mutations. The cases were identified by coagulation screening tests and further investigated by various methods. Fibrin polymerization had abnormal development with decreased maximal absorbance in all patients. Plasmin-induced fibrin degradation revealed different lytic phases of BβY416C and BβW403* than those of the control. Fibrinopeptide cleavage measured by reverse phase high pressure liquid chromatography of BβA68S showed impaired release of fibrinopeptide B. Morphological properties, studied through scanning electron microscopy, differed significantly in the fiber thickness of BβY416C, BβA68S, and BβW403*, and in the fiber density of BβY416C and BβW403*. Finally, homology modeling of BβA68S showed that mutation caused negligible alternations in the protein structure. In conclusion, all mutations altered the correct fibrinogen function or structure that led to congenital fibrinogen disorders.

Force performance of trawl system – III: mathematical modeling (part I)

The force performance of trawl systems directly depends on the work performed by these forces.The mechanical work of a trawl system is a physical quantity that depends on the vectors of force (hydrodynamic, tension, compression, etc.) and displacement. Thermodynamic work is the amount of energy transmitted or received by the trawl system by changing its external parameters. There is also the work of the forces of the electrostatic field when the charge moves from one point of the field to another. Equations are obtained for ideal flexible steel ropes and rope-rope products, characterizing the direct proportionality of the ratio of the productivity of forces that are directed perpendicular to each other and depend on the Poisson's ratio and the constructive elongation of ideal flexible steel ropes and cordage products. The ratio of the capacities of the forces or the ratio of the moduli of elasticity in the transverse and longitudinal directions, which arise when steel ropes and rope-rope products are stretched, are inversely proportional to the square of the coefficient k connecting the elongation λ, Poisson's ratio μ and the relative elongation ε at a constant volume of the product and its mass. There has been described an example of stretching perfectly flexible steel ropes and cordage. Such constructive parameters as lay, the number of strands, wire and fiber thickness, type of weaving were not taken into account.

A Reinterpretation of Evidence for the Endothelial Glycocalyx Filtration Structure

The endothelial glycocalyx (eGlx) is thought to be the primary macromolecular filter for fluid flux out of the vasculature. This filter maintains the higher protein concentration within the vessel lumen relative to the tissue. Whilst the arguments for the eGlx being the size filter are convincing the structural evidence has been limited to specialized stains of perfusion fixed tissue, which are further processed for resin embedding for transmission electron microscopy. The staining and processing of the delicate pore structure has left many researchers struggling to interpret the observed surface coat. Previous work has alluded to a 19.5 nm spacing between fibers; however, whilst repeatable it does not give an eGlx pore size consistent with known glycosaminoglycan (GAG) molecular structure due to the required fiber thickness of >10 nm. Here a new interpretation is proposed based on the likelihood that the electron micrographs of are often of collapsed eGlx. The 19.5 nm spacing measured may therefore be the core protein of the proteoglycans (PGs) with the GAGs wrapped up around them rather than in an expanded in vivo state. The concept is explored to determine that this is indeed consistent with experimental measurements of permeability if the syndecans are predominately dimerized. Further an alteration of core protein lattice from hexagonal packing to square packing dramatically changes the permeability which could be facilitated via known mechanisms such as transient actin binding.

Highly efficient evaporative cooling by all-day water evaporation using hierarchically porous biomass

We developed a 3D solar steam generator with the highest evaporation rate reported so far using a carbonized luffa sponge (CLS). The luffa sponge consisted of entangled fibers with a hierarchically porous structure; macropores between fibers, micro-sized pores in the fiber-thickness direction, and microchannels in the fiber-length direction. This structure remained after carbonization and played an important role in water transport. When the CLS was placed in the water, the microchannels in the fiber-length direction transported water to the top surface of the CLS by capillary action, and the micro-sized pores in the fiber-thickness direction delivered water to the entire fiber surface. The water evaporation rate under 1-sun illumination was 3.7 kg/m2/h, which increased to 14.5 kg/m2/h under 2 m/s wind that corresponded to the highest evaporation rate ever reported under the same condition. The high evaporation performance of the CLS was attributed to its hierarchically porous structure. In addition, it was found that the air temperature dropped by 3.6 °C when the wind passed through the CLS because of the absorption of the latent heat of vaporization. The heat absorbed by the CLS during water evaporation was calculated to be 9.7 kW/m2 under 1-sun illumination and 2 m/s wind, which was 10 times higher than the solar energy irradiated on the same area (1 kW/m2).

Macular and Peripapillary Retinal Nerve Fiber Thickness in Unilateral Amblyopic Eye

Amblyopia is the most common cause of monocular visual impairment in both children, and young to middle-aged adults, affecting 2%–5% of the general population. The objective of this study was to compare the peripapillary nerve fiber thickness and macular thickness in amblyopic eyes, fellow eyes and normal control eyes using spectral domain optical coherence tomography. This was a cross-sectional observational study conducted at R M Kedia Eye Hospital, Birgunj, Nepal from February 2020 to July 2020. Pediatric patients with unilateral amblyopia (anisometropic amblyopia, strabismic amblyopia or both) among the age group of 6-18 years attending pediatric department of RM Kedia Eye Hospital were enrolled for the study. All patients underwent a full ophthalmological assessment, including visual-acuity testing, anterior segment evaluation with Topcon slit lamp and fundus examination with Volk +90D lenses. All statistical analysis was done in SPSS V. 20. The average peripapillary retinal nerve fiber layer thickness was 120.6 μm (SD=14.6 μm) in the amblyopic eye, 118.1 μm (SD=15.6 μm) in the fellow eye and 113.2 μm (SD=9.4 μm) in the normal eye (p=0.104) respectively. The average macular thickness was 298.6 μm (SD=19.1 μm) in the amblyopic eye, 296.9 μm (SD=11.2 μm) in the fellow eye and 303 μm (SD=12.4 μm) in the normal eye (p=0.260) respectively. In conclusion, our study did not find any significant difference in the peripapillary retinal nerve fiber thickness or macular thickness when compared between amblyopic eyes, fellow eyes, gender and age matched normal eyes.

Dysfibrinogenemia—Potential Impact of Genotype on Thrombosis or Bleeding

The congenital dysfibrinogenemias, most often associated with bleeding disorders, encompass mutations in the amino-terminal end of fibrinogen α-chain consisting of Gly17-Pro18-Arg19-Val20, known as knob A, which is a critical site for fibrin polymerization. Here we review the studies reporting dysfibrinogenemia due to mutations affecting fibrinogen knob A and identified 29 papers. The number of reports on dysfibrinogenemias related to residues Gly17, Pro18, Arg19, and Val20 is 5, 4, 18, and 2, respectively. Dysfibrinogenemias related to residues Gly17, Pro18, and Val20 are exclusively associated with bleeding tendency. However, the clinical picture associated with dysfibrinogenemia related to residue Arg19 varies, with most patients suffering from bleeding tendencies, but also transitory ischemic attacks and retinal thrombosis may occur. The reason for this variation is unclear. To elaborate the genotype–phenotype associations further, we studied a Danish family with knob A-related dysfibrinogenemia caused by the Aα Arg19Gly (p.Arg19Gly) mutation using whole-exome sequencing and fibrin structure analysis. Our family is the first reported carrying the p.Arg19Gly mutation combined with one or more single nucleotide polymorphisms (SNP)s in FGA, FGB, and/or FGG and increased fibrin fiber thickness and fibrin mass-to-length ratio suffering from pulmonary emboli, suggesting that compound genotypes may contribute to the thrombogenic phenotype of these patients. Our review, accordingly, focuses on significance of SNPs, compound genotypes, and fibrin structure measures affecting the genotype–phenotype associations in fibrinogen knob A mutations.

Morphological Study of Color Doppler Ultrasound Imaging to Observe the Effect of Ocular Fundus Surgery

High myopia continues to progress and the eye axis continues to grow, resulting in mechanical dilatation of the eyeball wall, and with the increase of age, resulting in a variety of myopic fundus pathological changes. Considering that in the late stage of fundus disease, patients can obviously feel the impact of the disease on vision, and ophthalmologists are needed for direct diagnosis, intervention and treatment. The impact of early lesions on vision is relatively weak, and patients can not detect the emergence of these lesions in time, which can only be found by fundus survey. Therefore, the automatic detection of early lesions of fundus disease (especially microaneurysms) is not only of great significance for early diagnosis and early treatment of fundus disease, but also a good reference for the detection of other fundus diseases. In this paper, color ultrasound can effectively analyze the origin of fundus diseases. The results showed that with the changes of age, eye axis and posterior sclera shape in high myopia, the area and range of myopic arc and choroidal atrophy arc expanded, the thickness of nerve fiber and choroid became thinner, and the fovea of macula mainly shifted vertically. In addition, it was also found that myopic arc, choroidal atrophic arc area, retinal thickness, nerve fiber thickness, choroidal thickness, vertical distance from macular fovea to optic disc center were correlated with age and eye axis.

An Evaluation of the Relationship between Retinal Nerve Fiber Thickness, Cochlear Nerve Thickness, the Level of Tinnitus, and Hearing Loss in Unilateral Tinnitus Patients

Background: In this study, optic coherence tomography (OCT) examination was performed to check whether there was any interaction between ophthalmic axonal structures in unilateral tinnitus patients, and the relationship between optic nerve thickness and cochlear nerve thickness was evaluated. Objective: The aim of the study was to evaluate the relatioship between hearing loss, tinnitus, and nerve thicknesses. Study Design: Prospective study. Setting: Tertiary referral university hospital. Patients: The study included 88 patients with unilateral tinnitus, for which no organic cause could be found in physical examination, psychiatric evaluation, or with imaging methods. Study groups were formed of the tinnitus side and control groups were formed of the healthy side as follows: Group 1 (Non-tinnitus side normal hearing values – n = 30), Group 2 (non-tinnitus side minimal hearing loss – n = 27), Group 3 (non-tinnitus side moderate hearing loss – n = 31), Group 4 (tinnitus side normal hearing values – n = 25), Group 5 (tinnitus side minimal hearing loss – n = 25), and Group 6 (tinnitus side moderate hearing loss – n = 38). Intervention: Retinal nerve fiber layer (RNFL) thickness was evaluated with OCT, and the cochlear nerve cross-sectional area was evaluated with MRI. Main Outcome Measures: RNFL measurements were taken with OCT from the subfoveal area (RNFL-SF) and 1.5 mm temporal to the fovea (RNFL-T µm) and nasal (RNFL-N µm) sectors. On MRI, 3 measurements were taken along the nerve from the cerebellopontine angle as far as the internal auditory canal, and the mean value of these 3 measurements was calculated. Results: When the groups were evaluated in respect of cochlear nerve thickness, a significant difference was seen between Group 1 and both the groups with hearing loss and the tinnitus groups. In the subgroup analysis, a statistically significant difference was determined between Group 1 and Groups 3, 4, 5, and 6 (p = 0.013, p = 0.003, p < 0.001, and p < 0.001, respectively). When the groups were evaluated in respect of the RNFL-SF (µm), RNFL-T (µm), and RNFL-N (µm) values, the differences were determined to be statistically significant (p < 0.001 for all). In the correlation analysis, a negative correlation was determined between hearing loss and cochlear nerve diameter (r: −0.184, p = 0.014), and RNFL-N (r: −0.272, p < 0.001) and between tinnitus and cochlear nerve diameter (r: −0.536, p < 0.001), and RNFL-T (r: −0.222, p < 0.009). Conclusion: The study results clearly showed a relationship between cochlear nerve fiber thickness and hearing loss and the severity of tinnitus in cases with unilateral tinnitus and that there could be neurodegenerative factors in the disease etiology. A similar relationship seen with the RNFL supports the study hypothesis.