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Following a humiliating defeat in the Crimean War, the Russian Empire found herself exposed due to major deficiencies in her infrastructure. To gain from European scientific, technical and educational advancements, the Russian Government began to permit studies abroad and relaxed censorship, which brought a new flood of literature into the country. These measures enormously facilitated the growth of Russian science, medicine and education in the late nineteenth century, taking the Empire into a fascinating era of laboratory research, a new cultural and intellectual tradition. The Imperial Laboratory tells the story of the lives and studies of the leading Russian and German clinician-experimenters who played critical roles in the integration of physics and chemistry into physiology and clinical medicine. A principal theme is the major transformations undergone in military medicine and education. Using a wide range of Russian and German primary sources, this book offers a unique English-language insight into Russian physiology and medicine that will be of interest to both historians and doctors, as well as anyone interested in Russian science and culture.

AimsTo investigate the effect of succinic acid on the development of experimental autoimmune uveitis (EAU) and the underlying mechanism.MethodsSuccinic acid was administrated intraperitoneally to evaluate its effects on immune response and EAU in mice. Intraocular inflammation was evaluated by histopathological scoring. Frequencies of Th1/Th17 cells were measured by flow cytometry. Concentrations of IFN-γ/IL-17A, neutrophil elastase (NE) and myeloperoxidase (MPO) were determined by enzyme-linked immunosorbent test. Infiltration of neutrophils and generation of neutrophil extracellular traps (NETs) within the eye were assessed by immumofluorescence. NETs formation in extracellular matrix was visualised by laser scanning confocal microscopy. Succinate receptor (SUCNR1) antagonist was used to investigate its effect on the generation of NETs.ResultsIntraperitoneal injection of succinic acid exacerbated EAU severity as evidenced by severe histological changes in association with elevated frequencies of splenic Th1/Th17 cells, and upregulated levels of IFN-γ/IL-17A and NETs in plasma. In vitro experiments showed that succinic acid could promote the generation of NETs by neutrophils as shown by increased expression of NE and MPO.NETs could increase the frequencies of Th1/Th17 cells in CD4+ T cells and their expression of IFN-γ/IL-17A. In the experiment of receptor antagonism, the upregulatory effect of succinic acid on NETs could be significantly blocked by SUCNR1 antagonist.ConclusionsSuccinic acid could worsen EAU induced by IRBP in mice. This effect was possibly mediated by its upregulation on NETs generation and frequencies of Th1/Th17 cells in affiliation with increased production of IFN-γ/IL-17A through succinic acid-SUCNR1 axis.

Background/aimsNanophthalmos is a rare developmental, bilateral, sporadic or hereditary form of microphthalmos. In this study, the heterozygous variants c.781G>A and c.1066dup of the PRSS56 gene were identified in two patients with nanophthalmos. This study reports the clinical manifestation and the underlying pathogenic mechanism.MethodsWhole-exome sequencing was performed to identify the pathogenic genes in a Chinese family with nanophthalmos. The molecular simulation was used to predict the structures of wild-type or mutant PRSS56. The PRSS56 wild-type or mutation overexpression cellular models have been constructed accordingly. The subcellular localisation was then observed using immunofluorescence and Western-blot techniques. The Folin-Ciocalteu assay was carried out to evaluate serine-type endopeptidase activity, and a wound-healing assay was used to examine the cellular migratory ability.ResultsThe whole-exome sequencing revealed that heterozygous variants c.781G>A and c.1066dup of the PRSS56 gene might contribute to nanophthalmos. Both variants were not identified in the dbSNP, 1000 Genome project or ESP6500 databases. Furthermore, the variants were highly conserved and were involved in biological functions. The mutations result in destructive protein structure and impede serine-type endopeptidase activity, thereby impairing subcellular localisation and cellular migration.ConclusionThe c.781G>A and c.1066dup variants of the PRSS56 gene might negatively affect protein structures, subcellular localisation, serine-type endopeptidase activity and cellular migratory ability. Together, these changes could lead to the development of nanophthalmos. This study identifies the PRSS56 gene as a potential target for nanophthalmos diagnosis and treatment.

Glaucoma is one of the leading causes of vision loss in the world. Currently, pharmacological intervention for glaucoma therapy is limited to eye drops that reduce intraocular pressure (IOP). Recent studies have shown that various factors as well as IOP are involved in the pathogenesis of glaucoma, especially in the subtype of normal tension glaucoma. To date, various animal models of glaucoma have been established, including glutamate/aspartate transporter knockout (KO) mice, excitatory amino acid carrier 1 KO mice, optineurin E50K knock-in mice, DBA/2J mice and experimentally induced models. These animal models are very useful for elucidating the pathogenesis of glaucoma and for identifying potential therapeutic targets. However, each model represents only some aspects of glaucoma, never the whole disease. This review will summarise the benefits and limitations of using disease models of glaucoma and recent basic research in retinal protection using existing drugs.

Background/AimWith the popularity of endothelial keratoplasty (EK) procedures, Descemet membrane (DM) EK and pre-Descemet EK, considerable work has been done on understanding the posterior corneal anatomy. Most of the information available relates to the central cornea. We evaluated the peripheral cornea to explore the immunohistological and anatomical relationship between the pre-Descemet layer (PDL), DM and trabecular meshwork (TM).MethodsSix donor human sclerocorneal discs were studied. PDL, DM and TM were examined by light microscopy, transmission electron microscopy (TEM) and immunohistology. The DM was peeled from the centre to the limit of its peripheral attachment, to reach the transition zone (TZ) between TM and peripheral cornea. Ten-micron sections were stained with antibodies against collagens 1, 2, 3, 4, 5, 6, 12, elastin, myocilin, wnt-1, aquaporin, tenascin C, laminin and integrin alpha 3.ResultsCollagens 2, 3, 4, laminin and myocilin were predominantly seen in the TZ between TM and peripheral cornea. Wnt-1, integrin alpha 3 and tenascin C were highly concentrated in TM. Collagen 1 was present predominantly in the corneal stroma. On TEM; DM was thinner with a denser banded structure spread throughout its thickness in the periphery compared with the central cornea where it presents as the distinct anterior banded layer.ConclusionThe TZ between DM, PDL and TM shows a unique histological structure at the periphery. The collagen and elastin fibres of the TM are continuous with the PDL. The structures are firmly attached to each other. These findings provide structural information that is relevant to the preparation of DMEK donor tissue.

Although there are surely multiple contributors to the replication crisis in psychology, one largely unappreciated source is a neglect of basic principles of measurement. We consider 4 sacred cows-widely shared and rarely questioned assumptions-in psychological measurement that may fuel the replicability crisis by contributing to questionable measurement practices. These 4 sacred cows are: (a) we can safely rely on the name of a measure to infer its content; (b) reliability is not a major concern for laboratory measures; (c) using measures that are difficult to collect obviates the need for large sample sizes; and (d) convergent validity data afford sufficient evidence for construct validity. For items a and d, we provide provisional data from recent psychological journals that support our assertion that such beliefs are prevalent among authors. To enhance the replicability of psychological science, researchers will need to become vigilant against erroneous assumptions regarding both the psychometric properties of their measures and the implications of these psychometric properties for their studies. Bien qu'il soit certain que de nombreux facteurs contribuent à la crise de la reproductibilité en psychologie, l'un d'entre eux, largement méconnu, est la négligence des principes de base de la mesure. Nous examinons quatre principes « intouchables » de la mesure en psychologie - des hypothèses largement diffusées et rarement remises en question - qui, en rendant les pratiques de mesure discutables, peuvent alimenter la crise de la reproductibilité. Ces quatre intouchables sont les suivants : (A) nous pouvons nous fier en toute confiance au nom d'une mesure pour en déduire le contenu; (b) la fiabilité n'est pas une préoccupation majeure pour les mesures en laboratoire; (c) le recours à des mesures qui sont difficiles à recueillir écarte le besoin d'échantillons de taille plus importante; (d) des données convergentes sur la validité constituent des éléments de preuve suffisants de la validité conceptuelle. Pour les éléments a et d, nous fournissons des données provisoires issues de revues de psychologie récentes qui soutiennent notre affirmation selon laquelle de telles croyances prévalent parmi les auteurs. Afin d'améliorer la reproductibilité de la science de la psychologie, les chercheurs devront être vigilants face aux suppositions erronées concernant les propriétés psychométriques de ces mesures et aux répercussions de ces propriétés psychométriques pour leurs études. Public Significance Statement This article outlines four widely held but erroneous measurement assumptions that may adversely affect the accuracy and replicability of psychological findings. The effects of questionable measurement practices stemming from these assumptions are discussed, and new data bearing on the prevalence of these assumptions in academic journals are presented. In addition, this article offers several potential remedies that researchers and journals can implement to improve the measurement of psychological constructs.

BackgroundCorneal transplant failure with neovascularisation is a leading indication for full-thickness grafts in patients. Lymphangiogenesis is implicated in the pathology of graft failure, and here we systematically evaluate failed human corneal transplants with neovascularisation for the presence of lymphatic vessels.MethodsNine failed grafts with neovascularisation, based on H&E staining with subsequent immunoperoxidase staining for CD31, a blood vessel marker, were selected. Lymphatics were investigated by immunohistochemical and immunofluorescence approaches using podoplanin as a lymphatic marker. In two of nine cases, fluorescence in situ hybridisation (FISH) was used for detection of lymphatic mRNAs including podoplanin, VEGFR-3 and LYVE-1. All immunofluorescence and FISH samples were compared with positive and negative controls and visualised by confocal microscopy.ResultsCorneal neovascularisation was established in all cases by H&E and further confirmed by CD31 immunoreactive profiles. Immunohistochemistry for the podoplanin antibody was positive in all cases and showed morphologies ranging from distinct luminal structures to elongated profiles. Simultaneous immunofluorescence using CD31 and podoplanin showed lymphatic vessels distinct from blood vessels. Podoplanin immunofluorescence was noted in seven of nine cases and revealed clear lumina of varying sizes, in addition to lumen-like and elongated profiles. The presence of lymphatic mRNA was confirmed by FISH studies using a combination of at least two of podoplanin, VEGFR-3 and LYVE-1 mRNAs.ConclusionsThe consistent finding of lymphatic vessels in failed grafts with neovascularisation implicates them in the pathogenesis of corneal transplant failure, and points to the lymphatics as a potential new therapeutic target.

It is essential to expose students to real situations in science courses, to experience how classroom concepts are reflected in the real world. However, the materials and methods available are not always very adequate; for example, chemistry courses involve the supervision of reagents to avoid risky situations, in addition to the costs, logistics of preparing materials, and possible adverse environmental factors. As an alternative solution, the following experience was carried out using virtual reality (VR) equipment, with very realistic applications that allowed 304 fourth semester high school students to have an immersive, interactive, and contextualized experience of the disciplinary contents. The students were asked about their perception regarding the motivation and acceptance of the use of virtual reality. The results were 72% positive for attention, 61% positive for relevance, 64% positive for trust, and 71% positive for satisfaction. Also, they mentioned their intention to continue using this resource and create lines of research to study the different aspects that could form a disciplinary proposal for an entire course based on virtual reality.

Background/aimsCongenital cataracts, which are genetically heterogeneous eye disorders, result in visual loss in childhood around the world. CRYBA1/BA3 serves as an abundant structural protein in the lens, and forms homomers and heteromers to maintain lens transparency. In previous study, we identified a common cataract-causing mutation, βA3-glycine at codon 91 (G91del) (c.271–273delGAG), which deleted a highly conserved G91del and led to perinuclear zonular cataract. In this study, we aimed to explore the underlying pathogenic mechanism of G91del mutation.MethodsProtein purification, size-exclusion chromatography, spectroscopy and molecular dynamics simulation assays were used to investigate the effects on the heteromers formation and the protein structural properties of βA3-crystallin caused by G91del mutation. Intracellular βA3-G91del overexpression, MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) and cell apoptosis were used to investigate the cellular functions of βA3-G91del.ResultsβA3-crystallin and βB2-crystallin could form heteromers, which have much more stable structures than βA3 homomers. Interestingly, βA3/βB2 heteromers improved their resistance against the thermal stress and the guanidine hydrochloride treatment. However, the pathogenic mutation βA3-G91del destroyed the interaction with βB2, and thereby decreased its structural stability as well as the resistance of thermal or chemical stress. What’s more, the βA3-G91del mutation induced cell apoptosis and escaped from the protection of βB2-crystallin.ConclusionsβA3/βB2 heteromers play an indispensable role in maintaining lens transparency, while the βA3-G91del mutation destabilises heteromers formation with βB2-crystallin, impairs cellular viability and induces cellular apoptosis. These all might contribute to cataract development.

Background/aimsThis study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops.MethodsAt our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-β1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours.ResultsHigher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-β1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops.ConclusionPRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders.