An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma

In the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.

Colloidal Processing of Y0.08Zr0.92O2/La0.80Sr0.20MnO3 Semi-Cells Using a Sr-Doped Lanthanum Manganite Synthesized by a Citrate Route

In this paper, the interface between yttria stabilized zirconia (Y0.08Zr0.92O2, YSZ) electrolyte and Sr-doped lanthanum manganite (La0.80Sr0.20MnO3, LSM) cathode for solid oxide fuel cells (SOFCs) is studied. For such a purpose, the combination of a suitable synthesis route for obtaining fine powders and simple aqueous colloidal shaping routes is proposed. The synthesis of nanosized particles of La0.80Sr0.20MnO3 by a citrate route and their full characterization, including the colloidal stability and the densification and phase development determined by X-ray diffraction and electron microscopy at different temperatures, is reported. In a second step, YSZ tapes were obtained by aqueous tape casting and used as substrates for the preparation of LSM coatings by dip-coating using aqueous slurries. YSZ tapes were used either in the green state or after a pre-sintering treatment. Co-sintering at 1350 °C led to a sharp interface with excellent adhesion, also achieved when coating pre-sintered tapes. In both cases, the substrates are dense and the coatings are porous, with thicknesses of 85 and 60 μm for green and pre-sintered tapes, respectively. No diffusion of Zr and Y occurs at the LSM layer, but some diffusion of La and Mn towards the YSZ layer takes place.

Potentiodynamic corrosion behavior and microstructural features of gas tungsten constricted arc (GTCA)-welded superalloy 718 joints

The gas tungsten constricted arc welding (GTCAW) process was used to join thin Su-718 alloy sheets to minimize alloying segregation and Laves phase precipitation in the fusion zone (FZ). The potentiodynamic corrosion behavior of GTCAW Su-718 alloy joints was studied and correlated to the microstructural features of welds. The potentiodynamic corrosion test was done in a 3.56 wt.-% NaCl solution to determine the corrosion rate of Su-718 alloy joints. The optical microscopy (OM) technique was used to analyze the microstructure of corroded weldments. The scanning electron microscopy (SEM) technique was used to study the Laves phase development in FZ. The SEM X-ray energy dispersive spectroscopy (EDS) technique was used to for elemental mapping of FZ. The corrosion resistance of Su-718 joints is inversely proportional to the precipitation of Laves phase in FZ. The GTCA welded Su-718 alloy joints disclosed superior corrosion resistance for the joints with lower Laves phase precipitation. It is correlated to the refining of FZ microstructure, which aids in minimizing the Laves phase precipitation. The joints with higher Laves phase precipitation revealed inferior corrosion resistance. It is attributed to coarsening of FZ microstructure, which raises the alloying segregation and leads to depletion of alloying elements in FZ. The dendritic core regions showed severe corrosion compared to the interdendritic regions. The corrosion resistance of GTCA welded Su-718 joints is better than that of CC-GTAW and PC-GTGAW joints and comparable to that of EBW and LBW joints. It refers to the arc constriction and high frequency current pulsation.

Development of a New Measure of Intergenerational Contact

Intergenerational relationships are a predictor of greater physical, mental, and emotional well-being; they can reduce ageism and facilitate feelings of purpose and meaning, shown to be important for health and mortality. Surprisingly there are no measures of intergenerational contact (IGC) shown to be reliable and valid across age groups. Therefore, we aimed to develop a psychometrically sound survey measure of IGC. We utilized a three-phase development process, which included a Delphi-style expert panel review of items, focus groups, and validation of the survey via Amazon MTurk. The resulting 18-item survey captures details on and comparisons between both familial and non-familial contact and is appropriate for adults of all ages. We conducted confirmatory factor analyses with the 9-item family and 9-item non-family subscales for 380 young and 256 middle-aged adults reporting on contact with older adults, and 348 older adults reporting on contact with younger adults. The family scale had good model fit across all three groups (χ2 (78) = 245.74, p<.0001; RMSEA = 0.08, 90% CI = [0.07, 0.10]; CFI = .94; TLI = .92). After covarying for 2 pairs of items among the middle-age group, the non-family scale had good model fit across all groups (χ2(75) = 217.21, p<.0001; RMSEA = 0.08, 90% CI = [0.07, 0.09]; CFI = .95; TLI = .93), indicating construct equivalence across age groups. The new IGC measure can be used in all adult age groups, making it useful for scientific projects as well as program evaluations. Funded by the RRF Foundation on Aging

From 2D and 3D documentation to 4D interpretation. Building archaeological conclusions and workflow strategies gained by remote study of Insula V 1, Pompeii

The text describes new methods elaborated for and used in the building archaeological assessment of a city block, studied first on site, then remotely by members of the Swedish Pompeii Project. Use of a digital platform, with collected wall observations and analysis, systematic photographic documentation of all standing structures, and 3D models, allowed discussion to proceed after the fieldwork came to an end. The models provided new possibilities and new angles of approach, e.g. examining walls at any given point, studying boundary walls as wall-strings in their full extent, allowing all kinds of sectioning at will, introducing bird’s-eye views as a new perspective in study, and measuring wherever needed. The joint results obtained are summed up in a four-phase development of the use of space: the earliest structures; the late Samnite building boom (2nd century BC); the colony (second half of 1st century BC); the imperial era (until AD 79). This narrative includes conclusions concerning building process and development of masonry techniques and on changes in way of life. Many results affect Pompeian archaeology in general. Results of particular importance concern the character of the early plot division and the understanding of the building process creating the double-atrium house of Caecilius Iucundus, including an anchorage in time for this creation in the Claudian period. The relatively small impact in terms of damage that may be ascribed the literary recorded earthquake of AD 62/63 is also worth noting. The text ends with a suggestion of a new workflow for insula studies.

TECHNOLOGY TRANSFER FROM R & D TO PRODUCTION AND ITS DOCUMENTATION IN PHARMACEUTICAL INDUSTRY: A REVIEW

Technology transfer plays a milestone in the pharmaceutical industry during the citation of drug discovery to drug product development. Technology transfer technique transferred from Research & Development (R&D) department to production department through the process of the research phase, development phase, and production phase for further product commercialization. This study was an attempt to discuss the reasons and importance of technology transfer, processing steps for technology transfer, and its documentation report. Establishing confirmation technique for all kinds of documentation and will be inspected and accepted by quality assurance department before the technologies reaches the production department. Hence, the proposed transferring technique will help to develop the product through the processes mentioned in the documentation report.

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.

Ecology of zoophilic flies in livestock biocenoses of Ukraine

In modern animal husbandry of Ukraine, there are still some unresolved issues related to the high number of zoophilic flies in the territories of facilities and the spread of animal infectious and parasitic diseases. A detailed study of bioecological peculiarities of the dominant zoophilic fly species contributes to improving the effectiveness of measures to control ectoparasites. 27 zoophilic fly species have been found in animal breeding complexes. The maximum number of parasitic Diptera species was recorded on cattle-keeping premises. The biological properties of Neomyia cornicina (Fabricius, 1781) (size, shape, colour, duration of preimaginal phase development) were studied. Also, we studied the dynamics of the number and daily activity of dominant fly species (Musca domestica Linnaeus, 1758, M. autumnalis De Geer, 1776, Stomoxys calcitrans (Linnaeus, 1758)). When studying the intraspecies competition, a high-degree survival of M. domestica and M. autumnalis was determined in the conditions of critical nutritional deficiency (0.5 g of nutrient medium per larva) and increased density of individuals (the imago emergence was 38.6% and 34.0%, respectively). In similar maintenance conditions, the emergence of N. cornicina imago was low (14.6%). With a two-fold increase in the insectarium volume and in the amount of nutrient medium (1 g per larva), the imago emergence of M. domestica, M. autumnalis and N. cornicina increased to 64.0%, 39.2%, and 24.0%, respectively. With an even greater increase in the amount of nutrient medium (2 g per larva), the maximum emergence of imagoes of all the studied fly species was observed (M. domestica, M. autumnalis, and N. cornicina: 96.6%, 91.2% and 72.6%, respectively). In the conditions of interspecific competition, M. autumnalis suppressed N. cornicina even in conditions of a sufficient amount of nutrient substrate. In the competition between M. domestica and M. autumnalis, house fly dominated. Increasing the nutrient medium volume narrowed the gap between the competing species.