Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT.

Long-Term Outcomes After Melody Transcatheter Pulmonary Valve Replacement in the US Investigational Device Exemption Trial.

Background: The Melody valve was developed to extend the useful life of previously implanted right ventricular outflow tract (RVOT) conduits or bioprosthetic pulmonary valves, while preserving RV function and reducing the lifetime burden of surgery for patients with complex congenital heart disease.

Methods: Enrollment for the US Investigational Device Exemption study of the Melody valve began in 2007. Extended follow-up was completed in 2020.

A Novel Selective PKR Inhibitor Restores Cognitive Deficits and Neurodegeneration in Alzheimer Disease Experimental Models.

In Alzheimer disease (AD), the double-strand RNA-dependent kinase protein kinase R (PKR )/EIF2AK2 is activated in brain with increased phosphorylation of its substrate eukaryotic initiation factor 2 (eIF2). AD risk-promoting factors, such as ApoE4 allele or the accumulation of neurotoxic amyloid- oligomers (AOs), have been associated with activation of PKR-dependent signaling. Here, we report the discovery of a novel potent and selective PKR inhibitor (SAR439883) and demonstrate its neuroprotective pharmacological activity in AD experimental models.

Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

Background: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons.

Methods: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHADS-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication.

How the COVID-19 pandemic will change the future of critical care.

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness.

Two neurologic facets of CTLA4-related haploinsufficiency.

Objective: To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 () haploinsufficiency.

Methods: Three patients from 2 families had neurologic manifestations in the context of haploinsufficiency. Their clinical and MRI findings are presented.

Synergistic Antiproliferative Activity of the RAD51 Inhibitor IBR2 with Inhibitors of Receptor Tyrosine Kinases and Microtubule Protein.

Although cancer cell genetic instability contributes to characteristics that mediate tumorigenicity, it also contributes to the tumor-selective toxicity of some chemotherapy drugs. This synthetic lethality can be enhanced by inhibitors of DNA repair. To exploit this potential Achilles heel, we tested the ability of a RAD51 inhibitor to potentiate the cytotoxicity of chemotherapy drugs.

Methylprednisolone Does Not Reduce Persistent Pain after Cardiac Surgery.

Background: Persistent incisional pain is common after cardiac surgery and is believed to be in part related to inflammation and poorly controlled acute pain. Methylprednisolone is a corticosteroid with substantial antiinflammatory and analgesic properties and is thus likely to ameliorate persistent surgical pain. Therefore, the authors tested the primary hypothesis that patients randomized to methylprednisolone have less persistent incisional pain than those given placebo.

Unusual uses of holes--with input from biology.

This short review, some of it covering work not otherwise published in a peer-reviewed journal, is not meant to be exhaustive but rather to highlight some mechanical influences of holes that are apparently not much used in engineering. Apart from initiating fracture, holes can, if judiciously placed and of the right dimensions, improve the durability of a material or structure and generate information about its state of strain. By increasing the morphological complexity of the structure, they can also increase the potential for multifunctionality.

Biomimetics--a review.

Biology can inform technology at all levels (materials, structures, mechanisms, machines, and control) but there is still a gap between biology and technology. This review itemizes examples of biomimetic products and concludes that the Russian system for inventive problem solving (teoriya resheniya izobreatatelskikh zadatch (TRIZ)) is the best system to underpin the technology transfer. Biomimetics also challenges the current paradigm of technology and suggests more sustainable ways to manipulate the world.

Biomimetics: its practice and theory.

Biomimetics, a name coined by Otto Schmitt in the 1950s for the transfer of ideas and analogues from biology to technology, has produced some significant and successful devices and concepts in the past 50 years, but is still empirical. We show that TRIZ, the Russian system of problem solving, can be adapted to illuminate and manipulate this process of transfer. Analysis using TRIZ shows that there is only 12% similarity between biology and technology in the principles which solutions to problems illustrate, and while technology solves problems largely by manipulating usage of energy, biology uses information and structure, two factors largely ignored by technology.

Systematic technology transfer from biology to engineering.

Solutions to problems move only very slowly between different disciplines. Transfer can be greatly speeded up with suitable abstraction and classification of problems. Russian researchers working on the TRIZ (Teoriya Resheniya Izobretatelskikh Zadatch) method for inventive problem solving have identified systematic means of transferring knowledge between different scientific and engineering disciplines.

Deconstructing the design of a biological material.

By identifying the functional conflicts in its design, the cuticle of arthropods can be shown to cope with IR and UV irradiation in the same manner as our technology-by controlling spectral properties (transmission and reflection). However, the skeletal properties of cuticle are integrated with demands for sensory transmission, movement, etc, by controlling the local properties of the material rather than by changing global parameters (which would be the technical solution). On the basis of this study, the biomimetic similarity of cuticle with technology is only about 20%, suggesting that we can learn from the design of arthropod cuticle.

Biomimetic modelling.

Biomimetics is seen as a path from biology to engineering. The only path from engineering to biology in current use is the application of engineering concepts and models to biological systems. However, there is another pathway: the verification of biological mechanisms by manufacture, leading to an iterative process between biology and engineering in which the new understanding that the engineering implementation of a biological system can bring is fed back into biology, allowing a more complete and certain understanding and the possibility of further revelations for application in engineering.

From cellulose to cell.

The cell wall is often pictured as a more-or-less random feltwork of cellulose microfibrils in association with other polysaccharide and protein complexes. There is evidence from morphology, morphogenesis and mechanics that the structures in the cell wall are far more regular and that their interactions are driven by their chemical and morphological properties. In particular, a model based on liquid crystal structures has more than morphological implications.