By means of two supramolecular systems—peptide amphiphiles engaged in hydrogen-bonded β-sheets, and chromophore amphiphiles driven to assemble by π-orbital overlaps—we show that the minima in the energy landscapes of supramolecular systems are defined by electrostatic repulsion and the ability of the dominant attractive forces to trap molecules in thermodynamically unfavourable configurations. These competing interactions can be selectively switched on and off, with the order of doing so determining the position of the final product in the energy landscape. Within the same energy landscape, the peptide-amphiphile system forms a thermodynamically favoured product characterized by long bundled fibres that promote biological cell adhesion and survival, and a metastable product characterized by short monodisperse fibres that interfere with adhesion and can lead to cell death. Our findings suggest that, in supramolecular systems, functions and energy landscapes are linked, superseding the more traditional connection between molecular design and function.
We describe in this work the synthesis of microparticles with a doxorubicin drug conjugated alginate core and a shell of peptide amphiphile nanofibres functionalized for targeting the folate receptor.
In the modern era, patients often resort to the internet for answers to their health-related concerns, and clinics face challenges to providing timely response to patient concerns. This has led to a need to investigate the capabilities of AI chatbots for ophthalmic diagnosis and triage. In this in silico study, 80 simulated patient complaints in ophthalmology with varying urgency levels and clinical descriptors were entered into both ChatGPT and Bard in a systematic 3-step submission process asking chatbots to triage, diagnose, and evaluate urgency. Three ophthalmologists graded chatbot responses. Chatbots were significantly better at ophthalmic triage than diagnosis (90.0% appropriate triage vs. 48.8% correct leading diagnosis; p < 0.001), and GPT-4 performed better than Bard for appropriate triage recommendations (96.3% vs. 83.8%; p = 0.008), grader satisfaction for patient use (81.3% vs. 55.0%; p < 0.001), and lower potential harm rates (6.3% vs. 20.0%; p = 0.010). More descriptors improved the accuracy of diagnosis for both GPT-4 and Bard. These results indicate that chatbots may not need to recognize the correct diagnosis to provide appropriate ophthalmic triage, and there is a potential utility of these tools in aiding patients or triage staff; however, they are not a replacement for professional ophthalmic evaluation or advice.
Purpose: To investigate the relationship between disruption in different photoreceptor layers and deep capillary plexus (DCP) telangiectasias in eyes with macular telangiectasia type 2 (MacTel). Methods: 35 eyes (21 patients) with MacTel imaged with optical coherence tomography angiography (OCTA) were included. Circumscribed areas of DCP telangiectasia were traced from OCTA slabs and the corresponding spectral-domain OCT (SD-OCT) slabs were used to visualize the photoreceptor layer interdigitation zone (IZ) and ellipsoid zone (EZ). IZ attenuation, IZ loss, and EZ loss were graded by reviewing en face SD-OCT slabs for hypo-reflective areas and confirming their status on cross-sectional views. Total area of photoreceptor disruption and overlap with DCP telangiectasia were evaluated with respect to OCT-based MacTel stage. Longitudinal changes were evaluated in a subset of patients with follow-up imaging. Results: Overlap of DCP telangiectasia with IZ attenuation significantly decreased with MacTel severity, while overlap with IZ and EZ loss significantly increased. Overlap with IZ loss peaked in moderate MacTel (Stages 3–5). Longitudinal imaging showed that new EZ loss at 6 months was largely predicted by baseline IZ loss. Conclusions: Worsening MacTel severity is characterized by greater overlap between DCP telangiectasia and zones of increasing severity of photoreceptor disruption, with EZ loss enlarging over time within areas of preexisting IZ disruption. We suggest that IZ disruption may indicate early photoreceptor dysfunction that eventually progresses to EZ loss, with IZ loss being a more reliable metric than IZ attenuation. Additional studies will be necessary to further explore long-term photoreceptor changes and evaluate their relationship with visual function in MacTel.
In this cross-sectional observational study, we investigated the relationship between photoreceptor layer disruption and telangiectasia in patients diagnosed with early stage macular telangiectasia type 2 (MacTel). A total of 31 eyes (17 patients) with MacTel were imaged with adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography angiography (OCTA). Confocal AOSLO was used to visualize dark regions of nonwaveguiding outer segments, which we refer to as “photoreceptor lesions”. En-face OCTA images of the deep capillary plexus (DCP) were used in conjunction with confocal AOSLO to evaluate the topographic relationship between areas of capillary telangiectasias and photoreceptor lesions. Among seven eyes with early stage MacTel (stage 0–2 based on OCT), we identified ten photoreceptor lesions, all of which were located within parafoveal quadrants containing DCP telangiectasia on OCTA. Seven of the lesions corresponded to the intact ellipsoid zone on spectral-domain OCT (SD-OCT), and three of these also corresponded to the intact interdigitation zone. This work demonstrates a topographic relationship between AOSLO photoreceptor lesions and DCP telangiectasias, and it also suggests that these lesions with normal SD-OCT appearance may represent areas of photoreceptors at risk for dysfunction. Thus, confocal AOSLO may have a meaningful role in detecting early photoreceptor abnormalities in eyes with MacTel.
Objectives: To evaluate whether an institutionally created video-based educational module will improve obstetrics and gynecology residents’ understanding of surgical anatomy and principles for performing abdominal hysterectomy. Secondary aims included evaluating the trainees’ confidence levels and perceptions before and after the educational experience and ultimately implementing the module...