Outcomes of urgent coronary artery bypass grafting in patients who have recently recovered from COVID-19 infection, with a median follow-up period of twelve months: our experience.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) was declared a worldwide pandemic in 2020 by the World Health Organization (WHO). Certain individuals are at higher risk, (age > 65 years, pre-existing lung or heart conditions, diabetes and obesity) especially those requiring cardiac surgery, including Coronary Artery Bypass Grafting (CABG). Here we present a case series of 11 patients, operated between April 2020 and April 2022, all of whom had recently recovered from COVID-19, who presented with unstable angina, and therefore required urgent Coronary Artery Bypass Grafting (CABG). Similar cases reported in the past, have had a high morbidity and mortality rate. CASE PRESENTATION: The study included 11 males, and their age varied between 53 and 68 years (median of 65 years). They were either partially or fully vaccinated. All of them had a history of recent mild COVID-19 infection. The European system for cardiac operative risk evaluation, EuroSCORE II in-hospital mortality risk at admission, varied between 1.48% and 5.12%. Six out of 11 patients (54.55%) had a recent Acute Coronary Syndrome (ACS) which is associated with a higher risk and poor prognosis. All of them underwent urgent CABG (10 of them, 90.91% cases, using the off-pump technique and one patient had to be converted to the on-pump beating heart surgery technique during surgery). Ten of the 11 patients were operated using the off-pump technique, and there was one death (9.09%). All surviving patients made an uneventful recovery and have been followed up with a median follow-up period of 12 months. CONCLUSIONS: Previous studies on a similar group of patients have resulted in high morbidity and mortality. A conscious effort was made to perform all surgeries off-pump, thereby eliminating the inflammatory effects and other hazards of cardiopulmonary bypass in this case series, with only one out of 11 (9.09%) being converted to the on-pump beating heart technique due to the hemodynamic instability faced during surgery. Our findings show a mortality rate of 9.09%, with the surviving patients doing well at a median follow-up period of 12 months, suggesting that it is a safe procedure in this patient subset.

Threshold vision under full-field stimulation: Revisiting the minimum number of quanta necessary to evoke a visual sensation.

At the absolute threshold of vision, Hecht, Shlaer and Pirenne estimate that 5-14 photons are absorbed within a retinal area containing ~500 rods. Other estimates of scotopic threshold vision based on stimuli with different durations and focal areas range up to ~100,000 photons. Given that rod density varies with retinal eccentricity and the magnitude of the intrinsic noise increases with increasing stimulus area and duration, here we determine whether the scotopic threshold estimates with focal stimuli can be extended to full-field stimulation and whether summation explains inter-study differences. We show that full-field threshold vision (~1018 mm2, 10 ms duration) is more sensitive than at absolute threshold, requiring the absorption of ~1000 photons across ~91.96 million rods. A summation model is presented integrating our and published data and using a nominal exposure duration, criterion frequency of seeing, rod density, and retinal area that largely explains the inter-study differences and allows estimation of rods per photon ratio for any stimulus size and duration. The highest signal to noise ratio is defined by a peak rod convergence estimated at 53:4:1:2 (rods:rod bipolar cells:AII amacrine cells:retinal ganglion cells), in line with macaque anatomical estimates that show AII amacrine cells form the bottleneck in the rod pathway to set the scotopic visual limit. Our model estimations that the rods per photon ratio under full-field stimulation is ~3000X higher than at absolute threshold are in accordance with visual summation effects and provide an alternative approach for understanding the limits of scotopic vision.

Melanopsin hypersensitivity dominates interictal photophobia in migraine.

PURPOSE: To define the melanopsin and cone luminance retinogeniculate pathway contributions to photophobia in healthy controls and migraineurs. METHODS: Healthy controls and migraineurs were categorized according to the International Classification of Headache Disorders criteria. Photophobia was measured under full-field illumination using electromyography in response to narrowband lights spanning the melanopsin and cone luminance action spectra. Migraineurs were tested during their interictal headache-free period. Melanopsin-mediated post-illumination pupil responses quantified intrinsically photosensitive Retinal Ganglion Cell (ipRGC) function. RESULTS: A model combining the melanopsin and cone luminance action spectra best described photophobia thresholds in controls and migraineurs; melanopsin contributions were ∼1.5× greater than cone luminance. In the illumination range causing photophobia, migraineurs had lower photophobia thresholds (∼0.55 log units; p < 0.001) and higher post-illumination pupil response amplitudes (p = 0.03) than controls. CONCLUSION: Photophobia is driven by melanopsin and cone luminance inputs to the cortex via the retino-thalamocortical pathway. In migraineurs, lower photophobia thresholds reflect hypersensitivity of ipRGC and cone luminance pathways, with the larger and prolonged post-illumination pupil response amplitude indicative of a supranormal melanopsin response. Our findings inform artificial lighting strategies incorporating luminaires with low melanopsin excitation and photopic luminance to limit the lighting conditions leading to photophobia.

Rhodopsin and melanopsin contributions to human brightness estimation.

We examined the contributions of rhodopsin and melanopsin to human brightness estimation under dim lighting. Absolute brightness magnitudes were estimated for full-field, rhodopsin-, or melanopsin-equated narrowband lights (${\lambda _{\rm max}}:\;{462}$λmax:462, 499, 525 nm). Our data show that in scotopic illumination ($ - {5.1}$-5.1 to $ - {3.9}\;{\log}\;\unicode{x00B5} {\rm Watts}\cdot{\rm cm}^{ - 2}$-3.9logµWatts⋅cm-2), the perceptual brightness estimates of rhodopic irradiance-equated conditions are independent of their corresponding melanopic irradiance, whereas brightness estimates with melanopic irradiance-equated conditions increase with increasing rhodopic irradiance. In mesopic illumination ($ - {3.4}$-3.4 to $ - {1.9}\;{\log}\;\unicode{x00B5} {\rm Watts}\cdot{\rm cm}^{ - 2}$-1.9logµWatts⋅cm-2), the brightness estimates with both lighting conditions increase with increasing rhodopic or melanopic irradiances. Rhodopsin activation therefore entirely signals scotopic brightness perception and plateaus in mesopic illumination where intrinsic melanopsin contributions become first evident. We infer that all photoreceptor signals are transmitted to higher visual centers for representing scene brightness in scotopic and mesopic illumination through both conventional and melanopsin ganglion cell pathways.

Methods to Induce Chronic Ocular Hypertension: Reliable Rodent Models as a Platform for Cell Transplantation and Other Therapies.

Glaucoma, a form of progressive optic neuropathy, is the second leading cause of blindness worldwide. Being a prominent disease affecting vision, substantial efforts are being made to better understand glaucoma pathogenesis and to develop novel treatment options including neuroprotective and neuroregenerative approaches. Cell transplantation has the potential to play a neuroprotective and/or neuroregenerative role for various ocular cell types (e.g., retinal cells, trabecular meshwork). Notably, glaucoma is often associated with elevated intraocular pressure, and over the past 2 decades, several rodent models of chronic ocular hypertension (COH) have been developed that reflect these changes in pressure. However, the underlying pathophysiology of glaucoma in these models and how they compare to the human condition remains unclear. This limitation is the primary barrier for using rodent models to develop novel therapies to manage glaucoma and glaucoma-related blindness. Here, we review the current techniques used to induce COH-related glaucoma in various rodent models, focusing on the strengths and weaknesses of the each, in order to provide a more complete understanding of how these models can be best utilized. To so do, we have separated them based on the target tissue (pre-trabecular, trabecular, and post-trabecular) in order to provide the reader with an encompassing reference describing the most appropriate rodent COH models for their research. We begin with an initial overview of the current use of these models in the evaluation of cell transplantation therapies.

Can Corneal Biomechanical Properties Explain Difference in Tonometric Measurement in Normal Eyes?

SIGNIFICANCE: Corneal biomechanical parameters can affect intraocular pressure (IOP) measurements by different tonometers compared with Goldmann applanation tonometer. This study implies that corneal hysteresis (CH) and corneal resistance factor (CRF) better explain variability in IOP measurements. PURPOSE: The aim of this study was to evaluate the effect of corneal properties on the difference in IOP measured by the Ocular Response Analyzer (ORA), Rebound Tonometer (RBT), Dynamic Contour Tonometer (DCT), and Tono-Pen from the Goldmann applanation tonometer (GAT). METHODS: An observational study was done on healthy participants in a tertiary eye care center. Corneal curvature was measured with a manual keratometer prior to IOP measurements. Intraocular pressure was measured by a single trained examiner with ORA, RBT, DCT, GAT, and Tono-Pen. CH and CRF were measured using the ORA. Central corneal thickness was measured using the ultrasonic pachymeter. Only the right eye was included for analysis. One-way analysis of variance was performed to compare variables, Bland-Altman plots to assess agreement, and regression analyses to study associated factors. RESULTS: We included 82 eyes of 82 participants with a mean age of 40.9 (14.3) years. Mean ± SD DCT IOP (15.22 ± 1.98) mmHg was significantly higher than GAT IOP (13.73 ± 2.42) (P = .01) and ORA Goldmann correlated IOP (13.66 ± 3.16) (P = .003). The limits of agreement between GAT and other tonometers measurements ranged between -5.0 and 2.1 mmHg. With multiple linear regression analyses, CH and CRF were found to be associated with the measured IOP differences between GAT and ORA (corneal compensated IOP and Goldmann correlated IOP) (P < .001) and DCT (P = .014, <.001) whereas differences between GAT and RBT measurements were independently explained by corneal curvature (P = .035) and central corneal thickness (P = .045). CONCLUSIONS: There was good agreement between GAT and other tonometers, but was not good enough for them to be used interchangeably. A combination of CH and CRF may better explain the variability between GAT and tonometers.

Modification of foxtail millet starch by combining physical, chemical and enzymatic methods.

Modification of foxtail millet starch was carried out by heat moisture treatment (HT), acid hydrolysis (AH), enzymatic treatment (EH), Ultrasound treatment (UT) and their combinations. A total of 15 modified starches were prepared by combining the various methods and properties were compared with native starch. The solubilities of the starches modified by HT were found to decrease whereas for other single modifications it increased. It also increased with number of modifications applied. The swelling power decreased for all the modified starches and a decrease in swelling power was observed with increase in number of modifications. Freeze-thaw stability improved for starches modified by single physical modifications i.e. HT and UT. Decrease in viscosities was observed for the modified starches and was particularly affected by AH. The pasting temperature was found to increase for those modified starches where HT was carried out. The modified starches gave softer gels.

Single molecule studies of force-induced S2 site exposure in the mammalian Notch negative regulatory domain.

Notch signaling in metazoans is responsible for key cellular processes related to embryonic development and tissue homeostasis. Proteolitic cleavage of the S2 site within an extracellular NRR domain of Notch is a key early event in Notch signaling. We use single molecule force-extension (FX) atomic force microscopy (AFM) to study force-induced exposure of the S2 site in the NRR domain from mouse Notch 1. Our FX AFM measurements yield a histogram of N-to-C termini lengths, which we relate to conformational transitions within the NRR domain. We detect four classes of such conformational transitions. From our steered molecular dynamics (SMD) results, we associate first three classes of such events with the S2 site exposure. AFM experiments yield their mean unfolding forces as 69 ± 42, 79 ± 45, and 90 ± 50 pN, respectively, at 400 nm/s AFM pulling speeds. These forces are matched by the SMD results recalibrated to the AFM force loading rates. Next, we provide a conditional probability analysis of the AFM data to support the hypothesis that a whole sequence of conformational transitions within those three clases is the most probable pathway for the force-induced S2 site exposure. Our results support the hypothesis that force-induced Notch activation requires ligand binding to exert mechanical force not in random but in several strokes and over a substantial period of time.

Complete noise analysis of a simple force spectroscopy AFM setup and its applications to study nanomechanics of mammalian Notch 1 protein.

We describe a complete noise analysis and application of a custom made AFM force spectroscopy setup on pulling a recombinant protein with an NRR domain of mouse Notch 1. Our table top AFM setup is affordable, has an open architecture, and is easily transferable to other laboratories. Its calculated noise characteristics are dominated by the Brownian noise with 2% non-Brownian components integrated over the first thermally induced resonance of a typical cantilever. For a typical SiN cantilever with a force constant of ~15 pN nm(-1) and in water the force sensitivity and resolution are less than 10 pN, and the corresponding deflection sensitivities are less than 100 pm Hz(-1/2). Also, we obtain a sub-ms time resolution in detecting the protein length change, and only few ms cantilever response times as measured in the force clamp mode on a well-known protein standard. Using this setup we investigate force-induced conformational transitions in the NRR region of a mouse Notch 1. Notch is an important protein related to leukemia and breast cancers in humans. We demonstrate that it is feasible to develop AFM-based studies of the force-induced conformational transitions in Notch. Our results match recent steered molecular dynamics simulations of the NRR unfolding and constitute a first step towards a detailed study of Notch activation with AFM.