Cookeperry3877

CRISPR-Cas13 systems have been developed for precise RNA editing, and can potentially be used therapeutically when temporary changes are desirable or when DNA editing is challenging. We have identified and characterized an ultrasmall family of Cas13b proteins-Cas13bt-that can mediate mammalian transcript knockdown. We have engineered compact variants of REPAIR and RESCUE RNA editors by functionalizing Cas13bt with adenosine and cytosine deaminase domains, and demonstrated packaging of the editors within a single adeno-associated virus.

Metastatic triple-negative breast cancer (mTNBC) is treated mainly with chemotherapy. However, resistance frequently occurs as tumours enter dormancy. Statins have been suggested as effective against cancer but as they prolong and promote dormancy, it is an open question of whether the concomitant use would interfere with chemotherapy in primary and mTNBC. We examined this question in animal models and clinical correlations.

We used a xenograft model of spontaneous metastasis to the liver from an ectopic tumour employing a mTNBC cell line. Atorvastatin was provided to sensitise metastatic cells, followed by chemotherapy. read more The effects of statin usage on outcomes in women with metastatic breast cancer was assessed respectively by querying a database of those diagnosed from 1999 to 2019.

Atorvastatin had limited influence on tumour growth or chemotherapy effects in ectopic primary tumours. Interestingly, atorvastatin was additive with doxorubicin (but not paclitaxel) when targeting liver metastases. E-cadherin-expressing, dormant, breast cancer cells were resistant to the use of either statins or chemotherapy as compared to wild-type cells; however, the combination of both did lead to increased cell death. Although prospective randomised studies are needed for validation, our retrospective clinical analysis suggested that patients on statin treatment could experience prolonged dormancy and overall survival; still once the tumour recurred progression was not affected by statin use.

Atorvastatin could be used during adjuvant chemotherapy and also in conjunction withmetastatic chemotherapy to reduce mTNBC cancer progression. These preclinical data establish a rationale for the development of randomised studies.

Atorvastatin could be used during adjuvant chemotherapy and also in conjunction with metastatic chemotherapy to reduce mTNBC cancer progression. These preclinical data establish a rationale for the development of randomised studies.

To compare the progression of posterior vitreous detachment (PVD) between eyes that underwent cataract surgery and eyes that did not undergo surgery in non-highly myopic patients.

One-hundred twenty-five eyes of 125 patients scheduled for phacoemulsification and 125 eyes of 125 age-matched patients who did not undergo surgery were enrolled. PVD status was evaluated using swept-source optical coherence tomography at 2 days (baseline), and 1, 3, 6, and 12 months postoperatively, and classified into five stages 0 (no), 1 (paramacular), 2 (perifoveal), 3 (peripapillary), and 4 (complete). The PVD stage and incidence of progression to complete PVD were compared between groups.

The mean PVD stage significantly progressed over the 12 months in the surgery group (P = 0.0004), but did not change significantly in the non-surgery group. The PVD stage did not differ significantly between groups at 2 days, or 1, 3, and 6 months postoperatively, but was significantly more progressed in the surgery group than in the non-surgery group at 12 months (P = 0.0390). After adjusting for age, sex, axial length, and baseline PVD stage, the relative risk for progression to complete PVD was 7.1-fold higher in the surgery group than in the non-surgery group (P < 0.0001, 95% confidence interval 2.9-17.3).

PVD progressed significantly faster in eyes after cataract surgery compared with eyes that did not undergo surgery, and the relative risk of progression to complete PVD was approximately seven-fold higher within 1 year, indicating that the risk for PVD-related diseases is high after cataract surgery.

PVD progressed significantly faster in eyes after cataract surgery compared with eyes that did not undergo surgery, and the relative risk of progression to complete PVD was approximately seven-fold higher within 1 year, indicating that the risk for PVD-related diseases is high after cataract surgery.

Fundus autofluorescence (AF) using adaptive optics scanning laser ophthalmoscopy (AOSLO) enables morphometric analysis of individual retinal pigmented epithelial (RPE) cells. However, only a few excitation wavelengths in the visible and near-infrared have been evaluated. Visible light excitation (<600 nm) presents additional safety hazards and is uncomfortable for patients. Near-infrared excitation (>700 nm) overcomes those problems but introduces others, including decreased AF signal and cone signatures that obscure RPE structure. Here we investigated the use of an intermediate wavelength, 663 nm, for excitation and compared it to 795 nm.

Subjects were imaged using AOSLO equipped with a detection channel to collect AF emission between 814 and 850 nm. Two light sources (663 and 795 nm) were used to excite the retinal fluorophores. We recorded 90 s videos and registered them with custom software to integrate AF images for analysis.

We imaged healthy eyes and an eye with pattern dystrophy. Similar Athat balance efficiency, patient comfort, and efficacy.

To examine the relationship of visual function as assessed by visual acuity, contrast sensitivity, and multifocal electroretinography (mfERG) to macular structural and microvascular measures on optical coherence tomography (OCT) and angiography (OCTA) in individuals with diabetes.

This is a prospective observational study conducted at a tertiary eye care centre in India. Right eyes of 121 adults with type 2 diabetes with no diabetic retinopathy (DR), mild or moderate nonproliferative DR (NPDR) were examined. Severe NPDR, proliferative DR and diabetic macular oedema were excluded. Participants underwent assessment of glycated haemoglobin (HbA

), blood pressure, best corrected visual acuity (LogMAR), contrast sensitivity (CS), mfERG, ultrawide field fundus photography, OCT and OCTA. Correlations were assessed by Spearman's rank correlation (rho).

Of the total of 121 eyes, 89 had No DR, 32 had mild to moderate NPDR. In the No DR group, the LogMAR acuity was significantly and negatively correlated to central subfoveal thickness (CST) (rho = -0.420), macular vessel density (rho = -0.270) and perfusion (rho = -0.270). (ii) Contrast sensitivity correlated to foveal avascular zone circularity (rho = 0.297); (iii) mfERG P1 response densities were better with higher macular perfusion index (rho = 0.240). In the NPDR group, the LogMAR acuity also showed a significant negative correlation to CST (rho = -0.379). Other correlations were not significant.

Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

The aim of this study was to investigate the relationship between keratoconus disease and the antioxidant activities of catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD) and the level of the oxidative stress marker malondialdehyde (MDA) in serum.

The study included 50 patients diagnosed with keratoconus and 53 healthy age- and sex-matched control subjects. The keratoconus patients were grouped according to the four keratoconus stages based on the modified Krumeich keratoconus classification system. The CAT, GSH and SOD activities and MDA levels in the serum samples collected from the patient and control groups were compared.

The mean serum CAT, GSH, SOD and MDA levels in the keratoconus group were determined to be 0.075 (0.074-0.078)U/L, 0.002 (0.001-0.006) mmol/ml, 1.56 (1.51-1.62)U/L and 1.69 (1.65-1.99) mmol/L, respectively, and those in the control group were determined to be 0.024 (0.013-0.037)U/L, 0.029 (0.018-0.049) mmol/ml, 4.13 (4.01-4.17) U/L and 0.74 (0.65-0.82) mmol/L. The serum GSH levels and SOD activity were significantly lower in the keratoconus group (p < 0.001 for both) than in the control group while the CAT activity and MDA levels were significantly higher (p < 0.001 for both).

The low serum GSH levels and SOD activity and the high CAT activity and MDA levels observed in this study suggest the presence of oxidative stress and inadequate antioxidant defence mechanisms in keratoconus patients. The studied parameters may offer auxiliary markers for use in the diagnosis and treatment of the keratoconus disease and in its potential therapeutic targets in the future.

The low serum GSH levels and SOD activity and the high CAT activity and MDA levels observed in this study suggest the presence of oxidative stress and inadequate antioxidant defence mechanisms in keratoconus patients. The studied parameters may offer auxiliary markers for use in the diagnosis and treatment of the keratoconus disease and in its potential therapeutic targets in the future.

Ophthalmic disorders cause 8% of hospital clinic attendances, the highest of any specialty. The fundamental need for a distance visual acuity (VA) measurement constrains remote consultation. A web-application, DigiVis, facilitates self-assessment of VA using two internet-connected devices. This prospective validation study aimed to establish its accuracy, reliability, usability and acceptability.

In total, 120 patients aged 5-87 years (median = 27) self-tested their vision twice using DigiVis in addition to their standard clinical assessment. Eyes with VA worse than +0.80 logMAR were excluded. Accuracy and test-retest (TRT) variability were compared using Bland-Altman analysis and intraclass correlation coefficients (ICC). Patient feedback was analysed.

Bias between VA tests was insignificant at -0.001 (95% CI -0.017 to 0.015) logMAR. The upper limit of agreement (LOA) was 0.173 (95%CI 0.146 to 0.201) and the lower LOA -0.175 (95% CI -0.202 to -0.147) logMAR. The ICC was 0.818 (95% CI 0.748 to 0.869). DigiVis TRT mean bias was similarly insignificant, at 0.001 (95% CI -0.011 to 0.013) logMAR, the upper LOA was 0.124 (95% CI 0.103 to 0.144) and the lower LOA -0.121 (95% CI -0.142 to -0.101) logMAR. The ICC was 0.922 (95% CI 0.887 to 0.946). 95% of subjects were willing to use DigiVis to monitor vision at home.

Self-tested distance VA using DigiVis is accurate, reliable and well accepted by patients. The app has potential to facilitate home monitoring, triage and remote consultation but widescale implementation will require integration with NHS databases and secure patient data storage.

Self-tested distance VA using DigiVis is accurate, reliable and well accepted by patients. The app has potential to facilitate home monitoring, triage and remote consultation but widescale implementation will require integration with NHS databases and secure patient data storage.