Mechanisms by Which SARS-CoV-2 Invades and Damages the Central Nervous System: Apart from the Immune Response and Inflammatory Storm, What Else Do We Know?

Initially reported as pneumonia of unknown origin, COVID-19 is increasingly being recognized for its impact on the nervous system, despite nervous system invasions being extremely rare. As a result, numerous studies have been conducted to elucidate the mechanisms of nervous system damage and propose appropriate coping strategies. This review summarizes the mechanisms by which SARS-CoV-2 invades and damages the central nervous system, with a specific focus on aspects apart from the immune response and inflammatory storm. The latest research findings on these mechanisms are presented, providing new insights for further in-depth research.

Long-term outcomes after acute primary angle closure: case series from Moorfields Eye Hospital, UK.

BACKGROUND: There is limited data regarding the morbidity and progression to primary angle closure glaucoma in those presenting with acute primary angle closure (APAC) in the UK. We aim to report on the vision and intraocular pressure (IOP) outcomes and treatment required after an APAC episode and to identify any risk factors that could predict worse outcomes. METHODS: A retrospective observational case series review including 117 consecutive patients (121 eyes) attending Moorfields Eye Hospital, at a tertiary referral unit in the UK, with APAC was performed. RESULTS: Most patients (73%) had visual acuities of ≥6/12, meeting the UK driving standard, at the final follow-up. Only 15% (17 eyes) had severe visual impairment, as defined by the WHO, in the affected eye, of which 6.6% (eight eyes) were due to glaucoma. The delayed presentation was linked to a higher need for further medical treatment (OR=2.83, 95% CI 1.09 to 7.40, p=0.03). Patients who underwent phacoemulsification were at lower risk of having blindness in the affected eye (OR 0.18, 95% CI 0.05 to 0.69, p=0.01), having elevated IOP (OR 0.10, 95% CI 0.01 to 0.75, p=0.02) or requiring further medical treatment (OR 0.34, 95% CI 0.12 to 0.99, p=0.04). Older age (OR 1.26, 95% CI 1.08 to 1.48, p<0.01) was associated with worse visual outcomes. CONCLUSIONS: APAC causes low long-term visual and treatment morbidity in this largely Caucasian patient group in the UK. Phacoemulsification as a treatment may enhance visual outcomes and reduce the need for further IOP-lowering treatment.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

OBJECTIVE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and to determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age 57 years, 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score (PRS) comprising 2 673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, optical coherence tomography derived macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a one standard deviation increase in UNa:Cr was associated with higher IOP (0.14mmHg; 95% CI, 0.12 to 0.17; P<0.001) and greater prevalence of glaucoma (OR, 1.11; 95% CI, 1.07 to 1.14; P<0.001), but not mRNFL or GCIPL thickness. Compared to those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45mmHg; 95% CI, 0.36 to 0.53, P<0.001) and prevalence of glaucoma (OR, 1.30; 95% CI, 1.17 to 1.45; P<0.001). Stronger associations with glaucoma (P interaction=0.001) were noted in participants with a higher glaucoma PRS. CONCLUSIONS: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation as they may have important clinical and public health implications.

Structural correlations between brain magnetic resonance image-derived phenotypes and retinal neuroanatomy.

BACKGROUND AND PURPOSE: The eye is a well-established model of brain structure and function, yet region-specific structural correlations between the retina and the brain remain underexplored. Therefore, we aim to explore and describe the relationships between the retinal layer thicknesses and brain magnetic resonance image (MRI)-derived phenotypes in UK Biobank. METHODS: Participants with both quality-controlled optical coherence tomography (OCT) and brain MRI were included in this study. Retinal sublayer thicknesses and total macular thickness were derived from OCT scans. Brain image-derived phenotypes (IDPs) of 153 cortical and subcortical regions were processed from MRI scans. We utilized multivariable linear regression models to examine the association between retinal thickness and brain regional volumes. All analyses were corrected for multiple testing and adjusted for confounders. RESULTS: Data from 6446 participants were included in this study. We identified significant associations between volumetric brain MRI measures of subregions in the occipital lobe (intracalcarine cortex), parietal lobe (postcentral gyrus), cerebellum (lobules VI, VIIb, VIIIa, VIIIb, and IX), and deep brain structures (thalamus, hippocampus, caudate, putamen, pallidum, and accumbens) and the thickness of the innermost retinal sublayers and total macular thickness (all p < 3.3 × 10-5). We did not observe statistically significant associations between brain IDPs and the thickness of the outer retinal sublayers. CONCLUSIONS: Thinner inner and total retinal thicknesses are associated with smaller volumes of specific brain regions. Notably, these relationships extend beyond anatomically established retina-brain connections.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

Consistency Analysis of Programmed Death Ligand 1 Expression in Non-Small Cell Lung Cancer Between Pleural Effusion and Matched Primary Lung Cancer Tissues by Immunohistochemical Double Staining.

In clinical practice, programmed death ligand 1 (PD-L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD-L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD-L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD-L1 expression using 3 cutoffs (1%, 10%, and 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's κ = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ = 0.53), 78.9% (10%, Cohen's κ = 0.574), and 95.6% (50%, Cohen's κ = 0.754). The rates of PD-L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD-L1-positive tumor cells on a background with nonspecific staining. In conclusion, PD-L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD-L1 when histological specimens are unattainable, especially when PD-L1 expression is >50%. PD-L1 positivity rates were higher in MPE. Double staining can improve PD-L1 detection by reducing false-negative/positive results.

Synthesis and Antitumor Activity Evaluation of Novel Echinatin Derivatives with a 1,3,4-Oxadiazole Moiety.

A series of novel echinatin derivatives with 1,3,4-oxadiazole moieties were designed and synthesized. Most of the newly synthesized compounds exhibited moderate antiproliferative activity against the four cancer cell lines. Notably, Compound T4 demonstrated the most potent activity, with IC50 values ranging from 1.71 µM to 8.60 µM against the four cancer cell lines. Cell colony formation and wound healing assays demonstrated that T4 significantly inhibited cell proliferation and inhibited migration. We discovered that T4 exhibited moderate binding affinity with the c-KIT protein through reverse docking. The results were effectively validated through subsequent molecular docking and c-KIT enzyme activity assays. In addition, Western blot analysis revealed that T4 inhibits the phosphorylation of downstream proteins of c-KIT. The results provide valuable inspiration for exploring novel insights into the design of echinatin-related hybrids as well as their potential application as c-KIT inhibitors to enhance the efficacy of candidates.

The detection of PD-L1 expression on liquid-based cytology in pleural effusion of lung adenocarcinoma and its prognostic evaluation: Between paired liquid-based cytology and cell block samples.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression levels measured by immunohistochemistry have been proven to predict the outcome of immunotherapy in lung adenocarcinoma (LUAD). However, data on PD-L1 expression on liquid-based cytology (LBC) in malignant pleural effusion (MPE) is scarce. METHODS: This study cohort included 60 cases with MPE suffering from LUAD. PD-L1 SP263 assay was used for immunocytochemistry (ICC) on LBC and matched cell block (CB) to validate ICC protocols on LBC slides. Clinical outcomes were analyzed based on immunotherapy and PD-L1 tumor proportion scores (TPS) on LBC slides and CBs. RESULTS: PD-L1 expression with TPS ≥1% was lower in LBCs than in CBs (33 of 60 [55.0%] vs. 35 of 60 [58.3%]; p = .687). Even with the TPS ≥50% threshold, PD-L1 expression was lower in LBCs (10 of 60 [16.7%] vs. 15 of 60 [25%]; p = .125). Epidermal growth factor receptor (EGFR) exon 20 mutation, tumor cell proportion, and pleural fluid neutrophil-to-lymphocyte ratio were related to PD-L1 expression on CBs (p = .013, p = 0.022, and p = .011), respectively. Patients with subsequent immune checkpoint inhibitor therapy remained a better prognostic in subgroups of PD-L1 positive expression on LBC slides (TPS ≥1%, p = .041). CONCLUSIONS: LBC specimens had comparable performance to CBs in PD-L1 assessment and predicting treatment response to PD-L1-defined therapy.

Smoking, Corneal Biomechanics, and Glaucoma: Results From Two Large Population-Based Cohorts.

Purpose: Smoking may influence measured IOP through an effect on corneal biomechanics, but it is unclear whether this factor translates into an increased risk for glaucoma. This study aimed to examine the association of cigarette smoking with corneal biomechanical properties and glaucoma-related traits, and to probe potential causal effects using Mendelian randomization (MR). Methods: Cross-sectional analyses within the UK Biobank (UKB) and Canadian Longitudinal Study on Aging (CLSA) cohorts. Multivariable linear and logistic regression models were used to assess associations of smoking (status, intensity, and duration) with corneal hysteresis (CH), corneal resistance factor, IOP, inner retinal thicknesses, and glaucoma. Two-sample MR analyses were performed. Results: Overall, 68,738 UKB (mean age, 56.7 years; 54.7% women) and 22 845 CLSA (mean age, 62.7 years; 49.1% women) participants were included. Compared with nonsmokers, smokers had a higher CH (UKB, +0.48 mm Hg; CLSA, +0.57 mm Hg; P < 0.001) and corneal resistance factor (UKB, +0.47 mm Hg; CLSA, +0.60 mm Hg; P < 0.001) with evidence of a dose-response effect in both studies. Differential associations with Goldmann-correlated IOP (UKB, +0.25 mm Hg; CLSA, +0.36 mm Hg; P < 0.001) and corneal-compensated IOP (UKB, -0.28 mm Hg; CLSA, -0.32 mm Hg; P ≤ 0.001) were observed. Smoking was not associated with inner retinal thicknesses or glaucoma status in either study. MR provided evidence for a causal effect of smoking on corneal biomechanics, especially higher CH. Conclusions: Cigarette smoking seems to increase corneal biomechanical resistance to deformation, but there was little evidence to support a relationship with glaucoma. This outcome may result in an artefactual association with measured IOP and could account for discordant results with glaucoma in previous epidemiological studies.

Cascade N2 Reduction Process with DBD Plasma Oxidation and Electrocatalytic Reduction for Continuous Ammonia Synthesis.

Due to the extremely high bond energy of N≡N (∼941 kJ/mol), the traditional Haber-Bosch process of ammonia synthesis is known as an energy-intensive and high CO2-emission industry. In this paper, a cascade N2 reduction process with dielectric barrier discharge (DBD) plasma oxidation and electrocatalytic reduction as an alternative route is first proposed. N2 is oxidized to be reactive nitrogen species (RNS) by nonthermal plasma, which would then be absorbed by KOH solution and electroreduced to NH4+. It is found that the production of NOx is a function of discharge length, discharge power, and gas flow rate. Afterward, the cobalt catalyst is used in the process of electrocatalytic reduction of ammonia, which shows high selectivity (Faradic efficiency (FE) above 90%) and high yield of ammonia (45.45 mg/h). Finally, the cascade plasma oxidation and electrocatalytic reduction for ammonia synthesis is performed. Also, the performance of the reaction system is evaluated. It is worth mentioning that a stable and sustainable ammonia production efficiency of 16.21 mg/h is achieved, and 22.16% of NOx obtained by air activation is converted into NH4+. This work provides a demonstration for further industrial application of ammonia production with DBD plasma oxidation and electrocatalytic reduction techniques.

A microtubule stabilizer ameliorates protein pathogenesis and neurodegeneration in mouse models of repetitive traumatic brain injury.

Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Although the events leading to initial tau misfolding and subsequent tau spreading in patient brains are largely unknown, traumatic brain injury (TBI) may be a risk factor for tau-mediated neurodegeneration. Using a repetitive TBI (rTBI) paradigm, we report that rTBI induced somatic accumulation of phosphorylated and misfolded tau, as well as neurodegeneration across multiple brain areas in 7-month-old tau transgenic PS19 mice but not wild-type (WT) mice. rTBI accelerated somatic tau pathology in younger PS19 mice and WT mice only after inoculation with tau preformed fibrils and AD brain-derived pathological tau (AD-tau), respectively, suggesting that tau seeds are needed for rTBI-induced somatic tau pathology. rTBI further disrupted axonal microtubules and induced punctate tau and TAR DNA binding protein 43 (TDP-43) pathology in the optic tracts of WT mice. These changes in the optic tract were associated with a decline of visual function. Treatment with a brain-penetrant microtubule-stabilizing molecule reduced rTBI-induced tau, TDP-43 pathogenesis, and neurodegeneration in the optic tract as well as visual dysfunction. Treatment with the microtubule stabilizer also alleviated rTBI-induced tau pathology in the cortices of AD-tau-inoculated WT mice. These results indicate that rTBI facilitates abnormal microtubule organization, pathological tau formation, and neurodegeneration and suggest microtubule stabilization as a potential therapeutic avenue for TBI-induced neurodegeneration.

Migraine and the risk of cervical artery dissection: A systematic review and meta-analysis.

INTRODUCTION: Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have suggested an elevated risk of cervical artery dissection (CeAD) in patients with a history of migraine. We aimed to investigate this potential association using systematic review and meta-analytic methods. PATIENTS AND METHODS: We utilized a pre-defined search protocol to identify and screen studies related to migraine and CeAD in PubMed, Embase, and the Web of Science Core Collection. We assessed the risk of bias and performed a meta-analysis of selected studies to assess the association between migraine and CeAD. We also performed subgroup analyses by migraine subtype, biological sex, and the use of stroke versus non-stroke controls. RESULTS: We identified 11 studies (N = 9857 patients) for inclusion in the meta-analysis. Meta-analysis showed an association between migraine and CeAD with an odds ratio of 1.74 (95%CI 1.38-2.19). There was high heterogeneity among the included studies (I2 = 61%). Publication bias was present but the Trim-Fill imputation suggested that the impact on results was likely minimal. Subgroup analyses revealed an association between migraine without aura and CeAD (OR 1.86, 95%CI 1.55-2.24) but not migraine with aura and CeAD (OR 1.15, 95%CI 0.71-1.88). There was no difference in the association between migraine and CeAD in men compared to women. DISCUSSION AND CONCLUSION: A history of migraine is associated with an increased risk of CeAD. Further studies are needed to elucidate the potential pathophysiologic mechanisms underlying this association.

Survey of Time Series Data Generation in IoT.

Nowadays, with the rapid growth of the internet of things (IoT), massive amounts of time series data are being generated. Time series data play an important role in scientific and technological research for conducting experiments and studies to obtain solid and convincing results. However, due to privacy restrictions, limited access to time series data is always an obstacle. Moreover, the limited available open source data are often not suitable because of a small quantity and insufficient dimensionality and complexity. Therefore, time series data generation has become an imperative and promising solution. In this paper, we provide an overview of classical and state-of-the-art time series data generation methods in IoT. We classify the time series data generation methods into four major categories: rule-based methods, simulation-model-based methods, traditional machine-learning-based methods, and deep-learning-based methods. For each category, we first illustrate its characteristics and then describe the principles and mechanisms of the methods. Finally, we summarize the challenges and future directions of time series data generation in IoT. The systematic classification and evaluation will be a valuable reference for researchers in the time series data generation field.

The acetyltransferase BmCBP changes the acetylation modification of BmSP3 and affects its protein expression in silkworm, Bombyx mori.

BACKGROUND: Protein acetylation is an important post-translational modification (PTM) that widely exists in organisms. As a reversible PTM, acetylation modification can regulate the function of proteins with high efficiency. In the previous study, the acetylation sites of silkworm proteins were identified on a large scale by nano-HPLC/MS/MS (nanoscale high performance liquid chromatography-tandem secondary mass spectrometry), and a total of 11 acetylation sites were discovered on Bombyx mori nutrient-storage protein SP3 (BmSP3). The purpose of this study was to investigate the effect of acetylation level on BmSP3. METHODS AND RESULTS: In this study, the acetylation of BmSP3 was further verified by immunoprecipitation (IP) and Western blotting. Then, it was confirmed that acetylation could up-regulate the expression of BmSP3 by improving its protein stability in BmN cells. Co-IP and RNAi experiments showed acetyltransferase BmCBP could bind to BmSP3 and catalyze its acetylation modification, then regulate the expression of BmSP3. Furthermore, the knock-down of BmCBP could improve the ubiquitination level of BmSP3. Both acetylation and ubiquitination occur on the side chain of lysine residues, therefore, we speculated that the acetylation of BmSP3 catalyzed by BmCBP could competitively inhibit its ubiquitination modification and improve its protein stability by inhibiting ubiquitin-mediated proteasome degradation pathway, and thereby increase the expression and intracellular accumulation. CONCLUSIONS: BmCBP catalyzes the acetylation of BmSP3 and may improve the stability of BmSP3 by competitive ubiquitination. This conclusion provides a new functional basis for the extensive involvement of acetylation in the regulation of nutrient storage and utilization in silkworm, Bombyx mori.

Observational Study of the Natural Growth History of Peripheral Small-Cell Lung Cancer on CT Imaging.

BACKGROUND: This study aimed to investigate the natural growth history of peripheral small-cell lung cancer (SCLC) using CT imaging. METHODS: A retrospective study was conducted on 27 patients with peripheral SCLC who underwent at least two CT scans. Two methods were used: Method 1 involved direct measurement of nodule dimensions using a calliper, while Method 2 involved tumour lesion segmentation and voxel volume calculation using the "py-radiomics" package in Python. Agreement between the two methods was assessed using the intraclass correlation coefficient (ICC). Volume doubling time (VDT) and growth rate (GR) were used as evaluation indices for SCLC growth, and growth distribution based on GR and volume measurements were depicted. We collected potential factors related to imaging VDT and performed a differential analysis. Patients were classified into slow-growing and fast-growing groups based on a VDT cut-off point of 60 days, and univariate analysis was used to identify factors influencing VDT. RESULTS: Median VDT calculated by the two methods were 61 days and 71 days, respectively, with strong agreement. All patients had continuously growing tumours, and none had tumours that decreased in size or remained unchanged. Eight patients showed possible growth patterns, with six possibly exhibiting exponential growth and two possibly showing Gompertzian growth. Tumours deeper in the lung grew faster than those adjacent to the pleura. CONCLUSIONS: Peripheral SCLC tumours grow rapidly and continuously without periods of nongrowth or regression. Tumours located deeper in the lung tend to grow faster, but further research is needed to confirm this finding.

Dual sulfur defect engineering of Z-scheme heterojunction on Ag-CdS1-x@ZnIn2S4-x hollow core-shell for ultra-efficient selective photocatalytic H2O2 production.

Photocatalytic production of hydrogen peroxide (H2O2) using sunlight as an energy source, water and molecular oxygen as feedstock is considered as a green and sustainable promising strategy to solve the energy and environmental crisis. Despite significant improvements in photocatalyst design tuning, however, the relatively low photocatalytic H2O2 productivity is still far from satisfactory. Herein, we developed a multi-metal composite sulfide (Ag-CdS1-x@ZnIn2S4-x) with double S vacancies and hollow core-shell Z-type heterojunction structure for H2O2 generation by a simple hydrothermal method. The unique hollow structure improves the utilization of light source. The existence of Z-type heterojunction promotes the spatial separation of carriers, and the core-shell structure increases the interface area and active sites. Under visible light irradiation, Ag-CdS1-x@ZnIn2S4-x had a high hydrogen peroxide yield of 1183.7 µmol h-1 g-1, which was 6 times that of CdS. The electron transfer number (n = 1.53) obtained from the Koutecky-Levuch plot and DFT calculation confirm that the presence of dual disulfide vacancies provides good selectivity of 2e- O2 reduction to H2O2. This work provides new insights into the regulation of highly selective two-electron photocatalytic H2O2 production, and also provides new ideas for the design and development of highly active energy conversion photocatalysts.

The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank.

PURPOSE: To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR). DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n = 94 206 and n = 27 777, respectively), macular inner retinal OCT measurements (n = 36 274 and n = 9991, respectively), and glaucoma status (n = 86 803 and n = 23 556, respectively). METHODS: We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma. MAIN OUTCOME MEASURES: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status. RESULTS: In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by +0.57 µm (P < 0.001) and +0.42 µm (P = 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of +0.08 mmHg (P = 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome. CONCLUSIONS: Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cohort profile: rationale and methods of UK Biobank repeat imaging study eye measures to study dementia.

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

The Effect of Bovine Serum Albumin on Benzo[a]pyrene Removal by Lactobacillus Strains.

The aim of this study was to investigate the influence of bovine serum albumin (BSA) on the Lactobacillus-strain-mediated removal of benzo[a]pyrene (BaP). A combination of 0.5 mg/mL of BSA with 1.0 × 1010 CFU/mL bacterial cells had a removal of 49.61% BaP for strain 121, while a combination of 0.4 mg/mL of BSA with 1.0 × 1010 CFU/mL bacterial cells had a removal of 66.09% BaP for strain ML32. The results indicated that the binding of BaP to Lactobacillus-BSA was stable. BSA maintains Lactobacillus activity and BaP removal in the gastrointestinal environment. Heat and ultrasonic treatment of BSA reduced the BaP-binding ability of Lactobacillus-BSA. With the addition of BSA, the surface properties of the two strains affected BaP binding. The Fourier-transform infrared (FTIR) data demonstrated that O-H, N-H, C=O, and P=O groups were involved in the binding of BaP to Lactobacillus-BSA. Scanning electron microscopy (SEM) results revealed that the morphology of Lactobacillus-BSA bound to BaP was maintained. The adsorption of BaP by Lactobacillus-BSA was appropriately described by the pseudo-second-order kinetic model and Freundlich isotherm model. BSA enhances the affinity between the bacterial cells and BaP.

Associations Between HbA1c Across the Normal Range, Diagnosed, and Undiagnosed Diabetes and Retinal Layer Thickness in UK Biobank Cohort.

Purpose: The purpose of this study was to investigate the association between glycated hemoglobin (HbA1c) levels and retinal sub-layer thicknesses in people with and without diabetes. Methods: We included 41,453 UK Biobank participants aged 40 to 69 years old. Diabetes status was defined by self-report of diagnosis or use of insulin. Participants were categorized into groups: (1) those with HbA1c <48 mmol/mol were subdivided into quintiles according to normal range of HbA1c; (2) those previously diagnosed with diabetes with no evidence of diabetic retinopathy; and (3) undiagnosed diabetes: >48 mmol/mol. Total macular and retinal sub-layer thicknesses were derived from spectral-domain optical coherence tomography (SD-OCT) images. Multivariable linear regression was used to evaluate the associations between diabetes status and retinal layer thickness. Results: Compared with participants in the second quintile of the normal HbA1c range, those in the fifth quintile had a thinner photoreceptor layer thickness (-0.33 µm, P = 0.006). Participants with diagnosed diabetes had a thinner macular retinal nerve fiber layer (mRNFL; -0.58 µm, P < 0.001), photoreceptor layer thickness (-0.94 µm, P < 0.001), and total macular thickness (-1.61 µm, P < 0.001), whereas undiagnosed diabetes participants had a reduced photoreceptor layer thickness (-1.22 µm, P = 0.009) and total macular thickness (-2.26 µm, P = 0.005). Compared to participants without diabetes, those with diabetes had a thinner mRNFL (-0.50 µm, P < 0.001), photoreceptor layer thickness (-0.77 µm, P < 0.001), and total macular thickness (-1.36 µm, P < 0.001). Conclusions: Participants with higher HbA1c in the normal range had marginally thinner photoreceptor thickness, whereas those with diabetes (including undiagnosed diabetes) had meaningfully thinner retinal sublayer and total macular thickness. Translational Relevance: We showed that early retinal neurodegeneration occurs in people whose HbA1c levels are below the current diabetes diagnostic threshold; this might impact the management of pre-diabetes individuals.