COVID-19 and retinal layer thickness: A bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have reported that COVID-19 is associated with alterations in retinal layer thickness, including changes in the ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL). However, the causal relationships remain unknown. Therefore, we assessed the direction and strength of the causal relationship between COVID-19 and GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian randomization (MR) design. METHODS: Data were obtained from a large-scale COVID-19 Host Genetics Initiative (Nsample = 6,512,887), GCIPL dataset (Ncase = 31,434), and RNFL dataset (Ncase = 31,434). The inverse-variance weighted (IVW) method is the primary approach used to estimate causal effects. MR Egger, weighted median, weighted mode, MR Egger (bootstrap), and penalized weighted median methods were applied. Sensitivity analyses were implemented with RadialMR, MRPRESSO, MR-Egger regression, Cochran's Q statistic, leave-one-out analysis, and the funnel plot. RESULTS: Forward MR analysis revealed that genetically identified COVID-19 susceptibility significantly increased the risk of GCIPL thickness (OR = 2.428, 95 % confidence interval [CI]:1.493-3.947, PIVW = 3.579 × 10-4) and RNFL thickness (OR = 1.735, 95 % CI:1.198-2.513, PIVW = 3.580 × 10-3) after Bonferroni correction. Reverse MR analysis did not indicate a significant causal association between GCIPL and RNFL thicknesses and COVID-19 phenotypes. No significant horizontal pleiotropy was found in the sensitivity analysis. CONCLUSIONS: The host genetic liability to COVID-19 susceptibility was causally associated with increased GCIPL and RNFL thicknesses. Documenting this association increases our understanding of the pathophysiological mechanisms underlying COVID -19 susceptibility in retinopathy.

Genetically predicted processed meat, red meat intake, and risk of mental disorders: A multivariable Mendelian randomization analysis.

BACKGROUND: Previous observational studies have highlighted potential links between the consumption of processed meat and red meat (such as pork, mutton, and beef intake) and the occurrence of mental disorders. However, it is unclear whether a causal association exists. Therefore, we employed the Mendelian randomization (MR) study to investigate the causal effects of genetically predicted processed meat and red meat on mood disorders (MD), anxiety disorders (AD), and major depressive disorder (MDD). METHODS: Genetic instruments for processed and red meat were selected from the Genome-Wide Association Study (GWAS) of the UK Biobank Study. Their associations with MD (42,746 cases 254,976), AD (35,385 cases and 254,976 controls), and MDD (38,225 cases and 299,886 controls) were obtained from the FinnGen Consortium. The inverse variance weighted (IVW) method was the primary method for two-sample MR analysis. Additionally, we employed complementary analysis to assess the robustness of our MR findings (eg, MR Egger and weighted median). We also conducted multiple sensitivity analyses to investigate horizontal pleiotropy and heterogeneity. Moreover, we performed a univariate and multivariable MR (MVMR) study to evaluate these associations. RESULTS: In our univariate MR analysis, we observed that genetically predicted beef intake was associated with a reduced risk of MD [odds ratio (OR) = 0.403, 95 % confidence interval (CI) = 0.246-0.659; PIVW = 4.428 × 10-5], AD (OR = 0.443, 95 % CI = 0.267-0.734; PIVW = 1.563 × 10-3), and MDD (OR = 0.373, 95 % CI = 0.216-0.643; PIVW = 3.878 × 10-4). After adjusting for processed meat, pork, and mutton intake in the MVMR analysis, the protective association of beef intake against MD and MDD remained. However, there was no substantial evidence indicating a significant causal relationship between processed meat, pork, and mutton intake and the occurrence of mental disorders. Furthermore, our sensitivity analysis revealed no significant evidence of horizontal pleiotropy. CONCLUSION: These findings support a causal relationship between genetically predicted beef intake and reducing the risk of MD and MDD.

Accumulation and distribution of uranium in rats after implantation with depleted uranium fragments.

PURPOSE: The aim of our study was to clarify the accumulation and distribution of uranium in depleted uranium (DU) implanted rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at 3 dose levels (low, medium and high), and biologically inert tantalum (Ta) fragments were used as controls. At 1 day and 7, 30, 90, 180 and 360 days after implantation, the rats were euthanized and tissue samples including serum and urine were collected to analyze the uranium levels by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: At all time points, uranium levels in all the DU implanted groups were higher than that in Ta control group, and uranium concentrations in kidney and bone were significantly greater than that in other tissues. Otherwise, uranium concentrations increased with a close correlation to the implanted DU doses and duration of exposure, with a peak at 90 days post-implantation, after which followed by a decreasing period, but still maintained at a relatively high level even at 360 days post- implantation. The uranium concentrations in bone were 6.92 +/- 0.97 microg U/g, 16.35 +/- 1.67 microg U/g and 21.64 +/- 3.68 microg U/g in the low-, medium- and high-dose group animals, while values in kidney tissues were 10.66 +/- 1.10 microg U/g, 14.06 +/- 1.28 microg U/g and 17.79 +/- 2.87 microg U/g, respectively, at 360 days post-implantation. CONCLUSION: It was concluded that kidney and bone are the primary reservoirs for uranium redistributed from intramuscularly embedded fragments, and the accumulations in kidney, bone and many other tissues suggest the potential for unanticipated physiological consequences of chronic exposure to DU.

Renal dysfunction induced by long-term exposure to depleted uranium in rats.

Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in alignment. Compared to the control group, it was found that there was significant increase in the DU implantation group in terms of their blood urea nitrogen (BUN) and serum creatinine, urinary beta2-microglobulin (beta2-MG) and albumin, with a high correlation to the implanted DU dosage and periods. It was concluded that DU could accumulate in kidneys for a long period, and causes kidney injury by the toxic chemical/radioactive action such as renal dysfunction and structural damage.