The impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy optimization in men and women with familial hypercholesterolemia.

Background and aims: FH women are less likely to receive intensive statin treatment and to obtain a 50% reduction of LDL-C from baseline compared to men with FH. SLCO1B1 rs4149056 might influence statin therapy compliance and thus LDL-C target achievement. Our aim was to evaluate the impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy (LLT) optimization in men and women with FH. Methods: This was a retrospective observational study involving 412 FH subjects with a probable or defined clinical diagnosis of FH who had had genetic analysis from June 2016 to September 2022. Biochemical analysis was obtained from all subjects at baseline and at the last follow-up after LLT optimization. Results: After LLT optimization the percentage of FH subjects on high-intensity statins decreased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was found in LDL-C target distribution (for both p for trend < 0.01). The prevalence of SASE fear increased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was observed in reported myalgia distribution (for both p for trend < 0.01). Logistic regression analysis showed that the W/SCLO1B1-, M/SCLO1B1+ and W/SCLO1B1+ groups were inversely associated with LDL-C target achievement (p for trend < 0.001) and the W/SCLO1B1+ group exhibited the strongest association. Conclusion: A low prevalence of FH women with SLCO1B1 rs4149056 were on high intensity statins and they rarely achieved LDL-C target. The genotype effect of SLCO1B1 rs4149056 could be more pronounced in FH women than men.

Corrigendum: Ocular effects caused by viral infections and corresponding vaccines: An overview of varicella zoster virus, measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2.

[This corrects the article DOI: 10.3389/fmed.2022.999251.].

Ocular effects caused by viral infections and corresponding vaccines: An overview of varicella zoster virus, measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2.

Many viral infections can affect vision and the visual system. Vaccination to prevent diseases is commonplace today, acting by stimulating an immune response without developing the pathology. It involves the production of persisting antibodies against the pathogen and the activation of T cells. Certain diseases have already been eradicated by rigorous vaccination campaigns, while others are hoped to be eliminated soon. Vaccines currently available on the market are largely safe, even if they can rarely cause some adverse effects, such as ocular complications. Analyzing existing literature, we aimed to compare the pathological effects on the eye due to the most common viral infections [in particular varicella zoster virus (VZV), measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2] with the possible ocular adverse effects of their relative vaccines, in order to establish a risk-benefit relationship from an ophthalmological point of view.

Cerebral Modifications in Glaucoma and Macular Degeneration: Analysis of Current Evidence in Literature and Their Implications on Therapeutic Perspectives.

Glaucoma and macular degeneration are leading causes of irreversible blindness, significantly compromising the quality of life and having a high economic and social impact. Promising therapeutic approaches aimed at regenerating or bypassing the damaged anatomical-functional components are currently under development: these approaches have generated great expectations, but to be effective require a visual network that, despite the pathology, maintains its integrity up to the higher brain areas. In the light of this, the existing findings concerning how the central nervous system modifies its connections following the pathological damage caused by glaucoma and macular degeneration acquire great interest. This review aims to examine the scientific literature concerning the morphological and functional changes affecting the central nervous system in these pathological conditions, summarizing the evidence in an analytical way, discussing their possible causes and highlighting the potential repercussions on the current therapeutic perspectives.

Cerebral Modifications and Visual Pathway Reorganization in Maculopathy: A Systematic Review.

BACKGROUND: Macular degeneration (MD) is one of the most frequent causes of visual deficit, resulting in alterations affecting not only the retina but also the entire visual pathway up to the brain areas. This would seem related not just to signal deprivation but also to a compensatory neuronal reorganization, having significant implications in terms of potential rehabilitation of the patient and therapeutic perspectives. OBJECTIVE: This paper aimed to outline, by analyzing the existing literature, the current understanding of brain structural and functional changes detected with neuroimaging techniques in subjects affected by juvenile and age-related maculopathy. METHODS: Articles using various typologies of central nervous system (CNS) imaging in at least six patients affected by juvenile or age-related maculopathy were considered. A total of 142 were initially screened. Non-pertinent articles and duplicates were rejected. Finally, 19 articles, including 649 patients, were identified. RESULTS: In these sources, both structural and functional modifications were found in MD subjects' CNS. Changes in visual cortex gray matter volume were observed in both age-related MD (AMD) and juvenile MD (JMD); in particular, an involvement of not only its posterior part but also the anterior one suggests further causes besides an input-deprivation mechanism only. White matter degeneration was also found, more severe in JMD than in AMD. Moreover, functional analysis revealed differences in cortical activation patterns between MD and controls, suggesting neuronal circuit reorganization. Interestingly, attention and oculomotor training allowed better visual performances and correlated to a stronger cortical activation, even of the area normally receiving inputs from lesioned macula. CONCLUSION: In MD, structural and functional changes in cerebral circuits and visual pathway can happen, involving both cerebral volume and activation patterns. These modifications, possibly due to neuronal plasticity (already observed and described for several brain areas), can allow patients to compensate for macular damage and gives therapeutic perspectives which could be achievable through an association between oculomotor training and biochemical stimulation of neuronal plasticity.

Phosphatidic acid metabolism regulates neuroendocrine secretion but is not under the direct control of lipins.

Phosphatidic acid (PA) produced by phospholipase D1 has been shown to contribute to secretory vesicle exocytosis in a large number of cell models. Among various hypotheses, PA may contribute to recruit and/or activate at the exocytotic site a set of proteins from the molecular machinery dedicated to secretion, but also directly influence membrane curvature thereby favoring membrane rearrangements required for membrane fusion. The release of informative molecules by regulated exocytosis is a tightly controlled process. It is thus expected that PA produced to trigger membrane fusion should be rapidly metabolized and converted in a lipid that does not present similar characteristics. PA-phosphatases of the lipin family are possible candidates as they convert PA into diacylglycerol. We show here that lipin 1 and lipin 2 are expressed in neuroendocrine cells where they are cytosolic, but also partially associated with the endoplasmic reticulum. Silencing of lipin 1 or 2 did not affect significantly either basal or evoked secretion from PC12 cells, suggesting that it is unlikely that conversion of PA into a secondary lipid by lipins might represent a regulatory step in exocytosis in neurosecretory cells. However, in agreement with a model in which PA-metabolism could contribute to prevent entering into exocytosis of additional secretory vesicles, ectopic expression of lipin1B-GFP in bovine chromaffin cells reduced the number of exocytotic events as revealed by carbon fiber amperometry recording. Furthermore, individual spike parameters reflecting fusion pore dynamics were also modified by lipin1B-GFP, suggesting that a tight control of PA levels represents an important regulatory step of the number and kinetic of exocytotic events.