Antibiotic-induced gut microbiota depletion exacerbates host hypercholesterolemia.

Hypercholesterolemia is a major driver of atherosclerosis, thus contributing to high morbidity and mortality worldwide. Gut microbiota have been identified as modulator of blood lipids including cholesterol levels. Few studies have already linked certain bacteria and microbial mechanisms to host cholesterol. However, in particular mouse models revealed conflicting results depending on genetics and experimental protocol. To gain further insights into the relationship between intestinal bacteria and host cholesterol metabolism, we first performed fecal 16S rRNA targeted metagenomic sequencing in a human cohort (n = 24) naïve for cholesterol lowering drugs. Here, we show alterations in the gut microbiota composition of hypercholesterolemic patients with depletion of Bifidobacteria, expansion of Clostridia and increased Firmicutes/Bacteroidetes ratio. To test whether pharmacological intervention in gut microbiota impacts host serum levels of cholesterol, we treated hypercholesterolemic Apolipoprotein E knockout with oral largely non-absorbable antibiotics. Antibiotics increased serum cholesterol, but only when mice were fed normal chow diet and cholesterol was measured in the random fed state. These elevations in cholesterol already occurred few days after treatment initiation and were reversible after stopping antibiotics with re-acquisition of intestinal bacteria. Gene expression analyses pointed to increased intestinal cholesterol uptake mediated by antibiotics in the fed state. Non-targeted serum metabolomics suggested that diminished plant sterol levels and reduced bile acid cycling were involved microbial mechanisms. In conclusion, our work further enlightens the link between gut microbiota and host cholesterol metabolism. Pharmacological disruption of the gut flora by antibiotics was able to exacerbate serum cholesterol and may impact cardiovascular disease.

Management of Optic Disk Pit-associated Macular Detachment with Human Amniotic Membrane Patch.

PURPOSE: To report a new surgical technique involving a human amniotic membrane patch (hAM) to solve a serous macular detachment associated with optic nerve head pit. METHODS: Three eyes of three patients affected by macular detachment associated with optic nerve head pit were enrolled. A 23-gauge pars plana vitrectomy were performed. hAM patch was implanted inside the optic nerve pit; air was used as endotamponade. The patients were instructed to maintain face-down position for the first days after surgery. RESULTS: The subretinal fluid gradually resolved during 6 months of follow-up, and visual acuity improved to 20/25 at the sixth month after surgery. We did not observe a recurrence of subretinal fluid during the 6 months of follow-up. No postoperative complications were reported during the follow-up. CONCLUSION: Implant of the hAM may be effective to repair optic disk pit maculopathy. All the cases were successful with encouraging visual acuity recovery.

Intrascleral hydration for 23-Gauge Pars Plana Vitrectomy Sclerotomy Closure.

PURPOSE: To describe and evaluate the effectiveness of a new technique to close 23-gauge sclerotomies in transconjunctival pars plana vitrectomy. MATERIALS AND METHODS: A prospective, consecutive, interventional study of 90 eyes of 90 patients who underwent 23-gauge pars plana vitrectomy with the introduction of the new sealing technique was conducted. The 23-gauge sclerotomies were hydrated with a 30-gauge needle inserted in the scleral stroma near the scleral opening. RESULTS: A total of 90 eyes of 90 patients were recruited in the study. The number of the eyes requiring suture for sclerotomy closure was 3.3% (3 of 90), and the sclerotomies requiring suture were 1.4% (4 of 270). Three eyes had hypotony on Day 1. No statistically significant difference was registered between preoperative intraocular pressure and postoperative intraocular pressure on Days 15 and 30. No leaking of endotamponade bubble filling was noticed on Day 1. No postoperative complications were registered during the follow-up period. CONCLUSION: The intrascleral stroma hydration is a simple and fast technique that does not require extra surgical materials.

HUMAN AMNIOTIC MEMBRANE TO TREAT MACULAR HOLES THAT FAILED TO CLOSE, SULFUR HEXAFLUORIDE ENDOTAMPONADE VERSUS AIR ENDOTAMPONADE: A Prospective Comparative Study.

BACKGROUND/PURPOSE: To determinate the efficacy of the human amniotic membrane plugs with sulfur hexafluoride versus human amniotic membrane plug with air as endotamponade to treat macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Multimodal imaging was focused to evaluate preoperative features and postoperative changes. METHODS: Prospective interventional comparative study. Twenty eyes of 20 patients affected with macular hole that failed to close were divided into 2 groups: 10 eyes received an amniotic membrane plug with 20% sulfur hexafluoride tamponade and 10 eyes received an amniotic membrane plug with air tamponade. All eyes were studied using multimodal advanced diagnostic tools, such as spectral-domain optical coherence tomography, optical coherence tomography angiography, microperimetry, and adaptive optics to investigate the postoperative results. RESULTS: In both groups, all macular holes were found successfully closed after 12 months. Mean preoperative best-corrected visual acuity was 20/400 in the SF6 group and 20/250 in air group. Final mean best-corrected visual acuity was 20/63 in both groups. The superficial capillary plexus, studied using optical coherence tomography angiography, showed a statistically significant difference between the treated and the fellow eyes. Adaptive optics images revealed the presence of a photoreceptor cell mosaic in the area of the amniotic membrane plug. CONCLUSION: The human amniotic membrane combined with air endotamponade demonstrated its effectiveness to seal macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Advanced multimodal diagnostic imaging helped us to better understand the modifications associated with the use of the amniotic membrane in these cases.

Does higher sampling rate (multiband + SENSE) improve group statistics - An example from social neuroscience block design at 3T.

Multiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3 â€‹T scanner using five sequences, up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movie blocks showing complex actions with hand object interactions and (ii) control movie blocks without hand object interaction. Data were processed using a widely used analysis pipeline implemented in SPM12 including the unified segmentation and canonical HRF modelling. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7 â€‹mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit.

HUMAN AMNIOTIC MEMBRANE TO CLOSE RECURRENT, HIGH MYOPIC MACULAR HOLES IN PATHOLOGIC MYOPIA WITH AXIAL LENGTH OF ≥30 mm.

PURPOSE: To assess the effectiveness of the human amniotic membrane plug for recurrent high myopic macular hole (MH) that already underwent pars plana vitrectomy with internal limiting membrane peeling and gas endotamponade. METHODS: Sixteen eyes of 16 patients with recurrent high myopic MH were enrolled. A 23-gauge pars plana vitrectomy was performed. Human amniotic membrane plugs were implanted under the neuroretina inside the MH. Twenty percent sulfur hexafluoride or air was used as endotamponades. The patients were instructed to maintain facedown position for 5 days after surgery. RESULTS: Optical coherence tomography examinations showed that the MHs closed in 15 of the 16 patients (93.75%) 2 weeks after one surgical intervention, and in 100% of patients after second intervention. Mean best-corrected visual acuity improved from 1 logarithm of the minimum angle of resolution (20/200) to 0.67 logarithm of the minimum angle of resolution (20/100) 6 months after surgery. Best-corrected visual acuity remained stable during the 12-month follow-up. One patient had human amniotic membrane plug dislocation after gas absorption that needed a second intervention with new AM plug implantation. No adverse events were reported during the 12-month follow-up. CONCLUSION: The first case series of recurrent high myopic MH was reported, assessing the effectiveness of the human amniotic membrane plug to close recurrent MHs in pathologic myopia. All the cases were successful with encouraging best-corrected visual acuity recovery.

Functional roles of the fatty acid desaturases encoded by KlOLE1, FAD2 and FAD3 in the yeast Kluyveromyces lactis.

Functional properties of cell membranes depend on their composition, particularly on the relative amount of saturated, unsaturated and polyunsaturated fatty acids present in the phospholipids. The aim of this study was to investigate the effect of cell membrane composition on cell fitness, adaptation and stress response in Kluyveromyces lactis. To this purpose, we have deleted the genes FAD2 and FAD3 encoding Δ12 and ω3 desaturases in Kluyveromyces lactis, thus generating mutant strains with altered fatty acid composition of membranes. These strains were viable and able to grow in stressing conditions like hypoxia and low temperature. Deletion of the Δ9 desaturase-encoding gene KlOLE1 resulted in lethality, suggesting that this enzyme has an essential role in this yeast. Transcription of the desaturase genes KlOLE1, FAD2 and FAD3 and cellular localization of the corresponding enzymes, have been studied under hypoxia and cold stress. Our findings indicate that expression of these desaturase genes and membrane composition were modulated by hypoxia and temperature stress, although the changes induced by these and other assayed conditions did not dramatically affect the general cellular fitness.

Unsaturated fatty acids-dependent linkage between respiration and fermentation revealed by deletion of hypoxic regulatory KlMGA2 gene in the facultative anaerobe-respiratory yeast Kluyveromyces lactis.

In the yeast Kluyveromyces lactis, the inactivation of structural or regulatory glycolytic and fermentative genes generates obligate respiratory mutants which can be characterized by sensitivity to the mitochondrial drug antimycin A on glucose medium (Rag(-) phenotype). Rag(-) mutations can occasionally be generated by the inactivation of genes not evidently related to glycolysis or fermentation. One such gene is the hypoxic regulatory gene KlMGA2. In this work, we report a study of the many defects, in addition to the Rag(-) phenotype, generated by KlMGA2 deletion. We analyzed the fermentative and respiratory metabolism, mitochondrial functioning and morphology in the Klmga2Δ strain. We also examined alterations in the regulation of the expression of lipid biosynthetic genes, in particular fatty acids, ergosterol and cardiolipin, under hypoxic and cold stress and the phenotypic suppression by unsaturated fatty acids of the deleted strain. Results indicate that, despite the fact that the deleted mutant strain had a typical glycolytic/fermentative phenotype and KlMGA2 is a hypoxic regulatory gene, the deletion of this gene generated defects linked to mitochondrial functions suggesting new roles of this protein in the general regulation and cellular fitness of K. lactis. Supplementation of unsaturated fatty acids suppressed or modified these defects suggesting that KlMga2 modulates membrane functioning or membrane-associated functions, both cytoplasmic and mitochondrial.

Robot-assisted radical cystectomy with intracorporeal reconstruction of urinary diversion by mechanical stapler: prospective evaluation of early and late complications.

Introduction: Radical cystectomy with pelvic lymph node dissection is the gold standard treatment for non-metastatic muscle-invasive bladder cancer and high-risk non-muscle-invasive bladder cancer. For years, the traditional open surgery approach was the only viable option. The widespread of robotic surgery led to its employment also in radical cystectomy to reduce complication rates and improve functional outcomes. Regardless of the type of approach, radical cystectomy is a procedure with high morbidity and not negligible mortality. Data available in the literature show how the use of staplers can offer valid functional outcomes, with an acceptable rate of complications shortening the operative time. The aim of our study was to describe the perioperative outcomes and complications associated with robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) using a mechanical stapler. Material and methods: From January 2015 to May 2021, we enrolled patients who underwent RARC with pelvic node dissection and stapled ICUD (ileal conduit or ileal Y-shaped neobladder according to the Perugia ileal neobladder) in our high-volume center. Demographic features, perioperative outcomes and early (≤30 days) and late (>90 days) post-operative complications according to the Clavien-Dindo classification, were recorded for each patient. We also analyzed the potential linear correlation between demographic, pre-operative as well as operative features and the risk of post-operative complications. Results: Overall, 112 patients who underwent RARC with ICUD were included with a minimum follow-up of 12 months. Intracorporeal Perugia ileal neobladder was performed in 74.1% of cases while ileal conduit was performed in 25.9%. The mean operative time, estimated intraoperative blood loss, and LOS were 289.1 ± 59.7 min, 390.6 ± 186.2 ml, and 17.5 ± 9.8 days, respectively. Early minor and major complications accounted for 26.7% and 10.8%, respectively. Overall late complications were 40.2%. The late most common complications were hydronephrosis (11.6%) and urinary tract infections (20.5%). Stone reservoir formation occurred in 2.7% of patients. Major complications occurred in 5.4%. In the sub-analysis, the mean operative time and the estimated blood loss improved significantly from the first 56 procedures to the last ones. Conclusion: RARC with ICUD performed by mechanical stapler is a safe and effective technique. Stapled Y-shaped neobladder did not increase the complication rate.

Neuro-computational mechanisms and individual biases in action-outcome learning under moral conflict.

Learning to predict action outcomes in morally conflicting situations is essential for social decision-making but poorly understood. Here we tested which forms of Reinforcement Learning Theory capture how participants learn to choose between self-money and other-shocks, and how they adapt to changes in contingencies. We find choices were better described by a reinforcement learning model based on the current value of separately expected outcomes than by one based on the combined historical values of past outcomes. Participants track expected values of self-money and other-shocks separately, with the substantial individual difference in preference reflected in a valuation parameter balancing their relative weight. This valuation parameter also predicted choices in an independent costly helping task. The expectations of self-money and other-shocks were biased toward the favored outcome but fMRI revealed this bias to be reflected in the ventromedial prefrontal cortex while the pain-observation network represented pain prediction errors independently of individual preferences.

Toric trans-scleral plugs IOL to correct aphakia with significant corneal astigmatism.

PURPOSE: To describe the use of toric trans-plugs IOL to correct aphakia with significant corneal astigmatism. METHODS: Case report and literature review. RESULTS: A 62-year-old man with an history of aphakia in his left eye after a traumatic cataract extraction and significant corneal astigmatism was referred to our clinic. Surgery plan was cataract remnants removal and secondary IOL implantation of toric sutureless trans-scleral plugs fixated IOL (FIL SSF, Soleko, Italy). The postoperative course was uneventful. At 12 months, the IOL was well-centered and the optic alignment remained stable with minimal total astigmatism. The e uncorrected distance visual acuity (UDVA) was 20/25 Snellen while correct distance visual acuity (CDVA) was 20/20 with a manifest refraction of -0.25-50 40° D; the patient was satisfied by the visual outcome. CONCLUSION: This novel toric trans-scleral plug fixated lens provides valuable outcomes also for astigmatic correction for a comprehensive correction of the aphakia in patients with poor zonular support and high expectations for postoperative visual quality.

Trans-scleral plugs scleral fixation IOL and penetrating keratoplasty to restore vision in vitrectomized eyes.

PURPOSE: To report the surgical outcomes of penetrating keratoplasty (PKP) and sutureless scleral fixation (SSF) using Carlevale Lens (Soleko) combined procedure to solve corneal failure and aphakia in vitrectomized eyes and discuss eventual advantages of this new approach. METHODS: Two patients underwent primary wound repair and pars plana vitrectomy after a penetrating ocular trauma and were referred to the author's clinic. The PKP and SSF-Carlevale lens implantation were performed under retrobulbar anesthesia. Intraoperative and postoperative complications were recorded, intraocular lens positioning was evaluated using anterior segment optical coherence tomography (AS-OCT) and endothelial cell density was determined using an endothelial microscope. Both patients completed 12 months follow-up. RESULTS: The surgery was performed without intraoperative complications. After 1 month, the lens was fixed well, and the graft showed no sign of rejection. At the last visit after 12 months, the corneal graft remained transparent with good endothelial cell density in both cases; conjunctival scarring or inflammation and plugs externalization did not occur during follow-ups. Best-corrected visual acuity was 4/10 Snellen in the first case, while in the second case, we witnessed a limited visual recovery of 1/20 Snellen due to retinal issues. CONCLUSION: We report the feasibility of secondary IOL implantation using Carlevale with penetrating keratoplasty. The relative of ease of Carlevale lens implantation through the transscleral plugs reduces the open globe length resulting in a safer procedure, especially for vitrectomized eyes.

Predictive coding during action observation - A depth-resolved intersubject functional correlation study at 7T.

While the brain regions involved in action observation are relatively well documented in humans and primates, how these regions communicate to help understand and predict actions remains poorly understood. Traditional views emphasized a feed-forward architecture in which visual features are organized into increasingly complex representations that feed onto motor programs in parietal and then premotor cortices where the matching of observed actions upon the observer's own motor programs contributes to action understanding. Predictive coding models place less emphasis on feed-forward connections and propose that feed-back connections from premotor regions back to parietal and visual neurons represent predictions about upcoming actions that can supersede visual inputs when actions become predictable, with visual input then merely representing prediction errors. Here we leverage the notion that feed-back connections target specific cortical layers to help adjudicate across these views. Specifically, we test whether observing sequences of hand actions in their natural order, which permits participants to predict upcoming actions, triggers more feed-back input to parietal regions than seeing the same actions in a scrambled sequence that hinders making predictions. Using submillimeter fMRI acquisition at 7T, we find that watching predictable sequences triggers more action-related activity (as measured using intersubject functional correlation) in the parietal cortical area PFt at depths receiving feed-back connections (layers III and V/VI) than watching the exact same actions in scrambled and hence unpredictable sequence. In addition, functional connectivity analysis performed using intersubject functional connectivity confirms that these increased action-related signals in PFt could originate from ventral premotor region BA44. This data showcases the utility of intersubject functional correlation in combination with 7T MRI to explore the architecture of social cognition under more naturalistic conditions, and provides evidence for models that emphasize the importance of feed-back connections in action prediction.

Vitreoschisis and retinal detachment: New insight in proliferative vitreoretinopathy.

PURPOSE: To assess the occurrence of peripheral vitreoschisis-induced vitreous cortex remnants (p-VCRs) in primary rhegmatogenous retinal detachment (RD) and investigate whether the presence of p-VCRs results in a greater risk of RD recurrence, secondary to Proliferative Vitreoretinopathy (PVR) development after pars plana vitrectomy (PPV). METHODS: Patients who underwent PPV for primary rhegmatogenous RD between January 2016 and December 2018 were included. The presence of residual p-VCRs was confirmed intraoperatively using triamcinolone acetonide (TA). Patients with p-VCRs were divided into two groups: Group A comprised of patients who underwent PPV without p-VCR removal, while Group B included patients who underwent PPV with p-VCR removal. RESULTS: Four hundred-thirteen eyes with evidence of p-VCR were analyzed. Two-hundred-twenty-three eyes underwent PPV without VCR removal (Group A), while 190 eyes underwent PPV with p-VCR removal (Group B). Primary anatomical success was 91.5% in the Group A and 95.4% in the group B. Retinal re-detachment due to PVR occurred in 17 (7.6%) eyes in Group A and in four (2.1%) eyes in Group B within the first 3 months (p = 0.01). Among group A, in 11 eyes, there was a diffuse posterior PVR grade C, while six eyes were focal PVR grade C. In Group B, we observed four retinal re-detachment due to focal PVR grade C. CONCLUSION: The presence of p-VCRs seems to be associated with a higher incidence of PVR development and might also result in more complex RD recurrence, this suggests the need for more aggressive VCRs removal during the first surgery.

Amniotic membrane for retinal detachment due to paravascular retinal breaks over patchy chorioretinal atrophy in pathologic myopia.

PURPOSE: To describe a new surgical technique, using a human amniotic membrane patch, in two cases of retinal detachment with paravascular retinal breaks over patchy chorioretinal atrophy in pathologic myopia, already underwent pars plana vitrectomy with the internal limiting membrane peeling for myopic foveoschisis. METHODS: Surgical technique description with surgical video. A 23-gauge pars plana vitrectomy was performed. A human amniotic membrane patch was implanted under the neuroretina to seal the posterior retinal break. Standard silicone oil tamponade was performed at the end of the surgery. The patients were positioned face down after the operation for the first week. Optical coherence tomography scans were used in the follow-ups. RESULTS: The 2 weeks postoperative optical coherence tomography showed a new tissue growth over the human amniotic membrane patch. The 3 months optical coherence tomography showed the new tissue entirely covering the human amniotic membrane plug. Visual acuity improved from 20/2000 (2 LogMAR) to 20/250 (1.1 LogMAR) 3 months after the operation in both patients. The silicone oil was extracted 2 months after surgery, and no recurrences were observed. The patient's visual acuity remained stable at 20/250 after the silicone oil extraction. CONCLUSION: In these complex cases, human amniotic membrane transplantation can be a valid option, when internal limiting membrane has already been peeled in previous surgeries, to seal the posterior retinal breaks over high myopic chorioretinal atrophy, with encouraging results.

Applications of the Amniotic Membrane in Vitreoretinal Surgery.

Recently, the use of the human amniotic membrane (hAM) has been extended to treat retinal disorders, such as macular holes that failed to close and retinal tears. The hAM has demonstrated the induction of a recovery process of the external retinal layers involving the external limiting membrane (ELM) and the ellipsoid zone (EZ). After that, the application of the hAM for retinal pathologies was extended to large macular tears, high myopic retinal detachment associated with MH, paravascular tears, serous macular detachment associated with optic pit, complicated retinal detachment and advanced age-related macular degeneration (AMD). The hAM has shown a potential in repairing retinal tissue through a regeneration process. This review aims to highlight the use of the hAM in various vitreo-retinal surgical fields, and to confront it with other cutting-edge surgical techniques used to treat challenging vitreo-retinal pathologies.

Trans-scleral plugs fixated IOL: a new paradigm for sutureless scleral fixation.

PURPOSE: To assess the surgical and refractive outcomes of a new technique of sutureless scleral fixation (SSF) using a single-piece foldable acrylic intraocular lens (IOL) (Carlevale). SETTING: Department of Translational Surgery and Medicine, Ophthalmology, University of Florence, Careggi, Florence, Italy. DESIGN: Prospective observational case series. METHODS: Thirty-two eyes of 32 patients with aphakia, dislocated IOL, or subluxated lens who underwent SSF with a novel single-piece hydrophilic acrylic IOL were studied. Preoperative and postoperative refractive status and complications during and after surgery were recorded. The IOL tilt was evaluated using anterior segment optical coherence tomography (AS-OCT). RESULTS: Twenty-two eyes were IOL/bag luxations, 9 were aphakia, and 3 were subluxated crystalline lens. Mean preoperative corrected distance visual acuity was 0.46 ± 0.29 logarithm of the minimum angle of resolution (logMAR) and improved to 0.13 ± 0.12 logMAR (P < .05) at the 8-month follow-up, with a predictive error spherical equivalent of -0.24 ± 0.81 diopters (D); the IOL tilt was 2.08 ± 1.19 degrees. One patient (3.1%) experienced transient cystoid macular edema, and 1 (3.1%) experienced vitreous hemorrhage; pigment dispersion with AS-OCT findings of reverse pupillary block was found in 2 (6.2%) eyes. IOL dislocation, conjunctival erosion, and plug externalization were not observed in any eye during the follow-up. CONCLUSIONS: SSF using the novel IOL could be a viable option for the management of aphakia, lens subluxation, and IOL-bag complex dislocation with unique characteristics of stability. The advantages of this technique were the absence of haptic manipulation, self-centration, and firm fixation of the IOL.

A human Amniotic Membrane plug to manage high myopic macular hole associated with retinal detachment.

OBJECTIVE: To assess the efficacy of the human amniotic membrane (hAM) to treat (HMMH) associated with retinal detachment (RD). MATERIAL AND METHODS: Ten eyes of 10 patients with recurrent HMMH and RD, who had already undergone one or more pars plana vitrectomy (PPV), underwent a PPV with an hAM plug implanted in the macular hole. The initial five patients enrolled were tamponaded with (SO) while the subsequent five patients with 10% octafluoropropane (C3 F8 ). Silicon oil was removed in all five patients 2 months later. No statistical differences were reported between the two groups. RESULTS: Final retinal reattachment was achieved in all the patients. BCVA improved from 1.73 logMAR to 0.94 logMAR after 6 months. No adverse events were registered during follow-up. CONCLUSION: An hAM plug is an efficient substrate to manage HMMH associated with RD resulting in encouraging visual acuity recovery.

Correction: Frataxin deficiency induces lipid accumulation and affects thermogenesis in brown adipose tissue.

Since online publication of this article, the authors noticed that there was a basic citation error in PubMed citation data. Specifically, the name of the author "Piergiorgio La Rosa" is cited as "Rosa P" in the PubMed citation, when it should be "La Rosa P", "La Rosa" being the surname and "Piergiorgio" the name of the author.

Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment.

OBJECTIVE: The metabolic influence of gut microbiota plays a pivotal role in the pathogenesis of cardiometabolic diseases. Antibiotics affect intestinal bacterial diversity, and long-term usage has been identified as an independent risk factor for atherosclerosis-driven events. The aim of this study was to explore the interaction between gut dysbiosis by antibiotics and metabolic pathways with the impact on atherosclerosis development. METHODS: We combined oral antibiotics with different diets in an Apolipoprotein E-knockout mouse model linking gut microbiota to atherosclerotic lesion development via an integrative cross-omics approach including serum metabolomics and cecal 16S rRNA targeted metagenomic sequencing. We further investigated patients with carotid atherosclerosis compared to control subjects with comparable cardiovascular risk. RESULTS: Here, we show that increased atherosclerosis by antibiotics was connected to a loss of intestinal diversity and alterations of microbial metabolic functional capacity with a major impact on the host serum metabolome. Pathways that were modulated by antibiotics and connected to atherosclerosis included diminished tryptophan and disturbed lipid metabolism. These pathways were related to the reduction of certain members of Bacteroidetes and Clostridia by antibiotics in the gut. Patients with atherosclerosis presented a similar metabolic signature as those induced by antibiotics in our mouse model. CONCLUSION: Taken together, this work provides insights into the complex interaction between intestinal microbiota and host metabolism. Our data highlight that detrimental effects of antibiotics on the gut flora are connected to a pro-atherogenic metabolic phenotype beyond classical risk factors.