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β-thalassemia is an haemoglobinopathy characterized by a defective synthesis of the β-globin chain. To assess the current state of health of paediatric patients with β-thalassemia, data from the French national registry regarding children born between 2005 and 2020 with β-thalassemia intermedia (TI) or major (TM) were collected. A total of 237 patients (median age 7.1 years at last visit) were analysed, of whom 156 (65.8%) were born in France and 162 (68.4%) had a TM phenotype. The probability of survival for children with TM born in France was 98.3% at 15 years. Fifty-four (22.8%) children received a haematopoietic stem cell transplant with a success rate of 88.8%. Hepatic and cardiac iron overload monitoring in non-transplanted patients showed moderate overload in 15.7% (18/115) and 7.1% (7/99) of cases, respectively, while clinical complications were found in only 4 patients with TM (hepatic in 3 cases). At last visit, mean ferritinemia was 1293 ng/ml (±759). Overall, less than 10% of children underwent splenectomy. No significant impact of the disease on growth or academic achievement was observed. Deferasirox was the main first-line chelator, prescribed in 78.2% of cases, with side effects reported in 11.7% of instances.

The use of ultrafast laser pulses for eye anterior segment surgery has seen a tremendous growth of interest as the technique has revolutionized the field, from the treatment of myopia, hyperopia, and presbyopia in the cornea to laser-assisted cataract surgery of the crystalline lens. For the latter, a comprehensive understanding of the laser–tissue interaction has yet to be achieved, mainly because of the challenge of observing the interaction zone in situ with sufficient spatial and temporal resolution in the complex and multi-layered tissue of the crystalline lens. We report here on the dedicated characterization results of the laser–tissue interaction zone in the ex vivo porcine lens using three different methods: in situ and real-time microscopy, wide-field optical imaging, and phase-contrast microscopy of the histological cross sections. These complementary approaches together revealed new physical and biological consequences of laser irradiation: a low-energy interaction regime (pulse energy below ~1 µJ) with very limited cavitation effects and a stronger photo-disruption regime (pulse energy above 1 µJ) with a long cavitation duration from seconds to minutes, resulting in elongated spots. These advances in the understanding of the ultrafast laser’s interactions with the lens are of the utmost importance for the preparation of the next-generation treatments that will be applied to the lens.

The gut microbiome is emerging as an important susceptibility factor in Alzheimer’s disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naïve adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD.

The gut microbiome is emerging as an important susceptibility factor in Alzheimer’s disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naïve adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD.

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The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

The EAT-Lancet Commission devised a sustainable reference diet with the aim of reducing the incidence of non-communicable diseases and mortality globally while improving food system sustainability. The extent to which the reference diet supports cognitive function across the life course, however, has not yet been evaluated. This Review assesses the evidence for diet supporting cognitive function from childhood into old age. A comprehensive but non-exhaustive literature search was done, synthesising studies that investigated the effect of whole foods on cognition in healthy, community-dwelling human participants. We found that the current evidence base is weak with mixed conclusions and multiple methodological caveats, which precludes strong conclusions pertaining to the suitability of dietary recommendations for each food group per age group. Long-term intervention and prospective cohort studies are needed to reduce this knowledge deficit. Revising dietary recommendations with the aim of maintaining an adequate nutrient intake to sustain healthy cognitive function across the life course could be worthwhile. This Review outlines recommendations for future work to help improve the current knowledge deficit regarding dietary intake and cognitive function across the life course and its implications for dietary guidelines such as the EAT-Lancet Commission. ispartof: LANCET PLANETARY HEALTH vol:6 issue:9 pages:E749-E759 ispartof: location:Netherlands status: published

Senescence is a cellular stress response that involves prolonged cell survival, a quasi-irreversible proliferative arrest and a modification of the transcriptome that sometimes includes inflammatory gene expression. Senescent cells are resistant to apoptosis, and if not eliminated by the immune system they may accumulate and lead to chronic inflammation and tissue dysfunction. Senolytics are drugs that selectively induce cell death in senescent cells, but not in proliferative or quiescent cells, and they have proved a viable therapeutic approach in multiple mouse models of pathologies in which senescence is implicated. As the catalogue of senolytic compounds is expanding, novel survival strategies of senescent cells are uncovered, and variations in sensitivity to senolysis between different types of senescent cells emerge. We propose herein a mechanistic classification of senolytic drugs, based on the level at which they target senescent cells: directly disrupting BH3 protein networks that are reorganized upon senescence induction; downregulating survival-associated pathways essential to senescent cells; or modulating homeostatic processes whose regulation is challenged in senescence. With this approach, we highlight the important diversity of senescent cells in terms of physiology and pathways of apoptosis suppression, and we describe possible avenues for the development of more selective senolytics.

Background/aimRejection is the main cause of graft failure after penetrating keratoplasty (PK). Its prevention by repeated instillation of steroid eye-drops has not evolved in decades. Poor adherence and discontinuous nature of eye-drop treatment may explain some PK failures. In a rabbit model, we previously demonstrated that a subconjunctival dexamethasone implant was well tolerated and prevented rejection efficiently in the first 5–6 weeks. This clinical trial investigates its tolerance and safety after PK.MethodsSingle-centre, phase II non-randomised tolerance and safety pilot study (NCT02834260). Designed to analyse the risk of elevated intraocular pressure (IOP), discomfort and resorption time. Fourteen patients with a low rejection risk indication of PK were enrolled between January 2017 and August 2018. The implant was injected in the 12 o’clock position, 5 mm from the limbus, at the end of PK. A steroid eye-drop treatment was planned when implant resorption was complete. Patients were monitored regularly for 12 months: IOP (main outcome measure at 1 month), discomfort and redness scores, implant status, rejection episode and central corneal thickness by optical coherence tomography. An independent data safety monitoring committee verified safety aspects.ResultsNo increase in IOP or other adverse event related to the implant was observed. Average resorption time was 6 weeks. The switch to steroid eye-drops was uneventful. One patient, included despite preoperative corneal neovascularisation (unintended protocol deviation) experienced a rejection.ConclusionsThis is the first proof of concept that dropless immunosuppression is possible after low rejection risk PK.Trial registration numberNCT02834260.