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Our aim is to compare foveal microvascular structure, foveal retinal thickness, and best-corrected visual acuity (BCVA) in children with a history of premature retinopathy (ROP) and healthy children. It is also evaluated whether microvascular structural changes in the course of ROP had resulted from treatment modalities of ROP or the disease itself.

This is a cross-sectional observational comparative study. Seventy-one children were analyzed in four different groups children treated with bevacizumab (18), or laser (19) for ROP; or spontaneously regressed disease (18) and non-premature healthy children (16). We analyzed foveal avascular zone (FAZ) and vessel densities (VDs) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at foveal and parafoveal region with optical coherence tomography angiography (OCT-A). selleck kinase inhibitor Foveal thickness was measured by cross-sectional OCT. Correlations between FAZ area, foveal VD, central foveal thickness (CFT), BCVA, gestational age (GA), and birth weight (BW) were evaluated.

After comparing of OCT-A parameters between all premature children (groups 1-3) and non-premature children (group 4), significant differences were found in VD-SCP (whole), VD-SCP (foveal), VD-SCP (parafoveal), CFT, and VD-DCP (foveal) (all p < 0.001). Significantly smaller FAZ area was also noted in ROP children. Higher foveal VD of SCP, DCP, and smaller FAZ area were significantly associated with lower GA and BW.

By using OCT-A, significant foveal microvascular anomalies were identified in children with ROP irrespective of the treatment option or spontaneous regression. There has been a correlation between microvascular anomalies, CFT, and a lower BCVA.

By using OCT-A, significant foveal microvascular anomalies were identified in children with ROP irrespective of the treatment option or spontaneous regression. There has been a correlation between microvascular anomalies, CFT, and a lower BCVA.

To examine structural changes in retinal layers over time in patients with non-arteritic anterior ischaemic optic neuropathy (NAION) and determine the layers that predict visual outcomes.

The optical coherence tomography parameters in NAION eyes at <2 months, 2-5 months, and 6-18 months from the onset were compared to age-matched normal controls. Generalised estimating equation analysis was used to analyse the changes over time and regression analysis was performed to identify the layer that could predict visual field outcomes.

Less than 2 months from the onset, the peripapillary retinal nerve fibre layer (RNFL) (p = 0.001) and macular outer nuclear layer (ONL) (p = 0.024) were significantly thicker in the NAION eyes than in the control eyes. The average peripapillary RNFL, macular RNFL, and ganglion cell layer and inner plexiform layer (GCIPL) showed reductions in thickness within 2-5 months (peripapillary RNFL -19.8 μm/month, p < 0.001, macular RNFL -14.5 μm/month, p < 0.001, GCIPL -26.8 μm/month, p < 0.001). The change of thickness in temporal and superior peripapillary RNFL, GCIPL, inner nuclear layer (INL), and ONL by 2-5 months was associated with the final visual field results (p = 0.018, p < 0.001, p = 0.040, p = 0.020, and p = 0.002, respectively).

The peripapillary RNFL swelling initially observed started to decrease within 2-5 months along with macular RNFL and GCIPL thinning. The rate of thickness changes in the peripapillary RNFL, GCIPL, INL, and ONL by 2-5 months was associated with visual field outcomes.

The peripapillary RNFL swelling initially observed started to decrease within 2-5 months along with macular RNFL and GCIPL thinning. The rate of thickness changes in the peripapillary RNFL, GCIPL, INL, and ONL by 2-5 months was associated with visual field outcomes.Astrocytes functionally interact with neurons and with other brain cells. Although not electrically excitable, astrocytes display a complex repertoire of intracellular Ca2+ signalling that evolves in space and time within single astrocytes and across astrocytic networks. Decoding the physiological meaning of these dynamic changes in astrocytic Ca2+ activity has remained a major challenge. This Review describes experimental preparations and methods for recording and studying Ca2+ activity in astrocytes, focusing on the analysis of Ca2+ signalling events in single astrocytes and in astrocytic networks. The limitations of existing experimental approaches and ongoing technical and conceptual challenges in the interpretation of astrocytic Ca2+ events and their spatio-temporal patterns are also discussed.Reinforcement learning (RL) is a framework of particular importance to psychology, neuroscience and machine learning. Interactions between these fields, as promoted through the common hub of RL, has facilitated paradigm shifts that relate multiple levels of analysis in a singular framework (for example, relating dopamine function to a computationally defined RL signal). Recently, more sophisticated RL algorithms have been proposed to better account for human learning, and in particular its oft-documented reliance on two separable systems a model-based (MB) system and a model-free (MF) system. However, along with many benefits, this dichotomous lens can distort questions, and may contribute to an unnecessarily narrow perspective on learning and decision-making. Here, we outline some of the consequences that come from overconfidently mapping algorithms, such as MB versus MF RL, with putative cognitive processes. We argue that the field is well positioned to move beyond simplistic dichotomies, and we propose a means of refocusing research questions towards the rich and complex components that comprise learning and decision-making.

Erythropoietic protoporphyria (EPP), characterized by painful cutaneous photosensitivity, results from pathogenic variants in ferrochelatase (FECH). For 96% of patients, EPP results from coinheriting a rare pathogenic variant in trans of a common hypomorphic variant c.315-48T>C (minor allele frequency 0.05). The estimated prevalence of EPP derived from the number of diagnosed individuals in Europe is 0.00092%, but this may be conservative due to underdiagnosis. No study has estimated EPP prevalence using large genetic data sets.

Disease-associated FECH variants were identified in the UK Biobank, a data set of 500,953 individuals including 49,960 exome sequences. EPP prevalence was then estimated. The association of FECH variants with EPP-related traits was assessed.

Analysis of pathogenic FECH variants in the UK Biobank provides evidence that EPP prevalence is 0.0059% (95% confidence interval [CI] 0.0042-0.0076%), 1.7-3.0 times more common than previously thought in the UK. In homozygotes for the common c.315-48T>C FECH variant, there was a novel decrement in both erythrocyte mean corpuscular volume (MCV) and hemoglobin.

The prevalence of EPP has been underestimated secondary to underdiagnosis. The common c.315-48T>C allele is associated with both MCV and hemoglobin, an association that could be important both for those with and without EPP.

C allele is associated with both MCV and hemoglobin, an association that could be important both for those with and without EPP.

Biallelic variants in TBC1D24, which encodes a protein that regulates vesicular transport, are frequently identified in patients with DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [previously referred to as mental retardation], and seizures) syndrome. The aim of the study was to identify a genetic cause in families with DOORS syndrome and without a TBC1D24 variant.

Exome or Sanger sequencing was performed in individuals with a clinical diagnosis of DOORS syndrome without TBC1D24 variants.

We identified the same truncating variant in ATP6V1B2 (NM_001693.4c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. This variant was already reported in individuals with dominant deafness onychodystrophy (DDOD) syndrome. Deafness was present in all individuals, along with onychodystrophy and abnormal fingers and/or toes. All families but one had developmental delay or intellectual disability and five individuals had epilepsy. We also describe two additional families with DDOD syndrome in whom the same variant was found.

We expand the phenotype associated with ATP6V1B2 and propose another causal gene for DOORS syndrome. This finding suggests that DDOD and DOORS syndromes might lieon a spectrum of clinically and molecularly relatedconditions.

We expand the phenotype associated with ATP6V1B2 and propose another causal gene for DOORS syndrome. This finding suggests that DDOD and DOORS syndromes might lie on a spectrum of clinically and molecularly related conditions.

Pseudoxanthoma elasticum (PXE) is a heritable disorder affecting elastic fibers in the skin, eyes, and cardiovascular system. It is caused by biallelic pathogenic variants in the ABCC6 gene. To date, over 300 ABCC6 variants are associated with PXE, more than half being missense variants. Correct variant interpretation is essential for establishing a direct link between the variant and the patient's phenotype and has important implications for diagnosis and treatment.

We used a systematic approach for interpretation of 271 previously reported and 15 novel ABCC6 missense variants, based on the semiquantitative classification system Sherloc.

Only 35% of variants were very likely to contribute directly to disease, in contrast to reported interpretations in ClinVar, while 59% of variants are currently of uncertain significance (VUS). Subclasses were created to distinguish VUS that are leaning toward likely benign or pathogenic, increasing the number of (likely) pathogenic ABCC6 missense variants to 47%.

Besides highlighting discrepancies between the Sherloc, American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), ClinVar, and Leiden Open Variation Database (LOVD) classification, our results emphasize the need for segregation analysis, functional assays, and detailed evidence sharing in variant databases to reach a confident interpretation of ABCC6 missense variants and subsequent appropriate genetic and preconceptual counseling.

Besides highlighting discrepancies between the Sherloc, American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), ClinVar, and Leiden Open Variation Database (LOVD) classification, our results emphasize the need for segregation analysis, functional assays, and detailed evidence sharing in variant databases to reach a confident interpretation of ABCC6 missense variants and subsequent appropriate genetic and preconceptual counseling.The nucleolus is the most prominent nuclear body and serves a fundamentally important biological role as a site of ribonucleoprotein particle assembly, primarily dedicated to ribosome biogenesis. Despite being one of the first intracellular structures visualized historically, the biophysical rules governing its assembly and function are only starting to become clear. Recent studies have provided increasing support for the concept that the nucleolus represents a multilayered biomolecular condensate, whose formation by liquid-liquid phase separation (LLPS) facilitates the initial steps of ribosome biogenesis and other functions. Here, we review these biophysical insights in the context of the molecular and cell biology of the nucleolus. We discuss how nucleolar function is linked to its organization as a multiphase condensate and how dysregulation of this organization could provide insights into still poorly understood aspects of nucleolus-associated diseases, including cancer, ribosomopathies and neurodegeneration as well as ageing.