Alpha-klotho and peritoneal membrane status: A hypothesis generating study.

BACKGROUND: Long-term success of peritoneal dialysis relies on the integrity of the peritoneal membrane. This proof-of-concept study addressed the hypothesis that fibrosis is already present in the membrane at pre-dialysis and that the membrane status is related to the individual's uraemic fingerprint. METHODS: A clinical-mechanistic, transversal, single-centre study was conducted. Pre-dialysis peritoneal biopsies were scored considering the submesothelial compact zone thickness (STM), vasculopathy and inflammation. We investigated if the membrane status could be inferred from a panel of proteins (α-Klotho, Galectin-3, FGF21, FGF23, Tweak, TNFα and hsPCR) in blood. RESULTS: A total 58 incident patients aged 56 ± 15 years old were included, 31% female, 55% hypertension, 29% diabetic and 24% obese. Person-to-person STM was found to be highly variable and 38% of patients were fibrosis positive. Both α-Klotho (Spearman r = -.7491, p < 0.001) and FGF21 (Spearman r = -.5102, p < 0.001) were negatively associated with STM. α-Klotho, but not FGF21, was able to discriminate fibrosis from nonfibrosis with/without inflammation and vasculopathy. PLS models identified α-Klotho as the protein most relevant for fibrosis. α-Klotho was independently associated with fibrosis of the peritoneal membrane (OR = .991 (.896-.997), p = 0.002). CONCLUSION: Before the start of dialysis in incident patients, some patients already present fibrosis of the peritoneal membrane and other patients do not. Our findings suggest that α-Klotho may be implicated in fibrosis of the peritoneal membrane.

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis.

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.

Ergonomic intervention program for office workers: a case study about its effect in computer vision syndrome and musculoskeletal discomfort.

This study aims to develop and implement an ergonomic intervention program at the workplace of knowledge workers, and to evaluate its impact on the reduction of Computer Vision Syndrome (CVS) and musculoskeletal symptoms. 84 workers were part of the study (mean age 43.2 ± 9.7 years). The intervention included training, delivery of a packaging of artificial tears, and adjustments in workstations. It was conducted intensively along 6 weeks. Data was collected on-site, with questionnaires administered pre-intervention, 2 months after, and 4 months after. Participants exhibited behavioural changes, especially in workplace adjustments and visual rest. By the intervention's end, over 90% had correctly adjusted screens and adopted appropriate postures, while 42.7% adhered to the 20x20x20 rule. CVS severity and prevalence decreased, but not significantly across the three time points. Significant improvements were observed in upper back and neck musculoskeletal symptoms at the end of workdays. Findings suggest that an ergonomic intervention program can benefit employees by reducing visual and musculoskeletal symptoms.

Practitioner summary: This study addresses CVS and MSDs, commonly experienced by individuals working with display screen equipment. It was emphasised the significance of ergonomic interventions in reducing musculoskeletal discomfort. The major finding was the positive behavioural changes, such as improved workplace adjustments and visual rest practices.

Triplication of DYRK1A causes retinal structural and functional alterations in Down syndrome.

Down syndrome (DS) results from the triplication of approximately 300 human chromosome 21 (Hsa21) genes and affects almost all body organs. Children with DS have defects in visual processing that may have a negative impact on their daily life and cognitive development. However, there is little known about the genes and pathogenesis underlying these defects. Here, we show morphometric in vivo data indicating that the neural retina is thicker in DS individuals than in the normal population. A similar thickening specifically affecting the inner part of the retina was also observed in a trisomic model of DS, the Ts65Dn mouse. Increased retinal size and cellularity in this model correlated with abnormal retinal function and resulted from an impaired caspase-9-mediated apoptosis during development. Moreover, we show that mice bearing only one additional copy of Dyrk1a have the same retinal phenotype as Ts65Dn mice and normalization of Dyrk1a gene copy number in Ts65Dn mice completely rescues both, morphological and functional phenotypes. Thus, triplication of Dyrk1a is necessary and sufficient to cause the retinal phenotype described in the trisomic model. Our data demonstrate for the first time the implication of DYRK1A overexpression in a developmental alteration of the central nervous system associated with DS, thereby providing insights into the aetiology of neurosensorial dysfunction in a complex disease.

Development and aging of visual hemifield asymmetries in contrast sensitivity.

The relation of development and aging with models of visual anisotropies and their influence on low-level visual processing remain to be established. Our main goal was to explore visual performance asymmetries in development and normal aging using low-level contrast sensitivity behavioral tasks [probing two distinct spatiotemporal frequency channels, (a) intermediate spatial and null temporal frequency (3.5 cycles per degree (cpd) and 0 Hz); and (b) low spatial and high temporal frequency (0.25 cpd undergoing 25 Hz counterphase flicker)]. Different patterns of functional asymmetries were investigated within four (two neurodevelopmental and two adult) age groups (N = 258 participants; 8-65 years). We found a left visual hemifield/right hemisphere advantage for only the intermediate spatial frequency channel that was present early in life and remained stable throughout adulthood. In contrast, inferior/superior visual hemifield asymmetries, with a direct ecological meaning, were found for both spatiotemporal frequency channels. This inferior visual hemifield advantage emerged early in life and persisted throughout aging. These findings show that both right hemispheric and dorsal retinotopic patterns of dominance in low-level vision emerge early in childhood, maintaining during aging.

Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss.

Visual cortical plasticity induced by overt retinal lesions (scotomas) has remained a controversial phenomenon. Here we studied cortical plasticity in a silent model of retinal ganglion cell loss, documented by in vivo optical biopsy using coherence tomography. The cortical impact of non-scotomatous subtle retinal ganglion cell functional and structural loss was investigated in carriers of the mitochondrial DNA 11778G>A mutation causing Leber's hereditary optic neuropathy. We used magnetic resonance imaging (MRI) to measure cortical thickness and fMRI to define retinotopic cortical visual areas V1, V2 and V3 in silent carriers and matched control groups. Repeated Measures analysis of variance revealed a surprising increase in cortical thickness in the younger carrier group (below 21 years of age). This effect dominated in extrastriate cortex, and notably V2. This form of structural plasticity suggests enhanced plastic developmental mechanisms in extrastriate retinotopic regions close to V1 and not receiving direct retinocortical input.

Physiological evidence for impairment in autosomal dominant optic atrophy at the pre-ganglion level.

BACKGROUND: Functional studies in patients with autosomal dominant optic atrophy (ADOA) are usually confined to analysis of physiological and clinical impact at the ganglion cell (GG) and post GC levels. Here we aimed to investigate the impact of the disease at a pre-GC level and its correlation with GC/post-GC related measures. METHODS: Visual function was assessed in a population of 22 subjects (44 eyes) from 13 families with ADOA submitted to OPA1 mutation analysis. Quantitative psychophysical methods were used to assess konio and parvocellular chromatic pathways (Cambridge Colour Test) and distinct achromatic spatial frequency channels (Metropsis Contrast Sensitivity Test). Preganglionic and GC measures were assessed with the Multifocal Electroretinogram (mfERG) and Pattern Electroretinogram (PERG) respectively. Global Pattern and Multifocal VEP (visual evoked potentials) were used to assess retinocortical processing, in order to characterize impaired processing at the post GC level. Perimetric sensitivity, retinal and ganglion cell nerve fibre layer (RNFL) thickness measurements were also obtained. RESULTS: Chromatic thresholds were significantly increased for protan, deutan and tritan axes (p < < 0.001 for all comparisons) and achromatic contrast sensitivity (CS) was reduced for all studied six spatial frequency channels (p < < 0.001). We observed significant decreases in peripapillary (p ≤ 0.0008), macular (ring2: p = 0.02; ring 3: p < 0.0001) RNFL, as well as in overall retinal thickness (p < 0.0001 in all regions, except the central one). Interestingly, we found significant decreases in pre-ganglionic multifocal ERG response amplitudes (P1-wave: p ≤ 0.005) that were correlated with retinal thickness (ring 2: r = 0.512; p = 0.026/ring 3: r = 0.583; p = 0.011) and visual acuity (r = 0.458; p = 0.03, central ring 1). Reductions in GC and optic nerve responses amplitude (PERG: p < 0.0001, P50 and N95 components; Pattern VEP: p < 0.0001, P100) were accompanied by abnormalities of the MfVEP, primarily in central locations (ring 1: p = 0.0007; ring 2: p = 0.012). CONCLUSIONS: In the ADOA model of ganglion cell damage, parvo-, konio- and magnocellular pathways are concomitantly affected. Structural changes and physiological impairment also occurs at a preganglionic level, suggesting a retrograde damage mechanism with a significant clinical impact on visual function, as shown by correlation analysis. Cortical impairment is only moderately explained by the retinal phenotype, suggesting additional damage mechanisms at the cortical level.

Membranous nephropathy after a recent SARS-CoV-2 infection.

SARS-CoV-2 infections can induce kidney injury and glomerulopathy, with the most common pathology findings being acute tubular injury and collapsing glomerulopathy.Here we describe a rare case of membranous nephropathy in a man in his late 70s presented with nephrotic syndrome and rapidly progressive kidney dysfunction 1 month after SARS-CoV-2 infection. Phospholipase A2 receptor antibodies were positive. He was treated with rituximab, with proteinuria control. We review the cases reported in the literature.

Real-Time Blink Detection as an Indicator of Computer Vision Syndrome in Real-Life Settings: An Exploratory Study.

With the increase in the number of people using digital devices, complaints about eye and vision problems have been increasing, making the problem of computer vision syndrome (CVS) more serious. Accompanying the increase in CVS in occupational settings, new and unobstructive solutions to assess the risk of this syndrome are of paramount importance. This study aims, through an exploratory approach, to determine if blinking data, collected using a computer webcam, can be used as a reliable indicator for predicting CVS on a real-time basis, considering real-life settings. A total of 13 students participated in the data collection. A software that collected and recorded users' physiological data through the computer's camera was installed on the participants' computers. The CVS-Q was applied to determine the subjects with CVS and its severity. The results showed a decrease in the blinking rate to about 9 to 17 per minute, and for each additional blink the CVS score lowered by 1.26. These data suggest that the decrease in blinking rate was directly associated with CVS. These results are important for allowing the development of a CVS real-time detection algorithm and a related recommendation system that provides interventions to promote health, well-being, and improved performance.

Seascape genomics reveals limited dispersal and suggests spatially varying selection among European populations of sea lamprey (Petromyzon marinus).

Sea lamprey Petromyzon marinus is an anadromous and semelparous fish without homing behaviors. Despite being a freshwater, free-living organism for a large part of their life cycle, its adulthood is spent as a parasite of marine vertebrates. In their native European range, while it is well-established that sea lampreys comprise a single nearly-panmictic population, few studies have further explored the evolutionary history of natural populations. Here, we performed the first genome-wide characterization of sea lamprey's genetic diversity in their European natural range. The objectives were to investigate the connectivity among river basins and explore evolutionary processes mediating dispersal during the marine phase, with the sequencing of 186 individuals from 8 locations spanning the North Eastern Atlantic coast and the North Sea with double-digest RAD-sequencing, obtaining a total of 30,910 bi-allelic SNPs. Population genetic analyses reinforced the existence of a single metapopulation encompassing freshwater spawning sites within the North Eastern Atlantic and the North Sea, though the prevalence of private alleles at northern latitudes suggested some limits to the species' dispersal. Seascape genomics suggested a scenario where oxygen concentration and river runoffs impose spatially varying selection across their distribution range. Exploring associations with the abundance of potential hosts further suggested that hake and cod could also impose selective pressures, although the nature of such putative biotic interactions was unresolved. Overall, the identification of adaptive seascapes in a panmictic anadromous species could contribute to conservation practices by providing information for restoration activities to mitigate local extinctions on freshwater sites.

Misidentification of epithelial renal tubular cells as decoy cells in the urinary sediment of a kidney transplant recipient: the importance of adequate clinical information.

The examination of the urinary sediment of a kidney transplant recipient, carried out in blind conditions, showed the presence of a moderate number of cells which were identified as decoy cells. Most frequently these cells are a marker of BK polyomavirus reactivation, which can lead to BK virus nephropathy and graft loss. However, the patient's clinical history, the absence of BK viremia, and the renal biopsy findings excluded this condition. The careful examination of the renal biopsy demonstrated a severe tubular damage with cells resembling those identified in the urine as decoy cells. This paper is the first which demonstrates that damaged renal tubular epithelial cells can be misidentified as decoy cells. In addition, it highlights the importance of supplying adequate clinical information for a correct urinary sediment examination.

Non-diabetic metabolic nodular glomerulosclerosis.

Nodular glomerulosclerosis is classically associated with diabetes. Nowadays, it is well known that this histologic pattern can be the presentation of different diseases, including dysproteinemias and amyloidosis. Most recently, the previously thought to be idiopathic nodular glomerulosclerosis has been associated with hypertension, smoking, and obesity. We present a clinical case of a non-diabetic 74-year-old man, with hypertension and heavy smoking history, who presented with nephrotic proteinuria and chronic kidney disease. We review the literature and propose a different nomenclature for this pattern of metabolic glomerulopathy.

Pantoea in Peritoneal Dialysis: A Rare Cause of Peritonitis.

Peritonitis is the most common complication of peritoneal dialysis (PD) and an important cause of PD failure. There are numerous etiological agents, mostly bacteria. Pantoea spp is a rare cause of peritonitis. We describe three cases of Pantoea peritonitis in three PD patients. Previous reports have identified risk factors such as close contact with plants and animals. We review the typical clinical presentation and prognosis. It is fulcral to teach patients about the risks regarding proximity to plants and animals to prevent this type of infection.

Thrombotic microangiopathy triggered by podocytopathy.

Thrombotic microangiopathy (TMA) is a rare group of diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ damage. It can be divided into primary and secondary TMA. Herein we report a case of TMA associated to a primary glomerular disease. We report the case of a 31-year-old Black male from Cape Verde admitted in March 2018 with nephrotic syndrome and upper gastrointestinal bleeding, the latter due to severe erythematous gastritis. He was discharged after clinical stabilization. The patient came to Portugal 8 months later. On admission, he presented with rapid deterioration of kidney function and hyperkalemia. The etiologic study revealed microangiopathic hemolytic anemia, nephrotic syndrome and microscopic hematuria. Immunologic study and viral serology were negative. ADAMTS13 activity and inhibitor testing were within normal range, genetic complement evaluation showed CFH-H3 in homozygosity, functional complement studies revealed decreased function of alternative pathway. Kidney biopsy was consistent with the diagnosis of TMA, and electron microscopy was compatible with minimal change disease. Patient underwent plasmapheresis with resolution of hemolysis, fluid overload and recovery of renal function. Two months later, he presented with nephrotic syndrome and started prednisolone with remission. Six months later, the nephrotic syndrome relapsed, and it became steroid-, MMF-, and rituximab-resistant. Tacrolimus was initiated, achieving partial remission. Atypical hemolytic uremic syndrome is an uncommon disease and is rarely reported as secondary to glomerular diseases. This case showcases the challenges regarding treatment options in a resistant glomerulopathy and the implications of therapeutic choices and kidney outcomes with the coexisting TMA.

Asymmetry of visual sensory mechanisms: electrophysiological, structural, and psychophysical evidences.

Psychophysical visual field asymmetries are widely documented and have been attributed to anatomical anisotropies both at the retinal and cortical levels. This debate on whether such differences originate within the retina itself or are due to higher visual processing may be illuminated if concomitant anatomical, physiological, and psychophysical measures are taken in the same individuals. In the current study, we have focused on the study of objective functional and structural asymmetries at the retinal level and examined their putative correlation with visual performance asymmetries. Forty healthy participants (80 eyes; 13 male and 27 female subjects) were included in this study. Objective functional/structural asymmetries were probed using the multifocal electroretinogram (mfERG) technique and optical coherence tomography (OCT), respectively. A nasal/temporal pattern of asymmetry (nasal visual hemifield disadvantage) was found for all methods (retinal thickness, contrast sensitivity, and mfERG P1 amplitude). Furthermore, superior/inferior asymmetries could be documented only with psychophysics and structural measures. These patterns likely arise at different levels of the retina as inferred by partly independent correlation patterns. We conclude that patterns of structural/functional asymmetries arise at different levels of visual processing with a strong retinal contribution.

Retinal and cortical patterns of spatial anisotropy in contrast sensitivity tasks.

It has often been postulated that asymmetries in performance within the visual field (VF) are not characteristic of early visual processing. Here, human retinal (naso/temporal), cortical (left/right) and superior/inferior patterns of asymmetry were explored with achromatic contrast sensitivity (CS) tasks, that probed distinct spatiotemporal frequency channels. Low spatial, high temporal frequency stimuli (illusory frequency-doubling (FD)) yielded superior and temporal field disadvantage. Independent right and nasal visual hemifield patterns of disadvantage were found when probing an intermediate spatial frequency (ISF) channel, with stationary sinusoidal gratings. These findings show that asymmetries in spatial vision are explained by independent retinal and cortical mechanisms.

Pattern of Retinal Nerve Fiber Layer Thickness Loss in Fetal Alcohol Syndrome: A Spectral-Domain Optical Coherence Tomography Analysis.

INTRODUCTION: Optic disc hypoplasia is a common feature in fetal alcohol syndrome. Thus, we aimed to evaluate the optic disc morphology changes and the peripapillary retinal nerve fiber layer thickness in these patients. MATERIAL AND METHODS: We performed spectral-domain optical coherence tomography in a cohort of 11 patients (22 eyes) with fetal alcohol syndrome and in an age-matched control group. We evaluated optic nerve head parameters (optic disc area and diameter, rim area, cup/disc horizontal and vertical ratios) and peripapillary retinal nerve fiber layer thickness. RESULTS: Mean optic disc area, rim area and optic disc diameter were, respectively, in fetal alcohol syndrome patients and control subjects: 1.540 ± 0.268 and 1.748 ± 0.326 mm2; 1.205 ± 0.286 and 1.461 ± 0.314 mm2; 1.417 ± 0.124 and 1.501 ± 0.148 mm (p < 0.05). We found no significant differences between groups for cup/disc ratios. Mean retinal nerve fiber layer thickness was significantly lower in fetal alcohol syndrome patients (90.500 ± 9.344 µm) as compared to controls (111.000 ± 7.855 µm) (p < 0.0001). Analysis showed a significant decrease in retinal nerve fiber layer thickness for the superior, inferior and nasal quadrants (p < 0.005). The temporal quadrant showed no significant differences. DISCUSSION: Optic disc area, rim area and optic disc diameters were significantly reduced in fetal alcohol syndrome patients. Although mean peripapillary retinal nerve fiber layer thickness was decreased, the temporal quadrant was spared. CONCLUSION: In addition to a smaller optic disc area/ diameter and rim area, we found a heterogeneous peripapillary retinal nerve fiber layer thickness loss in fetal alcohol syndrome patients with sparing of the temporal quadrant. Spectral-domain optical coherence tomography may be useful to determine the presence of fetal alcohol syndrome status.

Introdução: A hipoplasia do disco ótico é característica comum na síndrome fetal-alcoólica. Assim, propusemo-nos a avaliar as alterações morfológicas do disco ótico e a espessura da camada de fibras nervosas retinianas peripapilares, nunca antes estudada nestes doentes. Material e Métodos: Realizamos tomografia de coerência óptica de domínio espectral num grupo de 11 doentes (22 olhos) com síndrome fetal-alcoólica e num grupo controlo ajustado à idade. Avaliamos alguns parâmetros morfológicos do disco ótico (área e diâmetro do disco ótico, área do anel neurorretiniano, razão escavação/disco horizontal e vertical) e a espessura da camada de fibras nervosas retiniana peripapilares. Resultados: Os valores médios da área do disco ótico, anel neurorretiniano e diâmetro do disco ótico foram, respetivamente, no grupo de doentes e no grupo controlo: 1,540 ± 0,268 e 1,748 ± 0,326 mm2; 1,205 ± 0,286 e 1,461 ± 0,314 mm2; 1,417 ± 0,124 e 1,501 ± 0,148 mm (p < 0,05). Não encontramos diferenças significativas entre as razões escavação/disco. A espessura média da camada de fibras nervosas foi significativamente menor nos pacientes (90,500 ± 9,344 µm) relativamente aos controlos (111,000 ± 7,855 µm) (p < 0,0001). Verificamos uma diminuição significativa nos quadrantes superior, inferior e nasal (p < 0,005). O quadrante temporal não revelou diferenças significativas. Discussão: As áreas do disco ótico e anel neurorretiniano e o diâmetro do disco ótico foram significativamente menores nos pacientes com síndrome fetal-alcoólica. Embora a espessura média da camada de fibras nervosas peripapilares se tenha revelado diminuída, o quadrante temporal parece estar poupado. Conclusão: Para além de uma área/diâmetro do disco ótico e área do anel neurorretiniano menores, descobrimos um padrão heterogéneo de perda da camada de fibras nervosas retinianas peripapilares em pacientes com síndrome fetal-alcoólica, sem atingimento do quadrante temporal. A tomografia de coerência óptica poderá ser útil no estabelecimento do diagnóstico da síndrome fetal-alcoólica.

European Lampreys: New Insights on Postglacial Colonization, Gene Flow and Speciation.

Ice ages are known to be the most dominant palaeoclimatic feature occurring on Earth, producing severe climatic oscillations and consequently shaping the distribution and the population structure of several species. Lampreys constitute excellent models to study the colonization of freshwater systems, as they commonly appear in pairs of closely related species of anadromous versus freshwater resident adults, thus having the ability to colonize new habitats, through the anadromous species, and establish freshwater resident derivates. We used 10 microsatellite loci to investigate the spatial structure, patterns of gene flow and migration routes of Lampetra populations in Europe. We sampled 11 populations including the migratory L. fluviatilis and four resident species, L. planeri, L. alavariensis, L. auremensis and L. lusitanica, the last three endemic to the Iberian Peninsula. In this southern glacial refugium almost all sampled populations represent a distinct genetic cluster, showing high levels of allopatric differentiation, reflecting long periods of isolation. As result of their more recent common ancestor, populations from northern Europe are less divergent among them, they are represented by fewer genetic clusters, and there is evidence of strong recent gene flow among populations. These previously glaciated areas from northern Europe may have been colonized from lampreys expanding out of the Iberian refugia. The pair L. fluviatilis/L. planeri is apparently at different stages of speciation in different locations, showing evidences of high reproductive isolation in the southern refugium, and low differentiation in the north.