ABSTRACT
Purpose
Evaluation of particle size distribution (PSD) of multimodal dispersion of nanoparticles is a difficult task due to inherent limitations of size measurement methods. The present work ...reports the evaluation of PSD of a dispersion of poly(isobutylcyanoacrylate) nanoparticles decorated with dextran known as multimodal and developed as nanomedecine.
Methods
The nine methods used were classified as batch particle i.e. Static Light Scattering (SLS) and Dynamic Light Scattering (DLS), single particle i.e. Electron Microscopy (EM), Atomic Force Microscopy (AFM), Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle Tracking Analysis (NTA) and separative particle i.e. Asymmetrical Flow Field-Flow Fractionation coupled with DLS (AsFlFFF) size measurement methods.
Results
The multimodal dispersion was identified using AFM, TRPS and NTA and results were consistent with those provided with the method based on a separation step prior to on-line size measurements. None of the light scattering batch methods could reveal the complexity of the PSD of the dispersion.
Conclusions
Difference between PSD obtained from all size measurement methods tested suggested that study of the PSD of multimodal dispersion required to analyze samples by at least one of the single size particle measurement method or a method that uses a separation step prior PSD measurement.
Heads-up three-dimensional (3D) surgical visualization systems allow ophthalmic surgeons to replace surgical microscope eyepieces with high-resolution stereoscopic cameras transmitting an image to a ...screen. We investigated the effectiveness and safety of the heads-up NGENUITY 3D Visualization System in a retrospective evaluation of 241 consecutive vitreoretinal surgeries performed by the same surgeon using conventional microscopy (CM group) over a 1-year period versus the NGENUITY System (3D group) over a consecutive 1-year period. We included for study vitreoretinal surgeries for treatment of retinal detachment (RD) (98 surgeries), macular hole (MH) (48 surgeries), or epiretinal membrane (ERM) (95 surgeries). A total of 138 and 103 eyes were divided into 3D and CM groups, respectively. We found no differences in 3-month postoperative rates of recurrence of RD (10% versus 18%, p = 0.42), MH closure (82% versus 88%, p = 0.69), or decrease in central macular thickness of ERMs (134 ± 188 µm versus 115 ± 105 µm, p = 0.57) between the 3D and CM groups, respectively. Surgery durations and visual prognosis were also similar between both groups. We consolidate that the NGENUITY System is comparable in terms of visual and anatomical outcomes, giving it perspectives for integration into future robotized intervention.
Oxazepam, one of the most frequently prescribed anxiolytic drugs, is not completely removed from wastewater with conventional treatment processes. It can thus be found at trace levels in ...environmental water, with human urine constituting the major source of contamination. This study focused on the development and characterization of molecularly imprinted polymers (MIPs) for the selective solid-phase extraction of oxazepam at trace levels from environmental water and human urine samples. Two MIPs were synthesized, and their selectivity in pure organic and aqueous media were assayed. After optimizing the extraction procedure adapted to a large sample volume to reach a high enrichment factor, the most promising MIP was applied to the selective extraction of oxazepam from environmental water. Extraction recoveries of 83 ± 12, 92 ± 4 and 89 ± 10% were obtained using the MIP for tap, mineral and river water, respectively, while a recovery close to 40% was obtained on the corresponding non-imprinted polymer (NIP). Thanks to the high enrichment factors, a limit of quantification (LOQ) of 4.5 ng L
−1
was obtained for river water. A selective extraction procedure was also developed for urine samples and gave rise to extraction recoveries close to 95% for the MIP and only 23% for the NIP. Using the MIP, a LOQ of 357 ng L
−1
was obtained for oxazepam in urine. The use of the MIP also helped to limit the matrix effects encountered for the quantification of oxazepam in environmental samples and in human urine samples after extraction on an Oasis HLB sorbent.
Graphical abstract
Background:
Leptomeningeal enhancement (LME) is a key feature of Susac syndrome (SuS) but is only occasionally depicted on post-contrast T1-weighted images (T1-WI).
Objective:
As post-contrast ...fluid-attenuated inversion recovery (FLAIR) may be more sensitive, our aim was to assess LME in SuS on this sequence.
Methods:
From 2010 to 2020, 20 patients with definite SuS diagnosis were retrospectively enrolled in this multicentre study. Two radiologists independently assessed the number of LME on post-contrast FLAIR and T1-WI acquisitions performed before any treatment. A chi-square test was used to compare both sequences and the interrater agreement was calculated.
Results:
Thirty-five magnetic resonance imagings (MRIs) were performed before treatment, including 19 post-contrast FLAIR images in 17 patients and 25 post-contrast T1-WI in 19 patients. In terms of patients, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (17/17 (100%) vs. 15/19 (79%), p < 0.05). In terms of sequences, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (19/19 (100%) vs. 16/25 (64%), p < 0.005). LME was disseminated at both supratentorial (19/19) and infratentorial (18/19) levels on post-contrast FLAIR, contrary to post-contrast T1-WI (3/25 and 9/25, respectively). Interrater agreement was excellent for post-contrast FLAIR (κ = 0.95) but only moderate for post-contrast T1-WI (κ = 0.61).
Conclusion:
LME was always observed and easily visible on post-contrast FLAIR images prior to SuS treatment. In association with other MRI features, it is highly indicative of SuS.
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•A methodology to validate protocols of size measurement by DLS was proposed.•A validation of 2 protocols was achieved using 2 standards at 60 and 203nm.•Protocols were found robust, ...accurate and consistent with standard ISO.•Expanded uncertainties were less than 10% for measurements performed at 25°C.•Protocols were suitable to determine the size of monodispersed nanomaterials.
Among physico-chemical properties used to characterize nanomaterials, size and size distribution are essential. Several methods are suitable to evaluate these characteristics including the well-established method based on dynamic light scattering (DLS). Size measurement protocols have been rarely standardized or totally validated. However, there is a need for having standardized and validated protocols for the characterization of nanomaterials due to the pressure of authorities interested by the evaluation of risk assessments on nanomaterials that are introduced in increasing number of applications. Standardization is paramount to provide comparable values between different laboratories. This paper proposes a standardization of two protocols for evaluating the size of nanomaterials by DLS at 20 and 25°C and a methodology to achieve their validation by investigating their robustness, precision and trueness using appropriate certified reference materials including standards of 60 and 203nm whose assigned values were traceable to the International System of Units. Data were interpreted using specifically designed methods of analysis of variance ANOVA. Uncertainties of protocols proposed in the present work were 7.0 and 3.8% for dispersions at 60 and 203nm respectively at temperature of measurement of 20°C and 6.8 and 3.8% for dispersions at 60 and 203nm respectively at temperature of measurement of 25°C. These values attested that both protocols give reliable size measurements of diverse nanomaterials.
Erdheim-Chester disease (ECD) is a rare histiocytic disorder, recently recognized to be neoplastic. The clinical phenotype of the disease is extremely heterogeneous, and depends on the affected ...organs, with the most frequently reported manifestations being bone pain, diabetes insipidus and neurological disorders including ataxia. In this article, we report on a case of a 48-year-old woman, whose initial symptom of gait instability was isolated. This was associated with positional nystagmus with central features: nystagmus occurring without latency, clinically present with only mild symptoms, and resistant to repositioning maneuvers. The cerebral MRI showed bilateral intra-orbital retro-ocular mass lesions surrounding the optic nerves and T2 hyperintensities in the pons and middle cerebellar peduncles. A subsequent CT scan of the chest abdomen and pelvis found a left "hairy kidney", while
F-FDG PET-CT imaging disclosed symmetric 18F-FDG avidity predominant at the diametaphyseal half of both femurs. Percutaneous US-guided biopsy of perinephric infiltrates and the kidney showed infiltration by CD68(+), CD1a(-), Langerin(-), PS100(-) foamy histiocytes with
mutation. The combination of the different radiological abnormalities and the result of the biopsy confirmed the diagnosis of ECD. Many clinical and radiological descriptions are available in the literature, but few authors describe vestibulo-ocular abnormalities in patients with ECD. Here, we report on a case of ECD and provide a precise description of the instability related to central positional nystagmus, which led to the diagnosis of ECD.
Neuro-ophthalmological changes named spaceflight associated neuro-ocular syndrome (SANS) reported after spaceflights are important medical issues. Dry immersion (DI), an analog to microgravity, ...rapidly induces a centralization of body fluids, immobilization, and hypokinesia similar to that observed during spaceflight. The main objectives of the present study were 2-fold: (1) to assess the neuro-ophthalmological impact during 5 days of DI and (2) to determine the effects of venoconstrictive thigh cuffs (VTC), used as a countermeasure to limit headward fluid shift, on DI-induced ophthalmological adaptations. Eighteen healthy male subjects underwent 5 days of DI with or without VTC countermeasures. The subjects were randomly assigned into two groups of 9: a control and cuffs group. Retinal and optic nerve thickness were assessed with spectral-domain optical coherence tomography (OCT). Optic nerve sheath diameter (ONSD) was measured by ocular ultrasonography and used to assess indirect changes in intracranial pressure (ICP). Intraocular pressure (IOP) was assessed by applanation tonometry. A higher thickness of the retinal nerve fiber layer (RNFL) in the temporal quadrant was observed after DI. ONSD increased significantly during DI and remained higher during the recovery phase. IOP did not significantly change during and after DI. VTC tended to limit the ONSD enlargement but not the higher thickness of an RNFL induced by DI. These findings suggest that 5 days of DI induced significant ophthalmological changes. VTC were found to dampen the ONSD enlargement induced by DI.
Introduction
The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with ...intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies).
Methods
This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24 months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups).
Results
Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8 years). After 24 months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters;
p
< 0.001) and CRT significantly decreased (388.6 ± 104 vs. 278.8 ± 51 μM;
p
< 0.001) with 21% of eyes showing signs of exudation. Over the 24 months, a mean total of 14.9 ± 4.0 injections and 8.6 ± 1.4 consultations were performed. Mean 24-month injection interval was 7.9 ± 2.3 weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3 ± 2.4 vs. 9.9 ± 2.5 weeks;
p
< 0.001). Patients in the strict RTE group received significantly less injections (13.9 ± 3.6 vs. 16.5 ± 3.9;
p
= 0.006) and mean 24-month injection interval was significantly longer (9.5 ± 2.7 vs. 6.5 ± 2.1 weeks;
p
< 0.001). Consultation number was similar (8.5 ± 1.9 vs. 8.8 ± 1.6;
p
= 0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes.
Conclusions
The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance.
Video Abstract available for this article.
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VIDEO ABSTRACT:
Vincent Soler and François-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB)
Dominant Optic Atrophy (DOA) is one of the most common inherited mitochondrial diseases, leading to blindness. It is caused by the chronic degeneration of the retinal ganglion cells (RGCs) and their ...axons forming the optic nerve. Until now, DOA has been mainly associated with genes encoding proteins involved in mitochondrial network dynamics. Using next-generation and exome sequencing, we identified for the first time heterozygous PMPCA variants having a causative role in the pathology of late-onset primary DOA in five patients. PMPCA encodes an α subunit of the mitochondrial peptidase (MPP), responsible for the cleavage and maturation of the mitochondrial precursor proteins imported from the cytoplasm into mitochondria. Recently, PMPCA has been identified as the gene responsible for Autosomal Recessive Cerebellar Ataxia type 2 (SCAR2) and another severe recessive mitochondrial disease. In this study, four PMPCA variants were identified, two are frameshifts (c.309delA and c.820delG) classified as pathogenic and two are missenses (c.1363G>A and c.1547G>A) classified with uncertain pathological significance. Functional assays on patients’ fibroblasts show a hyperconnection of the mitochondrial network and revealed that frameshift variants reduced α-MPP levels, while not significantly affecting the respiratory machinery. These results suggest that alterations in mitochondrial peptidase function can affect the fusion-fission balance, a key element in maintaining the physiology of retinal ganglion cells, and consequently lead to their progressive degeneration.
After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called "spaceflight associated neuro-ocular syndrome" (SANS). ...The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS.
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