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Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 and has recently been approved for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) and locally advanced unresectable (NSCLC). The present review aimed to analyse immune-mediated uveitis, secondary to durvalumab treatment, through a review of the literature and a presentation of two clinical cases.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing—a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.

BackgroundWe present the disease course and long-term follow-up of two patients who were phenotypically diagnosed with atypical Leber Hereditary Optic Neuropathy (LHON) 14 and 12 years ago, respectively, whereby whole exome sequencing revealed recently described recessive DNAJC30:c.152G>A 152 A>G (p.Tyr51Cys) homozygous pathogenic variant with significant spontaneous visual acuity recovery in one.Case presentationTwo presented unrelated males with atypical LHON with sequential visual acuity (VA) loss were followed for many years. Both patients had negative family history. At the presentation at ages 17 (Case 1) and 18 years (Case 2), both had reduced visual acuity (Snellen): (Case 1) right eye (RE):CF 3m, left eye (LE):0.6, (Case 2) RE:0.2, LE:0.15; and color vision (Ishihara): (Case 1) 1/15 and 13/15; (Case 2) 2/15 and 3/15. Both had hyperemic optic disks (PNO) and central scotoma in their visual fields. Electrophysiology in the acute phase showed reduced and delayed visually evoked potentials (VEP) P100 in both patients, with reduced N95 amplitude in Case 2, and initially normal N95 amplitude in Case 1. Fluorescein angiography showed no early leakage with some late pooling at optic disks. Extensive clinical workout, including brain magnetic resonance imaging (MRI), aquaporin 4 (Aq4), and anti-myelin oligodendrocyte protein (anti-MOG) antibodies, was negative. Intravenous corticosteroids did not improve vision. Both experienced further deterioration several months after the onset accompanied by thinning of the peripapillary retinal nerve fiber layer (RNFL). Genetic testing for typical LHON pathogenic variants and whole mitochondrial DNA (mtDNA) sequencing was negative. 1 year after the onset, modest VA improvement began in Case 2 and continued over the next 3 years. VA improved bilaterally to 0.7, color vision 15/15, and islands of vision appeared within the visual field scotoma. VEP P100 peak time shortened, and amplitude increased, despite further RNFL thinning on optical coherent tomography (OCT). The patient's visual function remained stable during the entire 12-year follow-up period. Case 1 experienced modest VA improvement to 0.1 with some improvement in the visual field seven years after the disease onset, remaining stable during the entire 14-year follow-up period. VEP P100 wave remained undetectable.ConclusionsPresented are two autosomal recessive LHON (arLHON, OMIM:619382) cases with the same DNAJC30:c.152G>A pathogenic variant and different degrees of spontaneous visual recovery despite progressive RNFL thinning during a long-term follow-up. This mutation should be screened in every atypical LHON patient.

BackgroundEach inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration.Methods and findingsWe used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients.ConclusionsThese results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in Stargardt disease. It can be very useful in the evaluation of novel therapeutic modalities in rare disorders.

People have been accompanied by colours throughout the history and through all periods of life. In different eras, colours were also associated with status symbols of different social classes or mythological beliefs. We are often addressed emotionally by colour combinations, since colour perception is always and exclusively a sensorial experience. Various colour combinations can have a pleasant effect on us or leave us cold as well as in a state of shock. All of the above, presented the starting point of this research. Detection and perception of sensations through colour was accomplished by preparing a questionnaire related to 12 selected colours. The research included 302 participants from Slovenia, of both sexes and different ages, born from 1940 to 2004. From the obtained results, it could be concluded how popular a certain colour is in a material, design and spiritual sense. Moreover, the results were validated and compared regarding the gender and age of participants, and further compared with the results of previous studies.

The main objective of the presented research was to study the possibility of using natural colourants obtained through the aqueous extraction of fresh leaves from the Junglans regia (J. regia), or common walnut tree, for the dyeing of wool yarn. A unique principle was explored by combining the phases of extraction and mordanting into one with the aim of shortening the dyeing procedure, while at the same time extracting more colouring components. Spectrophotometric studies revealed the signifi cant impact of both mordant addition and dye-bath pH on the absorbance curve and thus on the colour and K/S values of the dyed samples. A meta-ordanting technique using ferrous sulphate produced a greater depth of shade at a wavelength of 400 nm, with respect to the concentration of mordant and the liquid ratio of the extraction. Finally, wool yarn dyed with pure leaf extracts exhibited a potent inhibiting activity against Candida albicans (C. albicans) with a moderate reduction rate of 59%, and an inhibited response against Staphylococcus aureus (S. aureus) with a low reduction rate of 38.6%.

The aim of this research was to apply three different types of zeolites and the combination thereof in the form of a very fine powder, together with different chemicals and additives on polyamide knitted fabric according to an industrially acceptable exhaustion procedure in order to study changes in the morphology, optical properties and wettability of surfaces. Zeolites were analysed using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and gas physiosorption. Additionally, the morphology of zeolite-coated surfaces was examined closely using SEM, while changes in molecular-chemical level were examined by means of IR spectroscopy. Optical properties were studied using CIE colour measurement and diffuse refl ectance profile determination, while the hydrophilic/hydrophobic character was examined using goniometry. The obtained results show the suitability of the employed exhaustion procedure, depending on the type of zeolite and the composition of the treatment bath. The results also provided evidence of the enhanced wettability of PA fabrics using 4A and 13X zeolites in combination with selected additives.

The rapid growth in wearable technology has recently stimulated the development of conductive textiles for broad application purposes, i.e., wearable electronics, heat generators, sensors, electromagnetic interference (EMI) shielding, optoelectronic and photonics. Textile material, which was always considered just as the interface between the wearer and the environment, now plays a more active role in different sectors, such as sport, healthcare, security, entertainment, military, and technical sectors, etc. This expansion in applied development of e-textiles is governed by a vast amount of research work conducted by increasingly interdisciplinary teams and presented systematic review highlights and assesses, in a comprehensive manner, recent research in the field of conductive textiles and their potential application for wearable electronics (so called e-textiles), as well as development of advanced application techniques to obtain conductivity, with emphasis on metal-containing coatings. Furthermore, an overview of protective compounds was provided, which are suitable for the protection of metallized textile surfaces against corrosion, mechanical forces, abrasion, and other external factors, influencing negatively on the adhesion and durability of the conductive layers during textiles’ lifetime (wear and care). The challenges, drawbacks and further opportunities in these fields are also discussed critically.