Retraction Note: Autoantibodies detection in patients affected by autoimmune retinopathies.

The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.

Autoantibodies detection in patients affected by autoimmune retinopathies.

OBJECTIVE: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. PATIENTS AND METHODS: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. RESULTS: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). CONCLUSIONS: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Optical coherence tomography angiography in Purtscher-like retinopathy associated with dermatomyositis: a case report.

PURPOSE: To describe a multimodal imaging diagnosis of retinopathy in dermatomyositis. CASE PRESENTATION: A 21-year-old white woman with a history of fatigue and a cutaneous rash complained of visual impairment in her left eye. A funduscopic examination showed multiple confluent cotton-wool spots in both eyes. Swept source-optical coherence tomography presented macular edema in both eyes; optical coherence tomography angiography revealed superficial and deep capillary occlusion in all areas affected by cotton-wool spots; and fluorescein angiography showed vascular walls enhancement, veins dilatation, and capillary leakage. After large doses of intravenously administered glucocorticoid therapy, followed by a cyclophosphamide regimen, best corrected visual acuity returned to 20/20 in both eyes. CONCLUSIONS: This case report presents optical coherence tomography angiography clinical findings in a rare case of dermatomyositis-associated retinopathy, remarking the importance of a multi-imaging approach for a correct diagnosis and treatment of eye injuries, in order to avoid serious complications and permanent sequelae.

Visual function improvement using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by retinal diseases.

BACKGROUND: To evaluate functional visual parameters using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by central or peripheral scotoma due to retinal diseases. Sixty patients were enrolled in this study: 30 patients affected by central scotoma, group 1, and 30 affected by peripheral scotoma, group 2. Black on White Best Corrected Visual Acuity (BW-BCVA), White on Black Best Corrected Visual Acuity (WB-BCVA), Mars Contrast Sensitivity (CS) and a Glare Test (GT) were performed to all patients. Test results with blue-violet filter, a short-pass yellow filter and with no filters were compared. RESULTS: All scores from test results increased significantly with blue-violet filters for all patients. The mean BW-BCVA increased from 0.30 ± 0.20 to 0.36 ± 0.21 decimals in group 1 and from 0.44 ± 0.22 to 0.51 ± 0.23 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The mean WB-BCVA increased from 0.31 ± 0.19 to 0.38 ± 0.23 decimals in group 1 and from 0.46 ± 0.20 to 0.56 ± 0.22 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The letter count for the CS test increased from 26.7 ± 7.9 to 30.06 ± 7.8 in group 1 (Mean ± SD, p = 0.0005) and from 31.5 ± 7.6 to 33.72 ± 7.3 in group 2 (Mean ± SD, p = 0.031). GT was significantly reduced: the letter count increased from 20.93 ± 5.42 to 22.82 ± 4.93 in group 1 (Mean ± SD, p < 0.0001) and from 24.15 ± 5.5 to 25.97 ± 4.7 in group 2 (Mean ± SD, p < 0.0001). Higher scores were recorded with the Blue filter compared to Yellow filter in all tests (p < 0.05). No significant differences in any test results could be detected between the Yellow filter and the No filter condition. CONCLUSIONS: The use of a combination of photocromic lens with a selective blue-violet light filter showed functional benefit in all evaluated patients.

Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report.

BACKGROUND: We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). CASE PRESENTATION: A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. CONCLUSIONS: This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway.

Structure-function relationship in early diabetic retinopathy: a spatial correlation analysis with OCT and microperimetry.

PurposeTo study the correlation of the local ganglion cell layer-inner plexiform layer (GCL-IPL) thickness with corresponding retinal sensitivity as studied with microperimetry in patients with Type 2 diabetes and no signs of diabetic retinopathy.Patients and methodsWe analyzed 35 healthy subjects (68 eyes) and 26 Type 2 diabetic patients (48 eyes) with no signs of diabetic retinopathy. We tested best corrected visual acuity (BCVA), monocular and binocular constrast sensitivity (CS, Pelli - Robson chart) and retinal sensitivity with microperimetry, and acquired dense macular SD-OCT scans. We then studied the correlation between local GCL-IPL thickness and local sensitivity.ResultsMean BCVA was 1.09 (±1.03) decimals in diabetic subjects and 1.02 (±0.15) decimals in healthy subjects. Only binocular CS was significantly higher in healthy subjects (1.18±0.42 for healthy subjects, 1.62±0.63 for diabetic subjects). In both local and global analysis we observed higher GCL-IPL thickness and higher sensitivity in normal compared with diabetic subjects, but no difference reached significance (p<0.05). Using a mixed multivariate linear model, we found a significant correlation between retinal sensitivity and the correspondent GCL-IPL thickness in diabetic subjects (0.022±0.006 dB/µm, p=0.0007) but not in healthy subjects (-0.002±0.006 dB/µm, p=0.77).Conclusiondespite close similarities between the two groups, we found a significant difference in the structure-function relationship in diabetic subjects without diabetic retinopathy, suggesting that diabetes might act as an additional effect in the normal deterioration of the visual function related to the inner retina.

The microstructure and micromechanics of the tendon-bone insertion.

The exceptional mechanical properties of the load-bearing connection of tendon to bone rely on an intricate interplay of its biomolecular composition, microstructure and micromechanics. Here we identify that the Achilles tendon-bone insertion is characterized by an interface region of ∼500 µm with a distinct fibre organization and biomolecular composition. Within this region, we identify a heterogeneous mechanical response by micromechanical testing coupled with multiscale confocal microscopy. This leads to localized strains that can be larger than the remotely applied strain. The subset of fibres that sustain the majority of loading in the interface area changes with the angle of force application. Proteomic analysis detects enrichment of 22 proteins in the interfacial region that are predominantly involved in cartilage and skeletal development as well as proteoglycan metabolism. The presented mechanisms mark a guideline for further biomimetic strategies to rationally design hard-soft interfaces.

Effect of the addition of phytosterols and tocopherols on Streptococcus thermophilus robustness during industrial manufacture and ripening of a functional cheese as evaluated by qPCR and RT-qPCR.

The quality of functional food products designed for the prevention of degenerative diseases can be affected by the incorporation of bioactive compounds. In many types of cheese, the performance of starter microorganisms is critical for optimal elaboration and for providing potential probiotic benefits. Phytosterols are plant lipophilic triterpenes that have been used for the design of functional dairy products because of their ability to lower serum cholesterol levels in humans. However, their effect on the starter culture behavior during cheesemaking has not yet been studied. Here, we followed DNA and RNA kinetics of the bacterium Streptococcus thermophilus, an extensively used dairy starter with probiotic potential, during industrial production of a functional, semi-soft, reduced-fat cheese containing phytosterol esters and alpha-tocopherol as bioactive compounds. For this purpose, real-time quantitative PCR (qPCR) and reverse transcription-qPCR (RT-qPCR) assays were optimized and applied to samples obtained during the manufacture and ripening of functional and control cheeses. An experimental set-up was used to evaluate the detection threshold of free nucleic acids for extraction protocols based on pelleted microorganisms. To our knowledge, this straight-forward approach provides the first experimental evidence indicating that DNA is not a reliable marker of cell integrity, whereas RNA may constitute a more accurate molecular signature to estimate both bacterial viability and metabolic activity. Compositional analysis revealed that the bioactive molecules were effectively incorporated into the cheese matrix, at levels considered optimal to exert their biological action. The starter S. thermophilus was detected by qPCR and RT-qPCR during cheese production at the industrial level, from at least 30min after its inoculation until 81days of ripening, supporting the possible role of this species in shaping organoleptic profiles. We also showed for the first time that the addition of phytosterols at functional concentrations, not only did not affect starter performance but also correlated with a significant increase in target DNA and cDNA levels in most of the time points evaluated throughout cheesemaking. Therefore, these findings suggest that the growth and metabolism of S. thermophilus may be enhanced by the incorporation of these biologically active molecules during cheese production, providing important information for the industrial design of novel fermented foods.

Utilization of fluorescence spectroscopy as a novel approach to evaluate the oxidative stability in beef retail displayed.

Beef samples from grazing steers finished with different seed-supplemented diets were vacuum packaged for 3, 14 and 56days (VC) and subsequently exposed to aerobic conditions (AE) for 0 and 5days. Different fluorescent compounds of interest in the oxidation process were detected in meat, namely tryptophan residues, Schiff bases and porphyrins. Tryptophan intensity fluorescence increased with 14days of VC; while Schiff bases intensity increased (P<0.05) in beef samples stored under VC-56 and in all samples after AE-5days. Porphyrins increased (P<0.05) gradually with the extension of vacuum storage time, but were degraded in beef with long vacuum storage and 5days of AE. Higher levels of porphyrins in beef under VC were correlated (P<0.05) with lower redness and higher TBARS after AE-5. This study revealed the potential of fluorescence signals to detect oxidative changes in beef under different storage conditions using a fast and nondestructive method such as fluorescence spectroscopy.

Antioxidant status, lipid and color stability of aged beef from grazing steers supplemented with corn grain and increasing levels of flaxseed.

Angus steers were grazed on unsupplemented pasture (CNTRL), pasture supplemented with 0.7% BW cracked corn (FLAX-0), FLAX-0 with 0.125% and 0.250% BW of whole flaxseed (FLAX-1 and FLAX-2). Six steers were grazed per treatment for 70 days, with start and finish weights of 458 and 508 kg. At 24 h post slaughter, longissimus thoracis were harvested, and steaks assigned to treatments of postmortem aging time under vacuum (PM; 3, 14 and 56 days) with or without five days of aerobic exposure (AE). Meat antioxidant status was higher (P<0.05) when feeding CNTRL and FLAX-1 than FLAX-0 and FLAX-2. Under AE, lipid oxidation was highest for FLAX-2 (P<0.05), and lowest for FLAX-1. Greatest TBARs and lowest antioxidant capacity and redness values were obtained with AE and the longer PM (P<0.05). Beef oxidative stability through AE improved by adding a low flaxseed level to supplemented corn grain, but deteriorated by adding a high flaxseed level or by extending PM.

Choroidal Thickness Analysis in Patients with Usher Syndrome Type 2 Using EDI OCT.

To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), axial length (AL), automated visual field (VF), and EDI OCT. Both retinal and choroidal measures were measured. Statistical analysis was performed to correlate choroidal thickness with age, BCVA, IOP, AL, VF, and RT. Comparison with data about healthy people and nonsyndromic RP patients was performed. Results. Mean subfoveal choroidal thickness (SFCT) was 248.21 ± 79.88 microns. SFCT was statistically significant correlated with age (correlation coefficient -0.7248179, p < 0.01). No statistically significant correlation was found between SFCT and BCVA, IOP, AL, VF, and RT. SFCT was reduced if compared to healthy subjects (p < 0.01). No difference was found when compared to choroidal thickness from nonsyndromic RP patients (p = 0.2138). Conclusions. Our study demonstrated in vivo choroidal thickness reduction in patients with Usher Syndrome type 2. These data are important for the comprehension of mechanisms of disease and for the evaluation of therapeutic approaches.

Phenotype-genotype correlations in hemophilia A carriers are consistent with the binary role of the phase between F8 and X-chromosome inactivation.

BACKGROUND: The recessive X-linked disorder hemophilia A (HA) is rarely expressed in female carriers, most of whom express about half of normal factor VIII activity ( FVIII: C). OBJECTIVE: To propose an integrative assessment model for the binary role of the phase between the mutated F8 and the active X-chromosome (Xa) in FVIII: C in HA carriers. METHODS: We studied 67 females at risk of severe HA, comprising five symptomatic females ( FVIII: C < 1.5 IU dL(-1) ) and 14 controls. A correlation study between FVIII: C (observed vs. expected) and X-chromosome inactivation (XCI) patterns (XIPs; androgen receptor gene [AR] system) in blood leukocyte DNA was performed in carriers, by comparison of a model correlating FVIII: C and XIP with arbitrary models devoid of biological significance, and with FVIII: C levels in non-carriers (mean model) as a proxy from background data dispersion not influenced by XIP. RESULTS: We provide proof-of-concept example from a family presenting with extremely skewed XIPs in which the severe HA phenotype appeared in a heterozygous carrier of a crossover between AR and F8 loci that phased the mutated F8 with the maternally inherited Xa. Furthermore, four cases of severe HA affected women who had a combination of a heterozygous F8 mutation and extremely skewed XIPs in leukocytes or oral mucosa are presented. Correlation analyses between FVIII: C levels and XIPs in carriers (n = 38) but not in non-carriers (n = 20) showed highly significant differences between the proposed correlation model and models without biological significance. The data support a binary influence of XCI, either increasing or decreasing the FVIII: C, subject to the underlying phase set between the F8 mutation and XCI. CONCLUSIONS: Our evidence suggests that the phase between XCI and mutated F8 acts as a molecular switch conditioning FVIII: C levels and HA expression in carriers.

Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations.

Mutations in more than 60 different genes have been associated with non-syndromic and syndromic retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies. To increase the understanding of the molecular epidemiology of the disease in Italy, we analyzed 56 patients with syndromic and non-syndromic forms of RP attending the Retinitis Pigmentosa Center of San Paolo Hospital (Milan, Italy). Patients underwent detailed clinical examination. Genomic DNA isolated from peripheral blood samples was screened for mutations in different genes according to RP form by direct sequencing analysis. The impact of novel missense mutations on protein functions was predicted by in silico analysis and protein sequence alignment. Cosegregation analysis was performed between available family members. Forty-one of the 56 probands analyzed had non-syndromic and 15 had syndromic RP forms. Putative disease-causing mutations were identified in 19 of 56 unrelated RP probands. Mutation screening identified a total of 22 different heterozygous variants. Notably, 12 of these putative pathogenic mutations have not been previously reported. New variants were found to be located on the USH2A, RPGR, EYS, and RHO genes. All 3 new variants detected in X-linked RP probands were confirmed in other affected family members. We found a positivity rate of 24.4% and 60% for probands with non-syndromic and syndromic RP, respectively. This is the first report of RPGR X-linked RP proband-ORF15 mutations in Italian patients with X-linked (XL)-RP. In addition, this is the first report of data regarding the association between EYS mutations and non-syndromic RP forms in the Italian population.

Biotyping of cultivable lactic acid bacteria isolated from donkey milk.

UNLABELLED: The diversity of lactic acid bacteria (LAB) species in donkey's milk was analysed by culture-dependent microbial techniques. Dominant strains were isolated on agar media generally used for enumerating LAB. To enrich the number of acidifying LAB present, the milk samples were incubated at 37°C for 24 h (cultured milk samples, CM). One of the CM samples was heat-treated at 63°C for 10 min before incubation at 37°C (heat-treated and cultured milk sample, TCM) to select thermophilic LAB. The microflora in these CM and TCM samples was then compared to that of the raw milk samples (RM). Among the 129 LAB isolates, 10 different species (four Enterococcus, five Streptococcus and one Pediococcus) were identified by molecular methods. Although the 10 LAB species were present in the RM samples, only three and two isolates were found in CM and TCM samples, respectively. Despite the selection protocol being set up to favour the isolation of all LAB isolates present in donkey milk, relatively few species and biotypes were isolated. No LAB isolates belonging to the most technologically important dairy starter species were detected. The possible factors related to the limited LAB diversity in donkey's milk have been discussed below. SIGNIFICANCE AND IMPACT OF THE STUDY: There is increased interest in using donkey's milk as a source of human nutrition. The large amounts of antimicrobial components and defence factors present in donkey's milk provide protection from microbial infections and distinguish donkey's milk from the milks of other mammals. However, the microbiota in donkey's milk has so far been poorly characterized, specifically with regard to the lactic acid bacteria (LAB). This study has identified cultivable, acidifying and thermoduric LAB that could be used to develop starter cultures. This is the first study to investigate the culturable LAB microbiota present in donkey's milk.

Citicoline oral solution in glaucoma: is there a role in slowing disease progression?

PURPOSE: To assess the effect of citicoline on visual field rates of progression in patients with progressing glaucoma. PATIENTS AND METHODS: Forty-one patients with a diagnosis of progressing glaucoma received citicoline in oral solution for 2 years. Included were patients with a disease progression of at least -1 dB/year (at MD, mean deviation) for at least 3 years before entering the study despite controlled intraocular pressure (IOP). Patients were followed with 4 visual field examinations per year for 2 years. RESULTS: At baseline, the mean rate of progression was -1.1 (±0.7) dB/year despite the fact that the IOP had been below 18 mm Hg for at least 3 years. At study inclusion, the mean IOP was 15.5 (±2.6) mm Hg and the mean MD was -9.2 (±6.7) dB in the worst eye. Starting from the first cycle of treatment with citicoline, the mean rate of progression significantly changed to -0.15 (±0.3) dB/year at the end of the study (p = 0.01). CONCLUSIONS: This study seems to indicate that supplementation with citicoline might significantly slow down glaucomatous rates of progression.

Factor VIII genotype characterization of haemophilia A affected patients with transient and permanent inhibitors: a comprehensive Argentine study of inhibitor risks.

Inhibitor development against exogenous factor VIII is a severe impairment of replacement therapy affecting 18% of Argentine patients with severe haemophilia A (HA). To study the molecular predisposition for inhibitor development, we genotyped 260 HA patients with and without inhibitors, countrywide. The inhibitor-positive population (19 transients, 15 low responders, LR and 70 high responders, HR) of 104 severe-HA patients showed 59 Inv22 (intron 22 inversions), 18 small ins/del-frameshifts, 12 gross deletions, 12 nonsense, one splicing defect and two missense, p.Arg531Pro and p.Leu575Pro, both LR and thought to impair FVIII A2 domain secondary structure. In addition, a patient with mild HA and HR showed the missense p.Glu1704Lys associated with two neutral intronic substitutions potentially affecting the A3 domain. A case/control study (84/143) permitted estimation of F8 genotype-specific inhibitor risks [OR; prevalence (CI)] in severe-HA patients classifying a high-risk group including multi-exon deletions [3.66; 55% (19-100)], Inv22 [1.8; 24% (19-100)] and nonsense in FVIII-LCh [1.2; 21% (7-59)]; an average risk group including single-exon deletions, indel frameshifts and nonsense-HCh; and a low-risk group represented by missense defects [0.14; 3% (0.6-11)]. Analysis of inhibitor concordance/discordance in related patients indicated additional genetic factors other than F8 genotype for inhibitor formation. No significant inhibitor-predisposing factors related to FVIII product exposure were found in age- and F8 genotype-stratified populations of severe-HA patients. In conclusion, the Argentine HA patient series presents similar global and mutation-specific inhibitor risks than the HA database and other published series. This case-specific information will help in designing fitted therapies and follow-up protocols in Argentina.

Core elements of physiotherapy in cerebral palsy children: proposal for a trial checklist.

BACKGROUND: Currently international literature describes physiotherapy in cerebral palsy (CP) children only in generic terms (traditional / standard / background / routine). AIM: The aim of this study is to create a checklist capable of describing the different modalities employed in physiotherapeutic treatment by means of a non-bias, common, universal, standardised language. DESIGN: A preliminary checklist was outlined by a group of physiotherapists specialised in child rehabilitation. SETTING: For its experimentation, several physiotherapists from various paediatric units from all over Italy with different methodological approaches and backgrounds, were involved. METHODS: Using the interpretative model, proposed by Ferrari et al., and through collective analysis and discussion of clinical videos, the core elements were progressively selected and codified. A reliability study was then carried out by eight expert physiotherapists using an inter-rate agreement model. RESULTS: The checklist analyses therapeutic proposals of CP rehabilitation through the description of settings, exercises and facilitations and consists of items and variables which codify all possible physiotherapeutic interventions. It is accompanied by written explanations, demonstrative videos, caregiver interviews and descriptions of applied environmental adaptations. All checklist items obtained a high level of agreement (according to Cohen's kappa coefficient), revealing that the checklist is clearly and easily interpretable. CONCLUSION: The checklist should facilitate interaction and communication between specialists and families, and lead to comparable research studies and scientific advances. CLINICAL REHABILITATION IMPACT: The main value is to be able to correlate therapeutic results with core elements of adopted physiotherapy.