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published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons.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 This article has been retracted.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.

The Pacman Flap and Its Modifications for Reconstruction of Skin Cancer Surgical Wounds on the Scalp and Other Body Areas: A Review of 23 Cases. / [Artículo tradudico] El colgajo Pacman y sus modificaciones para la reconstrucción de heridas quirúrgicas oncológicas en el cuero cabelludo y otras áreas corporales: Revisión de 23 casos.

BACKGROUND: The Pacman flap is a modified V-Y advancement flap that showed to be versatile in repairing surgical and non-surgical wounds. Indeed, this flap has been used in any anatomical localization, except for the scalp, where its use has not been reported. Moreover, the versatility of the Pacman flap can be enhanced by applying simple modifications to its original design. MATERIALS AND METHODS: A case-series of 23 patients whose surgical breaches were repaired using standard or modified Pacman flap were included in this retrospective study. RESULTS: Most patients were male (65.2%) with a median age of 75.7 years. Squamous cell carcinoma was the tumor most commonly removed (60.9%), while scalp and face were the most frequent localizations (30.4%). Although 18 flaps were sculpted in the traditional Pacman shape, 5 were modified to fit the defect and localization. Complications occurred in 30% of flaps, but all of them were minor except for 1 extended necrosis. CONCLUSIONS: The Pacman flap can be used to repair surgical wounds localized in any body area, including the scalp. Three modifications can enhance the versatility of the flap and offer new repair options to dermatologic surgeons.

The Pacman Flap and Its Modifications for Reconstruction of Skin Cancer Surgical Wounds on the Scalp and Other Body Areas: A Review of 23 Cases.

BACKGROUND: The Pacman flap is a modified V-Y advancement flap that showed to be versatile in repairing surgical and non-surgical wounds. Indeed, this flap has been used in any anatomical localization, except for the scalp, where its use has not been reported. Moreover, the versatility of the Pacman flap can be enhanced by applying simple modifications to its original design. MATERIALS AND METHODS: A case-series of 23 patients whose surgical breaches were repaired using standard or modified Pacman flap were included in this retrospective study. RESULTS: Most patients were male (65.2%) with a median age of 75.7 years. Squamous cell carcinoma was the tumor most commonly removed (60.9%), while scalp and face were the most frequent localizations (30.4%). Although 18 flaps were sculpted in the traditional Pacman shape, 5 were modified to fit the defect and localization. Complications occurred in 30% of flaps, but all of them were minor except for 1 extended necrosis. CONCLUSIONS: The Pacman flap can be used to repair surgical wounds localized in any body area, including the scalp. Three modifications can enhance the versatility of the flap and offer new repair options to dermatologic surgeons.

Breathing patterns recognition: A functional data analysis approach.

BACKGROUND AND OBJECTIVE: The ongoing pandemic proved fundamental is to assess a subject's respiratory functionality and breathing pattern measurement during quiet breathing is feasible in almost all patients, even those uncooperative. Breathing pattern consists of tidal volume and respiratory rate in an individual assessed by data tracks of lung or chest wall volume over time. State-of-art analysis of these data requires operator-dependent choices such as individuation of local minima in the track, elimination of anomalous breaths and individuation of breath clusters corresponding to different breathing patterns. METHODS: A semi-automatic, robust and reproducible procedure was proposed to pre-process and analyse respiratory tracks, based on Functional Data Analysis (FDA) techniques, to identify representative breath curve and the corresponding breathing patterns. This was achieved through three steps: 1) breath separation through precise localization of the minima of the volume trace; 2) functional outlier breaths detection according to time-duration, magnitude and shape; 3) breath clustering to identify different pattern of interest, through K-medoids with Alignment. The method was firstly validated on simulated tracks and then applied to real data in conditions of clinical interest: operational volume change, exercise, mechanical ventilation, paradoxical breathing and age. RESULTS: The total error in the accuracy of minima detection and in was less than 5%; with the artificial outliers being almost completely removed with an accuracy of 99%. During incremental exercise and independently on the bike resistance level, five clusters were identified (quiet breathing; recovery phase; onset of exercise; maximal and intermediate levels of exercise). During mechanical ventilation, the procedure was able to separate the non-ventilated from the ventilatory-supported breathing and to identify the worsening of paradoxical breathing due to the disease progression and the breathing pattern changes in healthy subjects due to age. CONCLUSIONS: We proposed a robust validated automatic breathing patterns identification algorithm that extracted representative curves that could be implemented in clinical practice for objective comparison of the breathing patterns within and between subjects. In all case studies the identified patterns proved to be coherent with the clinical conditions and the physiopathology of the subjects, therefore enforcing the potential clinical translational value of the method.

Periodic event-triggered targeted shape control of Lagrangian systems with discrete-time delays.

We study the problem of periodic event-triggered targeted formation control for multi-agent Lagrangian systems. We assume that the equations of motion of each agent are derived from a Lagrangian function. Besides, each agent has information about a predefined convex set as a targeted set. The goal of the agents is to achieve the desired formation in the targeted sets, while the information is asynchronously shared by a periodic event-triggering specification, and there is also a time-delay in their communication. A novel distributed control law is proposed for the agents to reach the goal while their velocities are driven to zero. Applications and simulations are provided to validate the theoretical results.

Peripheral inflammation exacerbates α-synuclein toxicity and neuropathology in Parkinson's models.

AIMS: Parkinson's disease and related disorders are devastating neurodegenerative pathologies. Since α-synuclein was identified as a main component of Lewy bodies and neurites, efforts have been made to clarify the pathogenic mechanisms of α-synuclein's detrimental effects. α-synuclein oligomers are the most harmful species and may recruit and activate glial cells. Inflammation is emerging as a bridge between genetic susceptibility and environmental factors co-fostering Parkinson's disease. However, direct evidence linking inflammation to the harmful activities of α-synuclein oligomers or to the Parkinson's disease behavioural phenotype is lacking. METHODS: To clarify whether neuroinflammation influences Parkinson's disease pathogenesis, we developed: (i) a 'double-hit' approach in C57BL/6 naive mice where peripherally administered lipopolysaccharides were followed by intracerebroventricular injection of an inactive oligomer dose; (ii) a transgenic 'double-hit' model where lipopolysaccharides were given to A53T α-synuclein transgenic Parkinson's disease mice. RESULTS: Lipopolysaccharides induced a long-lasting neuroinflammatory response which facilitated the detrimental cognitive activities of oligomers. LPS-activated microglia and astrocytes responded differently to the oligomers with microglia activating further and acquiring a pro-inflammatory M1 phenotype, while astrocytes atrophied. In the transgenic 'double-hit' A53T mouse model, lipopolysaccharides aggravated cognitive deficits and increased microgliosis. Again, astrocytes responded differently to the double challenge. These findings indicate that peripherally induced neuroinflammation potentiates the α-synuclein oligomer's actions and aggravates cognitive deficits in A53T mice. CONCLUSIONS: The fine management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some behavioural aspects in α-synucleinopathies.

Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

How to manage thromboembolic risk in patient with SARS-CoV-2-related disease in the Emergency Department: A case report of cardiogenic shock due to massive pulmonary embolism.

BACKGROUND: Although the most known feature of SARS-CoV-2 associated infection is a mild to severe pneumonia, increasing evidence suggests the existence of an infection-associated risk of both arterial and venous thromboembolism (VTE), but the exact magnitude of this phenomenon is still unknown.Given that, it is important for the Emergency Physician to remember that a SARS-CoV-2 associated respiratory failure can be caused not only by the pulmonary parenchymal inflammation that characterizes the pneumonia, but also by an associated pulmonary thromboembolism. CASE REPORT: A healthy 73-years old woman admitted to the ED for dyspnea, fever and thoracic pain. Cardiac ultrasound, electrocardiogram and clinical findings suggested a diagnosis of cardiogenic obstructive shock due to acute pulmonary embolism, successfully treated with thrombolysis. A CT angiography confirmed the pulmonary embolism (EP) diagnosis and showed bilateral pneumonia, caused by SARS-CoV-2 infection. CONCLUSION: Considering the high prevalence of thromboembolic events in COVID-19 patients it is mandatory for the emergency physician to systematically evaluate signs of pulmonary thromboembolism, in order to perform the most patient-tailored therapy as soon as possible.

In vivo time-domain diffuse correlation spectroscopy above the water absorption peak.

Time-domain diffuse correlation spectroscopy (TD-DCS) is a newly emerging optical technique that exploits pulsed, yet coherent light to non-invasively resolve the blood flow in depth. In this work, we have explored TD-DCS at longer wavelengths compared to those previously used in literature (i.e., 750-850 nm). The measurements were performed using a custom-made titanium-sapphire mode-locked laser, operating at 1000 nm, and an InGaAs photomultiplier as a detector. Tissue-mimicking phantoms and in vivo measurements during arterial arm cuff occlusion in n=4 adult volunteers were performed to demonstrate the proof of concept. We obtained a good signal-to-noise ratio, following the hemodynamics continuously with a relatively fast (1 Hz) sampling rate. In all the experiments, the auto-correlation functions show a decay rate approximately five-fold slower compared to shorter wavelengths. This work demonstrates the feasibility of in vivo TD-DCS in this spectral region and its potentiality for biomedical applications.

Impact of COVID-19 epidemic on maxillofacial surgery in Italy.

Maxillofacial departments in 23 surgical units in Italy have been increasingly involved in facing the COVID-19 emergency. Elective surgeries have been progressively postponed to free up beds and offer human and material resources to those infected. We compiled an inventory of 32 questions to evaluate the impact of the SARS-COV2 epidemic on maxillofacial surgery in 23 selected Italian maxillofacial departments. The questionnaire focused on three different aspects: the variation of the workload, showing both a reduction of the number of team members (-16% among specialists, -11% among residents) due to reallocation or contamination and a consistent reduction of elective activities (the number of outpatient visits cancelled during the first month of the COVID-19 epidemic was about 10 000 all over Italy), while only tumour surgery and trauma surgery has been widely guaranteed; the screening procedures on patients and physicians (22% of maxillofacial units found infected surgeons, which is 4% of all maxillofacial surgeons); and the availability of Personal Protective Equipment, is only considered to be partial in 48% of Maxillofacial departments. This emergency has forced those of us in the Italian health system to change the way we work, but only time will prove if these changes have been effective.

Pitch angle control of a wind turbine operating above the rated wind speed: A sliding mode control approach.

The paper focuses on variable-rotor-speed/variable-blade-pitch wind turbines operating in the region of high wind speeds, where control is aimed at limiting the turbine energy capture to the rated power value. A robust sliding mode approach is proposed, using the blade pitch as control input, in order to regulate the rotor speed to a fixed rated value, in the presence of uncertainties characterizing the wind turbine model. Closed loop convergence of the overall control system is proved. The proposed control solution has been validated on a 5-MW three-blade wind turbine using the National Renewable Energy Laboratory (NREL) wind turbine simulator FAST (Fatigue, Aerodynamics, Structures, and Turbulence) code. A comparison with the standard FAST baseline controller (NWTC 2012 and Jonkman et al. 2009) has been also included.

Lumican is upregulated in osteoarthritis and contributes to TLR4-induced pro-inflammatory activation of cartilage degradation and macrophage polarization.

OBJECTIVE: Lumican (LUM) is a major extracellular matrix glycoprotein in adult articular cartilage and its expression is known to be upregulated upon cartilage degeneration. LUM is associated with the pathogen-associated molecular pattern (PAMP) activation of the TLR4 signalling cascade, with TLR4 being highly associated with inflammation in rheumatic diseases. However, the main role of the LUM structural molecule in osteoarthritis (OA) remains elusive. The aim of this study was, therefore, to understand the role of LUM during TLR4-mediated activation in OA. METHODS: After measuring LUM levels in synovial fluid (SF) of OA patients and lipopolysaccharide (LPS)-induced TLR4 activation, the role of LUM in the expression of pro-inflammatory molecules and cartilage degradation was assessed in vitro and ex vivo in a cartilage explant model. Primary macrophage activation and polarization were studied upon LUM co-stimulation with LPS. RESULTS: We demonstrate that LUM is not only significantly upregulated in SF from OA patients compared to healthy controls, but also that LUM increases lipopolysaccharide (LPS)-induced TLR4 activation. Furthermore, we show that a pathophysiological level of LUM augments the LPS-induced TLR4 activation and expression of downstream pro-inflammatory molecules, resulting in extensive cartilage degradation. LUM co-stimulation with LPS also provided a pro-inflammatory stimulus, upregulating primary macrophage activation and polarization towards the M1-like phenotype. CONCLUSIONS: These findings strongly support the role of LUM as a mediator of PAMP-induced TLR4 activation of inflammation, cartilage degradation, and macrophage polarization in the OA joint and potentially other rheumatic diseases.

Actions taken by the European commission to address the safety of sunbeds.

The safety of sunbed, especially when it comes to protecting young and vulnerable consumers, is a key concern that the Directorate-General for Health and Consumers has been trying to address in various ways. This document presents a brief overview of activities undertaken at European level to address the main concerns related to the use of this product.

Non-ohmic behavior and resistive switching of Au cluster-assembled films beyond the percolation threshold.

Networks based on nanoscale resistive switching junctions are considered promising for the fabrication of neuromorphic computing architectures. To date random networks of nanowires, nanoparticles, and metal clusters embedded in a polymeric matrix or passivated by shell of ligands or oxide layers have been used to produce resistive switching systems. The strategies applied to tailor resistive switching behavior are currently based on the careful control of the volume fraction of the nanoscale conducting phase that must be fixed close to the electrical percolation threshold. Here, by blending laboratory and computer experiments, we demonstrate that metallic nanostructured Au films fabricated by bare gold nanoparticles produced in the gas phase and with thickness well beyond the electrical percolation threshold, show a non-ohmic electrical behavior and complex and reproducible resistive switching. We observe that the nanogranular structure of the Au films does not evolve with thickness: this introduces a huge number of defects and junctions affecting the electrical transport and causing a dynamic evolution of the nanoscale electrical contacts under the current flow. To uncover the origin of the resistive switching behavior in Au cluster-assembled films, we developed a simple computational model for determining the evolution of a model granular film under bias conditions. The model exploits the information provided by experimental investigation about the nanoscale granular morphology of real films. Our results show that metallic nanogranular materials have functional properties radically different from their bulk counterparts, in particular nanostructured Au films can be fabricated by assembling bare gold clusters which retain their individuality to produce an all-metal resistive switching system.

In vivo time-gated diffuse correlation spectroscopy at quasi-null source-detector separation.

We demonstrate time domain diffuse correlation spectroscopy at quasi-null source-detector separation by using a fast time-gated single-photon avalanche diode without the need of time-tagging electronics. This approach allows for increased photon collection, simplified real-time instrumentation, and reduced probe dimensions. Depth discriminating, quasi-null distance measurement of blood flow in a human subject is presented. We envision the miniaturization and integration of matrices of optical sensors of increased spatial resolution and the enhancement of the contrast of local blood flow changes.

Author Correction: nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

In Situ Tissue Labeling of Cerebral Amyloid Using HIV-Related Tat Peptide.

Delivering peptide-based drugs to the brain is a major challenge because of the existence of the blood-brain barrier (BBB). To overcome this problem, cell-penetrating peptides derived from proteins that are able to cross biological membranes have been used as cell-permeable and brain-penetrant compounds. An example is the transactivator of transcription protein transduction domain (Tat) of the human immunodeficiency virus. The basic domain of Tat is formed of arginine and lysine amino acid residues. Tat has been used as brain-penetrant carrier also in therapies for Alzheimer disease (AD), the most common form of dementia characterized by extracellular cerebral deposits of amyloid made up of Aß peptide. The aim of our study was to assess whether Tat bind to amyloid deposits of AD and other amyloidoses. An in situ labeling using biotinylated Tat 48-57 peptide was employed in the brain tissue with amyloid deposits made up of Aß (patients with AD and transgenic AD mice), of prion protein (patients with Gerstmann-Straussler-Scheinker disease), and other amyloidosis, processed by different fixations and pretreatments of histological sections. Our results showed that Tat peptide binds amyloid deposits made up of Aß, PrP, and immunoglobulin lambda chains in the brain and other tissues processed by alcoholic fixatives but not in formalin-fixed tissue. The fact that biotinylated Tat peptide stains amyloid of different biochemical composition and the specific charge characteristics of the molecules suggests that Tat may bind to heparan sulfate glicosaminoglicans, that are present in amyloid deposits. Inhibition of the binding by Tat pre-incubation with protamine reinforces this hypothesis. Binding of Tat to amyloid deposits should be kept in mind in interpreting the results of studies employing this molecule as brain-penetrating compound for the treatment of cerebral amyloidoses. Our results also suggest that Tat may be helpful for the analysis of the mechanisms of amyloidogenesis, and in particular, the interactions between specific amyloid peptides and glicosaminoglicans.

Time domain diffuse correlation spectroscopy with a high coherence pulsed source: in vivo and phantom results.

Diffuse correlation spectroscopy (DCS), combined with time-resolved reflectance spectroscopy (TRS) or frequency domain spectroscopy, aims at path length (i.e. depth) resolved, non-invasive and simultaneous assessment of tissue composition and blood flow. However, while TRS provides a path length resolved data, the standard DCS does not. Recently, a time domain DCS experiment showed path length resolved measurements for improved quantification with respect to classical DCS, but was limited to phantoms and small animal studies. Here, we demonstrate time domain DCS for in vivo studies on the adult forehead and the arm. We achieve path length resolved DCS by means of an actively mode-locked Ti:Sapphire laser that allows high coherence pulses, thus enabling adequate signal-to-noise ratio in relatively fast (~1 s) temporal resolution. This work paves the way to the translation of this approach to practical in vivo use.