An analysis of the factors involved in IOL decentration after phacoemulsification using CASIA 2 anterior segment optical coherence tomography.

PURPOSE: To evaluate the magnitude of IOL transversal shift (ITS) after phacoemulsification and to analyse the factors contributing to IOL decentration and ITS. METHODS: 94 consecutive patients who underwent cataract surgery and IOL implantation was enrolled. Each patient underwent anterior segment optical coherence tomography with CASIA 2 (Tomey, Nagoya, Japan) to assess crystalline lens decentration, thickness and diameter seven days preoperatively and at one and sixty days postoperatively. Univariate and multivariate linear regression analysis were performed to evaluate the determinants of ITS and final decentration. RESULTS: The preoperative crystalline lens diameter was associated with the ITS and with the IOL final decentration. A positive association between the final IOL decentration and the first post-surgical day decentration was found (p < 0.0001). CONCLUSION: Greater crystalline lens diameter was associated with greater decentration and with greater ITS. Day-one IOL decentration seems to be the main determinant of final IOL decentration.

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids.

Organoids are self-organized, three-dimensional structures derived from stem cells that can mimic the structure and physiology of human organs. Patient-specific induced pluripotent stem cells (iPSCs) and 3D organoid model systems allow cells to be analyzed in a controlled environment to simulate the characteristics of a given disease by modeling the underlying pathophysiology. The recent development of 3D cell models has offered the scientific community an exceptionally valuable tool in the study of rare diseases, overcoming the limited availability of biological samples and the limitations of animal models. This review provides an overview of iPSC models and genetic engineering techniques used to develop organoids. In particular, some of the models applied to the study of rare neuronal, muscular and skeletal diseases are described. Furthermore, the limitations and potential of developing new therapeutic approaches are discussed.

Towards the Definition of Radiomic Features and Clinical Indices to Enhance the Diagnosis of Clinically Significant Cancers in PI-RADS 4 and 5 Lesions.

Prostate cancer (PC) is the most frequently diagnosed cancer among adult men, and its incidence is increasing worldwide [...].

Passive CAP-VAC: a simple and safe technique to clean the posterior capsule.

PURPOSE: To describe a new and less risky technique for the cleaning of posterior capsule during phacoemulsification called passive cap vac. METHOD: Passive cap vac consisted in the removal of residual posterior capsule opacities using a disconnected 0.3 mm aspiration cannula. The hole of the aspiration cannula was faced toward posterior capsule and gently rubbed against it to achieve a complete cleaning of posterior capsule. The video of the technique is available online. RESULT: With this new technique, the aspiration was ruled by the gravity and by the height of the balanced saline solution (BSS), in addition the Venturi's effect and the absence of active aspiration beyond the cannula avoided an excessive aspiration of posterior capsule. CONCLUSION: Passive cap vac allowed to clean posterior capsule using softer forces than traditional way, minimizing the risk of capsular tear.

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing.

Tau microtubule-associated proteins, encoded by the MAPT gene, are mainly expressed in neurons participating in axonal transport and synaptic plasticity. Six major isoforms differentially expressed during cell development and differentiation are translated by alternative splicing of MAPT transcripts. Alterations in the expression of human Tau isoforms and their aggregation have been linked to several neurodegenerative diseases called tauopathies, including Alzheimer's disease, progressive supranuclear palsy, Pick's disease, and frontotemporal dementia with parkinsonism linked to chromosome 17. Great efforts have been dedicated in recent years to shed light on the complex regulatory mechanism of Tau splicing, with a perspective to developing new RNA-based therapies. This review summarizes the most recent contributions to the knowledge of Tau isoform expression and experimental models, highlighting the role of cis-elements and ribonucleoproteins that regulate the alternative splicing of Tau exons.

Radiomics in PI-RADS 3 Multiparametric MRI for Prostate Cancer Identification: Literature Models Re-Implementation and Proposal of a Clinical-Radiological Model.

PI-RADS 3 prostate lesions clinical management is still debated, with high variability among different centers. Identifying clinically significant tumors among PI-RADS 3 is crucial. Radiomics applied to multiparametric MR (mpMR) seems promising. Nevertheless, reproducibility assessment by external validation is required. We retrospectively included all patients with at least one PI-RADS 3 lesion (PI-RADS v2.1) detected on a 3T prostate MRI scan at our Institution (June 2016-March 2021). An MRI-targeted biopsy was used as ground truth. We assessed reproducible mpMRI radiomic features found in the literature. Then, we proposed a new model combining PSA density and two radiomic features (texture regularity (T2) and size zone heterogeneity (ADC)). All models were trained/assessed through 100-repetitions 5-fold cross-validation. Eighty patients were included (26 with GS ≥ 7). In total, 9/20 T2 features (Hector's model) and 1 T2 feature (Jin's model) significantly correlated to biopsy on our dataset. PSA density alone predicted clinically significant tumors (sensitivity: 66%; specificity: 71%). Our model obtained a sensitivity of 80% and a specificity of 76%. Standard-compliant works with detailed methodologies achieve comparable radiomic feature sets. Therefore, efforts to facilitate reproducibility are needed, while complex models and imaging protocols seem not, since our model combining PSA density and two radiomic features from routinely performed sequences appeared to differentiate clinically significant cancers.

Structural and Functional Pulmonary Assessment in Severe COVID-19 Survivors at 12 Months after Discharge.

Long-term pulmonary sequelae in COVID-19 patients are currently under investigation worldwide. Potential relationships between blood sampling and functional and radiological findings are crucial to guide the follow-up. In this study, we collected and evaluated clinical status, namely symptoms and patients' reported outcome, pulmonary function tests (PFT), laboratory tests, and radiological findings at 3- and 12-months post-discharge in patients admitted between 25 February and 2 May 2020, and who survived severe COVID-19 pneumonia. A history of chronic pulmonary disease or COVID-19-unrelated complications were used as exclusion criteria. Unenhanced CTs were analyzed quantitatively (compromising lung volume %) and qualitatively, with main patterns of: ground-glass opacity (GGO), consolidation, and reticular configuration. Patients were subsequently divided into groups based on their radiological trends and according to the evolution in the percentage of compromised lung volume. At 12 months post-discharge, seventy-one patients showed significantly improved laboratory tests and PFT. Among them, 63 patients also underwent CT examination: all patients with negative CT findings at three months (n = 14) had negative CT also at 12 months; among the 49/63 patients presenting CT alterations at three months, 1/49 (2%) normalized, 40/49 (82%) improved, 7/49 (14%) remained stably abnormal, and 1/49 (2%) worsened. D-dimer values were low in patients with normal CT and higher in cases with improved or stably abnormal CT (median values 213 vs. 329 vs. 1000 ng/mL, respectively). The overall compromised lung volume was reduced compared with three months post-discharge (12.3 vs. 14.4%, p < 0.001). In stably abnormal CT, the main pulmonary pattern changed, showing a reduction in GGO and an increase in reticular configuration. To summarize, PFT are normal in most COVID-19 survivors 12 months post-discharge, but CT structural abnormalities persist (although sensibly improved over time) and are associated with higher D-dimer values.

A Panel of Eight miRNAs Is Deregulated in HTLV-2 Infected PBMCs and BJABGu Cell Line.

Despite human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 being retroviruses closely related at a genomic level, HTLV-2 differs from HTLV-1 in terms of pathogenicity in both single infection and coinfection contexts. Moreover, the HTLV-2 association with clinical outcomes is still debated and several mechanisms underlying HTLV-2 infection remain unexplored as well. Cellular miRNAs are key factors in the post-transcriptional regulation of gene expression and they are known to be potential targets for several pathogens to control the host microenvironment and, in particular, escape immune responses. Here, we identified a HTLV-2-related signature of eight miRNAs (miR-125a-3p, miR-381-3p, miR-502-5p, miR-708-5p, miR-548d-5p, miR-548c-5p, miR-1-3p, and miR-511-5p) in both HTLV-2 infected PBMC and BJABGu cell lines. Altered miRNA expression patterns were correlated with the impairment of Th cell differentiation and signaling pathways driven by cytokines and transcriptional factors such as the Runt-related transcription factor (RUNX) family members. Specifically, we demonstrated that the RUNX2 protein was significantly more expressed in the presence of Tax-2 compared with Tax-1 in an in vitro cell model. To the best of our knowledge, these data represent the first contribution to elucidating the HTLV-2 mediated alteration of host cell miRNA profiles that may impact on HTLV-2 replication and persistent infection.

Environmental Enrichment Induces Meningeal Niche Remodeling through TrkB-Mediated Signaling.

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli, including environmental enrichment (EE) acting through BDNF-TrkB signaling. We have recently identified NPs in meninges; however, the meningeal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of EE exposure on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of the meningeal cell number and proliferation, we observed an increased number of neural precursors in the meninges. A lineage tracing experiment suggested that EE-induced ß3-Tubulin+ immature neuronal cells present in the meninges originated, at least in part, from GLAST+ radial glia cells. To investigate the molecular mechanism responsible for meningeal reaction to EE exposure, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced meningeal niche changes. Overall, these data showed, for the first time, that EE exposure induced meningeal niche remodeling through TrkB-mediated signaling. Fluoxetine treatment further confirmed the meningeal niche response, suggesting it may also respond to other pharmacological neurogenic stimuli. A better understanding of the neurogenic stimuli modulation for meninges may be useful to improve the effectiveness of neurodegenerative and neuropsychiatric treatments.

Post-discharge chest CT findings and pulmonary function tests in severe COVID-19 patients.

PURPOSE: To evaluate chest computed tomography (CT) and pulmonary function test (PFT) findings in severe COVID-19 patients after discharge and correlate CT pulmonary involvement with PFT results. METHODS: COVID-19 patients admitted to our hospital between February 25 and May 2, 2020, were retrospectively included according to the following criteria: (a) COVID-19 defined as severe based on the WHO interim guidance (i.e., clinical signs of pneumonia plus respiratory rate > 30 breaths/min, severe respiratory distress, and/or SpO2 < 90 % on room air); (b) chest radiograph in the acute setting; (c) post-discharge unenhanced chest CT; and (d) post-discharge comprehensive PFT. Imaging findings were retrospectively evaluated in consensus by two readers, and volume of abnormal lung was measured on CT using 3D Slicer software. Differences between demographics, comorbidities, acute radiographic findings, PFT, and post-discharge clinical and laboratory data of patients with normal and abnormal CT findings were assessed by Mann-Whitney or Fisher tests, and the compromised lung volume-PFT association by Pearson correlation after removing possible outliers. RESULTS: At a median of 105 days from symptom onset, 74/91 (81 %) patients had CT abnormalities. The most common CT pattern was combined ground-glass opacity and reticular pattern (46/74, 62 %) along with architectural distortion (68/74, 92 %) and bronchial dilatation (66/74, 89 %). Compromised lung volume had a median value of 15 % [11-23], was higher in dyspneic patients, and negatively correlated with the percentage of predicted DLCO, VA, and FVC values (r = -0.39, -0.5, and -0.42, respectively). These PFT parameters were significantly lower in patients with CT abnormalities. Impairment of DLCO and KCO was found in 12 (13 %) cases, possibly implying an underlying pulmonary vasculopathy in this subgroup of patients. CONCLUSIONS: Most severe COVID-19 survivors still had physiologically relevant CT abnormalities about three months after the disease onset, with an impairment of diffusion capacity on PFT. A pulmonary vasculopathy was suggested in a minor proportion of patients.

Chest X-ray for predicting mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.

OBJECTIVES: To evaluate the inter-rater agreement of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) and to determine the value of initial CXR along with demographic, clinical, and laboratory data at emergency department (ED) presentation for predicting mortality and the need for ventilatory support. METHODS: A total of 340 COVID-19 patients who underwent CXR in the ED setting (March 1-13, 2020) were retrospectively included. Two reviewers independently assessed CXR abnormalities, including ground-glass opacities (GGOs) and consolidation. Two scoring systems (Brixia score and percentage of lung involvement) were applied. Inter-rater agreement was assessed by weighted Cohen's kappa (κ) or intraclass correlation coefficient (ICC). Predictors of death and respiratory support were identified by logistic or Poisson regression. RESULTS: GGO admixed with consolidation (n = 235, 69%) was the most common CXR finding. The inter-rater agreement was almost perfect for type of parenchymal opacity (κ = 0.90), Brixia score (ICC = 0.91), and percentage of lung involvement (ICC = 0.95). The Brixia score (OR: 1.19; 95% CI: 1.06, 1.34; p = 0.003), age (OR: 1.16; 95% CI: 1.11, 1.22; p < 0.001), PaO2/FiO2 ratio (OR: 0.99; 95% CI: 0.98, 1; p = 0.002), and cardiovascular diseases (OR: 3.21; 95% CI: 1.28, 8.39; p = 0.014) predicted death. Percentage of lung involvement (OR: 1.02; 95% CI: 1.01, 1.03; p = 0.001) and PaO2/FiO2 ratio (OR: 0.99; 95% CI: 0.99, 1.00; p < 0.001) were significant predictors of the need for ventilatory support. CONCLUSIONS: CXR is a reproducible tool for assessing COVID-19 and integrates with patient history, PaO2/FiO2 ratio, and SpO2 values to early predict mortality and the need for ventilatory support. KEY POINTS: • Chest X-ray is a reproducible tool for assessing COVID-19 pneumonia. • The Brixia score and percentage of lung involvement on chest X-ray integrate with patient history, PaO2/FIO2 ratio, and SpO2 values to early predict mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.

Freezing of gait and dementia in parkinsonism: A retrospective case-control study.

OBJECTIVES: To support the cognitive model of Freezing of Gait (FoG) we investigated FoG in a cohort of patients with Dementia with Lewy Bodies (DLB). MATERIALS AND METHODS: We assessed FoG frequency in 19 DLB patients compared to 19 control PD patients within 2 years from symptom onset and with at least 5 years follow-up. The two groups were matched by age and motor presentation at onset, severity of parkinsonism and disease duration. The presence and severity of FoG was identified as those with a score of 1 or greater on subitem 14 of the Unified Parkinson's Disease Rating Scale Part II  (UPDRS II). RESULTS: At T0, 68.4% DLB and 10.5% PD patients experienced FoG ≥1. The prevalence of FoG increased with disease progression (94.7% DLB and 47.3% PD subjects had FoG ≥1 at T5). DLB also showed a more severe FoG (FoG ≥2) than PD (21% vs. 0% at T0 and 52.6% vs. 10.5% at T5), consistently with previous studies reporting FoG prevalence in DLB. CONCLUSION: This is the first study looking specifically at FoG in DLB, identifying it as a frequent and early feature of DLB and emphasizing the crucial role of cognitive impairment in the occurrence of this mysterious phenomenon.

Continuous subcutaneous insulin infusion in Italy: third national survey.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is increasing worldwide, mostly because of improved technology. The aim of this study was to evaluate the current status of CSII in Italy. MATERIALS AND METHODS: Physicians from 272 diabetes centers received a questionnaire investigating clinical features, pump technology, and management of patients on CSII. RESULTS: Two hundred seventeen centers (79.8%) joined the study and, by the end of April 2013, gave information about 10,152 patients treated with CSII: 98.2% with type 1 diabetes mellitus, 81.4% adults, 57% female, and 61% with a conventional pump versus 39% with a sensor-augmented pump. CSII advanced functions were used by 68% of patients, and glucose sensors were used 12 days per month on average. Fifty-eight percent of diabetes centers had more than 20 patients on CSII, but there were differences among centers and among regions. The main indication for CSII was poor glucose control. Dropout was mainly due to pump wearability or nonoptimal glycemic control. Twenty-four hour assistance was guaranteed in 81% of centers. A full diabetes team (physician+nurse+dietician+psychologist) was available in 23% of adult-care diabetes centers and in 53% of pediatric diabetes units. CONCLUSIONS: CSII keeps increasing in Italy. More work is needed to ensure uniform treatment strategies throughout the country and to improve pump use.

The tarsal belt procedure for the correction of ectropion: description and outcome in 42 cases.

BACKGROUND/AIMS: Ectropion correction is a challenge in plastic surgery. Correction of the lower lid area, including restoration of the shape and position of lid margin, is the surgical goal. In this study, we describe a new surgical technique, the tarsal belt, for the correction of ectropion and evaluation of the effective outcome and complications of this procedure. METHODS: Between January 2008 and January 2012, a total of 42 patients aged between 48 and 75 years (average age 61.5 years) were treated with this technique. This procedure consists in a trans-tarsal mattress non-absorbable suture anchored to the periosteum of the lateral orbital rim, combined with a small wedge excision of a lateral portion of the tarsus close to the lateral canthal tendon. During the same period, 66 patients were treated with the standard lateral tarsal strip technique. Preoperative and postoperative Ectropion Grading Scale (EGS) was recorded to evaluate anatomical improvement. The average follow-up period was 24 months. RESULTS: Rate of success was 100% for involutional and cicatricial ectropions, 90% for lid retraction and 87.5% for paralytic ectropions. Anatomical success according to EGS scale was obtained in 41 patients. Recurrence of ectropion occurred in only one patient 6 months after the first surgery and required a further operation with a larger posterior lamella resection and new tarsal belt suture. CONCLUSIONS: The tarsal belt seems to be effective to correct the horizontal and vertical instability of the lid. The suture supports the lower eyelid along the entire tarsal plate length and corrects the outward buckling of the tarsal plate.

The Tuscany experimental registry for Alzheimer's disease and other dementias: how many demented people does it capture?

BACKGROUND AND AIMS: A Regional Registry for Alzheimer's Disease and Other Dementias is being tested in Tuscany (Italy) to provide a basis for epidemiological studies. Current results are presented and critically evaluated. METHODS: The Registry extracts data on cases of dementia from Hospital Discharge Records, Outpatient Service Records, Regional Mortality Registry and Disease-Specific Co-payment Exemption Records, based on ICD-9 codes of dementias, and from Prescription Records based on registered anti-dementia drug codes. A list of cases of dementia prevalent at the end of 2005 was produced by cross-checking captured cases with the Regional Mortality Registry. RESULTS: The Registry captured 47,889 cases, of which 27,796 were still alive at the end of 2005. Captured cases represent slightly less than half of all the cases of dementia estimated to be present in Tuscany among older residents (65+) according to recent prevalence studies. Conversely, of 87 subjects 65 years of age or older selected from the Registry and directly evaluated, 80 (92%) were truly cognitively impaired subjects. CONCLUSIONS: The Registry has low sensitivity, probably because not all demented individuals are diagnosed as such in current practice and/or use health services. Conversely, the Registry has high specificity, and the produced lists of prevalent dementia cases are the key to estimating health and quality-of-care indicators for the demented population, and may constitute a basis for epidemiological studies.

Percolation of particles on recursive lattices using a nanoscale approach. I. Theoretical foundation at the atomic level.

Powdered materials of sizes ranging from nanometers to micrometers are widely used in materials science and are carefully selected to enhance the performance of a matrix. Fillers have been used in order to improve properties, such as mechanical, rheological, electrical, magnetic, thermal, etc., of the host material. Changes in the shape and size of the filler particles are known to affect and, in some cases, magnify such enhancement. This effect is usually associated with an increased probability of formation of a percolating cluster of filler particles in the matrix. In this series of papers, we will consider lattice models. Previous model calculations of percolation in polymeric systems generally did not take into account the possible difference between the size and shape of monomers and filler particles and usually neglected interactions or accounted for them in a crude fashion. In our approach, the original lattice is replaced by a recursive structure on which calculations are done exactly and interactions as well as size and shape disparities can be easily taken into account. Here, we introduce the recursive approach, describe how to derive the percolation threshold as a function of the various parameters of the problem, and apply the approach to the analysis of the effect of correlations among monodisperse particles on the percolation threshold of a system. In the second paper of the series, we tackle the issue of the effect of size and shape disparities of the particles on their percolation properties. In the last paper, we describe the effects due to the presence of a polymer matrix.

Percolation of particles on recursive lattices using a nanoscale approach. II. The effect of size and shape disparities.

The preparation of many composites requires the intermixing of several macromolecular fluids along with the addition of rigid filler particles. These fillers are usually polydisperse and there is extensive experimental evidence that their size and shape profoundly affect the properties of the resulting material. In particular, it is generally found that the percolation threshold decreases as the size disparity between the different particles present in a system increases, and that the threshold decreases with increasing aspect ratio of the particles. Here, a recursive approach that we have recently introduced is applied to the study of the percolation of particles of different sizes and shapes, without the presence of a polymer matrix, on a lattice in various phases including metastable states. In our approach, the original lattice is replaced by a recursive structure on which calculations are done exactly and interactions as well as size and shape disparities are easily taken into account. In the previous paper of this series, we introduced the recursive approach and showed how correlations among particles of the same size can affect percolation. Before considering the complete system made of particles of various sizes and shapes embedded in a polymer matrix, in the third paper of the series, we describe here the properties of systems made of particles without any matrix. The approach appears to be extremely successful since it is able to capture most of the important features observed in experiments.

Percolation of particles on recursive lattices using a nanoscale approach. III. Percolation of polydisperse particles in the presence of a polymer matrix.

We use a recently developed lattice model of polymers to study the percolation of particles of different sizes and shapes in the presence of a polymer matrix. The polymer is modeled as an infinitely long chain to simplify the calculation but we make it more realistic by considering it semiflexible. We study the effects of the stiffness of the polymer, the size disparity of the filler particles, their aspect ratio, and the interactions between fillers and polymer on the percolation properties of the system. The lattice model is solved exactly on a recursive square Husimi lattice, which is an approximation for a square lattice. The solution represents an approximate solution for a square lattice. Our results are able to reproduce most of the experimental findings that have been observed in the literature. In particular, we observe how an increase in the size disparity of the filler particles dispersed in the matrix as well as an increase of their aspect ratio decreases the percolation threshold.

Localization of a multiblock copolymer at a selective interface: scaling predictions and Monte Carlo verification.

We investigate the localization of a hydrophobic-polar regular copolymer at a selective solvent-solvent interface with emphasis on the impact of block length M on the copolymer behavior. The considerations are based on simple scaling arguments and use the mapping of the problem onto a homopolymer adsorption problem. The resulting scaling relations treat the gyration radius of the copolymer chain perpendicular and parallel to the interface in terms of chain length N and block size M, as well as the selectivity parameter chi. The scaling relations differ for the case of weak and strong localization. In the strong localization limit a scaling relation for the lateral diffusion coefficient D( parallel) is also derived. We implement a dynamic off-lattice Monte Carlo model to verify these scaling predictions. For chain lengths in a wide range (32