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Abstract Background Type 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism. Objectives We aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease. Methods We combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n = 34) or without (n = 50) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy. Results T2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca2+ signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca2+ uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D. Conclusions Our data support a crucial role for mitochondrial Ca2+ signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca2+ uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS. Trial registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01862237. Graphical abstract

In this paper, the Klein – Gordon – Fock equation is derived from the first principles. There is no need to postulate the existence of wave functions or to axiomatically introduce values of equation coefficients within the framework of the applied approach. The equation was derived on an adiabatically variable manifold, locally described by the FRW metric with complete electrodynamics constructed on it. Here the transverse electromagnetic field (TEMF) is quantized due to the adiabatic change in the metric tensor and the Planck constant acts as an adiabatic invariant of the TEMF. Moreover, the wave functions appear in the equations in a natural way, being eigenfunctions of the Sturm – Liouville problem. These are the functions in which the TEMF function is expanded. To summarize, the proposed approach makes obvious the physical meaning both of the equation itself and of quantum mechanics in general.

We present new results obtained from the modeling of a tulip-like variable curvature mirror (VCM) in the case of a central force that reacts to its contour. From Nastran finite element analysis, we shows that 3-D optimizations, using non-linear static flexural option, with an appropriate solution sequence, provide an accurate tulip-like VCM thickness distribution. This allows us to take into account boundary conditions, including the thin outer collarette and its link to a rigid ring. Modeling with a quenched stainless steel chromium substrate provides diffraction-limited optical surfaces. Rayleigh’s quarter-wave criterion is performed over a zoom range from flat up to f/3.5 convexity over a 13 mm clear aperture and 10 daN central force. The optical testing results of a prototype tulip-like VCM elaborated from the previous analytic theory, show quasi-diffraction-limited figures for a zoom range up to f/5. The present modeling results should significantly help in the future construction of such VCMs with a zoom range extended up to f/3.5.

Abstract Background Papillary fibroelastomas (PFEs) are a rare subtype of benign primary cardiac tumours, which are most commonly found on the aortic valve. Although median sternotomy is still used frequently there has been different attempts to remove the aortic valve PFEs minimally invasively using robotic and Mini sternotomy approach. Case presentation We report herein a case of totally endoscopic non robotic removal of PFE of aortic valve. Conclusions The encouraging intra and post-operative outcomes and fast recovery using totally endoscopic approach for removal of PFE shows the potential benefits of this technique.

This study analyzes high-grade carbonate rocks from several strategic deposits in the Arabian Peninsula and neighboring countries. The rocks are used locally for quicklime and dololime production in twin-shaft regenerative kilns. Stable C-O-Sr isotopes, along with chemical, mineralogical-petrographic analyses, micropaleontological investigations, cathodoluminescence microscopy, organic carbon speciation, and electron paramagnetic resonance spectroscopy, were used to trace the provenance of these rocks from economically significant non-metallic deposits. The resulting database can help identify and differentiate industrial raw materials that may appear similar chemically and/or macroscopically but have different textures/microstructures that can affect the properties of the derived burnt lime products. Various technological tests, including slaking reactivity, sticking tendency at high-temperature (i.e., 1300 °C), and physico-mechanical behavior of the lime, were performed to evaluate their suitability and predict lime performance in twin-shaft regenerative kilns. Comparison of laboratory and plant results validated the resulting database.

This study analyses the implementation of a circularity measurement methodology at the University of Piemonte Orientale (UPO) in the early stages of the development of the UNI1608856 project “Measuring circularity - Methods and indicators for measuring circular processes in organisations, the first attempt to assess an organisation’s circularity under a standardized framework in an Italian University. The single-case study examines the organisation’s framework implementation, followed by an in-depth discussion of the phenomenon under study. The circularity measurement metrics applied to the UPO case have been extracted from a draft standard prepared by the Italian standardization body (UNI). The UPO case study considers the draft's general propositions with a focus on the metrics related to the management of human resources, assets, policy, and sustainability. Some useful insights emerge from the critical analysis of the norm proposal, both regarding adopting different types of measures and implementing the circularity measurement in terms of the organisation’s readiness to collect data for the metrics. As this study deals with a new framework applied to a public Organisation, several issues come to light. The first implementation of UNI1608856 allows discussion of the effective measurement of circularity at the micro level and how an organisation’s managerial processes need to evolve to provide the data required to measure circularity.

BackgroundCystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato, is a neglected zoonosis. Its diagnosis relies on imaging, supported by serology, while only imaging is useful for staging and follow-up. Since diagnostic tools and expertise are not widely available, new accurate and easily implementable assays for the diagnosis and follow-up of CE are highly needed.Methodology/principal findingsWe aimed to identify new E. granulosus antigens through a bioinformatics selection applied to the parasite genome, followed by peptide microarray screening and validation in ELISA, using independent panels of sera from patients with hepatic CE and clinically relevant controls. From 950 proteins selected in silico, 2,379 peptides were evaluated by microarray for IgG reactivity and eight candidates selected for validation. Reactivity to one peptide was significantly higher in the CE group (p = 0.044), but had suboptimal diagnostic accuracy.Conclusions/significanceHere we performed bioinformatics analysis and peptide microarray for antigen discovery, useful for the diagnosis of CE. Eight candidates were selected and validated. Reactivity to one peptide associated to CE but had suboptimal diagnostic accuracy. Importantly, the database developed in this study may be used to identify other antigenic candidates for CE diagnosis and follow-up.

Not available.

Cardiac surgery associated-acute kidney injury is a common and serious postoperative complication of cardiac surgery, which is associated with increased postoperative morbidity and mortality. This study aimed to explore the association between cardiopulmonary bypass (CPB) blood flow rate (BFR), and major adverse kidney events (MAKEs) at day 30. Retrospective single-center before–after observational study. Patients were divided in 2 groups according to CPB flow rates: a first group with an institutional protocol targeting a CPB-BFR of >2.2 L/min/m² (low CPB-BFR group), and a second group with a modified institutional protocol targeting a CPB-BFR of >2.4 L/min/m² (high CPB-BFR group). The primary outcome was MAKE at 30 days, defined as the composite of death, renal replacement therapy or persistent renal dysfunction. The data were collected from clinical routines in university hospital. Adult patients who underwent elective and urgent cardiac surgery without severe chronic renal failure, for whom CPB duration was ≥90 minutes. We included 533 patients (low CPB-BFR group, n = 270; high CPB-BFR group, n = 263). A significant decrease in MAKE at 30 days was observed in the high CPB-BFR group (3% v 8%; odds ratio [OR], 0.779; 95% confidence interval [CI], 0.661-0.919; p < 0.001) mainly mediated by a lower 30-day mortality in the high CPB-BFR group (1% v 5%; OR, 0.697; 95% CI, 0.595-0.817; p = 0.001), as was renal replacement therapy (1% v 4%; OR, 0.739; 95% CI, 0.604-0.904; p = 0.016). In patients undergoing cardiac surgery, increased CPB-BFR was associated with a decrease in MAKE at 30 days including mortality and renal replacement therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Localized melanoma is easy to remove by surgery, resulting in a high five-year relative survival rate. However, when disseminated the disease management is challenging. The use of immunotherapies, such as anti-checkpoint monoclonal antibodies, has improved treatment options but still only a small percentage of patients responds to these expensive treatments. In this work, we apply a bacteria-based immunotherapy using LVR01, an attenuated Salmonella enterica serovar Typhimurium, as neoadjuvant therapy one week before surgery in a preclinical disseminated murine melanoma model. LVR01 administration resulted in tumor growth retardation prior to tumor resection, due to a rapid upregulation of inflammatory genes in the tumor microenvironment. As a consequence, cell infiltration increased, particularly neutrophils, macrophages and NK cells, being the latter involved in Salmonella anti-tumor activity. Besides, tumor-draining lymph node infiltration is characterized by reinvigorated CD4+ and CD8+ lymphocytes. Induced immune response could account for the prevention or delay of tumor recurrence and appearance of metastasis, resulting in a prolonged overall survival after surgery. Furthermore, upon rechallenge mice show partial protection, suggesting the existence of specific memory against melanoma. We propose that neoadjuvant LVR01 treatment could represent an interesting inexpensive alternative that may ease tumor resection, while preventing tumor recurrence in patients with melanoma.

The eye should have a particular focal length in order to see an object. As there are many things to see, the focal length of the eye must vary because these things are not all at the same distance from the eye. We explore the eye accommodation from a geometrical optics point of view and present our results in this paper; the study includes a description of the accommodation mechanism and a scientific definition of near vision and far vision.

Introducción: la enfermedad de Hansen es una enfermedad infecciosa crónica, causada por Mycobacterium leprae, que afecta principalmente piel y nervios periféricos. Las reacciones leprosas son eventos agudos que se asocian a un aumento de la morbimortalidad de la enfermedad. Objetivo: presentar el caso clínico de un paciente con fenómeno de Lucio, a través del cual se llegó al diagnóstico de enfermedad de Hansen, y remarcar la importancia de tener presente esta enfermedad, poco frecuente en nuestro país, para su correcto diagnóstico. Discusión: el fenómeno de Lucio es un tipo de reacción leprosa mediada por inmunocomplejos. Se caracteriza clínicamente por máculas o placas eritematovioláceas, de aparición súbita, que evolucionan a úlceras necróticas y curan dejando cicatrices estrelladas atróficas. De no mediar tratamiento, puede ser fatal, debido a sobreinfección y sepsis. Este se basa en el tratamiento específico de la infección, asociado a prednisona y un correcto manejo de las heridas.

Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.

The field of self-access has spanned 50 years, and in this report, the authors give a brief overview of a recent event organized by the Research Institute for Learner Autonomy Education (RILAE) with the theme of ‘Landmarks in self-access’. The authors also make reference to some landmark and recent publications in learner autonomy and self-access that have influenced the field.

Abstract Background Progressive multifocal leukoencephalopathy (PML) can rarely occur in Multiple Sclerosis (MS) patients undergoing dimethyl fumarate (DMF) treatment. Our case stresses the limits of current diagnostic and stratification risk criteria, highlighting the potential role of Magnetic Resonance Imaging (MRI) in advising clinical choices. Case presentation A 54 years old MS male patient treated with DMF, after 3 years of clinical stability developed a subacute clinical worsening. He had no severe lymphopenia but MRI signs suggestive of a coexistence of PML and MS activity. Although his viral title was negative, DMF was discontinued, with clinical and radiological improvement. Conclusions This case highlights the challenges behind PML diagnosis, especially in patients not fulfilling the risk stratification criteria and that might present with concurrent disease activity, stressing the potential role of MRI in informing therapeutic decisions.

Background: Contrasting data are available in the literature regarding the superiority of percutaneous microwave ablation (MWA) or radiofrequency ablation (RFA) in very early or early (BCLA 0 or A) hepatocellular carcinoma (HCC). Aims: The primary outcome was to compare the efficacy of RFA and MWA in achieving complete response in cirrhotic patients with early and very early HCC. The secondary outcomes were to evaluate the overall survival and the recurrence rate. Methods: A retrospective, observational, single-center study was performed. Inclusion criteria were liver cirrhosis, new diagnosis of a single node of HCC measuring a maximum of 50 mm or up to three nodules with diameter up to 35 mm, treatment with RFA or MWA. Radiological response was evaluated with multiphasic contrast-enhanced Computed Tomography or Magnetic Resonance Imaging at 5–7 weeks after thermal ablation. Complete response was defined when no vital tissue was detected after treatment. Results: Overall, 251 HCC patients were included in this study; 81 patients were treated with MWA and 170 with RFA. The complete response rate was similar in MWA and RFA groups (out of 331 nodules, 87.5% (91/104) were treated with MWA and 84.2% (186/221) were treated with RFA, p = 0.504). Interestingly, a subanalysis demonstrated that for 21–35 mm nodules, the probability to achieve a complete response using MWA was almost 5 times higher than for RFA (OR = 4.88, 95% CI 1.37–17.31, p = 0.014). Moreover, recurrence rate in 21–35 mm nodules was higher with RFA with respect to MWA (31.9% versus 13.5%, p = 0.019). Overall survival was 80.4% (45/56) when treated with MWA and 62.2% (56/90) when treated with RFA (p = 0.027). No significant difference was observed between MWA and RFA treatment in the 15–20 mm nodules group. Conclusion: This study showed that MWA is more efficient than RFA in achieving complete response in HCC nodules with 21 to 35 mm diameter.

In 2020, the COVID-19 pandemic created disruption in many of the institutions we regularly rely on, including universities. While disruption may often bring with it a myriad of possible pitfalls, it affords potential opportunities for change and development by reflecting on and modifying practices. In this article, a group of learning advisors and administrators from a self-access center at an international university in Japan reflect on the ruptures we experienced as a result of changes due to unexpectedly working remotely and our attempts to find stability, the pitfalls we sought to avoid, and the opportunities that we found amidst the disruption. Specifically, we illustrate our experiences related to student-led learning communities, self-access curricula, and learning advising, considering the effect on students and advisors alike. We advocate that self-access practitioners actively promote the use of language, encourage the development of communities of learners who focus on their interests, offer full online services even when the center is open, and use the same effective practices whether supporting learners online or offline. Our intention is that this article will help others to support stability, connectivity, and positive development in their own contexts.

Abstract Purpose We aimed to assess the role of radiologists, cardiologists, and other medical and non-medical figures in cardiac magnetic resonance imaging (MRI) research in the last 34 years, focusing on first and last authorship, number of published studies, and journal impact factors (IF). Methods Articles in the field of cardiac MRI were considered in this systematic review and retrospective bibliometric analysis. For included studies, the first and last authors were categorized as cardiologists, radiologists/nuclear medicine physicians, medical doctors (MD) with specialties in both cardiology and radiology/nuclear medicine, and other MD and non-MD. Differences in the number of papers published overall and by year and institution location for the first and last author category were assessed. Mean IF differences between author categories were also investigated. Results A total of 2053 articles were included in the final analysis. For the first authors (n = 2011), 52% were cardiologists, 22% radiologists/nuclear medicine physicians, 16% other MD, 10% other non-MD, and 1% both cardiologists and radiologists/nuclear medicine physicians. Similarly, the last authors (n = 2029) resulted 54% cardiologists, 22% radiologists/nuclear medicine physicians, 15% other MD, 8% other non-MD, and 2% both cardiologists and radiologists/nuclear medicine physicians. No significant differences due to institution location in the first and last authorship proportions were found. Average journal IF was significantly higher for cardiologist first and last authors when compared to that of radiologists/nuclear medicine physicians (both p < 0.0001). Conclusion Over 50% of studies in the field of cardiac MRI published in the last 34 years are conducted by cardiologists.

BackgroundCystic echinococcosis (CE) is a complex disease for which clear understanding of clinical manifestations is needed to avoid misdiagnosis, inappropriate treatment, and severe complications. We evaluated the accuracy of a whole-blood stimulation test based on Interleukin (IL)-4 detection in response to Antigen B (AgB) of Echinococcus granulosus sensu lato to discriminate cyst viability and detect cyst reactivation in patients with hepatic CE.Methodology/principal findingsThirty patients with CE3b cysts and 37 patients with spontaneously-inactivated CE4-CE5 cysts were recruited (T0). After enrollment, 5 patients with CE3b cysts received albendazole, resulting in cyst solidification (CE4) in 4/5. Within a two-year follow-up, the whole-blood test was repeated at two time-points, in ≥14 (T1) and in ≥4 (T2) patients per group. IL-4 and a panel of other soluble factors were measured in the stimulated plasma. Baseline IL-4 levels were significantly higher in patients with CE3b compared to those with CE4 cysts (p = 0.006). Test accuracy for CE3b diagnosis had a sensitivity of 33-60% and a specificity of 76-95%, depending on the cut-off applied. Overall, IL-4 levels did not change significantly over time in either group; however, patients within the CE3b group showed a significant decrease of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF at T1 compared to T0 (p≤0.042).Conclusions/significanceWhole-blood IL-4-response to AgB is significantly higher in patients with active compared to inactive CE but apparently not modulated over time after treatment. On the contrary, the levels of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF significantly decreased in active CE during follow-up. Additional studies are needed to understand whether these findings might have a clinical significance for patients' follow-up.

Upper-respiratory-tract infections (URTIs) are among the main causes of antibiotic prescriptions in pediatric patients. Over one-third of all antibiotic prescriptions for URTIs in children are estimated to be inappropriate, as the majority of URTIs are caused by viral agents. Several strategies, including clinical scoring algorithms and different point-of-care tests (POCTs) have been developed to help discriminate bacterial from viral URTIs in the outpatient clinical setting. A systematic review of the literature was conducted following PRISMA guidelines with the objective of summarizing evidence from health–economic evaluations on the use of POCT for URTIs in pediatric outpatients. A total of 3375 records identified from four databases and other sources were screened, of which 8 met the inclusion criteria. Four studies were classified as being of high reporting quality, and three were of medium quality. Five out of eight studies concluded in favor of strategies that included POCTs, with an additional study finding several POCTs to be cost-effective compared to usual care but over an acceptable WTP threshold. This review found POCT could be a valuable tool for antimicrobial stewardship strategies targeted towards childhood URTIs in primary care.

Toxoplasma gondii is a protozoan parasite responsible for human toxoplasmosis. The three major clonal lineages and different recombinant strains of T. gondii have a varied global distribution. This study aimed at evaluating the epidemiological distribution of types II and I–III and recombinant or mixed T. gondii in Italians and foreigners residing in Italy, establishing an association between serotypes and demographic characteristics. We collected the sera of 188 subjects who had tested positive for specific T. gondii antibodies. The population was differentiated into groups based on sex, nationality, and place of birth (Italy, Africa, South America, Asia, or Europe (except Italy)). We then performed a homemade ELISA test that detected both the antibodies against the amino acid sequences of the three main genotype antigens (I–III) in human sera and discerned the T. gondii strains. Serotype II of T. gondii was the most prevalent in the Italian population, whereas type I–III was the most prevalent in the foreign group. Surprisingly, we observed a notable amount of recombinant or mixed serotypes in European and Italian subjects. Moreover, we showed a significant difference in the prevalence of T. gondii serotypes between men and women, Italians, and foreigners. This descriptive study is the first to investigate the epidemiological distribution of T. gondii serotypes in humans in Italy using a homemade ELISA. We considered this technique suitable for discriminating between serotypes II and I–III and, consequently, for an epidemiological study focusing on the observation of circulating T. gondii strains and clinical correlations.

The aim of this paper is to investigate the complex relationship between global business and biodiversity. Since business organizations impact biodiversity degradation and at the same time have to face the consequences of the loss of biodiversity, it seems necessary to further investigate the role played by business organizations in alleviating biodiversity loss (Reade, Goka, Thorp, Mitsuhata and Wasbauer, 2014). In order to study how business organizations comprise the topic of biodiversity in reality, this research primarily proposes a literature review on biodiversity in the field of accounting, management and organization. This assessment is significant being, as far as we know, one of the first systematic reviews of the literature on biodiversity and natural capital.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosis and monitoring of CE rely primarily on imaging while serology is used as a confirmatory test. However, imaging is not always conclusive and currently available serological assays have suboptimal sensitivity and specificity, lack standardization, and are not useful for patients´ follow-up. Seroassays for CE are usually based on hydatid fluid (HF), a complex, variable antigenic mixture, and cross-reactivity exists especially with alveolar echinococcosis. Recombinant proteins based on immunogenic antigens most abundant in HF, such as AgB1, AgB2 and Ag5, have been used to overcome these limitations. None of them so far showed potential to replace HF; however, their performance have been largely tested on a limited number of samples, and comparison of different antigens using the same cohort has been rarely performed. The combination of several immunogenic epitopes in a single recombinant protein could enhance test sensitivity. For the diagnosis and follow-up of patients with CE, we compared the performance of the crude HF, previously described recombinant 2B2t antigen, and GST-tagged version of 2B2t, and novel designed recombinants (GST-Ag5t and the GST-DIPOL chimera containing AgB1, AgBB2 and Ag5 epitopes) by IgG-ELISA format. Samples belong to a retrospective cohort of 253 well-characterized patients with CE, previously described for the evaluation of the 2B2t antigen, 92 patients with alveolar echinococcosis, and 82 healthy donors. The reference standard for CE diagnosis was the presence of a CE lesion as diagnosed by ultrasonography. The highest sensitivity was obtained with HF [86.7%, 95% confidence interval (CI): 81.2-91.0], followed by GST-2B2t (70.0%, 95% CI: 63.1-76.2), 2B2t (65.5%, 95% CI: 58.5-72.0), GST-Ag5t (64.5%, 95% CI: 57.5-71.1) and GST-DIPOL (63.1%, 95% CI: 56.0-69.7). The GST-2B2t had the best specificity (95.8%, 95% CI: 88.3-99.1) and the lowest cross-reactivity (38.7%, 95% CI: 27.6-50.6). Good response to treatment also correlated to negative test results in the GST-2B2t ELISA. While none of the tested recombinant antigen appears suitable to replace HF for the diagnosis of CE, GST-2B2t should be further explored as a confirmation test, based on its high specificity and low cross-reactivity, and for the follow-up after treatment in those patients with positive serology for this antigen.

Elasticity theory and active optics led us to the discovery of three geometrical configurations of variable curvature mirrors (VCMs) that are either cycloid-like or tulip-like thickness distributions. Cycloid-like VCMs are generated by a uniform load—air pressure—applied over the mirror rear surface, and reacts without any bending moment along its circular contour. This particular VCM configuration is of practical interest because it smoothly generates accurate optical curvatures, varying from plane at rest to spherical curvatures up to f/2.9 over 16-mm aperture under 6.5-bar air pressure. Starting from the thin plate theory of elasticity and modeling with NASTRAN finite element analysis, one shows that 3-D optimizations—using a non-linear static flexural option—provide an accurate cycloid-like thickness distribution. VCM elasticity modeling in quenched stainless steel–chromium substrates allows the obtaining of diffraction-limited optical surfaces: Rayleigh’s criterion is achieved over a zoom range from flat to f/3.6 over 13-mm clear aperture up to 6-bar loading. These VCMs were originally developed and built at the Marseille Observatory in 1975 and implemented as a cat’s-eye mirror of IR Fourier-transform interferometers for laboratory recording of fast events in gas molecular spectroscopy. Later, for high-angular resolution astronomy with the ESO VLTI array—an interferometer made of 8 m Unit Telescopes (UTs) and 1.8 m Auxiliary Telescopes (ATs)—such VCMs were inevitable components to provide in a 3″ co-phased field-of-view since 1998. They were implemented (1) as cat’s eye mirrors of the height delay-lines beam recombination lab and (2) as ATs mirror-pair for output pupil conjugation of the movable x–y baseline. From the ESO-AMU approved convention of making 10 VCM spares up to 2024, the present modeling should provide a diffraction-limited extended field-of-view. It is pure coincidence that present results from modeling with an outer collarette are identical to results from analytic theory without collarette.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids syndrome (CLIPPERS) is a newly described, underestimated CNS inflammatory disorder involving predominantly the midbrain and the cerebellum. CLIPPERS pathogenesis is largely unknown, and its clinical manifestations are polymorphic and sometimes confounding. Recently clinical, radiological and pathological diagnostic criteria have been proposed to discriminate CLIPPERS from potential mimickers, but the diagnosis still remains challenging. Here we present the case of a patient with radiological findings consistent with CLIPPERS but with atypical clinical presentation, highlighting the importance of a proper diagnostic assessment. Keywords: CLIPPERS, Inflammation, Central Nervous System, Magnetic Resonance Imaging