A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

During the last years, the management of heart failure (HF) made substantial progress, focusing on device-based therapies to meet the demands of this complex syndrome. In this case report, we present a multistep approach to deal with HF. Specifically, we report the first patient subjected to the implantation of both Optimizer Smart(R) (Impulse Dynamics Inc., Marlton, NJ, USA) and CardioMEMS devices. A 72-year-old male patient with HF and reduced ejection fraction (HFrEF) was admitted to our cardiology department in January 2021, following a progressive shortening of the time between hospitalizations for levosimendan infusions. Specifically, the patient was monitored daily by CardioMEMS, and a strategy of levosimendan infusions guided by the device had been adopted. He was also a carrier of MitraClips and cardiac resynchronization therapy defibrillator (CRT-D) and had optimized HF medical therapy. In January 2021, the patient implanted Optimizer Smart(R) device for cardiac contractility modulation (CCM) therapy because of poor response to therapy and elevated pulmonary artery pressure (PAP). CCM significantly reduced PAP values following discharge (systolic PAP 33.67 & PLUSMN; 2.92 vs. 40.6 & PLUSMN; 3.37 mmHg, diastolic PAP 14.5 & PLUSMN; 2.01 vs. 22.5 & PLUSMN; 2.53 mmHg, mean PAP 22.87 & PLUSMN; 2.20 vs. 30.9 & PLUSMN; 2.99 mmHg, HR 60.93 & PLUSMN; 1.53 vs. 80.83 & PLUSMN; 3.66 bpm; p < 0.0001), with persisting effect at 9 months. The usefulness of CCM is objectively demonstrated for the first time by continuous invasive monitoring of PAP by CardioMEMS, which can suggest the correct timing for CCM implantation

Diagnosis and Treatment of Pulmonary Disease in Sea Turtles (Caretta caretta)

The aim of this study was to describe the clinical signs, radiographic, endoscopic and CT findings, cytological and microbiological findings and treatments of pulmonary diseases in sea turtles, in order to obtain an accurate diagnosis that avoids unnecessary therapy and antibiotic-resistance phenomena. In total, 14 loggerheads (Caretta caretta), with clinical and/or radiographic findings of pulmonary pathology, were assessed through various combinations of clinical, radiological, CT, endoscopic examination and bronchoalveolar lavage, which recovered fluid for cytologic and microbiologic analysis. In all cases, radiographic examination led to a diagnosis of pulmonary disorders—4 unilateral and 10 bilateral. All bacteria cultured were identified as Gram-negative. Antibiotic resistance was greater than 70% for all beta-lactams tested. In addition, all bacterial strains were 100% resistant to colistin sulfate and tetracycline. Specific antibiotic therapies were formulated for seven sea turtles using Enrofloxacin, and for four sea turtles using ceftazidime. In two turtles, antibiotic therapy was not included due to the presence of antibiotic resistance against all the antibiotics evaluated. In both cases, the coupage technique and environmental management allowed the resolution of the lung disease without antibiotics. All 14 sea turtles were released back into the sea. Radiographic examination must be considered the gold standard for screening sea turtles that show respiratory signs or abnormal buoyancy. Susceptibility testing with antimicrobials allowed appropriate therapy, including the reduction of antibiotic-resistance

Correction to: A formulation of neem and hypericum oily extract for the treatment of the wound myiasis by Wohlfahrtia magnifica in domestic animals

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A Novel Combination of High-Load Omega-3 Lysine Complex (AvailOm®) and Anthocyanins Exerts Beneficial Cardiovascular Effects

Omega-3 fatty acids have been shown to exert several beneficial effects in the prevention of cardiovascular and cerebrovascular diseases. The objective of the present study was to analyze the effects of a novel high-load omega-3 lysine complex, AvailOm®, its related constituents and a novel mixture of AvailOm® with specific vasoactive anthocyanins on vascular function in mice resistance artery. Pressure myograph was used to perform vascular reactivity studies. Nitric oxide and oxidative stress were assessed by difluorofluorescein diacetate and dihydroethidium, respectively. Increasing doses of AvailOm® exerted a dose-response vasorelaxation via AMPK-eNOS-mediated signaling. Omega-3 Ethyl Ester was identified as the main bioactive derivative of AvailOm®, being capable of inducing vasorelaxant action to the same extent of entire product. The combination of AvailOm® with a mix of potent vasoactive anthocyanins (C3-glu + DP3-glu + Mal3-glu + Mal3-gal + PEO3-gal), strongly protected mesenteric arteries from vascular dysfunction and oxidative stress evoked by oxidized-LDL. These data demonstrate for the first time the direct effects of AvailOm® on resistance arteries. The evidence that the combination of specific vasoactive anthocyanins and AvailOm® further enhanced the vasculoprotective properties of these compounds, may offer new promising perspectives for preventing the onset of cardiovascular and cerebrovascular events

Patterns of inflammation, microstructural alterations, and sodium accumulation define multiple sclerosis subtypes after 15 years from onset

INTRODUCTION: Conventional MRI is routinely used for the characterization of pathological changes in multiple sclerosis (MS), but due to its lack of specificity is unable to provide accurate prognoses, explain disease heterogeneity and reconcile the gap between observed clinical symptoms and radiological evidence. Quantitative MRI provides measures of physiological abnormalities, otherwise invisible to conventional MRI, that correlate with MS severity. Analyzing quantitative MRI measures through machine learning techniques has been shown to improve the understanding of the underlying disease by better delineating its alteration patterns. METHODS: In this retrospective study, a cohort of healthy controls (HC) and MS patients with different subtypes, followed up 15 years from clinically isolated syndrome (CIS), was analyzed to produce a multi-modal set of quantitative MRI features encompassing relaxometry, microstructure, sodium ion concentration, and tissue volumetry. Random forest classifiers were used to train a model able to discriminate between HC, CIS, relapsing remitting (RR) and secondary progressive (SP) MS patients based on these features and, for each classification task, to identify the relative contribution of each MRI-derived tissue property to the classification task itself. RESULTS AND DISCUSSION: Average classification accuracy scores of 99 and 95% were obtained when discriminating HC and CIS vs. SP, respectively; 82 and 83% for HC and CIS vs. RR; 76% for RR vs. SP, and 79% for HC vs. CIS. Different patterns of alterations were observed for each classification task, offering key insights in the understanding of MS phenotypes pathophysiology: atrophy and relaxometry emerged particularly in the classification of HC and CIS vs. MS, relaxometry within lesions in RR vs. SP, sodium ion concentration in HC vs. CIS, and microstructural alterations were involved across all tasks

A Novel Vasoactive Peptide “PG1” from Buffalo Ice-Cream Protects from Angiotensin-Evoked High Blood Pressure

Arterial hypertension is the most important risk factor for cardiovascular diseases, myocardial infarction, heart failure, renal failure and peripheral vascular disease. In the last decade, milk-derived bioactive peptides have attracted attention for their beneficial cardiovascular properties. Methods: Here, we combined in vitro chemical assay such as LC-MS/MS analysis of buffalo ice cream, ex vivo vascular studies evaluating endothelial and smooth muscle responses using pressure myograph, and translational assay testing in vivo the vascular actions of PG1 administration in murine models. Results: We demonstrate that a novel buffalo ice-cream-derived pentapeptide “QKEPM”, namely PG1, is a stable peptide that can be obtained at higher concentration after gastro-intestinal digestions (GID) of buffalo ice-cream (BIC). It owns potent vascular effect in counteract the effects of angiotensin II-evoked vasoconstriction and high blood pressure levels. Its effects are mediated by the inhibitory effect on AT1 receptor leading to a downregulation of p-ERK½/Rac1-GTP and consequent reduction of oxidative stress. Conclusions: These results strongly candidate PG1, as a novel bioactive peptide for the prevention and management of hypertension, thus expanding the armamentarium of preventive strategies aimed at reducing the incidence and progression of hypertension and its related cardiovascular complication

What contributes to disability in progressive MS? A brain and cervical cord–matched quantitative MRI study

Background: We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability. // Methods: A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord–matched protocol with brain-and-cord–unified imaging readouts. Lesion and NA-tissue volumes and qMRI metrics reflecting demyelination and axonal loss were obtained. Random forest analyses identified the most relevant volumetric/qMRI measures to clinical outcomes. Confounder-adjusted linear regression estimated the actual MRI-clinical associations. // Results: Several qMRI/volumetric differences between patients and controls were observed (p < 0.01). Higher NA-deep grey matter quantitative-T1 (EDSS: beta = 7.96, p = 0.006; 9HPT: beta = −0.09, p = 0.004), higher NA-white matter orientation dispersion index (TWT: beta = −3.21, p = 0.005; SDMT: beta = −847.10, p < 0.001), lower whole-cord bound pool fraction (9HPT: beta = 0.79, p = 0.001) and higher NA-cortical grey matter quantitative-T1 (SDMT = −94.31, p < 0.001) emerged as particularly relevant predictors of greater disability. // Conclusion: Fast brain-and-cord–matched qMRI protocols are feasible and identify demyelination – combined with other mechanisms – as key for disability accumulation in PMS

CD99 Expression and Prognostic Impact in Glioblastoma: A Single-Center Cohort Study

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan-Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma

Exploring in vivo multiple sclerosis brain microstructural damage through T1w/T2w ratio: a multicentre study

Objectives: To evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in healthy controls and patients with multiple sclerosis, and its association with clinical disability. Methods: In this cross-sectional study, 270 healthy controls and 434 patients with multiple sclerosis were retrospectively selected from 7 European sites. T1w/T2w ratio was obtained from brain T2w and T1w scans after intensity calibration using eyes and temporal muscle. Results: In healthy controls, T1w/T2w ratio increased until 50-60 years both in white and grey matter. Compared with healthy controls, T1w/T2w ratio was significantly lower in white matter lesions of all multiple sclerosis phenotypes, and in normal-appearing white matter and cortex of patients with relapsing-remitting and secondary progressive multiple sclerosis (p≤0.026), but it was significantly higher in the striatum and pallidum of patients with relapsing-remitting, secondary progressive and primary progressive multiple sclerosis (p≤0.042). In relapse-onset multiple sclerosis, T1w/T2w ratio was significantly lower in white matter lesions and normal-appearing white matter already at Expanded Disability Status Scale (EDSS) <3.0 and in the cortex only for EDSS ≥3.0 (p≤0.023). Conversely, T1w/T2w ratio was significantly higher in the striatum and pallidum for EDSS ≥4.0 (p≤0.005). In primary progressive multiple sclerosis, striatum and pallidum showed significantly higher T1w/T2w ratio beyond EDSS=6.0 (p≤0.001). In multiple sclerosis, longer disease duration, higher EDSS, higher brain lesional volume and lower normalised brain volume were associated with lower lesional and cortical T1w/T2w ratio and a higher T1w/T2w ratio in the striatum and pallidum (β from -1.168 to 0.286, p≤0.040). Conclusions: T1w/T2w ratio may represent a clinically relevant marker sensitive to demyelination, neurodegeneration and iron accumulation occurring at the different multiple sclerosis phases

Dynamics of skyrmionic states in confined helimagnetic nanostructures

In confined helimagnetic nanostructures, skyrmionic states in the form of incomplete and isolated skyrmion states can emerge as the ground state in absence of both external magnetic field and magnetocrystalline anisotropy. In this work, we study the dynamic properties (resonance frequencies and corresponding eigenmodes) of skyrmionic states in thin film FeGe disk samples. We employ two different methods in finite-element based micromagnetic simulation: eigenvalue and ringdown method. The eigenvalue method allows us to identify all resonance frequencies and corresponding eigenmodes that can exist in the simulated system. However, using a particular experimentally feasible excitation can excite only a limited set of eigenmodes. Because of that, we perform ringdown simulations that resemble the experimental setup using both in-plane and out-of-plane excitations. In addition, we report the nonlinear dependence of resonance frequencies on the external magnetic bias field and disk sample diameter and discuss the possible reversal mode of skyrmionic states. We compare the power spectral densities of incomplete skyrmion and isolated skyrmion states and observe several key differences that can contribute to the experimental identification of the state present in the sample. We measure the FeGe Gilbert damping, and using its value we determine what eigenmodes can be expected to be observed in experiments. Finally, we show that neglecting the demagnetization energy contribution or ignoring the magnetization variation in the out-of-film direction—although not changing the eigenmode's magnetization dynamics significantly—changes their resonance frequencies substantially. Apart from contributing to the understanding of skyrmionic states physics, this systematic work can be used as a guide for the experimental identification of skyrmionic states in confined helimagnetic nanostructures