Lupin alkaloids (LAs) represent a class of toxic secondary metabolites in plants, in particular in
spp.; they are produced as a defense mechanism due to their strong bitter taste and are very ...dangerous for human and animals. In this work, a sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analytical method for the identification and quantification of thirteen lupin alkaloids was developed and validated according to FDA guidelines. Efficient extraction and clean-up steps, carried out by solid-phase extraction, were finely tuned on the basis of the characteristics of the analytes and lupin samples, providing good selectivity with minimized matrix interference. The effectiveness of the method was proven by the satisfactory recovery values obtained for most of the analytes and a matrix effect ≤23% for all tested levels. In addition, a sensitive and reliable determination of the target compounds was obtained; LOQs were between 1 and 25 µg Kg
, i.e., below the requested maximum levels (<200 mg Kg
). The method was applied to evaluate the LAs profile in different batches of raw
L. samples, varying in size and across farming treatments.
Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic ...disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20-356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions.
In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9%
/
and transethosomes based on phosphatidylcholine 0.9 or 2.7%
.../
plus polysorbate 80 0.3%
/
as an edge activator were prepared and characterized. The vesicle mean size, morphology and deformability were influenced by both phosphatidylcholine and polysorbate 80. Indeed, the mean diameters of ethosome were around 200 nm, while transethosome's mean diameters were 146 or 350 nm in the case of phosphatidylcholine 0.9 or 2.7%,
/
, respectively. The highest deformability was achieved by transethosomes based on phosphatidylcholine 0.9%,
/
. The three types of vesicular nanosystems were applied on explanted human skin maintained in a bioreactor. Transmission electron microscopy demonstrated that all vesicles were able to enter the skin, keeping their structural integrity. Notably, the vesicle penetration capability was influenced by their physical-chemical features. Indeed, ethosomes reached keratinocytes and even the dermis, phosphatidylcholine 0.9% transethosomes were found in keratinocytes and phosphatidylcholine 2.7% transethosomes were found only in corneocytes of the outer layer. These findings open interesting perspectives for a differentiated application of these vesicles for transdermal drug delivery as a function of the cutaneous pathology to be addressed.
Objectives
Although cardiovascular magnetic resonance (CMR) is widely used in the assessment of left ventricular non-compaction (LVNC), there are no universally accepted diagnostic criteria and ...limited data regarding their prognostic value. We assessed the long-term prognostic role of the planimetric global Grothoff’s criteria and of the CMR findings in predicting adverse cardiovascular events (CE).
Methods
We prospectively enrolled 78 patients (46.7 ± 18.7 years, 33.3% females) with documented positive Jenni’s echocardiographic criteria for LVNC. Cine images were used to quantify function parameters and to assess for the presence of all four quantitative Grothoff’s criteria (global Grothoff’s criteria). Late gadolinium enhancement (LGE) images were acquired to detect the presence of replacement myocardial fibrosis.
Results
Petersen’s CMR criterion for LVNC (NC/C ratio > 2.3 in at least one myocardial segment) was fulfilled in the whole population. Twenty-six patients fulfilled the global Grothoff’s criteria (four out of four). The mean duration of the follow-up was 44.2 ± 27.4 months and 28 CE were registered: 10 ventricular tachycardias, 12 episodes of heart failure (HF), four strokes, and two cardiac deaths. In the multivariate analysis, the independent predictive factors for CE were positive global Grothoff’s criteria (hazard ratio, HR = 3.33, 95% CI = 1.52–7.29;
p
= 0.003) and myocardial fibrosis (HR = 2.41, 95% CI = 1.08–5.36;
p
= 0.032).
Conclusions
Positive global Grothoff’s criteria and myocardial fibrosis were powerful predictors of CE in patients with a diagnosis of LVNC by CMR Petersen’s criterion. Thus, we strongly suggest a step approach confirming the diagnosis of LVNC by using the global planimetric Grothoff’s criteria, which showed a prognostic impact.
Key Points
• Positive global Grothoff’s criteria and replacement myocardial fibrosis were powerful predictors of cardiovascular events in patients with a diagnosis of LVNC by CMR Petersen’s criterion.
• Positive global Grothoff’s criteria were associated with a higher frequency of ventricular arrhythmias in patients with a diagnosis of LVNC by CMR Petersen’s criterion.
A method for the determination of six phthalate esters in wine samples has been developed. The phthalates were extracted from wine samples with an optimised solid-phase extraction method on C18 ...column and quantification was achieved via gas chromatography coupled with a mass spectrometer. The method was linear between 0.015 and 5.000
μg
mL
−1 for DMP, DEP and DEHP and between 0.018 and 5.000
μg
mL
−1 for iBP, DBP and BBP. The LOQs of DMP, DEP and DEH were 0.024
μg
mL
−1 while those of iBP, DBP and BBP were 0.029
μg
mL
−1. The intra-day method repeatability was between 10% and 15% RSD, whereas the inter-day method repeatability was between 13% and 21% RSD. A survey was performed on white and red wines (
n
=
62) from the market, winemakers and an experimental pilot plant. All the analysed samples were phthalate contaminated. Commercial wine showed higher detection frequency and level of total phthalate, DBP and BBP than those produced in a pilot plant. iBP and DEHP concentrations were similar in all the groups of samples. iBP concentration was higher in red wines than in white ones.
Background
MRI represents the most established liver iron content (LIC) evaluation approach by estimation of liver T2* value, but it is dependent on the choice of the measurement region and the ...software used for image analysis.
Purpose
To develop a deep‐learning method for unsupervised classification of LIC from magnitude T2* multiecho MR images.
Study Type
Retrospective.
Population/Subjects
A total of 1069 thalassemia major patients enrolled in the core laboratory of the Myocardial Iron Overload in Thalassemia (MIOT) network, which were included in the training (80%) and test (20%) sets. Twenty patients from different MRI vendors included in the external test set.
Field Strength/Sequence
A5 T, T2* multiecho magnitude images.
Assessment
Four deep‐learning convolutional neural networks (HippoNet‐2D, HippoNet‐3D, HippoNet‐LSTM, and an ensemble network HippoNet‐Ensemble) were used to achieve unsupervised staging of LIC using five classes (normal, borderline, middle, moderate, severe). The training set was employed to construct the deep‐learning model. The performance of the LIC staging model was evaluated in the test set and in the external test set. The model's performances were assessed by evaluating the accuracy, sensitivity, and specificity with respect to the ground truth labels obtained by T2* measurements and by comparison with operator‐induced variability originating from different region of interest (ROI) placements.
Statistical Tests
The network's performances were evaluated by single‐class accuracy, specificity, and sensitivity and compared by one‐way repeated measures analysis of variance (ANOVA) and one‐way ANOVA.
Results
HippoNet‐Ensemble reached an accuracy significantly higher than the other networks, and a sensitivity and specificity higher than HippoNet‐LSTM. Accuracy, sensitivity, and specificity values for the LIC stages were: normal: 0.96/0.93/0.97, borderline: 0.95/0.85/0.98, mild: 0.96/0.88/0.98, moderate: 0.95/0.89/0.97, severe: 0.97/0.95/0.98. Correctly staging of cases was in the range of 85%–95%, depending on the LIC class. Multiclass accuracy was 0.90 against 0.92 for the interobserver variability.
Data Conclusion
The proposed HippoNet‐Ensemble network can perform unsupervised LIC staging and achieves good prognostic performance.
Evidence Level
4
Technical Efficacy
Stage 2
Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or ...after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.
Objectives
Our aims were to obtain myocardial regional and global T2 values as a reference for normality for the first time using a GE scanner and to assess their association with physiological ...variables.
Methods
One hundred healthy volunteers aged 20–70 years (50% females) underwent cardiovascular magnetic resonance. Basal, mid-ventricular, and apical short-axis slices of the left ventricle were acquired by a multi-echo fast-spin-echo (MEFSE) sequence. Image analysis was performed with a commercially available software package. The T2 value was assessed in all 16 myocardial segments and the global value was the mean.
Results
The global T2 value averaged across all subjects was 52.2 ± 2.5 ms (range: 47.0–59.9 ms). Inter-study, intra-observer, and inter-observer reproducibility was good (coefficient of variation < 5%). 3.6% of the segments was excluded because of artifacts and/or partial-volume effects. Segmental T2 values differed significantly (
p
< 0.0001), with the lowest value in the basal anterolateral segment (50.0 ± 3.5 ms) and the highest in the apical lateral segment (54.9 ± 5.1 ms). Mean T2 was significantly lower in the basal slice compared to both mid-ventricular and apical slices and in the mid-ventricular slice than in the apical slice. Aging was associated with increased segmental and global T2 values. Females showed higher T2 values than males. T2 values were not correlated to heart rate. A significant inverse correlation was detected between global T2 values and mean wall thickness.
Conclusions
The optimized MEFSE sequence allows for robust and reproducible quantification of segmental T2 values. Gender- and age-specific segmental reference values must be defined for distinguishing healthy and diseased myocardium.
Key Points
• In healthy subjects, T2 values differ among myocardial segments and are influenced by age and gender.
• Normal T2 values in the myocardium, usable as a benchmark by other GE sites, were established.
Although the most widely agreed neurophysiological tool for investigating small fiber damage is laser-evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this ...clinical, neurophysiological, and skin biopsy study, we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed fiber polyneuropathy, and assessed the sensitivity and specificity of LEPs in diabetic small fiber neuropathy. From 288 LEP recordings from the face, hand, and foot in 73 healthy subjects, we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fiber diabetic neuropathy and 25 patients with possible small-fiber diabetic neuropathy. In the 100 patients with mixed fiber neuropathy, we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small fiber neuropathy, using the skin biopsy for assessing the intraepidermal nerve fiber density as a reference standard, we calculated LEP sensitivity and specificity. In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small fiber neuropathy. Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small fiber neuropathy.
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