Epiluminescence microscopy: Criteria of cutaneous melanoma progression

Background: Cutaneous melanoma develops through a series of evolutionary steps (intraepidermal, radial, and vertical growth phases) that are traceable in specific histologic features. Epiluminescence microscopy (ELM) is an in vivo technique that enables the visualization of morphologic structures in pigmented lesions correlated with specific histologic architectural characteristics. Many ELM criteria associated with cutaneous melanoma have been described, but their correlation with tumor progression has not yet been established. Objective: In this preliminary study our purpose was to explore the possibility of recognizing ELM criteria that allow the in vivo detection of the various phases of melanoma progression as well as tumor depth. Methods: Seventy-two cutaneous melanomas (41 'thin' melanomas [TnM], 0.75 mm thickness) were investigated with ELM for the presence of nine standard ELM criteria; their significance was determined by calculating the chi-square test of independence. Results: A significant association is found between the presence of pigment network and TaM and between the presence of gray-blue areas, vascular pattern, and TkM. Moreover, pigment network plus radial streaming is the most significant association of ELM criteria in TnM, whereas gray-blue areas plus vascular pattern is the greatest in TkM. Conclusion: This study shows a good correlation between certain ELM criteria and the histologic architecture of cutaneous melanoma for a preoperative evaluation of the tumor thickness. Further investigation is needed for verifying on a larger number of cases our pilot estimates of sensitivity and specificity of ELM criteria in thin and thick melanomas

Clinical and dermatoscopic criteria for the preoperative evaluation of cutaneous melanoma thickness

Background: Melanoma thickness measured according to the Breslow method is used to determine surgical margin and in patient selection for sentinel node biopsy. Previous studies did not confirm the reliability of melanoma palpability for clinical prediction of tumor thickness. Recently we reported the usefulness of epiluminescence microscopy (dermatoscopy) for in vivo detection of the phases of melanoma progression, as well as tumor depth. Objective: Our purpose was to determine whether the combination of clinical and dermatoscopic criteria could increase the accuracy in preoperative evaluation of melanoma thickness with respect to the clinical elevation and dermatoscopic assessments considered separately. Methods: In a blind retrospective study, 122 cutaneous melanomas were studied to evaluate the presence of several clinical and dermatoscopic criteria and their relation with the histologic thickness. An algorithm of combined criteria was constructed and statistically assessed. Results: Combinations of palpability, diameter of more than 15 mm, pigment network, gray-blue areas, and atypical vascular pattern allowed correct prediction of thickness in 89% of melanomas when categorized in two groups of less than 0.76 mm and more than 0.75 mm thickness, compared with 75% using palpability, and 80% using dermatoscopic criteria. Lower values were obtained in the further subdivision of melanomas into groups of 0.76 to 1.5 mm and more than 1.5 mm thickness. Conclusion: The combination of clinical and dermatoscopic criteria is a more precise guide for the preoperative evaluation of melanoma thickness than either is alone. However, further studies are needed to verify its applicability in establishing the surgical approach to cutaneous melanoma

Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular Dynamics Simulations

We analyzed a 100 μs MD trajectory of the SARS-CoV-2 main protease by a non-parametric data analysis approach which allows characterizing a free energy landscape as a simultaneous function of hundreds of variables. We identified several conformations that, when visited by the dynamics, are stable for several hundred nanoseconds. We explicitly characterize and describe these metastable states. In some of these configurations, the catalytic dyad is less accessible. Stabilizing them by a suitable binder could lead to an inhibition of the enzymatic activity. In our analysis we keep track of relevant contacts between residues which are selectively broken or formed in the states. Some of these contacts are formed by residues which are far from the catalytic dyad and are accessible to the solvent. Based on this analysis we propose some relevant contact patterns and three possible binding sites which could be targeted to achieve allosteric inhibition

Epiluminescence microscopy for the diagnosis of doubtful melanocytic skin lesions: Comparison of the ABCD rule of dermatoscopy and a new 7-point checklist based on pattern analysis

Objective: To compare the reliability of a new 7-point checklist based on simplified epiluminescence microscopy (ELM) pattern analysis with the ABCD rule of dermatoscopy and standard pattern analysis for the diagnosis of clinically doubtful melanocytic skin lesions. Design: In a blind study, ELM images of 342 histologically proven melanocytic skin lesions were evaluated for the presence of 7 standard criteria that we called the 'ELM 7-point checklist.' For each lesion, 'overall' and 'ABCD scored' diagnoses were recorded. From a training set of 57 melanomas and 139 atypical non-melanomas, odds ratios were calculated to create a simple diagnostic model based on identification of major and minor criteria for the '7-point scored' diagnosis. A test set of 60 melanomas and 86 atypical non-melanomas was used for model validation and was then presented to 2 less experienced ELM observers, who recorded the ABCD and 7-point scored diagnoses. Settings: University medical centers. Patients: A sample of patients with excised melanocytic lesions. Main Outcome Measures: Sensitivity, specificity, and accuracy of the models for diagnosing melanoma. Results: From the total combined sets, the 7-point checklist gave a sensitivity of 95% and a specificity of 75% compared with 85% sensitivity and 66% specificity using the ABCD rule and 91% sensitivity and 90% specificity using standard pattern analysis (overall ELM diagnosis). Compared with the ABCD rule, the 7-point method allowed less experienced observers to obtain higher diagnostic accuracy values. Conclusions: The ELM 7-point checklist provides a simplification of standard pattern analysis because of the low number of features to identify and the scoring diagnostic system. As with the ABCD rule, it can be easily learned and easily applied and has proven to be reliable in diagnosing melanoma

Cognitive modulation of psychophysical, respiratory and autonomic responses to cold pressor test

In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22) and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was administered without (CPT) and with suggestions for analgesia (CPT+AN). Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion) and pain tolerance, defined as the difference between cpt duration and pain threshold), respiratory (amplitude and frequency) and autonomic variables (tonic skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin blood flow) were studied. The suggestions for analgesia increased cpt duration and RR in both groups, but decreased pain intensity and enhanced pain threshold only in highs; in both groups they did not modulate systolic blood pressure, tonic skin conductance and skin blood flow; thus, increased parasympathetic activity appears responsible for the heart rate reduction induced by suggestions in both groups. In conclusion, our findings show that suggestions modulate pain experience differentially in highs and lows, and are partially effective also in lows. We hypothesize that the mechanisms responsible for the efficacy of suggestions in healthy lows may be involved also in their efficacy in chronic pain patients with low hypnotisability

On the Optimum Dispersion of a Storage Ring for Electron Cooling with High Space Charge

With the intense electron beams used for cooling, matching of the ion and electron velocity over the largest possible fraction of the beam profile becomes important. In this situation, a finite dispersion from the ring in the cooling section can lead to an appreciable gain in the transverse cooling speed. Based on a simple model of the cooling force, an expression for the "optimum" dispersion as a function of the electron beam intensity, the momentum spread and other properties of the ion beam will be derived. This simple theory will be compared to measurements made on the Low Energy Ion Ring (LEIR) at CERN during 1997

Electron cooling of PB54+^{54+} ions in the low energy ion ring (LEIR)

For the preparation of dense bunches of lead ions for the LHC, electron cooling will be essential for accumula tion in a storage ring at 4.2 MeV/u. Tests have been carried out on the LEAR ring (renamed LEIR for Low Energy Ion Ring) in order to determine the optimum parameters for a future state-of-the-art electron cooling device which would be able to cool linac pulses of lead ions in less than 100 ms. The experiments focused on the generation of a stable high intensity electron beam that is needed to free space in both longitudinal and transverse phase space for incoming pulses. Investigations on the ion beam lifetime in the presence of the electron beam and on the dependency of the cooling times on the optical settings of the storage ring will also be discussed. This paper concentrates on the cooling aspects with the multiturn injection, vacuum, and high intensity aspects discussed in a companion paper at this conference