Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation in vivo with line-field optical coherence tomography.

BACKGROUND: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. OBJECTIVES: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. METHODS: Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. RESULTS: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. CONCLUSIONS: LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Non-invasive, in vivo, characterization of cutaneous metastases using a novel multimodal RCM-OCT imaging device: a case-series.

BACKGROUND: Cutaneous metastases (CM) diagnosis is clinically challenging, requiring an invasive biopsy for confirmation. A novel, RCM-OCT device combines the advantage of horizontal high-resolution reflectance confocal microscopy (RCM) images and vertical deeper optical coherence tomography (OCT) images to aid in non-invasive diagnosis of CM from breast cancers. OBJECTIVE: Characterize CM from breast cancers using RCM-OCT device. METHODS: Seven patients suffering from breast cancers with suspicious CM were consented and imaged with RCM-OCT device. CM features were defined by comparing with histopathology. Tumour depths were measured on OCT and on H&E-images and correlated using statistical analysis Pearson test. 3D-OCT images were reconstructed to enhance tumour visualization. RESULTS: 6/7 lesions were CM from breast cancers, and one was vascular ectasia, on histopathology. CM appeared as greyish-darkish oval to round structures within the dermis on RCM and OCT-images. On RCM, individual tumour cells were seen, enabling identification of even small tumour foci; while, on OCT deeper tumours were detected. Inflammatory cells, dilated vessels and coarse collagen were identified in the dermis. Pearson correlation had an r2 of 0.38 and a significant P-value <0.004 for depth measurements. CM from breast cancers could be differentiated from ecstatic vessels on 3D-reconstructed OCT image. LIMITATION: Small sample size and lack of clinical mimickers. CONCLUSION: RCM-OCT can detect CM and has potential in aiding non-invasive diagnosis and management.

A dusty veil shading Betelgeuse during its Great Dimming.

Red supergiants are the most common final evolutionary stage of stars that have initial masses between 8 and 35 times that of the Sun1. During this stage, which lasts roughly 100,000 years1, red supergiants experience substantial mass loss. However, the mechanism for this mass loss is unknown2. Mass loss may affect the evolutionary path, collapse and future supernova light curve3 of a red supergiant, and its ultimate fate as either a neutron star or a black hole4. From November 2019 to March 2020, Betelgeuse-the second-closest red supergiant to Earth (roughly 220 parsecs, or 724 light years, away)5,6-experienced a historic dimming of its visible brightness. Usually having an apparent magnitude between 0.1 and 1.0, its visual brightness decreased to 1.614 ± 0.008 magnitudes around 7-13 February 20207-an event referred to as Betelgeuse's Great Dimming. Here we report high-angular-resolution observations showing that the southern hemisphere of Betelgeuse was ten times darker than usual in the visible spectrum during its Great Dimming. Observations and modelling support a scenario in which a dust clump formed recently in the vicinity of the star, owing to a local temperature decrease in a cool patch that appeared on the photosphere. The directly imaged brightness variations of Betelgeuse evolved on a timescale of weeks. Our findings suggest that a component of mass loss from red supergiants8 is inhomogeneous, linked to a very contrasted and rapidly changing photosphere.

Line-field confocal optical coherence tomography of basal cell carcinoma: a descriptive study.

BACKGROUND: Early diagnosis and subtype classification of basal cell carcinoma (BCC) are crucial to reduce morbidity and optimize treatment. Good accuracy in differentiating BCC from clinical imitators has been achieved with existing diagnostic strategies but lower performance in discriminating BCC subtypes. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to combine the technical advantages of reflectance confocal microscopy and OCT. OBJECTIVES: To identify and describe LC-OCT criteria associated with BCC and explore their association with BCC subtypes. METHODS: Basal cell carcinoma were imaged with a handheld LC-OCT device before surgical excision. LC-OCT images were retrospectively evaluated by three observers for presence/absence of criteria for BCC. Multivariate logistic regression models were used to find independent predictors of BCC subtypes. RESULTS: Eighty-nine histopathologically proven BCCs were included, of which 66 (74.2%) were pure subtypes [superficial BCC (sBCC): 19/66 (28.8%); nodular BCC (nBCC): 31/66 (47.0%); infiltrative BCC (iBCC): 16/66 (24.2%)]. Lobules, blood vessels and small bright cells within epidermis/lobules were the most frequent criteria for BCC. LC-OCT criteria independently associated with sBCC were presence of hemispheric lobules, absence of lobule separation from the epidermis, absence of stretching of the stroma; with nBCC were presence of macrolobules, absence of lobule connection to the epidermis; and with iBCC were presence of branched lobules. CONCLUSIONS: This was the first study describing the characteristics of BCC under LC-OCT examination. We proposed morphologic criteria, which could be potentially useful for diagnosis and subtype classification of BCC, as well as for its therapeutic management. Future studies are needed to assess these hypotheses.

In vivo characterization of healthy human skin with a novel, non-invasive imaging technique: line-field confocal optical coherence tomography.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive optical technique recently developed for skin examination in vivo. It provides real-time, high-resolution vertical images with an isotropic resolution of ~1 µm and a penetration depth of ~500 µm. OBJECTIVES: Study goals were to qualitatively/quantitatively characterize healthy skin at different body sites using LC-OCT. METHODS: The skin of young healthy volunteers was imaged with a handheld LC-OCT imaging device. Seven body sites (back of the hand, forehead, cheek, nose, chest, forearm and back) were investigated. An independent qualitative [cutaneous structures' description; visibility of keratinocytes' nuclei and dermal-epidermal junction (DEJ)] and quantitative [stratum corneum (SC)/epidermal thicknesses; height of dermal papillae] assessment of the LC-OCT images was performed. RESULTS: A total of 88 LC-OCT images were collected from 29 participants (20 females; nine males; mean age 25.9 years). Keratinocytes' nuclei and DEJ were visible in the totality of images. The different layers of the epidermis and the remaining cutaneous structures/findings were visualized. Body sites-related variability was detected for SC/epidermal thicknesses and height of dermal papillae. Inter-observer agreement was excellent (SC thickness), good-to-excellent (epidermal thickness) and moderate-to-good (papillae). CONCLUSIONS: Line-field confocal-OCT provides non-invasive, real-time imaging of the skin in vivo with deep penetration and high resolution, enabling the visualization of single cells. The histology-like vertical view provides an easy way to recognize/measure different cutaneous structures/findings. LC-OCT appears as a promising technique for the examination of physiological/pathological skin.

No Sun-like dynamo on the active star ζ Andromedae from starspot asymmetry.

Sunspots are cool areas caused by strong surface magnetic fields that inhibit convection. Moreover, strong magnetic fields can alter the average atmospheric structure, degrading our ability to measure stellar masses and ages. Stars that are more active than the Sun have more and stronger dark spots than does the Sun, including on the rotational pole. Doppler imaging, which has so far produced the most detailed images of surface structures on other stars, cannot always distinguish the hemisphere in which the starspots are located, especially in the equatorial region and if the data quality is not optimal. This leads to problems in investigating the north-south distribution of starspot active latitudes (those latitudes with more starspot activity); this distribution is a crucial constraint of dynamo theory. Polar spots, whose existence is inferred from Doppler tomography, could plausibly be observational artefacts. Here we report imaging of the old, magnetically active star ζ Andromedae using long-baseline infrared interferometry. In our data, a dark polar spot is seen in each of two observation epochs, whereas lower-latitude spot structures in both hemispheres do not persist between observations, revealing global starspot asymmetries. The north-south symmetry of active latitudes observed on the Sun is absent on ζ And, which hosts global spot patterns that cannot be produced by solar-type dynamos.

The expanding fireball of Nova Delphini 2013.

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common-envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 ± 0.59 kiloparsecs from the Sun.

Effect of O2 on the adsorption of SO2 on carbon-supported Pt electrocatalysts.

Adsorption of SO(2) in the presence of O(2) on Pt/C catalysts often used as electrocatalysts has been investigated by temperature programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). The amounts of SO(2) adsorption on Pt/C in the presence of O(2) were much higher than those in the absence of O(2) (SO(2)-N(2)) and from the carbon support (Vulcan XC-72) alone. Adsorption is dependent on oxygen concentration over the range 0-20% but reaches saturation at 20% O(2). The spillover of SO(2) from Pt to the carbon support has been proposed for 10, 20, and 40% Pt loadings, characterized by desorption temperatures of approximately 150 and 260 °C for SO(2) adsorbed on Pt and carbon, respectively. Adsorbed Pt-S, C-S, C-SO(x), and Pt-SO(4) species were identified by XPS as S-containing species on both Pt and carbon. Both TPD and XPS indicate that the carbon support plays a major role in SO(2) adsorption, primarily as SO(x) (x = 3, 4). The bonding of S and SO(x) on the carbon support was strong enough that back diffusion to the Pt surface did not occur.

SO2 adsorption on carbon-supported Pt electrocatalysts.

Adsorption of SO2 on a Pt/C catalyst typically used in proton exchange- membrane fuel cells (PEMFCs) has been investigated by temperature programmed desorption (TPD). SO2 concentrations in N2 were varied from 5 ppm to 1% (vol) and adsorption isotherms were determined at 25, 50, and 80 °C. Oxygen assisted (O-assisted) desorption experiments (i.e., successive TPD experiments following exposure to room temperature O2 after the first TPD event) produced an additional SO2 peak at a temperature higher than the initial SO2 peak. These two types of SO2 adsorption were identified as weakly adsorbed SO2 species desorbed between 140 and 200 °C, depending on concentration, and a strongly adsorbed, dissociated species. For the strongly adsorbed, dissociative species, (18)O2 isotope introduction during O-assisted desorption yielded ratios of 50%, 36%, and 14% for SO2 masses of 64, 66, and 68, respectively. The activation energy and kinetic constant of desorption are reported for weakly adsorbed SO2 at 1% and 20 ppm SO2 using the Polanyi-Wigner equation.

[Uni-axial tissular extension for covering skin defects of the limbs. A 31 cases review]. / Extension tissulaire uni-axiale dans la couverture des pertes de substance des membres. A propos de 31 cas.

INTRODUCTION: The skin property to adapt to external constraints is widely used in plastic surgery. Tissue expansion is the most known and codified application. Tissue extension appears to be an attractive alternative. The authors propose the usage of a simplified procedure to deal with skin loss in the superior or inferior members. MATERIAL AND METHOD: Thirty-one patients underwent uni-axial traction between February 2000 and October 2003. RESULTS: Closure of skin loss on the upper member has been obtained in 6 days and in 8 days on the inferior member. DISCUSSION: Efficiency, reliability and no subsequent aftermaths are strong arguments in favor of the development of a simplified extension procedure. CONCLUSION: The tissue extension procedure, although scarcely used is an attractive procedure for the coverage of skin losses.

Reduction of red blood cell disaggregability during submaximal exercise: relationship with fibrinogen levels.

Effects of exercise on erythrocyte aggregation were investigated in 19 elite athletes. High shear rate viscometry (1000 s(-1) evidenced an increase in blood viscosity explained by an increase in hematocrit (+8% p<0.01) and plasma viscosity (+7% p<0.01). Erythrocyte rigidity index and erythrocyte aggregability measured using the Myrenne erythroaggregometer did not change. However, using the laser backscattering technique (SEFAM erythroaggregometer), we observed significant changes in aggregability and desaggregability after 25 min of exercise. The initial aggregation time (TA) decreased by 33% (p<0.01), while the final aggregation time decreased by 13.6% (p<0.01). TA was correlated with aerobic working capacity (r=0.73; p=0.005), which was negatively correlated with blood viscosity at rest (r=-0.57; p=0.043). A significant relationship was observed between TA and the initial fibrinogen levels (r=0.71; p<0.01). The plasma volume contraction during exercise was found to be statistically explained by the water loss proportional to the total work load. Thus, laser backscattering demonstrates an increase in aggregability and a decrease in disaggregability of red cells during exercise, proportional to baseline fibrinogen values.

Exercise-induced central retinal vein thrombosis: possible involvement of hemorheological disturbances. A case report.

Exercise-induced impairment in blood fluidity has been supposed to increase cardiovascular risk but there is no data to support this hypothesis. We report the case of a 50 yr old marathon runner who underwent a central retinal vein thrombosis after a marathon run. We investigated his rheological response to exercise compared to control subjects of previous studies. During a standardized sub-maximal exercise-test, the increase in blood viscosity (+28%) and hematocrit (+25%) exceeded the control range but the most striking differences were found for red cell aggregation (Myrenne +47%) and disaggregation thresholds (Affibio +37%). Although some of this post-exercise hyperviscosity pattern may be due to the previous vascular event, these findings may also support the hypothesis of a role for hemorheological alterations during exercise in the pathogenesis of this marathon-induced retinal thrombosis, and indicate that after such an event hemorheological adaptation to exercise remains markedly disturbed.

[Marfan syndrome and pregnancy. Apropos of 4 cases]. / Syndrome de Marfan et grossesse. A propos de quatre cas.

OBJECTIVES: To create a follow-up protocol for pregnant patients with Marfan syndrome. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients who delivered in the Jeanne de Flandre University Hospital between June 1996 and June 1999. Four pregnant patients with Marfan syndrome were identified. RESULTS: Three of these patients had Bentall procedure. One of them had vaginal delivery and the two others underwent cesarean section. One of these two patients developed aortic valve thrombus at 14 weeks of amenorrhea. The fourth patient did not have surgery and had two vaginal deliveries. DISCUSSION: According to our results and after reviewing literature pregnant patients with Marfan syndrome were divided into two groups. The 1st group was comprised of patients who underwent Bentall procedure. The 2nd one was comprised of patients who did not undergo any surgical procedure. The possibility of vaginal delivery for patients who underwent Bentall procedure (one case) and the interest of Propanolol and anticoagulant treatment are emphasized. CONCLUSION: The multivariant approach of pregnant patients with Marfan syndrome is stressed out with special reference to the potential complications of this syndrome such as aortic dissection and to the problems related to the anticoagulant treatment.

Insulin-like growth factor-binding protein 1 and blood rheology in athletes.

The GH-IGF axis has been recently suggested to modulate blood rheology in trained athletes, via GH effects on body water status and a possible action of IGF-I on erythrocyte deformability and aggregability. Another potential candidate for such a rheologic effect of the GH-IGF axis is insulin-like growth factor binding protein-1 (IGF-BP1) which is increased in trained people and correlated to fitness: IGF-BP1 is elevated in patients with polycythemia vera and stimulates erythroid burst formation in vitro. We investigated the statistical relationships between IGF-BP1 and blood rheology in athletes. 21 soccer players, age 24.5+/-1.13 yr; body mass index 23.7+/-0.38 kg/m(2); VO2max 44.8+/-7 ml.min(-1).kg(-1)). The major statistical determinant of IGFBP1 (measured at rest after overnight fast) was age (r=0.752, p=0.00013) which was not correlated with rheological parameters. IGF BP1 was negatively correlated with blood viscosity eta (high shear rate r=-0.516, p=0.024) and positively correlated with the percentage of extracellular water in total body water (ECW/TBW) (r=0.488, p=0.039). The previously reported correlations between IGF-I and both eta (r=0.637, p=0.003) and red cell rigidity "Tk" (r=0.696, p=0.0137) were observed, but IGF-I and IGF-BP1 were not correlated to each other (r=-0.176 ns) and their correlations with eta and Tk appeared to be independent when studied by multivariate analysis. Consistent with these correlations, subjects in the upper tertile of IGF-BP1 (>23.4 ng/ml) compared to those in the lower (<7.5 ng/ml) had a higher percentage of ECW/TBW (40.8+/-0.4 vs 38+/-0.8%, p=0.033), a lower eta (2.7+/-0.05 vs 2.97+/-0.06 mPa.s, p=0.016), and a lower Tk (0.54+/-0.05 vs 0.63+/-0.01, p=0.027). Thus, beside GH and IGF-I, IGF-BP1, which is reported to act on erythroid progenitors, exhibits statistical relationships with blood fluidity and erythrocyte flexibility that may suggest a physiological role in improving blood rheology.

A coding region determinant of instability regulates levels of manganese superoxide dismutase mRNA.

The mitochondria-localized manganese superoxide dismutase (MnSOD), serves a key cytoprotective role against reactive oxygen species arising from a variety of cellular processes and immunological stresses. Previous data from our laboratory suggest that the regulation of the rat MnSOD gene may occur not only at the transcriptional but quite possibly at the post-transcriptional level. To verify this hypothesis, we have attempted to identify regions within the rat MnSOD cDNA that may be functionally involved in regulating the stability of the mRNA. Using a c-fos-based promoter activation system, we have identified an approximately 280-nucleotide fragment within the MnSOD mRNA coding region that, when fused to a rabbit beta-globin gene, destabilizes the normally stable beta-globin mRNA. This cis-directed destabilization phenomenon confers its effects independent of position and stimulus. Most importantly, the MnSOD coding region determinant functions when placed in the 3'-untranslated region of the beta-globin transcript, demonstrating its activity in the absence of ribosome transit. We feel that these data provide a mechanistic basis for both the basal and stimulus-dependent post-transcriptional regulation of MnSOD.

Tumor necrosis factor-alpha selectively induces MnSOD expression via mitochondria-to-nucleus signaling, whereas interleukin-1beta utilizes an alternative pathway.

Mitochondrial levels of the anti-oxidant enzyme, manganese superoxide dismutase (MnSOD), are dramatically elevated in response to stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and lipopolysaccharide (LPS). However, the precise intracellular signaling pathways responsible for this inducible expression are poorly understood. MnSOD expression in pulmonary epithelial and endothelial cells, treated with inflammatory mediators and various inhibitors, was studied by Northern analysis. The mitochondrial electron transport chain inhibitors, antimycin A and myxothiazol, selectively blocked TNF-alpha-inducible expression of MnSOD but not that of IL-1beta or LPS, indicating different signaling pathways. N-Acetylcysteine could reliably decrease inducible MnSOD expression by TNF-alpha, but not IL-1, linking reactive oxygen species (ROS) to the TNF-alpha signaling pathway. Elevated levels of arachidonic acid have been demonstrated previously to generate mitochondrial ROS. A specific cytoplasmic phospholipase A(2) inhibitor reduced stimulated MnSOD expression by TNF-alpha, but not by IL-1beta, further supporting the role of ROS. Other investigators have shown that MnSOD expression may be regulated by NF-kappaB. Our results with a specific inhibitory kappa-kinase inhibitor indicate that NF-kappaB modulates IL-1beta signaling but not the TNF-alpha pathway. Thus, we have demonstrated that although inducible MnSOD transcription may appear similar at the messenger RNA level, the intracellular signaling pathways are differentially regulated.

A dusty torus around the luminous young star LkH alpha101.

A star forms when a cloud of dust and gas collapses. It is generally believed that this collapse first produces a flattened rotating disk, through which matter is fed onto the embryonic star at the centre of the disk. When the temperature and density at the centre of the star pass a critical threshold, thermonuclear fusion begins. The remaining disk, which can still contain up to 0.3 times the mass of the star, is then sculpted and eventually dissipated by the radiation and wind from the newborn star. But this picture of the structure and evolution of the disk remains speculative because of the lack of morphological data of sufficient resolution and uncertainties regarding the underlying physical processes. Here we present images of a young star, LkH alpha101, in which the structure of the inner accretion disk is resolved. We find that the disk is almost face-on, with a central gap (or cavity) and a hot inner edge. The cavity is bigger than previous theoretical predictions, and we infer that the position of the inner edge is probably determined by sublimation of dust grains by direct stellar radiation, rather than by disk-reprocessing or viscous-heating processes as usually assumed.

Minimum instructional and program-specific administrative costs of educating residents in internal medicine.

BACKGROUND: The cost associated with education of residents is of interest from an educational as well as a political perspective. Most studies report a single institution's actual incurred costs, based on traditional cost accounting methods. We quantified the minimum instructional and program-specific administrative costs for residency training in internal medicine. METHODS: Using the Accreditation Council for Graduate Medical Education program requirements for internal medicine as minimum standards for teaching and administrative effort, we quantified the minimum instructional and administrative costs for sponsorship of an accredited residency program in internal medicine. We also analyzed the impact of resident complement and program curricular emphasis (outpatient, inpatient, or traditional) on the per-resident cost. The main outcome measure was the minimum annual per-resident cost of instruction and program-specific administration. RESULTS: Using the assumptions in this model, we estimated the annual cost per resident of implementing the program requirements to be $50,648, $35,477, $28,517, and $26,197 for inpatient intensive residency programs with resident complements of 21, 42, 84, and 126, respectively. For outpatient intensive residency programs of identical resident complements, we estimated the annual per-resident cost to be $58,025, $42,853, $35,894, and $33,574 for similar resident complements. Fixed costs mandated by the program requirements, which did not vary across program size or configuration, were estimated to be $640,737. CONCLUSIONS: There are fixed and variable costs associated with sponsorship of accredited internal medicine residency programs. The minimum cost per resident of education and departmental administration varies inversely with program size within the sizes examined.